AU2018378802B2 - Products and methods for assessing and increasing Klotho protein levels - Google Patents

Abstract

Disclosed are products and methods for monitoring Klotho protein levels and for stabilizing Klotho protein in a mammalian blood sample, especially at room temperature or without freezing, for a period of time. Methods of detecting and quantifying Klotho protein levels, particularly endogenous and/or exogenous soluble alpha Klotho protein levels, methods of diagnosing Klotho protein deficiency, and methods of increasing Klotho protein levels or production, particularly endogenous and/or exogenous soluble alpha Klotho protein level(s), expression, or production, in a mammalian subject, and products useful in performing the same, including diagnostic kits and compositions for treating Klotho protein deficiency, are disclosed. Compositions are configured or formulated to augment natural soluble alpha Klotho protein production, attenuate Klotho protein damage or degradation, and/or supplement Klotho protein levels with exogenous, recombinant protein. Treatment methods and uses include administration of the compositions to human or non-human mammalian subjects.

Description

PRODUCTS AND METHODS FOR ASSESSING AND INCREASING KLOTHO PROTEIN LEVELS

BACKGROUND 1. Technical Field

[0001] The present disclosure relates to assessing and increasing Klotho protein levels in a patient. In particular, the present disclosure relates to products and methods for monitoring, detecting, and/or qualifying the level of endogenous and/or exogenous Klotho protein and for diagnosing Klotho protein deficiency in a human or non-human animal (e.g., mammalian) subject, and to the production, purification, and administration of pharmaceutical or nutraceutical compositions for increasing Klotho protein levels in the subject. 2. Related Technology

[0002] Klotho (or alpha-Klotho, a-Klotho, etc.) is a recently characterized protein encoded by the KL (or klotho) gene, located on human chromosome 13. Two transcripts that arise from a single klotho gene through alternative RNA splicing have been identified. See Figures 1 and 2. The first transcript is predicted to encode Klotho isoform 1 - a full-length, 1,012 amino acid, single-pass transmembrane-membrane protein, with a short cytoplasmic tail (human residues 1003-1012), a transmembrane (TM) domain (human residues 982-1002), and extracellular region or domain (human residues 1-981) comprising two (largely) homologous (internal repeat) domains (termed KL1 (human residues 56-506, which is 450 residues long) and KL2 (human residues 515-953, which is 438 residues long), which each share 20%-40% amino acid sequence homology to 3-glucosidases, but may lack similar levels of glucosidase catalytic activity), and a signal sequence (SS) domain (human residues 1-33). The SS, KL1, and KL2 domain-containing extracellular region (human residues 1-981) may be enzymatically cleaved by a/p-secretases, and released into the circulatory stream as a 130 kDa circulating protein, termed soluble klotho (or sKlotho, s-Klotho, alpha soluble Klotho, etc.). The extracellular region can also be cleaved into separate 68 kDa protein (KL1 + SS) and 64 kDa protein (KL2).

[0003] The second transcript, a splicing variant of alpha-klotho mRNA, encodes a second isoform of Klotho protein corresponding mainly to the KL1 domain. The internal splice donor site is thought to be located in exon 3 of the klotho gene. The resultant alternatively spliced transcript contains a 50 bp insertion after exon 3 (Figure 1; gray), with an in-frame translation stop codon at the end thereof. The expressed protein product is secreted into the circulation and is termed secreted Klotho (or Klotho isoform 2), which differs from the canonical sequence of isoform 1 at amino acid residues 535-549: DTTLSQFTDLNVYLW- SQLTKPISSLTKPYH, and with amino acid residues 550-1012 missing.

[0004] Accordingly, there may be a number of different Klotho proteins in the circulation at any given time, depending on gene expression, RNA splicing, and enzymatic cleavage. Despite the existence of various forms of alpha-Klotho protein, only the full length, membrane-bound, isoform 1 is known to form a complex with fibroblast growth factor (FGF) receptors and functions as an obligatory co-receptor for FGF23 - a bone-derived hormone that induces phosphate excretion into urine and which has a regulatory role on Pi and vitamin D metabolism.

[0005] Klotho is highly expressed in the kidney, brain, and to a lesser extent in other organs, and may also be found in the blood, cerebrospinal fluid and urine of mammals. Circulating levels of soluble Klotho proteins in mammals, including humans, are thought to decrease with age. In addition, Klotho-deficient mice exhibit accelerated aging phenotypes, whereas over-expression of klotho in mice has been shown to extend lifespan. In addition, Klotho has been implicated in a number of cellular processes related to aging. In light of the foregoing, a developing hypothesis states that soluble Klotho may function as an anti-aging compound in the human body.

[0006] Aging is an inevitable and progressive biological process resulting in dysfunction and destruction of almost all tissues and organs, ultimately resulting in death. The aging of the human body, for instance, is associated with the decline of cellular function, which can lead to the development of a variety of diseases. Aging is thought to be driven by a tightly regulated and complex interplay between genetic and acquired factors and is typically characterized by an increase in senescence, a quantitative and qualitative decrease in stem cells, and abnormal structure at tissue levels.

[0007] As the so-called "baby boomers" generation continues to advance in age, the population of aging individuals (e.g., age 60-65) is rapidly increasing globally. The increased demand for health care for this aging population places significant financial burden on any healthcare system. Recombinant klotho proteins may provide promising therapeutic agents to counter age-related health conditions. To date, all relevant treatment data related to Klotho is pre-clinical, research trials in animal models. Developing strategies and health intervention products and methods based on (i) the production and/or purification (e.g., to substantial homogeneity) of recombinant s-Klotho proteins or protein variants and (ii) the administration of recombinant s-Klotho proteins or protein variants and/or s-Klotho protein level-increasing health supplements to subjects, especially humans and/or within an increasing aging population, may help to ameliorate this situation.

[0008] Currently, there is not a product or method for providing an exogenous form of human Klotho protein, such as recombinant soluble human alpha-Klotho protein or protein variant, suitable for human use, especially protein that is Current Good Manufacturing Practice (cGMP) regulation compliant, as determined and enforced by the U.S. Food and Drug Administration (FDA), whether alone or in combination with one or more additional active components.

[0009] Likewise, there is not currently a product or method for (naturally) increasing t0 endogenous Klotho protein levels or protein production, in a safe and effective manner, especially a product that complies with the Dietary Supplement Health and Education Act of 1994 (DSHEA) or that is Current Good Manufacturing Practice (cGMP) regulation compliant (e.g., as determined and enforced by the U.S. Food and Drug Administration (FDA)), whether alone or in combination with one or more additional active components, drugs,

[5 pharmaceuticals, or nutraceuticals.

[0010] Moreover, there is not currently a product (e.g., kit or system) or method for efficiently, reliably, reproducibly, practically, and/or (commercially or economically) viably monitoring Klotho protein levels, particularly a product or method for on-demand and/or real-time monitoring and/or quantification of endogenous and/or exogenous Klotho protein !o levels, and more particularly endogenous and/or exogenous soluble alpha Klotho protein or protein variant levels, or for diagnosing Klotho protein deficiency, particularly serum soluble Klotho protein deficiency, in human and non-human animals.

[0011] There is also not currently a suitable, large scale method for efficiently, reliably, reproducibly, practically, and/or (commercially or economically) viably producing and purifying recombinant Klotho proteins, particularly, pharmaceutical grade recombinant Klotho proteins, including recombinant Klotho protein fragments and recombinant Klotho fusion proteins. BRIEF SUMMARY

[0011a] In one aspect, the present invention provides a method of stabilizing Klotho protein in a mammalian blood sample, the method comprising: storing 20-800 pl of capillary blood from a mammalian subject in a container for at least 3 days at room temperature or without freezing, the capillary blood containing an amount of soluble Klotho protein, the container having a preservative or anti-coagulant disposed therein, the preservative or anti-coagulant being mixed with the capillary blood in the container, the preservative or anti-coagulant stabilizing the soluble Klotho protein for at least 3 days at room temperature or without freezing, the preservative or anti-coagulant comprising heparin or EDTA; and after the storing step, performing an assay to quantify the amount of soluble Klotho protein in the capillary blood based on the amount of stabilized soluble Klotho protein in the container.

[0012] Embodiments of the present disclosure solve one or more of the foregoing or other o problems in the art with products and methods for assessing and increasing Klotho protein levels in a patient. Some Embodiments include (1) compositions and methods for stabilizing Klotho protein in human or non-human animal (e.g., mammalian) blood or serum, (2) compositions and methods for monitoring, detecting, and/or quantifying Klotho protein level(s), particularly endogenous and/or exogenous soluble alpha Klotho protein level(s),

3a and/or for diagnosing Klotho protein deficiency in a human or non-human animal (e.g., mammalian) subject, and to products useful in performing the same, (3) pharmaceutical or nutraceutical compositions for increasing Klotho protein levels in the subject. Some embodiments include Klotho protein(s), or fragment(s) or variant(s) thereof, as a therapeutic agent, and more particularly, cGMP-grade, human (or non-human) recombinant soluble alpha-Klotho protein(s), or fragment(s) or variant(s) thereof, or a (pharmaceutical) composition comprising the same. Some embodiments include products and/or methods for manufacturing and administering (recombinant) Klotho protein(s), or fragment(s) or variant(s) thereof, to a human or non-human subject, and particularly for increasing serum soluble Klotho protein levels in the subject. Some embodiments include a nutraceutical or health supplement composition for increasing serum soluble Klotho protein levels in the subject. In particular, some embodiments include products that, when administered to the subject, cause an increase in Klotho protein (particularly endogenous soluble alpha Klotho protein) level(s), expression, or production, in the subject, and (4) methods of purifying recombinant Klotho proteins, particularly pharmaceutical grade recombinant Klotho proteins, recombinant Klotho protein fragments, and recombinant Klotho fusion proteins.

[0013] Various embodiments include a composition. The composition can comprise (i) one or more recombinant human Klotho proteins, protein fragments, and/or protein variants, expression nucleic acid constructs and/or vectors, cell lines and/or cell suspension cultures, and/or (ii) one or more ingredients that, when administered to the subject, cause or induce an increase Klotho protein level(s), expression, or production, particularly endogenous soluble alpha Klotho protein level(s), expression, or production, in the subject. Certain embodiments include methods of manufacturing, purifying, and administering a composition of the present disclosure to the (human or non-human animal) subjects. Some embodiments include methods for increasing Klotho protein (particularly (exogenous and/or endogenous) soluble alpha Klotho protein) level(s), expression, or production, in the subject. Some embodiments include products (e.g., diagnostic kits) and/or methods for monitoring, detecting, and/or quantifying Klotho protein level(s), particularly (endogenous and/or exogenous) soluble alpha Klotho protein level(s), and/or for diagnosing Klotho protein deficiency in the subject.

[0014] Some embodiments of the present disclosure can include one or more of: a recombinant human alpha soluble Klotho protein, protein fragment, and/or protein variant (e.g., cGMP-grade human recombinant soluble alpha-Klotho protein, protein fragment, and/or protein variant); a composition (e.g., therapeutic composition, pharmaceutical composition, medicament, formulation, etc.) comprising a recombinant human alpha soluble

Klotho protein, protein fragment, and/or protein variant; a composition comprising a recombinant human alpha soluble Klotho protein and a (pharmaceutically-acceptable) vehicle (e.g., a carrier or excipient); a composition comprising a recombinant human alpha soluble Klotho protein and at least one additional (active) ingredient; a nucleic acid construct or vector that encodes a recombinant human alpha soluble Klotho protein; a cell line that (i) contains a nucleic acid construct or vector that encodes a recombinant human alpha soluble Klotho protein and/or (ii) expresses a recombinant human alpha soluble Klotho protein; a cell suspension culture comprising one or more cells that (each) (i) contain a nucleic acid construct or vector that encodes a recombinant human alpha soluble Klotho protein and/or (ii) express a recombinant human alpha soluble Klotho protein; a method of manufacturing, and optionally purifying, a recombinant human alpha soluble Klotho protein; a method of manufacturing a medicament (or therapeutic composition - i.e., formulation) of recombinant human alpha soluble Klotho protein; a method of administering a recombinant human alpha soluble Klotho protein to a (human or non-human animal) subject; a diagnostic method for determining Klotho protein deficiency in a subject; a method of diagnosing Klotho protein deficiency in a subject; a method of diagnosing a subject as being in need of receiving a recombinant human alpha soluble Klotho protein by administration; a method for evaluating the efficacy and/or determining an effective dosage of the protein to a subject in need thereof, a recombinant human alpha soluble Klotho protein for use in treating a specific medical or other condition in a human or non-human animal (e.g., a non-human mammal); use of a recombinant human alpha soluble Klotho protein for the treatment of a specific medical or other condition in a human or non-human animal; use of a composition comprising a recombinant human alpha soluble Klotho protein for the treatment of a specific medical or other condition in a human or non-human animal; and/or use of a recombinant human alpha soluble Klotho protein in the manufacture of a medicament for the treatment of a specific medical or other condition in a human or non-human animal.

[0015] Some embodiments can include a recombinant Klotho protein, wherein at least a portion of the protein has at least 80% amino acid sequence identity to at least a portion of one of SEQ ID NO: 2 through SEQ ID NO: 70 or SEQ ID NO: 107 through SEQ ID NO: 120 or SEQ ID NO: 125 through SEQ ID NO: 128 or SEQ ID NO: 133 or SEQ ID NO: 152. Some embodiments can include recombinant protein comprising a Klotho protein sequence having at least 80% amino acid sequence identity to at least a portion of one of SEQ ID NO: 2 through SEQ ID NO: 70 or SEQ ID NO: 107 through SEQ ID NO: 120 or SEQ ID NO: 125 through SEQ ID NO: 128 or SEQ ID NO: 133 or SEQ ID NO: 152, preferably one of SEQ ID

NO: 52, SEQ ID NO: 54, SEQ ID NO: 66, SEQ ID NO: 125 through SEQ ID NO: 128, SEQ ID NO: 133, and SEQ ID NO: 152 and, optionally at least a portion of an immunoglobulin Fe domain sequence, human serum albumin sequence, His (e.g., 6His) tag sequence, and/or a Twin-Strep tag sequence, with or without an optional linker sequence therebetween. Some embodiments can include two or more recombinant Klotho proteins.

[0016] Some embodiments can include a pharmaceutical composition, comprising a pharmaceutically effective amount of the recombinant Klotho protein as described herein and a pharmaceutically-acceptable carrier. Some embodiments can include a pharmaceutical composition, comprising a pharmaceutically effective amount of a recombinant soluble Klotho protein, at least a portion of the protein having at least 80% amino acid sequence identity to at least a subset of amino acid residues 1-981, 29-981, 34-981, 36-981, 131-981, 1 549, 29-549, 34-549, 36-549, or 131-549 of human alpha Klotho isoform 1 or isoform 2, or at least a portion of one of SEQ ID NO: 2 through SEQ ID NO: 70 or SEQ ID NO: 107 through SEQ ID NO: 120 or SEQ ID NO: 125 through SEQ ID NO: 128 or SEQ ID NO: 133 or SEQ ID NO: 152, and a pharmaceutically-acceptable carrier. Some embodiments can include a pharmaceutical composition, comprising a pharmaceutically-acceptable carrier or excipient and an effective amount of a recombinant protein comprising a Klotho protein sequence having at least 80% amino acid sequence identity to at least a portion of one of SEQ ID NO: 2 through SEQ ID NO: 70 or SEQ ID NO: 107 through SEQ ID NO: 120 or SEQ ID NO: 125 through SEQ ID NO: 128 or SEQ ID NO: 133 or SEQ ID NO: 152, preferably one of SEQ ID NO: 52, SEQ ID NO: 54, SEQ ID NO: 66, SEQ ID NO: 125 through SEQ ID NO: 128, SEQ ID NO: 133, and SEQ ID NO: 152 and, optionally at least a portion of an immunoglobulin Fc domain sequence, human serum albumin sequence, His (e.g., 6His) tag sequence, and/or a Twin-Strep tag sequence, with or without an optional linker sequence therebetween. Some embodiments can include a composition, comprising a pharmaceutically effective amount of two or more recombinant Klotho proteins.

[0017] Some embodiments can include compositions that comprise a therapeutic Klotho protein and at least one other active component, such as a drug, antibody, hormone, human cell, tissue, cellular or tissue-based product (HCT/Ps), etc., and/or methods of administering the same to human or non-human subjects. Combinatorial compositions and methods can be useful for treating subjects having an age-related disorder or condition, a clinical (e.g., metabolic) disorder, a chronic disease, an acute injury, and so forth. The prophylactic administration of combination treatments to subjects with no apparent condition or disorder can also be useful to delay or prevent certain conditions or disorders described herein.

[0018] Some embodiments can include a nucleic acid or nucleic acid construct. For instance, embodiments can include an expression vector or nucleic acid. The nucleic acid can encode a recombinant human alpha soluble Klotho protein, protein fragment, or protein variant. The nucleic acid can encode a native or non-native signaling sequence. For instance, the nucleic acid can encode a non-native signaling sequence upstream of (or N-terminal to) an encoded Klotho protein sequence. Some embodiments can include a nucleic acid construct, comprising a nucleic acid sequence encoding a recombinant protein, the recombinant protein comprising a Klotho protein sequence having at least 80% amino acid sequence identity to at least a portion of one of SEQ ID NO: 2 through SEQ ID NO: 70 or SEQ ID NO: 107 through SEQ ID NO: 120 or SEQ ID NO: 125 through SEQ ID NO: 128 or SEQ ID NO: 133 or SEQ ID NO: 152, preferably one of SEQ ID NO: 52, SEQ ID NO: 54, SEQ ID NO: 66, SEQ ID NO: 125 through SEQ ID NO: 128, SEQ ID NO: 133, and SEQ ID NO: 152; and, optionally at least a portion of an immunoglobulin Fc domain sequence, human serum albumin sequence, His (e.g., 6His) tag sequence, and/or a Twin-Strep tag sequence, with or without an optional linker sequence therebetween.

[0019] Some embodiments can include a cell line. The cell line can comprise (a plurality of) Chinese hamster ovary (CHO) cell(s), HEK-293 cells, or other suitable (protein expression) cell line. In some embodiments, the cells can be dihydrofolate reductase (DFR)-deficient CHO cells, such as CHO-S cells, or glutamine synthetase (GS)-deficient CHO cells, such as GS -/- CHO cells. The cells can contain one or more (copies of an) exogenous nucleic acid (comprising a transgene or cDNA) that encodes a polypeptide with at least 80% amino acid sequence identity to at least a portion of one of SEQ ID NO: 2 through SEQ ID NO: 70 or SEQ ID NO: 107 through SEQ ID NO: 120 or SEQ ID NO: 125 through SEQ ID NO: 128 or SEQ ID NO: 133 or SEQ ID NO: 152. The polypeptide can comprise a human recombinant alpha soluble Klotho protein. The exogenous nucleic acid can include a transgene or cDNA, preferably having at least 80% nucleic acid sequence identity to one of SEQ ID NO: 76 through SEQ ID NO: 106 or SEQ ID NO: 121 through SEQ ID NO: 124. In some embodiments, the nucleic acid can (also) include or encode a promoter (associated with the transgene) and/or an optional (exogenous) enzyme, such as a (functional) dihydrofolate reductase (DHFR) enzyme, (functional) glutamine synthetase (GS) enzyme, etc.

[0020] At least one embodiment includes a suspension cell culture comprising the cell line growing in a liquid medium, preferably comprising a carbon source, a nitrogen source, and/or one or more vitamins, minerals, salts, amino acids, supplements, or additives, such that the cells express the polypeptide encoded by the nucleic acid. The liquid medium can be (human, bovine, fetal bovine, or other) serum-free and/or animal (or animal-derived) protein (component)-free. For instance, the liquid medium can be free of bovine serum albumin, human serum albumin, etc. In some embodiments, the suspension cell culture can comprise a liquid medium, preferably a serum-free and/or animal protein component-free liquid medium, wherein the liquid medium preferably comprises a carbon source, a nitrogen source, and one or more vitamins, minerals, salts, amino acids, supplements, or additives, more preferably wherein the liquid medium lacks hypoxanthine, thymidine, and/or glutamine, and the cell line growing in the liquid medium such that the cells express the polypeptide encoded by the nucleic acid, the polypeptide comprising a recombinant Klotho protein.

[0021] Some embodiments include an extract of or from the cells, the liquid medium, or both of the suspension cell culture, the extract containing a recombinant protein having at least 80% amino acid sequence identity to at least a portion of one of SEQ ID NO: 2 through SEQ ID NO: 70 or SEQ ID NO: 107 through SEQ ID NO: 120 or SEQ ID NO: 125 through SEQ ID NO: 128 or SEQ ID NO: 133 or SEQ ID NO: 152. Certain embodiments include a human recombinant alpha soluble Klotho protein-containing extract of or from cells, liquid medium, or both (e.g., of the suspension cell culture). At least one embodiment includes an isolated recombinant protein having at least 80% amino acid sequence identity to at least a portion of one of SEQ ID NO: 2 through SEQ ID NO: 70 or SEQ ID NO: 107 through SEQ ID NO: 120 or SEQ ID NO: 125 through SEQ ID NO: 128 or SEQ ID NO: 133 or SEQ ID NO: 152.

[0022] Some embodiments can include a method of manufacturing recombinant Klotho protein (e.g., a recombinant human alpha soluble Klotho protein). Illustrative methods can comprise producing a recombinant Klotho protein in, for example, Chinese hamster ovary (CHO) cells or HEK-293 cells, preferably in dihydrofolate reductase (DHFR)-deficient CHO cells, more preferably in CHO-S cells, or preferably in glutamine synthetase (GS)-deficient CHO cells, more preferably in GS -/- CHO cells, the protein preferably having at least 80% amino acid sequence identity to at least a portion of one of SEQ ID NO: 2 through SEQ ID NO: 70 or SEQ ID NO: 107 through SEQ ID NO: 120 or SEQ ID NO: 125 through SEQ ID NO: 128 or SEQ ID NO: 133 or SEQ ID NO: 152.

[0023] In some embodiments, the manufacturing method can include growing the cells in a liquid medium, producing the recombinant soluble Klotho protein in the cells, and/or purifying a recombinant soluble Klotho protein-containing extract from the cells, liquid medium, or both. The extract can include at least about 90%, preferably at least about 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% dry weight recombinant soluble Klotho protein and/or less than about 1-100 ppm host cell proteins (HCP). The cells can be HEK-293 cells or dihydrofolate reductase (DHFR)-deficient CHO cells, such as CHO-S cells, or glutamine synthetase (GS)-deficient CHO cells, such as GS -/- CHO cells. The produced (expressed) protein can be released (e.g., secreted) from the cells into the liquid medium and/or can have one or more glycans attached thereto.

[0024] The cells can contain one or more exogenous nucleic acids that encode the protein and, optionally, a functional enzyme, such as dihydrofolate reductase enzyme, glutamine synthetase (GS) enzyme, etc. The exogenous nucleic acid can include a promoter (e.g., a strong promoter, weak promoter, etc.), such as a promoter customary or typical for use for expression of exogenous protein in cell. The exogenous nucleic acid can include a transgene or cDNA (e.g., under control of the promoter), preferably having at least 80% nucleic acid sequence identity to one of SEQ ID NO: 76 through SEQ ID NO: 106 or SEQ ID NO: 121 through SEQ ID NO: 124, or any other suitable nucleic acid sequence encoding a Klotho protein as described herein (e.g., S-Klotho variants).

[0025] The method can include introducing, such as by transfection, the exogenous nucleic acid into the cells. The method can include growing the cells in a liquid medium, such as a (human, bovine, fetal bovine, or other) serum-free and/or animal (or animal-derived) protein (component)-free medium. The medium preferably comprises a carbon source, a nitrogen source, and/or one or more vitamins, minerals, salts, amino acids, supplements, or additives, preferably in a bioreactor. Depending on the particular cell line, the method can include introducing an effective amount of methotrexate (MTX), methionine sulphoximine (MSX), or other agent into the liquid medium and/or selecting (e.g., by cell sub-cloning, limited dilution, fluorescence activated cell sorting (FACS), etc.) a suspension culture of viable cells growing in the liquid medium.

[0026] In some embodiments, selection and/or gene amplification can be performed by culturing the transfected cells in a selection medium, such as a medium lacking hypoxanthine and/or thymidine (e.g., -HT medium), glutamine, etc. In at least one embodiment, a low concentration(s) of MTX can be added or used to amplify the transfected nucleic acid (or gene(s) thereof) and, thereby, select for increased protein expression (e.g., in DHFR-deficient cells transfected with a DHFR transgene). Alternatively (or in addition), selection and/or gene amplification can be performed by adding MSX (an inhibitor of (endogenous) glutamine synthetase (GS)) to suspension cultures of cells having at least one (exogenous) glutamine synthetase (GS) transgene.

[0027] The method can include sub-culturing surviving cells or cultures (e.g., MTX-resistant and/or MSX-resistant cells or cultures). The selected suspension culture and/or selected cells can have or exhibit an increased production of the protein (e.g., by the cell), an increased concentration of the protein (e.g., in the liquid medium), and/or an increased copy number of the exogenous nucleic acid (e.g., per cell) (e.g., as compared to a non-selected suspension culture or cell).

[0028] The liquid medium can also include an effective amount of MTX and/or MSX in some embodiments. The suspension culture (or cells thereof) can (be selected to): exhibit an increased production of the protein (e.g., by the cells); exhibit an increased concentration of the protein (e.g., in the liquid medium); secrete the protein (e.g., into the liquid medium); and/or have an increased copy number of the exogenous nucleic acid (e.g., per cell), preferably as compared to a non-selected suspension culture. The protein can have one or more glycans attached thereto.

[0029] Some embodiments of the present disclosure relate to compositions configured or formulated to augment, improve, or increase natural soluble alpha Klotho protein production. Some embodiments include a composition or method for increasing (endogenous) Klotho protein levels in a subject. Some embodiments include a (nutraceutical or health supplement) composition for increasing Klotho protein levels, particularly serum soluble Klotho protein levels, in a subject. Some embodiments include products that, when administered to the subject, cause an increase in Klotho protein level(s), expression, or production, particularly endogenous soluble alpha Klotho protein level(s), expression, or production, in the subject.

[0030] Some embodiments of the present disclosure relate to compositions configured or formulated to attenuate Klotho protein damage or degradation. Some embodiments of the present disclosure relate to methods of manufacturing compositions of the present disclosure. Some embodiments of the present disclosure relate to use of compositions of the present disclosure or methods of using the same to treat human or non-human animal subjects. Some embodiments of the present disclosure relate to treatment methods involving compositions of the present disclosure, including administration thereof to human or non-human animal subjects. Such uses and treatment methods can increase endogenous Klotho protein levels, such as by augmenting natural soluble alpha Klotho protein production and/or attenuating Klotho protein damage or degradation.

[0031] Certain embodiments include compositions of matter that comprise a health supplement that, when administered to human or non-human animal (e.g., mammalian) subjects, increases the levels of endogenous, soluble alpha-Klotho protein in the human or non-human animal subjects. The composition or health supplement formulation can comprise (synthetic) chemical and/or natural components or ingredients. In other words, components or ingredients of the composition or health supplement can be or originate from (synthetic) chemical and/or natural sources. An exemplary composition can be adapted (or chemical configured), or include a plurality of components adapted (or chemical configured), to raise serum soluble Klotho protein levels by increasing or enhancing endogenous production of soluble Klotho protein by the mammalian subject.

[0032] An exemplary composition can comprise one or more components, preferably selected from the group consisting of, for example, Vitamin D3, Vitamin E, Vitamin C, Vitamin K, 3,5,4'-trihydroxy-trans-stilbene (Resveratrol), Pterostilbene, N-acetylcysteine (NAC), Troglitazone, Rosiglitazone, Notopterygium incisum Ting, Gentian (Root; Extract), Cordyceps (Cordyceps Sinensis (CS) Mycelium), Isoflavones (Soy), Genistein, Daidzein, Quercetin (dihydrate; dill, bay leaf, oregano), Docosahexaenoic acid (DHA), Astaxanthin, Sesamin (Semen Sesamin Nigrum (Black)), Sesame (Seed Extract), Rosmarinic acid (RA; (Marjoram)), Tetradecylthioacetic Acid (TTA), Dicalcium Phosphate (Anhydrous), Mircrocrystalline cellulose (MCC), Croscarmellose Sodium (Primellose), Stearing Acid, Magnesium Stearate, Alpha Lipoic Acid, Conjugate (alpha) Linoleic Acid (CLA), Probiotics, Activated Charcoal, and others as known in the art.

[0033] An exemplary composition can comprise one or more components, preferably in suitable nutraceutical concentrations, and preferably selected from the group consisting of, for example, vitamin C, vitamin D3, vitamin E, N-acetylcysteine (NAC), quercetin (dihydrate), rosmarinic acid (RA), pterostilbene, docosahexaenoic acid (DHA), nicotinamide riboside (NR), nicotinamide adenine dinucleotide (NAD+), nicotinamide mononucleotide (NMN), and one or more probiotic. The one or more probiotic comprises an effective amount of the Bifidobacterium species and/or strains Bifidobacterium lactis BL-04, Bifidobacterium bifidum/lactis BB-02, and Bifidobacterium longum BL-05, and the Lactobacillus species and/or strains Lactobacillus acidophilus LA-14, Lactobacillus rhamnosus LR-32, and Lactobacillus paracasei LPC-37.

[0034] Certain ingredients or components can have positive benefits and very low side effects in treating or affecting one or more conditions that have been associated with cellular and tissue dysfunctions that occur with aging. Certain ingredients or components can (directly or indirectly) increase the circulating plasma level of soluble alpha Klotho (s Klotho) levels in human or non-human animal subjects following administration thereof.

[0035] In at least one embodiment, a composition of the present disclosure can be or comprise a Dietary Supplement Health and Education Act of 1994 (DSHEA)-compliant nutritional supplement, which may be sold OTC, marketed and/or sold direct-to-consumer

(DTC), and/or purchased without a prescription/physician order. In some embodiments, a composition of the present disclosure can be or comprise an approved Food and Drug Administration (FDA) pharmaceutical.

[0036] In some embodiments, ingredients can be co-administered, preferably via at least some co-formulation. In some embodiments, ingredients can be co-administered in separate formulations. For example, in some embodiments, ingredients can be co-administered in a multi-pill, -capsule, or dosage pack. Some ingredients can be provided in solid, granular, powdered, liquid, or other form.

[0037] Some embodiments can include one or more (additional) ingredients or components, as described herein. For instance, some embodiments can include one or more recombinant (e.g., human or mammalian) Klotho proteins, protein fragments, and/or protein variants, as described herein. Certain embodiments can include expression nucleic acid constructs and/or vectors, cell lines and/or cell suspension cultures, and methods of manufacturing, purifying, and administering the one or more recombinant (e.g., human or mammalian) Klotho proteins, protein fragments, and/or protein variants to (human or non-human animal) subjects. Some embodiments can include one or more active ingredients, such as a pharmaceutical or prescription medications (e.g., ARBs (e.g., Losartan, Valsartan), testosterone, Vit. D receptor agonists (e.g., calcitriol, paricalcitol), PPAR (gamma) agonists (e.g., thiazolidinediones, troglitazone, rosiglitazone), and/or others described in the patent references incorporated above).

[0038] Some embodiments can include a composition, comprising a pharmaceutically effective amount of one or more recombinant Klotho protein and an effective amount of a composition (e.g., health supplement) formulated to increase endogenous Klotho protein levels or production (e.g., in mammalian subjects). In some embodiments, the recombinant Klotho protein can be co-administered with the composition. In some embodiments, the recombinant Klotho protein can be combined with a pharmaceutically-acceptable carrier. In some embodiments, the administered recombinant Klotho protein can raise serum soluble Klotho protein levels by providing exogenous Klotho protein, while the composition can raise serum soluble Klotho protein levels by increasing or enhancing (natural) production of Klotho protein by the patient or subject.

[0039] Some embodiments can include a treatment method. The method can comprise administering to a subject in need thereof a (pharmaceutically) effective amount of a composition of the present disclosure. The composition can include (i) a pharmaceutically effective amount of one or more recombinant soluble Klotho protein or protein variant of the present disclosure and/or (ii) a pharmaceutically effective amount of a composition (e.g., health supplement) formulated to increase endogenous Klotho protein levels or production (e.g., in mammalian subjects).

[0040] Some embodiments can include a method of treating Klotho deficiency (e.g., in a human or non-human animal (e.g., mammalian) patient or subject). The method can comprise administering a composition to the mammalian subject, optionally or preferably after diagnosing the mammalian subject with Klotho deficiency. The composition can comprise, for example, one or more of. a pharmaceutical composition comprising a pharmaceutically acceptable carrier or excipient and a pharmaceutically effective amount of a recombinant Klotho protein, recombinant Klotho protein fragment, or recombinant Klotho fusion protein disposed in the carrier or excipient; and a nutraceutical composition comprising a plurality of components adapted to raise serum soluble Klotho protein levels by increasing or enhancing endogenous production of soluble Klotho protein by the mammalian subject.

[0041] Some embodiments can include a method of treating an aging-related or other condition, disease, or disorder. Some embodiments can include a method of treating and/or preventing acute kidney injury (AKI), chronic kidney disease (CKD), or other condition. The subject to whom the composition is administered can be suffering from or at risk for a variety of conditions (e.g., disorders, diseases, injuries, illnesses, etc.). For example, some embodiments include a method of treating one or more chronic diseases and/or aging-related condition, such as a physical, mental, neurological, or other condition associated with (human) aging. Some embodiments can promote healing, recovery, longevity, and/or other beneficial outcome through one or more mechanisms or action. Administration of the inventive composition(s) can have a positive therapeutic effect on the course and outcome of the condition, including chronic and/or age-related disease and longevity in human subjects, and characterization of the same.

[0042] The pharmaceutically effective amount of the composition(s) can be sufficient to raise or increase the serum soluble Klotho protein concentration of the subject to a predetermined level, such as greater than, equal to, or between about 50 to 3000 picograms of soluble Klotho protein per milliliter of serum. The amount can also or alternatively be sufficient to maintain the serum soluble Klotho protein concentration of the subject at or above a predetermined threshold for a predetermined period of time. Embodiments can also include administering the composition(s) to a subject in need thereof so as to maintain the serum soluble Klotho protein concentration of the subject at or above a predetermined threshold for a predetermined period of time.

[0043] Embodiments can also include determining a serum soluble Klotho protein concentration of the subject. Embodiments can also include calculating a pharmaceutically effective amount of a composition of the present disclosure. Embodiments can also include determining a rate of soluble Klotho protein decline in the serum of the subject. Embodiments can also include calculating a subsequent dosage time at which the serum soluble Klotho protein concentration of the subject will be at or below a second predetermined level based on the determined rate. Embodiments can also include calculating a subsequent dosage time and/or amount of the composition sufficient to raise the serum soluble Klotho protein concentration of the subject from the second predetermined level to the first predetermined level. Embodiments can also include administering the subsequent dosage amount of the composition to the subject. Certain embodiments can include prescribing a regular (e.g., daily) dose or dosage form of the composition to the subject (e.g., based on determined levels of serum soluble Klotho protein concentration of the subject).

[0044] In certain embodiments, the composition (e.g., protein or supplement) or raised soluble Klotho protein levels can (be effective to) modulate the IGF-1 and/or Wnt signaling pathways, exhibit -glucuronidase and/or sialidase activity, suppress the p53/p2I signaling pathway, and/or reduce H202-induced cell senescence and apoptosis, preferably through suppression of the p53/p21 signaling pathway. The protein or raised protein levels can function or be functional as a humoral factor, preferably exhibiting pleiotropic activity and/or preferably in the regulation of oxidative stress, growth factor signaling, ion homeostasis, and/or regulation of activity of glycoproteins on the cell surface, such as one or more ion channel proteins and/or growth factor receptors, such as Insulin/Insulin-Like Growth Factor-i receptor.

[0045] In certain embodiments, the composition (e.g., protein or supplement) or raised soluble Klotho protein levels can (be effective to) treat one or more aging-related condition (or condition associated with (human) aging), such as frailty, bone density loss or bone mineral density loss, weight loss, muscular atrophy or degeneration, decline in muscle mass, decline in muscle strength, hand strength, leg strength, or physical fitness, decline in movement, freedom of movement, quality of life assessment, ejection fraction, or exercise capacity, decline in learning, learning capacity, memory, or intellectual quotient, cognitive deterioration or forgetfulness, decline in cognitive capacity or function, decline in synaptic plasticity or synaptic function, and cellular senescence.

[0046] In certain embodiments, the composition (e.g., protein or supplement) or raised soluble Klotho protein levels can (be effective to) treat one or more aging-related condition

(or condition associated with (human) aging), such as Alzheimer's disease, Parkinson's disease, dementia or vascular dementia, amyotrophic lateral sclerosis (ALS) or motor neuron disease (MND), atrial fibrillation, chronic obstructive pulmonary disease (COPD), fibromyalgia, adult onset diabetes, arthritis or rheumatoid arthritis, osteoarthritis, osteoporosis, glaucoma, cataracts, macular degeneration and other eye diseases/disorders, multiple sclerosis (MS), lupus, and/or ulcerative colitis.

[0047] In certain embodiments, the composition (e.g., protein or supplement) or raised soluble Klotho protein levels can (be effective to) treat one or more other diseases or conditions. For instance, some embodiments of the present disclosure can be useful in one or more of treating cancer, lowering serum phosphate levels in a patient, treating diabetes or a diabetes-related condition (e.g., Type 1 diabetes mellitus, etc.) in a subject in need of such treatment, treating a heart condition (e.g., cardiovascular disease, left ventricular hypertrophy (LVH), pathological LVH and/or congestive heart failure, etc.) in a subject, treating acute lung injury in a subject (e.g., using nanoparticles), protecting the lung of a patient against oxidant injury, detecting early acute kidney injury in critically ill patients, attenuating vascular calcification in a subject, improving cognition, treating renal and/or liver ischemia, modulating stress response in (human) senescent endothelial cells, prophylactically and/or therapeutically treating, preventing, attenuating, arresting, and/or reversing acute and/or chronic kidney injury, disease, or disease progression and/or uremic cardiomyopathy, reversing or attenuating age-related therapy resistance in melanoma or other cancers, targeting apoptosis of senescent cells, preferably restoring tissue homeostasis thereby, and a variety of other indications.

[0048] Accordingly, embodiments can also include a composition for use in treating one or more aging-related or other conditions. An exemplary method of treating an aging-related or other condition, disease, or disorder, the method comprising administering to a subject in need thereof an effective amount of a composition of the present disclosure. The composition can include (i) a supplement, as described herein, and/or (ii) a recombinant soluble Klotho protein (e.g., having at least 80% amino acid sequence identity to at least a portion of one of SEQ ID NO: 2 through SEQ ID NO: 70 or SEQ ID NO: 107 through SEQ ID NO: 120 or SEQ ID NO: 125 through SEQ ID NO: 128 or SEQ ID NO: 133 or SEQ ID NO: 152). Optionally, the composition can include a pharmaceutically-acceptable carrier or excipient.

[0049] Some embodiments include a method of detecting and/or quantifying endogenous and/or exogenous Klotho protein, and more particularly endogenous and/or exogenous soluble alpha Klotho protein. Some embodiments include a method of diagnosing Klotho protein deficiency in a subject. Some embodiments include a product (e.g., a system or kit) for detecting and quantifying Klotho protein levels, and more particularly endogenous and/or exogenous soluble alpha Klotho protein levels. Some embodiments include methods of diagnosing Klotho protein deficiency in a subject. Some embodiments can include a method of treating Klotho deficiency in a subject.

[0050] Certain embodiments can include or utilize a blood or serum sample of the (mammalian) subject, preferably capillary blood and/or blood obtained from a finger-prick or other non-phlebotomic (non-venesectic) blood draw technique. It will be appreciated, however, that phlebotomic (venesectic) and other suitable blood draw techniques are also contemplated herein.

[0051] Some embodiments include a kit. Embodiments can include, for example, a sample collection container. The container can have an opening configured for receiving capillary blood. The capillary blood can contain, or be suspected of containing, an amount of soluble Klotho protein in some embodiments. Embodiments can include a sample preservative or anti-coagulant, preferably comprising one or more of EDTA and Heparin. The sample preservative or anti-coagulant can be disposed in a sample collection compartment of the container in some embodiments. The solution can be configured to stabilize soluble Klotho protein for at least 24 hours, and up to 7 days or more, at room temperature or without freezing. Embodiments can optionally include a capillary blood sampling device, preferably comprising a lancing device or lancet.

[0052] Some embodiments include a method. For example, some embodiments can include a method of stabilizing Klotho protein in a mammalian blood sample. Embodiments can include, for example, drawing or obtaining capillary blood from a mammalian subject and storing the capillary blood in a container for at least 24 hours at room temperature or without freezing. The container can have a preservative or anti-coagulant disposed therein, such that the preservative or anti-coagulant is mixed with the capillary blood in the container. The preservative or anti-coagulant can stabilize the soluble Klotho protein for at least 24 hours at room temperature or without freezing. The preservative or anti-coagulant can be or comprise one or more of heparin, lithium heparin, EDTA, and K 2 EDTA.

[0053] Embodiments can also include collecting the capillary blood in a container, and/or mixing the capillary blood with a preservative or anti-coagulant to form a mixture. In some embodiments, drawing capillary blood can include lancing skin of the mammal with a lancet. In some embodiments, the step of collecting the capillary blood in the container can include collecting at least or about 10-1000ul, preferably about 50-200ul of the capillary blood in the container Some embodiments can include storing the mixture or allowing the mixture to be stored for at least 3 days at room temperature or without freezing, the preservative or anti coagulant stabilizing the soluble Klotho protein for the at least 3 days at room temperature or without freezing.

[0054] Some embodiments can optionally include assaying the mixture for the presence of the soluble Klotho protein. The step of assaying the mixture for the presence of the soluble Klotho protein can include detecting the soluble Klotho protein and/or quantifying the amount of soluble Klotho protein. Detecting the soluble Klotho protein and/or quantifying the amount of soluble Klotho protein can include contacting the mixture with an antibody configured to bind the soluble Klotho protein. Detecting the soluble Klotho protein and/or quantifying the amount of soluble Klotho protein can include performing ELISA on the mixture using an antibody configured to bind the soluble Klotho protein. Other detection methods may include mass spectrometry or Multi-Analyte Profiling (xMAP), such as Luminex technology (e.g., miniaturized liquid array bioassay, small lasers, light emitting diodes (LEDs), digital signal processors, photo detectors, and/or charge-coupled device imaging), etc.

[0055] Some embodiments include a method of diagnosing Klotho deficiency in a mammalian subject or a method of treating Klotho deficiency in a mammalian subject. Embodiments can include, for example, providing or obtaining a fluid biological sample. The sample can include mammalian serum, preferably in the form of capillary blood. The method can optionally include mixing the mammalian serum with a preservative or anti-coagulant to form a mixture. The sample can also or alternatively include a mixture comprising mammalian serum, preferably in the form of capillary blood, and a preservative or anti coagulant. The method can include assaying the mixture for the presence of soluble Klotho protein. The step of assaying the mixture for the presence of the soluble Klotho protein can include detecting the presence of the soluble Klotho protein, if any, in the mixture and/or quantifying the amount of the soluble Klotho protein, if any, in the mixture, optionally after storing the Klotho-stabilized mixture for a period of time at room temperature or without freezing. The method can include diagnosing the mammalian subject with Klotho deficiency when no soluble Klotho protein is detected in the mixture or when the amount of quantified soluble Klotho protein in the mixture is less than a predetermined amount. In some embodiments, diagnosing the mammalian subject with Klotho deficiency can include displaying the Klotho deficiency determination or diagnosis on a user interface of the computer system and/or producing a file or report, in physical or electronic form, that displays the Klotho deficiency determination or diagnosis.

[0056] In some embodiments, providing or obtaining a fluid biological sample can include drawing capillary blood from the mammalian subject and/or collecting capillary blood in a container. In some embodiments, the step of assaying the mixture for the presence of soluble Klotho protein can include performing ELISA on the mixture using an antibody configured to bind the soluble Klotho protein. Some embodiments can include administering a composition to the mammalian subject when no soluble Klotho protein is detected in the mixture or when the amount of quantified soluble Klotho protein in the mixture is less than a predetermined amount. Mass spectrometry can also or alternatively be performed.

[0057] The disclosed strategies, products, and/or health intervention methods specifically configured to increase circulating and/or endogenous levels of soluble Klotho may help to ameliorate the situation and problems associated with decreased Klotho levels in patients.

[0058] Some embodiments may include any of the features, options, and/or possibilities set out elsewhere in the present disclosure, including in other aspects or embodiments of the present disclosure. It is also noted that each of the foregoing, following, and/or other features described herein represent a distinct embodiment of the present disclosure. Moreover, combinations of any two or more of such features represent distinct embodiments of the present disclosure. Such features or embodiments can also be combined in any suitable combination and/or order without departing from the scope of this disclosure. Thus, each of the features described herein can be combinable with any one or more other features described herein in any suitable combination and/or order. Accordingly, the present disclosure is not limited to the specific combinations of exemplary embodiments described in detail herein.

[0059] Additional features and advantages of exemplary embodiments of the present disclosure will be set forth in the description that follows, and in part will be obvious from the description, or may be learned by the practice of such exemplary embodiments. The features and advantages of such embodiments may be realized and obtained by means of the instruments and combinations particularly pointed out in the appended claims. These and other features will become more fully apparent from the following description and appended claims, or may be learned by the practice of such exemplary embodiments as set forth hereinafter. DETAILED DESCRIPTION

[0060] Embodiments of the present disclosure relate to compositions and methods for increasing serum soluble Klotho protein levels in a human or non-human animal (or mammal) subject and to compositions and methods for monitoring, detecting, and/or quantifying Klotho protein level(s), particularly endogenous and/or exogenous soluble alpha Klotho protein level(s), and/or for diagnosing and/or treating Klotho protein deficiency in the subject. Some embodiments include one or more compositions, comprising (i) recombinant human Klotho proteins, protein fragments, and/or protein variants, expression nucleic acid constructs and/or vectors, cell lines and/or cell suspension cultures, and/or (ii) products (e.g., supplements) that, when administered to the subject, cause an increase Klotho protein level(s), expression, or production, particularly endogenous soluble alpha Klotho protein level(s), expression, or production, in the subject. Certain embodiments include methods of manufacturing, purifying, and administering the compositions of the present disclosure to the (human or non-human animal) subjects and/or methods for increasing Klotho protein level(s), expression, or production, particularly (exogenous and/or endogenous) soluble alpha Klotho protein level(s), expression, or production, in the subject. Some embodiments include methods for monitoring, detecting, and/or quantifying Klotho protein level(s), particularly (endogenous and/or exogenous) soluble alpha Klotho protein level(s), and/or for diagnosing Klotho protein deficiency in the subject.

[0061] Before describing various embodiments of the present disclosure in detail, it is to be understood that this disclosure is not limited only to the specific parameters, verbiage, and description of the particularly exemplified systems, methods, and/or products that may vary from one embodiment to the next. Thus, while certain embodiments of the present disclosure will be described in detail, with reference to specific features (e.g., configurations, parameters, properties, steps, components, ingredients, members, elements, parts, and/or portions, etc.), the descriptions are illustrative and are not to be construed as limiting the scope of the present disclosure and/or the claimed invention. In addition, the terminology used herein is for the purpose of describing the embodiments, and is not necessarily intended to limit the scope of the present disclosure and/or the claimed invention.

[0062] While the detailed description is separated into sections, the section headers and contents within each section are for organizational purposes only and are not intended to be self-contained descriptions and embodiments or to limit the scope of the description or the claims. Rather, the contents of each section within the detailed description are intended to be read and understood as a collective whole, where elements of one section may pertain to and/or inform other sections. Accordingly, embodiments specifically disclosed within one section may also relate to and/or serve as additional and/or alternative embodiments in another section having the same and/or similar products, methods, and/or terminology.

[0063] To facilitate understanding, like references (i.e., like naming of components and/or elements) have been used, where possible, to designate like elements common to different embodiments of the present disclosure. Similarly, like components, or components with like functions, will be provided with similar reference designations, where possible. Specific language will be used herein to describe the exemplary embodiments. Nevertheless it will be understood that no limitation of the scope of the disclosure is thereby intended. Rather, it is to be understood that the language used to describe the exemplary embodiments is illustrative only and is not to be construed as limiting the scope of the disclosure (unless such language is expressly described herein as essential).

[0064] For the sake of brevity, the present disclosure may recite a list or range of numerical values. It will be appreciated, however, that where such a list or range of numerical values (e.g., greater than, less than, up to, at least, and/or about a certain value, and/or between two recited values) is disclosed or recited, any specific value or range of values falling within the disclosed values or list or range of values is likewise specifically disclosed and contemplated herein. By way of illustrative example, disclosure of "up to 1,000 mg" of a particular ingredient or component includes a specific disclosure of. (i) any value greater than zero and less than or equal to 1,000 milligrams, including but not limited to 0.01 mg, 1 mg, 5 mg, 10 mg, 50 mg, 100 mg, 500 mg, 750 mg, 990 mg, and 1,000 mg; and/or (ii) any range of values from or between greater than zero and less than or equal to 1,000 milligrams, including but not limited to 0.01-1,000 mg, 1 mg - 990 mg, 5 mg - 750 mg, 10 mg - 500 mg, and 50 mg 100 mg. Similarly, disclosure of "at least 80% amino acid sequence identity" or "80%-100% amino acid sequence identity" includes a specific disclosure of: (i) any whole percentage value between 80% and 100%, including 81%, 8 2 %, 8 3 %, 8 4 %, 8 5 %, 8 6 %, 8 7 %, 8 8 %, 8 9 %,

9 0% , 9 1%, 9 2 %, 93%, 94%, 95%, 9 6 %, 97%, 9 8 %, 99%, and 100%, as well as any fraction of a percent value therebetween; and/or (ii) any range of percentage values between 80% and 100%, including, by way of non-limiting example, 81%-100%, 82%-100%, 83%-100%, 84%-100%, 85%-100%, 86%-100%, 87%-100%, 88%-100%, 89%-100%, 90%-100%, 91% 100%, 92%-100%,93%-100%,94%-100%,95%-100%,96%-100%,97%-100%,98%-100%, and 99%-100%. Abbreviated list of defined terms

[0065] To assist in understanding the scope and content of the foregoing and forthcoming written description and appended claims, a select few terms are defined directly below.

[0066] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present disclosure pertains.

[0067] Various aspects of the present disclosure, including systems, methods, and/or products may be illustrated with reference to one or more embodiments, which are exemplary in nature. As used herein, the terms "embodiment" mean "serving as an example, instance, or illustration," and should not necessarily be construed as preferred or advantageous over other aspects disclosed herein. In addition, reference to an " embodiment" of the present disclosure or invention is intended to provide an illustrative example without limiting the scope of the invention, which is indicated by the appended claims.

[0068] As used in this specification and the appended claims, the singular forms "a," "an" and "the" each contemplate, include, and specifically disclose both the singular and plural referents, unless the context clearly dictates otherwise. For example, reference to a "protein" contemplates and specifically discloses one, as well as a plurality of (e.g., two or more, three or more, etc.) proteins. Similarly, use of a plural referent does not necessarily require a plurality of such referents, but contemplates, includes, specifically discloses, and/or provides support for a single, as well as a plurality of such referents, unless the context clearly dictates otherwise.

[0069] As used throughout this disclosure, the words "can" and "may" are used in a permissive sense (i.e., meaning having the potential to), rather than the mandatory sense (i.e., meaning must). Additionally, the terms "including," "having," "involving," "containing," "characterized by," variants thereof (e.g., "includes," "has," and "involves," "contains," etc.), and similar terms as used herein, including the claims, shall be inclusive and/or open-ended, shall have the same meaning as the word "comprising" and variants thereof (e.g., "comprise" and "comprises"), and do not exclude additional, un-recited elements or method steps, illustratively.

[0070] Except in the examples, or where otherwise expressly indicated, all numerical quantities in this description indicating amounts of material or conditions of reaction and/or use are to be understood as modified by the word "about". As used herein, the term "about," with regard to a value, means +/-10% of the stated value or amount represented thereby. For instance, throughout the present disclosure, the term "about" is used in connection with a percent concentration or composition of a component or ingredient (e.g., in a mixture, such as a fluid or liquid mixture, aqueous mixture, solution, etc., optionally or preferably measured as a w/w percent, w/v percent, v/v percent, etc.). In such instance, the term "about" and/or the term "+/- 10 % " implies and/or includes +/-10% of the stated numeric value, as opposed to +/ 10 percentage points of the recited percent. By way of example, where 20% w/w of a component or ingredient reflects 20g of the component or ingredient per 100mL of total mixture, the term "about" and/or the term "+/-10%" implies and/or includes a recited range from 18g to 22g (i.e., from 18% w/w to 22% w/w), not a range of 10% w/w to 30% w/w. Alternatives for so-called "about" values and/or +/-10% include +/-1%, +/-2%, +/-3%, +/ 4%, +/-5%, +/-6%, +/-7%, +/-8%, or +/-9% of the stated value, each of which is contemplated as a suitable alternative to or substitute for the term "about" or the use of+/ 10% herein.

[0071] As used herein, the terms "approximately" and "substantially" represent or imply an (or any) amount close to the stated amount (e.g., that still performs a desired function or achieves a (desired or expected) result). For example, the terms "approximately" and "substantially" may refer to an amount that is within, or less than, 10%, 5%, 1%, 0.1%, 0.01%, or other percent of a stated amount. As used herein, the term "substantially devoid" means (1) an undetectable or unquantifiable amount, (2) less than or below an amount generally considered by those skilled in the art to reflect a detectable or quantifiable amount, and/or (3) less than or below an amount generally considered by those skilled in the art to be functional or able to achieve a (desired or expected) result (e.g., less than 10%, 5%, 1%, 0.1%, 0.01%, or other percent).

[0072] By "Quantum satis" (also referred to as "q.s." or "qs") is meant the amount that is enough. Accordingly, a component or ingredient "qs 100%," "provided at qs 100%," or "qs to 100%" indicates that the component or ingredient is provided or included in an amount sufficient to complete the composition or to bring the total (of all components, whether recited or not) to 100%. It is noted, however, that a (final) component or ingredient "qs 100%," "provided at qs 100%," or "qs to 100%" does not indicate that the mixture consists of, consists essentially of, or only contains the components listed or recited immediately before the "qs 100%" component. In other words, "qs 100%," and similar terms, is meant to be an open-ended expression indicating the source of the remainder, whatever that remainder may be.

[0073] As used herein, the term "product(s)" includes compositions, formulations, and mixtures, as well as devices, apparatus, assemblies, kits, systems, and so forth. Similarly, the term "method" includes processes, procedures, steps, and so forth.

[0074] As used herein, a "feature" or "aspect" of the present disclosure or embodiment disclosed herein refers to a property, attribute, component, ingredient, element, member, part, portion, (method) step, or other facet of the subject matter at hand.

[0075] The word "or" as used herein generally means any one member of a particular list, but also includes any combination of two or more members of said list. Similarly, the term "and" can be interchangeable with the terms "or," either of which can be understood to mean "and/or".

[0076] The term "comprising" is synonymous with "including," "having, "containing," or "characterized by." These terms are inclusive and open-ended and do not exclude additional, unrecited elements or method steps.

[0077] The phrase "consisting of' excludes any element, step, or ingredient not specified in the claim. When this phrase appears in a clause of the body of a claim, rather than immediately following the preamble, it limits only the element set forth in that clause; other elements are not excluded from the claim as a whole.

[0078] The phrase "consisting essentially of' limits the scope of a claim to the specified materials or steps, plus those that do not materially affect the basic and novel characteristic(s) of the claimed subject matter.

[0079] The terms "comprising", "consisting of', and "consisting essentially of' can be alternatively used. When one of these three terms is used, the presently disclosed and claimed subject matter can include the use of either of the other two terms.

[0080] The terms "plurality" and "at least two" are used interchangeably.

[0081] The term "condition" refers to any disorder, disease, injury, or illness, as understood by those skilled in the art, that is manifested or anticipated in a patient. Manifestation of such a condition can be an early, middle, or late stage manifestation, as known in the art, including pre-condition symptoms, signs, or markers. Anticipation of such a condition can be or include the predicted, expected, envisioned, presumed, supposed, and/or speculated occurrence of the same, whether founded in scientific or medical evidence, risk assessment, or mere apprehension or trepidation.

[0082] The term "patient," as used herein, is synonymous with the term "subject" and generally refers to any animal under the care of a medical professional, as that term is defined herein, with particular reference to (i) humans (under the care of a doctor, nurse, or medical assistant or volunteer) and (ii) non-human animals, such as non-human mammals (under the care of a veterinarian or other veterinary professional, assistant, or volunteer).

[0083] The terms "medical professional" as used herein, generally refers to any individual or entity that is responsible for or participates in providing health care to an animal, including human and non-human animals, such as non-human mammals, with particular emphasis on licensed health care providers or unlicensed providers, such as assistants, technicians, and/or volunteers, particularly those covered under the (blanket) license or insurance of a health care provider. This term may, when contextually appropriate, include an oncologist, a surgeon, a physician's assistant, a nurse, a phlebotomist, a veterinarian, etc.

[0084] The term "cancer" refers to an abnormal, typically uncontrolled, growth of cells. A "cancerous cell" as used herein comprises a malignant cell having an abnormal, typically uncontrolled, growth. As such, the term cancer is an umbrella term encompassing a plurality of different distinctive diseases characterized by malignant cells growing in a typically uncontrolled manner.

[0085] The term "diagnosis," or diagnosing," and similar terms, as used herein, is not intended to convey or require (in all cases) a certified, regulatory-compliant, medical diagnosis, as required or regulated by the U.S. Food and Drug Administration (FDA) or any other government or non-government entity, organization, or agency. Rather, "diagnosis," or diagnosing," and similar terms, as used herein, relates to providing information that may be indicative of a condition and/or helpful in making a determination related to the condition.

[0086] The term "co-administration" and similar terms refer to concurrent, sequential, and/or combined administration of two or more components. For instance, two components can be co-administered by administering each component in a separate dosage concurrently, simultaneously, or sequentially (e.g., distinct administrations separated by a period of time). The period of time can be very small (e.g., substantially, immediately following a first administration) or longer (e.g., 1-60 seconds, 1-60 minutes, 1-24 hours, 1-7 days, 1-4 weeks, 1-12 months, and so forth, or any valueorrangeofvalues therebetween). Concurrent or simultaneous administration can include overlapping administration timeframes for the two or more components or administration of a combination product comprising a mixture of the two or more components.

[0087] As used herein, "room temperature" may refer to any temperature above freezing (0°C, or other (equivalent) freezing temperature, depending on the presence of freezing point adjusting components) and below normal human body temperature (37°C, or other (equivalent) boiling temperature, depending on the presence of boiling point adjusting components), preferably above about 4°C and below about 35°C, more preferably between about 5°C and about 32°C, between about 8°C and about 30°C, between about 10°C and about

30°C, between about 10°C and about 25°C, between about 10°C and about 20°C, between about 10°C and about 15°C, between about 15°C and about 30°C, between about 15°C and about 25°C, between about 15°C and about 20°C, between about 20°C and about 30°C, between about 20°C and about 25°C, between about 20°C and about 22°C, or any value or range of values therebetween.

[0088] As used herein, "refrigeration" may refer to any temperature above freezing (0°C) and below about 32°C, preferably between about 1C and about 30°C, between about 1C and about 25°C, between about 1C and about 20°C, between about 1C and about 15°C, between about 2°C and about 20°C, between about 2°C and about 15°C, between about 3C and about 20°C, between about 3C and about 15°C, between about 4°C and about 20°C, between about 4°C and about 15°C, or any value or range of values therebetween.

[0089] As used herein, "nucleic acid," and similar terms, refer to a naturally occurring or synthetic oligonucleotide or polynucleotide, whether DNA or RNA or DNA-RNA hybrid, single-stranded or double-stranded, sense or antisense. In particular, nucleic acids can include, without limitation, DNA, RNA, cDNA, gDNA, ssDNA, dsDNA or any combination thereof Nucleic acids of the disclosure can also include nucleotide or nucleic acid analogs (e.g., BrdU), and non-phosphodiester (internucleoside) linkages or backbones (e.g., peptide nucleic acid (PNA) or thiodiester linkages), known in the art.

[0090] The terms "peptide" or "protein" as used herein refers to any peptide, oligopeptide, polypeptide, gene product, expression product, or protein. A peptide is comprised of consecutive amino acids. The terms "peptide" or "protein" encompass naturally occurring or synthetic molecules.

[0091] As used herein, the term "standard amino acid" includes: alanine - ala - A; arginine - arg - R; asparagine - asn - N; aspartic acid - asp - D; cysteine - cys - C; glutamine - gln Q; glutamic acid - glu - E; glycine - gly - G; histidine - his - H; isoleucine - ile - I; leucine leu - L; lysine - lys - K; methionine - met - M; phenylalanine - phe - F; proline - pro - P; seine - ser - S; threonine - thr - T; tryptophan - trp - W; tyrosine - tyr - Y; and valine - val V.

[0092] As used herein, "codon optimized" or "codon optimization" refers to the process of modifying or changing codons in a nucleotide sequence to codons that are preferred or more closely match the pattern of codon usage in the organism used for expression of the molecule. Thus, codons can be optimized for usage in a particular organism in which expression is desired based on known codon usage in the organism in order to enhance the effectiveness of expression of the nucleic acid, e.g., to achieve faster translation rates and high accuracy. The codon usage in a particular organism is known.

[0093] The encoding nucleic acid molecule can be a modified wild-type or a codon optimized sequence, where the codons are optimized for expression in a particular host cell, such as mammalian cells, e.g., CHO cells or 293 cells, or in a yeast, or a plant cell, eukaryotic cells.

[0094] In particular examples, the nucleic acid sequence can be codon optimized, for example, to increase expression levels of the encoded sequence. The particular codon usage is dependent on the host organism in which the modified polypeptide is expressed. One of skill in the art is familiar with optimal codons for expression in mammalian or human cells, bacteria or yeast, including for example E. coli or Saccharomyces cerevisiae. For example, codon usage information is available from the Codon Usage Database available at kazusa.or.jp.codon (see e.g., Richmond (2000) Genome Biology, 1:241 for a description of the database. See also, Forsburg (2004) Yeast, 10:1045-1047; Brown et al. (1991) Nucleic Acids Research, 19:4298; Sharp et al. (1988) Nucleic Acids Res., 12:8207-8211; Sharp et al. (1991) Yeast, 657-78).

[0095] The first definition of an acronym or other abbreviation applies to all subsequent uses herein of the same abbreviation and applies mutatis mutandis to normal grammatical variations of the initially defined abbreviation; and, unless expressly stated to the contrary, measurement of a property is determined by the same technique as previously or later referenced for the same property. Illustrative Embodiments

[0096] Illustrative embodiments of the present disclosure include, but are not limited to, compositions, compositions of matter, products, articles of manufacture, formulations, combination products, co-administrations, co-formulations, dosages, process, methods, treatment protocols, diagnostic methods, kits, and so forth. Products and Methods for Stabilizing Klotho Protein in Blood

[0097] The stability of Klotho proteins (e.g., soluble Klotho) in blood or serum, especially at room temperature, and more especially for (extended) periods of time, has not been reported previously. Figure 3 illustrates the surprising and unexpected stability of Klotho protein in human serum at room temperature, as well as other temperatures, over extended periods of time.

[0098] Without being bound to any theory, typical blood or serum protein diagnostics require a venous blood draw to collect a suitable amount of blood for monitoring, detecting, and/or quantifying protein (levels). Moreover, the drawn blood samples are typically processed soon after sampling (e.g., same day, within minutes or hours of sampling, etc.) or refrigerated (below room temperature) to preserve protein and/or sample stability. The Inventors have found, however, that Klotho protein in blood can be stable for up to 7 days, 9 days, 14 days, or more, at room temperature, in some embodiments of the present disclosure. In some embodiments, for instance, adding EDTA and/or Heparin to the sample can stabilize Klotho protein for at least 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 15 days, 16 days, 17 days, 18 day, 19 days, 20 days, 21 days, 22 days, 23 days, 24 days, 25 days, 26 days, 27 days, 28 days, 29 days, or 30 days at room temperature (data not shown). By way of non-limiting example, levels of Klotho in blood samples collected from four donors were relatively constant over a 7-day period (and over a 14-day period), at room temperature, with added EDTA and/or Heparin (see Figure 3). Additionally, both tested anticoagulants, EDTA and Heparin, showed no significant difference in terms of Klotho concentration. This was surprising and unexpected to the inventors.

[0099] Room temperature storage may be important for commercial diagnostic applications, in which refrigeration of hundreds, thousands, tens of thousands, etc., of samples may not be commercially practical (logistically and/or monetarily). With a suitable room temperature stabilizing method, as described here, commercial diagnostic testing of Klotho blood or serum levels can be accomplished.

[00100] In light of the foregoing, an embodiment of the present disclosure can include a method and/or product that combines EDTA and/or Heparin to a biological sample (e.g., blood or serum) that contains Klotho protein. Some illustrative products can include a sample collection kit comprising a sample collection container and a sample preservation composition.

[00101] Some embodiments include a method of stabilizing Klotho protein in a mammalian blood sample. The method can include obtaining capillary blood from a mammalian subject. The capillary blood can contain (or be suspected of containing) an amount of soluble Klotho protein. The method can include storing the capillary blood (e.g., in a container) for at least 24 hours (or, preferably, at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 18, 21, 28, or 30 days, or more), preferably at room temperature. The capillary blood sample can be mixed with a preservative or anti-coagulant. For example, the container can have a preservative or anti coagulant disposed therein or added thereto, such that the preservative or anti-coagulant is mixed with the capillary blood in the container. The preservative or anti-coagulant can be or comprise one or more of heparin, lithium heparin, EDTA, and K 2 EDTA. The preservative or anti-coagulant can stabilize the soluble Klotho protein for the at least 24 hours (or longer), preferably at room temperature. It will be appreciated, however, that refrigeration and/or freezing are also contemplated herein.

[00102] In addition, the Inventors have found that measured Klotho protein levels from finger stick (about 10-1000ul, preferably about 50-200ul of blood) are consistent with Klotho protein levels measured from venous blood draw in the same subject. Thus, Klotho protein can be accurately, reproducibly, and reliably measured in relatively small, commercially practical volumes of blood. This was surprising and unexpected to the inventors. In particular, the Inventors had expected that the quantity of blood collected in a standard vial may be required in order to accurately, reproducibly, and reliably measure Klotho protein in blood.

[00103] Without being bound to any theory, venous blood draws (e.g., for FDA-approved or other diagnostics) typically require a professional phlebotomist. Venous blood draws are also inconvenient and painful to the patient. A finger stick method, on the other hand, is convenient and low cost. Commercially, direct-to-consumer applications (e.g., diagnostic kits) may require at-home blood sampling. In such cases, a venous blood draw may be undesirable and/or impractical. Embodiments of the present disclosure can permit capillary blood sampling with a simple and convenient finger prick (or other means of sampling capillary blood). The amount of capillary blood sampled can be, for example, between about 10-1000ul, preferably about 20-800ul, more preferably about 30-600ul, still more preferably about 40-400ul, still more preferably about 50-200ul of capillary blood.

[00104] In light of the foregoing, some embodiments of the present disclosure can include products and methods for capillary (non-venous, non-phlebotomic, etc.) sampling of blood or serum. Some embodiments can include a capillary blood sampling device. Illustratively, the capillary blood sampling device can be or comprise a lancing device and/or comprise a (blood) lancet). In some embodiments, the blood sampling or lancing device can be or comprise a finger stick apparatus, such as a (spring-loaded) finger pricker. It will be appreciated, however, that the present disclosure is not limited to fingers and quick-prick devices. In some embodiments, the lancing device or lancet thereof can be disposable and/or replaceable. Embodiments can also include written instructions for using the kit to collect a blood sample.

[00105] An illustrative method of stabilizing Klotho protein in a mammalian blood sample can comprise obtaining capillary blood from a mammalian subject, the capillary blood containing an amount of soluble Klotho protein, and storing the capillary blood in a container for at least 24 hours at room temperature, the container having a preservative or anti coagulant disposed therein, the preservative or anti-coagulant being mixed with the capillary blood in the container, the preservative or anti-coagulant stabilizing the soluble Klotho protein for at least 24 hours at room temperature, the preservative or anti-coagulant comprising one or more of heparin, lithium heparin, EDTA, and K 2 EDTA. In some embodiments, storing the capillary blood mixed with the preservative or anti-coagulant for at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 18, 21, 28, or 30 days at room temperature, the preservative or anti-coagulant stabilizing the soluble Klotho protein for at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 18, 21, 28, or 30 days at room temperature. The sample of mixture may also be refrigerated in certain embodiments.

[00106] In certain embodiments, a small amount of blood (1-4 drops, about 10-1000ul, preferably about 50-200ul can be collected (e.g., at home) and sent via unfrozen, unrefrigerated, or uncooled (e.g., ambient or room temperature), normal shipping methods to a diagnostic facility. This provides a substantial benefit over existing methods and products. Accordingly, personal, at-home, or other non-clinic-based testing or diagnostics (e.g., lateral flow with quantification/measurement indicator, home ELISA kits, etc.) are contemplated herein. It will also be appreciated, however, that clinical or clinic-based testing or diagnostics are contemplated herein. Products and Methods for Measuring Klotho Protein Levels

[00107] Some embodiments include a method of detecting and/or quantifying endogenous and/or exogenous Klotho protein, and more particularly endogenous and/or exogenous soluble alpha Klotho protein. Some embodiments include a method of diagnosing Klotho protein deficiency in a subject. Some embodiments include a product (e.g., a system or kit) for detecting and quantifying Klotho protein levels, and more particularly endogenous and/or exogenous soluble alpha Klotho protein levels. Some embodiments include methods of diagnosing Klotho protein deficiency in a subject.

[00108] It has been postulated that levels of circulating, soluble Klotho protein in the serum of mammals decrease with increasing age. Prior to the present disclosure, however, reliable, reproducible data as to what age this postulated decrease in serum Klotho levels may begin to take place, what the normal level (or range) of naturally-occurring, circulating soluble Klotho protein is in human and non-human animals, what the rate of decline in circulating Klotho is in human and non-human animals, and how low the level (or range) of naturally-occurring, circulating soluble Klotho protein gets in human and non-human animals, was not available or widely accepted. Commercially-available antibodies may not be suitable for reliable, reproducible, and/or cost-effective detection of (both endogenous and exogenous) Klotho protein in a (crude and/or substantially unpurified) mammalian blood or serum sample. Accordingly, suitable antibodies (e.g., for blood sample ELISA detection) were developed in accordance with the following procedure.

[00109] Phase-1: Klotho Protein Expression: (mouse and human) alpha Klotho proteins of various sizes (e.g., amino acid residues 34-981, 34-549, etc. for human) with a (C-terminal) 6xHis tag, (C-terminal) Fc tag, or (N- or C-terminal) HAS tag were manufactured. Gene constructs corresponding to the above proteins were synthesized and cloned into a commercially-available expression vector, which were then transfected into HEK-293 cells or CHO cells for Klotho protein production. Expressed Klotho protein was purified by methods, known and described in the present disclosure. Illustratively, IMAC and IE protein chromatography were used, yielding 0.78 mg/mL protein sample (measured by UV absorbance at 280nm) in 330 mM NaCl, 20 mM Na-Phosphate buffer, pH 8.0. Similarly, Protein A chromatography followed by size exclusion chromatography, as described herein, yielded active protein in monomeric and multimeric (e.g., dimer and tetramer) form.

[00110] Quality control: protein purity and integrity of purified protein was analyzed in 4 20% SDS-PAGE (reducing and non-reducing) stained with GelCode Blue reagent. See e.g., Figure 4, in which:

[00111] Lane 1: Klotho ECD, Lot# 170918A, 2ug/lane, reduced.

[00112] Lane M: Protein molecular weight marker.

[00113] Lane 2: Klotho ECD, Lot# 170918A, 2ug/lane, non-reduced.

[00114] Lane 3: BSA standard, 2ug/lane, reduced

[00115] The theoretical, calculated molecular weight of the expressed protein was 109.97 kDa.

[00116] Phase-2: Chicken Polyclonal (IgY) and Mouse Monoclonal (hybridoma) development: Expressed protein was used as an antigen to immunize mice and chickens for development of mono- and polyclonal antibodies. Mouse monoclonal is preferred in some embodiments for ELISA antibodies. After the fusion process (splenocytes with myeloma cells), two rounds of hybridoma selection were performed, around 3,000 clones were initially screened and finally narrowed to 10 clones, based on activity. These 10 clones were banked and also cultured and purified to produce -5mg of purified antibody from each.

[00117] The tables below present illustrative mouse sera IgG titer evaluations using target antigens, by indirect ELISA (Standard ELISA protocol. TMB 5 min.).

[00118] Antigen 1 - 6xHis tagged Klotho 0.5ug/mL in 50 mMNa-bicarbonate buffer.

[00119] Antigen 2 -Klotho-Fc 0.5ug/mL in 50 mMNa-bicarbonate buffer.

PC x4 4

Q '4 Q 4

X CC tPK]

C C6

ClC ',. Y 4: -iC bTD 1 4 .... Z.. -r " InC

d

In in

r r'. C C

cor6ar~~ et enoA M oioo 4 4u

en z w C0r- 0tto e

ti 9 N xJ .•

-1E ~ E

- - c Q N..

0zfli~flW ~WI 0 6ro io32

o Q)C2

-- C

C. - 00

000

C) o -0 0 r. CA

c-t - - - - -00

0 2

C) O

-e . Cn 0 C) N

C AAN o S oo CA -e -- - -a0

0A-4 +)n C 0-- -eoo

- o -c +- .

0 o

tenj

00Z - -0

0CAA - --- .2 in C fl .

2 s ~o o

- - - Es d oo 0 0 e 0p- CCA co CAj -T0

2 -. 00 rT1''

t V-t1 i -- o- 14

CA -0 .

r 33

.. ... ......

Alfl 666~~: 6666 Uc .... ...... ........ ...

..... ... .. ... ..... . . ..... ...

. ........~...... ... .. .... ......

SII

Y0lj 0 C:: Q060 1C

14f r-' n ro '~

[P NIs Jf , N ' '

CD

r- rtj QN 05h N C)C f

NI N000o,1

666 606 6660(500(5, IA IFS

m44nhhN4C4 Q t

[A1) tAOA

-,I CH N H

666 6 6 6 666 666

ff') Ln C 0

C4N

PN CO 3) N r j 'b ef 9~ 'C f

ri-L kr '4"'iN

C C" .. ...... .. ... .. .... .

in ... N ........0' 0 ..... ... ... ..... .... 0000000 00..0000.. .

-ad. r, .... . .....

.. .. . .

.. 0 0 0 ........ ... . ..... .... . ..... .... ~ r ... OC ........ ... ... f ......... O H ....... ccc~ ~V cc 66 Ncc c cr C; '

... ... .

LflNNN OOHH iOMENr

H IJ COif inN C35

4~ 1" t6A4 r C 7 Ctr4 .0%fl|fl g

14 rN .-M-e

s o C

r 0r m r.to C) 0 C, Cr o0 0 00000

coa doaQoo o oo oooe ca

000000n0 0000

N rM O-- r cz m N <: 7

ch La [M 6 O6 (Cu 03 c, Nooo NO Oo!

IC rz rQ ci C QQQ

d dd d dd d 0d3 d d, rxg

Srs "m r, tOWo ~m "o oD Q sr

336

Or'I CC) S TCC) s"C C In 6666d o oooooo

ItsI

(N'

r 6 ~ O r~ ceo IN o rD 00

+4000 00 000 00 0 to r

00 O O-g

~r~6e~36

)n f: d ("N) ri

/ Xd CO CO to O) -A CPM

al 6

N~ N ry;tCC rf)Li ryC-t a N oro o tio o o C~; COo o o NOo

ur 0t t H N N or C X

a~~ ~ 000')CCfl -- zllfC q oao a --- Iooo

C OCNCCOC 00u0000©CCN

j' Ci N iC D r)Gi iX f' ON L UjN

N r

O r - N0if) 0 0 un L0 I0 0 1 N

S uN N hMi 4 it WcN4N

z4 4N4000NC0 N i oCX ~4 I QOA' 0 4NOCCCo QtC [I C N

ONOO s-I N 3 OC CO OCO

N NOC O CO NX ©O C-I C C0C N 0<06000 00006000 O

i L

CO A.

rI N rA'QCC-0 r-r"-0 C r

N-) N D1 CD

0 0 r r , 0 . . .-- Z r

r~t ~ ooo0 Tnr~ r-C.

Nf LA rN © p - A N 0 s I s

CD t ~rflCO - w n C, (,Arn oto- «gr c c .'sunrn ©

Qo0t ooo Oo o oocN r4 ol ru r1 hl 6o MNj AV) M.3

4 r- ,o e,; Q -l

oc dd od dd dd o

rlri

C

ooodaaa Q.) m0 i.r0 oooooo' m ro Gi N

000

C3

'A 4A

o to38

0QI 0 ONJLflNO rIDN-4 ",-.1O fl 17 N N H.- N -D

'A r-aACr-'-rn4r,

t4 N f 4 o N4 "44 <,,fV~r 0 ;X mlt: H1~)4~ N l OC ~ N~~~ tO NON N000 0000000 000000.0

... ....... .. ....... ....... ..............0 V Q...C....0 ......0.

...... ........ 0. 0

r-4~~Gl Osi NO CT,- IN'Nr~n~-N

N NN

..... ..... C ri' 9 i4 ~ l ~ t )

.. ........ N .......6.. .. ...... .. 6.66... .

..... . .. ... N ....... ....... .. . . ..... N ........ ... C..1 0. f) ... ... ... N..

~~~~~4~~" ) C ~ ~ fll 0 Of) N -I unOC C 60 66 o 0z 1-66 6 tr r CI-C ,i

we4 ii1" rf 4I rN

N'l' N r'- -r' O~ O 0 ~p-Ksa) ~0N0 NO)

LO NQ c~~ C) c' C t *

-- A~~~ 9f an 1.1. 4 o -466 m -4 CooCr-, oo -A N... N... .... .. .... N (1)4....I.......C 4 I) 'P l 0~~ '~C ... ~ il 4 ) lnONO C ....... r-JNN0.. ....... ooodOj 666666

1*oz,

C) (b . . . . .... .

39 ...........

0 '1$ N Lflr N 0 c~ ~ N '~ '5 ~ ONOOCOQO

N 40 r 0 NO -<t-0 t~ 0 ~'4 0 N 000 ,o 0 .1 ~ 0 ad N (fl r- on ad ~r~ri0-100~-d0 ooo~~~oo

0N00~Ni~ N 00 ~ 000 rl ~00r100r100 00000000 00000000

400 v4(flNOLOOO Om ~ 000 0 000 ~qq0~tt 0000000rd 0 r~l 0 0 00000000 00000000

~t4 ~r4 OO00riO0Nrd OOdOOOOOrd 000000CC 0QQ200Q~ 0

r~.M*&~1.M00 00 N oooc5c~666 ad 4 Iv kA.3) (0 .1) ?T fO0Nr~4Nr'1N4 r LflON 0 OOON ~n~& ~is ~ 00000000 6666 6o! 4

66666666 666~66 4

0LnN'~tn0Lnco

00000000 oood66oo on 4

c-i 4 in ON mON on N ad rl RI mono 0 0 0rd~p>c~2~9r rd c 66626666 N 66666666 di '0 s'delrlt2 el4$0 4 Z "'I

U', ~ C-40 '00000 mON N00 00t(, 10

666666oo c346666oo

NNNOrO'Dtfl 00 OrNN-adadLn *0r1r~NQ30 r~ ~t ~ 000"~0 - ~~~$00 4$ 0 l'4 ¶k~P ~ C-) 00000000 00000000 ~1"' ~1"' .3) (4.i a a ufl 4aduflwu~0r 4~.i(4) 4t000UWQT w

It' (V I- I

Cv C C CD 0

0 1:D C r fl " 'DC-1. Doo

~~~f~tCM!'rDOCt 0r, wl t (b CO d .....tp . (A

'D i)if it: 0N 0 1

d, c oc6

rt Y 6T~6o tit.

(C0 M 0C0 10T

M i o-"0 M c~ooo C')'iT' 0,0".1

Cfl

0000000 u,0 w u0000 00

tfl 41

~ to l c-a l em C-: PA WCD PA 'A k

Q oe o oo o oo e do o

f r if C, O'Z CA NN r.

F 2r, so cI si ; r1 V2 V2 in 13 13-© c: - d •~ O CD O C C Q CD NO O P OO C

. S0 0 5 0r 000 f; 000 U)a N. 7,T g ml eotqrsl o18!

00o 00 p~ C 00 C0 0 0

Q1 to n Cw N t.

rf) ©o u- m th lf) e I'fl~4 fl N"i In)

~0m 0.0000i0m Q44 t t- xcM- r flm r o ta 0; © r

4

n n

C nas cy 13 d vy r-o r o

0 0e 0 66O s-(X o -,10 - (; m d i

0~62 2 5 2t, C4Q ZI Cn14C

tin 0 CA P as Its CD 0p©

0 0 --- 1 C0

IT,~~ Jnrr, r- DO oI oci roCn

7t 7 Wt eo

rto rs. to r~~ VO no r CO N CO CO CO CO N (d

00C 000 ooooo-6 ()Clml tNO) J4y0C,4O N1- CO~ril 0Q0I- illsr-% 11) f

(Z) 0 -) Z0 C! 0O N r-d. d d0 N

r >7 1 nO C '-4- ;: flr 00' " i'~ - nC C an in 90' :n ,Ar

N NN

a, o c, o C' I)a)N40 C_ 4

0Q!0O.Q r666o

CON~.J~r W43 1 0N0nnCO~g) ~143

N_' O C;0 ;Z.4 C' D --,flr

C) :ci CD rc~ O il c) -t o~ -'

C0 0Q 0 ' 4 -4400000000-4 ,'

81 'SN ~ 4 r4

-.P NA- D o. T '

t!" !1! 7 7A 0 O 1A4 N LAl D "",, HN0- H c~ elf) P0 f 0

I f"N

44N

A -- i 0C-Cr --i (C-01 CC , CCCa 9

Cl Q C; Cl •

up r- . rW

r C bCC

rs r- e, t N - t rr m

r. r2 *i rs . 1 r Z N

000 A O C COCO O~~ () clorcon Q3©

eN I

Q c6 co$6

C 4CC-.'C C O O '

4D en~ NM Atj)c lt ii r t in N t o (Jc • C3 i. r, r-, rdas

tN N 0

1 10

^j 04ay 9X C0 O Qt Q 000L UQ A Q 0 a0r m rm o L O~tC 'flm < C f -,QONOQ rin OC r r 02 rrt' 03 O ar$ NItXo

IP H s -, C

r~ C D C,

n- oo -T

N N Orr-tbifO L.ON

ri 4 0 j rJLqz ~%N NtON t

d dd tt'j W 0 ,C

tlJ4 CY

c") oeD

~ ., o 4 ~--- In v5 Q iO

N C Y'- O 88O ? ON 't8ftl i N eq

tON St nO ~ cn menr-or- mIf in O ec) O0CD o- t o r-~ao N N to o C a '

cd 6 &oo6 doo6 v', O in Ftrx)ONN

Ct (',- Ca C "

~4 464 A Vi

(11 0) IM I~a ( Q tA I c - n i0n000C NrN0) .,. N'.tn N.iO~- (0) CN CC 00 h e g, 'n ro j o-r m/ c"' a6) 4fX rc. ry: ."1 C I '0 1 .O oo nQ QQ f-,, 0 r .t if-, rm kyoo ;* cr% ' q

N r

0) l l Q ro *7a ?d6

pe .J r," o C ; )

4-AM .c Or N o

N n to ftoo i

Soo66 ooo 00o 00oo0o0

-- c,- :T r 0- + 3

Sooo oo o o oo o Oo oo o

01

rN CnN

00 i dT r o r d. C cc rI O - 40 0 c

N 4'r N to;

d C 8a7 A kA

C- r N~~~ rC i) 7 0 ~ co cti ~ cn d7, 0 C) 675 CD 0

W ) JIMU

d666 6 -n o'71 Qi ') 11

d o (n C, d 0 75C o 'd

0 (DOnC CC' t OC0 0

r esv ane-jr Ct oooo

H 6f C& - 6 0 6

a' 48 N N, '4N r[ d d pdd ~ Cc 000 00 0 0 00 0C

~H N~flttC 'f ~ C CC

fr& mo~~c~oc48

_ _ _ _ ( __B l -n -r-0 CA

CA r, Z

00~ 0 c)

©t~f '.1 r-a. Wi 0

. o 9A A2 .A -

+ cn; o oo ;oa o -)o t o CID D

0 0 C;CF,; cs 00 cn

+ 00 C

:Q r, Ni n Vn C

W V to o. 0 0 6 c- f, C6 c56 j

a) A)nm >

rC C vZ CI. i 0s 5 . . .CI

o Too oa ) s- cocicoqoci co n 49 C C)j

- ".0 -L CA ©© o N N 0 a)a (5 0k

40 cn~ CA~

o49 r07 cs%C." Rt- i~AllOc

U)) Goj t

14'

CU1

C5C

ex.'

'50

N° Lf 6 Cl C) C4. - o o lC a) A-- -

o0 oo A 0j

6 6 -- C) I~ 0 C A

-4-e

x 6 © © V- o o O O -N

d i ddd1

60 o = o G-el- 00

ds d en -e -e

o a) a) t/ o

t/m 0000 trt)IflLC o Co o00 -0 - - -e Cv

oo oQ o2 ~-AC d ,o ~cc5

nnn n o oo 6

.0 oc - - -o t -o -o C oJ oCl J t CC 0~ OClJ -I V) -o +-~ Ctj oc

- -- 51 2 9 cc C Z., C) N zA 0000(5e t *'n2 - C .

~Al Ctj C j

T- l ~ 0-e\ 0-o Zo\; 0 0600

V)- 51

CAC

Ct *.,.fl-...L f lI i l .....0.. ....... Cj CA

rll

Ct 0 -s 73c) cr rn c, .... ....

.....Ctj

-4 CA C)j

C4

oo- 0 O ;- 00 ..... ...... .. 2 t....... .

CA C ....0....C t ..... .......

*-4 CA

0 CA -ej o 4- ~Cf C) C

0. .. ....... e 0. .. ...... ....... H...

Ctj

C) .... Sj -. ... .

..... ..... H.... . ....-... - -... - -... & S .

4 .. ... ...-... ~ ooo tzs o... Ho.a -~ a a .2. . . . . ....... .

c~i C52

1. ftHis tagged Klotho protein

[Ab] 1F, 2E12, 444, 4 1 8G1L 11rg, ng/mL Lot#8O410A Lot#180410 iot#180410C Lot#180410D Lot#180410E tot#180410F 500 0.051 0,048 0.04? RG.040.04 .8 . 4 ,045 0,046 004 0.048 0.048 Noantigen 500 1.782 1793 2.533 2531 1.822 1662 1759 1.726 1.861 1,9 2.977 2.993 100 0.827 0,852 .398 132? 0.681 0,684 0,712 0.67 0,695 0789 1994 2,207 20 0.266 0,271 0.452 0.426 0.209 0.194 0.199 0.21? 0.259 0.223 0.862 0.946 4 0,096 0.102 0.152 0143 0.09 0.08 0,082 0,006 .091 0.087 0.251 0.32 0.8 0,064 0.061 0.065 0.074 0,058 0.061 0.06 0.06 0,062 0.06 0.105 0 124 0,16 0.056 0 055 0.06' 0058 0.052 00 0.0.056 0,05210.055 0.062 0.064 0.06? 0 0.051 0.049 0.052 0.5 0.051 0.049 0.05 0.052 0.052 0.052 0.054 0.061

[Ab], 1[9. 1F7, 14B12,.63 2F1 ngfml Lot#180410F Lot#18O410G Lot#180410H Lot#180410 Lot1804101 500 0,071 0.067 0059 0.058 0.06 0.062 008 0.072 0.076[0.073 No antigen 500 3.023 2.876 1.754 L779 1S.63 1.856 2.975 2.92 2,572 2.586 100 2.171 1.859 0.472 0506 0.88 0,57 2.103 2.145 L44 L65 20 0.988 0.864 0.154 0.137 0.29 0.253 0.994 1001 0.513 0.586 4 028 0.282 0.075 0.072 0.122 0.102 0.291 0.341 0 175 0.191 0.8 0.114 0.104 0.059 0.06 0.066 0.06 0.107 0.126 0.082[0,081 0.16 0.051 0.068 0,057 0.054 0,053 0.055 0.075 0.065 0..057[0.059 0 0.072 0.057 0,06 0.06 0,057 0,059 0.06 0.063 0.068[ 0062

2, Kltho-Fe protein (Ab], 16, 2E12, 44, 4H5, 8611 1109, ng/mL Lot#180410A Lot#180410B Lt0180410C Lot4180410D tot#180410E [ot4180410F 500 {0.06 08.0 ,056 Q.059 0.058 (1058 0.059 0,06 0.058 0.056 0.06 0.065 Noantigen 500 1328 1 30? 178 L838 1333 1.37 L366 125 1325 1352 2.74 2756 100 0 m50.462 0.749 0.765 0.466 0.44 0.423 0.43 0.455 0,412 1.801 1,187 20 0,176 0 1460,241 0.223 0.151 0.147 0.14 0.135 0.15 0,144 0.742 0732 4 U.087 0.088 0.094 0.075 0.076 0076 0.078 0,079 0.072 0.231 0.322 0 o0.0 73 0,0:65 0.062 0.063 0.057 (107 0.058 0 061 0.06 0.058 0101 0127 0.16 0168 065 0061 0.058 .056 0.057 0.057 0.058 0.055 0055 0.067 0.148 0.7 0.07 [0.065 0.057 0.07 0.059 0.056 0,075 0.06 0.063 0096 0112

(Ab], 119, 11F7, 14812 26G3, 28F11 ng/ml Lot0180410F Lot1804106 Lot4180410H La4t180410 tot#180410i 500 0.072 O05 0.058 0.057 0.06 0.06 0.066 0.063 0-063 0065 No antigen 5OO 2.6232.613 0.798 02 2.044 2085 2.t41 2607 2.417 2325 100 1886 1686 0291 0.288 1.047 1.012 1.822 1.784 1.337 1.427 20 816 07 0.104 0108 0.3 0.316 0.828 0.78 0.54 0.558 4 0,23 0 24 0 0066 ,67 0 125 0.135 0.265 0.267 0165 0171 08 0.183 0 101 0.56 0061 0.071 0069 0.106 0104 0083 &083 .16 0.078 0.068 0 059 0.058 0.057 0 0.063 C58 0.058 .059 0059 0 0.076 0066[1 066 0.061 .O057 006 O.57 0.057 0.59 .066

Table 5

[00143] See also, dose responsive curve illustrated in Figures 5A, 5B, and 6 respectively.

[00144] Quality control: Purity and integrity of purified antibody were analyzed in 4-20% SDS-PAGE (reducing and non-reducing) stained with GelCode Blue reagent. See Figures 7A and 7B, respectively.

[00145] Polyclonal IgY antibodies: Polyclonal IgY antibodies were also developed. The above design was adapted as necessary for production of polyclonal IgY antibodies in chickens.

[00146] Chicken serum IgY titer evaluation using target antigens, by indirect ELISA (TMB: 5 min). Read at 450nm

[00147] Antigen: Klotho 1 ug/mL (0.78 mg/mL, Lot# 170918A) in 50 mM Na-bicarbonate.

[00148] Samples: Chicken #1, #2, RT, lhr (5% milk in PBS). Immunization antigen Klotho

bleed serum Chicken1D dilution 1 2 Pre-bleed 11,000 0.05 0.048 0051 0.051 No Antigen Pre-bLeed 1:1,000 0.123 0.06 0.064 0.062 Bleed 1 11000 2.686 2.64 3166 3.291 10,000 1,125 0.931 2.689 2.76 _100.000 0,156 0.153 .927 0.924 Klotho Bleed 2 1:1,000 2.278 2,215 2.895 2963 1,10,000 0.985 0.858 2,679 3543 1 100,000 0,171 0.144 1.02 1.065

Table 6

[00149] An ELISA plate was coated with 6xHis tagged Klotho protein or Klotho-Fc protein at 0.5 ug/ml overnight at +4°C in 50 mM Na-bicarbonate buffer. Purified anti-Klotho IgY antibody (lot# 180327A) was applied in 5-fold serial dilutions starting at 1000 ng/mL and the secondary antibody, goat anti-chicken HRP, was applied at 0.16 g/ml. Reaction was developed for 5 minutes. Raw absorbance data at 450 nm and corresponding antibody titration curve. See also, Figures 8A-8B.

Antgen

Klotho Kiothc-Fc ng/mL 1000 0.047 0.046 0.046 0,054 No Antigen 1000 2.192 2.179 2.137 2,171 200 1.916 1.795 1.797 1.942 40 L076 1.032 0,865 0,9 8 0.354 0.337 0.328 0,293 1.6 0.123 0.118 0.106 0.109 0,32 0,063 0.073 0.058 0,062 0 0,046 0.047 0.047 0,045

Table 7

[00150] Summary: Both HRP and Biotin-anti-Klotho IgY show significant signal in indirect ELISA. Bio-IgY has stronger signal than HRP-IgY.

[00151] As illustrated in Figures 9A and 9B, there is a relatively weak signal in IgY/HRP IgY pair. IgY/Bio-IgY shows relatively high background, even at low concentration (0.25 pg/mL). IgY/Bio-4H5 pair appears to work better than IgY/labled-IgY pair.

[00152] It has been postulated that levels of circulating, soluble Klotho protein in the serum of mammals decrease with increasing age. Baseline measurement for naturally-occurring, circulating soluble Klotho protein in a human subject has been reported in various publications. A thorough literature review yielded the following average range(s) for circulating soluble Klotho protein in the indicated human subject (see Tables 8-9). Age group Sex Healthy male Healthy female 0-15 1692(372,5694) 2487(964,5866) 15-35 459.4 (335.1-617.2)- 508 (448-661) 459.4 (335.1-617.2)- 508 (448-661) 35-50 476.9 (416.9-545.5)-692 (618-866) 476.9 (416.9-545.5)-692 (618-866) 141.8 (94.7-189.2)-377.17 (359.46 50-65 394.90) 141.8 (94.7-189.2)-377.17 (359.46-394.90) >65 354 (264-410)-999.5 (887.7-1186.4) 354 (264-410)-999.5 (887.7-1186.4) Age group Disease GH deficiency CKD all 0-15 340(433,7826) 1746(671-3438) 15-35 35-50 396.3 (306.3-558.4)-478 (348-658) 50-65 613.0 (504.0 to 811.0)-809 (674-981) Men 596.0 (464.3 to 790.3); Women 614.0 >65 (558.0 to 811.0) Age group CKD stage 1-2 CKD stage 3 0-15 1418 (501-3314)-1736.5 (1272-2737) 1418 (501-3314)-1736.5 (1272-2737) 15-35 35-50 540.5 (371.3-824.8)-482.7 (360.2-683.1) 386.4 (319.2-456.7) 50-65 388(254-532) 316 (199-464)-337 (217-489) >65 Age group CKDstage4 CKD stage 5 0-15 1019 (502-1592)-1418 (501-3314) 1019 (502-1592)- 1418 (501-3314) 15-35 35-50 337.8 (251.0-444.2) 295.6 (207.7-387.5) 50-65 215(135-331) 249(100-452) >65 Mean±SEM 473.9±121.4 Mean±SEM 546±164.3 Age group Kidney transplant TiD 0-15 1698(1110-2123) 15-35 454(420-492) 35-50 659.3 (525.3, 827.6)- 787.7 (629.5, 1007) 50-65 550(304-651)-605 (506-784) >65 Age group T2D CAD 0-15 15-35 35-50 572.4 (541.9-604.6) Men 67.3 (52.8-69.3); Women 65.7 (51.6 50-65 71.6) 490.5 (349.0-549.4) Men 45.1 (33.7-54.1); Women 40.7 (31 >65 493.7 (287.8-777.7) 56.4) Age group COPD MS 0-15 new cases Mean±SEM 585.56 ±153.99; 15-35 chronic cases Mean±SEM 696.94 ±170.52 35-50 50-65 >65 250(168-330)

Table 8 Age group KL-VS genotype Non carrier Heterozygous Homozygous >65 Mean±SEM 780.9 19.6 Mean±SEM 891.7 ±45.3 Mean±SEM 599.1 ±75.7

Table 9

[00153] In the table, above, CKD: chronic kidney disease; GH: growth hormone; TID: type 1 diabetes; T2D: type 2 diabetes; CAD: coronary artery disease; COPD: chronic obstructive pulmonary disease; MS: multiple sclerosis.

[00154] In light of the variability observed in the literature, a more robust, more consistent, and/or more accurate means of measuring serum Klotho levels is needed. Embodiments of the present disclosure include a Klotho diagnostic kit and method of using the same, as described in further detail, below.

[00155] Table 10 presents a baseline measurement for naturally-occurring, circulating soluble Klotho protein in a human subject (prior to receiving any treatment, e.g., health supplement, pharmaceutical, therapeutic protein, etc.). Figure 10 is a graphical representation of the (daily) change in circulating Klotho protein levels in a human subject

Time Collected [Klotho] (ng/mL) 0650 0.579 0750 0.782 0850 0.66 0950 0.717 1050 0.611 1150 0.596 1255 0.597 1645 0.56 1745 0.556 1845 0.588 1945 0.592 2045 0.638 2155 0.551

Table 10

[00156] Once per hour, beginning at 0650 hours, a blood sample was taken from the human subject and Klotho protein levels were measured by ELISA.

[00157] Quantitative ELISA according to an embodiment of the present disclosure is able to detect (1) Native (e.g., endogenous) Klotho, (2) recombinant Klotho-Fc fusion, and (3) recombinant 6xHis Klotho in human plasma samples.

[00158] Further measurements of Klotho protein are illustrated and presented in Figures 11A-I1B and Table 11, below.

Pooled Human Serumn 1gY4wth ueiGi Diuton1i.Kit g/H Asylun igY/14812

Table 11 Klotho Stability in Human Plasma Using ELISA Kit

[001591 Samples of venous and capillary ("finger") blood were collected from four donors (A, B, C, D)and stored in(i) EDTA or(ii)heparin containing tubes. 1.5 ng/mL of Klotho (lot# 170918A - human soluble alpha Klotho) was spiked into aset of venous and capillary samples collected from donor A. Collected blood (blood samples) were stored at room temperature for 0, 1,4,16,24, 48,72, 96, or168 h,thenspun-down. Plasma fromeach sample was stored at -80°C prior to ELISA test. ELISA plate maps, raw data, standard curve data, and concentrations are presented in Tables 12-21, below.

ELISA plate map 1: STD, 6 ng/mL A (o h) EDTA A (1h) EDTA A (4 h) EDTA A (16 h) EDTA A (24 h) EDTA STD, 3 ng/mL A (48 h) EDTA A (72 h) EDTA A (96 h) EDTA A (168 h) EDTA A (Finger) EDTA STD, 1.5 ng/mL A (0 h) Heparin A (1 h) Heparin A (4 h) Heparin A (16 h) Heparin A (24 h) Heparin STD, 0.75 ng/mL A (48 h) Heparin A (72 h) Heparin A (96 h) Heparin A (168 h) Heparin A (Finger) Heparin STD, 0.375 ng/mL B (0 h) EDTA B (1 h) EDTA B (4 h) EDTA B (16 h) EDTA B (24 h) EDTA STD, 0.188 ng/mL B (48 h) EDTA B (72 h) EDTA B (96 h) EDTA B (168 h) EDTA B (Finger) EDTA STD, 0.094 ng/mL B (0 h) Heparin B (1 h) Heparin B (4 h) Heparin B (16 h) Heparin B (24 h) Heparin STD, 0 ng/mL B (48 h) Heparin B (72 h) Heparin B (96 h) Heparin B (168 h) Heparin B (Finger) Heparin

Table 12 ELISA plate map 2: STD, 6 ng/mL C (0 h) EDTA C (1 h) EDTA C (4 h) EDTA C (16 h) EDTA C (24 h) EDTA STD, 3 ng/mL C (48 h) EDTA C (72 h) EDTA C (96 h) EDTA C (168 h) EDTA C (Finger) EDTA STD, 1.5 ng/mL C (0 h) Heparin C (1 h) Heparin C (4 h) Heparin C (16 h) Heparin C (24 h) Heparin STD, 0.75 ng/mL C (48 h) Heparin C (72 h) Heparin C (96 h) Heparin C (168 h) Heparin C (Finger) Heparin STD, 0.375 ng/mL D (0 h) EDTA D (1 h) EDTA D (4 h) EDTA D (16 h) EDTA D (24 h) EDTA STD, 0.188 ng/mL D (48 h) EDTA D (72 h) EDTA D (96 h) EDTA D (168 h) EDTA D (Finger) EDTA STD, 0.094 ng/mL D (0 h) Heparin D (1 h) Heparin D (4 h) Heparin D (16 h) Heparin D (24 h) Heparin STD, 0 ng/mL D (48 h) Heparin D (72 h) Heparin D (96 h) Heparin D (168 h) Heparin D (Finger) Heparin

Table 13 ELISA plate map 3: STD, 6 ng/mL Spike (0 h) EDTA Spike (168 h) EDTA Spike (72 h) Heparin STD, 3 ng/mL Spike (1 h) EDTA Spike (Finger) EDTA Spike (96 h) Heparin STD, 1.5 ng/mL Spike (4 h) EDTA Spike (0 h) Heparin Spike (168 h) EDTA STD, 0.75 ng/mL Spike (16 h) EDTA Spike (1 h) Heparin Spike (Finger) Heparin STD, 0.375 ng/mL Spike (24 h) EDTA Spike (4 h) Heparin STD, 0.188 ng/mL Spike (48 h) EDTA Spike (16 h) Heparin STD, 0.094 ng/mL Spike (72 h) EDTA Spike (24 h) Heparin STD, 0 ng/mL Spike (96 h) EDTA Spike (48 h) Heparin

Table 14 ELISA 450 nm absorbance raw data (plate 1): 3.44 3.39 0.238 0.231 0.231 0.247 0.235 0.233 0.248 0.244 0.261 0.276 2.03 2.005 0.235 0.235 0.242 0.235 0.247 0.248 0.254 0.264 0.283 0.282 1.117 1.077 0.239 0.241 0.229 0.236 0.236 0.248 0.253 0.264 0.256 0.283 0.593 0.573 0.237 0.23 0.241 0.248 0.239 0.26 0.252 0.248 0.254 0.258 0.31 0.328 0.162 0.157 0.16 0.163 0.162 0.161 0.173 0.173 0.184 0.181 0.206 0.202 0.167 0.178 0.17 0.172 0.173 0.177 0.18 0.174 0.182 0.199 0.133 0.131 0.162 0.173 0.175 0.172 0.174 0.172 0.173 0.176 0.176 0.185 0.059 0.059 0.177 0.18 0.181 0.182 0.176 0.163 0.165 0.185 0.182 0.19

Table 15 ELISA 450 nm absorbance raw data (plate 2): 3.409 3.302 0.228 0.223 0.237 0.237 0.232 0.233 0.24 0.233 0.26 0.275

.986 1.904 0.246 0.239 0.242 0.247 0.244 0.242 0.251 0.256 0.227 0.251 1.066 1.052 0.229 0.226 0.222 0.228 0.226 0.236 0.234 0.246 0.244 0.251 0.589 0.56 0.225 0.233 0.242 0.238 0.266 0.239 0.25 0.251 0.244 0.23 0.329 0.327 0.192 0.181 0.165 0.174 0.187 0.174 0.196 0.168 0.174 0.163 0.195 0.195 0.174 0.176 0.184 0.188 0.196 0.184 0.205 0.172 0.169 0.17 0.136 0.129 0.136 0.165 0.177 0.165 0.163 0.171 0.191 0.168 0.177 0.186 0.064 0.072 0.19 0.177 0.184 0.177 0.198 0.188 0.197 0.18 0.17 0.167

Table 16 ELISA 450 nm absorbance raw data (plate 3): 3.482 3.393 0.449 0.442 0.553 0.558 0.51 0.506 2.04 1.976 0.438 0.429 0.587 0.603 0.501 0.509 1.11 1.087 0.426 0.427 0.506 0.498 0.481 0.503 0.6 0.577 0.442 0.441 0.514 0.518 0.568 0.524 0.341 0.331 0.471 0.453 0.506 0.522 0.202 0.201 0.47 0.462 0.537 0.548 0.137 0.137 0.514 0.517 0.54 0.537 0.062 0.064 0.558 0.539 0.564 0.57

Table 17 Calculation: Standard curve 1:

Sample Concentration Wells BCaCic. Values Mean Value Std. Dev. CV%

Stol 6 Al 6.062 3.44 3.415 0.035 1 A2 5.934 3.39 St02 3 BI 3.03 2.03 2.018 0.018 0.9 B2 2.985 2.005 St03 1.5 C1 1.525 1.117 1.097 0.028 2.6 C2 1.464 1.077 StO4 0.75 D1 0.758 0.593 0.583 0.014 2.4 D2 0.73 0.573 St05 0.375 El 0.358 0.31 0.319 0.013 4 E2 0.384 0.328 St06 0.188 F1 0.21 0.206 0.204 0.003 1.4 F2 0.204 0.202 St07 0.094 GI 0.102 0.133 0.132 0.001 1.1 G2 0.099 0.131 St08 0 HI Range 0.059 0.059 0 0 H2 Range 0.059 1 1 1

Table 18 Concentration: ly = ((A - D)/(1 + (x/C)^B)) + D: A B C D RA2 Std (Standards: Concentration vs MeanValue) 0.069 1.0781 0.627 9.614 1

Calculation: Standard curve 2:

Sample Concentration Wells Back Conc. Values Mean Value Std. Dev. CV% (ng/mL) Calc. Stol 6 Al 6.13 3.409 3.356 0.076 2.3

A2 5.868 3.302 St02 3 BI 3.082 1.986 1.945 0.058 3 B2 2.931 1.904 St03 1.5 C1 1.504 1.066 1.059 0.01 0.9 C2 1.482 1.052 StO4 0.75 D1 0.769 0.589 0.575 0.021 3.6 D2 0.726 0.56 St05 0.375 El 0.385 0.329 0.328 0.001 0.4 E2 0.382 0.327 St06 0.188 F1 0.188 0.195 0.195 0 0 F2 0.188 0.195 St07 0.094 GI 0.1 0.136 0.133 0.005 3.7 G2 0.09 0.129 St08 0 HI Range 0.064 0.068 0.006 8.3 H2 0.002 0.072

Table 19 Concentration: ly = ((A - D)/(1 + (x/C)^B)) + D: A B C D RA2 Std (Standards: Concentration vs MeanValue) 0.071 1.039 14.67 11.673 1

Calculation: Standard curve 3:

Sample Concentration Wells BackCacc. Values Mean Value Std. Dev. CV% (ng/mL) ____ Calc. Stol 6 Al 6.108 3.482 3.438 0.063 1.8 A2 5.89 3.393 St02 3 B1 3.063 2.04 2.008 0.045 2.3 B2 2.948 1.976 St03 1.5 C1 1.514 1.11 1.099 0.016 1.5 C2 1.479 1.087 StO4 0.75 D1 0.757 0.6 0.589 0.016 2.8 D2 0.724 0.577 St05 0.375 El 0.389 0.341 0.336 0.007 2.1 E2 0.375 0.331 St06 0.188 F1 0.193 0.202 0.202 0.001 0.4 F2 0.192 0.201 St07 0.094 G1 0.1 0.137 0.137 0 0 G2 0.1 0.137 St08 0 H1 Range 0.062 0.063 0.001 2.2 H2 Range 0.064 1 1 1

Table 20 Concentration: ly = ((A - D)/(1 + (x/C)AB)) + D: A B C D RA2 Std (Standards: Concentration vs MeanValue) 0.07 1.043 13.427 11.242 1

Calculation: human plasma samples:

Resl Std.Dev. CV% Dilution nlotho Sample Wells Values Result

A (0 h) A3 0.238 0.256 0.251 0.007 2.8 4 1.003 EDTA A4 0.231 0.246

A (1 h) A5 0.231 0.246 0.257 0.016 6.3 4 1.028 EDTA A6 0.247 0.269 A (4 h) A7 0.235 0.251 0.25 0.002 0.8 4 1 EDTA A8 0.233 0.249 A (16 h) A9 0.248 0.27 0.267 0.004 1.5 4 1.068 EDTA A1O 0.244 0.264 A (24 h) All 0.261 0.289 0.299 0.015 5 4 1.197 EDTA A12 0.276 0.31 A (48 h) B3 0.235 0.251 0.251 0 0 4 1.006 EDTA B4 0.235 0.251 A (72 h) B5 0.242 0.261 0.256 0.007 2.8 4 1.026 EDTA B6 0.235 0.251 A (96 h) B7 0.247 0.269 0.269 0.001 0.4 4 1.077 EDTA B8 0.248 0.27 A (168 h) B9 0.254 0.279 0.286 0.01 3.5 4 1.143 EDTA B1O 0.264 0.293 A (Finger) B1I 0.283 0.32 0.319 0.001 0.3 4 1.276 EDTA B12 0.282 0.318 A (0 h) C3 0.239 0.257 0.259 0.002 0.8 4 1.034 Heparin C4 0.241 0.26 A (1 h) C5 0.229 0.243 0.248 0.007 2.9 4 0.991 Heparin C6 0.236 0.253 A (4 h) C7 0.236 0.253 0.261 0.012 4.6 4 1.046 Heparin C8 0.248 0.27 A (16 h) C9 0.253 0.277 0.285 0.011 3.9 4 1.14 Heparin C1O 0.264 0.293 A (24 h) C1I 0.256 0.281 0.301 0.027 9 4 1.202 Heparin C12 0.283 0.32 A (48 h) D3 0.237 0.254 0.249 0.007 2.8 4 0.997 Heparin D4 0.23 0.244 A (72 h) D5 0.241 0.26 0.265 0.007 2.7 4 1.06 Heparin D6 0.248 0.27 A (96 h) D7 0.239 0.257 0.272 0.021 7.8 4 1.088 Heparin D8 0.26 0.287 A (168 h) D9 0.252 0.276 0.273 0.004 1.5 4 1.091 Heparin D1O 0.248 0.27 A (Finger) D1I 0.254 0.279 0.279 0 0 4 1.114 Heparin D12 0.066 Range B (0 h) E3 0.162 0.146 0.142 0.005 3.7 4 0.568 EDTA E4 0.157 0.138 B (1 h) E5 0.16 0.143 0.145 0.003 2.2 4 0.579 EDTA E6 0.163 0.147 B (4 h) E7 0.162 0.146 0.145 0.001 0.7 4 0.579 EDTA E8 0.161 0.144 B (16 h) E9 0.173 0.162 0.162 0 0 4 0.647 EDTA E1O 0.173 0.162 B (24 h) Eli 0.184 0.178 0.176 0.003 1.8 4 0.702 EDTA E12 0.181 0.173 B (48 h) F3 0.167 0.153 0.161 0.011 7.1 4 0.644 EDTA F4 0.178 0.169

B (72 h) F5 0.17 0.157 0.159 0.002 1.3 4 0.635 EDTA F6 0.172 0.16 B (96 h) F7 0.173 0.162 0.165 0.004 2.5 4 0.659 EDTA F8 0.177 0.168 B (168 h) F9 0.18 0.172 0.168 0.006 3.7 4 0.67 EDTA F1O 0.174 0.163 B (Finger) Fl 0.182 0.175 0.187 0.017 9.3 4 0.749 EDTA F12 0.199 0.2 B (0 h) G3 0.162 0.146 0.154 0.011 7.4 4 0.615 Heparin G4 0.173 0.162 B (1 h) G5 0.175 0.165 0.162 0.003 1.9 4 0.65 Heparin G6 0.172 0.16 B (4 h) G7 0.174 0.163 0.162 0.002 1.3 4 0.647 Heparin G8 0.172 0.16 B (16 h) G9 0.173 0.162 0.164 0.003 1.9 4 0.656 Heparin G1O 0.176 0.166 B (24 h) Gil 0.176 0.166 0.173 0.009 5.4 4 0.691 Heparin G12 0.185 0.179 B (48 h) H3 0.177 0.168 0.17 0.003 1.8 4 0.679 Heparin H4 0.18 0.172 B (72 h) H5 0.181 0.173 0.174 0.001 0.6 4 0.697 Heparin H6 0.182 0.175 B (96 h) H7 0.176 0.166 0.157 0.013 8.6 4 0.626 Heparin H8 0.163 0.147 B (168 h) H9 0.165 0.15 0.165 0.021 12.6 4 0.658 Heparin H1O 0.185 0.179 B (Finger) HI 0.182 0.175 0.181 0.008 4.6 4 0.723 Heparin H12 0.19 0.187 C (0 h) A3 0.228 0.236 0.233 0.005 2.2 4 0.931 EDTA A4 0.223 0.229 C (1 h) A5 0.237 0.25 0.25 0 0 4 0.998 EDTA A6 0.237 0.25 C (4 h) A7 0.232 0.242 0.243 0.001 0.4 4 0.972 EDTA A8 0.233 0.244 C (16 h) A9 0.24 0.254 0.249 0.007 2.9 4 0.996 EDTA AlO 0.233 0.244 C (24 h) All 0.26 0.283 0.294 0.016 5.3 4 1.177 EDTA A12 0.275 0.305 C (48 h) B3 0.246 0.263 0.258 0.007 2.8 4 1.031 EDTA B4 0.239 0.253 C (72 h) B5 0.242 0.257 0.261 0.005 2 4 1.042 EDTA B6 0.247 0.264 C (96 h) B7 0.244 0.26 0.258 0.002 0.8 4 1.034 EDTA B8 0.242 0.257 C (168 h) B9 0.251 0.27 0.274 0.005 1.9 4 1.095 EDTA B1O 0.256 0.277 C (Finger) Bl 0.227 0.235 0.253 0.025 9.9 4 1.01 EDTA B12 0.251 0.27 1 1 1 1 C (0 h) C3 0.229 0.238 0.236 0.003 1.3 4 0.943 Heparin C4 0.226 0.233

C (1 h) C5 0.222 0.228 0.232 0.006 2.7 4 0.928 Heparin C6 0.228 0.236 C (4 h) C7 0.226 0.233 0.241 0.01 4.3 4 0.963 Heparin C8 0.236 0.248 C (16 h) C9 0.234 0.245 0.254 0.012 4.9 4 1.016 Heparin C1O 0.246 0.263 C (24 h) C1I 0.244 0.26 0.265 0.007 2.7 4 1.06 Heparin C12 0.251 0.27 C (48 h) D3 0.225 0.232 0.238 0.008 3.5 4 0.951 Heparin D4 0.233 0.244 C (72 h) D5 0.242 0.257 0.254 0.004 1.6 4 1.016 Heparin D6 0.238 0.251 C (96 h) D7 0.266 0.292 0.272 0.028 10.3 4 1.089 Heparin D8 0.239 0.253 C (168 h) D9 0.25 0.269 0.269 0.001 0.4 4 1.078 Heparin D1O 0.251 0.27 C (Finger) D1i 0.244 0.26 0.25 0.015 5.8 4 0.998 Heparin D12 0.23 0.239 D (0 h) E3 0.192 0.183 0.175 0.011 6.5 4 0.701 EDTA E4 0.181 0.167 D (1 h) E5 0.165 0.144 0.15 0.009 6.3 4 0.601 EDTA E6 0.174 0.157 D (4 h) E7 0.187 0.176 0.166 0.014 8.2 4 0.666 EDTA E8 0.174 0.157 D (16 h) E9 0.196 0.189 0.169 0.029 17.3 4 0.675 EDTA E1O 0.168 0.148 D (24 h) Eli 0.174 0.157 0.149 0.012 7.7 4 0.595 EDTA E12 0.163 0.141 D (48 h) F3 0.174 0.157 0.158 0.002 1.3 4 0.633 EDTA F4 0.176 0.16 D (72 h) F5 0.184 0.172 0.175 0.004 2.4 4 0.698 EDTA F6 0.188 0.178 D (96 h) F7 0.196 0.189 0.18 0.013 6.9 4 0.722 EDTA F8 0.184 0.172 D (168 h) F9 0.205 0.203 0.178 0.034 19.3 4 0.713 EDTA F1O 0.172 0.154 D (Finger) F1I 0.169 0.149 0.15 0.001 0.7 4 0.601 EDTA F12 0.17 0.151 D (0 h) G3 0.136 0.1 0.122 0.03 25 4 0.488 Heparin G4 0.165 0.144 D (1 h) G5 0.177 0.161 0.152 0.013 8.2 4 0.61 Heparin G6 0.165 0.144 D (4 h) G7 0.163 0.141 0.147 0.008 5.7 4 0.586 Heparin G8 0.171 0.152 D (16 h) G9 0.191 0.182 0.165 0.024 14.6 4 0.66 Heparin G1O 0.168 0.148 D (24 h) Gil 0.177 0.161 0.168 0.009 5.6 4 0.672 Heparin G12 0.186 0.175 D (48 h) H3 0.19 0.181 0.171 0.014 7.9 4 0.684 Heparin H4 0.177 0.161

D (72 h) H5 0.184 0.172 0.166 0.007 4.4 4 0.666 Heparin H6 0.177 0.161 D (96 h) H7 0.198 0.192 0.185 0.01 5.6 4 0.74 Heparin H8 0.188 0.178 D (168 h) H9 0.197 0.191 0.178 0.018 9.9 4 0.713 Heparin H1O 0.18 0.166 D (Finger) HI 0.17 0.151 0.149 0.003 2.1 4 0.595 Heparin H12 0.167 0.147 Spike (0 h) A3 0.449 0.542 0.537 0.007 1.3 4 2.147 EDTA A4 0.442 0.532 Spike (1 h) B3 0.438 0.526 0.52 0.009 1.7 4 2.079 EDTA B4 0.429 0.513 Spike (4 h) C3 0.426 0.509 0.51 0.001 0.2 4 2.039 EDTA C4 0.427 0.511 Spike (16 D3 0.442 0.532 0.531 0.001 0.2 4 2.124 h) EDTA D4 0.441 0.53 Spike (24 E3 0.471 0.573 0.56 0.018 3.2 4 2.24 h) EDTA E4 0.453 0.547 Spike (48 F3 0.47 0.571 0.566 0.008 1.4 4 2.263 h) EDTA F4 0.462 0.56 Spike (72 G3 0.514 0.634 0.636 0.003 0.5 4 2.545 h) EDTA G4 0.517 0.638 Spike (96 H3 0.558 0.697 0.683 0.019 2.8 4 2.733 h) EDTA H4 0.539 0.67 Spike (168 A5 0.553 0.69 0.693 0.005 0.7 4 2.773 h) EDTA A6 0.558 0.697 Spike B5 0.587 0.738 0.75 0.016 2.2 4 3 (Finger) EDTA B6 0.603 0.761 Spike (0 h) C5 0.506 0.623 0.617 0.008 1.3 4 2.468 Heparin C6 0.498 0.611 Spike (1 h) D5 0.514 0.634 0.637 0.004 0.6 4 2.548 Heparin D6 0.518 0.64 Spike (4 h) E5 0.506 0.623 0.634 0.016 2.5 4 2.536 Heparin E6 0.522 0.645 Spike (16 F5 0.537 0.667 0.675 0.011 1.6 4 2.699 h) Heparin F6 0.548 0.683 Spike (24 G5 0.54 0.671 0.669 0.003 0.5 4 2.676 h) Heparin G6 0.537 0.667 Spike (48 H5 0.564 0.705 0.71 0.006 0.9 4 2.839 h) Heparin H6 0.57 0.714

Spike (72 A7 0.51 0.628 0.625 0.004 0.6 4 2.502 h) Heparin A8 0.506 0.623 Spike (96 B7 0.501 0.616 0.621 0.008 1.3 4 2.485 h) Heparin B8 0.509 0.627 Spike (168 C7 0.481 0.587 0.603 0.022 3.7 4 2.411 h) Heparin C8 0.503 0.618 Spike D7 0.568 0.711 0.68 0.044 6.5 4 2.719 (Finger) Heparin D8 0.524 0.648

Table 21

[00160] Figure 12 illustrates Klotho level at different incubation time at RT.

[00161] Table 22, below presents average Klotho protein level (ng/mL) in plasma: Blood sample Venous Capillary (finger) Anticoagulant EDIA Heparin EDIA Heparin A 1.06 1.07 1.28 1.11 B 0.63 0.66 0.75 0.72 C 1.03 1.08 1.01 1.00 D 0.67 0.65 0.60 0.60 A, Spiked 2.33 2.57 3.00 2.72

Table 22

[00162] Table 23, below presents spiked Klotho recovery rate (%) Blood sample Venous Capillary (finger) Anticoagulant EDIA Heparin EDIA Heparin A, Spiked 84% 100% 115% 107%

Table 23 Klotho Stability Testing at Various Temperatures Emulating Shipping Stress

[00163] Phlebotomist(s) collected >12 mL blood (sample) from each of four donors into heparinized blood tubes. Technician(s) immediately dispensed 300-400uL of blood from the collected sample of each donor into separate heparinized Micro Tubes (from BD). Tubes were stored and processed according to the study design (see table below). Blood was processed at each timepoint or centrifuged and stored (plasma) at -80°C. All samples were tested at approximately day 17.

[00164] For the study, 120 data points were collected, representing 6 conditions, over 14 days (see below).

x~~ X

000

x> >

cKT M~ r' N,

'½ ( m m mM mo f

NI

a L

o o (D L. >,

co 00oca

C)~ _ _ ... ..... ..... .. ................I .........N... . H.... 0 .

......... * .. .. ....... .. ...... .. ... ...... ........ 0.. . . .. fl ... .. . .... .... .... U u > - N ... ..... .... .............. .

... ... N. ................- 0 a ~ H o co ccc .. . .. ..--------------------------------------- .... ..... -............. & & -C JZ &

...... . .... C CC 00N) .... ....:::: .. 2 . N.......N... ... .. .. .. ... ..

..... ....N... N...... n C .. . . ...... 0 N....... ct H H .)U . .......z. N N ..)

C -j

. . . .........~~ ...- .... -...... 2 - ---...... ........ .. ..N .H..... C.. N.... .... .. ... .. .. .. .. .. .....

.... ................ ........ ... .- .. .. O.. ..... ......k.. .. .. . .

.......... .... .......................... .. . . . .. ... . ...... .... L

...-.... ....... .... .... ... f l.. .. . . . .............Qj _ _ . . . . . .... .... . .... .

EN EN CC

66 c

[00166] ELISA protocol was conducted according to instructions of soluble Klotho ELISA kit (human), IBL, Cat# 27998). Raw data are given below in Tables 26-29: Plate 1, Donor 1:

2.689 2.577 0.138 0.141 0.09 0.088 0.133 0.125 0.107 0.109 0,047 1481 1.423 0.174 0.162 0.107 0.177 0.169 0,161 0.142 0.159 0.053 0801 0.833 0.128 0.131 0,8 0.085 :0.125 0,124 0114 0.11 0.128 0443 0.414 0.129 0.123 0.123 0.126 0.121 0.12 0111 0.111 0.065 0.26 0.253 0.111 0.128 0.132 0.129 0.116 0,118 0111 0.115 0.06 0162 0.154 0.109 0.116 0.128 0.131 0.135 0,127 0113 0.111 0.062 0.15 0.114 0.087 0.092 0.126 0.131 0.137 0.137 0.099 0.124 0.062 0.148 0.058 0.219 0.098 0.115 0.277 0.243 0.128 0.052 0.056 0.087

Table 26 Plate 2, Donor 2:

2.799 2.887 0.218 0.223 0.124 0.122 0.217 0.201 0.174 0.167 0.088 1.594 1.596 0.222 0.218 0.112 0.105 0.208 0.208 0.161 0.153 0.092 0.91 0.898 0.223 0.219 0.108 0.109 0.202 0.202 0.172 0.168 0.154 0.49 0.475 0.207 0.21 0.208 0.201 0.199 0.203 0.17 0.175 0.067 0.288 0.284 0.217 0.212 0.21 0.208 0.162 0.165 0.163 0.167 0.086 0.175 0.162 0.174 0.173 0.203 0.201 0.203 0.202 0.161 0.157 0.105 0.114 0.114 0.116 0.11 0.208 0.206 0.211 0.219 0.173 0.147 0.486 0.08 0.064 0.175 0.123 0.175 0.186 0.237 0.203 0.058 0.051 0.082

Table 27 Plate 3, Donor 3:

2.768 2.8 0.155 0.156 0.108 0.102 0.161 0.159 0G14 0.137 0.132 1.629 1.642 0.161 0.158 0.1 0.093 0.156 0.16 0.131 0.13 0.057 0.926 0.911 0.159 0.159 0.099 0.105 0.15 0.152 0.139 0.145 0.053 0.51 0.484 0,15 0.151 0.15 0.146 0.154 0.149 0.137 0.138 0.057 0.288 0.284 0,16 0.162 0.156 0.157 0.132 0.133 0.134 0.134 0.111 0.188 0.165 0.131 0.136 0151 0.152 0.15 0.152 0.133 0.129 0.068 0.119 0.121 0.114 0.115 0154 0.156 0.164 0.164 0.122 0.123 0.066

0.092 0.071 0.158 0.113 0.149 0.155 0.17 0.164 0.059 0.061 0.078

Table 28 Plate 4, Donor 4:

2.787 2.699 0.177 0.207 0.137 0.128 0.196 0.185 0.144 0.14 0.132 1.614 1.622 0.199 0.186 0.112 0.104 0.18 0.178 0.139 0,133 0.057 0.911 0.884 0.199 0.187 0-109 0.104 0.168 0.17 0.139 0.135 0.053 0.494 0.475 0.177 0.173 0.182 0.178 0.166 0.168 0.147 0.148 0.058 0.302 0.287 0.164 0.17 0.19 0.188 0.15 0.156 0.14 0.137 0.111 0.179 0.175 0.164 0.169 0.183 0.179 0.187 0.191 0.144 0.14 0.068 0.122 0.122 0.125 0.122 0.171 0.164 0.174 0.172 0.133 0.133 0,067 0.083 0.062 0.165 0.128 0.165 0.162 0.176 0.173 0.049 0.048 0,079

Table 29

[00167] Data analysis is given below in Tables 30-41: Plate 1, Donor 1: Standard calculations

Sample concentration Wells BackCongCyt kaues MeanValue Std Dev. CV% StD1 6 A1 5.965 2.611 2555 0.079 3,1 A2 5.7 2.499 StD2 3 B1 3.133 1.403 1,374 0.041 3 B2 2.998 1.345 SD3 1.5 C1 1.575 0.723 0,739 0.023 3.1 C2 1.647 0.755

S04 0.75 D1 0.775 0.365 0.35 0.021 5.9 D2 0.711 0.336 St05 0 375 E1 0.376 0.182 0.178 0.005 2.8 E2 0.361 0.175 St06 0.188 F1 0.168 0.084 0.08 0.006 7.1 F2 0.151 0.076 5107 0.094 G1 0.143 0.072 0.054 0.025 47,6 G2 0.069 0.036

Table 30 Sample calculations

A ~3 O.A6 0.112 0.1I 0.4 315 4 R435 .AllG, S0.3 Z0.124

4 a 0 95G 0.19S TM.5 Mg01 S3 4 0323 149 94'4 0.6

0.09OA 0.39S 0-1).1 C0.004 4.24>3.03 :

7 3 Q051 M. I a094 ams0 9.3 4 0375 3.7 D4 34 0.02S RT C4ay9- E3 !1032 0.0 63 .0.38 .0 31a.4. 4. 12 ' 369 34 ~ 0.0s .09 R'TDay 14_CGR £3:-.0.5 .15 .1 11 4 3.26.5 0 1.5

4 532 G'.035 0311 02. .07 33.3 4 30201 ,G 4 &0:014 I025S

5 3 3.41 0.22Z 0.1153 0.1,73 109m1 4 61 1-34 H4 0.02. n037

7 A5 30 'o12 0.022 3Q0Z2 QI.C3:3 14 4 03832 4.60.31 0.018

8hr.D'sy 5 0 52 0355S 0-127 0.13LC2 80.2 4 3. 5C9 LOS3 96 ID.3 02

Sh.: Day i4 CS G.003 0.004 N.0 50 654Z 4 0.3313 0.07 cv, :,1.7 0.0CI12

Da 4 D-04 03 ~ 0091 11004 4. 4 3.3K5 0.74

06 33'043 9 DAN 0g: ____ ___

DayS5 ES305 0. I:C6 0. 13 LI 004M 4.2 4. 0.412 C3, zc ES 3.51 0.%

D 7y OAS 0.05 .3 0-101 cWQa4 434 C.0 0.3 £6S 005''oS3 0.104

D9 65.08 0.094 0.099 0.07 T.3 4 0.31a~

Da.. 007.12 0.-241 9.3S 4 3.985B 103

0C, 24hrt Day 4 A7 2055 0.108 0.1 0.012 11-6 4 01399 062 As 047 0.092 OC, 24h, D' 5 87 2091 0.183 0.174 0.022 6.8 4 0.98 L44 8 083 0.166 0C, 24hr Day 7 C7 2047 0.092 0.91 0.001 16 4 :,362 074 C7 .046 G SC, 24hr Day 9 07 043 0.093 0.02 0.0:1 1.7 4 0.33 0.6s DS 042 0.081 O.C 24hr' Day 14 E7 0.038 0.073 0.75 0.003 18 4 0.3D0 0.62 EIS 0.04 0.077 37C, Shr Day 4 F7 2057 0.112 0.1:04 0.012 11.2 4 .A16 &.6 FS 1049 0.06

Day 5 G7 0059 0.116 0.116 0 0 4 2465 0.%6 GS 0.059 0.116 37C' &.h. Day7 H? 0.165 0.34 0.219 0.171 78.2 4 3.875 1.80 HS 0.05 0.098.______________

Day9 AS 2029 0.055 0.057 0.0C3 5 4 0223 .47 A1D 0.031 0.059 37C Shr. DayB14 B9 0.64 0.127 0.144 0.025 17.3 4 2577 19 BIC 2081 0.162 37C 24hr, DayC4 C. 2036 0.069 0.05 0.006 8 4 .261 54 C032 0.061

:24hr, Day 5 D2 C033 0.063 0.063 0 0 4 0.253 052 D10 2033 0.063

24mr, Day 7 ES 0.033 0.063 0.067 00306 Si 4 0.269 05 E10 C037 0.071 37c,

Day 9 FS 0035 0.067 0.065 0.003 4.4 4 261 .54 F10 033 0.063

24hr, Day 14 G3 f021 0.039 0.064 0.036 55.3 4 3256 053 G10 046 0.

Table 31 Klotho Concentration Changes in Time Course

Room Temp -15C 8hr 0C 8hr 0C 24hr 37C 8hr 37C 24hr Day 4 149% 17% 74% 82% 86% 54% Day 5 83% 134% 85% 144% 96% 52%

Day 7 77% 16% 83% 74% 180% 55% Day 9 66% 105% 81% 68% 47% 54% Day 14 55% 7% 199% 62% 119% 53%

Table 32 Plate 2, Donor 2: Standard calculations Sample Concentration Wells BackConcCalc Values MeanValue Std.Dev. CV% Stol 6 Al 5.451 2.736 2.78 0.062 2.2 A2 5.633 2.824 St02 3 BI 2.983 1.531 1.532 0.001 0.1 B2 2.987 1.533 St03 1.5 C1 1.613 0.847 0.841 0.008 1 C2 1.589 0.835 StO4 0.75 D1 0.792 0.427 0.419 0.011 2.5 D2 0.763 0.412 St05 0.375 El 0.407 0.225 0.223 0.003 1.3 E2 0.399 0.221 St06 0.188 F1 0.197 0.112 0.105 0.009 8.7 F2 0.173 0.099 St07 0.094 GI 0.087 0.051 0.051 0 0 G2 0.087 0.051

Table 33 Sample calculations

AB 0155 0276 611 a7 W24L

H3 0,.Ls9 0.294 cllS 022 t9s is IU 1120 94 0.155 CUE7

5 3 16 i12-86 32K3 &ME0 is1DL Q4 0156 0.279 1-J:Day 7 [3 W.44 0.256 3159? GI IS20 15 I03 5 0.5IS2 0D4 .1417 0.26.1 RT Ds 6 3 2154 0.274 02 a022 24 4 2.379 0. n 6E4 219 0.265s

24 F3 .111 o0.195 Ii 3.294 .1 -,-71 a 9-777 0.691 FK 012L 0.19 3

3Z'&rDay 40.053 0.09 3.065H 0202R Ell' 4 &3-4 0.30~

.12Z5 017 0.15' 0,D670S 44A 4 O.s 0.5S3 H4 0.0w C.1,3

3Zh.:Day AS 0.062 0. .05 C.203 &%03 2s C 4 .12 a.17

Sl'rr.Day 9 :5 ~ !IB O-SLO377 &0.059 12. 44 33202 B-6 D0.42 C.071

38'." Da y i ~ C50&4s 0:076 C.077 0201l L6 4 . 23IM 0.2 7

Ds .30 1r,

faj4 3E 15 3.2:51 .,5 022 OW6 4 0.0 32

30..022 5I C<av5 ES 1s7) 0.2:45 01267 0W23 2 I all2 FS 135 0.252:

30,.2Z'r, Esay? F5 Hs 1¼1 0245 %1.207 0.2213 4 21 4 3923 0.22-S :HG 012a 0.25017_____

cc.B72

0GC, 24r, Day 4 A7 0.154 0.274 &026 Q21 61 4 lOS3 032 A8 0.138 11245_ 0G,24hr, DayS :B7 0Q145 0258 025 0 0 4 1031 0.92 BS 0.145 0.2538 _____

0GC. 24h, Day 7 C7 Q1.39 0247 0247 0 C 4 037 0.38 C0.139 0.247 GC, 24hT Day9i D7 0.135 D241 0.245 0.005 2.1 4 09719 0.37 ID 0.14 G.249 0GC, 24hT. Day 14 £7 0.099 0.173 1 176 0.004 2.2 4 a704 0.63 ES .102 0 179 .37,, Sh'. Day : F7 0.14 11249 024- 0001 0.5 4 0.59 0.88 FS 0.139 0.247 37c, R, Day5 G7 C14a G.263 0271 0.01 33 4 1S08 0.36 G80.156 0.278 _____

37C .h, Day7 H7 Q174 0.312 023S .04 153 4 112 1.00 H8 0.4 11249 37, Eh,. Day A9 0.111 0.195 0.1& 0.009 4.8 4 0.755 0.S7 A1 104 182 37% ht.

Day 4 0.09 0.171 0164 0.01 6.3 4 .657 0.59 B20 0.09 0.157 37C, 24hr. Day 4 C9 0409 .192 0138 0005 2 4 0752 0.37 C10 0105 0,184

24hr, Day5 03 0Q107 0.188 0-,2 06 3A 4 .77 0.9 D10 0.112. 11197 37c 24hr,

Day 7 E9 01 0.175 .0.79 .0 5 2.9 4 .715 0.4 E____:10 0.104 0.122_____

241hr, Day 9 F9 C0.98 0.171 0168 0.0305 31 4 0.671 0.60 FZO 0.094 .154 .37c 24hr, Day 14 G9 0.11 0.193 0.17 0.033 197 4 0.79 0.0 G10 0.084 0.146

Table 34 Klotho Concentration Changes in Time Course Room Temp -15°C 8hr 0°C 8hr 0°C 24hr 37°C 8hr 37°C 24hr Day 4 100% 30% 89% 92% 88% 67% Day 5 100% 53% 92% 92% 96% 69% Day 7 92% 37% 88% 88% 100% 64%

Day 9 96% 27% 91% 87% 67% 60% Day 14 69% 27% 74% 63% 58% 60%

Table 35 Plate 3, Donor 3: Standard calculations Sample Concentration Wells BackConcCalc Values MeanValue Std.Dev. CV% Stol 6 Al 6.24 2.768 2.784 0.023 0.8 A2 6.333 2.8 St02 3 BI 3.15 1.629 1.636 0.009 0.6 B2 3.182 1.642 St03 1.5 Cl 1.52 0.926 0.919 0.011 1.2 C2 1.489 0.911 St04 0.75 Dl 0.705 0.51 0.497 0.018 3.7 D2 0.659 0.484 St05 0.375 El 0.337 0.288 0.286 0.003 1 E2 0.331 0.284 St06 0.188 F1 0.195 0.188 0.177 0.016 9.2 F2 0.164 0.165 St07 0.094 G1 0.108 0.119 0.12 0.001 1.2 G2 0.11 0.121

Table 36 Sample calculations

'' 43 0155~ W3152 014t 01 3 69 10

A3 0.161 3a159 0WK 000? a 4 (63c~q -A4- 0.158- 3. 1 3 ___

:s £3 0.159 0.157 A,157 0l 0 4 ar627 1.33 £4 i.£59 G1.157

7 33 0.15 0.145 0 .46 f0. 00I1 36 4 13594 135S CA4 G.151 314 FT Days Q3 1316 3.159 0.9 f1&012 1-1 4 GE637 ai E4 a,162 1.1651 ____

14 F3 a13£31 C.1.22 0. 125 0.00 3.N 4 3.0 35 £4 0.136 0.128 _____

4 53 111 4 &.102 01103 13001 as 4 T411 3.67 W4 1115 Giza0 C-,

:s H3I 0.155 0156 0. 128 1135 '3312 4 s0.513 084 H4 I i £1 11.01 _____ ________

8hr:T Day 450.102a C.09 5 0.0.R2 0.05s 5.2 4 a133S7 a3SO

AL C. 132 &.0,89

9.3 0.0a2CCSk TZ2 ams0 ELE 4 33223

BY.Day

cc h c 0.093 fm.38G15 0.058 W90 5i4 A 0572 £6 13£05C 0.913.5

lav45 E5 0l.153 153 13 TIM. 4 2.5 4 a06572 E3S C,1576 0 154 9

DZyo ES GC151 0147 0.1547 11001 14 31 FS f, 5 112 1 0£,Mr, Day7 £5 ar:'151 01- AI14 0.00 1.2 4 0.52

DayS1 HC- 0-h.4 C5 114S 0.002- .1. 4 1307

Ha$-S 13Is £1.5 018 0.0l364 .3

0C, 24hr Day4 A7 0.161 .15 L158 5 002: 1.1 4 .632 A8 0.153 0.157 1.04 OC, 24hr Da5 27 0156 0.153 0.156 0.04 2-3 4 0.622 B.3 0.2iD .158 1 oC, 24hr,. Day 7 C7 0.15 0.145 C147 0.032 1.2 4 0587 CZ D.152 a14. 136 0C, 24hr Day 9 07 G.154 0 15 0147 0BJ4 3 4 1589 DS 149 144 0 97 GC, 24h, Day 24 E7 0132 123 3424 I]l 07 4 DA96 E8 G.133 0125 01:182.1 37c, Shr Day 4 F7 0.15 0145 0147 0.02 1.2 4 3587 FD .152. .148 D _IS 036 37C.Sh Dav.5 G7 0154 2153 Q.163 0 3 4 :653 G8 R64 163 1.)7

37 Sh Day7 H7 0.17 0.171 0467 0.035 3,3 4 ES8 HS 164 0153 1-10 37c, SRhr Day 9 AS 3.24 133 131 003 2 4 525 A10 L.137 0129 _ 86 37c, sh Day14 G. 0131 2122 1122 QC01 U'7 4 GA86 BI0 0.23 Z.121 BO 37c,

Day 4 CS 0139 132 .136 U05 39 4 Q542 C10 0145 0a139 E095 37c, 24hr, Day5 09 0237 0.129 0.13 2Q01 0.7 4 &.S2 D10 0138 . Q131 37c, 24hr. Day 7 ES 2134 0.126 26 0 G 4 0.503 E10 1134 0.126 '0.83 37C, 24hr, Day9 F9 0.133 1122 U15 093 28 4 GA89 FI. 0.129 0.22 .80 .37c, 24hr, Day 14 G9 0122 2111 0.12 2C01 0:7 4 0.448 GI0 0123 23al_ 0.74 Table 37 Klotho Concentration Changes in Time Course

Room Temp -15 0C 8hr 0°C 8hr 0°C 24hr 37 0C 8hr 370 C 24hr Day 4 100% 67% 94% 104% 96% 89% Day 5 103% 84% 101% 102% 107% 85% Day 7 103% 60% 97% 96% 110% 83% Day 9 96% 54% 100% 97% 86% 80% Day 14 105% 58% 97% 81% 80% 74%

Table 38 Plate 4, Donor 4: Standard calculations

Sample Concentration Wells BackConcCalc Values MeanValue Std.Dev. CV% Stol 6 Al 5.507 2.715 2.671 0.062 2.3 A2 5.321 2.627 St02 3 BI 3.058 1.542 1.546 0.006 0.4 B2 3.074 1.55 St03 1.5 C1 1.623 0.839 0.825 0.019 2.3 C2 1.569 0.812 StO4 0.75 Dl 0.794 0.422 0.412 0.013 3.3 D2 0.757 0.403 St05 0.375 El 0.422 0.23 0.222 0.011 4.8 E2 0.393 0.215 St06 0.188 F1 0.19 0.107 0.105 0.003 2.7 F2 0.182 0.103 St07 0.094 G1 0.086 0.05 0.05 0 0 G2 0.086 0.05

Table 39 Sample calculations

Oh 0.0-4 02425

84 0.124 10242

ES a30127 W.27 0-215 M.Y 7.9 035 1.02 £4 ,-UL4 0.203 RT0 03c 0405 a.127 02K3 M.Y0 T3 4s I.I 0

CA MCI0 0.179 RTD:k~y9 E3 0.092 r.:452 0.263 000, C1131 4.7 4 0620.73

F4 C.097 0:.173 RT0c, G353 _-a 1 4 nai ac____3 C34___ 0. 0 2

5____ 03452 3 05 GW

AE 010576 .7

as l.0 Los91K OAK0 I.0. 3 4 :01.24 0.428 964 .0D5 10528

14 CS 0.037 W.62 0.13 0.036 36<7, 4 &0232 a27

DS .1 I5 0.0.95012 l 1,3- 74 - . 370 1

Da 7 AS It.5 04239 0.205 0.0 2S 2.7 4 0:74 0.59

Da 24 5 3 0 .053 0. I6 I . 04 2A 4 02202 26 0.03 0.129

Sh:~.fl78

GC, 24h, Day 4 A7 0.124 .222 L21 014 63 024S &99 AS G.113 &201 CC, 24h, Day E 57 .102 192 019 1003 1.4 4 0.76 089 H3 0.106 &.132 00, 24hr Day 7 C7 0.096 0.17 l.7. 0.003 15 4 :6E66 0.80 C 11099 &.173 0C, 24hr Day9 07 0.94 &.166 0.266 0.003 16 4 0:671 0.7B 08 0.096 0.17 ___

C, 24h, Day14 E7 11079 0.136 Q142 0.10Z 5-5 4 0.568 0.66 EB 0.84 0147 370s Shr Day4 F7 0115 0205 0.208 005 2.5 4 0.834 097 FS 0.9 R212 37001he Day5 G7 0.102 0I79 0.J3 f0181 1 4 1715 083 G8 11 0177 37C .h.0 Day7 H7 G-104 0.184 082 0094 2-2 4 1726 0.5 HS G-101 0179; 370Sh Day9 A9 G.072 0.12 0122 .005 4,2 4 057 0,47 A10 R068 B.11 37C0She DayB14 9 G067 0116 0L1 1 0009 63 4 :44 0,S2 B20 R061 0.105 ____

37C,, 24a.r, Day4 C9 00C67 11116 0113 0J5 46 4 045 053 CIO CD63 0.1095 241hr Day 5 09 .,075 0.131 Q.132 Q0.01 1 4 Q.528 0.62 D10 C'076 0.133

24hrw '24hr Day7 £9 068 118 0115 0.&34 3.3 4 Q.462 0.54

37C*

DayS 7 S EC072 .125 0122 1Q05 4.2 4 0A87 S37 F10 Q%6 01IS 37C; 241he; Day 14 9a061 G9 105 0105 0 G 4 Q4:22 0.49 G0- 1C. 0.061 01,05

Table 40 Klotho Concentration Changes in Time Course

Room Temp -15°C 8hr 0°C 8hr 0°C 24hr 37°C 8hr 37C 24hr

Day 4 100% 41% 89% 99% 97% 53% Day 5 101% 61% 97% 89% 83% 62% Day 7 85% 49% 90% 80% 85% 54% Day 9 78% 28% 79% 78% 57% 57% Day 14 78% 27% 75% 66% 52% 49%

Table 41

[00168] In light of the foregoing, at least one embodiment includes a Klotho detection kit and/or assay. The inventive kit and/or assay may be suitable for CLIA lab testing of clinical samples. The kit can be configured (specifically) for use in monitoring, detecting, and/or quantifying, or diagnosing deficiency of one or more proteins selected from (1) Native (e.g., endogenous) Klotho, (2) recombinant Klotho-Fc fusion, and (3) recombinant 6xHis Klotho. The Klotho protein can be detected in a biological sample. The sample can be (substantially) unpurified in some embodiments. For example, the sample can be or comprise mammalian (e.g., human) blood and/or plasma.

[00169] In at least one embodiment, a kit can comprise one or more lancets adapted, configured, or suitable for a finger prick, a sample collection container adapted, configured, or suitable for collecting blood from a finger prick, one or more antiseptic elements, such as disposable (e.g., alcohol) wipe(s), one or more adhesive bandages, a foil envelope or other biopackaging, and a shipping container, such as an envelope.

[00170] Some embodiments can include a method of diagnosing Klotho deficiency in a mammalian subject. The method can include obtaining a fluid sample mixture selected from the group consisting of: (i) mammalian serum, optionally in the form of capillary blood, mixed with a preservative or anti-coagulant comprising one or more of heparin, lithium heparin, EDTA, and K2 EDTA, the mammalian serum having an amount of soluble Klotho protein; and (ii) mammalian serum, optionally in the form of capillary blood, the mammalian serum having an amount of soluble Klotho protein, the method further comprising mixing the mammalian serum with a preservative or anti-coagulant comprising one or more of heparin, lithium heparin, EDTA, and K2 EDTA to form the mixture. The method can also include storing the mixture for at least 24 hours, or more, at room temperature, the preservative or anti-coagulant stabilizing the soluble Klotho protein for the at least 24 hours, or more, at room temperature. After the storing step, the method can include quantifying the amount of the soluble Klotho protein in the mixture. The method can also include diagnosing the mammalian subject with Klotho deficiency when the quantified amount of soluble Klotho protein in the mixture is less than a predetermined threshold amount.

[00171] As described above, the fluid sample mixture comprises about 10-1000ul, preferably about 50-200ul of capillary blood from the mammalian subject, or wherein the step of obtaining the fluid sample mixture comprises obtaining about 10-1000ul, preferably about 50-200ul of capillary blood from the mammalian subject. The step of quantifying the amount of the soluble Klotho protein in the mixture comprises detecting the soluble Klotho protein using a first antibody that binds to a portion of the soluble Klotho protein, and optionally, detecting the soluble Klotho protein using a detection antibody that binds to a portion of the first antibody or performing an enzyme-linked immunosorbent assay (ELISA) to detect and optionally quantify the soluble Klotho protein. Mass spectrometry can also be used to detect proteins.

[00172] In some embodiments, a diagnostic or informational report can be prepared. The report can include an indication or display of measured Klotho level(s) for one or more Klotho proteins. In some embodiments, the report can display a comparison chart or graph depicting the measured level overlaid on an age-based graph illustrating average or median Klotho levels for various ages and, optionally, indication of the 2 5thpercentile and/or 7 5th

percentile for the various ages. Figure 13 illustrates an example report graph or chart. Thus, in some embodiments, diagnosing the mammalian subject with Klotho deficiency comprises displaying a Klotho deficiency determination, indication, or diagnosis on a user interface of a computer system and/or producing a file or report, in physical or electronic form, that displays the Klotho deficiency determination, indication, or diagnosis, the Klotho deficiency determination, indication, or diagnosis optionally including the quantified amount of the soluble Klotho protein and/or the predetermined threshold amount.

[00173] It will be appreciated that the term "diagnosis," or diagnosing," and similar terms, as used herein, is not intended to convey or require (in all cases) a certified, regulatory compliant, medical diagnosis, as required or regulated by the U.S. Food and Drug Administration (FDA) or any other government or non-government entity, organization, or agency. Rather, "diagnosis," or diagnosing," and similar terms relates to providing information that may be indicative of a condition and/or helpful in making a determination related to the condition.

[00174] In some embodiments, one or more additional analytes can be monitored, detected, and/or quantified. Illustratively, the additional analytes can be related to Kidney disease, fibrotic diseases, and/or aging. In some embodiments, the one or more additional analytes can be selected from the group consisting of FGF, PTH, non-oxidized PTH, Vit D, Vit E, KIM-1, NGAL, Interleukins and other inflammatory bio-markers, testosterone, estrogen, etc.

Therapeutic Proteins

[00175] Embodiments of the present disclosure can include one or more therapeutic and/or recombinant human alpha soluble Klotho proteins, protein fragments, and/or protein variants.

[00176] The protein can comprise all or a subset of amino acid residues 1-1012, 1-981, 29 981, 34-981, 36-981, 131-981, 1-549, 29-549, 34-549, 36-549, or 131-549 of human alpha Klotho isoform 1 or 2. The protein can have at least and/or about 80% amino acid sequence identity to all or a subset of amino acid residues 1-1012, 1-981, 29-981, 34-981, 36-981, 131 981, 1-549, 29-549, 34-549, 36-549, or 131-549 of human alpha Klotho isoform 1 or 2. For instance, at least a portion of the protein can have at least 80%, etc. amino acid sequence identity to at least a portion of one of SEQ ID NO: 2 through SEQ ID NO: 70 or SEQ ID NO: 107 through SEQ ID NO: 120 or SEQ ID NO: 125 through SEQ ID NO: 128 or SEQ ID NO: 133 or SEQ ID NO: 152, or a combination of two or more thereof Other portions or fragments of the protein sequences described in the present application are also contemplated herein. For instance, some embodiments can include a protein having at least a portion with at least 80%, etc. amino acid sequence identity to any suitable portion of one of SEQ ID NOS: 1-75, or a combination of two or more thereof.

[00177] Some embodiments can include a protein having one or more amino acid variations as compared to human alpha Klotho isoform 1. Illustratively, the protein can comprise a human C370 variant. For instance, the protein can include a C370S alteration, thereby comprising S370. The protein can include human F352 or other than F352V in some embodiments. In at least one embodiment, the protein can include the C370S alteration, thereby comprising S370, without a F352V variant, preferably with F352. The protein can include H193 or other than the H193R variant. All other standard amino acid substitutions at amino acid residue (or position) 193, 352, and/or 370 of human alpha Klotho isoform 1 are contemplated and explicitly disclosed herein.

[00178] Some embodiments can include a variation at amino acid residue 45 of human alpha Klotho isoform 1. At position 45, the residue can be a valine (Val; V), a phenylalanine (Phe; F), or another amino acid.

[00179] The protein can also include one or more glycans (attached thereto). For instance, native human alpha Klotho isoform 1 can have glycans attached (via glycosylation) at amino acids 106, 159, 283, 344, 604, 612, and/or 694. Accordingly, the proteins of the present disclosure, or Klotho protein sequences thereof, can have one or more of the same (or similar) glycans attached (via glycosylation) thereto (e.g., at the same amino acid position(s)).

In a preferred embodiment, the protein includes all of the same or similar (native-type) glycans attached thereto, at the same amino acid position(s).

[00180] In some embodiments, the protein can include a signal peptide or signaling sequence. For example, the protein can include a native Klotho signaling sequence. The protein can include a non-native or synthetic signaling sequence. In some embodiments, the signaling sequence can be an N-terminal signaling sequence and/or upstream of (or N terminal to) a Klotho protein sequence. In other embodiments, the signaling sequence can be C-terminal or otherwise disposed. Preferably, the signaling sequence can be, comprise, or have at least 80% amino acid sequence identity to native human alpha Klotho isoform 1 signaling sequence, native human alpha Klotho isoform 2 signaling sequence, SEQ ID NO: 71 or SEQ ID NO: 72.

[00181] In some embodiments, the protein can include an amino acid tag. The tag can be a C-terminal tag and/or downstream of (or C-terminal to) a Klotho protein sequence. In other embodiments, the tag can be N-terminal or otherwise disposed. The tag can be or comprise an Fc-peptide (or Fc-fusion tag, Fc domain, etc.). For instance, the tag can be or comprise an IgG1-Fc protein sequence. Preferably, the tag can be, comprise, or have at least 80% amino acid sequence identity to SEQ ID NO: 74.

[00182] The tag can also, or alternatively, be or comprise a peptide comprising a Twin-Strep protein sequence, such as a Twin-Strep tag or protein sequence (e.g., as known in the art). Preferably, the signaling sequence can be, comprise, or have at least 80% amino acid sequence identity to SEQ ID NO: 75, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104.

[00183] The tag can also, or alternatively, be or comprise a polysialic acid (PSA). In at least one embodiment, the PSA tag can render the conjugated (Klotho) protein resistant to one or more proteases. In some embodiments, maintaining an amount (e.g., even a relatively small amount) of sialic acid in the protein conjugate can prevent protease attack and subsequent targeting, breakdown, and clearance of the molecule (e.g., through the liver).

[00184] In at least one embodiment, the tag can be cleaved from the protein. In other embodiments, the tag can be retained as part of the protein. In some embodiments, the tag can enhance solubility and/or (serum) half-life of the protein. In some embodiments, the tag can be utilized during protein purification (e.g., as part of a purification mechanism).

[00185] In some embodiments, the protein can include a linker (e.g., amino acid linker) disposed between a Klotho protein sequence and an amino acid tag. Illustratively, the linker can comprise between 1 and 40 amino acids, preferably between 5 and 20 amino acids, more preferably between 6 and 12 amino acids, most preferably between about 8 to 10 amino acids. The linker can be or comprise a GS linker (e.g., a (G4 S) 2 linker) or other linker (e.g., a GGENLYFQ linker) in some embodiments. Preferably, the linker can be, comprise, or have at least 80% amino acid sequence identity to SEQ ID NO: 73 or SEQ ID NO: 105.

[00186] In at least one embodiment, the protein can be cGMP regulation compliant, as determined and enforced by the U.S. Food and Drug Administration (FDA). For instance, the Klotho protein can be at least 90%, 92%, 95%, 96%, 97%, 98%, or 99% pure, dry weight. In some embodiments, the Klotho protein sample can include less than about 1-100 parts per million (ppm), less than about 100-1000 parts per billion (ppb), or less than about 1-100 ppb CHO host cell proteins (HCP), nucleic acid, and/or other cellular components, or any value or range of values disposed therebetween. Klotho Protein Variants

[00187] Therapeutic S-Klotho proteins of various lengths (e.g., S-Klotho, isoform 1 or 2, 1 981, 29-981, 34-981, 36-981, 131-981, 1-549, 29-549, 34-549, 36-549, 131-549, and so forth) can be modified in a variety of ways to achieve various beneficial effects and/or results not exhibited in native Klotho proteins. Illustratively, the QuickChange XL Site-Directed Mutagenesis Kit (Stratagene) can be used to alter the nucleic acid sequence of various S Klotho constructs. Other mutagenesis methods and kits as known in the art can also be used. For instance, various sub-cloning methods and kits are known in the art and commercially available. Amino acid changes may affect (e.g., improve, enhance, decrease, etc.) protein expression, protein stability, protein solubility, protein binding, protein specificity, protein activity, protein function, immunogenicity, toxicity, etc.

[00188] In at least one embodiment of the present disclosure, a protein is modified with one or more C-terminal tags and/or N-terminal tags. Such tags can function to extend the serum and/or soluble half-life of the protein (in one or more therapeutic or other environments). Tags can also be useful as markers for the presence or diagnostic localization of the protein, isolation or removal of the protein, delivery or transport of the protein, binding of the protein to one or more targets (e.g., protein, nucleic acid, organelle, cellular structural component, etc.), enzymatic processing or cleavage, and so forth. In at least one embodiment, the C terminus of the protein can be tagged with a TEV-Twin-Strep tag or sequence, an immunoglobulin (IgG) Fc domain tag or sequence, or other tag or sequence as known in the art and/or described further herein. Additional description can be found in the articles "Fusion Proteins for Half-Life Extension of Biologics as a Strategy to Make Biobetters," "What is the future of PEGylated therapies?" and "Strategies for extended serum half-life of protein therapeutics," the entirety of each of which is incorporated herein by specific reference. In certain embodiments, a linker or linker peptide can be inserted and/or disposed between the (native or variant) Klotho protein sequence and the tag.

[00189] In some embodiments, the modified Klotho protein can include an alternative (e.g., native, non-native, and/or synthetic) signal peptide. For instance, in some embodiments, the native signal peptide sequences can be replaced and/or supplemented with an alternative signal peptide or signaling sequence (SS). In some embodiments, a native Methionine residue of a Klotho protein can be removed and a Methionine residue at the N-terminus of the SS can be included. Additional description can be found in the thesis "Generation of high expressing CHO cell lines for the production of recombinant antibodies using optimized signal peptides and a novel ER stress based selection system," the entirety of which is incorporated herein by specific reference. In certain embodiments, a linker or linker peptide can be inserted and/or disposed between the (native or variant) Klotho protein sequence and the alternative SS.

[00190] Some embodiments can include one or more amino acid variants. It will be appreciated that the present disclosure contemplates variation of any one or more of the native amino acids in any of the disclosed Klotho proteins to any other amino acid, whether naturally-occurring, synthetic, or otherwise configured. S-Klotho V45F Protein Variant

[00191] Substituting a Phenylalanine in the place of the Valine at (native) position 45 of human alpha Klotho (V45F) has been found by the Inventors to have surprising and unexpected benefits. For example, V45F soluble Klotho, and fragments or fusion proteins thereof, express at higher levels in CHO and HEK-293 cells than does the native, wild type V45 protein. Commercially, achieving higher levels of soluble protein expression can be desirable. Accordingly, some embodiments of the present disclosure include a Klotho protein having the V45F substitution. S-Klotho C370S Protein Variant

[00192] In humans, the Klotho gene maps on chromosome 13ql2. A variant, known as KL VS, is present in approximately 15-25% of Caucasians. The variant is composed of six single nucleotide polymorphisms (SNPs), two of which cause amino acid substitutions (i.e. F352V and C370S - Phenylalanine 352 changed to Valine and Cysteine 370 changed to Serine). In vitro transfection assays have shown that secreted levels of klotho are reduced 6-fold for the V352 variant, while they are increased almost 3-fold for the S370 form. However, these two variants in the human KLOTHO gene segregate together and form the KL-VS haplotype that increases klotho secretion in the range of 1.6-fold. For instance, it has been reported that in a screening of over 300 individuals taken from the geographically and/or ethnically distinct cohorts, not a single individual was found to harbor only one of the V352 variant or the S370 variant.

[00193] An embodiment of the present disclosure includes a recombinant S-Klotho protein having the C370S homovariant (i.e., without the presence (or with deletion) of the F352V variant). The C370S variant can be produced and/or expressed in the context of any protein construct described herein. For instance, the C370S variant can be produced or expressed in the context of S-Klotho, isoform 1 or 2, 1-981, 29-981, 34-981, 36-981, 131-981, 1-549, 29 549, 34-549, 36-549, 131-549, and so forth, with or without a tag (e.g., (IgG) Fc tag, TEV Twin-Strep tag, TEV sequence, etc.). Accordingly, the nucleic acid construct or cDNA from which the protein is expressed can be of corresponding length.

[00194] Embodiments can include producing a S370 heterozygous or homozygous variant construct, transferring (e.g., via transfection) the resulting construct, which encodes the S Klotho C370S protein, into an appropriate expression system (e.g., CHO cells), and/or transiently expressing the S-Klotho S370 protein. The S370 Klotho protein may be expressed at higher levels than the F352V/C370S protein and/or wild-type F352/C370 protein. Embodiments can include purifying (and optionally quality-control testing) the expressed protein for therapeutic administration. Embodiments can include administering a therapeutic or therapeutically-effective amount of the S-Klotho C370S protein to a subject in need thereof The subject may, for example, harbor or express the KL-VS variant. Alternatively, the subject may be of wild-type of other mutant or variant type. Administration of the recombinant S-Klotho C370S protein can lead to a beneficial increase in blood S-Klotho levels. Accordingly, the circulating concentration of S-Klotho in subjects that receive the therapeutic, recombinant, S-Klotho C370S protein may not be subjected to the dilutive effects that are observed when the F352V variant is present.

[00195] Nucleic Acids and Expression Vectors

[00196] Some embodiments can include a nucleic acid or nucleic acid construct. For instance, embodiments can include an expression vector or nucleic acid construct. The nucleic acid can encode a recombinant human alpha soluble Klotho protein, protein fragment, or protein variant, as described herein. In at least one embodiment, the nucleic acid can encode a Klotho protein sequence, an optional (native or non-native) signaling sequence (e.g., at the N-terminus or N-terminal of the Klotho protein sequence), an optional linker sequence (e.g., GS linker), and/or an amino acid tag (e.g., IgG1-Fc or TEV-Twin-Strep), as described herein.

[00197] In some embodiments, the nucleic acid can express a protein that includes all or a subset of amino acid residues 1-1012, 1-981, 29-981, 34-981, 36-981, 131-981, 1-549, 29 549, 34-549, 36-549, or 131-549 of human alpha Klotho isoform 1 or 2. At least a portion of the protein can have at least or about 80% amino acid sequence identity to all or a subset of amino acid residues 1-1012, 1-981, 29-981, 34-981, 36-981, 131-981, 1-549, 29-549, 34-549, 36-549, or 131-549 of human alpha Klotho (isoform 1 or 2). For instance, at least a portion of the protein can have at least and/or about 80% amino acid sequence identity to all or a portion of one of SEQ ID NO: 1 through SEQ ID NO: 75, or a combination of two or more thereof In a preferred embodiment, the protein can have at least and/or about 80% amino acid sequence identity to all or a portion of one of SEQ ID NO: 2 through SEQ ID NO: 70 or SEQ ID NO: 107 through SEQ ID NO: 120 or SEQ ID NO: 125 through SEQ ID NO: 128 or SEQ ID NO: 133 or SEQ ID NO: 152.

[00198] In some embodiments, at least a portion of the nucleic acid can have at least and/or about 80% (e.g., at least about 8 2 %, 8 5%, 8 6 8 7 %, 8 8 %, 8 9 %, 9 2 %, 9 3 %, %, 90%, 91%, 94%, 95%, 96%, 97%, 98%, or 99%, or 100% nucleotide sequence identity to one of SEQ ID NO: 76 through SEQ ID NO: 106 or SEQ ID NO: 121 through SEQ ID NO: 124, or a combination of two or more thereof In a preferred embodiment, the nucleic acid can have at least and/or about 80% nucleotide sequence identity to one of SEQ ID NO: 76 through SEQ ID NO: 106 or SEQ ID NO: 121 through SEQ ID NO: 124.

[0199] Nucleic acid sequences of the present disclosure can also include a stop codon, as known in the art (e.g., TGA, TAG, TAA). Cell Lines and Methods of Manufacture

[0200] An embodiment of the present disclosure can include a cell line. The cell line can comprise any suitable cell type, such as CHO cells, HEK cells, HL-60 cells, or other cell line as known in the art. Illustratively, the cell line can comprise CHO cells (e.g., a plurality of CHO cells). For the sake of brevity, reference to CHO cells contemplates a specific reference to HEK cells (e.g., HEK-293 cells), HL-60 cells, and/or any other (protein expression) cell(s) or cell line(s) known in the art. In some embodiments, the cells can (each) contain (one or more copies of) an exogenous nucleic acid. The nucleic acid can encode a polypeptide with at least and/or about 80% amino acid sequence identity to at least a portion of one of SEQ ID NO: 1 through SEQ ID NO: 75, or a combination of two or more thereof, preferably to one of SEQ ID NO: 2 through SEQ ID NO: 70.

[0201] The nucleic acid can comprise at least one transgene or cDNA. In some embodiments, at least a portion of the nucleic acid can have at least and/or about 80% nucleic acid sequence identity to one of SEQ ID NO: 76 through SEQ ID NO: 106 or SEQ ID NO: 121 through SEQ ID NO: 124, or a combination of two or more thereof, preferably one of SEQ ID NO: 76 through SEQ ID NO: 106 or SEQ ID NO: 121 through SEQ ID NO: 124. The nucleic acid can be or comprise a plasmid or other (structural) form of nucleic acid.

[0202] In some embodiments, the exogenous nucleic acid can encode a functional enzyme, such as dihydrofolate reductase (DHFR) and/or glutamine synthetase (GS). In at least one embodiment, the cells can be or comprise dihydrofolate reductase (DFR)-deficient CHO cells, such as CHO-S cells or CHO-M cells. The nucleic acid can include a promoter (e.g., a weak up to a strong promoter, as understood by those skilled in the art). For instance, in some embodiments, the nucleic acid can include a (strong) promoter associated with the transgene having at least 80%, etc. nucleic acid sequence identity to one of SEQ ID NO: 2 through SEQ ID NO: 70 or SEQ ID NO: 107 through SEQ ID NO: 120 or SEQ ID NO: 125 through SEQ ID NO: 128 or SEQ ID NO: 133 or SEQ ID NO: 152. Thus, the transgene can be under the control of a promoter.

[0203] For convenience, CHO cells and/or cell lines are referred to throughout the present disclosure. It is noted, however, that other cells, cell lines and/or host cells (besides CHO cells) are also contemplated within the scope of the present disclosure. Accordingly, a reference to CHO cells and/or cell lines also contemplates reference to and/or use of other known cells, cell lines and/or host cells (e.g., HEK cells, such as HEK-293 cells, HL-60 cells, and so forth). Transfection

[0204] A method of manufacturing the cell line can include introducing the exogenous nucleic acid into the cells, preferably via transfection, or other technique, as known in the art. In at least one embodiment, a serum-free growth optimized, cell-suspension of a cell line was used as the host cell line for insertion of a nucleic acid (plasmid) containing a promoter, a human alpha S-klotho transgene encoding a polypeptide with at least 80% amino acid sequence identity to at least a portion of one of SEQ ID NO: 2 through SEQ ID NO: 70 or SEQ ID NO: 107 through SEQ ID NO: 120 or SEQ ID NO: 125 through SEQ ID NO: 128 or SEQ ID NO: 133 or SEQ ID NO: 152, and a selectable (enzyme) marker. The transgenes, respectively, encode amino acids 1 through 981, 29 through 981, or 34 through 981 of human alpha soluble Klotho. In particular embodiments, the transgenes had sequence portion(s) corresponding to one or more of SEQ ID NO: 76 through SEQ ID NO: 106 or SEQ ID NO: 121 through SEQ ID NO: 124 (or had at least 80% nucleic acid sequence identity to one of SEQ ID NO: 76 through SEQ ID NO: 106 or SEQ ID NO: 121 through SEQ ID NO: 124).

For DHFR-deficient CHO cell lines (such as the CHO-S cell line), the selectable (enzyme) marker was exogenous DHFR. For other cell lines, the selectable (enzyme) marker was exogenous GS. Growth, Selection and/or Gene Amplification

[0205] Some embodiments can include growing the cells (e.g., transfected cells) on a solid medium and/or in a liquid medium (e.g., in suspension cell culture), preferably in a serum free and/or animal (or animal-derived) protein (component) free medium. For instance, cells can be plated on solid growth media for a period of time. The cells can also or alternatively be grown in suspension culture and/or in liquid medium. The liquid medium preferably comprises a carbon source, a nitrogen source, and one or more vitamins, minerals, salts, amino acids, supplements, or additives. In some embodiments, the medium can also lack hypoxanthine and thymidine (HT), glutamine, etc.

[0206] In at least one embodiment, after a certain period of time (e.g., 48 hours post transfection), the cells can be gathered (e.g., detached), optionally centrifuged (e.g., at 100 x g for 5 min.), and/or seeded (e.g., at approximately 2000 cells/well), such as into a 96 well adherent culture plate (e.g., containing serum supplemented, -HT and/or -glutamine media). The medium can also include MTX and/or MSX in certain embodiments. Non transfected cells may die within 7-14 days after selection (e.g., after exposure to MTX and/or MSX in -HT and/or -glutamine media.

[0207] In certain embodiments, the cells can (be selected to) contain at least about 2 to 10 copies, at least about 10 to 20 copies, at least about 20 to 30 copies, or at least about 30 to 50 copies of the exogenous nucleic acid (e.g., per cell). Accordingly, the method can include selecting cells that contain at least about 2 to 10 copies, at least about 10 to 20 copies, at least about 20 to 30 copies, or at least about 30 to 50 copies of the exogenous nucleic acid (e.g., per cell). For instance, (successively increasing levels of) MTX and/or MSX can be administered to the cells (e.g., at a concentration of about 1 nM - 1 M, about 10 - 100 nM, etc.).

[0208] Dihydrofolate reductase (DHFR) gene amplification in DHFR-deficient CHO cells (such as the CHO-S cell line) transfected with exogenous DHFR, was accomplished by successively increasing levels of methotrexate (MTX) in growth medium. Because the plasmid contains DHFR, this allows for the amplification of the S-klotho gene (fragment) within the host cell upon exposure to MTX (10 - 100 nM). The GS gene expression system was also used to amplify cells transfected with exogenous GS (e.g., upon exposure to MSX). Alternatively, GS -/- host cell lines were also used, which removed the need for MSX. These steps resulted in the production of numerous copies of the S-klotho gene (e.g., between 10 to 30 copies of the gene per cell) and resultant high levels of expression of the S-klotho protein in the transgenic cell line.

[0209] In suspension culture, the protein can be secreted from the cells into the liquid medium in some embodiments. For instance, certain cells and/or cell lines of the present disclosure can secrete (or be selected to secrete) up to a concentration of 200 - 500 mg of protein per liter of liquid medium, 500 - 2000 mg of protein per liter of liquid medium, 2000 5000 mg of protein per liter of liquid medium, or any value or range of values therebetween (without concentrating the protein). In at least one embodiment, high producing cell lines (or suspension cultures) can be selected, such that the concentration of human recombinant alpha soluble Klotho protein in the medium (of the selected suspension culture or suspension cultures of the selected cell lines) is at least 200 mg/L, preferably at least 500 mg/L, more preferably at least 1000 mg/L, even more preferably at least 2000 mg/L, still more preferably at least 5000 mg/L, without concentrating the protein.

[0210] Sub-cloning of the resultant high S-klotho producing, transgene-containing colonies by limited cell dilution was conducted to further produce S-klotho-secreting cell lines that secrete in the range of 500 to 2000 mg/L S-klotho into the cells conditioned media. All cell constructs were restriction digested and sequence verified.

[0211] In some embodiments, the cells can be grown in a bioreactor having a volume or working volume of at least 10 liters, preferably at least 25 liters, more preferably at least 50 liters, even more preferably at least 100 liters, still more preferably at least 250 liters, still more preferably at least 500 liters, still more preferably at least 1,000 liters, still more preferably at least 2,000 liters, still more preferably at least 2,500 liters, still more preferably at least 5,000 liters, still more preferably at least 10,000 liters. Cell Line Maintenance

[0212] For the amplified high-producing S-Klotho cell lines (e.g., produced by DHFR/MTX or GS/MSX systems), optionally followed by cell subcloning, judicious use of concentrated media feeds administered to the production cell lines during scale-up and up to the final bioreactor run were done in serum-free and animal protein component-free basal media.

[0213] Scale-up of high producer cell lines was done by cell inoculum expansion in cell suspension in shake flasks or in the Wave Bag systems followed by the successive inoculation of the cells produced in OOL and then 500L capacity bioreactors. Cell viability was maintained at greater than 85% viable cells throughout the growth cycle in shake flasks,

Wave Bags, or bioreactors; and then at 80% or greater viable cell counts in bioreactors during the plateau phase of CHO S cellular growth with the concomitant production of up to 1-3 g/L of S-klotho produced (designated as the "high producers"). Protein Production

[0214] Certain embodiments can employ recombinant DNA strategies that utilize strong promoter sequences and/or high copy number plasmids for production of therapeutic amounts of the Klotho protein in mammalian (e.g., CHO) cells. In at least one embodiment, for example, dihydrofolate reductase (DHFR) gene amplification in DHFR-deficient CHO cells can include providing and/or the use of (successively increasing levels of) methotrexate (MTX). Similarly, exogenous glutamine synthetase (GS) gene-containing cells can be treated with methionine sulphoximine (MSX).

[0215] The Klotho protein can also include one or more glycans (attached thereto). For instance, the native human alpha Klotho isoform 1 (SEQ ID NO: 1) can have glycans attached (via glycosylation) at amino acids 106, 159, 283, 344, 604, 612, and/or 694. The Klotho protein of the present disclosure can have one or more of the same (or similar) glycans attached (via glycosylation) thereto (e.g., at the same amino acid(s)).

[0216] In at least one embodiment, the protein can be cGMP regulation compliant, as determined and enforced by the U.S. Food and Drug Administration (FDA). For instance, the Klotho protein can be at least 90%, 92%, 95%, 96%, 97%, 98%, or 99% pure, dry weight. In some embodiments, the Klotho protein sample can include less than about 1-100 parts per million (ppm), less than about 100-1000 parts per billion (ppb), or less than about 1-100 ppb CHO host cell proteins (HCP), nucleic acid, and/or other cellular components, or any value or range of values disposed therebetween.

[0217] Glycan structures present on the S-Klotho proteins produced can be similar or identical in comparison to the structures on native S-klotho proteins isolated from human fluids (i.e., blood, serum, urine, cerebrospinal fluid). In at least one embodiment, confirmation of native-like glycans can ensure that the right native post-translation modifications (PTMs) are produced and stably maintained in the cell-produced S-Klotho protein. Solubility and/or half-life extension of Klotho proteins

[0218] Disclosed are methods and compositions for extending the half-life and increasing the solubility of the human S-Klotho protein. Also, the purification and characterization of the protein constructs so produced to achieve these results are also the subject matter of the present disclosure. Relevant information regarding nucleic acid changes made in the sequence of the klotho gene or nucleic acid construct (see SEQ ID NOS: 76-96) and/or of changes, or chemical alterations in the amino acid sequence of a Klotho protein (see SEQ ID NOS: 1-70), and/or additions or subtraction of chemical groups, peptides, or proteins to the amino acid sequence of a Klotho protein is taught in the present disclosure in order to obtain resultant human Klotho variant proteins (novel compositions) with increased biological half life or increased solubility in biological matrices (such as in blood, cerebrospinal fluid, urine, or various human tissues) than that of native Klotho molecules. These novel compositions can be made through the methods described herein for the modification of the S-Klotho protein.

[0219] Illustratively, fusion protein constructs can be produced by combining the S-Klotho protein with the Fc domains of an antibody (IgG), an albumin, such as human serum albumin (HSA), a transferrin, such as human transferrin (TF), and/or a proprietary recombinant polypeptide such as XTEN. The novel proteins can also be produced by conjugating (or modifying) the S-Klotho protein with a posttranslational modification, such as polysialic acid (PSA) or pegylation. Moreover, a novel S-Klotho protein can be produced through pegylation. The foregoing and other (half-life extension) methodologies can improve the performance of the S-Klotho protein by one or more of. increasing the S-Klotho dosing interval; providing superior patient convenience and likely compliance; reducing dosing frequency requirement, resulting in lower drug use in the aggregate; reducing the cost of the drug; lowering drug quantities at the same dosing interval as the parent protein; simplifying dosage formulation and enabling subcutaneous formulation; providing higher drug levels using the same dose and dosing interval as the parent protein resulting in longer drug exposure and potentially better efficacy; and decreasing the immunogenicity of S-Klotho. Production of Fc domain fusion protein constructs of S-Klotho

[0220] Antibody Fc domain, human serum albumin (HSA), and polysialic acid (PSA) were tested for effectiveness in extending the half-life and increasing the solubility of the human S Klotho protein. Fc fusions involve the fusion of peptides, proteins or receptor exodomains to the Fc portion of an antibody. Both Fc and albumin fusions achieve extended half-lives not only by increasing the size of the peptide drug, but both also take advantage of the body's natural recycling mechanism through binding of the extended protein to the neonatal Fc receptor, FcRn. After binding of the extended protein to the FcRn receptor, degradation of the fusion protein in the cells' endosome is prevented. Fusions based on the addition of Fc or albumin can result in biological half-lives in the range of 3-16 days, much longer than which has been reported for typical pegylated or lipidated peptides. For a review that describes the use of protein fusion technologies such as Fc fusion proteins, fusion to human serum albumin, fusion to carboxy-terminal peptide, and other polypeptide fusion approaches to make biobetter drugs with more desirable pharmacokinetic profiles see Strohl WR. Fusion Proteins for Half-Life Extension of Biologics as a Strategy to Make Biobetters. Biodrugs. 2015;29(4):215-239, the entirety of which is incorporated herein by specific reference.

[0221] Fc domains were thusly added to the parent protein (S-Klotho) to increase binding affinity to the Fc receptor (FcRn). FcRn is present inside lysosomes in endothelial cells lining the blood vessels and functions to rescue antibodies from the degradation that makes most proteins short-lived in circulation. As a result of interactions with FcRn, proteins have half lives ranging from a few days to a few weeks, allowing for less frequent dosing of the extended form of the protein drugs than biologics that do not have this newly-produced composition-of-matter.

[0222] The dimeric nature of Fc versus the monomeric structure of HSA can lead to the presentation of a Fc fused peptide as a dimer or a monomer in contrast to HSA. The dimeric nature of a peptide Fc fusion can produce an avidity effect if the target receptors for S-Klotho are spaced closely enough together or are themselves dimers in particular human target organs. This may be desirable or not depending on the target. Fusion of the S-Klotho protein to antibody Fc is also taught in the present disclosure to improve the solubility and stability of S-Klotho. Surprisingly, Fc-fusion Klotho proteins appear to have improved binding, activity, and/or immunogenicity. The addition of Fc domains to S-Klotho will also allow the fusion protein to be less immunogenic upon administration in human subjects. Conjugation of the S-Klotho protein with human serum albumin (HSA)

[0223] The 66.5 kDa protein HSA, similar to human IgGs, has a long average half-life in the 19-day range. At a concentration of -50 mg/mL (-600 pM), HSA is the most abundant protein in human plasma, where it has several functions, including maintenance of plasma pH, metabolite and fatty acid transport, and a role in maintaining blood pressure. HSA, which is at the upper limit of size for glomerular filtration of proteins by the kidney, is also strongly anionic, which helps even more to retard its filtration via the kidney. Like IgGs, HSA also binds FcRn in a pH-dependent manner, albeit at a site different from-and via a mechanism distinct from-that of IgG binding, and is recycled similarly to IgGs, resulting in its extended half-life. HSA also tends to accumulate in tumors and in inflamed tissues, which suggests that fusion or binding to albumin may potentially help to target proteins or peptides to those sites.

[0224] The fusion of peptides or proteins with inherently short-half-life properties to HSA for prolongation of the serum half-life of these molecules has been investigated broadly since the early 1990s. Since then, dozens of different peptides and small proteins have been fused to HSA as both innovative and potential biobetter molecules. The first HSA-peptide or protein fusion product to be approved for marketing was Tanzeum® (marketed as Eperzan® in the European Union) a DPP-4-resistant GLP-1-HSA fusion protein discovered at Human Genome Sciences and developed and marketed by GlaxoSmithKline. Tanzeum® (albiglutide) was approved by the European Medicines Agency (EMA) and the FDA in March and April of 2014, respectively. HSA thus improved the half-life of pharmacologically active GLP-1 from 1-2 min for native GLP-1 to 4-7 days, which allows for once weekly dosing. Seven other known HSA fusion protein product candidates are either now in development or recently have been in development. Also, Novozyme, has been developing modified versions of recombinant HSA with improved FcRn binding for construction of "next-generation" HSA-protein fusions that may possess even longer half-life properties. This was based on the use of a K573P mutant of HSA, which was found to possess 12-fold greater affinity for FcRn, conferred a longer half-life on HSA than the wild type molecule in both mice and cynomolgus monkeys. The expectation is that these longer-half-life mutants of HSA may be of further use as fusion proteins to improve the half-life of fusion proteins.

[0225] The Inventors herein therefore disclose the fusion of Klotho proteins to wild type HSA or to a mutant form of HSA to produce a Klotho fusion molecule(s) with significantly prolonged half-life in human blood, cerebral spinal fluid, and other human biological matrices in order to bring about a strategic therapeutic benefit such as superior patient convenience and likely compliance, reduced dosing frequency resulting in lower drug use in aggregate, and/or reduced cost of goods. Also, lower drug quantities at the same dosing interval as the parent protein may simplify dosage formulation and enable subcutaneous formulation or decrease in the immunogenicity of S-Klotho. Surprisingly, HAS-fusion Klotho proteins appear to have improved binding, activity, and/or immunogenicity. Conjugation of the S-Klotho protein with human transferrin (TF)

[0226] Transferrin is a highly abundant serum glycoprotein, found in serum at 3-4 mg/mL, which binds iron tightly but reversibly and functions to carry iron to tissues. Transferrin has 679 amino acid residues, is about 80 kDa in size, and possesses two high-affinity Fe3+ binding sites, one in the N-terminal domain and the other in the C-terminal domain. Human transferrin has a half-life reported to be 7-10 days or 10-12 days. The aglycosylated form of human transferrin, which makes up about 2-8 % of the total transferrin pool, has a slightly longer half-life of 14-17 days. The extended persistence of transferrin in human serum is due to a clathrin-dependent transferrin receptor-mediated mechanism, which recycles receptor bound transferrin back into the circulation.

[0227] Fusions of peptide and proteins have been made to human transferrin to the N- and C- termini, as well as to the centrally located hinge region that links the two major lobes of transferrin together. The N terminus of transferrin is free and can be fused directly. The C terminus is more buried and is constrained by a nearby disulfide bond, so flexible linkers are typically used when proteins are fused to the C terminus. This capability was extended by making libraries of peptides against specific targets and then fusing binders from those libraries into aglyco-transferrin (N-terminal, C-terminal, loops, or linker region) to be developed into therapeutic fusion proteins with extended half-lives.

[0228] The biotechnology company BioRexis Technologies, Inc., was founded in 2002 to develop the transferrin fusion protein platform, which they termed the "Trans Body" platform, as a therapeutic platform. Their lead molecule, BRX-0585, was a transferrin-GLP-1 fusion protein for treatment of type 2 diabetes mellitus (T2DM). Fusion of GLP-1 to transferrin was demonstrated to significantly enhance the half-life of GLP-1. BioRexis was acquired by Pfizer in March 2007. As far as can be determined, no BioRexis-derived fusion proteins are currently in the clinic. Klotho protein can be fused to human transferrin to produce a Klotho fusion molecule, which can be administered clinically to significantly prolong half-life or stability in human biological matrices in vivo. Conjugation of the S-Klotho protein with XTEN from Amunix

[0229] XTEN@ is a proprietary recombinant polypeptide that extends the in vivo half-life of therapeutic payloads. XTEN consists of naturally-occurring hydrophilic amino acids and is biodegradable. Pharmaceuticals such as proteins, peptides, and synthetic compounds can be XTENylated via chemical conjugation or genetic fusion. XTEN proteins lack secondary and tertiary structure and their solution behavior resembles chemically prepared polymers with very large hydrodynamic radii. By size exclusion chromatography, XTEN protein polymers appear much larger than typical globular proteins of similar molecular weight. The bulking effect of XTEN greatly reduces renal clearance of attached molecules, thus greatly increasing their in vivo half-lives. In the current invention, the length of XTEN polymers added to a Klotho protein will be customized to optimize the pharmacokinetics as well as the bio distribution of the attached Klotho protein payloads.

[0230] XTEN thusly can be recombinantly-fused to S-Klotho protein(s) to increase the molecules in vivo half-life. One benefit is that with the genetic S-Klotho-XTEN fusion constructs, a molecule is produced that has the convenience of expression, purification and characterization of a single molecule which includes both the therapeutic and bulking moieties. Recombinant fusion allows the attaching of multiple XTEN chains per protein in precisely-defined locations and has been successfully used by therapeutic drug manufacturers, resulting in best-in-class pharmacokinetics as exemplified by XTENylated growth hormone (Somavaratan, from the company, Versartis) and FVIII-XTEN (from Biogen). For example, pharmacokinetic studies conducted in children receiving different doses of Somavaratan) have shown that XTENylation resulted in best-in-class half-life due to reduced receptor-mediated elimination in addition to kidney clearance.

[0231] XTEN protein polymers can be produced as free intermediates for chemical conjugation to peptides, peptidomimetics, and other synthetic molecules. Reactive groups (thiol, amine) are inserted in precisely-defined positions via introduction of cysteine or lysine residues into XTEN-encoding genes. Amunix has developed XTENs containing 1 to 9 thiol groups with various spacing which can be provided to partners. Thus, in the present invention, orthogonal conjugation to amino and thiol groups in XTEN facilitates the production of Klotho-XTEN molecules. Purification of Proteins

[0232] The Klotho protein can be extracted from cell suspension culture of cells (e.g., of a CHO cell line). The cells can produce and optionally secrete the Klotho protein (e.g., into liquid medium). Secretion of S-klotho into the spent media was also observed.

[0233] Purification of the recombinant proteins of the present disclosure can be carried out by any suitable method known in the art or described herein, for example, any conventional procedures involving extraction, precipitation, chromatography and/or electrophoresis. A further purification procedure that can be used for purifying proteins includes affinity chromatography using monoclonal antibodies which bind to target protein(s). Some embodiments can include an IgG-tagged protein, Fc-tagged protein, His-tagged protein, HSA-tagged protein, GST-tagged protein, etc., that can be purified by affinity chromatography. For instance, some embodiments can include at least a portion of an Fc domain of an IgG, such as IgG1. Generally, crude preparations containing a recombinant protein are passed through a column on which a suitable monoclonal antibody is immobilized. For other tags, a corresponding, tag-binding affinity entity can be disposed in the column. After washing the column, the protein is eluted from the gel by changing pH or ionic strength. For example, the spent media from the CHO-S high producer cell lines were concentrated via tangential flow filtration; and S-klotho protein was purified by affinity chromatography followed by ion exchange cartridge or column chromatography. Size exclusion chromatography can also be used to purify the proteins. It will be appreciated that various ordering of chromatography types can be applied. Any suitable combination of chromatography steps or columns is contemplated herein.

[0234] In alternative protocols, one or more pre- or post-affinity purification steps were performed. Such steps can include, for example, (ultra) centrifugation, dialysis, membrane and/or tangential flow filtration, chromatographic separation, such as ion exchange, liquid liquid extraction, such as (aqueous) two-phase extraction, or other known purification steps. One or more post purification processing steps were performed in certain embodiments. Such post purification processing steps can include, for example, tandem anion/cation flow through chromatography (as opposed to bind-and-elute chromatography), viral and/or bacterial removal by membrane filtration (e.g., 0.2 micron, 0.1 micron, etc.) or by other means known to one of ordinary skill in the art.

[0235] Certain embodiments include a method of purifying a recombinant Klotho protein. The method can include expressing the recombinant Klotho protein in suspension cell culture. The method can include harvesting the Klotho protein, such as by collecting suspension culture medium and/or cells. In at least one embodiment, the method can include a first purification step. It will be appreciated that the "first" purification step need not occur first or prior to any other purification step(s), or after any other purification step(s). The first purification step can comprise, involve, or use chromatography, such as High Performance Liquid Chromatography (IPLC), Fast Protein Liquid Chromatography (FPLC), ion exchange chromatography, affinity chromatography, etc. The first purification step can comprise, involve, or use affinity chromatography. The affinity chromatography can be based on a tag or other protein fusion entity of the Klotho protein. For example, a His-tagged protein can be purified by His-tag affininty chromatography (e.g., HisTrap or nickel column chromatography). Similarly, a GST-conjugated protein can be purified by GST-affinity chromatography. Depending on the specific tag(s), a corresponding, tag-binding affinity entity can be disposed in a chromatography column for use in protein purification.

[0236] In at least one embodiment, the first purification step can comprise, involve, or use affinity chromatography using, for example, Protein A or Protein A-conjugated particles or beads (e.g., Protein A Sepharose 4 Fast Flow column (0.75 ml) (0.5 cm x 3 cm) for purification of Ig-tagged or Fc-fusion Klotho proteins. The column can be equilibrated in an appropriate solution. The solution can include a buffering agent at a suitable concentration (e.g., 10 mM Tris-HCl, pH 8.0). A suitable amount of protein-containing sample (e.g., suspension cell culture supernatant, optionally adjusted to pH 8.0, with 1.5 M Tris-HCl, pH

8.0) can be loaded on to the column (e.g., at a flow rate of 0.75 ml/min), optionally washed with a suitable wash buffer (e.g., 10 mM Tris/Arginine-HCl, pH 8.0), and eluted from the column with a suitable elution buffer (e.g., 4 M MgCl2, pH 3 (i.e., low pH, high salt)), at a suitable flow rate (e.g., about 0.50-0.25 ml/min, or equivalent), and/or to produce a concentrated sample.

[0237] In at least one embodiment, the elution buffer can have a pH of about 3. In some embodiments, the elution buffer can have a pH between about pH 2 and about pH 6, preferably between about pH 2 and about pH 5, more preferably between about pH 2 and about pH 4, still more preferably between about pH 2.5 and about pH 3.5.

[0238] In at least one embodiment, the elution buffer can include at least one salt. Illustratively, the salt can be or comprise MgCl2, preferably at a concentration of about 4 M. In some embodiments, the elution buffer can have a salt concentration between about 1 M and about 6 M, preferably between about 2 M and about 5 M, more preferably between about 3 M and about 5 M, still more preferably between about 3.5 M and about 4.5 M.

[0239] Additional purification step(s) can comprise, involve, or use chromatography, such as High Performance Liquid Chromatography (HPLC), Fast Protein Liquid Chromatography (FPLC), ion exchange chromatography, affinity chromatography, size exclusion (or gel filtration) chromatography, etc. In at least one embodiment, the method can include a second purification step. It will be appreciated that the "second" purification step need not occur second, prior to, or before any other purification step(s). The second purification step can comprise, involve, or use size exclusion chromatography (and a suitable mobile phase buffer) to fractionate, resolve, clarify, or purify the protein-containing sample(s). For example, in an illustrative second purification step, protein-containing elution sample(s) (from the first purification step) can be optionally buffer exchanged, and purified using size exclusion chromatography (e.g., Superdex 200 (1 cm x 30 cm) column) in a suitable mobile phase buffer. In at least one embodiment, the mobile phase buffer can include a suitable buffering agent (e.g., 100 mM Tris-HCl) and one or more optional reducing agent (e.g., 5 mM L Methionine and/or 0.6% Sodium Thioglycolate), at a suitable pH (e.g., about pH 8). In at least one embodiment, the buffering agent can be other than a phosphate-containing buffer (e.g., Tris, Citrate, etc.). In at least one embodiment, the reducing agent can be or comprise L Methionine and/or Sodium Thioglycolate, preferably at effective reducing concentration(s). Alternative reducing agents may include an acetylcysteine (i.e., N-acetylcysteine (NAC), including N-acetyl-L-cysteine, N-acetyl-D-cysteine, and racemic N-acetylcysteine or a (racemic) mixture of N-acetyl-L-cysteine and N-acetyl-D-cysteine), ascorbic acid, dithionite, erythiorbate, cysteine, glutathione, dithiothreitol, 2-mercaptoethanol, dierythritol, a resin supported thiol, a resin-supported phosphine, vitamin E, and/or trolox, or salts thereof, sodium citrate, potassium citrate, potassium iodide, ammonium chloride, guaiphenesin (or guaifenesin), Tolu balsam, Vasaka, ambroxol, carbocisteine, erdosteine, mecysteine, dornase alfa, and so forth.

[0240] In at least one embodiment, the mobile phase buffer can have a pH of about 8. In some embodiments, the elution buffer can have a pH between about pH 6 and about pH 10, preferably between about pH 7 and about pH 9, more preferably between about pH 7.2 and about pH 8.8, still more preferably between about pH 7.5 and about pH 8.5.

[0241] In at least one embodiment, the eluted protein can be or include monomeric Klotho protein. In at least one embodiment, the eluted protein can be or include multimeric Klotho protein. In some embodiments, the eluted protein can be or include dimeric Klotho protein. In some embodiments, the eluted protein can be or include tetrameric Klotho protein. In some embodiments, the eluted protein can be or include hexameric Klotho protein. In some embodiments, the eluted protein can be or include octameric Klotho protein. In at least one embodiment, the eluted protein can be or include both monomeric and multimeric Klotho proteins. In at least one embodiment, the eluted protein can be or include a single species of either monomeric or multimeric Klotho protein. In at least one embodiment, the eluted protein can be or include greater than or equal to about 80% of the single species of either monomeric or multimeric Klotho protein. In at least one embodiment, the eluted protein can be or include greater than or equal to about 82%, 85%, 88%, 90%, 92%, 95%, 96%, 97%, 98%, or 9 9 % of the single species of either monomeric or multimeric Klotho protein.

[0242] Additional purification step(s) can comprise, involve, or use chromatography, such as High Performance Liquid Chromatography (HPLC), Fast Protein Liquid Chromatography (FPLC), ion exchange chromatography, affinity chromatography, size exclusion (or gel filtration) chromatography, etc. Analysis of Klotho proteins

[0243] Protein purity can be demonstrated by SDS-PAGE or other assays or means known in the art. For instance, in at least one embodiment, Klotho protein samples (50 tg) were fractionated on precast SDS-PAGE gels (4-15%, 10 wells; catalog no. 456-1083; BioRad) and stained with Coomassie blue stain. All samples were run with either an empty lane in between or on separate gels to avoid sample-to-sample contamination. S-klotho of greater than 98% was shown to be isolated from the CHO S conditioned media as determined by Coomaise blue stain and densitometry tracing, or by silver stain visualization, or by HPLC or

RP-IPLC. In order to obtain sequence information, the proteins (after reduction and S carboxymethylation) can be cleaved with cyanogen bromide, trypsin, and/or proteinase K and the peptides separated by IPLC according to known methods of protein chemistry. Thus prepared samples were then sequenced in an automatic gas phase microsequencing apparatus (Applied Biosystems Model 470A, ABI, Foster City, Calif., USA) with an on-line automatic HPLC PTH amino acid analyzer (Applied Biosystems Model 120, ABI see above) connected to the outlet.

[0244] Proteins were also analyzed through mass spectroscopic methods. Concerning sample preparation for mass spectrometry, in order to restrict analyses to the correct S-klotho protein, only the gel band between 75 and 150 kDa was resected for analysis. Gel fractions were macerated with a sterile blade and subjected to in-gel digestion. Gel fractions were de stained by three washes with 80 tL of 50% acetonitrile (ACN)/50 mM ammonium hydrogen carbonate and washed with 100% ACN. The alkylation step was omitted, given the absence of cysteine residues from the target a-Klotho peptides. Tryptic digestion was carried out overnight at 37°C with 60 tL of trypsin (sequencing grade modified, catalog no. V511A; Promega) in 50 mM ammonium hydrogen carbonate (0.005 tg/tL). This process yielded 25 tL, of which 5 tL (1 tL for S-Klotho) was subjected to liquid chromatography-electrospray ionization tandem mass spectrometry (MS/MS) and PRM analysis in an Orbitrap nano-ESI Q-Exactive mass spectrometer (Thermo Scientific), coupled to a nanoLC (Dionex Ultimate 3000 UHPLC). MS/MS analysis confirmed that the human recombinant alpha S-klotho produced by embodiments of the present disclosure was substantially similar (e.g., identical in corresponding amino acid sequence) to that found in human blood, serum, urine or cerebrospinal fluid.

[0245] Using the above purification methods, the level of contaminating CHO host cell proteins (HCP) was determined to be acceptable in the purified S-Klotho protein. In the final S-Klotho product, HCP was removed to < 1-100 ppm. S-klotho protein products of at least 90%, and up to 98% purity were isolated from the spent CHO S production cell line (cells and/or liquid medium). Specifically, cGMP-grade human alpha S-klotho that had an analytical profile suitable for clinical administration in human subjects was produced and purified. For example, the analytical profile of human recombinant alpha S-Klotho is designated by reference number PXD002775 in the ProteomeXchange Database, which can be found at http://proteomecentral.proteomexchange.org/cgi/GetDataset?ID=PXD002775. The NIH full S-Klotho protein dataset is at http//www[dot]ncbi[dot]nlm[dot]nih[dot]gov/ protein/Q9UEF7.

[0246] An analytical profile for S-Klotho suitable for clinical administration and that obtained in an embodiment of the present disclosure included an endotoxin level less than 0.1 ng per tg (1 EU/tg) of S-Klotho. In addition, the purified human recombinant S-Klotho was also shown to have > or = 98% purity by SDS PAGE.

[0247] Glycan structures present on the CHO S cell-produced S-Klotho were identical in comparison to the structures on native S-Klotho isolated from human fluids (i.e., blood, serum, urine, and cerebrospinal fluid). This ensured that the same, native post-translation modifications (PTMs) were produced and stably maintained in the cell produced S-Klotho protein. Accordingly, using production and purification method described herein, the Inventors have been successful in producing cGMP-grade human S-klotho that had an analytical profile suitable for clinical administration in human subjects. Therapeutic compositions

[0248] Some embodiments of the present disclosure can include a pharmaceutical composition, such as a therapeutic composition. Pharmaceutical compositions of the present disclosure can generally include a therapeutically effective amount of a recombinant soluble alpha Klotho protein admixture with a (pharmaceutically-acceptable) vehicle, carrier, or excipient comprised of one or more additional components. The Klotho protein can be included in any suitable amount, such as about 0.001-1000 mg, about 0.01-100 mg, about 0.1-10 mg, about 1-5 mg, or any amount or range of amounts therebetween. In some embodiments, the composition can include a pharmaceutically or therapeutically effect amount of Klotho protein (e.g., to raise serum Klotho levels to a predetermined level in a subject to which the composition is administered).

[0249] The components can include one or more aggregation inhibitors, buffers, tonicity modifiers, and additional excipients. The primary solvent in the carrier can be either aqueous or non-aqueous in nature. The composition can be prepared by combining a purified Klotho protein of the present disclosure with a pharmaceutically-acceptable carrier.

[0250] It will be understood by one of ordinary skill in the art that the combining of the various components to be included in the composition can be done in any appropriate order, namely, the buffer can be added first, middle or last and the tonicity modifier can also be added first, middle or last. It is also to be understood by one of ordinary skill in the art that some of these chemicals can be incompatible in certain combinations, and accordingly, are easily substituted with different chemicals that have similar properties but are compatible in the relevant mixture.

[0251] Aggregation inhibitors reduce a polypeptide's tendency to associate in inappropriate or unwanted ternary or quaternary complexes. The amino acids L-arginine and/or, L-cysteine, can act to reduce aggregation of Fc domain containing polypeptides in a formulation for long periods, e.g., two years or more. The concentration of the aggregation inhibitor in the formulation is preferably between about 1 mM to 1 M, more preferably about 10 mM to about 200 mM, more preferably about 10 mM to about 100 mM, even more preferably about 15 mM to about 75 mM, and yet more preferably about 25 mM. These compounds are available from commercial suppliers.

[0252] Compositions of the present disclosure can include a buffering agent. Buffering agents maintain pH in a desired range. Various buffers suitable for use in the pharmaceutical composition of the present disclosure include histidine, potassium phosphate, alkali salts, sodium or potassium phosphate or their hydrogen or dihydrogen salts, sodium citrate or potassium citrate /citric acid, sodium acetate/acetic acid, maleic acid, ammonium acetate, tris (hydroxymethyl)-aminomethane (tris), various forms of acetate and diethanolamine, and any other pharmaceutically acceptable pH buffering agent known in the art, to maintain the pH of the solution within a desired range. Mixtures of these buffering agents may also be used.

[0253] The amount of buffering agent useful in the composition depends largely on the particular buffer used and the pH of the solution. For example, acetate is a more efficient buffer at pH 5 than pH 6 so less acetate may be used in a solution at pH 5 than at pH 6. The preferred pH of the preferred formulations will be in the range of 4.0 to 5.0, and pH-adjusting agents such as hydrochloric acid, citric acid, sodium hydroxide, or a salt thereof, may also be included in order to obtain the desired pH.

[0254] One preferred buffer is sodium phosphate as its buffering capacity is at or near pH 6.2. It will be appreciated, however, that other buffers may be selected to achieve any desirable pH buffering. The concentration of the buffer in the formulation is preferably between about 1 mM to about 1 M, more preferably about 10 mM to about 200 mM. Buffers are well known in the art and are manufactured by known methods and available from commercial suppliers.

[0255] When the pH of the pharmaceutical composition is set at or near physiological levels comfort of the patient upon administration is maximized. In particular, it is preferred that the pH be within a range of pH about 5.8 to 8.4, with about 6.2 to 7.4 being preferred, however, it is to be understood that the pH can be adjusted as necessary to maximize stability and solubility of the polypeptide in a particular formulation and as such, a pH outside of physiological ranges, yet tolerable to the patient, is within the scope of the disclosure.

[0256] The formulations of the present disclosure may further include one or more tonicity modifiers (e.g., to render the solution isotonic with a patient's blood for injection). A tonicity modifier is understood to be a molecule that contributes to the osmolality of a solution. The osmolality of a pharmaceutical composition is preferably regulated in order to maximize the active ingredient's stability and also to minimize discomfort to the patient upon administration. Where serum is approximately 300+/-50 milliosmoles per kilogram. It is generally preferred that a pharmaceutical composition be isotonic with serum, i.e., having the same or similar osmolality, which is achieved by addition of a tonicity modifier, thus it is contemplated that the osmolality can be from about 180 to about 420 milliosmoles, however, it is to be understood that the osmolality can be either higher or lower as specific conditions require.

[0257] Typical tonicity modifiers are well known in the art and include but are not limited to various salts, amino acids or polysaccharides. Non-limiting examples of suitable amino acids include glycine. Non-limiting examples of suitable polysaccharides include sucrose, mannitol and sorbitol. It is understood that more than one tonicity modifier may be used at once, for example, sorbitol and glycine can be used in combination to modify a formulation's tonicity.

[0258] Additional examples of tonicity modifiers suitable for modifying osmolality include, but are not limited to amino acids (e.g., arginine, cysteine, histidine and glycine), salts (e.g., sodium chloride, potassium chloride and sodium citrate) and/or saccharides (e.g., sucrose, glucose and mannitol). The concentration of the tonicity modifier in the formulation is preferably between about 1 mM to 1 M, more preferably about 10 mM to about 200 mM. Tonicity modifiers are well known in the art and are manufactured by known methods and available from commercial suppliers.

[0259] Excipients, also referred to as chemical additives, co-solutes, or co-solvents, that stabilize the polypeptide while in solution (also in dried or frozen forms) can also be added to a pharmaceutical composition. Excipient is defined herein as a non-therapeutic agent added to a pharmaceutical composition to provide a desired effect, e.g. stabilization, isotonicity. Common attributes of desirable excipients are aqueous solubility, non-toxicity, non reactivity, rapid clearance from the body, and the absence of immunogenicity. In addition, the excipients should be capable of stabilizing the native conformation of the protein so as to maintain the efficacy and safety of the drug during processing, storage and administration to the patient. Examples include but are not limited to sugars/polyols such as: sucrose, lactose, glycerol, xylitol, sorbitol, mannitol, maltose, inositol, trehalose, glucose; polymers such as: serum albumin (bovine serum albumin (BSA), human SA or recombinant HA), dextran, PVA, hydroxypropyl methylcellulose (HPMC), polyethyleneimine, gelatin, polyvinylpyrrolidone (PVP), hydroxyethylcellulose (HEC); non-aqueous solvents such as: polyhydric alcohols, (e.g., PEG, ethylene glycol and glycerol) dimethylsulfoxide (DMSO) and dimethylformamide (DMF); amino acids such as: proline, L-serine, sodium glutamic acid, alanine, glycine, lysine hydrochloride, sarcosine and gamma-aminobutyric acid; surfactants such as: Tween-80TM (polysorbate 80), Tween-20TM (polysorbate 20), SDS, polysorbate, polyoxyethylene copolymer; and miscellaneous excipients such as: potassium phosphate, sodium acetate, ammonium sulfate, magnesium sulfate, sodium sulfate, trimethylamine N-oxide, betaine, metal ions (e.g., zinc, copper, calcium, manganese, and magnesium), CHAPS, monolaurate, 2-0-beta-mannoglycerate or any combination of the above. As a matter of caution, it is noted that the highly toxic white hellebore (Veratrum album) can be mistaken for gentian.

[0260] The concentration of one or more excipients in a formulation of the disclosure is/are preferably between about 0.001 to 5 weight percent, more preferably about 0.1 to 2 weight percent. Excipients are well known in the art and are manufactured by known methods and available from commercial suppliers.

[0261] In one illustrative embodiment, a formulation of the disclosure can comprise about 150 mM NaCl buffered to pH 7.3 to 7.4 with HEPES, MES, or Tris-HCl, and, optionally, one or more additional components as described herein.

[0262] In one illustrative embodiment, a formulation of the disclosure can comprise a (therapeutically-effective) amount of Klotho protein in about 10 mM to about 100 mM L arginine, about 10 mM to about 50 mM sodium phosphate, about 0.75% to about 1.25% sucrose, and/or about 50 mM to about 150 mM NaCl, at about pH 6.0 to about pH 7.0. In another embodiment, L-arginine can be replaced with L-cysteine (at about 1 to about 500 micromolar) in the formulation. In yet another embodiment, the pH can be about pH 7.0. In another specific embodiment, a formulation of the disclosure can comprise a (therapeutically effective) amount of Klotho protein in about 25 mM L-arginine, about 25 mM sodium phosphate, about 98 mM sodium chloride, and/or about 1% sucrose at about pH 6.2.

[0263] In another embodiment, a formulation of the disclosure can comprise a (therapeutically-effective) amount of Klotho protein in about 10 mM to about 100 mM L arginine, about 10 mM to about 50 mM sodium phosphate, about 0. 7 5 % to about 1. 25 %

sucrose, about 50 mM to about 150 mM NaCl, at about pH 6 to about pH 7. In a specific embodiment, the formulation of the disclosure comprises a (therapeutically-effective) amount of Klotho protein in about 25 mM sodium phosphate, about 98 mM sodium chloride, and/or about 1% sucrose at about pH 6.2.

[0264] In yet another embodiment, a formulation of the disclosure can comprise an effective amount of an Fc domain containing Klotho fusion protein, about 10 mM to about 100 mM L -arginine, about 10 mM to about 50 mM sodium phosphate, about 0 to 5% Mannitol and/or 0 to 0.2% Tween-20TM (polysorbate 20) at about pH 6 to 7. In another embodiment, a formulation of the disclosure can comprise an effective amount of a Klotho protein, about 25 mM L-arginine, about 25 mM sodium phosphate, about 4% Mannitol, about 0.02% Tween-20 TM (polysorbate 20), and/or at about pH 6.0.

[0265] In yet another embodiment, the disclosure provides a method of treating a mammal comprising administering a therapeutically effective amount of the pharmaceutical composition described herein, wherein the mammal has a disease or disorder that can be beneficially treated with a Fc domain containing polypeptide in the composition. In yet another embodiment, the Fc domain containing polypeptide is derived from the same species of mammal as is to be treated with the composition. In a particular embodiment, the mammal is a human patient in need of treatment. When the Fc domain containing polypeptide of the composition is Klotho:Fc, examples of diseases or disorders that can be treated include but are not limited to rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Wegener's disease (granulomatosis), Crohn's disease (or inflammatory bowel disease), chronic obstructive pulmonary disease (COPD), Hepatitis C, endometriosis, asthma, cachexia, psoriasis, and atopic dermatitis, or persons with a genetic disorder with mutations in one or more Klotho genes. Additional diseases or disorders that can be treated with KlothoFc include those described in WO 00/62790, WO 01/62272 and U.S. Patent Application No. 2001/0021380, the entirety of each of which is incorporated herein by reference.

[0266] In yet another embodiment, the disclosure provides a method for accelerated stability testing of the stability an Fc domain containing polypeptide in a pharmaceutical composition of the disclosure comprising the steps of testing the activity of the polypeptide formulated according to the disclosure prior to storage, i.e., time zero, storing the composition at 37 C. for one month and measuring the stability of the polypeptide, and comparing the stability form time zero to the one month time point. This information is helpful for early elimination of batches or lots that appear to have good stability initially, yet do not store well for longer periods.

[0267] Moreover, the pharmaceutical composition provides long-term storage such that the active ingredient, e.g., an Fc domain containing polypeptide, is stable over the course of storage either in liquid or frozen states. As used herein, the phrase "long-term" storage is understood to mean that the pharmaceutical composition can be stored for three months or more, for six months or more, for one year or more, and preferably for two year or more. Long term storage is also understood to mean that the pharmaceutical composition is stored either as a liquid at 2-8° C. or is frozen, e.g., at -20° C. or colder (e.g., -20 0 C or -80 C). It is also contemplated that the composition can be frozen and thawed more than once. The term "stable" with respect to long-term storage is understood to mean that the active polypeptide of the pharmaceutical composition does not lose more than 20%, or more preferably 15%, or even more preferably 10%, and most preferably 5% of its activity relative to activity of the composition at the beginning of storage.

[0268] One or more anti-oxidants can be included in the formulations of the present disclosure. Anti-oxidants contemplated for use in the preparation of the formulations include amino acids such as glycine and lysine, chelating agents such as EDTA and DTPA, and free radical scavengers such as sorbitol and mannitol.

[0269] Other effective administration forms such as (an oral or parenteral) modified release formulations (e.g., coated, encapsulated, slow-release, controlled-release, extended-release, delayed-release, sustained-release, time-release, depot, etc.), inhalant mists, orally-active formulations, suppositories, and implants or implantable medical devices are also contemplated herein. As such, the formulations may also involve particulate preparations of polymeric compounds such as bulk erosion polymers (e.g., poly(lactic-co-glycolic acid) (PLGA) copolymers, PLGA polymer blends, block copolymers of PEG, and lactic and glycolic acid, poly(cyanoacrylates)); surface erosion polymers (e.g., poly(anhydrides) and poly(ortho esters)); hydrogel esters (e.g., pluronic polyols, poly(vinyl alcohol), poly(vinylpyrrolidone), maleic anhydride-alkyl vinyl ether copolymers, cellulose, hyaluronic acid derivatives, alginate, collagen, gelatin, albumin, and starches and dextrans) and composition systems thereof; or preparations of liposomes or microspheres. Such formulations may influence the physical state, stability, rate of in vivo release, and rate of in vivo clearance of the present proteins and derivatives. The optimal pharmaceutical formulation for a desired protein can be determined by one skilled in the art depending upon the route of administration and desired dosage. Exemplary pharmaceutical formulations are disclosed in Remington's Pharmaceutical Sciences, 18th Ed. (1990), Mack Publishing Co., Easton, Pa. 18042, pages 1435-1712, the disclosure of which is incorporated herein by reference. Biological activity

[0270] Methods for evaluating the efficacy and/or determining an effective dose of human recombinant alpha soluble Klotho (to a patient, subject, or individual exhibiting an age related disorder or clinical (e.g., metabolic) disorder) can (preliminarily) include performing organismal-based assays (e.g., using a mammal (e.g., a mouse, rat, primate, or some other non-human). The Klotho protein can be administered to the organism once or as a regimen (regular or irregular). For instance, the protein can be administered a suitable number of times (e.g., once, twice, etc.) in a given period of time (e.g., monthly, semi-monthly, weekly, semi weekly, daily, etc.). A parameter of the organism (e.g., an age-associated parameter) can then be evaluated. Klotho proteins of interest can effectuate or result in a change in the parameter relative to a reference (e.g., a parameter of a control organism). Other parameters (e.g., related to toxicity, clearance, and pharmacokinetics) can also be evaluated.

[0271] The klotho proteins of the present disclosure may be evaluated using an animal (model) that has or exhibits a particular disorder or condition, such as an age-related or age associated disorder or condition, a clinical (e.g., metabolic) disorder or condition, etc. Such disorders and conditions can also provide a sensitized system in which the effect of the protein on physiology can be observed. Exemplary disorders include, for example, denervation, disuse atrophy, clinical (e.g., metabolic) disorders (e.g., disorder of obese and/or diabetic animals such as db/db mouse, ob/ob mouse, etc.), cerebral disorders, liver ischemia or other liver disorders, cisplatin/taxol/vincristine models, kidney idschemia/reperfusion models, various tissue (xenograft) transplants, transgenic bone models, pain syndromes (e.g., inflammatory and neuropathic disorders), Paraquat, genotoxic, oxidative stress models, and tumor (I) models.

[0272] To evaluate the S-Klotho protein of the present disclosure, the protein can be administered to a suitable animal (for a suitable treatment period) and the parameter of the animal is evaluated (e.g., after a suitable period of time, such as 10 to 60 minutes, 1 to 24 hours, 1 to 30 days, 1 to 12 months, 1 to 5 years, or any value or range of values therebetween). The animal can be fed ad libitum or normally (e.g., not under caloric restriction, although some parameters can be evaluated under such conditions). Typically, a cohort of such animals is used for the assay. Generally, a test polypeptide can be indicated as favorably altering lifespan regulation in the animal if the test polypeptide affects the parameter in the direction of the phenotype of a similar animal subject to caloric restriction. Such test polypeptides may cause at least some of the lifespan regulatory effects of caloric restriction (e.g., a subset of such effects) without having to deprive the organism of caloric intake.

[0273] The parameter(s) to be tested may be age-associated or disease associated parameter(s) (e.g., a symptom of the disorder associated with the animal model). A test protein that is favorably indicated can cause an amelioration of the symptom relative to a similar reference animal not treated with the polypeptide. Other parameters relevant to a disorder or to aging can include: antioxidant levels (e.g. antioxidant enzyme levels or activity), stress resistance (e.g., paraquat resistance), core body temperature, glucose levels, insulin levels, thyroid-stimulating hormone levels, prolactin levels, and luteinizing hormone levels.

[0274] To measure the effectiveness of the S-Klotho protein of the present disclosure for treating an age-related disorder, an animal having decreased Klotho expression may be used (e.g., a mouse with a mutant or deleted klotho gene). For example, the test protein can be administered to the mutant mouse and age-related parameters are monitored. A test protein that is favorably indicated can cause an amelioration of the symptom relative to a similar reference animal not treated with the protein.

[0275] A parameter relevant to a clinical (e.g., metabolic) disorder or to aging can be assessed by measurement of body weight, examination on the acquisition of reproductive ability, measurement of blood sugar level, observation of life span, observation of skin, observation of motor functions such as walking, and the like. The assessment can also be made by measurement of thymus weight, observation of the size of calcified nodules formed on the inner surface of thoracic cavity, and the like. Further, quantitative determination of mRNA for the klotho gene or the Klotho protein can also be useful for the assessment.

[0276] Still other (in vivo) models and organismal assays include evaluating an animal for a clinical (e.g., metabolic) parameter, e.g., a parameter relevant to an insulin disorder, type II diabetes. Exemplary metabolic parameters include: glucose concentration, insulin concentration, and insulin sensitivity.

[0277] In assessing whether a test protein is capable of altering life span regulation, a number of age-associated parameters or biomarkers can be monitored or evaluated. Exemplary age associated parameters include:(i) lifespan of the cell or the organism; (ii) presence or abundance of a gene transcript or gene product in the cell or organism that has a biological age-dependent expression pattern; (iii) resistance of the cell or organism to stress; (iv) one or more metabolic parameters of the cell or organism (exemplary parameters include circulating insulin levels, blood glucose levels; fat content; core body temperature and so forth); (v) proliferative capacity of the cell or a set of cells present in the organism; and (vi) physical appearance or behavior of the cell or organism.

[0278] The term "average lifespan" refers to the average of the age of death of a cohort of organisms. In some cases, the "average lifespan" is assessed using a cohort of genetically identical organisms under controlled environmental conditions. Deaths due to mishap are discarded. Where average lifespan cannot be determined (e.g., for humans) under controlled environmental conditions, reliable statistical information (e.g., from actuarial tables) for a sufficiently large population can be used as the average lifespan.

[0279] Characterization of molecular differences between two such organisms, e.g., one reference organism and one organism treated with a S-Klotho protein can reveal a difference in the physiological state of the organisms. The reference organism and the treated organism are typically the same (or substantially the same) chronological age and/or sex. The term "chronological age" as used herein refers to time elapsed since a preselected event, such as conception, a defined embryological or fetal stage, or, more preferably, birth. A variety of criteria can be used to determine whether organisms are of the "same" chronological age for the comparative analysis.

[0280] Typically, the degree of accuracy required is a function of the average lifespan of a wildtype organism. For example, for the nematode C. elegans, for which the laboratory wildtype strain N2 lives an average of about 16 days under some controlled conditions, organisms of the same age may have lived for the same number of days. For mice, organism of the same age may have lived for the same number of weeks or months; for primates or humans, the same number of years (or within 2, 3, or 5 years); and so forth. Generally, organisms of the same chronological age may have lived for an amount of time within 15, 10, 5, 3, 2 or 1% of the average lifespan of a wildtype organism of that species. Preferably, the organisms are adult organisms (e.g., the organisms have lived for at least an amount of time in which the average wildtype organism has matured to an age at which it is competent to reproduce).

[0281] The organismal screening assay can be performed before the organisms exhibit overt physical features of aging. For example, the organisms may be adults that have lived only 10, 30, 40, 50, 60, or 70% of the average lifespan of a wildtype organism of the same species. Age-associated changes in metabolism, immune competence, and chromosomal structure have been reported. Any of these changes can be evaluated, either in a test subject (e.g., for an organism based assay), or prior, during or after treatment with a therapeutic described herein (e.g., for a (human, or mammal) patient).

[0282] A marker associated with caloric restriction can also be evaluated in a subject organism of a screening assay (or a treated subject). Although these markers may not be age associated, they may be indicative of a physiological state that is altered when a Klotho or Klotho-related pathway is modulated. The marker can be an mRNA or protein whose abundance changes in calorically restricted animals. Cellular models derived from cells of an animal described herein or analogous to an animal model described herein can be used for a cell-based assay.

[0283] Models for evaluating the effect of a test protein on muscle atrophy include: 1) rat medial gastrocnemius muscle mass loss resulting from denervation, e.g., by severing the right sciatic nerve at mid-thigh; 2) rat medial gastrocnemius muscle mass loss resulting from immobilization (e.g., by fixed the right ankle joint at 90 degrees of flexion); 3) rat medial gastrocnemius muscle mass loss resulting from hind limb suspension; 4) skeletal muscle atrophy resulting from treatment with the cachectic cytokine, interleukin-1 (IL-1); and 5) skeletal muscle atrophy resulting from treatment with the glucocorticoid, dexamethasone. Products, Compositions, Formulations, Supplements, Etc.

[00284] Some embodiments of the present disclosure relate to compositions configured or formulated to augment natural soluble alpha Klotho protein production and/or attenuate Klotho protein damage or degradation, and to methods, kits, formulations, combination products, co-administrations, co-formulations, dosages, process, methods, treatment protocols, and diagnostic methods related to the same. Some embodiments of the present disclosure relate to methods of manufacturing compositions of the present disclosure. Some embodiments of the present disclosure relate to use of compositions of the present disclosure or methods of using the same to treat human or non-human animal subjects. Some embodiments of the present disclosure relate to treatment methods involving compositions of the present disclosure, including administration thereof to human or non-human animal subjects. Such uses and treatment methods can increase endogenous Klotho protein levels, such as by augmenting natural soluble alpha Klotho protein production and/or attenuating Klotho protein damage or degradation.

[00285] Certain embodiments include compositions of matter that comprise a health supplement that, when administered to human or non-human animal (e.g., mammalian) subjects, increases the levels of endogenous, soluble alpha-Klotho protein in the human or non-human animal subjects. The composition or health supplement formulation can comprise (synthetic) chemical and/or natural components or ingredients. In other words, components or ingredients of the composition or health supplement can be or originate from (synthetic) chemical and/or natural sources.

[00286] An exemplary composition can comprise one or more components, preferably selected from the group consisting of, for example, Vitamin D3, Vitamin E, Vitamin C, Vitamin K, 3,5,4'-trihydroxy-trans-stilbene (Resveratrol), Pterostilbene, N-acetylcysteine (NAC), Troglitazone, Rosiglitazone, Notopterygium incisum Ting, Gentian (Root; Extract), Cordyceps (Cordyceps Sinensis (CS) Mycelium), Isoflavones (Soy), Genistein, Daidzein, Quercetin (dihydrate; dill, bay leaf, oregano), Docosahexaenoic acid (DHA), Astaxanthin, Sesamin (Semen Sesamin Nigrum (Black)), Sesame (Seed Extract), Rosmarinic acid (RA; (Marjoram)), Tetradecylthioacetic Acid (TTA), Dicalcium Phosphate (Anhydrous), Mircrocrystalline cellulose (MCC), Croscarmellose Sodium (Primellose), Stearing Acid, Magnesium Stearate, Alpha Lipoic Acid, Conjugate (alpha) Linoleic Acid (CLA), Probiotics, Activated Charcoal, and others as known in the art.

[00287] Certain ingredients or components can have positive benefits and very low side effects in treating or affecting one or more conditions that have been associated with cellular and tissue dysfunctions that occur with aging. Certain ingredients or components can (directly or indirectly) increase the circulating plasma level of soluble alpha Klotho (s Klotho) levels in human or non-human animal subjects following administration thereof.

[00288] The following examples are illustrative only. The following examples illustrate various optional ingredients, components, method steps, etc. that may be useful in the practice of the embodiments of the present disclosure.

[00289] Embodiments of the present disclosure include formulations (compositions, co administrations, etc.) of several components (or ingredients) that, individually, can have a potential for positive benefits and/or very low side effects in addressing, treating, affecting, and/or countering one or more conditions that have been associated with cellular and tissue dysfunctions and/or that can occur with aging.

[00290] Without being bound to any theory, some of the components or ingredients of the present disclosure may activate the promoter of the klotho gene (e.g., in the human HEK293/kl cell line), or reverse age-related declines in expression of Klotho in hepatic, kidney, and other tissues. Some of the components may attenuate, decrease, inhibit, and/or prevent oxidative or other damage to Klotho protein or the klotho gene.

[00291] Without being bound to any theory, some of the components have been shown by one or more animal and human clinical studies to have a potential for positive benefits and/or very low side effects in addressing, treating, affecting, and/or countering one or more conditions that have been associated with cellular and tissue dysfunctions and/or that can occur with aging. The present disclosure utilizes these various components in compositions and methods for increasing endogenous Klotho protein levels. Specifically, the present disclosure utilizes these various components in compositions configured or formulated to augment natural soluble alpha Klotho protein production and/or attenuate Klotho protein damage or degradation.

[00292] Without being bound to any theory, certain of the individual ingredients in some embodiments can increase the circulating plasma level of soluble alpha-Klotho in mammalian (e.g., human or non-human) animals. Example ingredients may include, but are not limited to: N-acetylcysteine (NAC), an antioxidant; D vitamins, such as Vitamin D3 (1,25 dihydroxyvitamin D3 [1,25(OH)2D3]); and/or vitamin D receptor agonist (e.g., calcitriol, paricalcitol), which are thought to increase Klotho expression, increase phosphaturia, correct hyperphosphatemia, and lower serum fibroblast growth factor-23 (FGF-23) resulting in associated decreasing aortic calcification in mice suffering from chronic kidney disease; and Vitamin C and/or Vitamin E, which are thought to ameliorate age-related crystalluria and kidney damage at the proximal tubule.

[00293] Further example ingredients may include, but are not limited to non-prescription ingredients that may supplement the anti-aging properties of alpha Klotho, such as, for example: docosahexaenoic acid (DHA), linoleic acid, conjugated linoleic acid (CLA), isoflavones (e.g., genistein, daidzein, quercetin), rosmarinic acid, sesamin and astaxanthin (food-derived antioxidants), and tetradecylthioacetic acid (TTA). Without being bound to any theory, the aging brain is particularly prone to inflammatory and oxidative alterations which may underlie decreases in learning and memory and omega-3 polyunsaturated fatty acids (PUFAs) such as DHA, protect the aging brain from the development of neurodegenerative diseases. Accordingly, certain formulaE can include alpha linoleic acid or conjugated alpha linoleic acid because alpha linoleic acid can serve as a precursor molecule used in the human body in the manufacture of DHA.

[00294] In at least one embodiment, one or more DHA precursors or omega-3 fatty acids, such as LA or CLA can be omitted from the formulation. Without being bound to any theory, omega-3 fatty acids such as LA or CLA may increase the effects of blood-thinning medications and raise the risk of bleeding. Example medications include, without limitation, warfarin (Coumadin), clopidogrel (Plavix), and aspirin, among others. In some embodiments, DHA can be included in the formulation. Without being bound to any theory, DHA may not directly cause blood thinning.

[00295] Without being bound to any theory, mitochondrial damage can be the cause and outcome of cell injury resulting from a variety of toxic insults, hypoxia, or trauma. Increasing mitochondrial biogenesis after renal proximal tubular cell (RPTC) injury may accelerate the recovery of mitochondrial and cellular functions after such injury. Relevant to these observations, isoflavones, such as daidzein and genistein, may increase peroxisome proliferator-activated receptor gamma coactivator (PGC)-1 alpha expression and result in mitochondrial biogenesis as indicated by increased expression of ATP synthase beta and NADH:ubiquinone oxidoreductase core subunit 6 (ND6), which may result in a 1.5-fold increases in respiration and ATP in RPTC and which benefits recovery in injured RPTC. Without being bound to any theory, daidzein may be metabolized within the gut, by particular intestinal flora, to produce the bioactive compound equol. Equol can also be included in certain embodiments. The isoflavone, quercetin, on the other hand, may counter detrimental effects of aging by increasing oxidative stress resistance in the proteasome - large protein complexes responsible for the proper regulation of the cellular protein load that play a major role in the maintenance of redox balance by recognizing and removing oxidatively modified or damaged proteins.

[00296] Rosmarinic acid can also be added as an ingredient in some formulations. Rosmarinic acid (RA) is a naturally occurring phenolic compound, which may contribute to the beneficial and health-promoting effects of herbs, spices and medicinal plants. Administration of RA at a dosage of 200 mg per kg, once a day for 30 days to aging mice, can significantly (p < 0.05 or p < 0.01) increase the activity of superoxide dismutase (SOD) catalase (CAT) and glutathione peroxidase (GSH-Px), with a decrease in malondialdehyde (MDA), in comparison to an aging control that did not receive RA. Thus, RA may promote significant antioxidant enzyme activity in liver and kidney tissues of aging mice.

[00297] Some embodiments may also contain the food-derived antioxidants, such as astaxanthin (A) and/or sesamin (S). Without being bound to any theory, when both of these ingredients (astaxanthin is a red carotenoid found in salmon, shrimp, crab, and microalgae while sesamin is a major lignan found in sesame extract) were combined (i.e., AS) and administered daily to subjects with mild cognitive impairment (MCI), significant improvements in psychomotor speed and processing speed was observed in the AS group compared with a placebo group. Accordingly, daily supplementation of AS may improve cognitive functions related to the ability to comprehend and perform complex tasks quickly and accurately.

[00298] One or more peroxisome proliferator-activated receptor (PPAR-y) agonists, such as Tetradecylthioacetic Acid (TTA), may also be added to certain embodiments. PPAR-y agonists may have beneficial effects on heart muscle through the regulation of amino acids metabolism and L-carnitine biosynthesis.

[00299] In addition to the purified chemical compounds described above, some embodiments may contain one or more (e.g., several) natural ingredients or extracts. These include, but are not limited to, extracts of gentian root extract, Cordyceps mushroom, and Notopterygium incisum Ting.

[00300] Certain embodiments can include one or more (selective) strains of (probiotic) bacteria, such as: Lactobacillus sp. (e.g., acidophilus, brevis, bulgaricus, case, gasseri, johnsonii, lactis, plantarum, paracasei, rhamnosus, salivarius, sake, etc.), Bifidobacterium sp. (e.g., bifidum, breve, infantis, lactis, longum, etc.), Streptococcus sp. (e.g., thermophiles, etc.), Bacillus sp. (e.g., laterosporus,etc.), Pediococcus sp. (e.g., acidilactici,etc.), and others as known in the art. Without being bound to any theory, probiotics may alleviate age-inflicted oxidative stress and improve expression of biomarkers of aging (e.g., in mice). Additional information regarding probiotics, which may be included in certain embodiments of the present disclosure, can be found in a literature by Sabina Fijan, "Microorganisms with Claimed Probiotic Properties: An Overview of Recent Literature," published in Int JEnviron Res PublicHealth, 2014 May; 11(5): 4745-4767, the entirety of which is incorporated herein by specific reference.

[00301] Table 42 provides a list of ingredients that can be formulated into a particular embodiment (designated KSF 101). KSF 101 Formulation Ingredient Amount!Dose Vitamin D3 1,000 IU Vitamin E 2,000 IU Vitamin C 1000 mg Resveratrol (3,5,4'-trihydroxy-trans-stilbene) 1000 mg Pterostilbene 5mg NAC (N-acetylcysteine) 600 mg Troglitazone 1360 mg Rosiglitazone 136 mg Notopterygium incisum Ting 3000 mg Gentian Root Extract 500 mg Cordyceps 1000 mg Genistein 10 mg Daidzein 40 mg Quercetin 150 mg Docosahexaenoic acid (DHA) 1000 mg Astaxanthin 3mg Sesamin (S) 5mg

Rosmarinic acid (RA) 500 mg Tetradecylthioacetic Acid (TTA) 500 mg Alpha Linoleic Acid 3200 mg Conjugate Alpha Linoleic Acid (CLA) 1000 mg Probiotics 8g Activated Charcoal 5000 mg

Table 42

[00302] By way of non-limiting example, the KSF 101 formulation can be or comprise an orally administered, DSHEA-compliant formulation or composition. Accordingly, in some instances, the KSF 101 supplement may be marketed and/or sold directly-to-consumer (DTC) and/or without requiring a prescription/physician order. It will be appreciated, however, that KSF 101 can be formulated in other dosage forms and/or as an FDA-approved drug without departing from the scope of this disclosure. The concentration of ingredients in KSF 101 are based on a standard adult reference of a 150-pound person (68 kilograms). Alternative dosage(s), as understood by those skilled in the art, are also contemplated herein.

[00303] Table 43 lists potential (e.g., preferred and optional) ingredients that can be formulated into another embodiment of the present disclosure. Illustrative Ingredients Ingredient (potential max.) Amount/ Dose Preferred Ingredients Vitamin D3 1,000 IU Vitamin E 2,000 IU Vitamin C 1,250 mg Pterostilbene 5 mg NAC (N-acetylcysteine) 600 mg Notopterygium incisum Ting 3,000 mg Gentian Root Extract 500 mg Cordyceps 1,000 mg Optional or Alternative Ingredients 2,3,5,4'-Tetrahydroxystilbene-2-0-3-D-glucoside (THSG) 4,000 mg Resveratrol (3,5,4'-trihydroxy-trans-stilbene) 1,000 mg Rosiglitazone 136 mg Troglitazone 1,360 mg Genistein 10 mg Daidzein 40 mg Quercetin (from dill, bay leaves, and oregano) 500 mg Isoflavones (Genistein, Daidzein, Equol) 10 mg Docosahexaenoic acid (DHA) 1,000 mg Astaxanthin 3mg Sesamin (S) 200 mg

Illustrative Ingredients Rosmarinic acid (RA) (marjoram) 500 mg Tetradecylthioacetic Acid (TTA) 500 mg Conjugate Linoleic Acid (CLA) 3,200 mg Alpha Lipoic Acid (ALA) 1000 mg Probiotics 10 - 20 billion CFU Activated Charcoal 5,000 mg Vitamin K 90 - 120 mcg

Table 43

[00304] Table 44 lists potential (e.g., preferred and optional) ingredients that can be formulated into another embodiment of the present disclosure. Label Claim Optimized Ingredient mg Potency mg/Tab Amount/Day **9 TABLETS (excluding Probiotics and Charcoal) 1303.22 Vitamin D3 (100,000 lu/Gm 10001U 1.22 1000IU Vitamin E 1210 lu (D-Alpha Tocopherol Succinate 11621u 20001U 202.02 2000IU Vitamin C 97% (Ascorbic Acid) Granular 1250mg 97% 157.5 1000 mg Pterostilbene Powder 5mg 0.58 5mg N-Acetyl L-Cysteine (NAC) 600mg 70 600 mg Notopterygium Incisum Ting 3000mg 350 0 Gentian Root 10:1 (Powder) 500mg 58.33 500 mg Cordyceps Sinensis (CS) Mycelium Powder 1000mg 116.67 0 to 300 mg Soy Isoflavones 40% 10mg 40% 2.92 10 mg Dha Powder 17% from Algae 170mg 17% 116.67 170 mg Semen Sesamin Nigrum (Black) Powder 200mg 23.33 100 - 150 mg Quercetin From Dill, Bay Leaves and Oregano 500mg 98% 59.52 150 mg Rosmarinic Acid (RA)(Marjoram) 500mg 58.33 500 mg Tetradecylthioacetic acid (TTA) 500mg 58.33 500 mg Dicalcium Phosphate Anhydrous Powder 5.56 Mcc (Mircrocrystalline Cellulose) Ph 102 5.56 Stearing Acid Nf 5.56 Croscarmellose Sodium (Primellose) 5.56 Magnesium Stearate 5.56 Probiotics 0 Charcoal (organic coconut) 260mg

Table 44

[00305] The ingredients of Tables 42-44 can be optionally combined in any suitable combination. By way of non-limiting example, the alternative formulation(s) can be or comprise an orally administered, DSHEA-compliant formulation or composition. It will be appreciated, however, that alternative formulation(s) can be formulated in other dosage forms and/or as an FDA-approved drug without departing from the scope of this disclosure. The respective concentrations of ingredients in the alternative formulation(s) are based on a standard adult reference of a 150-pound person (68 kilograms). Alternative dosage(s), as understood by those skilled in the art, are also contemplated herein.

[00306] An illustrative composition (e.g., a nutraceutical composition) can comprise two or more components selected from the group consisting of vitamin C, vitamin D3, vitamin E, N acetylcysteine (NAC), quercetin (dihydrate), rosmarinic acid (RA), pterostilbene, docosahexaenoic acid (DHA), nicotinamide riboside (NR), nicotinamide adenine dinucleotide (NAD+), nicotinamide mononucleotide (NMN), and one or more probiotic. The one or more probiotic can include an effective amount of one or more of. (i) one or more Bifidobacterium species and/or strains selected from Bifidobacterium lactis BL-04, Bifidobacterium bifidum/lactis BB-02, and Bifidobacterium longum BL-05, and/or (ii) one or more Lactobacillus species and/or strains selected from Lactobacillus acidophilus LA-14, Lactobacillus rhamnosus LR-32, and Lactobacillus paracasei LPC-37.

[00307] Illustratively, the composition (or formulation) includes up to, at least, and/or about 50 billion CFU (per daily dose) of a Probiotic ingredient. Alternative embodiments can include up to, at least, between, and/or about 20 billion CFU (per daily dose), 30 billion CFU (per daily dose), 40 billion CFU (per daily dose), 60 billion CFU (per daily dose), 70 billion CFU (per daily dose), and/or 80 billion CFU (per daily dose) of the Probiotic ingredient. Illustratively, the Probiotic ingredient can comprise or include a single probiotic (bacterial) species or strain, or up to, at least, and/or between 2, 3, 4, 5, 6, 7, 8, 9, and 10 probiotic (bacterial) species or strains. In at least one embodiment, the Probiotic ingredient comprises the following probiotic (bacterial) species or strains: 30 billion CFU/day each of the Bifidobacterium species and/or strains Bifidobacterium lactis BL-04, Bifidobacterium bifidum/lactis BB-02, and Bifidobacterium longum BL-05. It will be appreciated, however, that certain embodiments may include one or two of the foregoing Bifidobacterium species and/or strains and/or in an amount of up to, at least, between, and/or about 10 billion CFU (per daily dose), 20 billion CFU (per daily dose), 30 billion CFU (per daily dose), 40 billion CFU (per daily dose), and/or 50 billion CFU (per daily dose). In at least one embodiment, the Probiotic ingredient comprises the following probiotic (bacterial) species or strains: 20 billion CFU/day each of the Lactobacillus species and/or strains Lactobacillus acidophilus LA-14, Lactobacillus rhamnosus LR-32, and Lactobacillus paracasei LPC-37. It will be appreciated, however, that certain embodiments may include one or two of the foregoing Lactobacillus species and/or strains and/or in an amount of up to, at least, between, and/or about 5 billion CFU (per daily dose), 10 billion CFU (per daily dose), 20 billion CFU (per daily dose), 30 billion CFU (per daily dose), and/or 40 billion CFU (per daily dose).

[00308] In at least one embodiment, vitamin C can be included in a daily dose and/or concentration of about 500 mg, or between about 100-2000 mg, preferably about 200-1500 mg, more preferably about 250-1200 mg, still more preferably about 400-1000 mg, still more preferably about 500-1000 mg, still more preferably about 500-750 mg (per day or per dosage). In at least one embodiment, vitamin C can be included in a daily dose and/or concentration of at least about 100 mg, 200 mg, 250 mg, 300 mg, 400 mg, 500 mg, 750 mg, or 1000 mg (per day or per dosage). In at least one embodiment, vitamin C can be included in a daily dose and/or concentration of less than or equal to about 2500 mg, 2000 mg, 1500 mg, 1000 mg, or 750 mg (per day or per dosage).

[00309] In at least one embodiment, vitamin D3 can be included in a daily dose and/or concentration of about 1000 mg, or between about 100-2500 mg, preferably about 200-2000 mg, more preferably about 250-1800 mg, still more preferably about 400-1500 mg, still more preferably about 500-1500 mg, still more preferably about 750-1250 mg (per day or per dosage). In at least one embodiment, vitamin D3 can be included in a daily dose and/or concentration of at least about 100 mg, 200 mg, 250 mg, 300 mg, 400 mg, 500 mg, 750 mg, 1000 mg, 1250 mg, 1500 mg, or 2000 mg (per day or per dosage). In at least one embodiment, vitamin D3 can be included in a daily dose and/or concentration of less than or equal to about 3000 mg, 2500 mg, 2000 mg, or 1500 mg (per day or per dosage).

[00310] In at least one embodiment, vitamin E can be included in a daily dose and/or concentration of about 400 mg, or between about 100-2000 mg, preferably about 150-1500 mg, more preferably about 200-1200 mg, still more preferably about 250-1000 mg, still more preferably about 250-750 mg, still more preferably about 250-500 mg, still more preferably about 300-750 mg, still more preferably about 300-500 mg (per day or per dosage). In at least one embodiment, vitamin E can be included in a daily dose and/or concentration of at least about 100 mg, 200 mg, 250 mg, 300 mg, 400 mg, 500 mg, 750 mg, or 1000 mg (per day or per dosage). In at least one embodiment, vitamin E can be included in a daily dose and/or concentration of less than or equal to about 2000 mg, 1500 mg, 1000 mg, 750 mg, or 500 mg (per day or per dosage).

[00311] In at least one embodiment, N-acetylcysteine (NAC) can be included in a daily dose and/or concentration of about 600 mg, or between about 100-2000 mg, preferably about 150 1500 mg, more preferably about 200-1200 mg, still more preferably about 250-1000 mg, still more preferably about 250-750 mg, still more preferably about 500-750 mg. In at least one embodiment, N-acetylcysteine (NAC) can be included in a daily dose and/or concentration of at least about 100 mg, 200 mg, 250 mg, 300 mg, 400 mg, 500 mg, 750 mg, or 1000 mg (per day or per dosage). In at least one embodiment, N-acetylcysteine (NAC) can be included in a daily dose and/or concentration of less than or equal to about 2000 mg, 1500 mg, 1000 mg, or 750 mg (per day or per dosage).

[00312] In at least one embodiment, quercetin (dihydrate) can be included in a daily dose and/or concentration of about 150 mg, or between about 10-1000 mg, preferably about 25 750 mg, more preferably about 50-500 mg, still more preferably about 100-250 mg, still more preferably about 100-200 mg (per day or per dosage). In at least one embodiment, quercetin (dihydrate) can be included in a daily dose and/or concentration of at least about 10 mg, 20 mg, 25 mg, 30 mg, 40 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, or 250 mg (per day or per dosage). In at least one embodiment, quercetin (dihydrate) can be included in a daily dose and/or concentration of less than or equal to about 1000 mg, 750 mg, 500 mg, 400 mg, 300 mg, 250 mg, or 200 mg (per day or per dosage).

[00313] In at least one embodiment, rosmarinic acid (RA) can be included in a daily dose and/or concentration of about 500 mg, or between about 100-2000 mg, preferably about 200 1500 mg, more preferably about 250-1200 mg, still more preferably about 400-1000 mg, still more preferably about 500-1000 mg, still more preferably about 500-750 mg (per day or per dosage). In at least one embodiment, rosmarinic acid (RA) can be included in a daily dose and/or concentration of at least about 100 mg, 200 mg, 250 mg, 300 mg, 400 mg, 500 mg, 750 mg, or 1000 mg (per day or per dosage). In at least one embodiment, rosmarinic acid (RA) can be included in a daily dose and/or concentration of less than or equal to about 2500 mg, 2000 mg, 1500 mg, 1000 mg, or 750 mg (per day or per dosage).

[00314] In at least one embodiment, pterostilbene can be included in a daily dose and/or concentration of about 50 mg, or between about 10-200 mg, preferably about 20-150 mg, more preferably about 25-120 mg, still more preferably about 25-120 mg, still more preferably about 40-100 mg, still more preferably about 50-100 mg, still more preferably about 50-75 mg (per day or per dosage). In at least one embodiment, pterostilbene can be included in a daily dose and/or concentration of at least about 10 mg, 20 mg, 25 mg, 30 mg, 40 mg, 50 mg, 75 mg, or 100 mg (per day or per dosage). In at least one embodiment, pterostilbene can be included in a daily dose and/or concentration of less than or equal to about 250 mg, 200 mg, 150 mg, 100 mg, or 75 mg (per day or per dosage).

[00315] In at least one embodiment, DHA (preferably vegetarian DHA) can be included in a daily dose and/or concentration of about 200 mg, or between about 10-1000 mg, preferably about 25-750 mg, more preferably about 50-500 mg, still more preferably about 100-250 mg, still more preferably about 150-250 mg, still more preferably about 100-200 mg (per day or per dosage). In at least one embodiment, quercetin (dihydrate) can be included in a daily dose and/or concentration of at least about 10 mg, 20 mg, 25 mg, 30 mg, 40 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 400 mg, or 500 mg (per day or per dosage). In at least one embodiment, quercetin (dihydrate) can be included in a daily dose and/or concentration of less than or equal to about 2000 mg, 1500 mg, 1000 mg, 750 mg, 500 mg, 400 mg, 300 mg, or 250 mg (per day or per dosage).

[00316] In at least one embodiment, Nicotinamide Riboside (NR) can be included in a daily dose and/or concentration of about 500 mg, or between about 100-2000 mg, preferably about 200-1500 mg, more preferably about 250-1200 mg, still more preferably about 400-1000 mg, still more preferably about 500-1000 mg, still more preferably about 500-750 mg (per day or per dosage). In at least one embodiment, Nicotinamide Riboside (NR) can be included in a daily dose and/or concentration of at least about 100 mg, 200 mg, 250 mg, 300 mg, 400 mg, 500 mg, 750 mg, or 1000 mg (per day or per dosage). In at least one embodiment, Nicotinamide Riboside (NR) can be included in a daily dose and/or concentration of less than or equal to about 2500 mg, 2000 mg, 1500 mg, 1000 mg, or 750 mg (per day or per dosage).

[00317] In at least one embodiment, Nicotinamide adenine dinucleotide (NAD+) can be included in a daily dose and/or concentration of about 300 mg, or between about 50-2000 mg, preferably about 100-1000 mg, more preferably about 150-750 mg, more preferably about 200-600 mg, still more preferably about 200-500 mg, still more preferably about 200-400 mg, still more preferably about 250-500 mg, still more preferably about 250-400 mg, still more preferably about 300-500 mg, still more preferably about 300-400 mg (per day or per dosage). In at least one embodiment, Nicotinamide adenine dinucleotide (NAD+) can be included in a daily dose and/or concentration of at least about 50 mg, 100 mg, 200 mg, 250 mg, 300 mg, 400 mg, 500 mg, 750 mg, or 1000 mg (per day or per dosage). In at least one embodiment, Nicotinamide adenine dinucleotide (NAD+) can be included in a daily dose and/or concentration of less than or equal to about 2000 mg, 1500 mg, 1000 mg, 750 mg, 500 mg, 400 mg, or 350 mg (per day or per dosage).

[00318] In at least one embodiment, Nicotinamide Mononucleotide (NMN) can be included in a daily dose and/or concentration of about 200 mg, or between about 10-1000 mg, preferably about 25-750 mg, more preferably about 50-500 mg, still more preferably about 100-250 mg, still more preferably about 150-250 mg, still more preferably about 100-200 mg (per day or per dosage). In at least one embodiment, Nicotinamide Mononucleotide (NMN) can be included in a daily dose and/or concentration of at least about 10 mg, 20 mg, 25 mg, 30 mg, 40 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 400 mg, or 500 mg

(per day or per dosage). In at least one embodiment, Nicotinamide Mononucleotide (NMN) can be included in a daily dose and/or concentration of less than or equal to about 2000 mg, 1500 mg, 1000 mg, 750 mg, 500 mg, 400 mg, 300 mg, or 250 mg (per day or per dosage).

[00319] Without being bound to any theory, in embodiments that include NAD+ and/or NAD+ precursor(s) (NR and/or NMN), the NAD+ and/or NAD+ precursor(s) may be in the form of a Lozenge for sublingual application (e.g., to get into the bloodstream, initially bypassing the liver and extending the time until the liver converts them into NAM). Other components may also be administered separately or co-administered. In some embodiments, ingredients can be co-administered, preferably via at least some co-formulation, or formulated as a multi-dosage composition. For example, some embodiments can be, comprise, or be provided as a multi-pill, -capsule, or other dosage kit or pack. Embodiments can include one, two, three, four, five, six, seven, eight, nine, ten, or more dosed components, such as pills, capsule, etc. Some ingredients can be provided in solid, granular, powdered, liquid, or other form.

[00320] Table 45 presents an illustrative formulation according to an embodiment of the present disclosure. Ingredient for Capsules Amount/Dose Unit vitamin C 500 mg vitamin D3 1000 IU Vitamin E 400 IU N-acetylcysteine (NAC) 600 mg quercetin dihydrate 150 mg rosmarinic acid (RA) 500 mg pterostilbene 50 mg DHA (Vegetarian) 200 mg Nicotinamide Riboside (NR) 500 mg Nicotinamide adenine dinucleotide (NAD+) 300 mg Nicotinamide Mononucleotide (NMN) 200 mg Probiotics (50B CFU - 6 Strains, below) 50 Billion CFU Table 45

[00321] The ingredients of Table 45 can be optionally combined in any suitable combination. By way of non-limiting example, the alternative formulation(s) can be or comprise an orally administered, DSHEA-compliant formulation or composition. It will be appreciated, however, that alternative formulation(s) can be formulated in other dosage forms and/or as an FDA-approved drug without departing from the scope of this disclosure. The respective concentrations of ingredients in the alternative formulation(s) are based on a standard adult reference of a 150-pound person (68 kilograms). Alternative dosage(s), as understood by those skilled in the art, are also contemplated herein.

[00322] Some embodiments can include a composition, comprising an effective amount of a composition (e.g., health supplement), as described herein, formulated or co-formulated to increase endogenous Klotho protein levels or production (e.g., in mammalian subjects). The pharmaceutically effective amount of the composition can be sufficient to increase or raise the serum soluble Klotho protein concentration of the subject (e.g., to a predetermined level, such as greater than, equal to, or between about 50 to 3000 picograms of soluble Klotho protein per milliliter of serum). The pharmaceutically effective amount of the composition can also or alternatively be sufficient to maintain the serum soluble Klotho protein concentration of the subject at or above a predetermined threshold (e.g., for a predetermined period of time).

[00323] In certain embodiments, sufficient or suitable increase in Klotho protein levels can (be effective to) modulate the IGF-1 and/or Wnt signaling pathways, exhibit -glucuronidase and/or sialidase activity, suppress the p53/p2I signaling pathway, and/or reduce H 2 0 2 induced cell senescence and apoptosis, preferably through suppression of the p53/p21 signaling pathway. The (raised) protein can function or be functional as a humoral factor, preferably exhibiting pleiotropic activity and/or preferably in the regulation of oxidative stress, growth factor signaling, ion homeostasis, and/or regulation of activity of glycoproteins on the cell surface, such as one or more ion channel proteins and/or growth factor receptors, such as Insulin/Insulin-Like Growth Factor-i receptor.

[00324] The formulated composition (e.g., health supplement) of the present disclosure can raise serum soluble Klotho protein levels by increasing or enhancing (natural) production of Klotho protein by the patient or subject or attenuating (e.g., decreasing, inhibiting, and/or preventing) oxidative or other damage or degradation to/of Klotho protein or the klotho gene.

[00325] Some embodiments of the present disclosure can include a pharmaceutical composition, such as a therapeutic composition or drug. For example, some embodiments can include one or more active ingredients, such as a pharmaceutical or prescription medications (e.g., ARBs (e.g., Losartan, Valsartan), testosterone, Vit. D receptor agonists (e.g., calcitriol, paricalcitol), PPAR (gamma) agonists (e.g., thiazolidinediones, troglitazone, rosiglitazone), or others. Some embodiments can include a formulation or co-formulation, in combination with prescribed medications such as angiotension receptor blockers (ARBs) (i.e., losartan, valsartan) or Vitamin D receptor agonists (VDRAs) (i.e., calcitriol or paricalcitol). Other prescription medications that may be administered with formulations include troglitazone (at 200 mg/kg/day) and rosiglitazone (at 20 mg/kg/day), both Peroxidase Proliferator-Activated Receptor (PPAR-y) agonists. Without being bound to any theory, klotho is thought to be a target gene of PPAR-y in the cultured human kidney cells, as well as in mouse kidneys in vivo. Moreover, Klotho protein expression may be enhanced (or upregulated) by treatment with PPAR-y agonists (e.g., at the described oral dosages).

[00326] Without being bound to any theory, losartan may (significantly) increase circulating a-Klotho levels in human type 2 diabetics by an average of 23% (from 542 pg/ml to 668 pg/ml, p=0.001). Also, linear regression analysis suggests that the increment in plasma a Klotho achieved enhanced healthy renal function as seen by an associated decrease in urine albumin/creatinine ratio (p=-0.263, p=0.029). Similarly, valsartan may significantly increase a-Klotho levels (from 432.7±179 to 506.4±226.8 pg/ml).

[00327] Also, in regard to the above, it is thought that treatment of mice with chronic kidney disease (CKD) with calcitriol or paricalcitrol (at VDRAs doses extrapolated from human subjects that are currently approved for the treatment of secondary hyperparathyroidism) result in half the amount of aortic calcification as compared to no VDRAs. In particular, mice given i.p. calcitriol or paricalcitol 3x per week for 3 weeks (dosing: calcitriol at 30 ng/kg (C30), or paricalcitol at 100 ng/kg (P100), or paricalcitol at 300 ng/kg (P300)) may exhibit increased serum and urine Klotho levels, increased phosphaturia, correction of hyperphosphatemia, and lowering of serum fibroblast growth factor-23. Klotho and osteopontin may also be upregulated by VDRA therapy independent of changes in serum parathyroid hormone and calcium.

[00328] Some embodiments, or pharmaceutical components thereof, can include one or more recombinant (e.g., human or mammalian) Klotho proteins, protein fragments, and/or protein variants. Such active ingredients or pharmaceutical components can contribute to increased levels of endogenous Klotho protein (production) in the patient or subject. Additional description of (various and/or additional) active ingredients, such as therapeutics, recombinant proteins, pharmaceutical, and/or prescription medications, are described in the patent references incorporated above (i.e., (i) PCT/US2017/035755 filed June 2, 2017, (ii) PCT/US2017/063149 filed November 22, 2017, and (iii) U.S. Provisional Application Serial No. 62/595,567 filed December 6, 2017). Such active ingredients can contribute to increased levels of endogenous Klotho protein (production) in the patient or subject.

[00329] Pharmaceutical compositions or components, regardless of type, can, generally, include a drug component, optionally admixed with a (pharmaceutically-acceptable) vehicle, carrier, or excipient comprised of one or more additional components. The components can include one or more aggregation inhibitors, buffers, tonicity modifiers, and additional excipients. The primary solvent in the carrier can be either aqueous or non-aqueous in nature.

[00330] Some embodiments can include a combination product, composition, or formulation comprising a recombinant Klotho protein and one or more additional active ingredients. The one or more additional active ingredients can be selected from among the components, drugs, substances, treatment compositions, etc. described herein or others known in the art. For instance, the Klotho protein and one or more additional active ingredients can be co formulated into an injectable (e.g., intramuscular, intravenous, etc.), ingestible, transdermal, inhalable, topical, or other formulation. Alternatively, a combination treatment or co administration can include treatment or administration of a Klotho protein and one or more additional active ingredients, but without the Klotho protein and one or more additional active ingredients being combined or formulated into a combination product, composition, or formulation. For instance, the Klotho protein and one or more additional active ingredients can each comprise or be in a separate injectable (e.g., intramuscular, intravenous, etc.), ingestible, transdermal, inhalable, topical, or other formulation.

[00331] Some embodiments can include a composition, comprising an effective amount of a composition (e.g., health supplement) and, optionally, an effective (e.g., a pharmaceutically effective) amount of the recombinant Klotho protein and/or pharmaceutical or prescription medications, as described herein, formulated or co-formulated to increase endogenous Klotho protein levels or production (e.g., in mammalian subjects). In some embodiments, the recombinant Klotho protein and/or pharmaceutical or prescription medications can be co administered with the composition. In some embodiments, the recombinant Klotho protein and/or pharmaceutical or prescription medications can be combined with a pharmaceutically acceptable carrier. In some embodiments, the optionally administered, optional recombinant Klotho protein can raise serum soluble Klotho protein levels by providing exogenous Klotho protein, while the optionally administered, optional pharmaceutical or prescription medications can raise serum soluble Klotho protein levels by increasing or enhancing (natural) production of Klotho protein by the patient or subject or attenuating (e.g., decreasing, inhibiting, and/or preventing) oxidative or other damage or degradation to/of Klotho protein or the klotho gene.

[00332] It will also be appreciated that co-administration can comprise simultaneous administration of two or more components or distinct administrations of two or more components, the distinct administrations preferably being separated by a period of time. The period of time can be very small, in some embodiments. For instance, a second component can be administered substantially, immediately following administration of a first component. Alternatively, the first and second administrations can be separated by a time period of 1-60 seconds, 1-60 minutes, 1-24 hours, 1-7 days, 1-4 weeks, 1-12 months, and so forth, or any value or range of values therebetween. Similarly, simultaneous administration can include overlapping administration timeframes for the two or more components.

[00333] Any of the foregoing or other compositions, formulations, and/or co-administrations can have additive or synergistic effects over those of any of the individual components, alone. For instance, co-administration of various health supplement ingredients or a health supplement composition with an active component (e.g., a recombinant Klotho protein, pharmaceutical drug, etc.) can result in treatment outcomes greater than the sum of the individual outcomes of administering the individual components alone at similar concentrations. In addition, synergistic effects can include treatment outcomes similar to those of the individual outcomes of administering the components alone, but at lower concentrations. Synergistic effects can also include increasing the maximum effective dose of one or more of the components, reducing toxicity of one or more of the components, or any other beneficial result that is more than a mere additive effect of the individual treatment outcomes. In addition, additive effects of the individual treatment outcomes can comprise one or more synergistic effects. Such additive/synergistic effects may not be predicted or expected given the nature and understanding of the individual components.

[00334] Certain embodiments can include expression nucleic acid constructs and/or vectors, cell lines and/or cell suspension cultures, and methods of manufacturing, purifying, and administering the one or more recombinant (e.g., human or mammalian) Klotho proteins, protein fragments, and/or protein variants to (human or non-human animal) subjects.

[00335] It will be appreciated that each of the forging, including but not limited to health supplements, formulations, co-formulations, co-administrations, combination products, and so forth, can be referred to as a "composition" or "composition of the present disclosure". Administration of exogenous S-Klotho

[0336] The present disclosure relates to S-Klotho formulations, clinical dosages, and administration (e.g., to increase and/or maintain serum concentrations of S-Klotho within the range of a normal and/or young (e.g., 18 - 30 years of age) person (e.g., without any chronic conditions).

[0337] Aspects or embodiments of the present disclosure include, for example, administering a (cGMP- and/or clinical grade) human recombinant alpha soluble Klotho protein or protein fragment (of isoform 1) to a (human) subject in need thereof. Embodiments can also include measuring (in the (human) subject) serum S-Klotho levels or concentration (e.g., by Mass Spectroscopy (MS) or ELISA). Such measuring can occur before, after, and/or during S-Klotho administration, and can be repeated, as necessary, to determine serum S Klotho levels and/or a rate of metabolism, degradation, or reduction of serum S-Klotho levels. MS is a technique well known in the art. MS can be used to identify and even quantify the level of one or more (native and/or recombinant) Klotho proteins in the serum of a subject.

[0338] One or more additional proteins can also be measured in the subject's serum. For instance, one or more Klotho-related and/or aging-related proteins (e.g., FGF21, GDF-11, TIMP2, NAD+, CCL11, hormones testosterone, estrogen, etc.) and/or kidney function proteins (e.g., KIM-1, Cystatin-C, creatinine, BUN, creatinine, NGAL, etc.) can be measured separate from or in combination with measuring Klotho in the serum.

[0339] In at least one embodiment, a serum sample is obtained, such as a blood sample. The sample can be obtained by a blood draw, as known in the art. In a preferred embodiment, a finger prick or other less invasive means of obtaining a blood sample can be used. Accordingly, blood samples can be taken more frequently (e.g., throughout the day and/or every 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 hours).MS can be used to measure the total Klotho protein serum concentration, as well as the serum concentration of various alpha Klotho protein species, such as native Klotho species (e.g., soluble Klotho, cleaved Klotho, secreted Klotho, etc.) and/or one or more Klotho proteins of the present disclosure. In some embodiments, Klotho levels can be measured before therapeutic recombinant Klotho protein administration and again throughout the day and/or every (or one or more of) 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 hours post-administration. Alternatively, or in addition, Klotho levels can be measured every (or one or more of) 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 18, 20, 21, 25, 28, 30, 36, 40, 45, 50, 60, or 90 days (or weeks) post-administration.

[0340] Embodiments can also include determining such a rate and/or calculating a treatment protocol (e.g., including frequency, amount, and/or duration of (subsequent) administration(s) of S-Klotho) for maintaining within the serum of such subject a S-Klotho concentration within the range of a normal young person's serum concentration of S-Klotho. In at least one embodiment, the concentration of S-Klotho can be maintained at approximately 1000 picograms of (the S-Klotho) protein per milliliter of serum (pg/mL).

[0341] In at least one embodiment, a S-Klotho administration strategy (in humans) can include the measurement of one or more pharmacokinetic parameters of S-Klotho. For instance, measurements can be made of resultant changes in vivo of S-Klotho levels in the serum, urine and cerebrospinal fluid in response to S-Klotho administration. Some embodiments can include measuring the effectiveness of S-Klotho administration on one or more clinical indicators. Clinical indicators for various conditions, diseases, and disorders are known in the art and described further herein.

[0342] Embodiments can also include taking a (baseline) S-Klotho level measurement(s) (e.g., at zero time (before any administration of exogenous S-Klotho) and/or at different times of day before and/or throughout the treatment protocol (e.g., before and after administration of S-Klotho) in order to account for any circadian rhythm effects in the (human) subject(s)).

[0343] Embodiments can also include determining a suitable frequency, amount, and/or duration of S-Klotho administration. For instance, subjects with low S-Klotho serum levels (e.g., as determined by MS or ELISA immunoassay quantification), can be given (e.g., via any suitable route of administration) a first administration of klotho configured and/or adapted to bring the subjects serum S-Klotho levels to a first predetermined level (e.g., about 1000 pg/mL), measuring (the resultant change in) serum S-Klotho concentration in the subject (e.g., by MS or ELISA), measuring the levels and/or a rate of metabolism, degradation, or reduction of serum S-Klotho levels (following the first administration), calculating a half-life of the administered S-Klotho, and/or determining a frequency and/or timeframe in which a second, subsequent administration of S-Klotho should be given (e.g., in order to maintain serum S-Klotho levels above a second predetermined level). In at least one embodiment, the second predetermined level can be between and/or about 95%, 90%, 85%, 80%,75%,70%,65%,60%,55%, 50%,45%, 40%,35%, 30%,25%,20%,15%, 10%, and/or 5% of the first predetermined level.

[0344] Further administrations can be given over a timeframe suitable to produce in the subject (long-term) S-Klotho serum level equivalent to that of normal sex-matched young person's serum maintenance level (e.g., approximately 1000 pg/ml). The total timespan of the S-Klotho administration (to (human) subjects) can range from 1 day to 5 years, or more. Measurements and/or determinations of frailty in the subject based on the use of the clinical frailty score and other measurements can also be made over the timeframe.

[0345] Embodiments of the present disclosure further include increasing the S-Klotho dosage to maintain a 5%, 10%, 15%, 20%, 25%, 30%, 35%, 4 60 0%, 45%, 50%, 55%, %, 65%, 70%, 75%, 8 0%, 85%, 90%, 95%, 100% or more increase in S-Klotho levels above the normal range (e.g., at least about 500-1000 pg/ml serum, illustratively).

[0346] Certain embodiments include administering the S-Klotho protein. Non-limiting examples of suitable routes of administration include injection (e.g., bolus, gradual, intravenous, intradermal, intraperitoneal, intramuscular, intracutaneous, and/or subcutaneous injection), oral or oral-related administration (e.g., ingestion, buccal administration, and/or sublingual administration), topical administration, transdermal administration, rectal administration, vaginal administration, inhalation, and so forth.

[0347] An illustrative embodiment can include administering the S-Klotho protein or composition in a single bolus or extended (IV) injection (e.g., drip over an extended period of time). In at least one embodiment, 0.01, 0.05, 0.1, 0.5, 1, 1.5, 2, 2.5, 2.75, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 12, 15, 18, 20, or more micrograms of S-Klotho per kilogram of subject body weight can be administered per treatment. A suitable administration amount can be calculated through one or more methods known in the art. One such method is the allometric scaling method. For example, in rat experiments, 0.01 mg of S-Klotho /kg body weight per administration was used, or 10 ug/kg. Using the human allometric scaled equivalent of 0.16, illustratively, the human equivalent dose (HED) = 10 ug/kg x 0.16 = 1.6 ug/kg. Hence a 70 kg human individual would require, 70 kg x 1.6 ug/kg = 112 ug and a 60 kg human would require, 60 kg x 1.6 = 96 ug, illustratively. Table 46, below, demonstrates conversion of various animal doses to human equivalent doses (HED) based on body surface area. The conversions assume a 60kg human.

[0348] The HED was established using normalization to body surface area, a process described by Reagan-Shaw (2008), incorporated herein by reference. This process, termed allometric scaling, corrects for basal differences in metabolism rate between different species, and may be preferred over simple dose extrapolation. Illustratively, when the animal species dose is known, then the HED can be calculated as: HED = animal dose in mg/kg x allometric scaling factor for that appropriate animal species. The actual dose to be administered to a patient can then be calculated by multiplying the HED times the patient's weight.

T 6 C

55

alaw 7

Table 46

[0349] Multiple factors can be considered or taking in account in determining, measuring, and/or estimating the amount and/or bioavailability of S-Klotho in humans (before and/or after recombinant protein administration), the total amount and/or concentration of S-Klotho to be administered, and/or the serum level response (over time) after recombinant protein administration. Such factors can include, for example, composition of the diluent, route of administration, site of administration, distribution into the tissues and organs of the subject, metabolic or other rate of the subject, pharmacokinetics (PK), pharmacodynamics (PD), toxicology (Tox), and so forth.

[0350] In at least one embodiment, a (normal) concentration of S-Klotho (e.g., in a healthy, young (18-30 years old) human adult) can be approximately 1000 pg/ml in serum. A typical adult can have a blood volume of approximately 5 liters, with females generally having less blood volume than males. Approximately 55% of human blood can be comprised of serum. Thus, (5 liters of blood / adult) x (0.55 serum/liter blood) = 2.75 liters (2750 ml) of serum/adult. Assuming no endogenous serum S-klotho, to achieve a final concentration of 1000 pg/ml in the total blood serum; 2750 ml X 1000 pg/ml = 2,750,000 pg (or 2750 ng, or 2.75 tg) exogenous S-Klotho can be administered per adult subject.

[0351] To increase soluble Klotho to 50% greater than typical healthy levels (e.g., to 1500 pg/ml serum), a dose of 4.125 micrograms/subject can be administered. To increase soluble

Klotho to 100% greater than typical healthy levels (e.g., to 2000 pg/ml serum) a dose of 5.5 micrograms/subject can be administered, and so forth.

[0352] A pharmaceutically effective and/or sufficient amount of purified recombinant S klotho protein can be administered so as to raise the serum soluble Klotho protein concentration of the subject to any suitable level, such as greater than, equal to, or between about 50, 100, 250, 500, 750, 1000, 1250, 1500, 1750, 2000, 2250, 2500, 2750, 3000, 3500, 4000, 4500, 5000, 5500, 6000, 6500, 7000, 7500, 8000, 8500, 9000, 9500, 10,000, 11,000, 12,000, 13,000, 14,000, 15,000 20,000, 25,000, 30,000 40,000, 50,000, 75,000, 100,000 or more picograms of soluble Klotho protein per milliliter of serum, or greater than, equal to, or between about 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 400%, 500%, 600%, 700%, 800%, 900%, 1000%, 1200%, 1500%, 2000%, 2500%, 3000%, 4000%, 5000%, or more greater than typical healthy levels of soluble Klotho protein in serum.

[0353] In some embodiments, subjects can be administered one or more (bolus) intravenous, intradermal, intraperitoneal, intramuscular, intracutaneous, subcutaneous, and/or other injection of recombinant human S-Klotho protein at a dosage of greater than, equal to, or between about 0.01 mg/kg body weight in a suitable volume of Klotho buffer (e.g., 150 mM NaCl and 10 mM HEPES pH 7.4) or other pharmaceutically acceptable carrier. Thus, a 160 pound subject (i.e., body weight of 72.57 kg) can be administered a (bolus) injection of about 0.73 mg of S-Klotho per administration (based on the calculation of 0.01 mg of S Klotho/kg X 72.57 kg body weight). Likewise, a 170 pound person can receive a 0.77 mg of S-Klotho per administration. The total number and frequency of administrations can be determined based on achieving and maintaining in serum, a concentration of, for example, 1000 pg/ml of S-Klotho (equivalent to 0.000001 mg/ml serum). The latter can be ascertained as measured by MS or by a human S-Klotho ELISA assay.

[0354] In other embodiments, the dosage can be greater than, equal to, or between about 0.0001 - 10 mg/kg body weight, 0.0001 - 10 tg/kg body weight, 0.0001 - 10 ng/kg body weight, 0.0001 - 10 pg/kg body weight, or any value or range of values therebetween. Urine and/or blood can be collected at one or more time points, such as greater than, less than, equal to, between, and/or about 5 minutes, 10 minutes, 15 minutes, 20 minutes, 25 minutes, 30 minutes, 40 minutes, 45 minutes, 60 minutes, 90 minutes, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 9 hours, 12 hours, 18 hours, 24 hours, 36 hours, 48 hours, 2.5 days, 3 days, 5 days, 7 days, 10 days, 14 days, 21 days, 4 weeks, 1 month, 2 months, 3 months, or more after a medical procedure or a first administration (dose) of recombinant Klotho protein (e.g., to measure, test, and/or determine serum S-Klotho levels and changes in response to administration and/or over time).

[0355] One or more embodiments include production and/or (subsequent) administration of a unique formulation of the S-Klotho active drug product and/or in combination with a pharmaceutically-acceptable carrier. The carrier can be suitable for IV and/or bolus injection. Embodiments can also include production and/or (subsequent) administration of a unique inactive prodrug formulation of the S-Klotho and/or in combination with a pharmaceutically acceptable carrier (so that an inactive S-Klotho can be activated in vivo to release biologically effective S-Klotho in animals or in human subjects. Such prodrug formulation can include a coating or time-release formulation. Treatment Methods, Uses, Etc.

[00356] Some embodiments include a method or treatment method (e.g., comprising one or more method steps). Some embodiments can include administering one or more compositions, as described herein, to a subject (e.g., a subject in need thereof). Administration of the inventive composition(s) can be sufficient to raise the serum soluble Klotho protein concentration of the subject to or above a predetermined threshold, or to maintain the serum soluble Klotho protein concentration of the subject at or above a predetermined threshold, for a period of time.

[00357] The composition can comprise, for example, (i) a therapeutic recombinant Klotho protein or fragment or fusion protein thereof, as described in the present disclosure, and/or (ii) a product that increases, enhances, augments, and/or supports endogenous Klotho protein production and/or level(s) in a patient to which the product is administered, optionally with (iii) one or more additional (active or inactive) ingredients or compositions. Those skilled in the art will appreciate that each of the therapeutic effects, indications, and/or treatments outlined herein in relation to recombinant, therapeutic Klotho proteins and products, compositions, and methods related thereto can be achieved by (naturally) increasing, enhancing, augmenting, and/or supporting endogenous Klotho protein production and/or level(s). Those skilled in the art will also appreciate that each of the therapeutic effects, indications, and/or treatments outlined herein in relation to (naturally) increasing, enhancing, augmenting, and/or supporting endogenous Klotho protein production and/or level(s) can be achieved by administering recombinant, therapeutic Klotho proteins and products, compositions, and through methods related thereto. Accordingly, and for the sake of brevity, the present disclosure need not rehearse each of the disclosed therapeutic effects, indications, and/or treatments with reference to both (i) the administration of recombinant, therapeutic

Klotho proteins, and (ii) the administration of the health supplement or nutraceutical compositions of the present disclosure, as such are clearly contemplated herein.

[00358] Certain embodiments can include a composition, as described herein, for use in treating one or more diseases, disorders, injuries, and/or (medical) conditions. Similarly, embodiments can include a method of treating (or alleviating, addressing, preventing, inhibiting, etc.) one or more diseases, disorders, injuries, and/or (medical) conditions. An exemplary treatment method comprises administering to a subject in need thereof an effective amount of a composition of the present disclosure. Without being bound to any theory, administering an effective amount of the composition to a subject in need thereof can cause or result in elevated (or raised) serum soluble Klotho protein concentration in the subject. Accordingly, the "effective amount" of a composition of the present disclosure can be an amount effective to raise or elevate the serum soluble Klotho protein concentration of the subject to or above a predetermined threshold, or to maintain the serum soluble Klotho protein concentration of the subject at or above a predetermined threshold, for a predetermined period of time. Alternatively, or in addition, the "effective amount" of a composition of the present disclosure can be an amount effective to achieve a beneficial therapeutic effect in a patient to which the composition is administered.

[00359] The method, composition or (raised) protein can also be effective to treat one or more diseases, disorders, injuries, and/or (medical) conditions. Illustratively, the condition can be or comprise an age-related or aging-related condition (or condition associated with (human) aging), such as frailty, bone density loss or bone mineral density loss, weight loss, muscular atrophy or degeneration, decline in muscle mass, decline in muscle strength, hand strength, leg strength, or physical fitness, decline in movement, freedom of movement, quality of life assessment, ejection fraction, or exercise capacity, decline in learning, learning capacity, memory, or intellectual quotient, cognitive deterioration or forgetfulness, decline in cognitive capacity or function, decline in synaptic plasticity or synaptic function, and cellular senescence. It will be appreciated, however, that the condition can also, or alternatively, be or comprise any physical, mental, emotional, or other deficiency, need, or desire that increased serum Klotho levels can provide a beneficial therapeutic effect, including those described in the present disclosure and those known to those skilled in the art.

[00360] The method, composition or (raised) protein can also be effective to treat one or more aging-related condition (or condition associated with (human) aging), such as Alzheimer's disease, Parkinson's disease, dementia or vascular dementia, amyotrophic lateral sclerosis (ALS) or motor neuron disease (MND), atrial fibrillation, chronic obstructive pulmonary disease (COPD), fibromyalgia, adult onset diabetes, arthritis or rheumatoid arthritis, osteoarthritis, osteoporosis, glaucoma, cataracts, macular degeneration and other eye diseases/disorders, multiple sclerosis (MS), lupus, and/or ulcerative colitis.

[00361] Some embodiments of the present disclosure can be useful in one or more of treating cancer, lowering serum phosphate levels in a patient, treating diabetes or a diabetes related condition (e.g., Type 1 diabetes mellitus, etc.) in a subject in need of such treatment, treating a heart condition (e.g., cardiovascular disease, left ventricular hypertrophy (LVH), pathological LVH and/or congestive heart failure, etc.) in a subject, treating acute lung injury in a subject (e.g., using nanoparticles), protecting the lung of a patient against oxidant injury, detecting early acute kidney injury in critically ill patients, attenuating vascular calcification in a subject, improving cognition, treating renal and/or liver ischemia, modulating stress response in (human) senescent endothelial cells, prophylactically and/or therapeutically treating, preventing, attenuating, arresting, and/or reversing acute and/or chronic kidney injury, disease, or disease progression and/or uremic cardiomyopathy, reversing or attenuating age-related therapy resistance in melanoma and other cancers, as well as muscular dystrophy, including DMD, targeting apoptosis of senescent cells, preferably restoring tissue homeostasis thereby, and a variety of other indications.

[00362] Some embodiments of the present disclosure can be useful for treating one or more other conditions. Such conditions may be described or disclosed herein. Such conditions may be known by those skilled in the art to be related to Klotho serum levels.

[00363] As described briefly, above, the present disclosure includes and contemplates various dosage forms and/or methods of administration of compositions of the present disclosure. Some embodiments can be dosed in an oral dosage form and/or administrated orally (e.g., in one or more convenient forms including tinctures, tablets, capsules, powders, teas, etc.). For instance, a tincture, comprised of an alcohol- or glycerin-based extract of a herb or natural ingredient can be packaged in a glass dropper bottle. Glycerin-based tinctures can provide a sweet taste, making the formulation more easily to swallow. Tinctures may also be administered in a dropper. Tinctures may include a dosage range on the label (e.g., 20 to 40 drops per adult dose).

[00364] Capsules and tablets are also popular form for the oral administration of supplements. For example, a dried herb can be powdered and pressed into gelatin capsules. The supplement may be supplied as a capsule and/or tablet. The supplement may be supplied as a powder within a bottle or envelope with dosage amounts to be used listed on the container. An appropriate amount of powder per dose may also be obtained by opening up a dosage capsule and sprinkling the content into a drink or on food.

[00365] Teas (e.g., herbal infusions) are common forms of herbal remedy and a soothing way to take herbs. An herbal infusion can be made by placing a small amount of the herb in a cup, filling the cup with boiling water and letting it steep. In a tea form, herbal ingredients of the supplements may increase in potency with extended steeping time and the tea is best left to steep for at least 10 minutes. Covering the cup (a small saucer works well) keeps the steam in and keeps the tea hot longer.

[00366] Some embodiments can include a method of treating an aging-related or other condition, disease, or disorder, the method comprising administering to a subject in need thereof an effective amount of a composition of the present disclosure. Some embodiments can include a method of treating and/or preventing a condition, disease, or disorder, preferably a condition, disease, or disorder associated with aging, in a mammalian subject, the method comprising administering to a subject in need thereof an effective amount of a composition of the present disclosure. Some embodiments can include a method of treating or preventing acute kidney injury (AKI), chronic kidney disease (CKD), or other condition, the method comprising administering to a subject in need thereof an effective amount of a composition of the present disclosure. Some embodiments can include a method of treating and/or preventing kidney injury in a mammalian subject, the method comprising administering to the subject, optionally prophylactically, prior to a medical procedure or administration of a nephrotoxin and/or following a medical procedure or administration of a nephrotoxin, an effective amount of a composition of the present disclosure. Some embodiments can include a method of administering a composition of the present disclosure to a human or non-human animal (e.g., mammalian) subject in need thereof. The subject to whom the composition is administered can be suffering from or at risk for a variety of conditions (e.g., disorders, diseases, injuries, illnesses, etc.). For example, some embodiments include a method of treating one or more chronic diseases and/or aging-related condition, such as a physical, mental, neurological, or other condition associated with (human) aging. Some embodiments can promote healing, recovery, longevity, and/or other beneficial outcome through one or more mechanisms or action.

[00367] The pharmaceutically effective amount of the composition can be sufficient to increase or raise the serum soluble Klotho protein concentration of the subject (e.g., to a predetermined level, such as greater than, equal to, or between about 50 to 3000 picograms of soluble Klotho protein per milliliter of serum). The pharmaceutically effective amount of the composition can also or alternatively be sufficient to maintain the serum soluble Klotho protein concentration of the subject at or above a predetermined threshold (e.g., for a predetermined period of time).

[00368] In certain embodiments, suitable increase in protein levels can (be effective to) modulate the IGF-1 and/or Wnt signaling pathways, exhibit3-glucuronidase and/or sialidase activity, suppress the p53/p2I signaling pathway, and/or reduce H202-induced cell senescence and apoptosis, preferably through suppression of the p53/p2I signaling pathway. The (raised) protein can function or be functional as a humoral factor, preferably exhibiting pleiotropic activity and/or preferably in the regulation of oxidative stress, growth factor signaling, ion homeostasis, and/or regulation of activity of glycoproteins on the cell surface, such as one or more ion channel proteins and/or growth factor receptors, such as Insulin/Insulin-Like Growth Factor-i receptor.

[00369] Certain embodiments can include determining a serum soluble Klotho protein concentration of the subject, calculating the effective amount, determining a rate of soluble Klotho protein decline in the serum of the subject, calculating a subsequent dosage time at which the serum soluble Klotho protein concentration of the subject will be at or below a second predetermined level based on the determined rate, calculating a subsequent dosage amount of the composition sufficient to raise the serum soluble Klotho protein concentration of the subject from the second predetermined level to the first predetermined level, and/or administering the subsequent dosage amount of the composition to the subject. Certain embodiments can include prescribing a regular (e.g., daily) dose or dosage form of the composition to the subject (e.g., based on determined levels of serum soluble Klotho protein concentration of the subject).

[0370] An illustrative embodiment comprises a (treatment) method. The treatment method can be similar to and/or modeled after a study of the therapeutic effect or health benefits of various compositions of the present disclosure. The results of administration of various compositions are monitored in human subjects. Once a subject has voluntarily agreed to be in the study, and signed the Patient Consent Form, they are given a physical examination and blood and saliva tests. Upon meeting the Inclusion Criteria in the Study Protocol, the subject is then enrolled in the study. Illustratively, the study may include 100 healthy individuals that are not currently on vitamin D supplementation and that do not live in a sunny environment. Subjects with a KLVS variant (Klotho over-expressor) and/or other genetic variant of klotho gene(s) may be excluded from the study. Following enrollment, the subjects receive a 3-month supply of a Klotho supplement formulation of the present disclosure or a placebo in a double-blind study. Subjects receive unmarked bottles of supplement formulation or placebo at no cost. Subjects take this supplement daily for 3 months.

[0371] At the end of this 3-month period, blood is drawn for a fasting blood test, and the subject's weight, blood pressure is measured and recorded along with the concentration of plasma alpha soluble Klotho determined by an Alpha Klotho (a - Klotho) Human Soluble ELISA Assay Kit (from for example, Catalog No. 27998, from IBL America, Minneapolis, MN, USA).

[0372] The Study/Design Procedures regarding the human subjects in this study is given below. Study Design/Procedures:

[0373] Up to 100 patients

[0374] Duration: 3 months to first endpoint, crossover, second endpoint at 6 months including placebo patients that elected to take the supplement.

[0375] Baseline Questionnaire to include: Current medications (statins, ARBs), nutritional supplements, blood pressure, exercise frequency, alcohol consumption.

[0376] Prior to enrolling:

[0377] Collect blood sample and cheek swab (PI office or mobile phlebotomist)

[0378] Determine KLVS variant (KLOTHO overexpressor) - send cheek swab to lab to determine KLVS variant (Klotho over-expressor) status

[0379] Lab analysis of Klotho level, Vitamins D & E, and other analyses for pre-treatment baseline

[0380] Supplementation: (3-month supply) shipped to participant. (Active supplement and placebo controls, equal # of active and placebo controls)

[0381] Outcomes measure: Participant downloads mobile application to monitor compliance and questionnaires (exercise, blood pressure)

[0382] Follow up blood sample collection at 3 months and 6 months

[0383] The ingredients in the supplement are comprised of nutritional components that pose very low risk. If subject experiences any discomfort or adverse reaction to the formulation he or she will be instructed to stop taking the product and contact the study doctor.

[0384] Any significant adverse reactions will be reported to the study's IRCM Institutional review Board (IRB) within 48 hours. Example Conditions

[0385] In some embodiments, the condition, disease, or disorder treated with the composition(s) and/or method(s) of the present disclosure can, preferably, be selected from the group consisting of, for example: frailty; bone density loss; bone mineral density loss; weight loss; muscular atrophy; muscular degeneration; decline in muscle mass; decline in muscle strength; decline in hand strength; decline in leg strength; decline in physical fitness; decline in movement; decline in freedom of movement; decline in quality of life assessment; decline in ejection fraction; decline in exercise capacity; decline in learning; decline in learning capacity; decline in memory; decline in intellectual quotient; cognitive deterioration; forgetfulness; decline in cognitive capacity; decline in cognitive function; decline in synaptic plasticity; decline in synaptic function; cellular senescence; chronic kidney disease (CKD); chronic kidney disease - mineral and bone disorder (CKD-MBD); polycystic kidney disease (PKD); autosomal dominant polycystic kidney disease (ADPKD); acute kidney injury (AKI); acute tubular necrosis (ATN); acute allergic interstitial nephritis (AAIN); glomerulonephritis; kidney disease; renal failure; Alport Syndrome; nonoliguric renal failure; alcoholism; hyperphosphatemia; muscular dystrophy (MS); type 1 diabetes; type 2 diabetes; cardiovascular disease (CVD); cardiovascular calcification; cerebrovascular insufficiency; vascular calcification; coronary artery disease; heart failure; left ventricular hypertrophy; uremic cardiomyopathy; abnormalities in blood pressure; salt-sensitive hypertension; tissue calcification; calcific atherosclerotic plaque burden; calcinosis; familial tumoral calcinosis; cancer; one or more tumors; myelin-related diseases; demyelinating diseases; neurodegenerative disease; neurovascular diseases; progressive supranuclear palsy (PSP); Pompe disease; Niemann-Pick disease; microgliosis; Farber disease (FD); bone mass diseases; osteoporosis; osteopenia; osteopenia (particularly loss ofBMD of cortical bone); pulmonary emphysema; pulmonary fibrosis; cystic fibrosis, idiopathic (i.e., cause unknown) pulmonary fibrosis, radiation-induced lung injury, cirrhosis, biliary atresia, atrial fibrosis, endomyocardial fibrosis, (old) myocardial infarction, glial scar, arterial stiffness, arthrofibrosis, Crohn's disease, Dupuytren's contracture, keloid, mediastinal fibrosis, myelofibrosis, Peyronie's disease, nephrogenic systemic fibrosis, progressive massive fibrosis, retroperitoneal fibrosis, scleroderma/systemic sclerosis, adhesive capsulitis, skin atrophy; thymic atrophy; accumulation of renal interstitial matrix; glomerulosclerosis; anemia; albuminuria; proteinuria; infertility; Alzheimer's disease; Parkinson's Disease; dementia; vascular dementia; amyotrophic lateral sclerosis (ALS); motor neuron disease (MND); atrial fibrillation; chronic obstructive pulmonary disease (COPD); fibromyalgia; adult onset diabetes; arthritis; rheumatoid arthritis; osteoarthritis; glaucoma; cataracts; macular degeneration; multiple sclerosis (MS); lupus; ulcerative colitis; cachexia; obesity; vitamin D-related conditions; bone diseases; bone diseases through bone remodeling; gut diseases and related conditions; stem cell depletion; sea sickness; space adaptation syndrome (SAS); nausea; vertigo; non-alcoholic steatohepatitis (NASH), cirrhosis of the liver and alcoholic steatohepatitis.

[0386] Klotho serum levels have also been reported as being associated with muscle recovery, such as postinjury muscle healing. In particular, and without being bound to any theory, age-related declines in a-Klotho may drive progenitor cell mitochondrial dysfunction and impaired muscle regeneration. Clinically, this could translate to treatment of older adults who either sustained a muscle injury or underwent muscle-damaging surgery. Embodiments of the present disclosure can include administering a composition, as described herein, prophylactically and/or post-operatively. Administration at the appropriate timepoint(s) can enhance or support muscle regeneration and lead to a more complete recovery. Serum Klotho protein levels may also enhance or support muscle regeneration in athletes and other patients. Accordingly, embodiments of the present disclosure can include administering a composition, as described herein, prophylactically (pre-workout) and/or following exercise. Administration of compositions to treat age-related frailty in humans and non-human mammals

[0387] An exemplary embodiment of the present disclosure relates to the administration of a composition to treat age-related frailty (e.g., in humans or non-human animals). s-Klotho may rescue myogenic stem cells, improve muscle repair, and/or suppress fibrosis in animal models of human disease. Compositions that increase s-Klotho levels may, therefore, be a promising approach to counter muscle degeneration in aging human subjects showing signs of frailty.

[0388] For instance, the present disclosure relates to s-Klotho level-increasing compositions, formulations, and dosages, and administration thereof to a fragile and/or elderly (e.g., 60 - 95 years of age) person in order to maintain in the subject a maintenance serum concentration of s-Klotho within the range of a normal and/or young (e.g., 18 - 30 years of age) person (e.g., without any chronic conditions).

[0389] Such Klotho treatment over an extended period of time can recover and/or improve one or more aging-related indicator or conditions in the elderly, frail, or otherwise physiologically aging. Administration of compositions to treat (decrease) muscle atrophy in humans and non-human mammals

[0390] An exemplary embodiment of the present disclosure relates to the administration of compositions of the present disclosure to treat (e.g., decrease (the rate of)) muscle atrophy in human, as measured by skeletal muscle tissue mass and, preferably, the concurrent use of the above compositions and molecular indicators to provide guidance on the effects of administration in countering muscle atrophy.

[0391] Muscle atrophy can include numerous neuromuscular, metabolic, immunological and neurological disorders and diseases as well as starvation, nutritional deficiency, metabolic stress, diabetes, aging, muscular dystrophy, or myopathy. Muscle atrophy can occur during the aging process. Muscle atrophy can also result from reduced use or disuse of the muscle. Symptoms include a decline in skeletal muscle tissue mass. In human males, muscle mass declines by one-third between the ages of 50 and 80. Some molecular features of muscle atrophy can include the upregulation of ubiquitin ligases, and the loss of myofibrillar proteins. The breakdown of these proteins, which can be monitored (e.g., by measuring 3-methyl-histidine production, which is a specific constituent of actin), for example, in certain muscles of myosin. Release of creatine kinase (a cell damage marker) can also be indicative. Administration of compositions to treat (improve) muscle repair or recovery in humans and non-human mammals

[0392] Klotho serum levels have also been reported as being associated with muscle recovery, such as postinjury muscle healing. In particular, and without being bound to any theory, age-related declines in a-Klotho may drive progenitor cell mitochondrial dysfunction and impaired muscle regeneration. Clinically, this could translate to treatment of older adults who either sustained a muscle injury or underwent muscle-damaging surgery. Embodiments of the present disclosure can include administering a composition, as described herein, prophylactically and/or post-operatively. Administration at the appropriate timepoint(s) can enhance or support muscle regeneration and lead to a more complete recovery. Serum Klotho protein levels may also enhance or support muscle regeneration in athletes and other patients. Accordingly, embodiments of the present disclosure can include administering a composition, as described herein, prophylactically (pre-workout) and/or following exercise.

[0393] Administration of compositions to treat mental and/or cognitive decline in old age and/or throughout the human lifespan

[0394] An exemplary embodiment of the present disclosure relates to the administration of compositions of the present disclosure to improve and/or counteract (aging-related) decline in cognitive function(s). At the time of the present disclosure, it was unknown whether administration of compositions of the present disclosure may counteract cognitive decline in humans. However, transgenic mice with systemic over-expression of klotho performed better than controls in multiple tests of learning and memory. Elevating klotho in mice also enhanced long-term potentiation, a form of synaptic plasticity, and enriched synaptic GluN2B, an N-methyl-D-aspartate receptor (NMDAR) subunit with key functions in learning and memory. Blockade of GluN2B abolished klotho-mediated effects.

[0395] Klotho-regulated pathways may be relevant to slowing the progression of Alzheimer's disease and other forms of dementia. Brain scans of more than 400 healthy men and women aged 53 and over found that those who carried a single copy of a particular Klotho gene variant had a larger brain region that deals with planning and decision making. Further tests on the group found that those with an enlarged right dorsolateral prefrontal cortex (rDLPFC) fared better on a series of mental tasks.

[0396] About one in five people inherits a single copy of the gene variant, or allele, known as KL-VS, which improves heart and kidney function, and on average adds about three years to human lifespan. However as to the brain function, having a larger rDLPFC accounted for only 12% of the improvement in people's mental test scores while, on the other hand, as the editorial points out, carrying one copy of the KL-VS allele appears to confer a decade of resilience against the expected decline in structure and function of the rDLPFC. Thus, KL-VS heterozygosity appears to be associated with greater volume in right dorsolateral prefrontal cortex (rDLPFC).

[0397] Because rDLPFC is important for executive function, the investigators also analyzed working memory and processing speed in individuals. KL-VS heterozygosity may be associated with enhanced executive function across the lifespan examined. In short, results may suggest that variation in the klotho gene may be associated with bigger brain volume and better function.

[0398] An exemplary embodiment of the present disclosure relates to the administration of compositions of the present disclosure to augment in vivo Klotho protein levels and/or (cellular, molecular, and/or downstream) effects (e.g., in order to enhance cognition and counteract cognitive deficits throughout the human lifespan). Administration of s-Klotho level-increasing compositions can preserve and/or improve cognitive function (e.g., in humans). Administration of compositions to treat (prolong) human longevity and/or lifespan

[0399] An exemplary embodiment relates to the administration of compositions of the present disclosure to chronological (e.g., age-matched from birth) and sex-matched human subjects to improve average lifespan. The results on average lifespan obtained with composition administration (the experimental group of human subjects) can be compared reliably to those individuals not receiving a composition (the control group) and/or with statistical information (e.g., from actuarial tables) for a sufficiently large human population. Administration of compositions to treat other clinical indications

[0400] An exemplary embodiment of the present disclosure relates to the administration of compositions of the present disclosure to treat any age-associated or otherwise non-age associated condition, including, but not limited to (increase in) human frailty, (decrease in) longevity, (decrease in) cellular senescence, (decline in) muscle strength, (decrease in) bone loss or density, (decrease in) cognition, (decline in) muscle mass, (decline in) physical fitness, (decline in) hand strength, (decline in) leg strength, and so forth. The present disclosure also relates to the administration of compositions of the present disclosure to increase bone mineral density (BMD) (e.g., in women but not in men), to increase BMID (e.g., in elderly women), which is reduced after menopause, to regenerate or reduce the degeneration of (degenerative) skeletal muscle, to improve walking gait, to improve (or reduce the decline in) spatial learning and memory, movement, freedom of movement, quality of life assessment, ejection fraction, exercise change, exercise improvement, and so forth. The present disclosure further relates to the administration of compositions of the present disclosure to decrease cognitive deterioration or forgetfulness, to increase cognitive capacity, to improve cognitive function and synaptic plasticity, to decrease a decline in learning, learning capacity or IQ, to improve learning, learning capacity or IQ, and so forth. Administration of compositions to treat Acute Kidney Injury (AKI)

[0401] Acute kidney injury (AKI), previously called acute renal failure (ARF), is often defined as an abrupt onset of renal dysfunction ranging from minor loss of function to failure. AKI is a common clinical complication that develops in approximately 4%-7% of hospitalized patients each year and the prognosis can be poor. Mortality rates associated with AKI range from 5%-35%. Renal Klotho expression has been shown to be suppressed following AKI. Adenoviral gene transfer of Klotho can be cytoprotective in AKI.

[0402] Acute Kidney Injury (AKI) has been report in approximately 4.9%-7% of hospitalized patients each year. The rate of AKI may be as high as 60% in (hospitalized) elderly persons and 20-30% in elderly or critically ill patients. AKI is also associated with increased mortality, length of stay (LOS), 30 day re-administration rates and hospital cost.

[0403] AKI may result at least in part from kidney transplant or other surgery, acute tubular necrosis (ATN), acute allergic interstitial nephritis (AAIN), nephritis (e.g., glomerulonephritis), nephrotoxicity (e.g., drug-induced nephrotoxicity), low blood pressure, sepsis or septic condition, or other contributing factor(s). Kidney transplant and other surgeries can cause acute damage or injury to the kidneys, cause renal disease and/or failure. Nephrotoxicity can contribute to AKI, ATN, AAIN, nephritis, etc. It has been reported that drugs (e.g., clinically-administered, prescription, illegal, or other drugs) are associated with 15% to 25% of all cases of AKI. Contrast media alone accounts for 10% of all causes of hospital-acquired acute renal failure (e.g., via contrast-induced acute kidney injury CIAKI) and represents the third leading cause of in-hospital renal function deterioration after decreased renal perfusion and postoperative renal insufficiency.

[0404] In some cases, drug-induced AKI can be or comprise anti-microbial-induced nephrotoxicity (resulting from anti-microbial treatment). For instance, certain (gram negative) bacterial infections can be treated with one or more aminoglycosides, such as paromomycin, tobramycin, gentamicin, amikacin, kanamycin, neomycin, and so forth. Aminoglycosides have been shown to be nephrotoxic. Table 47 presents treatment data collected on the adult patients receiving the aminoglycosides. As illustrated in Table 47, nearly 23% of patients treated with amikacin, a common aminoglycoside, developed acute kidney disease and over 17% of patients treated with amikacin died prior to being discharged. Other aminoglycosides, including gentamicin, and tobramycin also induced (or were associated with or contributed to) kidney disease.

Length of Stay 11S8287 ID4 92 Discharged Home 55 1% 72.0% 62i%63% Did17.1% 41% 63% 5.8% lCU [£%18,2% 218% 18.7%' Pediatric Patient (<clyrsj) 0.0% 21.6% 6A1% 16.5% NursingIHome Patient 22t% 12.5% 20 2 1 6 Kidney Disease 22,9% 13.5% i65% 14.8%_____ UTi/cystitis UTl/cystits Pneumnonia UTi/cystitis Sepsis Sepsis UTi/cystitis Sepsis TopS5Dx Pneumonia Skinlnfection Sepsis Pneumnia SkinInfection Pneurnonia Skininfection SkininfEc lon ___________________Pelvc infection FUO Pelvic ifection Pelvc Infection

Table 47 104051 As.illustrated in Figures.13A and 13B,.over 1.2.million adult.patients,in.variousage groups, were treated with aminoglycosides in the year 2010. Other anti-microbial agents include, for example, penicillins, ampicillin, cephalosporins, sulfonamides, ciprofloxacin, vancomycin, macrolides, tetracyclines, rifampin, and so forth.

[0406] Drug-induced nephrotoxicity can also result from treatment with one or more non steroid anti-inflammatory drugs (NSAIDs), such as aspirin (acetylsalicylic acid), celecoxib, diclofenac, diflunisal, etodolac, ibuprofen, indomethacin, ketoprofen, ketorolac, nabumetone, naproxen, oxaprozin, piroxicam, salsalate, sulindac, tolmetin, and so forth.

[0407] Drug-induced nephrotoxicity can also result from treatment with one or more cyclooxygenase-2 (COX-2) inhibitors (e.g., valdecoxib, rofecoxib, celecoxib, etc.), proton pump inhibitors (e.g., omeprazole, lansoprazole, etc.), anticonvulsants (e.g., phenytoin, valproic acid, etc.), histamine H2 receptor antagonist (e.g., nizatidine, ranitidine, famotidine, cimetidine, etc.), diuretics (e.g., carbonic anhydrase inhibitors, loop diuretics (e.g., bumetanide, ethacrynic acid, torsemide, furosemide, etc.), potassium-sparing diuretics (e.g., triamterene, spironolactone, amiloride, etc.), thiazide diuretics (e.g., indapamide, chlorthalidone, metolazone, methyclothiazide, hydrochlorothiazide, chlorothiazide, bendroflumethiazide, polythiazide, hydroflumethiazide, etc.), or other diuretics, such as pamabrom, mannitol, and so forth.

[0408] Drug-induced nephrotoxicity can also result from treatment with lithium, which can affect the flow of sodium through nerve and muscle cells in the body and can be used to treat manic episodes of bipolar disorder, often characterized by hyperactivity, rushed speech, poor judgment, reduced need for sleep, aggression, and anger. Lithium can also help to prevent or lessen the intensity of manic episodes. Drug-induced nephrotoxicity can also result from treatment with or exposure to gold, mercury, copper, or other elemental matter.

[0409] Drug-induced nephrotoxicity can also result from treatment with (D-) penicillamine; a medication of the chelator class, which can be used to treat scleroderma, Wilson's disease (by binding to accumulated copper for elimination through urine), cystinuria (by binding with cysteine to yield a mixed disulfide which is more soluble than cysteine), direct-acting smooth muscle relaxant (e.g., hydralazine), spasmolytics (e.g., carisoprodol, cyclobenzaprine, metaxalone, methocarbamol, benzodiazepines, such as diazepam, clonidine and other imidazoline compounds, tizanidine, baclofen, hydantoin derivatives, dantrolene, and so forth.

[0410] Other forms of drug-induced nephrotoxicity can include, for example: contrast induced nephrotoxicity (e.g., following exposure to (iodinated) contrast media, also known as radiocontrast-induced nephropathy (CIN)); narcotic- (opioid-) induced nephrotoxicity (e.g., following use or abuse of certain narcotics (e.g., opioids), such as cocaine, heroin, etc.); chemotherapy-induced nephrotoxicity (e.g., following treatment with a cancer therapeutic, such as: cisplatin; carboplatin; oxaliplatin; alkylating agents, such as bendamustine, cyclophosphamide, ifosfamide, nitrosoureas, temozolomide, melphalan, etc.; antitumor antibiotics, such as mitomycin C, bleomycin, anthracyclines and related agents, etc.; antimetabolites, such as capecitabine, hydroxyurea, methotrexate, pemetrexed, pralatrexate, pentostatin, fludarabine, cladribine, gemcitabine, cytarabine, etc.; vinca alkaloids; topotecan; etoposide; taxanes; irinotecan; lenalidomide; eribulin; arsenic trioxide; ixazomib; etc.); and so forth. Indeed, a wide variety of nephrotoxic drugs can induce nephrotoxicity, leading to AKI. Drug-induced nephrotoxicity (and other forms of AKI) can be life-threatening if untreated and can incur enormous costs (to patients, hospitals, and insurers) to treat.

[0411] Embodiments of the present disclosure can include a method of treating or preventing (e.g., prophylactically or in response to at least one event) acute kidney injury (AKI), chronic kidney disease (CKD), or other condition. The method can comprise administering a composition of the present disclosure to a subject in need thereof For instance, the method can comprise administering to a subject in need thereof, an effective amount of a composition of the present disclosure (e.g., so as to raise and/or maintain a serum soluble Klotho protein concentration of the subject at or above a predetermined threshold for a predetermined period of time). The composition can comprise (i) a therapeutic recombinant Klotho protein or fragment or fusion protein thereof and/or (ii) a product that increases, enhances, augments, and/or supports endogenous Klotho protein production and/or level(s) in a patient to which the product is administered, optionally with one or more additional ingredients or compositions.

[0412] In some embodiments, the condition can comprise: (i) acute tubular necrosis (ATN), acute allergic interstitial nephritis again) , nephritis, glomerulonephritis, and/or nephrotoxicity; or (ii) AKI resulting at least in part from sepsis, kidney transplant or other surgery or medical procedure, acute tubular necrosis (ATN), acute allergic interstitial nephritis (AAIN), nephritis, glomerulonephritis, nephrotoxicity, or low blood pressure. The condition can comprise a drug-induced (e.g., aminoglycosides-induced) nephrotoxicity. The protein can be administered prophylactically, for example, prior to kidney transplant, nephrotoxin administration, or other activity, treatment, or event known or anticipated to cause or contribute to AKI. Alternatively, or in addition, the protein can be administered in response to AKI, such as after kidney transplant or other surgery, aminoglycoside or other nephrotoxin administration, or other activity, treatment, or event known or anticipated to cause or contribute to AKI.

[0413] In some embodiments, the nephrotoxin or other drug can be or comprise, for example: one or more aminoglycosides (e.g., paromomycin, tobramycin, gentamicin, amikacin, kanamycin, neomycin, etc.); one or more anti-fungal agents (e.g., amphotericin B, flucytosine, etc.); one or more contrast agents (e.g., (iodinated) radiocontrast media, high osmolality contrast media (HOCM) having an iodine to molecule ratio of about 1.5: 1, low osmolality, nonionic contrast media (LOCM) having an iodine to molecule ratio of about 3 : 1, isosmolar (isoosmolality) contrast media (IOCM) having an iodine to molecule ratio of about 6 : 1), etc.); one or more antiretroviral agents (e.g., adefovir, cidofovir, tenofovir, foscarnet, etc.); one or more cancer (or chemo-) therapeutics (e.g., cisplatin, carboplatin, oxaliplatin, alkylating agents (such as bendamustine, cyclophosphamide, ifosfamide, nitrosoureas, temozolomide, melphalan, etc.), antitumor antibiotics (such as mitomycin C, bleomycin, anthracyclines and related agents, etc.), antimetabolites (such as capecitabine, hydroxyurea, methotrexate, pemetrexed, pralatrexate, pentostatin, fludarabine, cladribine, gemcitabine, cytarabine, etc.), vinca alkaloids, topotecan, etoposide, taxanes, irinotecan, lenalidomide, eribulin, arsenic trioxide, ixazomib, etc.); one or more bisphosphonates, or derivatives thereof (e.g., zoledronate / zoledronic acid, ibandronate, alendronate, alendronate/cholecalciferol, etidronate, risedronate (optionally, with calcium carbonate), pamidronate, tiludronate, etc.); and/or one or more narcotics (e.g., opioids), such as cocaine, heroin, etc.);

[0414] Embodiments of the present disclosure can include a method of administering a composition of the present disclosure. The method can include administering the composition of the present disclosure to a human or non-human subject to treat or prevent (prophylactically) AKI or one or more conditions associated with AKI. The method can include determining a level of serum soluble klotho level in the subject, calculating a first dosage of a composition of the present disclosure sufficient to raise the serum soluble klotho level in the subject to a predetermined level or percent of normal levels, administering the first dosage to the subject, such as by oral, bolus or gradual administration, determining a rate of soluble Klotho decline in the serum of the subject, such as following administration of the first dosage, calculating a subsequent dosage time and amount, and/or administering the subsequent dosage of protein to the subject. Administration of compositions to treat Chronic Kidney disease (CKD)

[0415] Without being bound to any theory, klotho may be involved in human chronic kidney disease. Soluble Klotho in the circulation starts to decline early in chronic kidney disease (CKD) stage 2 and urinary Klotho possibly even earlier in CKD stage 1. Therefore, soluble Klotho could serve as an early and sensitive marker of kidney function decline. Moreover, preclinical animal data support Klotho deficiency is not just merely a biomarker, but a pathogenic factor for CKD progression and extrarenal CKD complications including cardiovascular disease and disturbed mineral metabolism. Prevention of Klotho decline, re activation of endogenous Klotho production, or supplementation of exogenous Klotho could all contribute to attenuation of renal fibrosis, retardation of CKD progression, improvement of mineral metabolism, amelioration of cardiomyopathy, and alleviation of vascular calcification in CKD.

[0416] CKD is characterized by progressive deterioration of renal function with high risk of ESRD. CKD risk increases with age, and about half of the CKD stage > 3 cases occurs in subjects > or= 70 years old. CKD can be viewed as a state of accelerated aging. The relative risk for cardiovascular mortality of a 25 to 34-year-old dialysis patient is similar to a non CKD patient of > or = 75 years of age. Cardiovascular disease is the principal killer in CKD and ESRD patients. CKD and ESRD patients have low renal Klotho expression and low levels of circulating Klotho. Renal Klotho deficiency in early stages of CKD may be attributed mainly to suppression of Klotho expression rather than loss of viable renal tubules. Furthermore, some dialysis patients still have detectable circulating Klotho, suggesting that renal Klotho expression is not completely suppressed, and Klotho may come from extra-renal source(s), although its origin is not clear to date. Establishing extra-renal sources of Klotho and characterizing how these can be up-regulated when renal production fails is of paramount importance.

[0417] Administration of compositions of the present disclosure can help to prevent, retard, and decrease the burden of comorbidity in CKD. Administration of compositions to treat gut diseases and related conditions

[0418] Without being bound to any theory, Interstitial Cells of Cajal (ICCs) are interstitial cells that are between other cells in the GI tract with an ongoing function in controlling peristalsis. ICCs (main) function may be to create the electrical signals that control the rhythmic smooth muscle contraction in the gut (different regions of the gastrointestinal system have different frequencies of contraction called peristalsis). ICCs may guide the migration of mesenchymal stem cells in the gut (and many other organs).

[0419] In the gut, ICCs may produce and/or become activated by klotho, leading to optimized regenerative processes. In Klotho knockout mice, ICCs are diminished, leading to impairment of the peristaltic process, mimicking gut disorders that occur in older humans.

[0420] Administration of compositions of the present disclosure can help to prevent, retard, and decrease impairment of the peristaltic process and/or augment, support, and/or optimize the regenerative processes, at least in the gut. These effects may further support gut health and/or prevent, retard, and decrease the occurrence and/or severity of gut diseases and related conditions. Therapeutic Treatment of Age-related Conditions

[0421] Investigators have discovered an association between Klotho and biological parameters commonly accepted as indicators of the clinical status in hospitalized older patients. The investigators genotyped the single-nucleotide polymorphisms (SNPs) rs9536314, rs1207568, and rs564481 at the KL locus in 594 hospitalized older patients (65 99 years), consecutively attending a geriatric ward, and tested the association of these KL variants with biological quantitative traits using analyses of covariance and genetic risk score models. Significant associations of rs9536314 with serum levels of hemoglobin, albumin, and high-density lipoprotein cholesterol (HDL-C) as well as significant associations of rs564481 with serum levels of hemoglobin, fasting insulin, and fasting glucose were observed. Gender segregated analyses confirmed these associations and suggests that the associations of KL genotypes with HDL-C, fasting glucose and fasting insulin levels may be driven by the female gender, while the association with serum levels of hemoglobin may be driven by the male gender. The association of KL genotypes with creatine levels was found in females, while the association with insulin-like growth factor-1 (IGF-1) and lymphocytes count (LC) was found in males. The genetic risk score (GRS) models further confirmed significant associations among KL SNPs and hemoglobin, total cholesterol, and HDL-C. Gender segregated analyses with the GRS-tagged approach confirmed the associations with HDL-C, fasting glucose, and fasting insulin levels in females, and with hemoglobin and LC in males. The findings suggested that KL locus may influence quantitative traits such as serum levels of lipid, fasting glucose, albumin and hemoglobin in hospitalized older patients, with some gender differences suggested for creatine, IGF-1 levels, and LC, thus being one of the genetic factors possibly contributing to age-related diseases and longevity.

[0422] Embodiments of the present disclosure can include administering a composition of the present disclosure to a subject in need thereof (e.g., an individual or patient, optionally elderly and/or suffering from an aging-related condition, low endogenous s-Klotho protein expression, and/or symptoms of age-related condition or decreased longevity). Administration of the composition(s) of the present disclosure can lead to a beneficial increase in blood s-Klotho levels. The administration may reverse or counteract the deleterious effects of the aging-related condition and/or influence, in a positive therapeutic manner, quantitative traits such as serum levels of total cholesterol, HDL-C, fasting glucose, fasting insulin, albumin, creatine, IGF-1, hemoglobin, and lymphocytes count (e.g., in hospitalized and/or elderly patients). Prophylactic Composition Administration

[0423] In addition to the foregoing, embodiments of the present disclosure can include administering a composition of the present disclosure to an individual or subject in need thereof for prophylactic purposes and/or maintenance of certain health attributes. For example, administration of certain compositions of the present disclosure can help maintain youthfulness in optionally aging patients not yet suffering from a diagnosed aging-related condition. Accordingly, while certain embodiments of the present disclosure can relate to and/or comprise treating a condition in a patient, other embodiments can relate to and/or comprise preventing, inhibiting development of, and/or prophylactically addressing one or more conditions. Administration of exogenous S-Klotho to treat genetic defects

[0424] An exemplary embodiment of the present disclosure relates to the administration of exogenous S-Klotho to treat (e.g., correct) known human genetic defects. For example, a 13 year-old girl with familial tumoral calcinosis and a Klotho mutation has been reported. Familial tumoral calcinosis is an autosomal recessive metabolic disease characterized by ectopic calcifications and hyperphosphatemia due to inactivating mutations in FGF23 or GALNT3. FGF23 is a hormone necessary for the renal excretion of phosphate, while GALNT is an enzyme contributing to the maturation and secretion of FGF23. A homozygous mutation in the klotho gene has been identified in the 13-year old girl. Klotho encodes a secreted protein necessary to the transmission of the signal emitted by FGF23 toward its receptors. The administration of exogenous human recombinant S-Klotho constitutes a highly targeted and effective therapy to address the malfunction and symptoms associated with familial tumoral calcinosis. Compositions and treatments including S-Klotho and/or Supplement in combination with other component(s)

[0425] In at least one embodiment, a composition, medicament, dosage, or therapeutic treatment can include a therapeutic human recombinant soluble alpha Klotho (S-Klotho) protein and a natural supplement composition that increases endogenous Klotho production or one or more component thereof Klotho, whether endogenous or exogenous (recombinant) can also act in an additive or synergistic matter with other compounds and/or components to influence one or more aspects of human health and well-being. For instance, treatments that include a therapeutic human recombinant soluble alpha Klotho (S-Klotho) protein, and/or natural supplement composition that increases endogenous Klotho production, in combination and/or concurrently with one or more additional active components can benefit human patients. Such treatments can be prophylactic or responsive to any human condition on which the Klotho protein and/or other component(s) can have a therapeutic effect. Such conditions can include, for example, an age-related condition, a clinical (e.g., metabolic) condition, a chronic or acute condition, and so forth. Specific, non-limiting examples of specific conditions are disclosed herein.

[0426] S-klotho may exist in the human body along with other blood borne anti-aging compound such as growth/differentiation factor 11 (GDF-11). Accordingly, in certain embodiments, therapeutic S-klotho can be co-administered (e.g., concurrently, sequentially, and/or in combination) with therapeutic GDF-11. Such administration can have additive or synergistic anti-aging or other effects in some embodiments. Likewise, the co-administration S-klotho to human subjects with (neutralizing) antibodies to or suppressor of CCL11 may work in unison to counter aging or other condition (as CCL11 (also known as eotaxin-1) is understood to be a negative regulator of stem cell rejuvenation). S-klotho can also or alternatively be co-administered with other eotaxins, such as eotaxin-2 (CCL24) and/or eotaxin-3 (CCL26).

[0427] In some embodiments, S-klotho can be co-administered with suppressors of or antibodies to Transforming Growth Factor -1 (TGF-1). S-klotho administration may oppose the action of the TGF-31 signal pathways involved in an endogenous anti-cellular epithelial-to-mesenchymal transition (anti-EMT) that leads to renal and other tissue fibrosis. Anti-EMT is also relevant in cancer cells where inhibiting EMT may confer on cancer cells the ability to metastasize - this latter process is understood to be opposed by klotho. Accordingly, co-administration of S-klotho and a suppressor of or antibody to Transforming Growth Factor 3-1 (TGF-1) can have synergistic or additive effects.

[0428] In some embodiments, S-klotho can be co-administered with antibodies to or suppressors of Insulin Growth Factor-i (IGF-1). Klotho is understood to be a hormone that inhibits the intracellular insulin/IGF-1 signaling cascade, and this inhibition increases resistance to oxidative stress at the cellular and organismal level in mammals; a mechanism which is considered to be evolutionarily conserved for extending life span. Accordingly, co administration of S-klotho and a suppressor of or antibody to Insulin Growth Factor-i (IGF 1) can have synergistic or additive effects.

[0429] In some embodiments, S-klotho can be administered in combinations with vitamin D (e.g., Vitamin D3) or 1,25-dihydroxyvitamin D 3 [1,25(OH) 2D 3], FGF-15, FGF-19, and/or Klotho ; since numerous studies have revealed a comprehensive regulatory scheme of mineral homeostasis involving the mutually regulated positive/negative feedback actions of Klotho a-Kl, FGF23, and 1,25(OH) 2D and/or an analogous regulatory network composed of Klotho -Kl, FGF15/humanFGF19, and bile acids that regulate bile acid/cholesterol metabolism. Such co-administration can have synergistic or additive effects on numerous conditions and/or processes in the body. In some embodiments, S-klotho can be administered in combinations with FGF-21,

[0430] In some embodiments, S-klotho can be co-administered with carbonic anhydrase inhibitors, such as acetazolamide, methazolamide, dichlorphenamide, dorzolamide, brinzolamide, and/or topiramate. Such combinatorial administration can be useful in the treatment of ankylosing spondylitis (AS), rheumatoid arthritis (RA), and a variety of other conditions. Various investigations have shown that increased bone resorption is a characteristic of AS and RA and that carbonic anhydrase inhibitors play an antiarthritic role by inhibiting bone resorption. At the bone level, through a different mechanism, S-klotho stimulates bone resorption and phosphate release by acting on TRPV5, which is a recently identified osteoclast function modulator. Increased levels of 1,25(OH) 2D 3 caused by S-Klotho administration can also stimulate osteoclast differentiation and bone resorption and, thereby, phosphate release. Thus, co-administration of S-Klotho and carbonic anhydrase inhibitors can have an additive or synergistic effect, especially in promoting bone health, particularly in AS and RA.

[0431] S-Klotho can be administered in combination with one or more disease-modifying antirheumatic drugs (DMARDs) - for the treatment of severe active rheumatoid arthritis.

[0432] S-Klotho can be administered in combination with cyclosporine, since cyclosporine decreases klotho mRNA and protein and increases oxidative stress leading to cyclosporine induced-renal injury (CsA). The associated decrease of klotho mRNA and protein and increases oxidative stress can be countered by exogenous co-administration of S-Klotho.

[0433] In some embodiments, S-klotho can be co-administered with losartan and/or cyclosporine. Treatment with losartan, an angiotensin II type 1 (ATI) receptor blocker, reversed the decrease in klotho expression seen with cyclosporine. Losartan also produced a concurrent improvement in renal histology (with losartan decreasing the tubulointerstitial fibrosis that is caused by cyclosporine).

[0434] In some embodiments, S-klotho can be co-administered with one or more aminoglycosides, such as amikacin, gentamicin, tobramycin, etc. Such treatment can be useful to prevent nephrotoxicity and/or acute kidney injury (AKI) when aminoglycosides are used to treat (gram-negative) pathogen infection, which may greatly expand the use of aminoglycosides to treat infections. The administration of S-Klotho with verapamil and/or diltiazem, which have been used to block AKI, can be therapeutic in the treatment and/or prevention of renal dysfunction from AKI.

[0435] In some embodiments, S-klotho can be co-administered with testosterone or androgen receptor (AR) up-regulating compounds. Recent reports indicate no beneficial effect of testosterone treatment in men in regards to personality, psychological well-being, or mood is observed. In addition, the prescription of testosterone supplementation for low-T for cardiovascular health, sexual function, physical function, mood, or cognitive function was considered to be without support from randomized clinical trials. However, testosterone supplementation was consistently found to increase muscle strength but did not have beneficial effects on physical function. S-Klotho administration in combination with testosterone and/or androgen receptor (AR) up-regulating compounds can significantly increase muscle strength and/or physical function in elderly, frail, or low-T men beyond any effect that testosterone or S-Klotho may have alone in these treatment groups.

[0436] In some embodiments, S-klotho can be co-administered with estrogen or an estrogen hormone (e.g., estradiol, estriol, estrone, etc.). Such co-administration can improve health indicators in women (e.g., menstrual, menopausal, or menopausal transitioning women) and/or treat infertility, polycystic ovarian disease or disorder, obesity, hormone imbalance and related conditions, and/or other female health conditions.

[0437] In some embodiments, S-klotho can be co-administered with one or more nootropics - also called smart drugs or cognitive enhancers. Nootropics drugs, supplements, and/or other substances can improve cognitive function, particularly executive functions, memory, creativity, motivation, task saliency (motivation to perform a task), performance (especially on tedious tasks that require a high degree of effort), and can be useful in treating cognitive or motor function difficulties attributable to disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and ADHD. The most commonly used class of drug that is known to improve some aspect of cognition is stimulants, especially the classes of stimulants that demonstrate cognition-enhancing effects in humans by acting as direct agonists or indirect agonists of dopamine receptor D1, adrenoceptor A2, or both receptors in the prefrontal cortex. Stimulants include, for example: amphetamines (e.g., amphetamine, dextroamphetamine, lisdexamfetamine, etc.), which can benefit a range of cognitive functions (e.g., inhibitory control, episodic memory, working memory, and aspects of attention), especially in individuals with ADHD; dimethylamylamine (DMAA), such as 1,3 dimethylamylamine, which can improve physical performance, alertness, reaction time, etc.; methylphenidate - a substituted phenethylamine that can improve a range of cognitive functions (e.g., working memory, episodic memory, and inhibitory control, aspects of attention, and planning latency); eugeroics (e.g., armodafinil, modafinil, etc.), which can function as wakefulness promoting agents that can increase alertness, particularly in sleep deprived individuals, facilitate reasoning and problem solving, treat narcolepsy, shift work sleep disorder, and daytime sleepiness remaining after sleep apnea treatments, and so forth; xanthines (e.g., caffeine, etc.), which can increase alertness, performance, and/or memory; nicotine, and so forth.

[0438] In some embodiments, S-klotho can be co-administered with one or more osteoporosis and/or osteopenia medications, as known in the art. Klotho may play a role in regulating bone mineral density, as the absence of Klotho can lead to reduced bone mineral density in animals. For instance, Klotho knockout mice show reduced bone mineral density over time. Klotho expression can rescue bone defect, such as reduced bone mineral density shown by Klotho knockout mice over time. Epidemiological studies have shown associations between various Klotho gene variants and changes in bone mineral density and prevalence of hand osteoarthritis.

[0439] S-Klotho can be administered in combination with one or more anti-cancer treatments and/or preventions, such as a chemotherapeutic. In lung cancers, such as non small cell lung cancer (NSCLC), for example, S-klotho administration can affect the resistance of lung cancer cells to cisplatin and/or other chemotherapy. In addition, S-klotho can function as a potential tumor suppressor in lung cancer, gastric cancer, pancreatic cancer (adenocarcinoma), and other forms of cancer. S-Klotho can be administered in combination with sorafenib chemotherapy for the treatment of hepatocellular carcinoma (HCC). Overexpression of klotho as well as treatment with soluble klotho protein can reduce hepatoma cell growth in vitro and in vivo. Other cancer types that can be treated with S klotho co-administration include hepatocellular carcinoma (HCC), central nervous system (CNS) cancers (e.g., brain (e.g., glioma, craniopharyngioma, medulloblastoma and meningioma), spinal cord, and other tumors, lymphoma, etc.), (metastatic) colon cancer, and so forth.

[0440] S-Klotho can also be administered in combination with chemotherapeutic(s) to treat chemotherapy-induced frailty in cancer patients. S-Klotho can also be administered to treat cancer-induced frailty in cancer patients following other known treatments.

[0441] S-Klotho can be administered in combination with kidney dialysis or other procedures. S-Klotho can be administered to treat frailty in dialysis patients, as frailty is associated with poor outcomes for patients on dialysis.

[0442] S-Klotho can be administered in combination with one or more Alzheimer's Disease treatment or preventions, or with brain-derived neurotrophic factor (BDNF), as an adequate amount of BDNF can help to develop and maintain normal neuronal circuits in the brain.

[0443] S-Klotho can be administered in combination with one or more molecules that increase the ability of klotho to cross the blood-brain barrier in order to increase the ability of klotho to enter the central nervous system (CNS) to treat or prevent CNS-relates conditions. For example, neither S-Klotho nor BDNF are known to cross the blood-brain barrier. Embodiments of the present disclosure include utilizing blood-brain barrier delivery techniques for the administration of S-klotho and/or S-klotho with BDNF to the CNS to treat Alzheimer's Disease and/or improve cognition in individuals not affected by Alzheimer's Disease.

[0444] S-Klotho can be administered in combination with 5' adenosine monophosphate activated protein kinase (AMPK) or AMPK activating drugs or ingredients that positively regulate signaling pathways that replenish cellular ATP supplies, including fatty acid oxidation and autophagy; or that negatively regulate ATP-consuming biosynthetic processes including gluconeogenesis, lipid and protein synthesis.

[0445] S-Klotho can be administered in combination with one or more anti-diabetic drugs such as insulin, phloridzin or the antioxidant tiron and these combination treatments may have merit in the prevention of renal damage from oxidative stress produced in diabetic disorders. The co-administration of S-Klotho with other antidiabetic drugs for type 1 diabetes can protect 3-cells by inhibiting 3-cell apoptosis through activation of the integrin 31 FAK/Akt pathway, leading to inhibition of caspase 3 cleavage.

[0446] S-Klotho can be administered in combination with one or more type 2 anti-diabetes drugs such as metformin for improving glycemic control and vascular function in overweight and obese diabetic subjects.

[0447] S-Klotho can be administered in combination with one or more blood pressure medications, calcium regulators, or treatments or preventions of chronic kidney disease (CKD). For example, soft-tissue calcification is a prominent feature in CKD and Klotho can ameliorate vascular calcification by enhancing phosphaturia, preserving glomerular filtration, and directly inhibiting phosphate uptake by vascular smooth muscle.

[0448] S-Klotho can be administered in combination with TM5441 or other inhibitors of PA-1 (plasminogen activator 1), since it is thought that PA-1 inhibition or deficiency retards the development of senescence and protects organ structure and function while prolonging the lifespan of Klotho-deficient (kl/kl) mice.

[0449] S-Klotho can be administered in combination with sirtuinI (SIRT1) or SIRTI activating compounds (STACs) such as resveratrol. SIRTI, a type III protein deacetylase, is thought to be a novel anti-aging protein involved in regulation of cellular senescence/aging and inflammation. SIRT1 level and activity are decreased during lung inflammation caused by oxidative stress. The mechanism of SIRT1-mediated protection against inflammation is associated with the regulation of inflammation, premature senescence, telomere attrition, senescence associated secretory phenotype, and DNA damage response. A variety of dietary polyphenols and pharmacological activators are shown to regulate SIRT1 so as to intervene the progression of type 2 diabetes, cancer, cardiovascular diseases, and chronic obstructive pulmonary disease associated with inflammation. Thus some or all of the health benefits of SIRT-1 may be augmented by co-administration of SIRTI and/or SIRTI-activating compounds given with S-Klotho.

[0450] S-Klotho can be administered in combination with one or more Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps), as recognized by the FDA. Such products can include, for example, one or more of bone (including demineralized bone, ligaments, tendons, fascia, cartilage, ocular tissues (corneas & sclera), skin, vascular grafts (veins and/or arteries), optionally (or other than) preserved umbilical cord veins, pericardium, amniotic membrane (when used alone (-without added cells-) for ocular repair), dura mater, heart valve allografts, hematopoietic stem cells derived from peripheral or umbilical cord blood, semen, oocytes, or embryos. In at least one embodiment, the HCT/P can be or comprise one or more stem cells. Stem cell treatment for damaged bodily tissues and organs continues to grow in popularity. Administration of therapeutic, recombinant Klotho protein in combination with stem cells provided surprising, unexpected, and even synergistic outcomes for subjects in need thereof.

[0451] Embodiments of the present disclosure further include a combination product, comprising a therapeutic, recombinant Klotho protein in combination with human stem cells. The composition can also include a pharmaceutically-acceptable carrier as described herein. Such compositions can comprise or be classified as regenerative medicines, to treat, modify, reverse, or cure a serious or life-threatening disease or condition, as recognized by the FDA. Preliminary clinical evidence indicates that the composition (drug) has the potential to address unmet medical needs for such disease or condition.

[0452] Illustratively, stem cells can be or comprise mesenchymal stem cells (MSCs), such as from human umbilical cords or placentas. In at least one embodiment, the composition comprising huMSCs and a therapeutic, recombinant Klotho protein of the present disclosure attenuated the inflammatory and oxidative stress responses occurring in AKI, and/or reduced the expression of senescence-related proteins and microRNAs.

[0453] S-Klotho can be administered in combination with one or more senescence inhibitors. For instance, Klotho protein can be combined with Pin-FOXM1 and/or other senescence inhibitors to enhance outcomes in patients receiving such treatment.

[0454] S-Klotho can be administered in combination with one or more of the following: Klotho stimulators (e.g., Vit. D, Losartan, Testosterone), GDF-11, Trichostatin A anti-fungal (e.g., GDF-11 Stimulator), TIMP-2, CCL-11 Inhibitor/antibodies, Dasatinib, Nicotinamide Riboside (e.g., NAD+), nicotinamide mononucleotide (NMN) (e.g., NDA+), AMPK Stimulators (e.g., Resveratrol, Aspirin, Salicylate, phytochemicals, DR), C60 Fullerene, Rapamycin, FGF inhibitor, Senolytics drugs/compounds such as FOXO4 p53 interfering peptides (e.g. FOXO4-DRI), inhibitors of the anti-apoptotic proteins BCL-2 and BCL-xL.

[0455] Any of the foregoing or other treatments or co-administrations can have additive or synergistic effects over those of any of the treatments alone. For instance, co-administration of a Klotho protein with one or more of the foregoing can result in treatment outcomes greater than the sum of the individual outcomes of administering the components alone at similar concentrations. In addition, synergistic effects can include treatment outcomes similar to those of the individual outcomes of administering the components alone, but at lower concentrations. Synergistic effects can also include increasing the maximum effective dose of one or more of the components, reducing toxicity of one or more of the components, or any other beneficial result that is more than a mere additive effect of the individual treatment outcomes. In addition, additive effects of the individual treatment outcomes can comprise one or more synergistic effects. Such additive/synergistic effects may not be predicted or expected given the nature and understanding of the individual components.

[0456] As used herein, a combination treatment or co-administration can include treatment or administration of a combination product, composition, or formulation comprising a Klotho protein and one or more additional active ingredients. The one or more additional active ingredients can be selected from among the components, drugs, substances, treatment compositions, etc. described herein or others known in the art. For instance, the Klotho protein and one or more additional active ingredients can be co-formulated into an injectable (e.g., intramuscular, intravenous, etc.), ingestible, transdermal, inhalable, topical, or other formulation.

[0457] Alternatively, a combination treatment or co-administration can include treatment or administration of a Klotho protein and one or more additional active ingredients, but without the Klotho protein and one or more additional active ingredients being combined or formulated into a combination product, composition, or formulation. For instance, the Klotho protein and one or more additional active ingredients can each comprise or be in a separate injectable (e.g., intramuscular, intravenous, etc.), ingestible, transdermal, inhalable, topical, or other formulation.

[0458] It will also be appreciated that co-administration can comprise simultaneous administration of two or more components or distinct administrations of two or more components, the distinct administrations preferably being separated by a period of time. The period of time can be very small, in some embodiments. For instance, a second component of the Klotho protein and one or more additional active ingredients can be administered (e.g., injected) substantially, immediately following administration of a first component of the Klotho protein and one or more additional active ingredients. Alternatively, the first and second administrations can be separated by a time period of 1-60 seconds, 1-60 minutes, 1-24 hours, 1-7 days, 1-4 weeks, 1-12 months, and so forth, or any value or range of values therebetween. Similarly, simultaneous administration can include overlapping administration timeframes for the two or more components. Therapeutic Treatment of Hyperphosphatemic Familial Tumoral Calcinosis (HFTC)

[0459] In affected human individuals, IFTC is caused by a histidine (H) to arginine (R) mutation at amino acid (AA) position 193 of S-Klotho - rs121908423. Without being bound to any theory, it is thought that the H193R mutation in IFTC individuals impairs the ability of S-Klotho to form a ternary complex with FGF23 and FGFRlc, which impairs KL dependent FGF23 signaling. As a result, affected subjects present a severe metabolic disorder that manifests with hyperphosphatemia and massive calcium deposits in the skin and subcutaneous tissues. Some patients manifest recurrent, transient, painful swellings of the long bones associated with the radiographic findings of periosteal reaction and cortical hyperostosis and absence of skin involvement.

[0460] An embodiment of the present disclosure includes a S-Klotho protein having H193. The H193 protein can be produced or expressed in the context of any protein construct described herein. For instance, the H193 variant can be produced or expressed in the context of S-Klotho, isoform 1 or 2, 1-981, 29-981, 34-981, 36-981, 131-981, 1-549, 29-549, 34-549, 36-549, 131-549, and so forth, with or without a tag (e.g., Fc tag, TEV-Twin-Strep tag, TEV sequence, etc.). Accordingly, the nucleic acid construct or cDNA from which the protein is expressed can be of corresponding configuration.

[0461] Embodiments can include producing a H193 heterozygous or homozygous variant construct, transferring (e.g., via transfection) the resulting construct, which encodes the S Klotho H193 protein, into an appropriate expression system (e.g., CHO cells), and/or transiently expressing the S-Klotho H193 protein. The H193 Klotho protein may also be expressed at higher levels than the R193 (or H193R) protein. Embodiments can include purifying (and optionally quality-control testing) the expressed protein for therapeutic administration. Embodiments can include administering a therapeutic or therapeutically effective amount of the S-Klotho H193 protein to a subject in need thereof (e.g., HFTC individuals, individual diagnosed with HFTC, or patient harboring the H193R (rs121908423) or other variant). Alternatively, the subject may be of wild-type of other mutant or variant type. Administration of the recombinant S-Klotho H193 protein can lead to a beneficial increase in blood S-Klotho levels. The administration may reverse or counteract the deleterious effects of the R193 mutation that is transcribed and circulated in HFTC individuals as a result of the H-to-R193 point mutation found in the human klotho gene in individuals affected with HFTC. Accordingly, the circulating concentration of S-Klotho H193 may help to counter the effects observed in H193R or HFTC individuals. Therapeutic Treatment in CC Genotype Patients with End-Stage Renal Disease (ESRD)

[0462] Approximately 350,000 patients with end-stage renal disease (ESRD) suffer exceptionally high mortality rates in their first year of chronic hemodialysis. Both vitamin D and fibroblast growth factor (FGF)-23 levels correlate with survival in these patients. Without being bound to any theory, Klotho is a protein in the vitamin D/FGF-23 signaling pathway that has been linked with accelerated aging and early mortality in animal models. It has been hypothesized that genetic variation in the Klotho gene may be associated with survival in subjects with ESRD. Investigators tested the association between 12 single nucleotide polymorphisms (SNPs) in the Klotho gene and mortality in a cohort of ESRD patients during their first year on hemodialysis (n = 1307 white and Asian). A significant association was discovered between the CC genotype of one tag SNP, rs577912 (a common HapMap variant with a minor allele frequency [MAF] > 0.05 within the Klotho gene sequence located in intron 1), and increased risk for 1-yr mortality (RR, 1.76; 95% CI, 1.19-2.59; p = 0.003). This effect in individuals with the CC genotype was even more marked among patients who were not treated with activated vitamin D supplementation (HR, 2.51; 95% CI, 1.18-5.34; p = 0.005). In lymphoblastoid cell lines derived from HapMap subjects, the CC genotype was associated with a 16 - 2 1 % lower Klotho expression compared with the AA or AC genotypes. However, none of the rs577912 SNPs nucleotide change described above result in an amino acid change in the Klotho protein. Accordingly, this functional SNP (rs577912) may quantitatively affect Klotho gene expression at the mRNA level.

[0463] An embodiment of the present disclosure includes a S-Klotho protein expressed from the AA or AC genotype. The protein can be produced or expressed in the context of any protein construct described herein. For instance, the protein can be produced or expressed in the context of S-Klotho, isoform 1 or 2. 1-981, 29-981, 34-981, 36-981, 131-981, 1-549, 29 549, 34-549, 36-549, 131-549, and so forth, with or without a tag (e.g., Fc tag, TEV-Twin Strep tag, TEV sequence, etc.). Accordingly, the nucleic acid construct or cDNA from which the protein is expressed can be of corresponding length.

[0464] Embodiments can include producing a AA or AC heterozygous or homozygous construct, transferring (e.g., via transfection) the resulting construct, which encodes the S Klotho protein, into an appropriate expression system (e.g., CHO cells), and/or transiently expressing the S-Klotho protein. Klotho protein expressed in AA or AC heterozygous or homozygous cells may be expressed at higher levels than in CC cells. Embodiments can include purifying (and optionally quality-control testing) the expressed protein for therapeutic administration. Embodiments can include administering a therapeutic or therapeutically effective amount of the S-Klotho protein to a subject in need thereof (e.g., an individual or patient harboring the CC mutation at the one tag SNP, rs577912, having low endogenous S Klotho protein expression, and/or with end-stage renal disease (ESRD)). Alternatively, the subject may be of wild-type of other mutant or variant type. Administration of the recombinant S-Klotho protein can lead to a beneficial increase in blood S-Klotho levels. The administration may reverse or counteract the deleterious effects of the CC mutation that is transcribed and circulated in individuals as a result of the point mutation(s) found in the human klotho gene in affected individuals. Accordingly, the circulating concentration of S Klotho may help to counter the effects observed in CC individuals, especially those with end stage renal disease (ESRD), namely mortality in the first year in ESRD patients undergoing chronic hemodialysis.

Therapeutic Treatment of Radiographic Hand Osteoarthritis (OA) and Osteophyte

[0465] Osteoarthritis (OA) is a common complex disease with strong heritable components. Investigators studied the association between four putatively functional genetic variants in klotho gene and hand OA in a large female Caucasian population. The investigators found significant association between SNP G-395A and the presence/absence of radiographic hand OA and osteophyte formation. Allele G significantly increased the risk for radiographic hand OA and osteophytes with odds ratios (ORs) of 1.44 (P=0.008, 95% confidence interval (CI) 1.09-1.91) and 1.36 (P=0.006, 95% CI 1.09-1.70), respectively. From logistic regression modelling, genotype GG showed more than three-fold increased risk for both radiographic hand OA (OR=3.10, 95% CI 1.10-8.76) and osteophyte (OR=3.10, 95% CI 1.10-8.75) when compared to genotype AA. After adjustment for age, ORs for genotype GG further increased to 4.39 (P=0.006, 95% CI 1.51-12.74) for radiographic hand OA and to 4.47 (P=0.005, 95% CI 1.56-12.77) for osteophytes. The investigators also suggested that one variant (SNP G 395A) in the klotho gene is associated with the susceptibility of hand OA and appears to act through osteophyte formation rather than cartilage damage.

[0466] An embodiment of the present disclosure includes a S-Klotho protein expressed from a construct having SNP G395A. The resulting protein can be produced or expressed in the context of any protein construct described herein. For instance, the A395 variant can be produced or expressed in the context of S-Klotho, isoform 1 or 2, 1-981, 29-981, 34-981, 36 981, 131-981, 1-549, 29-549, 34-549, 36-549, 131-549, and so forth, with or without a tag (e.g., Fc tag, TEV-Twin-Strep tag, TEV sequence, etc.). Accordingly, the nucleic acid construct or cDNA from which the protein is expressed can be of corresponding length.

[0467] Embodiments can include producing a G395A heterozygous or homozygous construct, transferring (e.g., via transfection) the resulting construct, which encodes the S Klotho protein, into an appropriate expression system (e.g., CHO cells), and/or transiently expressing the S-Klotho protein. Klotho protein expressed in A395 heterozygous or homozygous cells may be expressed at higher levels than in G396 cells. Embodiments can include purifying (and optionally quality-control testing) the expressed protein for therapeutic administration. Embodiments can include administering a therapeutic or therapeutically effective amount of the S-Klotho protein to a subject in need thereof (e.g., an individual or patient harboring the G395 SNP and/or (at risk of developing) radiographic hand osteoarthritis (OA) and/or osteophytes). Alternatively, the subject may be of wild-type of other mutant or variant type. Administration of the recombinant S-Klotho protein can lead to a beneficial increase in blood S-Klotho levels. The administration may reverse or counteract the deleterious effects of the G395 SNP that is transcribed and circulated in affected individuals. Accordingly, the circulating concentration of S-Klotho may help to counter the effects observed in G395 individuals, especially those at risk of developing radiographic hand osteoarthritis (OA) and/or osteophytes. Administration of the G-395A S-Klotho protein may, therefore, decrease the risk of radiographic hand osteoarthritis (OA) and osteophyte formation in patients (e.g., patients harboring the G395 SNP. Therapeutic Treatment of Metabolic Syndrome

[0468] The risk and/or incidence of metabolic syndrome (MetS), a cluster of cardiometabolic risk factors including abdominal obesity, hyperglycemia, dyslipidemia and hypertension, increases with age. In elderly adults, MetS not only increases the risk of cardiovascular diseases and type 2 diabetes, but also is associated with cognitive decline and disability. Current evidence suggests that MetS is partly heritable, and genetic factors play a greater role than environment factors on the incidence of MetS. Investigators discovered an association between the G-395A polymorphism and metabolic syndrome (MetS) among a population of Chinese nonagenarians and centenarians. Subjects were from the Project of Longevity and Aging in Dujiangyan (PLAD). The genotyping of G-395A (rs1207568) in the promoter region of the Klotho gene was performed using the TaqMan allelic discrimination assay. MetS was diagnosed according to the International Diabetes Federation criteria. Included were 695 subjects aged 93.5 3.2 years. G and A allele frequencies were 0.852 and 0.148, respectively. In the whole population, the frequency of MetS was 10.8 % and 5.9 % in the GG and GA + AA genotype group, respectively (p = 0.004). The -395A allele carriers had significantly lower risk of MetS in the whole population (odds ratio [OR] 0.50, 95 %

confidential interval [CI] 0.25 to 0.98) and in women (OR 0.51, 95 % CI 0.24 to 0.97), but not in men (OR 0.42, 95 % CI 0.05 to 3.85). In the whole population and women, the relationship between the Klotho G-395A SNP and MetS might be due to its influence on high blood pressure (OR 0.48, 95 % CI 0.34 to 0.67; OR 0.47, 95 % CI 0.31 to 0.71, respectively) and hypertriglyceridemia (OR 0.66, 95 % CI 0.39 to 0.95; OR 0.54, 95 % CI 0.31 to 0.98, respectively). In men, this relationship might be due to its influence on high blood pressure (OR 0.47, 95 % CI 0.25 to 0.90) and low HDL-C (OR 0.69, 95 % CI 0.27 to 0.93). Investigators concluded that the -395A allele carriers of the Klotho gene were correlated with lower risk of MetS among Chinese nonagenarians and centenarians, especially in women.

[0469] An embodiment of the present disclosure includes a S-Klotho protein expressed from a construct having the -395A allele. The resulting protein can be produced or expressed in the context of any protein construct described herein. For instance, the A395 allele can be produced or expressed in the context of S-Klotho, isoform 1 or 2, 1-981, 29-981, 34-981, 36 981, 131-981, 1-549, 29-549, 34-549, 36-549, 131-549, and so forth, with or without a tag (e.g., Fc tag, TEV-Twin-Strep tag, TEV sequence, etc.). Accordingly, the nucleic acid construct or cDNA from which the protein is expressed can be of corresponding length.

[0470] Embodiments can include producing a -395A heterozygous or homozygous construct, transferring (e.g., via transfection) the resulting construct, which encodes the S Klotho protein, into an appropriate expression system (e.g., CHO cells), and/or transiently expressing the S-Klotho protein. Klotho protein expressed in A395 heterozygous or homozygous cells may be expressed at higher levels than in G396 cells. Embodiments can include purifying (and optionally quality-control testing) the expressed protein for therapeutic administration. Embodiments can include administering a therapeutic or therapeutically effective amount of the S-Klotho protein to a subject in need thereof (e.g., an individual or patient harboring the G395 SNP and/or (at risk of developing) metabolic syndrome (MetS). Alternatively, the subject may be of wild-type of other mutant or variant type. Administration of the recombinant S-Klotho protein can lead to a beneficial increase in blood S-Klotho levels. The administration may reverse or counteract the deleterious effects of the G395 SNP that is transcribed and circulated in affected individuals. Accordingly, the circulating concentration of S-Klotho may help to counter the effects observed in G395 individuals, especially those at risk of developing metabolic syndrome (MetS). Administration of the G 395A S-Klotho protein may, therefore, decrease the risk of metabolic syndrome (MetS) in patients (e.g., patients harboring the G395 SNP, in elderly human, and/or in women). Therapeutic Treatment of Cancer

[0471] S-Klotho is thought to inhibit basal Wnt signaling activity, thereby functioning as a tumor suppressor for colorectal cancer (CRC). In addition, klotho gene variants associated with lifespan differences may repress butyrate-mediated Wnt hyperactivation, and thus increase the risk of CRC. It has been hypothesized that in this manner, the type of klotho variant present, and its relative expression, can interact with levels of butyrate derived from diet to modify CRC risk. Moreover, mTOR signaling has also been linked to human aging, and crosstalk between Wnt and mTOR signaling may influence colonic tumorigenesis

[0472] The KL-VS variant or other construct can serve as a vehicle for investigating which SNPs (e.g., within KL-VS) are responsible for influencing S-Klotho to produce a decrease in basal Wnt signaling and/or the suppression of butyrate-mediated Wnt hyperactivation - the latter Wnt-related activities which have been associated with S-Klotho tumor suppression. Embodiments include modifying the appropriate amino acids (e.g., in the KL-VS stretch of S

Klotho) shown to influence the tumor suppressing action of the KL-VS variant. An embodiment of the present disclosure includes a recombinant S-Klotho protein having one or more amino acid alterations in the KL-VS stretch of 6 SNPs. The proteins can be produced and/or expressed in the context of any protein construct described herein. For instance, the proteins can be produced or expressed in the context of S-Klotho, isoform 1 or 2, 1-981, 29 981, 34-981, 36-981, 131-981, 1-549, 29-549, 34-549, 36-549, 131-549, and so forth, with or without a tag (e.g., Fc tag, TEV-Twin-Strep tag, TEV sequence, etc.). Accordingly, the nucleic acid construct or cDNA from which the protein is expressed can be of corresponding length.

[0473] Embodiments can include producing a heterozygous or homozygous variant construct, transferring (e.g., via transfection) the resulting construct, which encodes the S Klotho protein, into an appropriate expression system (e.g., CHO cells), and/or transiently expressing the S-Klotho protein. The Klotho protein may be expressed at higher levels than the other Klotho proteins, including wild-type. Embodiments can include purifying (and optionally quality-control testing) the expressed protein for therapeutic administration. Embodiments can include administering a therapeutic or therapeutically-effective amount of the S-Klotho protein to a subject in need thereof (e.g., a patient with or at risk of developing colorectal cancer (CRC) or another tumor). The subject may, for example, harbor or express a Klotho variant with decreased Wnt inhibition activity. Alternatively, the subject may be of wild-type of other mutant or variant type. Administration of the recombinant S-Klotho protein can lead to a beneficial increase in blood S-Klotho levels. Therapeutic Treatment of Non-human Mammals

[0474] In addition to the foregoing, one or more non-human, mammalian Klotho proteins or protein sequences (or portion(s) thereof) can be useful in implementing certain embodiments of the present disclosure. SEQ ID NOS: 121-124 present DNA sequences for encoding various non-human mammalian Klotho proteins. SEQ ID NOS: 111-120 present amino acid sequences for various non-human mammals. These Klotho protein sequences (or portion(s) thereof) can be expressed, purified, formulated into compositions, and/or administered to animals in a manner similar to that described above. Therapeutics administration of recombinant Klotho (fusion) proteins can be effective in treating the non human mammal version of the medical and other conditions outlined herein. In particular, embodiments of the present disclosure can include veterinary treatment method, proteins, and compositions, as will be understood by those skilled in the art.

Examples Example 1

[0475] Table 48 illustrates the results from transient expression and purification of the recited Klotho variants in HEK and/or CHO cell lines. In the results provided in Table 48, below, the following abbreviated protocols were followed.

[0476] For Fc fusion proteins, protein expression vectors transfected into HEK293.sus or CHO using standard methods. Briefly, cells were grown for 7 days and harvested. Cell counts are given in notes section. Supernatant pH was adjusted with 1 M Hepes pH 7.4 and sodium azide added. KanCap A resin was used to capture proteins. Resin was washed with PBS. Resin was washed with PBS plus 1 M NaCl. Resin was washed with PBS. Proteins were eluted with 50 mM Citrate pH 3.5, 100 mM NaCl. Proteins were immediately neutralized with 1 M Tris pH 8, 0.5M Arginine. SDS PAGE gel samples were removed at this stage. Proteins were buffer exchanged into PBS. Protein was quantified by OD280, quantity and concentration was determined using calculated extinction coefficient. Reduced and non reduced SDS-PAGE (Biorad criterion Tris/Glycine/SDS, 4-20%) were used to determine purity and approximate molecular mass. Aggregation status was determined by HPLC, with detection at 280nm using a Sepax Zenix-C SEC-300, 3um, 300A, 4.6*150 mm size exclusion column and PBS running buffer. Proteins were shipped as aliquots after filter sterilization, snap frozen in liquid nitrogen. Loss of protein was observed for some Fc proteins during desalting into PBS, as determined from samples run on SDS-PAGE before and after purification. These proteins are expressed but from the HPLC, problems arose during desalting or assay on the silica HPLC column in PBS. Accordingly, buffer selection was optimized to reduce protein loss.

[0477] For Strep tagged proteins, protein expression vectors transfected into HEK293.sus or CHO using standard methods. Briefly, cells were grown for 7 days and harvested. Supernatant pH was adjusted with 1 M Hepes pH 7.4 and sodium azide added. BioLock biotin sequestration reagent was added. StrepTactin superflow resin was used to capture proteins. Resin was washed with 100 mM Tris pH 8, 150 mM NaCl, 1 mM EDTA. Proteins were eluted with 100 mM Tris pH 8, 150 mM NaCl, 1 mM EDTA plus 2.5 mM Desthiobitin. Protein was quantified by OD280, quantity and concentration was determined using calculated extinction coefficient. Reduced and non-reduced SDS-PAGE (Biorad criterion Tris/Glycine/SDS, 4-20%) were used to determine purity and approximate molecular mass. Aggregation status was determined by HPLC, with detection at 280nm using a Sepax Zenix C SEC-300, 3 um, 300A, 4.6*150 mm size exclusion column and PBS running buffer.

Proteins were shipped as aliquots after filter sterilization, snap frozen in liquid nitrogen. It should be noted that for the Strep tagged proteins, samples were assayed in elution buffer. This elution buffer is very 'neutral' and is not detrimental to proteins. Also, the running buffer for the SEC column was PBS, so the proteins underwent a buffer exchange during assay. Absorbance at times above 7 minutes are small molecules.

OD280n Conc. Extinction Molecular Titer Protein Name m (mg/mL) Coefficient Weight (Da) (mg/L) Native Klotho ECD (34-981)- 2.01 0.95 246780 116615 6.18 nativeSS-strep-HEK Native Klotho ECD (34-981)- 1.73 0.79 246780 113119 5.16 nonNativeSS-strep-HEK Klotho ECD variant-1(36-981)- 0.89 0.41 246780 112893 2.64 nonNativeSS-strep-HEK Native secreted/Isoform 2 (34 1.33 0.63 140510 66255 4.07 549)-nativestrep-HEK Native secreted/Isoform 2 (34 2.84 1.27 140510 62760 8.24 549)-SS-strep-HEK Secreted variant (36-549)- 1.40 0.62 140510 62534 4.04 nonNativeSS-strep-HEK Klotho ECD variant-2 (131-981)- 1.12 0.52 221800 103079 3.40 nonNativeSS-strep-HEK Native Klotho ECD (34-981)- 0.02 0.01 270075 138668 0.27 nativeSS-Fc-HEK Native Klotho ECD (34-981)- 0.01 0.00 270075 135172 0.12 nonNativeSS-Fc-HEK Klotho ECD variant-1(36-981)- -0.04 -0.02 270075 134946 -0.48 nonNativeSS-Fc-HEK Native secreted/Isoform 2 (34 0.03 0.02 163805 88308 0.43 549)-nativeSS-Fc-HEK Native secreted/isoform 2 0.05 0.03 163805 84813 0.76 (34-549)-nonNativeSS-Fc-HEK Secreted variant (36-549)- -0.01 -0.00 163805 84587 -0.08 nonNativeSS-Fc-HEK Klotho ECD variant-2 (131-981)- -0.01 -0.01 245095 125132 -0.15 nonNativeSS-Fc-HEK Native Klotho ECD (34-981)- 0.42 0.20 246780 116615 1.97 nativeSS-strep-CHO Native Klotho ECD (34-981)- 0.28 0.13 246780 113119 1.30 nonNativeSS-strep-CHO Klotho ECD variant-1(36-981)- 0.15 0.07 246780 112893 0.68 nonNativeSS-strep-CHO Native secreted/Isoform 2 0.26 0.12 140510 66255 1.24 (34-549)-nativeSS-strep-CHO Native secreted/Isoform 2 0.36 0.16 140510 62760 1.61 (34-549)-nonNativeSS-strep-CHO Secreted variant (36-549)- 0.22 0.10 140510 62534 0.98 nonNativeSS-strep-CHO Klotho ECD variant-2 (131-981)- 0.19 0.09 221800 103079 0.86 nonNativeSS-strep-CHO Native secreted/Isoform 2 (34 0.12 0.06 163805 88308 1.54 549)-nativeSS-Fc-CHO Native secreted/Isoform 2 (34 0.16 0.08 163805 84813 2.05 549)-nonNativeSS-Fc-CHO

Table 48

[0478] In certain embodiments, EDTA and/or other metal chelating agent(s) were removed from (or not included in) one or more (e.g., all) of the purification steps and/or buffers. In some embodiments, EDTA and/or other metal chelating agent(s) may contribute to or cause deactivation of the Klotho protein.

[0479] In a follow up study, transiently-expressed Fc-Klotho proteins were purified using Aquity UPLC BEH200 SEC analytical column: 1.7 um, 4.6 X 150 mm; Mobile Phase: 100 mM Sodium Phosphate, 200 mM Sodium Chloride, pH 6.8; Flow Rate: 0.35 mL/min; Run Time: 9 minutes; Detection: A280, MALS & RI detector; Ambient sample compartment, 30C column compartment; 100 uL of sample injected (37 ug). Figure 14 illustrates a chromatograph of Klotho-Fc protein. The majority of Fc Klotho protein appears to overlay with the first peak of MW markers near the void volume. This corresponds to a very high molecular weight seen for the main peak (in mega daltons), which is much higher than native Klotho. By SDS-PAGE, non-reducing, the peak (fractions) contains protein the size of a monomer, suggesting non-covalent association in solution. A minor shoulder is observed on the tail of the main Klotho peak (marked with dashed oval); this is <1% of total Klotho peak area with a MW larger than IgG by elution time on the SEC column relative to the MW markers and 700 kDa by light scattering (the LS signal is very low and has tailing of the aggregates, so might be over-estimated). This peak corresponds to a multimer, perhaps a dimer or tetramer.

[0480] Various alternative purification schemes, including different columns, buffers, conditions, etc. were used to address the issue with protein aggregation and multimer formation. However, in at least one embodiment, a multimer (dimeric, tetrameric, etc.) Klotho protein can be purified. Example 2

[0481] Stable expression of the (human) Klotho derived proteins represented in SEQ ID NO: 52 (N'-human alpha Klotho 34-981 isoform 1_(G 4 S) 2 linkerhuman IgGI Fc-C'), SEQ ID NO: 54 (N'-human alpha Klotho 34-549 isoform 2_(G 4 S) 2 linkerhuman IgGI Fc-C'), and SEQ ID NO: 66 (N'-human alpha Klotho 34-981 isoform 1_Twin-Strep cleavage site residues) was performed in CHO cells. Each of the three Klotho protein constructs was expressed with a non-naturally-occurring N-terminal signal sequence, which was then cleaved during the stable expression/purification process to yield the N-terminal (Klotho protein) amino acid. C-terminal to the Klotho protein sequence in SEQ ID NOS: 52 and 54 is a GS linker (GGGGSGGGGS) and an Fc-fusion tag (human IgGI Fc domain), which are (or appear to be) retained in the expressed protein. C-terminal to the Klotho protein sequence in SEQ ID NOS: 52 is a TEV-Twin-Strep tag (with GS linker) (GGENLYFQ/SSAWSHPQFEK-GGGSGGGSGGS-SAWSHPQFEK), which is cleaved following the glutamine 8 (Q8) of the TEV-Twin-Strep tag (i.e., GGENLYFQ--), to release the Twin-Strep tag portion (SSAWSHPQFEK-GGGSGGGSGGS-SAWSHIPQFEK) and retain at least a portion of the TEV (protease recognition or consensus) sequence (GGENLYFQ-C').

[0482] The coding sequences were codon optimized using DNA2.0 proprietary algorithms. The genes were synthesized and Pd3600 transposon backbone-based expression constructs were assembled.

[0483] A GS knockout CHOKI derivative host cell line was used to express the human Klotho variants. The cells have been co-transfected, with Leap-In transposon based expression plasmids coding for the three different hKlotho designs and Leap-In transposases. The transfections were performed by electroporation using a Neon apparatus (Thermo). Transfected cells were selected under glutamine free conditions and the resulting stable pools were cryopreserved. Cells from the established stable pools were inoculated into shake flasks and fed batch production studies were conducted using small scale established feeding and cell culture conditions. Clarified harvest samples were collected and submitted for Western blot analysis using anti-Fc antibody- (SEQ ID NOS: 52 and 54) or Strep-Tactin- (SEQ ID NO: 66) HRP conjugate based detection. Example Western blots are shown in Figures 15A 16B.

[0484] Stable pool 291645 expressing the FL-ECD (34-981)-Fc Klotho derivative (SEQ ID NO: 52) produces the protein predominantly at the expected size (see Figure 15A). The predicted size of the full-length extracellular domain-Fc fusion protein monomer is 139 kDa. The predominant anti-Fc positive band is at the predicted -140kDa size (arrow) indicating that expression construct 291645 expresses the correct size fusion protein. The protein dimerizes under native and non-reducing conditions (see Figure 15B). Under non-reducing conditions the full-length extracellular domain-Fc fusion protein may form homodimers. The size of the predominant band detected by anti Fc antibody on a non-reducing Western blot (arrow) is consistent with the formation of the predicted homodimers.

[0485] The FL-ECD (34-981)-TEV-Twin-Strep molecule expressed by stable pool 291647 (SEQ ID NO: 66), also shows the correct size on Western blots and remains a monomer under native and non-reducing conditions (see Figures 16A-16B). The expected size isoform 2 -Fc variant represents the secreted human Klotho protein. The predicted molecular mass of the mature full length ECD (34-981)-twin-strep tagged Klotho protein (SEQ ID NO: 66), is ~ 109 kDa. Non-reduced Western blot analysis demonstrates the successful expression of the correct size protein from CHO cells coded by expression construct 291647 (see Figure 16A). Non-reduced denatured Western blot analysis indicates that the full-length extracellular domain of hKlotho does not form covalent homodimers when secreted from CHO cells (see Figure 16B). Other protein constructs represented in the accompanying Sequence Listing were also prepared. Figure 17 is a gel of the various indicated recombinant Klotho protein constructs. Figure 18 is a series of gels for the respective indicated recombinant Klotho protein constructs.

[0486] It should be appreciated that the expression and/or purification of the Klotho variants disclosed in Table 48 and/or shown in Figures 15A through 18, in addition to one or more other Klotho variants disclosed herein but not shown in Table 48, can, in some embodiments, result in advantages over the expression and/or purification of native Klotho. For example, there can be a reduction in the number and/or types of alternative products when expressing and/or purifying Klotho variants. Additionally, or alternatively, there can be an increase in expression level of the desired Klotho variant compared to the expression level of native Klotho. Additionally, or alternatively, the desired Klotho variant is expressed and/or purified in a purer form under comparable conditions and methods (e.g., the concentration of the desired Klotho variant is increased with a concomitant decrease in side products expressed and/or purified). Preliminary results indicated that designed recombinant fusion proteins are being expressed and purified in suitable titer ranges and are soluble in acceptable buffers, carriers, and excipients.

[0487] Further cell lines were developed and assessed for density, viability and production. Data from the top 10 clones are illustrated in Figures 19-22. Data from the top 4 clones are illustrated in Figures 23-26. Based on fed batch ranking, the top two clones appear to be 138 D9 and 145 G8. Based on pseudo-perfusion cumulative productiveity, 138 D9 appears to be the top performer. 140 F6 reached the highest VCD. Copy number stability was also assessed as illustrated in Figure 27. Total RNA was extracted and RNA isolation was performed using RNeasy Mini Kit (Qiagen, catalog # 74104). Following RNA isolation, amplification of templates was carried out using Omniscript RT Kit (Qiagen, catalog # 205111). All cDNA sequences were as expected.

[0488] Stability of five of the clones was further tested as illustrated in Figures 28-32. These clones were grown in growth media with and without glutamine, and shown to have higher growth rates in the presence of 4 mM glutamine, compared to the glutamine-free condition. No growth rate change was observed during >60 population doublings in either sets. Viable cell density and percent viability of clones over a 7 day time course is illustrated in Figure 30-31. Volumetric productivity of clones in 7 day fed batch cultures of Time 0, 60PD in the presence (+) and in the absence (-) of 4 mM glutamine is illustrated in Figure 32. The volumetric productivity by the TO and PD60 no glutamine cells are comparable. The PD60 + glutamine volumetric productivities are either comparable or somewhat lower, but never lower than the ~ 7 0 % of the TO values.

[0489] Cells were adapted to 100% for EX-CELL, ActiPro, and CD OptiCHO media, and nearly 100% adapted to CD CHO, CD FortiCHO, BalanCD CHO Growth A, and Select CD1000 media. Example 3

[0490] Purified Klotho proteins were observed on gel following ELISA, as shown in Figure 33. Table 49 presents an ELISA plate map key (upper two segments) and heat map-labeled ELISA 450nm data (lower two segments). Table 50 presents the ELISA data for the Klotho proteins from cell culture supernatants and human serum samples. Table 51 presents the average concentration of Klotho in each sample group.

[0491] Table 52 presents an ELISA plate map key for human serum Klotho levels before (upper two segments) and after (lower two segments) recombinant Klotho protein injection. Table 53 presents heat map-labeled ELISA 450nm data for Klotho protein levels in human serum samples before (upper two segments) and after (lower two segments) recombinant Klotho protein injection as measured by ELISA. Human serum samples were diluted 2-fold and cell culture supernatants were diluted 5,000-fold using Klotho ELISA assay sample dilution buffer. Serum B1 and cell culture supernatants were included in both ELISA plates as controls. TMB 30 minutes. Table 54 presents a summary of average concentration of Klotho protein in the samples indicated.

A SRon&?n~m Kocnatvt5g/rL 5gn

D f WGhC5rlga I.J naW 4 75nts K KteFO,75% th FSTD375an/m K Gtaan 375 rphnt KknMthac t1375 ngjm. F SiTD,0188rught NKo a4 0188 ngbe KNM kFQ 088 coghn G ST.0A94 ng/m Wnthonatve. (104 KfotbcrF-', .304 ngin1 H STD Dgmt Kio nat~i sg/t itho-K 0 nglhn 7 8 9 30 1 12 KFtho GW, 6 wg/L KLA-645 :100) KLA-647 ( 0L70) K[otho GW, KLA-647 (1:10$000) 3 ng/0L KLA-45 (1:0,000 Klctho GW,2 15 nig/mL KLA-645 (1:100,000) KLA4AI(1:100800 K od GW, 0.75 ng/mt KLA#45 1:0000KLA-647 (1-AJXK00 KlthoaGW O ~75rt&g'mt SesumIA Smrm UA iKlotho W, 6:188 ngrmL SerumrnIA(1:2) Se rum 13A (1:2) Klotho GW, CK094 ng&(mt Serum 1A(1 4) Serurn 1A{1:41 Klotho GW, U ng/mL Seru m 1A (1:8) Serum 13A (1 8)

1 2 3 4 S __ 6 A 313$ 31102 0173 0.075 3.085 0.075 0 ' 7 a .5 rsiooB 602 ____077__ ___D7_

L 0.9%- 0,952 0.071 0742 30 79 ____0_

0 0 4 0.52 0.07 0.07 0 064 01 F I 1319 (0DB 0.076 074 61:74 F 0.1 0194SI 0.1 0.7 305 06 S 0 I3 01i3 0.71 0.068 0.096 0.024 H ) 71 0.075 00 8 0.075 0.071 0168' 7 8____ 9 1) 11 12 1773 3.853 0.97 0.9 3.521 '3.383 3,247 3,27 0.185 0,183 0,548 0.574 .886 L92 C.088 (.0 33 D.144 3.5 L128 OD(40 97 0.09: IS596 0.615 0.397 0AD > A49 (42 S34 3.38 0.261 ___255 0 29 0.~301. 6 0 7 0 167 0 U1. 1854 1% 0Al7 .081 013 0,13 0.142 0.13

Table 49

So k

&&

"'>~' A

A'oil W"y O\

as0 MO O.4

\&t -------- ----- ----------

to a

--- - ---- -------

all~ GAn 9 WM K i&u

4 &*&v

~cal

4- oil~

ala TO I' .

all anm n n aawe

Tabe50 samples W

, $Jotho from (AenWay 13.5$ Supern tt KLA-645 1599.46 Supernatant.1",'A4C47 87M99$ Humian erm Base, IA C.56 HumanslermProtein,A Mc07n

Tabe51

34 5 :

A SM 6 I ...... 1A -------- : a Sr15<rNE 3 7A ~S~"QIIA --r ----- ....-. - -.........

..... .................. "NIA

--- - - - - - - - - - - - - I 'l "'l"'l "Il" Il"l .... ....

0 STD 4 I7 C ----- 7 7 _____55 T WA_____ _ 1A ---------

261A1

G, TO, QmL KL A - A A 0K b96 1

Tabe52

~~.. ..... ~ 4.. ~ -~ ~~ ~ ~ 4------------ ------------------- -----..... ...... ...... ------ ----

------- - - - - -------- ....

......... ........... 1

-- --" --N ------

' ................ ..... .............. I3 ............... ................ .................. 2'~t~. 4 '~'¾ _____ ______ 032

i~j.. ....

.' .% ... ... J

4-4

77- .4' 4>7___ ____ ________

............. . ....... ........... .....

........... ..... ........ -3 -l 2> ----- _ ..................

......... .............. _ _ ~ -- -__ 02 ------------------

----- -- -- -- ----- - -- -- --- -- -- -- -- --- ----- -- --- -- -- -- ---- -- -- -- -- --- -- -- -- -- -

PO --------- ------ ~----------- 2 K 42 3 .2... I ............ ..... .'' ........

Tal 53

2A A A 57 13_

A __1_A___I

Table 54 i

[0492] Tabl p s noa55.. {44 21A _____

protein-- sample

Lan Mehod1 Meho

2KLO-138-8 A7 108. 79.-4t yes_

B LanOe5-11 Method1 2.3thos

6 KLO-145-E11 A4 941 62.3 yes

8 KLO-137-G6 Al 88.7 50.9 yes 9 KLO-139-G5 A5 83.9 53.7 yes 10 KLO-137-D8 A6 83.4 51.2 yes 11 KLO-139-G17 A9 81.7 49.1 yes 12 KLO-140-D6 B6 76.88 63.2 yes 13 KLO-138-E2 A3 76.8 33.0 yes 14 KLO-140-G3 All 74.4 44.9 yes 15 KLO-138-Ell B5 73.04 53.2 questionable 16 KLO-143-G6 B2 70.6 40.5 yes 17 KLO-140-G4 A2 68.2 36.2 no 18 KLO-137-D5 A1O 66.7 38.7 yes 19 KLO-137-D6 A8 66.1 36.8 yes 20 KLO-144-C4 B4 60.5 30.3 very likely 21 KLO-138-G8 B7 58.11 40.1 no 22 KLO-139-D11 C5 49.99 40.4 questionable 23 KLO-139-Fll C3 49.37 41.4 yes 24 KLO-138-G2 C4 47.5 37.6 Unknown 25 KLO-645-146-B2 C8 47.39 34.4 Unknown 26 KLO-138-G4 Cl 35.59 24.3 Unknown 27 KLO-138-B1O B1O 35.27 38.8 Unknown 28 KLO-144-G6 B1 34.8 20.4 Unknown 29 KLO-139-Bll B12 34.66 32.7 Unknown 30 KLO-140-F6 B11 34.53 34.6 Unknown 31 KLO-645-143-D7 C7 30.28 15.7 Unknown 32 KLO-645-143-F9 Dl 28.04 22.1 Unknown 33 KLO-645-168-A8 C1O 26.92 16.3 Unknown 34 KLO-645-142-G2 B9 22.71 18.8 Unknown 35 KLO-645-169-D7 D3 21.08 17.1 Unknown 36 KLO-645-168-G12 C12 18.46 11.7 Unknown 37 KLO-645-167-B1O C9 8.49 0.0 Unknown 38 KLO-645-146-C1O D2 7.71 17.4 Unknown 39 KLO-645-168-F1O C11 0 43.0 Unknown

Table 55

[0493] An illustrative method for estimation of concentration involved quantitation (quantification) by PAGE against a BSA standard. An illustrative method for estimation of concentration involved measurement against purified Klotho standard.

[0494] One interpretation of the data could be that native-like, recombinant (TwinStrep TEV tag-removed) Klotho protein expresses better, purifies cleaner, and/or retains more activity than does the recombinant Fc-tagged Klotho protein. This was surprising and unexpected. An alternative interpretation is that neither protein, or the Fc-fusion protein more so than the native-like protein, showed levels of klotho protein reaction to the ELISA antibody. Accordingly, we may have identified that expression, purification, storage, and/or administration of native-like recombinant Klotho protein and Fc-fusion Klotho protein was not as simple as expected and that standard techniques did not work well. Proceeding based on the later interpretation, procedures were modified to obtain more active protein, while continuing to process the data for further interpretation.

[0495] Three commercially-available ELISA detection kits for Klotho protein were also tested for suitability in accordance with certain embodiments of the present disclosure. See Tables 57 and 58, below. The IBL Kits shows low background, liner dilution of serum samples, acceptable spike recovery after 1:4 dilution. The Cloud-clone Kits shows high background, no liner dilution of serum samples, no acceptable spike recovery. The EIAab Kits shows low background, very low Klotho concentration in serum sample, no liner dilution of serum samples, no acceptable spike recovery.

[0496] Total 8 human serum samples were diluted with each kit's dilution buffer at 1:2, 1:4, 1:8. 4 of these smsamples were spiked with top concentration of Standard from each kit at 1:20 dilution. The protocol from each kit was followed per instructions provided.

[0497] Figures 34A-34C illustrate Klotho protein concentration measured and spike recovery observed in the respective samples.

IBL 93 8-6000 pg/mL Cud-Clone 15.6-1000 pg/mL E I~a b 7 -500pg/mL

C oud-Clone5

Table 58 a) r E 42

I In Ue ~on

23C Z3 LA- n

4-5i __ E 21 EEC - Z5 n 0 w0 41 On0 C0 N

CU c Q ~-nr i Ee o

- 0 en 0 xxn x~

ro 4 o- nU

4-~~4 ~ 4-d 00~

en vn-e

~n 0 I7 I 024-

en c Ecc Vc S~ V 0 4 ~~ C CA Inm -a ~e .0a u£2 cnE I E en 01 )

4-1 r-4- V~ee ne ~-~ a In ".~ 4- '- C I en In Ie

a en (U

l Ct C0 n - CD"

o - In

.O -C I di£ -10 In - B 2 to ~ 4

Z In At V,. ~ ~ %C 176

CC C~C

CeJ C~

CAC j a)176 cn colf

0 ;.,p~siL

Ctj

CA C)j

CIO

1C4

r r-5

Ctj

r+ ~ fl C' '177

.......... ....... .... .... .....-.-... .. . . .... ... . ... ..... ...... .. .... .. . .. .

.. ... . (4l

IAI ... .... ....

..... .. ..... .... kI X . ...-.. ......... CA ....... Cj .....X All .... .. . .... ... ..... .. .. ... .... .... ....

...... U . ..... .. .... .... . ...... . .. ... . . ........

... .... 178

... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... .. .. .. .. .. .. .. .. .. .. .. ........... ......... ............ ......... ..-..... .-.-.-. . :. ::::::::. : ..:::::.. .. ........ - .. .. .. .. .. .. .. ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... .... ..... ..... ..... ..... ..... ..... ..... ..... ..... .... ..... ..... ..... ..... ..... ................... ... .... .... .... .... .... .... .... .... .... .... .... .... . . . . . . . . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. ... ... ... ... ... ... .x........... - ._j . . . . . . . . . . . .. . .i.i .M-N . . . . . . . .i lv# .:::. . .O..... .". . .:::. . :... .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .... .... .... .... .... .... .... ....... ..... ::::::O .. , i i i "`:"""` o :::: ... 'N .... X: ... ....... ... :::.,.,.,., :::ff :::. . ..'-i i ...........'m ............. N .. . .. .. .. .. .. .. ........ ......... ... ... ... ... ... ... .x .. .." ........... F zp .. .. .. .."... .. . ............ ............... . .. .. .. .. .. .. .. .. "o .......... ... ..:':.. .... ..... . ....... ... ........... ............ .. .. .. .. .. .. .. .. .. I.. i.im ............. . . . . . ii i ........ .. .. .. .. .. .. ....... ...... ..... . . .. ....... ....... .... .............................,.....

. n .,.................... ......... .......... ... ......... .......... ::............... .......... ,, ........ .. ... .. ... .. . ......... .... .... .... .... .... .... .... .... .... ..... ......... ..... ......... ..... ... ... ... ... ... ... ... ... ... ... ... ............. .. .. .. .. .. .. .. .. .. .. ... ... ... ... ... ... ... ... ... ... ... . .. .. .. .. .. .. .. .. .. .. .... ... ... ... ... ... ... ... ... ..... .............. .. .. .. .. .. .. .. .. ... ... ... ... ... ... ... ... ... ... ......... ............. ... ... ... ... ... ... ... ...- ... ... ... ... ... ... ... H.......... i ......... ........... .............. ............ .............. ............... ..W .. .. .. .. .. .. ...... ........ .. .. .. .. .. .......... .............. .... .... .... .... .... .... .... .... .... ............ .... .... .... .... .... .... .... .... .... .... ............ ............ .......... ............ .. .. .. .. .. .. .. .. .. .., ......... ......... . . . . . .. ..... .. . . . . . .. . ".. : .............. ........ .............. :....... ................

, ..................... .......... .......... .. .. .. .. .. .. .. .. .. " .. .. .. .. .. .. .. .. .. -,", .......... ." ,."..........:":"""', . ........... .......... .......... ............. ........... .......... ........ ........... . ............ ............. , .... .,.. .... .... .... .... .... .... .... m . ........... ...........-. ..,.,.... .",.: :. - I :........... ::............ I ........ . . . :::. ......... ., ,...:::.::: orl :::I; ..: ,.., ....... .::. -.-,....... ....9":::::: . ."..--.. .. NI :":":::::: .... .,. t,.. .-.,.,ii:: -..........-....... ......... . .......... ........... ...... . . . . . -." ..... . . . . ,: N ,. . ...Ii.:.:W.4;., :.:.:,?i.-::".....",.... .:::......... .X.......l. ..:X. '!" : . . ,-...-. - .-":::::::: ,- ::::::to-,:j:::: .:.:...: . P,-) ::::::i= , W ...... :. " .. W 4. .. . .

. ,; ) , -:,*V -................... -:, ..,.-":..:..:.. 'p ::::::W ... j::::. . f ::: : .V . ,0::::: O :....::: ...... ... r ..: ... ............. (V, :::*. . . ,:,.., .....

,, .0 -T ::::M ..... .:.:.:. ,v ........... .. ...... :.:.:.%P .:..:. .:. . W, ::::::V ................... ::: . ::M -:- .. .......... Is..:...: ,"!i .... .. .. ..... .. ...... .. ...

." . .......... ........... ............ .......... .......... ......... :."......-- -1 1 .......... .:............ ... ..... ..... ..... ..... .......... ........... ............. . ... ... ... ... ... ... ... ... ... .. .......... .. ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ...... ............ ... .. .. .. .. ..]!.. ;.. .. .. .. ,..,.: W .:::J::::. :" : , , :1.9 :, 11 1: ........................................ ........... .......... . . . . . .-. . .... =**.:, ..j, . : :: ............ .. .. .. .. .. .. .. .. .. . , ............. ................... .................. . . . . . . .... .. ............ .... ......................... .............. ........ .""11- '.:. c ...: A ............. ". . ........ ....... .................. ..... . . . . . . . .... .. .::.:.:? . . . . . ..:...:..... .:..:. 0 :-:-:-: --:-:-:-: r-, .::::::: ................,."...7. , :gI I.:.::" -00 ...,. ..... ,. ....

. r . .:..:.:. -, .:..:.:.f., .:..:.:. : r, , .......... . ,,, . :...-:.:* .-....... .... .- .:::::::: 'P :... iv .. .- -.......P-f n :: .... , : ::-::-M..-. -:-:-:-:: ... .... ... .....""" .... ::,::,.. . .,..-,

. . , :::::=.::::: f,; ', ::::::.WK*::: r;P : A, ,,,.:: ::: . :::::: :::: :W ..... ,X-:-::

. . ,,-. .- :: :I,-", ..: "C, , . .. f ti+l ................. ..... ......... .. v XA :. TA

, f : .... : 1 : --- :: k- ....... ..

' , ,j .... F : i .... . : I.I... .: u : M .. -,: .. ....... 81, ::: ::W l: . .:.:.:.., .... . ...:.:.:. ....... : .O.": S .. : -,

. , Q ..... CZ , , ,"": ::.:. :,:,:,:."..:,:-:

. N 'o M : W.I.:... 6) : .. ... :::,.. ::::,:, ,...: ..... , 9::: ,,; :::::"N-:-i:::: ::.........'....... :::.":.:.:.: ,- 'r.- :::.:.M.... ,V- ::::: :::: ") w> :::::::imi :ii: ::::::W ......... ::::.w:: :: ol 11, ::::::: ... :::: .. ....-,-- a. ........ " aw :1.1 : :::..-...; * lililili 1:.:....." """" .::::: * *...... :i

, . ..... ............. .......... ....... N ...... .......... ........... , . ............ .::: .:::::: .......... ....... ......... .................... ................. ..................... ...................... ........... .... :

, ............. .................... ........... ................. ...................... .................. ......... .................. ..... .......... .......... .................... t ,....... ................ ........ .......... " :.:.:. .....i - ... ..-::. I ....... 1, ..................... ..................... .................... .................... Q ...I.... o::: ......... ...... ... ..................... ....................

" ..................... ........... ........... .................... .................... X. . '...... I - ..... ......

" "................", ..................... ..................... ..................... .................... .................... .................... .................... ..................... .......... .......... ..................... .......... ........... .................... ................. : , 111. iW

. ........... ..................... ........... ...... .......... .......... ............. i64", ..................... .................... ..................... ..................... .......... .................... .......... .................... ..................... .......... ............... ........... ,.................... ................. .... - .......... ................. .................. ......... ..................... .......... ..................... ................... ............. : ..... .... ..: .. I :,: .0

, .................... .......... ............. .......... .................... .................... ... $;'-'-'. ... ........ ........... :::,: :::: , :::.,.,.,.,.:.:.: ,-,, x.:M ......... .................... : ."... :::NM i i - ii i S i i i = :::W X" -:-:-:-:-: ::: , -::ii : ,,,,, ::", ::X..... ..... : .'. ::: I.. V ..*.... ............... ,-W : ........ : :V "',:". ... ......

. ............... ::.M ........... iz ,4 :,.,.,.,.,.,.,.,-:-:- ........... .:.:.:.x.:.:.:.:.:. I- :-:-:-:-:-: .. .......... .................... .................... : : . ..... +0 I ...... a) . ... ........... ..................... ........... .......... .................... ..... ...........

. ..................... .................... ....................... -,-,-,-,-,-,-,-::: : ........ : "-. .......... ......

" ..................... .......... ... .......... ............ ... ......... ........ , ..................... '.....'T .................... ,',',',`,:"::: ....... - ..................... .................... .......... .................... ,.,.,.,.,..,.,:: : :.-........... . .......... .......... ........ ........ ........... ..................... ..................... ........... ..................... ..................... ..................... .................... " " " "..... = ........... ............ ........... ..........

, .................... .......... ........... ........... .......... .......... .......... ........ ::::: ..................... .................... .......... ..................... ..................... .......... ..................... ..................... ........... .................... .................... .......... ....... :.:.: ........ ....... ............... -. - ............ ............. ............. ........... ........... ........... ........... ........... ......... ....... ............. ............. ........... ........... ................... .................... .................... ..................... ..................... ................... ..................... = ............. ........... .................... .................... ..................... ..................... ..................... ..................... ..................... ....................." ............. ........... ...... .................. " ........... .......... .......... ........... ,.................... ...... ...... :",,.. a) ....... ............. ........... .......... .......... ........... .......... .......... ........... .......... ..................... ...... ........ .................... :: ...... ..... .................... .................. ..................... ........... ..................... .......... ........... ...'...... .................... ............... ....... ...... r- ............ .......... .......... ..................... .......... ........... ..................... ........... .......... ........... ..................... ......... ........ :: ..................... ::: u ............. ........... ............. ........... 7, ::. -.,n O : : : .ft : : W ::::::i" ... ,..::::::: ,, , :::::::.W :::::: cr, : ,`-' .. ............. ............. ........... ........... . : .... ..i...::: ": : : : to ...... :::: .. ..." ... : 6 : .,...... ... .. ..... : ... ... : !!.... = ............. ............. ........... ........... ........... ............. .

,:,:': 60 . f-mz :: M ............ .......... I. ea -, :::::: .M .", K .... ::.:. X. ,- "., .:.4v.-:-:-:- :.:.:.M ...... .... ::: ....... . : :::--'ll...... :::..*:::: ...... ::: Q ::::. .::: :: : o . ii...... u ............. .......... it, ,-, ... ...... ... - . ....... V:::. -.-.- X.... ............... Cj . .:.:.:.:.:.:. ............. ........... ........... ..... ..................... ,.................... ..................... ................ .... ,: . ..... ...........

. >1 ............. .

.-; ......... .............. " X.................... ..................... ..................... ..................... ..................... .................... ........... ............... ........ ............. ........... , .................... ..................... ..................... ..................... ..................... ..................... ..................... ................ MX.: .................. :::::::::::., .................... .................... ..................... ..................... ..................... ......................... ..................... ... ,.,.,::::... ........ I:::::::::::: ............ ................. .. ..................... .................... , ..................... .......... ........... Ix.................... .................. ..................... ..................... : = ..................... ..................... ..................... , ::::::::::::::::::::: ..................... .::::::::::::::::.. ............... ....... : .. 0 - :;:;:;:;:;:; ....... ............ 0 .................... ............... "... , ..................... ..................... ........... ..................... ..................... .................... . ........... ................... clz , ............ ............

, ............ .................. .......... .................... ............ ............ ..................... ..................... .................... .

..... ......... ............. ........... ........... ........... .................... ............ ............ ........... a :::':A ... f ....... ........:

) ..F.W . ... ... ,::: ...:: :: P... ,......... ::: - ,: >1 . ............ ........... ............ Pd :.:.:. - -:-:-:f -,-:-:-::... : rw- ....... :,:,: ............ -0

, : ; ;::::::. f'- Ck ::: O.... :::::: ...... :. - :-:-:-:-:-: =- :1 : ... i i'.W.:... :: --,-, : : : ..... .... : : :. k+ :.. i:*::::: ::::: ... c-,- -,::::::: + ::::::::O-,: i : :-- -a) zs ............ ............ ............ ,T :":::::.4..:.:.: ... : + ........ .... T .": .:.:.:.+..:.:.:.: :::::*:::::::: + ::::::::!,:::.:::: ...... ..... C ,.,;. P :.::.:W.:.:.:. ... - ::: ... ... WX ... :::: LU ,..... W:::: :::::: .::: ..... jj , : ..... ....:::: ,::::: W . .::: w : ::: :,::.... , ,... -. -- : ::..-. CA :.".".".".". ............ ............ ............ W ..... ...... ...... . ...... , ..... ... .... ... ...........

) ... , :::::: :::: > c4z. ............ "",::::::: I'D ............. ............ ... :R ..'. .;",- :::::: 0 ".- ::::::,ff:::::: i ::: 0j? ::::,.:.:.,jRj :::O, .,. .... .:.:.:. ,X, ::::::I .:::::: A g *4= ............ ... ............ . :,.,. .... : ... .,.:.:.:. .... ::: I ....:.:.: 4..-:-:-: -:-:-:-:-:-. . w : .. ... : :::::::-:-:: :::::: .,.,.- - .,.,., u 0 ........... ...... .. ............ ............ :::::::::::: ...... a) -;-A- ,1 - "i, ': *: A m ...... ............ : :::*,*::::: N

. ::: .. ::: ::: N : 4 - : ::::: N. ............ ,, , ::: ........... .......... .................... ... , - ............... ............... ............. ..................... : ," .................... ,.,.,.,.,.,.,.,::I I'D a) -0 : . -1 : .......... ............. .................... , ....... ... .... ' : -I-yx - : Z --Co, .................... .................... I

. ................ . - .......... ....... ..................... .................... .................... ............... ........ .... ............... ........ ............ , ............ ........ ............ ,, - ": M ....................... ..................... ........... ............... ............. ..... a) . . ..I . I a ..... I ................. .................... .................. ..................... .......... ..................... .. ... ................. ... .. .................... ... ...................... ,.,.,.,.,.,.,.,.::::: - CA a) a) CA : ..... :: M. ...... +........": -;, " ! +4 X.......... :.:......4: '.2 [..... ................. ............... .................... .............. ..................... ..................... ..................... , .... : . ..:. ..

, ................. ....... , .: ................ ......... .................. ..................... ...... ..................... ...... ..................... ..................... ..................... ..................... ............... .................. -0 . CA v X: .... . . , -0 ..................

. . , :................... ......... .................. ........... ..................... ..................... ..................... ..................... -'-'-'.,.,.::::::::: .................. a) : .. .. ..:: ................. ... .................. ,,... ,,,, ..................... ........... ..................... ....... .. ..::: Cj CA : ..... . ....... aW ..: ., .,..: a)

. .......... .................. .......... ..................... ........ CA ,.V. ;W,' .................... """""', ::: .................. ... : :.......... V "I""..., .. P-- a) CA : .... 'A, .......... ... P-

. ,....': - .......... -- "'. ; : ib, "... .. ,...... .9 ,:::" : : :.,.,.,.,.,.,.,.,.,., .. " ................. ..................... j C :::" .:::, : :::. ::: ..... ::" ::,:," ...... .. :,:,:,: ..... ... X: : , :: : :',O ... : : ;g : m,..i = ,

...... .......... ......... ............. .............. ... ..... ... ... : I""'4 , ........... - : : " .I.: ..-: .... - ................... ................... ............. ..................... .................. ..................... ................... ..................... ....................... C, : ...... : 0- M, a) CA ......... ........... ....... ........... ,..................... .......... ..................... ........... " " `,: : : ........... zs : - ; : reA :::::,-,-,-,-,-,-,-, ....... ..................... ... ........... ..................... .......... ..................... ........ .,.,.,.,.,.,.,.::: u Cj : " ::.. 10" :-,. a) ................. ............ ........... ..................... .................... ..................... ..................... ................. .................... .................... ..................... .................. ..................... ... ,...................................... ..................... , ................. .................... : -. 0. .. : . ..... ... .....................

. ................... .................... ............. ....... . ............. ... ,.................... ..................... ..................... .......... .......... ......... ',',',',',',",::.. ... . . : : -A ..':- , , I :.....-... O : -). - - - . .......... ............ ... 4: ..................... ..................... .................. ..................... ..................... ................. .................... ................. .............. ..... ,.................. :""+"*: :.......... .',-'.'. ,..................... .................... , ................. ... ..................... ..................... .................... ................. ... ............... ............... ,".. ............... .... : X ..,.. I: " I",j CA ..................... ........... .......... .................. ....... ,,,,, ................ ..................... ......... .................... .::::: .Z - , :' -- ----,2 : 1. : ,- ..................... -- - . .................. .................. ... .. ..................... ........... ......... .......... ................. ....................... ............... ': ................. p 'r .: : ...... .; ;, , :w - -.- ;: .............. ........... ........... ................. ......... ........... . *z .................. ........................ ............. ..... : : 0 fA - ..:: .::. ..,I.! :t "If' - ::::::"","`,`, ......: ... ,,.,..,,,,... ::.: : ,........ "....':"A""', ...... N .::............. : ,t -, .......... ::::::W ,::::::: op, .................... .:.:.:N .:.:.: .. :::::: t: . ....... 7",:.:.. ::::-:- -0 - a) 0 :m - .0 1, : = =:..... .... .x:::::. ..... : -A .. ... ii , ::::::.,.,,::::::: ::::::.":.. .. ::: I ............ , ..:::: = ..I ?'., f. ", ,

'a ..e :"`:,.... ,:, ,,; ":" ......."".,:.:.:.: :.:.:.f :::: ::: :::t ... ::::::i, ....... ....... I-.- : .*. - ,T...: -, ', '. :::::AO. ...... *..::: ,.,...: ,::::.5..:::: -;-. :.:.: ...... ,p ...... ::::::o -.......::: r-- ...... :::::: " ,.,.::: ...... ,, -5 ......4,"ifi.....:::: , ...... :::::::.*,.:.:.: Cj -0 14 , I. :.. ... - ,-x........... .... ::: .:.:...... ........... :::) !.:::: .:.:.: ..:.:.: ..................... ........... . .:::::: .................. ........ :9 . .. _ ! : -M :? : ................. ... ......................... ..................... ................... . ........... ........... .......... ....... ............. ....... ... ..................... .......... ...... .. , , :--j:: -a) ..................... ..................... ..................... ..................... .................... ................. .......... ..................... ............... ... 'C.; ........... ..................... ........... ..................... ..................... ..................... .............. , I'D :.:: J i M u ,

..................... ..................... ..................... ................. ............... ..... i .......... ..................... .......... .................... ........... :::::::::::::::::::::I ..................... 1::::::::::::::::::::: .................... ..................... , .,...,.,.,.,.,.,::::: .- .:. . ..... ..... >1 "",:::::::::::::::I ..................... 1:::::::::::::::::::::l 7-- : .. = :-X ............... .................... :::::::::::::::,.,., ...................... ........ ..................... .......... ........... ..................... ..................... .......... ........... ..................... .......... .................... ............. ................. ........... ................... ................ .................. 2 : ::': VJ,,::: - : u ;s .................... ............. ....... ..................... ....................., .................... ............. .................... ............ ........... ..... .................... .:" - : i:... i......... . . I :1-* Cj .

: .................... . . . . . . . . . ........... .................... ..................... ....... .................... ................. >, -,7f "

Z .................... ..................... ... ............. .,.,.,.,.,.,.,.:" .... : .... .......... ..... i a .................... ..................... :.................... .......... )

z- 7 ... ... ........... .......... ... ........ ....... X X: .:a .-.. .,/.i X: .- . :::::*",.:.:.: &, ,..,..,::.:.:.:::::: :*X., .,.K*::: ::.:.:.:.:.X.:.:.:. -::::M *::: : :.:.:.:..:.:.:.:.: ( ;-. ,:,:,:'w' ... :,:,: ..:.:. :.:.:.:.:.:.:+:- ::.. t- ,:::: "- ............... .:..."4. . + .:::::: -,..... > : .::: : ::);;", : , :...X:i 0 ,-.... (+ ,. .

: .: ::::: c '--, ::::::W.: : : : ,zf)I .:.:.:.:.:.X.::::: ::::::.;= ::.:.: a) : ,.: : 0 4'-- 1;1'- :::ii. .z :.::: .:::::: ::::::m ...= n .:::. ....ii:i::: ..-::::a; x.. . . . ,7n:::= :::::::,;;) : ..................... a) : ..:.:::)w : ::= .:.:.: : 2,.:...' : : Ir ... ...... ..... .... +... .......... -:-:-: .......... .......... , ,: = ........ :::::':::::':':, :X ................ ..................... ..................... ..................... ........... .... ................. .:-:-: .................. .......... ..... (7,4 .................... .................. :,":`M ....... .``": .. :.:.:.:.:. .......... W ..... : , VA,

1, , :::::: : ...... .....

..... ..... .....

54- ... .... ......

... ............ ........ ... . .... ... ... . .... .... .. ..-. .. .. ..... .. ..

. .. ... . .. . ..... ........ 0...

. ..... .... .......

at.. ... .....

N- C. . .. C)........ 4 ... ..... ...... 0~ .... 0... 0 Ct.fJ 0.. .. 0..n....0 ..... .... . . ....

... ...... ....... .C.. . . ... ..... .. .

9. .. .. .

.. . ..... ..... ....

CA CA 0 C0 .. . ..... ..... ..... j CA C 00

o o CA CA .......... ........ o.. .....~* 180...

Example 5

[0508] Western blot analysis was performed on expressed protein pools as illustrated in Figures 39A-39B. Figure 39A illustrates Klotho ECD (34-981) 6x His Protein, and Figure 39B illustrates the indicated Klotho protein. Unexpectedly, Klotho proteins appear to aggregate into higher molecular weight multimers.

[0509] A 5L bioreactor expression run was carried out, followed by adapter purification protocols. In a first purification step, Protein A Sepharose 4 Fast Flow (0.75 ml) (0.5 cm x 3 cm) column was equilibrated in 10 mM Tris-HCl, pH 8.0. Protein sample (100 ml of Cell Supernatant adjusted to pH 8.0, with 1.5 M Tris-HCl, pH 8.0 (~ 1 ml)) was loaded at a flow rate of 0.75 ml/min, washed with 10 mM Tris/Arginine-HCl, pH 8.0 buffer, and eluted with 4 M MgC2, pH 3 (i.e., low pH, high salt) at 0.50-0.25 ml/min to produce a concentrated sample. See Figure 40A. The column was re-equilibrated with 10 mM Tris-HCl, pH 8.0 (to prevent salt precipitate), and sanitized with 0.1 M NaOH: 0.5-0.3 ml/ml to avoid over pressurization. Minimal Klotho protein was eluted during re-equilibration and sanitation.

[0510] Peak #1 and Peak #2 from the Protein A elution were analyzed separately, buffer exchanged, and fractionated using Superdex 200 (1 cm x 30 cm) size exclusion chromatography column with 100 mM Tris-HCl/5 mM L-Methionine/0.6% Sodium Thioglycolate, pH 8.0 mobile phase at 0.5 mL/min flow rate. See Figure 40B. Tris was used to buffer the mobile phase instead of a phosphate-containing buffer to prevent the precipitation of magnesium salts. Reducing agent (L-methionine) was used to prevent the oxidation of Klotho-Fc. Sodium Thioglycolate was used to prevent the scrambling of free sulfhydryl cysteine groups of Klotho-Fc. Buffer components are GRAS listed by the FDA.

[0511] Superdex 200 fractions from single isolated Peak #1 and Peak #2 each show different MW species of klotho-Fc protein. See Figure 41A and 41B. In summary, analysis of harvested proteins (in media) by SDS-PAGE, suggests that Klotho-Fc exists in various states of aggregation. The purification produced two populations of multimeric Klotho-Fc corresponding to a dimer (< 300 kDa) and a tetramer ( < 600 kDa).The binding/elution protocol from Protein A shows far superior product elution profile and produces minimal protein after sanitation. As the formulation has thioglycolate as a reducing agent, the product separates as monomer after heating, and monomer and dimer without heating in gel electrophoresis. These new purification procedures resulted in non-aggregated Fc-klotho protein.

Example 6

[0512] A bioassay was developed to test the activity of both native and Fc-Klotho proteins, and particularly to test the binding affinity of Klotho proteins to FGF 23 using BLITZ by ForteBio. Initially, the binding affinity of Recombinant Mouse Klotho to Mouse FGF-23 using Surface Plasmon Resonance (SPR) binding methods was assessed. SPR is an optical technique utilized for detecting molecular interactions between an analyte, a mobile molecule, and a ligand, an immobilized molecule bound to the sensor, which upon interaction change the refractive index of the sensor. In this study, the Inventors compared the affinity of six concentrations of Recombinant Mouse Klotho (2-fold serial dilutions from 400 ug/mL to 12.5 ug/mL) antibody to Mouse FGF-23. Using anti-HIS (HIS2) sensors, Mouse FGF-23 is bound to the sensors and then subsequently these sensors are used to produce binding curves for six different concentrations of the Mouse Klotho. From the six association and disassociation curves produced for the antibody, the disassociation constant (K) value of the antibody is determined. Assays were performed and data verified (data not shown).

[0513] For human recombinant Klotho protein, IHIS-Tag biosensor tips were hydrated in PBS for 10 minutes at RT. HIS-Tag labeled FGF23 (ProSpec, Cat#CYT-374) at 300ug/ml in PBS was coupled to biosensor for 2 minutes. Base line was established for 30 seconds on BLITZ instrument. Then, the binding of native and Fc-sKlotho proteins at five two-fold serial dilutions (from 400ug/ml to 12.5 ug/ml) to immobilized FGF23 was tested for 2 minutes in PBD, and subsequently dissociated for 2 minutes in PBS. The Kon (association), Ko (dissociation), and KD (Koff/Kon) was analyzed using global analysis. See Figure 42.

[0514] Further assays were performed to test the bioactivity of Klotho proteins using cell based functional assay, and particularly to test the bioactivity of both native and Fc-Klotho proteins by measuring their effect on stimulating NIH/3T3 cell proliferation. Based on biology of Klotho, the rationale of this assay development is to test the effect of Klotho on stimulating the proliferation of NIH-3T3 cells that expressed FGFR.

[0515] Growing phase cells were seeded in culture media (10%FBS-DMEM) at a density of 5000 cells/well/96-well plate, and cultured overnight, followed by a media change to 0.5% FBS and overnight culture. Cells were treated with 10 doses of respective Klotho protein starting at 30 ug/ml, 2-fold serial dilution, each dose in triplicate, and incubated for 48 hours. Cell proliferation was measured using Cell Titer-Glu assay kit, and data was analyzed using 4 parameter-fit curve with GraphPad Prism. The data indicate that purified Klotho proteins, both Native-His and Fc Klotho, stimulated cell proliferation in a dose-dependent manner. See Figures 43A-43E. Example 7

[0516] A study to determine the Acute Tolerated Dose (ATD) of Alpha Human Native Klotho and Alpha Human Fc-Fusion Klotho proteins following intravenous administration in male Sprague-Dawley rats was conducted. In the acute tolerated dose study, the safety of the test articles Alpha Human Native Klotho and Alpha Human Fc-Fusion Klotho proteins was assessed in male Sprague-Dawley rats. Prior to dose administration, 21 animals were subcutaneously implanted with transponders. On Study Day -1, animals were randomized into seven groups of three, based on body weights. Alpha Human Native Klotho protein was tested at three dose concentrations of 10 pg/kg, 30 ptg/kg, and 100 ptg/kg (based on individual body weight) administered intravenously at a dose volume of 1 ml/kg (based on individual body weight) in vehicle (PBS, pH 7.2) on Study Day 0.

[0517] Alpha Human Fc-Fusion Klotho protein was also tested at three dose concentrations of 3 ptg/kg, 10 ptg/kg and 30 ptg/kg (based on individual body weight) administered intravenously at a dose volume of 1 ml/kg (based on individual body weight) in vehicle (PBS, pH 7.2) on Study Day 0. Dosing began with a vehicle-only (PBS, pH 7.2) Group, 10 pg/kg Alpha Human Native Klotho protein Group, and 3 pg/kg Alpha Human Fc-Fusion Klotho protein Group on Study Day 0 and were staggered by at least 24 hours between each test article dose level group. All dosing was given once on the respective start date. Animals were observed for any adverse effects for maximum of 14 days following treatment.

[0518] In-life measurements included twice-daily checks for morbidity and mortality, and clinical observations were noted daily. Body weight measurements were recorded daily. Following completion of the observation phase, all animals were euthanized via cardiac exsanguination. Terminal measurements included blood hematology, serum biochemistry and coagulation. Gross pathology changes were recorded for all animals at necropsy and weights of ten organs (adrenals, brain, epididymides, heart, kidneys, liver, spleen, testes, thyroid/parathyroid and thymus) were taken.

[0519] Table 67 presents a summary of study animals. Species/Strain/Sex Age Range Total Number NumberofAnimals Numberof of Animals per Group Groups

Rat/Sprague Dawley/M 8 weeks 21 3 7

Table 67

[0520] Table 68 presents a summary of study design. Group Test Article Dose Level pg/kg 1 PBS, pH 7.2 - 2 Alpha Human Native Klotho 10 3 Alpha Human Native Klotho 30 4 Alpha Human Native Klotho 100 5 Alpha Human Fc- Fusion Klotho 3 6 Alpha Human Fc- Fusion Klotho 10 7 Alpha Human Fc- Fusion Klotho 30

Table 68

[0521] For Group Assignment: Matched Pair Distribution, an optimized distribution method

using an algorithm that matches the individual measurement values with the mean of all selected

animals was performed. The method begins by taking matching pairs that average close to the

mean of all selected animals and then distributes them into groups that will then match the

average (or as close as possible) of the mean of all selected animals. Animals are distributed so

that the average of the measurement for each group will be as close to the mean of all selected animals as possible.

[0522] For Statistical Analyses, descriptive statistics were generated from Study data. Data

was assessed to determine whether parametric or non- parametric analysis was appropriate. For

parametric data, analysis of variance (ANOVA) followed by post-hoc tests was performed to determine significant differences between treatments, time points, and/or groups. For non

parametric data, appropriate statistical analyses were performed (e.g., Kaplan-Meier Survival,

Kruskal-Wallis One-way ANOVA, Mann- Whitney or Wilcoxon Rank Sum, etc.).

[0523] Table 69 summarizes sample collection procedure. Task Method & Collection Sample Info/Special Instructions Blood for clinical biochemistry collected into non-heparinized stored at -809C and tubes for serum preparation shipped on dry ice Blood for coagulation analyses collected into sodium citrate stored at -809C and tubes shipped on dry ice Whole blood for CBC count collected into K 2EDTA tubes stored at 2-89C and hematology analysis shipped

Table 69

[0524] Table 70 summarizes sample collection tasks. Task Frequency Body weight Daily Adrenals, brain, epididymides, heart, kidneys, liver, spleen, testes, At termination thyroid/parathyroid and thymus to be excised and weighted Clinical Observation Daily Morbidity Check 2x daily Mortality Observation 2x daily

Table 70

[0525] Any animal whose body weight dropped below 85% of initial body weight, or displays severe, prolonged adverse clinical signs was to be euthanized. Animals were to be euthanized via cardiac bleed for collection of plasma, serum and whole blood as indicated above.

[0526] Preliminary results indicated that the rats tolerate relatively high doses of recombinant Klotho proteins administered thereto. Example 8

[0527] A study to determine Pharmacokinetics of Alpha Human Native Klotho and Alpha Human Fc-Fusion Klotho Proteins Following IV Dosing in Male Sprague Dawley Rats was conducted. Prior to Study Day 0, animals were subcutaneously implanted with transponders. On Study Day -1 body weights were acquired and animals were randomized based on body weight. On Study Day 0, animals in Groups 5, 6, and 7 (10 animals per group) received a single dose of Alpha Human Fc-Fusion Klotho protein intravenously via the tail vein (see detailed dosing schedule, below) at 3, 10, and 30 pg/kg in 1 ml/kg vehicle (PBS, pH 7.2), respectively. On Study Day 1, animals in Groups 2, 3 and 4 (10 animals per group) received a single dose of Alpha Human Native Klotho protein intravenously via the tail vein (see detailed dosing schedule, below) at 10, 30 and 100 ptg/kg protein in 1 ml/kg vehicle (PBS, pH 7.2), respectively. Animals in the vehicle Group 1 (3 animals) was also dosed on Study Day 1 at 1 ml/kg vehicle (PBS, pH 7.2) without protein. The volume of dosing solution administered to each animal was calculated and adjusted based on individual body weight measured acquired on Study Day -1.

[0528] Three blood samples were obtained from each group (2-7) for all time points, equating to three blood samples per rat (see detailed blood collection schedule, below). Time-point blood samples were obtained pre-dose, 3 min, 10 min, 20 min, 30 min, 1hr, 2 hr, 4 hr, 8 hr and 24 hr post-dose (Groups 2, 3 and 4), as presented in Table 71, below.

Rat ID min 3 min 0 min 20 mm 30min I hr 2 hr 4 hr 8 hr 24it X_ X X 2 X X X

4 KX _X

5_ x x 6 _ _ _ _ _ _ K _ _ _

7 N xX ____ _ __ _

9 x _ _ x Ix

Table 71

[0529] Time-point blood samples were obtained pre-dose, 3 min, 1hr, 4 hr, 8 hr, 24 hr, 48 hr, 72 hr, 96 hr and 7 days post-dose (Groups 5, 6, and 7), as presented in Table 72, below. An additional blood collection at 14 days post dosing was obtained in Groups 5, 6, and 7.

Grups5.6and7 -7

RatT) Ofmin 3 mn lhr 4hr 8hr 244r 48 hr 72 hr 4hr 7day determined) I X X X 2 X xX X- x x x ___

3 -- X -X X X 4 X X X 5 X X X _ _

6 X X X X 7 X X X 8 X X X 9 X X X 10 X X X X

Table 72

[0530] Vehicle Group 1 animals were bled terminally once, 1 hr post dose administration, as presented in Table 73, below.

RatID ... hr

3 X

Table 73

[0531] Resulting serum samples were analyzed via Alpha Klotho Human Soluble ELISA kit.

[0532] Table 74 presents a summary of study animals. Species/Strain/Sex Age Range TotalNumber NumberofAnimals Numberof of Animals per Group Groups Rat/Sprague Dawley/M 8-11 weeks 63 3-10 7

Table 74

[0533] Table 75 presents a summary of study design.

Group Test Article Dose Level pg/kg 1 PBS, pH 7.2 - 2 Alpha Human Native Klotho 10 3 Alpha Human Native Klotho 30 4 Alpha Human Native Klotho 100 5 Alpha Human Fc- Fusion Klotho 3 6 Alpha Human Fc- Fusion Klotho 10 7 Alpha Human Fc- Fusion Klotho 30

Table 75

[0534] For Group Assignment: Stratified Sampling, a non-optimized randomization method that uses "binning" of the animals with measurement values of similar size was used. By this method, the pool of animals is stratified by sorting them by the measurement value of interest in ascending order. Animals are then organized into "bins" or strata according to the size of the measurement value. The number of strata is determined by the number of animals that are to be assigned per group. For example, if there are three animals per group, then three bins would be created: small, medium and large. One animal from each size bin is assigned randomly to each group. Stratified sampling ensures that each group receives one animal randomly from each size bin and the means of each group will remain similar to the other groups. This method balances differences between group means and standard deviations and controls for pool order bias.

[0535] For Statistical Analyses, Descriptive statistics were generated from Study data. Data were assessed to determine whether parametric or non-parametric analysis was appropriate. For parametric data, analysis of variance (ANOVA) followed by post-hoc tests was performed to determine significant differences between treatments, time points, and/or groups. For non parametric data, appropriate statistical analyses were performed (e.g., Kaplan-Meier Survival, Kruskal-Wallis One-way ANOVA, Mann-Whitney or Wilcoxon Rank Sum, etc.).

[0536] Table 76 summarizes sample collection procedure. Task Method & Collection Sample Info/Special Instructions

Serum preparation for PK Blood collected via saphenous Samples processed sampling vein or cardiac puncture into non- to serum and stored heparinized tubes for serum at -80C prior to ELISA analysis

Table 76

[0537] Table 77 summarizes sample collection tasks. Task Frequency Body weight On Study Day -1 and twice weekly thereafter Clinical Observation 2x weekly Mortality Observation As required

Table 77

[0538] Any animal whose body weight dropped below 85% of initial body weight or displays

severe, prolonged adverse clinical signs was euthanized (data not shown). Animals were euthanized via cardiac bleed for collection of plasma, serum and whole blood as indicated above.

Example 9

[0539] A study to determine Dose-Dependent Effects of Alpha Human Fc-Klotho and Alpha

Human Native Klotho on I/R Induced-AKI and Renal Biomarkers (by measuring renal I/R

induced increases in plasma renal injury biomarkers) in Wistar Rats was performed. Specifically,

the objective of this study was to evaluate the dose-dependent effects of alpha human Fc-Klotho

and alpha human native Klotho on renal I/R-induced increases in plasma renal injury biomarkers

in rats. The study was designed to provide data from or related to bilateral renal ischemia

reperfusion (I/R) injury (30' ischemia duration) surgery (n=63) verses sham surgery (n=4),

Compound dosing (one i.v. injection/rat), serial urine collections via metabolic cage housing (3

collections/rat; D1, D2 & D7), clinical chemistry analysis of serial urine specimens for creatinine

and protein (D1, D2 & D7), serial blood collections (3 collections/rat; D1, D2 & D7), clinical

chemistry analysis of serial plasma specimens for creatinine and BUN (D1, D2 & D7), daily

body weights and health observations post-surgery through endpoint, and endpoint tissue

collection and processing, with data presented in tabular and graphical format.

[0540] In addition, analysis of serial urine specimens for Kim-i via species specific ELISA

(D1, D2 &D7), analysis of serial urine specimens for NGAL via species specific ELISA (D1, D2 & D7), left and/or right kidney mRNA expression analysis (1-2 kidney/animal: n = 67

samples; 10 analytes, includes 3 normalization genes; performed using the Affymetrix

Quantigene Plex 2.0 platform); MCP-1, TGF-, c-SMA, CollAl, Col3A1, Fn-1, CTGF), and left and/or right renal cortical immunohistochemistry and quantitation of macrophage infiltration via specific staining and quantitation of ED-1+ macrophage staining were also optionally performed.

[0541] Table 78 presents that study parameters. Compounds: Alpha Human Fc- Klotho: 10 or 30ag/kg Alpha human Native Klotho: 10 or 30ag/kg Route / Frequency: Alpha Human Fc-Klotho: i.v./ dose once at either t-0.5 hour or t+1 hour relative to time of ischemia inception Native Klotho: i.v./ dose once at either t-0.5 hour or t+1 hour relative to time of ischemia inception Vehicle / Dose Volume: Alpha Human Fc-Klotho: PBS / 1 ml/kg i.v. Native Klotho: PBS / 1 ml/kg i.v. Compound Requirement: Alpha Human Fc-Klotho: 0.221 mg Native Klotho: 0.221 mg

Table 78

[0542] Table 79 presents a summary of study design. Compound &

Group N/group Administration Interval Dose Volume & Challenge (Animal #s) (0 hr = time of ischemia Route inception)

N =4 Vehicle 1 ml/kg Sham operated 1 (4528 - 4531) +1 Hr. i.v. 7 Days Post-Sx

N =9 Vehicle 1 ml/kg 30' Ischemia 2 (4532 - 4540) +1 Hr. i.v. 7 Days Reperfusion N =9 10 ag/kg Fc-Klotho 1 ml/kg 30' Ischemia (4541 - 4549) +1 Hr. i.v. 7 Days Reperfusion

N =9 30 ag/kg Fc-Klotho 1 ml/kg 30' Ischemia 4 (4550 - 4558) +1 Hr. i.v. 7 Days Reperfusion N =9 10 ag/kg Native Klotho 1 ml/kg 30' Ischemia (4559 - 4567) +1 Hr. i.v. 7 Days Reperfusion

N =9 30 ag/kg Native Klotho 1 ml/kg 30' Ischemia 6 (4568 - 4576) +1 Hr. i.v. 7 Days Reperfusion N =9 30 ag/kg Fc-Klotho 1 ml/kg 30' Ischemia 7 (4577 - 4585) -0.5 Hr. i.v. 7 Days Reperfusion

N =9 30 ag/kg Native Klotho 1 ml/kg 30' Ischemia 8 (4586 - 4594) -0.5 Hr. i.v. 7 Days Reperfusion

Table 79

[0543] Sixty-seven (67) male Wistar rats weighing approximately 151-175g were acquired and

fed a standard chow diet (Harlan 8640), group housed under standard conditions, and allowed to

acclimate for at least 7 days before enrolling in study. Prior to study inception, the study rats

were placed into weight-matched treatment groups. Animals were enrolled to study using a balanced design, such that approximately equal numbers of animals were enrolled per group per surgical day, and the heaviest animals enrolled first to minimize differences in animal age. When not in metabolic cage housing, rats were group housed under standard conditions in static caging.

[0544] At t-0.5 hours, study rats were anesthetized with isoflurane anesthesia on a nosecone, prepared for surgery and core temperature allowed to equilibrate prior to renal I/R operative procedure. Rats were administered 10 ml/kg warm, sterile saline (s.c.; 25% pre- and 75% post

surgery) to minimize perturbations in body fluid volume. Core temperatures were maintained normative (37±0.2°C) throughout ischemia duration. At t-0.5 hours, animals in Groups 7 and 8 also received an i.v. injection of compound as appropriate.

[0545] A laparotomy was then performed. At t, rats were subjected to either sham (Group 1, n=4) or bilateral renal arterial ischemia (Groups 2-8; n=9/grp) using heat sterilized instruments, vascular occlusive clamps, and aseptic surgical technique. Following thirty (30) minutes of continuous ischemia time (t+0.5), the occlusive clamps were removed, the kidneys reperfused and the abdominal wound closed with sterile silk suture. Rats were administered 0.01 mg/kg buprenorphine as post-operative analgesic and allowed to recover briefly in a clean, heated cage. At t+1 hour, rats in Groups 1-6 were briefly restrained and received an i.v. injection of vehicle or Klotho compound in vehicle as appropriate. Rats in Groups 7 and 8 were also briefly restrained (but not injected) to control for handling stress. Rats were then immediately placed into metabolic cages.

[0546] Twenty-four (24) hours following reperfusion (D1), all animals had urine volumes determined and sampled. All animals then had blood (500 pl) collected on Li-Heparin by direct tail vein stick. Immediately post-bleed, rats received 500 pl warm saline. Urine and blood collection was repeated again on D2 (48 hours post-reperfusion) and D7 (168 hours post reperfusion). On D2-D5, all rats were grouped housed under standard conditions in static caging and weighed, and underwent health observations daily. Whole blood (500 pl) was processed appropriately for the production of plasma and processed as described.

[0547] Clinical observations were conducted once daily following inception of dosing. With regard to data/tissues to be collected/calculated, animal health was observed daily following surgical procedure, and kidney mass (left and right kidney weights) was indexed to tibia length and body weight. Urine was collected at D1, D2 and D7 (targeting n=3 samples/animal; 500 pl/sample). At least one sample was subjected to clinical chemistry analysis (creatinine, protein) and at least one sample was optionally used for Kim- and NGAL analysis. Plasma was collected on Li-Heparin at D1, D2 and D7 (targeting n=2 samples/animal; 125 p.l/sample). At least one sample was subjected to clinical chemistry analysis (creatinine, BUN).

[0548] On D7, rats were anesthetized with isoflurane immediately following bleed and tissues were harvested. Both left and right kidneys were immediately placed in ice-cold 0.9% NaCl, de encapsulated and weighed. After tissue harvest (for histological and other analysis), all remaining inner cortical/outer medullary (i.e. S3/THAL enriched) from each sham and ischemic kidney (left and right kidney from each animal; 1 tube/kidney/animal) were snap frozen in appropriately labeled tube and stored at -80°C for future potential biochemical analysis. Prior to any analyses being performed, cortical tissue was optionally cryogenically powdered and mixed to enable better homogeneity of the tissue sample across biochemical assays as well as limit introduction of sampling bias that may occur with cortical biopsies. At least one mid-transverse section of each sham and ischemic kidney (left and right from each animal) was optionally collected and immersion fixed in 10% neutral buffered formalin for histological analysis. The rats were then sacrificed. Example 10

[0549] The body weight of study rats were measured to test for the effect of Klotho protein administration on subjects. Table 80 presents a summary of study animals. Group Test Article Group 01 Vehicle only, PBS, pH 7.2 Group 02 Alpha Human Native Klotho,10 ag/kg Group 03 Alpha Human Native Klotho, 30 ag/kg Group 04 Alpha Human Native Klotho, 100 ag/kg Group 05 Alpha Human Fc-Fusion Klotho, 3 ag/kg Group 06 Alpha Human Fc-Fusion Klotho, 10 ag/kg Group 07 Alpha Human Fc-Fusion Klotho, 30 ag/kg

Table 80

[0550] Figure 44 illustrates, graphically, the average (mean) body weight (+/-standard error of the mean; SEM bars) of rats in each group over the course of the 12-day study (daily). Table 81, below, presents the corresponding data for mean body weight illustrated in Figure 44, Table 82, below, presents the corresponding SEM illustrated in Figure 44, and Table 83, below, presents the percent change in mean body weight of rats in each group over the course of the 12-day study (daily).

Example 11

[0551] To study the therapeutic effect of Klotho administration on Acute Kidney Injury (AKI) following renal ischaemia reperfusion injury (IRI), Sprague-Dawley rats were randomly divided into either Sham or AKI groups, and the animals in each group were randomly allocated into vehicle or Klotho treatment. In humans, AKI is a formidable clinical problem resulting primarily from ischemia or nephrotoxins, with outcomes ranging from full recovery to the development of chronic kidney disease with dialysis dependence, or death. Animals in the Klotho group received one bolus intraperitoneal injection of recombinant mouse Klotho protein (0.01 mg/kg body weight) 30 or 60 min after reperfusion; rats in vehicle group received the same volume of Klotho buffer (150 mM NaCl and 10 mM HEPES pH 7.4). Twenty-four-hour urine and blood were collected on days 1, 2, and 7 after surgery. This study showed that a single bolus injection of murine S-Klotho 30 min post-injury was effective in attenuating (AKI) in animal model of the human condition. Example 12

[0552] To determine whether Klotho protects the lung against oxidant injury, Sprague-Dawley rats (body weight -300 g) were exposed to normoxia (N: 21% inspired 0 ) or hyperoxia (H: 90% 0 ) for 3 days while receiving intra-peritoneal injections of one of 3 preparations: Dulbeco's modified Eagle's Medium (DMEM) or conditioned medium (CM) from CHO cells overexpressing either Klotho (Klotho CM; -60 pmol) or empty vector (Control CM) (n=6-8 animals each). Injections were given 12h before, and repeated at 24h and 48h during exposure.

[0553] Also, 3LL cells were transplanted at the flanks of athymic mice by subcutaneous injection (2 x 106 cells per mouse) and treated with Klotho protein (0.01 mg/kg, intraperitoneal) or vehicle every other day for 10 days. Lungs were harvested 21 days after transplantation and the number of metastatic nodules was counted.

r- t CIA N Ln mc0ai00r r~- car-0 -1 CA .WLn 00 0 0Ln >- o* > qr!nq p ! " 0 >W,- C O 0Ln 0) 6 6 ti6 -i- -mrm- r m0)Q m -t Qm 6r m m4 r

.- wn~ rn m rn -n mn on nm >m m -~0 r '00,'01, 10 Om m Rl m L wL >-o ir: y Q6 rr L !" o -mi -o 0 1Rl Ommmmmmm r " r 0LnL 0 nL - 6r r 4

rn nn nnnn - ---- - ',r, r NN "0 "00CO r,) kD "' r-m m m 0m n 0'10 00 '1,'00 0m,'10 00 r-ir- 01 -ir-irn t rn-i kr - ,= ri 00 l - - zl n r- 00 liL >- or- r* r ry >-r, L q c r:-1CW NrI-i - O L Rl

WkOQrmN00 n w0 h l 1t 00qr:Lqk 0 0 aRl HI r-jm I ~ -r- H- zl O r z-0 00 >w o6 Q rLti 6 oo onQ Q rnLlfl ~ lf -n NNrn flOn C Cl

C, rQw" C, C, "'ry- "0 00 rn rn rn rLnn-rl m >, oq r 0 1qo q 0 Q n0i ~L 0 ,,00 ,,',,00 00 00

kD> 1 )0 M > 0 1r n Rl-rO r >c66n~ W

0 0 -j j 0 r- r-j (a . . kD C aJ - C aN0)

0 N NN0 NNN0 rn 0rn

rn" n tLq nf 00 lrnci0 n k ,0 ,,00 ,, 00 00 00 1 00 -100r-Rz- cO RzO - O r O Lf nfr- t 0 YM C kD CJ0 aN n nk M NRzNr CNjNj 6N Q 6Q 4 L q

w Q nL- r-~m~L ~Ln w -n . mn .

cli Li kD D kD t193

Conclusion

[0554] Existing Klotho protein measurement may be prohibitively expensive and/or technically challenging for at-home collection and/or quantitative diagnostic. Embodiments of the present disclosure provide methods for monitoring, detecting and/or quantifying Klotho protein level(s), particularly endogenous and/or exogenous soluble alpha Klotho protein level(s), and more particularly soluble alpha Klotho protein levels, diagnosing Klotho protein deficiency, and/or increasing Klotho protein level(s), expression, or production, particularly endogenous and/or exogenous soluble alpha Klotho protein level(s), expression, or production, in a subject, and products useful in performing the same, including diagnostic kits and compositions for treating Klotho protein deficiency.

[0555] In addition, while gene therapy can be effective to increase certain protein levels in animal models or studies, the safety of gene therapy, especially for human treatment, is still questionable. Compared to viral delivery of the klotho gene to animal (cells), the administration of exogenous and/or recombinant protein in humans may be a safer, easier, and more direct modality to restore (endocrine) klotho levels. Preclinical data supports the therapeutic potential of soluble Klotho protein for age-related disorders and klotho deficiency-associated diseases. Epidemiological data has shown that soluble Klotho is lower in the elderly than in young adults, and that levels of soluble Klotho are inversely correlated with age, indicating that aging may be associated with soluble Klotho decline. Generally, however, the production and administration of exogenous and/or recombinant protein to humans is tightly regulated by government and other entities. Because of the time and expense associated with regulatory compliance, the cost of such treatments can be prohibitive for developers, manufactures, and patients alike. Compositions and methods of the present disclosure, however, can provide a viable and effective option for increasing endogenous Klotho protein levels in humans and non-human animals without one or more of the drawbacks associated with other solutions. In particular, some embodiments of the present disclosure include products, compositions, and/or methods of manufacturing and/or using recombinant human Klotho proteins, such as (Current Good Manufacturing Practice (cGMP) grade) human recombinant soluble alpha-Klotho proteins, protein fragments, and/or protein variants. In addition, some embodiments of the present disclosure include (nutraceutical or health supplement) products, compositions, and/or methods for (naturally) increasing (endogenous and/or serum soluble) Klotho protein level(s), expression, or production in a patient or subject.

[0556] Those skilled in the art will appreciate that each of the therapeutic effects, indications, and/or treatments outlined herein in relation to recombinant, therapeutic Klotho proteins and products, compositions, and methods related thereto can be achieved by (naturally) increasing, enhancing, augmenting, and/or supporting endogenous Klotho protein production and/or level(s). Those skilled in the art will also appreciate that each of the therapeutic effects, indications, and/or treatments outlined herein in relation to (naturally) increasing, enhancing, augmenting, and/or supporting endogenous Klotho protein production and/or level(s) can be achieved by administering recombinant, therapeutic Klotho proteins and products, compositions, and through methods related thereto. Accordingly, and for the sake of brevity, the present disclosure need not rehearse each of the disclosed therapeutic effects, indications, and/or treatments with reference to both (i) the administration of recombinant, therapeutic Klotho proteins, and (ii) the administration of the health supplement or nutraceutical compositions of the present disclosure, as such are clearly contemplated herein.

[0557] While the foregoing detailed description makes reference to specific exemplary embodiments, the present disclosure may be embodied in other specific forms without departing from its spirit or essential characteristics. Accordingly, the described embodiments are to be considered in all respects only as illustrative and not restrictive. For instance, various substitutions, alterations, and/or modifications of the inventive features described and/or illustrated herein, and additional applications of the principles described and/or illustrated herein, which would occur to one skilled in the relevant art and having possession of this disclosure, can be made to the described and/or illustrated embodiments without departing from the spirit and scope of the disclosure as defined by the appended claims. Such substitutions, alterations, and/or modifications are to be considered within the scope of this disclosure.

[0558] The scope of the invention is, therefore, indicated by the appended claims rather than by the foregoing description. The limitations recited in the claims are to be interpreted broadly based on the language employed in the claims and not limited to specific examples described in the foregoing detailed description, which examples are to be construed as non exclusive and non-exhaustive. All changes which come within the meaning and range of equivalency of the claims are to be embraced within their scope.

[0559] It will also be appreciated that various features of certain embodiments can be compatible with, combined with, included in, and/or incorporated into other embodiments of the present disclosure. For instance, systems, methods, and/or products according to certain embodiments of the present disclosure may include, incorporate, or otherwise comprise features described in other embodiments disclosed and/or described herein. Thus, disclosure of certain features relative to a specific embodiment of the present disclosure should not be construed as limiting application or inclusion of said features to the specific embodiment.

[0560] In addition, unless a feature is described as being required in a particular embodiment, features described in the various embodiments can be optional and may not be included in other embodiments of the present disclosure. Moreover, unless a feature is described as requiring another feature in combination therewith, any feature herein may be combined with any other feature of a same or different embodiment disclosed herein. It will be appreciated that while features may be optional in certain embodiments, when features are included in such embodiments, they can be required to have a specific configuration as described in the present disclosure.

[0561] Likewise, any steps recited in any method or process described herein and/or recited in the claims can be executed in any suitable order and are not necessarily limited to the order described and/or recited, unless otherwise stated (explicitly or implicitly). Such steps can, however, also be required to be performed in a specific order or any suitable order in certain embodiments of the present disclosure.

[0562] Furthermore, various well-known aspects of illustrative systems, methods, products, and the like are not described herein in particular detail in order to avoid obscuring aspects of !o the example embodiments. Such aspects are, however, also contemplated herein.

[0563] A reference herein to a patent document or any other matter identified as prior art, is not to be taken as an admission that the document or other matter was known or that the information it contains was part of the common general knowledge as at the priority date of any of the claims.

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT SEQUENCE LISTING SEQUENCE LISTING

<110> Klotho Therapeutics Inc. <110> Klotho Therapeutics Inc. TARSIO, Joseph F. TARSIO, Joseph F. <120> Therapeutic Recombinant Klotho Protein and Compositions and <120> Therapeutic Recombinant Klotho Protein and Compositions and Methods Involving the Same Methods Involving the Same

<130> 20780.2a <130> 20780.2a

<160> 152 <160> 152

<170> PatentIn version 3.5 <170> PatentIn version 3.5

<210> 1 <210> 1 <211> 1012 <211> 1012 <212> PRT <212> PRT <213> Homo sapiens <213> Homo sapiens

<400> 1 <400> 1

Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser 1 5 10 15 1 5 10 15

Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg 20 25 30 20 25 30

Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro 35 40 45 35 40 45

Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly 50 55 60 50 55 60

Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp 65 70 75 80 70 75 80

Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His 85 90 95 85 90 95

Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly 100 105 110 100 105 110

Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser 115 120 125 115 120 125

Page 1 Page 1

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val 130 135 140 130 135 140

Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly 145 150 155 160 145 150 155 160

Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu 165 170 175 165 170 175

Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr 180 185 190 180 185 190

His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala 195 200 205 195 200 205

Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe 210 215 220 210 215 220

Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro 225 230 235 240 225 230 235 240

Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly 245 250 255 245 250 255

Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu 260 265 270 260 265 270

Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro 275 280 285 275 280 285

Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn 290 295 300 290 295 300

Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu 305 310 315 320 305 310 315 320

Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp 325 330 335 325 330 335

Page 2 Page 2

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe 340 345 350 340 345 350

Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala 355 360 365 355 360 365

Leu Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Leu Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met 370 375 380 370 375 380

Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp 385 390 395 400 385 390 395 400

Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly 405 410 415 405 410 415

Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr 420 425 430 420 425 430

Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp 435 440 445 435 440 445

Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe 450 455 460 450 455 460

Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp 465 470 475 480 465 470 475 480

Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe 485 490 495 485 490 495

Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn 500 505 510 500 505 510

Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val 515 520 525 515 520 525

Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu 530 535 540 530 535 540

Page 3 Page 3

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Asn Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asn Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val 545 550 555 560 545 550 555 560

Asp Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Asp Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala 565 570 575 565 570 575

Ala Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Ala Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His 580 585 590 580 585 590

Phe Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Phe Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln 595 600 605 595 600 605

Ser Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Ser Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser 610 615 620 610 615 620

Glu Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Glu Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro 625 630 635 640 625 630 635 640

Met Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Met Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala 645 650 655 645 650 655

Trp Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Trp Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu 660 665 670 660 665 670

Cys Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Cys Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn 675 680 685 675 680 685

Glu Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Glu Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu 690 695 700 690 695 700

Lys Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Lys Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His 705 710 715 720 705 710 715 720

Ala Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Ala Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu 725 730 735 725 730 735

Pro Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Pro Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val 740 745 750 740 745 750

Page 4 Page 4

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly 755 760 765 755 760 765

Asp Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Asp Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe 770 775 780 770 775 780

Leu Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Leu Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr 785 790 795 800 785 790 795 800

Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser 805 810 815 805 810 815

Glu Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Glu Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu 820 825 830 820 825 830

Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val 835 840 845 835 840 845

Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly 850 855 860 850 855 860

Asp Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Asp Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His 865 870 875 880 865 870 875 880

Ala Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Ala Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn 885 890 895 885 890 895

Glu Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Glu Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr 900 905 910 900 905 910

Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr 915 920 925 915 920 925

Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr 930 935 940 930 935 940

Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu 945 950 955 960 945 950 955 960

Page 5 Page 5

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Arg Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe Arg Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe 965 970 975 965 970 975

His Thr Arg Lys Ser Leu Leu Ala Phe Ile Ala Phe Leu Phe Phe Ala His Thr Arg Lys Ser Leu Leu Ala Phe Ile Ala Phe Leu Phe Phe Ala 980 985 990 980 985 990

Ser Ile Ile Ser Leu Ser Leu Ile Phe Tyr Tyr Ser Lys Lys Gly Arg Ser Ile Ile Ser Leu Ser Leu Ile Phe Tyr Tyr Ser Lys Lys Gly Arg 995 1000 1005 995 1000 1005

Arg Ser Tyr Lys Arg Ser Tyr Lys 1010 1010

<210> 2 <210> 2 <211> 981 <211> 981 <212> PRT <212> PRT <213> Homo sapiens <213> Homo sapiens

<400> 2 <400> 2

Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser 1 5 10 15 1 5 10 15

Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg 20 25 30 20 25 30

Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro 35 40 45 35 40 45

Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly 50 55 60 50 55 60

Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp 65 70 75 80 70 75 80

Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His 85 90 95 85 90 95

Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly 100 105 110 100 105 110

Page 6 Page 6

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser 115 120 125 115 120 125

Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val 130 135 140 130 135 140

Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly 145 150 155 160 145 150 155 160

Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu 165 170 175 165 170 175

Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr 180 185 190 180 185 190

His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala 195 200 205 195 200 205

Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe 210 215 220 210 215 220

Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro 225 230 235 240 225 230 235 240

Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly 245 250 255 245 250 255

Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu 260 265 270 260 265 270

Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro 275 280 285 275 280 285

Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn 290 295 300 290 295 300

Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu 305 310 315 320 305 310 315 320

Page 7 Page 7

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp 325 330 335 325 330 335

Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe 340 345 350 340 345 350

Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala 355 360 365 355 360 365

Leu Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Leu Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met 370 375 380 370 375 380

Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp 385 390 395 400 385 390 395 400

Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly 405 410 415 405 410 415

Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr 420 425 430 420 425 430

Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp 435 440 445 435 440 445

Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe 450 455 460 450 455 460

Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp 465 470 475 480 465 470 475 480

Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe 485 490 495 485 490 495

Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn 500 505 510 500 505 510

Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val 515 520 525 515 520 525

Page 8 Page 8

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu 530 535 540 530 535 540

Asn Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asn Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val 545 550 555 560 545 550 555 560

Asp Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Asp Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala 565 570 575 565 570 575

Ala Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Ala Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His 580 585 590 580 585 590

Phe Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Phe Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln 595 600 605 595 600 605

Ser Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Ser Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser 610 615 620 610 615 620

Glu Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Glu Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro 625 630 635 640 625 630 635 640

Met Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Met Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala 645 650 655 645 650 655

Trp Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Trp Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu 660 665 670 660 665 670

Cys Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Cys Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn 675 680 685 675 680 685

Glu Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Glu Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu 690 695 700 690 695 700

Lys Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Lys Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His 705 710 715 720 705 710 715 720

Ala Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Ala Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu 725 730 735 725 730 735

Page 9 Page 9

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Pro Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Pro Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val 740 745 750 740 745 750

Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly 755 760 765 755 760 765

Asp Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Asp Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe 770 775 780 770 775 780

Leu Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Leu Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr 785 790 795 800 785 790 795 800

Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser 805 810 815 805 810 815

Glu Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Glu Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu 820 825 830 820 825 830

Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val 835 840 845 835 840 845

Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly 850 855 860 850 855 860

Asp Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Asp Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His 865 870 875 880 865 870 875 880

Ala Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Ala Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn 885 890 895 885 890 895

Glu Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Glu Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr 900 905 910 900 905 910

Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr 915 920 925 915 920 925

Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr 930 935 940 930 935 940

Page 10 Page 10

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. - TXT Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu 945 950 955 960 945 950 955 960

Arg Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe Arg Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe 965 970 975 965 970 975

His Thr Arg Lys Ser His Thr Arg Lys Ser 980 980

<210> 3 <210> 3 <211> 953 <211> 953 <212> PRT <212> PRT <213> Homo sapiens <213> Homo sapiens

<400> 3 <400> 3

Arg Arg Leu Arg Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Arg Arg Leu Arg Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg 1 5 10 15 1 5 10 15

Phe Ser Arg Pro Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Ser Arg Pro Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr 20 25 30 20 25 30

Phe Pro Asp Gly Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Phe Pro Asp Gly Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr 35 40 45 35 40 45

Glu Gly Gly Trp Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Glu Gly Gly Trp Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr 50 55 60 50 55 60

Phe Thr His His Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Phe Thr His His Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser 65 70 75 80 70 75 80

Leu Pro Leu Gly Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Leu Pro Leu Gly Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val 85 90 95 85 90 95

Ala Ser Asp Ser Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Ala Ser Asp Ser Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg 100 105 110 100 105 110

Glu Leu Gly Val Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Glu Leu Gly Val Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val 115 120 125 115 120 125

Leu Pro Asn Gly Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Leu Pro Asn Gly Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Page 11 Page 11

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 130 135 140 130 135 140

Tyr Arg Arg Leu Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Tyr Arg Arg Leu Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val 145 150 155 160 145 150 155 160

Val Thr Leu Tyr His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Val Thr Leu Tyr His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr 165 170 175 165 170 175

Gly Gly Trp Ala Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Gly Gly Trp Ala Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala 180 185 190 180 185 190

Glu Leu Cys Phe Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Glu Leu Cys Phe Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr 195 200 205 195 200 205

Ile Asp Asn Pro Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Ile Asp Asn Pro Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg 210 215 220 210 215 220

Leu Ala Pro Gly Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala Leu Ala Pro Gly Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala 225 230 235 240 225 230 235 240

His Asn Leu Leu Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr His Asn Leu Leu Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr 245 250 255 245 250 255

Ser Phe Arg Pro Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser Ser Phe Arg Pro Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser 260 265 270 260 265 270

His Trp Ile Asn Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys His Trp Ile Asn Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys 275 280 285 275 280 285

Gln Lys Ser Leu Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Gln Lys Ser Leu Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe 290 295 300 290 295 300

Ile Asp Gly Asp Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Ile Asp Gly Asp Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile 305 310 315 320 305 310 315 320

Leu Pro Asp Phe Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Leu Pro Asp Phe Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala 325 330 335 325 330 335

Asp Phe Phe Ala Leu Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Phe Phe Ala Leu Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Page 12 Page 12

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 340 345 350 340 345 350

Asp Pro His Met Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Asp Pro His Met Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln 355 360 365 355 360 365

Leu Leu Ser Trp Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Leu Leu Ser Trp Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile 370 375 380 370 375 380

Val Glu Asn Gly Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Val Glu Asn Gly Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala 385 390 395 400 385 390 395 400

Lys Tyr Met Tyr Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Lys Tyr Met Tyr Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala 405 410 415 405 410 415

Ile Lys Leu Asp Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Ile Lys Leu Asp Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu 420 425 430 420 425 430

Met Asp Gly Phe Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Met Asp Gly Phe Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu 435 440 445 435 440 445

Phe Tyr Val Asp Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Phe Tyr Val Asp Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser 450 455 460 450 455 460

Ser Ala Leu Phe Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Ser Ala Leu Phe Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro 465 470 475 480 465 470 475 480

Leu Pro Glu Asn Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Leu Pro Glu Asn Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala 485 490 495 485 490 495

Trp Gly Val Val Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Trp Gly Val Val Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln 500 505 510 500 505 510

Phe Thr Asp Leu Asn Val Tyr Leu Trp Asp Val His His Ser Lys Arg Phe Thr Asp Leu Asn Val Tyr Leu Trp Asp Val His His Ser Lys Arg 515 520 525 515 520 525

Leu Ile Lys Val Asp Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Leu Ile Lys Val Asp Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys 530 535 540 530 535 540

Val Asp Phe Ala Ala Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met Val Asp Phe Ala Ala Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met Page 13 Page 13

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 545 550 555 560 545 550 555 560

His Val Thr His Phe Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro His Val Thr His Phe Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro 565 570 575 565 570 575

Leu Gly Asn Gln Ser Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Leu Gly Asn Gln Ser Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg 580 585 590 580 585 590

Cys Met Ala Ser Glu Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Cys Met Ala Ser Glu Leu Val Arg Val Asn Ile Thr Pro Val Val Ala 595 600 605 595 600 605

Leu Trp Gln Pro Met Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Leu Trp Gln Pro Met Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala 610 615 620 610 615 620

Arg Gln Gly Ala Trp Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Arg Gln Gly Ala Trp Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu 625 630 635 640 625 630 635 640

Tyr Ala Arg Leu Cys Phe Gln Glu Leu Gly His His Val Lys Leu Trp Tyr Ala Arg Leu Cys Phe Gln Glu Leu Gly His His Val Lys Leu Trp 645 650 655 645 650 655

Ile Thr Met Asn Glu Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly Ile Thr Met Asn Glu Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly 660 665 670 660 665 670

His Asn Leu Leu Lys Ala His Ala Leu Ala Trp His Val Tyr Asn Glu His Asn Leu Leu Lys Ala His Ala Leu Ala Trp His Val Tyr Asn Glu 675 680 685 675 680 685

Lys Phe Arg His Ala Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Lys Phe Arg His Ala Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala 690 695 700 690 695 700

Asp Trp Ile Glu Pro Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Asp Trp Ile Glu Pro Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val 705 710 715 720 705 710 715 720

Ala Glu Arg Val Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Ala Glu Arg Val Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile 725 730 735 725 730 735

Phe Gly Ser Gly Asp Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Phe Gly Ser Gly Asp Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln 740 745 750 740 745 750

Arg Asn Asn Phe Leu Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Arg Asn Asn Phe Leu Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Page 14 Page 14

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 755 760 765 755 760 765

Ile Gln Gly Thr Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Ile Gln Gly Thr Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile 770 775 780 770 775 780

Leu Val Asp Ser Glu Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Leu Val Asp Ser Glu Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu 785 790 795 800 785 790 795 800

Glu Val Gln Glu Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Glu Val Gln Glu Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln 805 810 815 805 810 815

Val Ala Val Val Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Val Ala Val Val Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys 820 825 830 820 825 830

Phe Lys Tyr Gly Asp Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Phe Lys Tyr Gly Asp Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp 835 840 845 835 840 845

Asp Gly Leu His Ala Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asp Gly Leu His Ala Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln 850 855 860 850 855 860

Asn Tyr Ile Asn Glu Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Asn Tyr Ile Asn Glu Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn 865 870 875 880 865 870 875 880

Leu Cys Gly Tyr Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Leu Cys Gly Tyr Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg 885 890 895 885 890 895

Phe Gly Leu Tyr Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Phe Gly Leu Tyr Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser 900 905 910 900 905 910

Met Lys His Tyr Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Met Lys His Tyr Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro 915 920 925 915 920 925

Glu Thr Leu Glu Arg Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Glu Thr Leu Glu Arg Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu 930 935 940 930 935 940

Cys Ser Phe Phe His Thr Arg Lys Ser Cys Ser Phe Phe His Thr Arg Lys Ser 945 950 945 950

<210> 4 <210> 4 Page 15 Page 15

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT <211> 948 <211> 948 <212> PRT <212> PRT <213> Homo sapiens <213> Homo sapiens

<400> 4 <400> 4

Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro 1 5 10 15 1 5 10 15

Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe 20 25 30 20 25 30

Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln 35 40 45 35 40 45

Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro 50 55 60 50 55 60

Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala 65 70 75 80 70 75 80

Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr 85 90 95 85 90 95

Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr 100 105 110 100 105 110

His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser 115 120 125 115 120 125

Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu 130 135 140 130 135 140

Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His 145 150 155 160 145 150 155 160

Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn 165 170 175 165 170 175

Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg 180 185 190 180 185 190

Page 16 Page 16

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr 195 200 205 195 200 205

Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile 210 215 220 210 215 220

Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu 225 230 235 240 225 230 235 240

Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr 245 250 255 245 250 255

Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro 260 265 270 260 265 270

Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp 275 280 285 275 280 285

Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr 290 295 300 290 295 300

Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr 305 310 315 320 305 310 315 320

Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu 325 330 335 325 330 335

Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys 340 345 350 340 345 350

Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile 355 360 365 355 360 365

Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp 370 375 380 370 375 380

Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr 385 390 395 400 385 390 395 400 Page 17 Page 17

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly 405 410 415 405 410 415

Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu 420 425 430 420 425 430

Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe 435 440 445 435 440 445

Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr 450 455 460 450 455 460

Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln 465 470 475 480 465 470 475 480

Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp 485 490 495 485 490 495

Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn 500 505 510 500 505 510

Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp 515 520 525 515 520 525

Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala 530 535 540 530 535 540

Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe 545 550 555 560 545 550 555 560

Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser 565 570 575 565 570 575

Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu 580 585 590 580 585 590

Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met 595 600 605 595 600 605

Page 18 Page 18

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp 610 615 620 610 615 620

Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys 625 630 635 640 625 630 635 640

Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu 645 650 655 645 650 655

Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys 660 665 670 660 665 670

Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala 675 680 685 675 680 685

Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro 690 695 700 690 695 700

Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu 705 710 715 720 705 710 715 720

Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp 725 730 735 725 730 735

Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu 740 745 750 740 745 750

Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe 755 760 765 755 760 765

Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu 770 775 780 770 775 780

Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met 785 790 795 800 785 790 795 800

Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro 805 810 815 805 810 815

Page 19 Page 19

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp 820 825 830 820 825 830

Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala 835 840 845 835 840 845

Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu 850 855 860 850 855 860

Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe 865 870 875 880 865 870 875 880

Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg 885 890 895 885 890 895

Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg 900 905 910 900 905 910

Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg 915 920 925 915 920 925

Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His 930 935 940 930 935 940

Thr Arg Lys Ser Thr Arg Lys Ser 945 945

<210> 5 <210> 5 <211> 946 <211> 946 <212> PRT <212> PRT <213> Homo sapiens <213> Homo sapiens

<400> 5 <400> 5

Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro Ala Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro Ala Pro 1 5 10 15 1 5 10 15

Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Leu Trp Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Leu Trp 20 25 30 20 25 30

Page 20 Page 20

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Gln His Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Gln His 35 40 45 35 40 45

Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Leu Ala Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Leu Ala 50 55 60 50 55 60

Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Pro Ser Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Pro Ser 65 70 75 80 70 75 80

Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Asn Asn Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Asn Asn 85 90 95 85 90 95

Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr His Tyr Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr His Tyr 100 105 110 100 105 110

Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala Gly Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala Gly 115 120 125 115 120 125

Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu Arg Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu Arg 130 135 140 130 135 140

Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Trp Asp Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Trp Asp 145 150 155 160 145 150 155 160

Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Arg Ala Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Arg Ala 165 170 175 165 170 175

Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His Phe Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His Phe 180 185 190 180 185 190

Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val Val Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val Val 195 200 205 195 200 205

Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg Gly Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg Gly 210 215 220 210 215 220

Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala His Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala His 225 230 235 240 225 230 235 240

Page 21 Page 21

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln Gly Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln Gly 245 250 255 245 250 255

Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg Arg Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg Arg 260 265 270 260 265 270

Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Val Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Val 275 280 285 275 280 285

Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Pro Glu Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Pro Glu 290 295 300 290 295 300

Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Glu Ser Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Glu Ser 305 310 315 320 305 310 315 320

Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Cys Phe Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Cys Phe 325 330 335 325 330 335

Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Arg Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Arg 340 345 350 340 345 350

Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Asp Leu Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Asp Leu 355 360 365 355 360 365

Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Val Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Val 370 375 380 370 375 380

Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Lys Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Lys 385 390 395 400 385 390 395 400

Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Val Asp Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Val Asp 405 410 415 405 410 415

Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp His Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp His 420 425 430 420 425 430

Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu Ser Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu Ser 435 440 445 435 440 445

Page 22 Page 22

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys 450 455 460 450 455 460

Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu 465 470 475 480 465 470 475 480

Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Tyr Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Tyr 485 490 495 485 490 495

Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Val Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Val Tyr 500 505 510 500 505 510

Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Gly Val Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Gly Val 515 520 525 515 520 525

Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Ile Gln Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Ile Gln 530 535 540 530 535 540

Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe Arg Phe Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe Arg Phe 545 550 555 560 545 550 555 560

Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Gln Val Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Gln Val 565 570 575 565 570 575

Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu Leu Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu Leu Val 580 585 590 580 585 590

Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met Ala Pro Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met Ala Pro 595 600 605 595 600 605

Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp Glu Asn Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp Glu Asn 610 615 620 610 615 620

Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys Phe Gln Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys Phe Gln 625 630 635 640 625 630 635 640

Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu Pro Tyr Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu Pro Tyr 645 650 655 645 650 655

Page 23 Page 23

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Ala His Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Ala His 660 665 670 660 665 670

Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala Gln Asn Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala Gln Asn 675 680 685 675 680 685

Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Ala Cys Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Ala Cys 690 695 700 690 695 700

Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu Glu Phe Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu Glu Phe 705 710 715 720 705 710 715 720

Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Tyr Pro Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Tyr Pro 725 730 735 725 730 735

Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu Leu Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu Leu Pro 740 745 750 740 745 750

Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe Asp Phe Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe Asp Phe 755 760 765 755 760 765

Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu Lys Glu Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu Lys Glu 770 775 780 770 775 780

Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Thr Asp Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Thr Asp 785 790 795 800 785 790 795 800

Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Trp Gly Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Trp Gly 805 810 815 805 810 815

Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp Leu Pro Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp Leu Pro 820 825 830 820 825 830

Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala Glu Asp Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala Glu Asp 835 840 845 835 840 845

Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu Ala Leu Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu Ala Leu 850 855 860 850 855 860

Page 24 Page 24

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe Ala Tyr Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe Ala Tyr 865 870 875 880 865 870 875 880

Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg Tyr Ala Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg Tyr Ala 885 890 895 885 890 895

Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Lys Ile Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Lys Ile 900 905 910 900 905 910

Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Phe Cys Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Phe Cys 915 920 925 915 920 925

Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His Thr Arg Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His Thr Arg 930 935 940 930 935 940

Lys Ser Lys Ser 945 945

<210> 6 <210> 6 <211> 851 <211> 851 <212> PRT <212> PRT <213> Homo sapiens <213> Homo sapiens

<400> 6 <400> 6

Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr His Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr His 1 5 10 15 1 5 10 15

Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala 20 25 30 20 25 30

Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu 35 40 45 35 40 45

Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Trp Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Trp 50 55 60 50 55 60

Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Arg Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Arg 65 70 75 80 70 75 80

Page 25 Page 25

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His 85 90 95 85 90 95

Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val 100 105 110 100 105 110

Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg 115 120 125 115 120 125

Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala 130 135 140 130 135 140

His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln 145 150 155 160 145 150 155 160

Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg 165 170 175 165 170 175

Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe 180 185 190 180 185 190

Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Pro Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Pro 195 200 205 195 200 205

Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Glu Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Glu 210 215 220 210 215 220

Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Cys Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Cys 225 230 235 240 225 230 235 240

Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe 245 250 255 245 250 255

Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Asp Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Asp 260 265 270 260 265 270

Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe 275 280 285 275 280 285

Page 26 Page 26

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu 290 295 300 290 295 300

Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Val Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Val 305 310 315 320 305 310 315 320

Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp 325 330 335 325 330 335

His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu 340 345 350 340 345 350

Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln 355 360 365 355 360 365

Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro 370 375 380 370 375 380

Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn 385 390 395 400 385 390 395 400

Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Val Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Val 405 410 415 405 410 415

Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Gly Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Gly 420 425 430 420 425 430

Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Ile Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Ile 435 440 445 435 440 445

Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe Arg Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe Arg 450 455 460 450 455 460

Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Gln Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Gln 465 470 475 480 465 470 475 480

Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu Leu Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu Leu 485 490 495 485 490 495

Page 27 Page 27

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met Ala Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met Ala 500 505 510 500 505 510

Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp Glu Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp Glu 515 520 525 515 520 525

Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys Phe Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys Phe 530 535 540 530 535 540

Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu Pro Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu Pro 545 550 555 560 545 550 555 560

Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Ala Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Ala 565 570 575 565 570 575

His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala Gln His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala Gln 580 585 590 580 585 590

Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Ala Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Ala 595 600 605 595 600 605

Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu Glu Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu Glu 610 615 620 610 615 620

Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Tyr Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Tyr 625 630 635 640 625 630 635 640

Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu Leu Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu Leu 645 650 655 645 650 655

Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe Asp Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe Asp 660 665 670 660 665 670

Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu Lys Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu Lys 675 680 685 675 680 685

Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Thr Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Thr 690 695 700 690 695 700

Page 28 Page 28

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing TXT Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Trp Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Trp 705 710 715 720 705 710 715 720

Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp Leu Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp Leu 725 730 735 725 730 735

Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala Glu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala Glu 740 745 750 740 745 750

Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu Ala Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu Ala 755 760 765 755 760 765

Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe Ala 770 775 780 770 775 780

Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg Tyr Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg Tyr 785 790 795 800 785 790 795 800

Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Lys Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Lys 805 810 815 805 810 815

Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Phe Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Phe 820 825 830 820 825 830

Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His Thr Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His Thr 835 840 845 835 840 845

Arg Lys Ser Arg Lys Ser 850 850

<210> 7 <210> 7 <211> 549 <211> 549 <212> PRT <212> PRT <213> Homo sapiens <213> Homo sapiens

<400> 7 <400> 7

Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser 1 5 10 15 1 5 10 15

Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg Page 29 Page 29

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing TXT 20 25 30 20 25 30

Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro 35 40 45 35 40 45

Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly 50 55 60 50 55 60

Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp 65 70 75 80 70 75 80

Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His 85 90 95 85 90 95

Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly 100 105 110 100 105 110

Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser 115 120 125 115 120 125

Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val 130 135 140 130 135 140

Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly 145 150 155 160 145 150 155 160

Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu 165 170 175 165 170 175

Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr 180 185 190 180 185 190

His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala 195 200 205 195 200 205

Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe 210 215 220 210 215 220

Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Page 30 Page 30

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 225 230 235 240 225 230 235 240

Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly 245 250 255 245 250 255

Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu 260 265 270 260 265 270

Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro 275 280 285 275 280 285

Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn 290 295 300 290 295 300

Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu 305 310 315 320 305 310 315 320

Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp 325 330 335 325 330 335

Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe 340 345 350 340 345 350

Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala 355 360 365 355 360 365

Leu Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Leu Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met 370 375 380 370 375 380

Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp 385 390 395 400 385 390 395 400

Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly 405 410 415 405 410 415

Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr 420 425 430 420 425 430

Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Page 31 Page 31

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 435 440 445 435 440 445

Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe 450 455 460 450 455 460

Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp 465 470 475 480 465 470 475 480

Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe 485 490 495 485 490 495

Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn 500 505 510 500 505 510

Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val 515 520 525 515 520 525

Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu 530 535 540 530 535 540

Asn Val Tyr Leu Trp Asn Val Tyr Leu Trp 545 545

<210> 8 <210> 8 <211> 521 <211> 521 <212> PRT <212> PRT <213> Homo sapiens <213> Homo sapiens

<400> 8 <400> 8

Arg Arg Leu Arg Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Arg Arg Leu Arg Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg 1 5 10 15 1 5 10 15

Phe Ser Arg Pro Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Ser Arg Pro Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr 20 25 30 20 25 30

Phe Pro Asp Gly Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Phe Pro Asp Gly Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr 35 40 45 35 40 45

Glu Gly Gly Trp Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Glu Gly Gly Trp Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr 50 55 60 50 55 60 Page 32 Page 32

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Phe Thr His His Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Phe Thr His His Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser 65 70 75 80 70 75 80

Leu Pro Leu Gly Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Leu Pro Leu Gly Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val 85 90 95 85 90 95

Ala Ser Asp Ser Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Ala Ser Asp Ser Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg 100 105 110 100 105 110

Glu Leu Gly Val Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Glu Leu Gly Val Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val 115 120 125 115 120 125

Leu Pro Asn Gly Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Leu Pro Asn Gly Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr 130 135 140 130 135 140

Tyr Arg Arg Leu Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Tyr Arg Arg Leu Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val 145 150 155 160 145 150 155 160

Val Thr Leu Tyr His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Val Thr Leu Tyr His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr 165 170 175 165 170 175

Gly Gly Trp Ala Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Gly Gly Trp Ala Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala 180 185 190 180 185 190

Glu Leu Cys Phe Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Glu Leu Cys Phe Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr 195 200 205 195 200 205

Ile Asp Asn Pro Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Ile Asp Asn Pro Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg 210 215 220 210 215 220

Leu Ala Pro Gly Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala Leu Ala Pro Gly Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala 225 230 235 240 225 230 235 240

His Asn Leu Leu Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr His Asn Leu Leu Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr 245 250 255 245 250 255

Ser Phe Arg Pro Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser Ser Phe Arg Pro Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser 260 265 270 260 265 270 Page 33 Page 33

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

His Trp Ile Asn Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys His Trp Ile Asn Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys 275 280 285 275 280 285

Gln Lys Ser Leu Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Gln Lys Ser Leu Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe 290 295 300 290 295 300

Ile Asp Gly Asp Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Ile Asp Gly Asp Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile 305 310 315 320 305 310 315 320

Leu Pro Asp Phe Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Leu Pro Asp Phe Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala 325 330 335 325 330 335

Asp Phe Phe Ala Leu Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Phe Phe Ala Leu Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu 340 345 350 340 345 350

Asp Pro His Met Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Asp Pro His Met Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln 355 360 365 355 360 365

Leu Leu Ser Trp Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Leu Leu Ser Trp Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile 370 375 380 370 375 380

Val Glu Asn Gly Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Val Glu Asn Gly Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala 385 390 395 400 385 390 395 400

Lys Tyr Met Tyr Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Lys Tyr Met Tyr Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala 405 410 415 405 410 415

Ile Lys Leu Asp Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Ile Lys Leu Asp Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu 420 425 430 420 425 430

Met Asp Gly Phe Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Met Asp Gly Phe Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu 435 440 445 435 440 445

Phe Tyr Val Asp Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Phe Tyr Val Asp Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser 450 455 460 450 455 460

Ser Ala Leu Phe Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Ser Ala Leu Phe Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro 465 470 475 480 465 470 475 480 Page 34 Page 34

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Leu Pro Glu Asn Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Leu Pro Glu Asn Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala 485 490 495 485 490 495

Trp Gly Val Val Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Trp Gly Val Val Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln 500 505 510 500 505 510

Phe Thr Asp Leu Asn Val Tyr Leu Trp Phe Thr Asp Leu Asn Val Tyr Leu Trp 515 520 515 520

<210> 9 <210> 9 <211> 516 <211> 516 <212> PRT <212> PRT <213> Homo sapiens <213> Homo sapiens

<400> 9 <400> 9

Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro 1 5 10 15 1 5 10 15

Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe 20 25 30 20 25 30

Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln 35 40 45 35 40 45

Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro 50 55 60 50 55 60

Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala 65 70 75 80 70 75 80

Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr 85 90 95 85 90 95

Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr 100 105 110 100 105 110

His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser 115 120 125 115 120 125

Page 35 Page 35

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu 130 135 140 130 135 140

Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His 145 150 155 160 145 150 155 160

Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn 165 170 175 165 170 175

Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg 180 185 190 180 185 190

His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr 195 200 205 195 200 205

Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile 210 215 220 210 215 220

Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu 225 230 235 240 225 230 235 240

Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr 245 250 255 245 250 255

Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro 260 265 270 260 265 270

Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp 275 280 285 275 280 285

Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr 290 295 300 290 295 300

Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr 305 310 315 320 305 310 315 320

Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu 325 330 335 325 330 335

Page 36 Page 36

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing TXT

Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys 340 345 350 340 345 350

Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile 355 360 365 355 360 365

Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp 370 375 380 370 375 380

Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr 385 390 395 400 385 390 395 400

Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly 405 410 415 405 410 415

Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu 420 425 430 420 425 430

Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe 435 440 445 435 440 445

Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr 450 455 460 450 455 460

Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln 465 470 475 480 465 470 475 480

Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp 485 490 495 485 490 495

Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn 500 505 510 500 505 510

Val Tyr Leu Trp Val Tyr Leu Trp 515 515

<210> 10 <210> 10 <211> 514 <211> 514 <212> PRT <212> PRT Page 37 Page 37

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT <213> Homo sapiens <213> Homo sapiens

<400> 10 <400> 10

Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro Ala Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro Ala Pro 1 5 10 15 1 5 10 15

Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Leu Trp Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Leu Trp 20 25 30 20 25 30

Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Gln His Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Gln His 35 40 45 35 40 45

Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Leu Ala Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Leu Ala 50 55 60 50 55 60

Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Pro Ser Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Pro Ser 65 70 75 80 70 75 80

Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Asn Asn Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Asn Asn 85 90 95 85 90 95

Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr His Tyr Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr His Tyr 100 105 110 100 105 110

Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala Gly Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala Gly 115 120 125 115 120 125

Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu Arg Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu Arg 130 135 140 130 135 140

Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Trp Asp Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Trp Asp 145 150 155 160 145 150 155 160

Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Arg Ala Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Arg Ala 165 170 175 165 170 175

Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His Phe Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His Phe 180 185 190 180 185 190

Page 38 Page 38

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val Val Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val Val 195 200 205 195 200 205

Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg Gly Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg Gly 210 215 220 210 215 220

Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala His Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala His 225 230 235 240 225 230 235 240

Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln Gly Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln Gly 245 250 255 245 250 255

Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg Arg Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg Arg 260 265 270 260 265 270

Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Val Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Val 275 280 285 275 280 285

Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Pro Glu Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Pro Glu 290 295 300 290 295 300

Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Glu Ser Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Glu Ser 305 310 315 320 305 310 315 320

Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Cys Phe Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Cys Phe 325 330 335 325 330 335

Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Arg Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Arg 340 345 350 340 345 350

Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Asp Leu Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Asp Leu 355 360 365 355 360 365

Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Val Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Val 370 375 380 370 375 380

Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Lys Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Lys 385 390 395 400 385 390 395 400

Page 39 Page 39

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Val Asp Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Val Asp 405 410 415 405 410 415

Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp His Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp His 420 425 430 420 425 430

Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu Ser Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu Ser 435 440 445 435 440 445

Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys 450 455 460 450 455 460

Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu 465 470 475 480 465 470 475 480

Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Tyr Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Tyr 485 490 495 485 490 495

Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Val Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Val Tyr 500 505 510 500 505 510

Leu Trp Leu Trp

<210> 11 <210> 11 <211> 419 <211> 419 <212> PRT <212> PRT <213> Homo sapiens <213> Homo sapiens

<400> 11 <400> 11

Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr His Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr His 1 5 10 15 1 5 10 15

Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala 20 25 30 20 25 30

Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu 35 40 45 35 40 45

Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Trp Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Trp Page 40 Page 40

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 50 55 60 50 55 60

Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Arg Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Arg 65 70 75 80 70 75 80

Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His 85 90 95 85 90 95

Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val 100 105 110 100 105 110

Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg 115 120 125 115 120 125

Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala 130 135 140 130 135 140

His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln 145 150 155 160 145 150 155 160

Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg 165 170 175 165 170 175

Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe 180 185 190 180 185 190

Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Pro Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Pro 195 200 205 195 200 205

Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Glu Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Glu 210 215 220 210 215 220

Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Cys Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Cys 225 230 235 240 225 230 235 240

Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe 245 250 255 245 250 255

Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Asp Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Asp Page 41 Page 41

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing TXT 260 265 270 260 265 270

Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe 275 280 285 275 280 285

Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu 290 295 300 290 295 300

Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Val Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Val 305 310 315 320 305 310 315 320

Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp 325 330 335 325 330 335

His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu 340 345 350 340 345 350

Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln 355 360 365 355 360 365

Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro 370 375 380 370 375 380

Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn 385 390 395 400 385 390 395 400

Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Val Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Val 405 410 415 405 410 415

Tyr Leu Trp Tyr Leu Trp

<210> 12 <210> 12 <211> 981 <211> 981 <212> PRT <212> PRT <213> Homo sapiens <213> Homo sapiens

<400> 12 <400> 12

Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser 1 5 10 15 1 5 10 15 Page 42 Page 42

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg 20 25 30 20 25 30

Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro 35 40 45 35 40 45

Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly 50 55 60 50 55 60

Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp 65 70 75 80 70 75 80

Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His 85 90 95 85 90 95

Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly 100 105 110 100 105 110

Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser 115 120 125 115 120 125

Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val 130 135 140 130 135 140

Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly 145 150 155 160 145 150 155 160

Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu 165 170 175 165 170 175

Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr 180 185 190 180 185 190

His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala 195 200 205 195 200 205

Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe 210 215 220 210 215 220 Page 43 Page 43

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro 225 230 235 240 225 230 235 240

Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly 245 250 255 245 250 255

Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu 260 265 270 260 265 270

Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro 275 280 285 275 280 285

Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn 290 295 300 290 295 300

Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu 305 310 315 320 305 310 315 320

Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp 325 330 335 325 330 335

Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe 340 345 350 340 345 350

Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala 355 360 365 355 360 365

Leu Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Leu Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met 370 375 380 370 375 380

Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp 385 390 395 400 385 390 395 400

Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly 405 410 415 405 410 415

Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr 420 425 430 420 425 430 Page 44 Page 44

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp 435 440 445 435 440 445

Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe 450 455 460 450 455 460

Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp 465 470 475 480 465 470 475 480

Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe 485 490 495 485 490 495

Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn 500 505 510 500 505 510

Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val 515 520 525 515 520 525

Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu 530 535 540 530 535 540

Asn Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asn Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val 545 550 555 560 545 550 555 560

Asp Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Asp Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala 565 570 575 565 570 575

Ala Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Ala Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His 580 585 590 580 585 590

Phe Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Phe Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln 595 600 605 595 600 605

Ser Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Ser Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser 610 615 620 610 615 620

Glu Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Glu Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro 625 630 635 640 625 630 635 640 Page 45 Page 45

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Met Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Met Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala 645 650 655 645 650 655

Trp Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Trp Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu 660 665 670 660 665 670

Cys Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Cys Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn 675 680 685 675 680 685

Glu Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Glu Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu 690 695 700 690 695 700

Lys Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Lys Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His 705 710 715 720 705 710 715 720

Ala Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Ala Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu 725 730 735 725 730 735

Pro Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Pro Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val 740 745 750 740 745 750

Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly 755 760 765 755 760 765

Asp Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Asp Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe 770 775 780 770 775 780

Leu Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Leu Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr 785 790 795 800 785 790 795 800

Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser 805 810 815 805 810 815

Glu Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Glu Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu 820 825 830 820 825 830

Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val 835 840 845 835 840 845 Page 46 Page 46

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly 850 855 860 850 855 860

Asp Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Asp Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His 865 870 875 880 865 870 875 880

Ala Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Ala Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn 885 890 895 885 890 895

Glu Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Glu Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr 900 905 910 900 905 910

Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr 915 920 925 915 920 925

Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr 930 935 940 930 935 940

Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu 945 950 955 960 945 950 955 960

Arg Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe Arg Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe 965 970 975 965 970 975

His Thr Arg Lys Ser His Thr Arg Lys Ser 980 980

<210> 13 <210> 13 <211> 953 <211> 953 <212> PRT <212> PRT <213> Homo sapiens <213> Homo sapiens

<400> 13 <400> 13

Arg Arg Leu Arg Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Arg Arg Leu Arg Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg 1 5 10 15 1 5 10 15

Phe Ser Arg Pro Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Ser Arg Pro Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr 20 25 30 20 25 30

Page 47 Page 47

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Phe Pro Asp Gly Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Phe Pro Asp Gly Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr 35 40 45 35 40 45

Glu Gly Gly Trp Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Glu Gly Gly Trp Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr 50 55 60 50 55 60

Phe Thr His His Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Phe Thr His His Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser 65 70 75 80 70 75 80

Leu Pro Leu Gly Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Leu Pro Leu Gly Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val 85 90 95 85 90 95

Ala Ser Asp Ser Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Ala Ser Asp Ser Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg 100 105 110 100 105 110

Glu Leu Gly Val Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Glu Leu Gly Val Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val 115 120 125 115 120 125

Leu Pro Asn Gly Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Leu Pro Asn Gly Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr 130 135 140 130 135 140

Tyr Arg Arg Leu Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Tyr Arg Arg Leu Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val 145 150 155 160 145 150 155 160

Val Thr Leu Tyr His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Val Thr Leu Tyr His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr 165 170 175 165 170 175

Gly Gly Trp Ala Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Gly Gly Trp Ala Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala 180 185 190 180 185 190

Glu Leu Cys Phe Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Glu Leu Cys Phe Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr 195 200 205 195 200 205

Ile Asp Asn Pro Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Ile Asp Asn Pro Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg 210 215 220 210 215 220

Leu Ala Pro Gly Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala Leu Ala Pro Gly Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala 225 230 235 240 225 230 235 240

Page 48 Page 48

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

His Asn Leu Leu Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr His Asn Leu Leu Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr 245 250 255 245 250 255

Ser Phe Arg Pro Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser Ser Phe Arg Pro Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser 260 265 270 260 265 270

His Trp Ile Asn Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys His Trp Ile Asn Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys 275 280 285 275 280 285

Gln Lys Ser Leu Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Gln Lys Ser Leu Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe 290 295 300 290 295 300

Ile Asp Gly Asp Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Ile Asp Gly Asp Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile 305 310 315 320 305 310 315 320

Leu Pro Asp Phe Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Leu Pro Asp Phe Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala 325 330 335 325 330 335

Asp Phe Phe Ala Leu Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Phe Phe Ala Leu Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu 340 345 350 340 345 350

Asp Pro His Met Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Asp Pro His Met Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln 355 360 365 355 360 365

Leu Leu Ser Trp Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Leu Leu Ser Trp Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile 370 375 380 370 375 380

Val Glu Asn Gly Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Val Glu Asn Gly Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala 385 390 395 400 385 390 395 400

Lys Tyr Met Tyr Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Lys Tyr Met Tyr Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala 405 410 415 405 410 415

Ile Lys Leu Asp Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Ile Lys Leu Asp Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu 420 425 430 420 425 430

Met Asp Gly Phe Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Met Asp Gly Phe Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu 435 440 445 435 440 445

Page 49 Page 49

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. - TXT

Phe Tyr Val Asp Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Phe Tyr Val Asp Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser 450 455 460 450 455 460

Ser Ala Leu Phe Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Ser Ala Leu Phe Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro 465 470 475 480 465 470 475 480

Leu Pro Glu Asn Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Leu Pro Glu Asn Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala 485 490 495 485 490 495

Trp Gly Val Val Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Trp Gly Val Val Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln 500 505 510 500 505 510

Phe Thr Asp Leu Asn Val Tyr Leu Trp Asp Val His His Ser Lys Arg Phe Thr Asp Leu Asn Val Tyr Leu Trp Asp Val His His Ser Lys Arg 515 520 525 515 520 525

Leu Ile Lys Val Asp Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Leu Ile Lys Val Asp Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys 530 535 540 530 535 540

Val Asp Phe Ala Ala Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met Val Asp Phe Ala Ala Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met 545 550 555 560 545 550 555 560

His Val Thr His Phe Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro His Val Thr His Phe Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro 565 570 575 565 570 575

Leu Gly Asn Gln Ser Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Leu Gly Asn Gln Ser Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg 580 585 590 580 585 590

Cys Met Ala Ser Glu Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Cys Met Ala Ser Glu Leu Val Arg Val Asn Ile Thr Pro Val Val Ala 595 600 605 595 600 605

Leu Trp Gln Pro Met Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Leu Trp Gln Pro Met Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala 610 615 620 610 615 620

Arg Gln Gly Ala Trp Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Arg Gln Gly Ala Trp Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu 625 630 635 640 625 630 635 640

Tyr Ala Arg Leu Cys Phe Gln Glu Leu Gly His His Val Lys Leu Trp Tyr Ala Arg Leu Cys Phe Gln Glu Leu Gly His His Val Lys Leu Trp 645 650 655 645 650 655

Page 50 Page 50

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Ile Thr Met Asn Glu Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly Ile Thr Met Asn Glu Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly 660 665 670 660 665 670

His Asn Leu Leu Lys Ala His Ala Leu Ala Trp His Val Tyr Asn Glu His Asn Leu Leu Lys Ala His Ala Leu Ala Trp His Val Tyr Asn Glu 675 680 685 675 680 685

Lys Phe Arg His Ala Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Lys Phe Arg His Ala Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala 690 695 700 690 695 700

Asp Trp Ile Glu Pro Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Asp Trp Ile Glu Pro Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val 705 710 715 720 705 710 715 720

Ala Glu Arg Val Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Ala Glu Arg Val Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile 725 730 735 725 730 735

Phe Gly Ser Gly Asp Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Phe Gly Ser Gly Asp Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln 740 745 750 740 745 750

Arg Asn Asn Phe Leu Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Arg Asn Asn Phe Leu Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu 755 760 765 755 760 765

Ile Gln Gly Thr Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Ile Gln Gly Thr Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile 770 775 780 770 775 780

Leu Val Asp Ser Glu Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Leu Val Asp Ser Glu Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu 785 790 795 800 785 790 795 800

Glu Val Gln Glu Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Glu Val Gln Glu Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln 805 810 815 805 810 815

Val Ala Val Val Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Val Ala Val Val Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys 820 825 830 820 825 830

Phe Lys Tyr Gly Asp Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Phe Lys Tyr Gly Asp Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp 835 840 845 835 840 845

Asp Gly Leu His Ala Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asp Gly Leu His Ala Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln 850 855 860 850 855 860

Page 51 Page 51

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Asn Tyr Ile Asn Glu Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Asn Tyr Ile Asn Glu Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn 865 870 875 880 865 870 875 880

Leu Cys Gly Tyr Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Leu Cys Gly Tyr Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg 885 890 895 885 890 895

Phe Gly Leu Tyr Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Phe Gly Leu Tyr Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser 900 905 910 900 905 910

Met Lys His Tyr Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Met Lys His Tyr Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro 915 920 925 915 920 925

Glu Thr Leu Glu Arg Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Glu Thr Leu Glu Arg Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu 930 935 940 930 935 940

Cys Ser Phe Phe His Thr Arg Lys Ser Cys Ser Phe Phe His Thr Arg Lys Ser 945 950 945 950

<210> 14 <210> 14 <211> 948 <211> 948 <212> PRT <212> PRT <213> Homo sapiens <213> Homo sapiens

<400> 14 <400> 14

Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro 1 5 10 15 1 5 10 15

Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe 20 25 30 20 25 30

Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln 35 40 45 35 40 45

Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro 50 55 60 50 55 60

Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala 65 70 75 80 70 75 80

Page 52 Page 52

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr 85 90 95 85 90 95

Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr 100 105 110 100 105 110

His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser 115 120 125 115 120 125

Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu 130 135 140 130 135 140

Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His 145 150 155 160 145 150 155 160

Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn 165 170 175 165 170 175

Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg 180 185 190 180 185 190

His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr 195 200 205 195 200 205

Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile 210 215 220 210 215 220

Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu 225 230 235 240 225 230 235 240

Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr 245 250 255 245 250 255

Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro 260 265 270 260 265 270

Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp 275 280 285 275 280 285

Page 53 Page 53

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr 290 295 300 290 295 300

Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr 305 310 315 320 305 310 315 320

Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu 325 330 335 325 330 335

Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys 340 345 350 340 345 350

Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile 355 360 365 355 360 365

Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp 370 375 380 370 375 380

Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr 385 390 395 400 385 390 395 400

Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly 405 410 415 405 410 415

Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu 420 425 430 420 425 430

Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe 435 440 445 435 440 445

Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr 450 455 460 450 455 460

Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln 465 470 475 480 465 470 475 480

Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp 485 490 495 485 490 495

Page 54 Page 54

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn 500 505 510 500 505 510

Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp 515 520 525 515 520 525

Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala 530 535 540 530 535 540

Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe 545 550 555 560 545 550 555 560

Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser 565 570 575 565 570 575

Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu 580 585 590 580 585 590

Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met 595 600 605 595 600 605

Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp 610 615 620 610 615 620

Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys 625 630 635 640 625 630 635 640

Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu 645 650 655 645 650 655

Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys 660 665 670 660 665 670

Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala 675 680 685 675 680 685

Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro 690 695 700 690 695 700

Page 55 Page 55

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing TXT Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu 705 710 715 720 705 710 715 720

Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp 725 730 735 725 730 735

Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu 740 745 750 740 745 750

Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe 755 760 765 755 760 765

Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu 770 775 780 770 775 780

Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met 785 790 795 800 785 790 795 800

Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro 805 810 815 805 810 815

Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp 820 825 830 820 825 830

Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala 835 840 845 835 840 845

Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu 850 855 860 850 855 860

Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe 865 870 875 880 865 870 875 880

Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg 885 890 895 885 890 895

Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg 900 905 910 900 905 910

Page 56 Page 56

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg 915 920 925 915 920 925

Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His 930 935 940 930 935 940

Thr Arg Lys Ser Thr Arg Lys Ser 945 945

<210> 15 <210> 15 <211> 946 <211> 946 <212> PRT <212> PRT <213> Homo sapiens <213> Homo sapiens

<400> 15 <400> 15

Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro Ala Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro Ala Pro 1 5 10 15 1 5 10 15

Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Leu Trp Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Leu Trp 20 25 30 20 25 30

Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Gln His Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Gln His 35 40 45 35 40 45

Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Leu Ala Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Leu Ala 50 55 60 50 55 60

Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Pro Ser Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Pro Ser 65 70 75 80 70 75 80

Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Asn Asn Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Asn Asn 85 90 95 85 90 95

Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr His Tyr Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr His Tyr 100 105 110 100 105 110

Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala Gly Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala Gly 115 120 125 115 120 125

Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu Arg Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu Arg Page 57 Page 57

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 130 135 140 130 135 140

Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Trp Asp Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Trp Asp 145 150 155 160 145 150 155 160

Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Arg Ala Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Arg Ala 165 170 175 165 170 175

Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His Phe Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His Phe 180 185 190 180 185 190

Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val Val Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val Val 195 200 205 195 200 205

Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg Gly Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg Gly 210 215 220 210 215 220

Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala His Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala His 225 230 235 240 225 230 235 240

Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln Gly Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln Gly 245 250 255 245 250 255

Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg Arg Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg Arg 260 265 270 260 265 270

Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Val Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Val 275 280 285 275 280 285

Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Pro Glu Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Pro Glu 290 295 300 290 295 300

Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Glu Ser Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Glu Ser 305 310 315 320 305 310 315 320

Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Ser Phe Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Ser Phe 325 330 335 325 330 335

Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Arg Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Arg Page 58 Page 58

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 340 345 350 340 345 350

Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Asp Leu Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Asp Leu 355 360 365 355 360 365

Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Val Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Val 370 375 380 370 375 380

Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Lys Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Lys 385 390 395 400 385 390 395 400

Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Val Asp Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Val Asp 405 410 415 405 410 415

Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp His Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp His 420 425 430 420 425 430

Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu Ser Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu Ser 435 440 445 435 440 445

Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys 450 455 460 450 455 460

Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu 465 470 475 480 465 470 475 480

Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Tyr Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Tyr 485 490 495 485 490 495

Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Val Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Val Tyr 500 505 510 500 505 510

Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Gly Val Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Gly Val 515 520 525 515 520 525

Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Ile Gln Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Ile Gln 530 535 540 530 535 540

Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe Arg Phe Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe Arg Phe Page 59 Page 59

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing TXT 545 550 555 560 545 550 555 560

Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Gln Val Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Gln Val 565 570 575 565 570 575

Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu Leu Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu Leu Val 580 585 590 580 585 590

Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met Ala Pro Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met Ala Pro 595 600 605 595 600 605

Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp Glu Asn Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp Glu Asn 610 615 620 610 615 620

Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys Phe Gln Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys Phe Gln 625 630 635 640 625 630 635 640

Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu Pro Tyr Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu Pro Tyr 645 650 655 645 650 655

Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Ala His Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Ala His 660 665 670 660 665 670

Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala Gln Asn Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala Gln Asn 675 680 685 675 680 685

Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Ala Cys Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Ala Cys 690 695 700 690 695 700

Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu Glu Phe Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu Glu Phe 705 710 715 720 705 710 715 720

Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Tyr Pro Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Tyr Pro 725 730 735 725 730 735

Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu Leu Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu Leu Pro 740 745 750 740 745 750

Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe Asp Phe Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe Asp Phe Page 60 Page 60

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 755 760 765 755 760 765

Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu Lys Glu Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu Lys Glu 770 775 780 770 775 780

Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Thr Asp Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Thr Asp 785 790 795 800 785 790 795 800

Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Trp Gly Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Trp Gly 805 810 815 805 810 815

Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp Leu Pro Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp Leu Pro 820 825 830 820 825 830

Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala Glu Asp Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala Glu Asp 835 840 845 835 840 845

Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu Ala Leu Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu Ala Leu 850 855 860 850 855 860

Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe Ala Tyr Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe Ala Tyr 865 870 875 880 865 870 875 880

Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg Tyr Ala Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg Tyr Ala 885 890 895 885 890 895

Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Lys Ile Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Lys Ile 900 905 910 900 905 910

Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Phe Cys Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Phe Cys 915 920 925 915 920 925

Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His Thr Arg Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His Thr Arg 930 935 940 930 935 940

Lys Ser Lys Ser 945 945

<210> 16 <210> 16 Page 61 Page 61

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT <211> 851 <211> 851 <212> PRT <212> PRT <213> Homo sapiens <213> Homo sapiens

<400> 16 <400> 16

Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr His Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr His 1 5 10 15 1 5 10 15

Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala 20 25 30 20 25 30

Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu 35 40 45 35 40 45

Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Trp Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Trp 50 55 60 50 55 60

Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Arg Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Arg 65 70 75 80 70 75 80

Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His 85 90 95 85 90 95

Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val 100 105 110 100 105 110

Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg 115 120 125 115 120 125

Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala 130 135 140 130 135 140

His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln 145 150 155 160 145 150 155 160

Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg 165 170 175 165 170 175

Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe 180 185 190 180 185 190 Page 62 Page 62

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Pro Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Pro 195 200 205 195 200 205

Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Glu Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Glu 210 215 220 210 215 220

Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Ser Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Ser 225 230 235 240 225 230 235 240

Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe 245 250 255 245 250 255

Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Asp Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Asp 260 265 270 260 265 270

Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe 275 280 285 275 280 285

Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu 290 295 300 290 295 300

Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Val Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Val 305 310 315 320 305 310 315 320

Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp 325 330 335 325 330 335

His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu 340 345 350 340 345 350

Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln 355 360 365 355 360 365

Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro 370 375 380 370 375 380

Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn 385 390 395 400 385 390 395 400 Page 63 Page 63

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Val Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Val 405 410 415 405 410 415

Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Gly Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Gly 420 425 430 420 425 430

Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Ile Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Ile 435 440 445 435 440 445

Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe Arg Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe Arg 450 455 460 450 455 460

Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Gln Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Gln 465 470 475 480 465 470 475 480

Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu Leu Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu Leu 485 490 495 485 490 495

Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met Ala Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met Ala 500 505 510 500 505 510

Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp Glu Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp Glu 515 520 525 515 520 525

Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys Phe Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys Phe 530 535 540 530 535 540

Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu Pro Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu Pro 545 550 555 560 545 550 555 560

Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Ala Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Ala 565 570 575 565 570 575

His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala Gln His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala Gln 580 585 590 580 585 590

Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Ala Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Ala 595 600 605 595 600 605 Page 64 Page 64

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu Glu Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu Glu 610 615 620 610 615 620

Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Tyr Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Tyr 625 630 635 640 625 630 635 640

Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu Leu Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu Leu 645 650 655 645 650 655

Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe Asp Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe Asp 660 665 670 660 665 670

Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu Lys Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu Lys 675 680 685 675 680 685

Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Thr Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Thr 690 695 700 690 695 700

Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Trp Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Trp 705 710 715 720 705 710 715 720

Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp Leu Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp Leu 725 730 735 725 730 735

Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala Glu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala Glu 740 745 750 740 745 750

Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu Ala Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu Ala 755 760 765 755 760 765

Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe Ala 770 775 780 770 775 780

Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg Tyr Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg Tyr 785 790 795 800 785 790 795 800

Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Lys Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Lys 805 810 815 805 810 815 Page 65 Page 65

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Phe Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Phe 820 825 830 820 825 830

Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His Thr Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His Thr 835 840 845 835 840 845

Arg Lys Ser Arg Lys Ser 850 850

<210> 17 <210> 17 <211> 549 <211> 549 <212> PRT <212> PRT <213> Homo sapiens <213> Homo sapiens

<400> 17 <400> 17

Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser 1 5 10 15 1 5 10 15

Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg 20 25 30 20 25 30

Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro 35 40 45 35 40 45

Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly 50 55 60 50 55 60

Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp 65 70 75 80 70 75 80

Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His 85 90 95 85 90 95

Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly 100 105 110 100 105 110

Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser 115 120 125 115 120 125

Page 66 Page 66

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val 130 135 140 130 135 140

Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly 145 150 155 160 145 150 155 160

Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu 165 170 175 165 170 175

Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr 180 185 190 180 185 190

His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala 195 200 205 195 200 205

Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe 210 215 220 210 215 220

Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro 225 230 235 240 225 230 235 240

Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly 245 250 255 245 250 255

Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu 260 265 270 260 265 270

Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro 275 280 285 275 280 285

Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn 290 295 300 290 295 300

Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu 305 310 315 320 305 310 315 320

Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp 325 330 335 325 330 335

Page 67 Page 67

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe 340 345 350 340 345 350

Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala 355 360 365 355 360 365

Leu Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Leu Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met 370 375 380 370 375 380

Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp 385 390 395 400 385 390 395 400

Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly 405 410 415 405 410 415

Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr 420 425 430 420 425 430

Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp 435 440 445 435 440 445

Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe 450 455 460 450 455 460

Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp 465 470 475 480 465 470 475 480

Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe 485 490 495 485 490 495

Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn 500 505 510 500 505 510

Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val 515 520 525 515 520 525

Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu 530 535 540 530 535 540

Page 68 Page 68

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Asn Val Tyr Leu Trp Asn Val Tyr Leu Trp 545 545

<210> 18 <210> 18 <211> 521 <211> 521 <212> PRT <212> PRT <213> Homo sapiens <213> Homo sapiens

<400> 18 <400> 18

Arg Arg Leu Arg Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Arg Arg Leu Arg Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg 1 5 10 15 1 5 10 15

Phe Ser Arg Pro Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Ser Arg Pro Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr 20 25 30 20 25 30

Phe Pro Asp Gly Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Phe Pro Asp Gly Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr 35 40 45 35 40 45

Glu Gly Gly Trp Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Glu Gly Gly Trp Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr 50 55 60 50 55 60

Phe Thr His His Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Phe Thr His His Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser 65 70 75 80 70 75 80

Leu Pro Leu Gly Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Leu Pro Leu Gly Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val 85 90 95 85 90 95

Ala Ser Asp Ser Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Ala Ser Asp Ser Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg 100 105 110 100 105 110

Glu Leu Gly Val Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Glu Leu Gly Val Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val 115 120 125 115 120 125

Leu Pro Asn Gly Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Leu Pro Asn Gly Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr 130 135 140 130 135 140

Tyr Arg Arg Leu Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Tyr Arg Arg Leu Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val 145 150 155 160 145 150 155 160

Page 69 Page 69

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Val Thr Leu Tyr His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Val Thr Leu Tyr His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr 165 170 175 165 170 175

Gly Gly Trp Ala Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Gly Gly Trp Ala Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala 180 185 190 180 185 190

Glu Leu Cys Phe Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Glu Leu Cys Phe Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr 195 200 205 195 200 205

Ile Asp Asn Pro Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Ile Asp Asn Pro Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg 210 215 220 210 215 220

Leu Ala Pro Gly Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala Leu Ala Pro Gly Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala 225 230 235 240 225 230 235 240

His Asn Leu Leu Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr His Asn Leu Leu Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr 245 250 255 245 250 255

Ser Phe Arg Pro Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser Ser Phe Arg Pro Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser 260 265 270 260 265 270

His Trp Ile Asn Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys His Trp Ile Asn Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys 275 280 285 275 280 285

Gln Lys Ser Leu Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Gln Lys Ser Leu Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe 290 295 300 290 295 300

Ile Asp Gly Asp Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Ile Asp Gly Asp Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile 305 310 315 320 305 310 315 320

Leu Pro Asp Phe Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Leu Pro Asp Phe Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala 325 330 335 325 330 335

Asp Phe Phe Ala Leu Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Phe Phe Ala Leu Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu 340 345 350 340 345 350

Asp Pro His Met Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Asp Pro His Met Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln 355 360 365 355 360 365

Page 70 Page 70

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing TXT Leu Leu Ser Trp Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Leu Leu Ser Trp Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile 370 375 380 370 375 380

Val Glu Asn Gly Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Val Glu Asn Gly Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala 385 390 395 400 385 390 395 400

Lys Tyr Met Tyr Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Lys Tyr Met Tyr Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala 405 410 415 405 410 415

Ile Lys Leu Asp Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Ile Lys Leu Asp Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu 420 425 430 420 425 430

Met Asp Gly Phe Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Met Asp Gly Phe Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu 435 440 445 435 440 445

Phe Tyr Val Asp Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Phe Tyr Val Asp Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser 450 455 460 450 455 460

Ser Ala Leu Phe Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Ser Ala Leu Phe Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro 465 470 475 480 465 470 475 480

Leu Pro Glu Asn Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Leu Pro Glu Asn Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala 485 490 495 485 490 495

Trp Gly Val Val Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Trp Gly Val Val Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln 500 505 510 500 505 510

Phe Thr Asp Leu Asn Val Tyr Leu Trp Phe Thr Asp Leu Asn Val Tyr Leu Trp 515 520 515 520

<210> 19 <210> 19 <211> 516 <211> 516 <212> PRT <212> PRT <213> Homo sapiens <213> Homo sapiens

<400> 19 <400> 19

Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro 1 5 10 15 1 5 10 15

Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Page 71 Page 71

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing TXT 20 25 30 20 25 30

Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln 35 40 45 35 40 45

Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro 50 55 60 50 55 60

Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala 65 70 75 80 70 75 80

Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr 85 90 95 85 90 95

Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr 100 105 110 100 105 110

His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser 115 120 125 115 120 125

Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu 130 135 140 130 135 140

Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His 145 150 155 160 145 150 155 160

Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn 165 170 175 165 170 175

Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg 180 185 190 180 185 190

His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr 195 200 205 195 200 205

Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile 210 215 220 210 215 220

Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Page 72 Page 72

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 225 230 235 240 225 230 235 240

Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr 245 250 255 245 250 255

Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro 260 265 270 260 265 270

Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp 275 280 285 275 280 285

Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr 290 295 300 290 295 300

Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr 305 310 315 320 305 310 315 320

Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu 325 330 335 325 330 335

Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys 340 345 350 340 345 350

Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile 355 360 365 355 360 365

Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp 370 375 380 370 375 380

Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr 385 390 395 400 385 390 395 400

Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly 405 410 415 405 410 415

Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu 420 425 430 420 425 430

Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Page 73 Page 73

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 435 440 445 435 440 445

Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr 450 455 460 450 455 460

Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln 465 470 475 480 465 470 475 480

Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp 485 490 495 485 490 495

Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn 500 505 510 500 505 510

Val Tyr Leu Trp Val Tyr Leu Trp 515 515

<210> 20 <210> 20 <211> 514 <211> 514 <212> PRT <212> PRT <213> Homo sapiens <213> Homo sapiens

<400> 20 <400> 20

Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro Ala Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro Ala Pro 1 5 10 15 1 5 10 15

Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Leu Trp Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Leu Trp 20 25 30 20 25 30

Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Gln His Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Gln His 35 40 45 35 40 45

Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Leu Ala Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Leu Ala 50 55 60 50 55 60

Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Pro Ser Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Pro Ser 65 70 75 80 70 75 80

Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Asn Asn Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Asn Asn 85 90 95 85 90 95 Page 74 Page 74

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr His Tyr Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr His Tyr 100 105 110 100 105 110

Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala Gly Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala Gly 115 120 125 115 120 125

Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu Arg Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu Arg 130 135 140 130 135 140

Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Trp Asp Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Trp Asp 145 150 155 160 145 150 155 160

Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Arg Ala Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Arg Ala 165 170 175 165 170 175

Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His Phe Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His Phe 180 185 190 180 185 190

Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val Val Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val Val 195 200 205 195 200 205

Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg Gly Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg Gly 210 215 220 210 215 220

Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala His Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala His 225 230 235 240 225 230 235 240

Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln Gly Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln Gly 245 250 255 245 250 255

Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg Arg Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg Arg 260 265 270 260 265 270

Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Val Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Val 275 280 285 275 280 285

Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Pro Glu Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Pro Glu 290 295 300 290 295 300 Page 75 Page 75

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Glu Ser Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Glu Ser 305 310 315 320 305 310 315 320

Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Ser Phe Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Ser Phe 325 330 335 325 330 335

Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Arg Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Arg 340 345 350 340 345 350

Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Asp Leu Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Asp Leu 355 360 365 355 360 365

Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Val Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Val 370 375 380 370 375 380

Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Lys Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Lys 385 390 395 400 385 390 395 400

Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Val Asp Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Val Asp 405 410 415 405 410 415

Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp His Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp His 420 425 430 420 425 430

Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu Ser Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu Ser 435 440 445 435 440 445

Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys 450 455 460 450 455 460

Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu 465 470 475 480 465 470 475 480

Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Tyr Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Tyr 485 490 495 485 490 495

Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Val Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Val Tyr 500 505 510 500 505 510 Page 76 Page 76

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Leu Trp Leu Trp

<210> 21 <210> 21 <211> 419 <211> 419 <212> PRT <212> PRT <213> Homo sapiens <213> Homo sapiens

<400> 21 <400> 21

Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr His Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr His 1 5 10 15 1 5 10 15

Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala 20 25 30 20 25 30

Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu 35 40 45 35 40 45

Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Trp Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Trp 50 55 60 50 55 60

Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Arg Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Arg 65 70 75 80 70 75 80

Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His 85 90 95 85 90 95

Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val 100 105 110 100 105 110

Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg 115 120 125 115 120 125

Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala 130 135 140 130 135 140

His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln 145 150 155 160 145 150 155 160

Page 77 Page 77

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg 165 170 175 165 170 175

Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe 180 185 190 180 185 190

Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Pro Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Pro 195 200 205 195 200 205

Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Glu Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Glu 210 215 220 210 215 220

Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Ser Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Ser 225 230 235 240 225 230 235 240

Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe 245 250 255 245 250 255

Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Asp Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Asp 260 265 270 260 265 270

Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe 275 280 285 275 280 285

Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu 290 295 300 290 295 300

Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Val Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Val 305 310 315 320 305 310 315 320

Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp 325 330 335 325 330 335

His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu 340 345 350 340 345 350

Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln 355 360 365 355 360 365

Page 78 Page 78

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro 370 375 380 370 375 380

Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn 385 390 395 400 385 390 395 400

Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Val Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Val 405 410 415 405 410 415

Tyr Leu Trp Tyr Leu Trp

<210> 22 <210> 22 <211> 1012 <211> 1012 <212> PRT <212> PRT <213> Homo sapiens <213> Homo sapiens

<400> 22 <400> 22

Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser 1 5 10 15 1 5 10 15

Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg 20 25 30 20 25 30

Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro 35 40 45 35 40 45

Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly 50 55 60 50 55 60

Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp 65 70 75 80 70 75 80

Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His 85 90 95 85 90 95

Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly 100 105 110 100 105 110

Page 79 Page 79

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser 115 120 125 115 120 125

Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val 130 135 140 130 135 140

Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly 145 150 155 160 145 150 155 160

Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu 165 170 175 165 170 175

Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr 180 185 190 180 185 190

His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala 195 200 205 195 200 205

Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe 210 215 220 210 215 220

Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro 225 230 235 240 225 230 235 240

Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly 245 250 255 245 250 255

Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu 260 265 270 260 265 270

Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro 275 280 285 275 280 285

Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn 290 295 300 290 295 300

Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu 305 310 315 320 305 310 315 320

Page 80 Page 80

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp 325 330 335 325 330 335

Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe 340 345 350 340 345 350

Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala 355 360 365 355 360 365

Leu Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Leu Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met 370 375 380 370 375 380

Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp 385 390 395 400 385 390 395 400

Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly 405 410 415 405 410 415

Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr 420 425 430 420 425 430

Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp 435 440 445 435 440 445

Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe 450 455 460 450 455 460

Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp 465 470 475 480 465 470 475 480

Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe 485 490 495 485 490 495

Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn 500 505 510 500 505 510

Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val 515 520 525 515 520 525

Page 81 Page 81

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu 530 535 540 530 535 540

Asn Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asn Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val 545 550 555 560 545 550 555 560

Asp Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Asp Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala 565 570 575 565 570 575

Ala Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Ala Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His 580 585 590 580 585 590

Phe Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Phe Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln 595 600 605 595 600 605

Ser Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Ser Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser 610 615 620 610 615 620

Glu Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Glu Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro 625 630 635 640 625 630 635 640

Met Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Met Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala 645 650 655 645 650 655

Trp Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Trp Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu 660 665 670 660 665 670

Cys Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Cys Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn 675 680 685 675 680 685

Glu Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Glu Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu 690 695 700 690 695 700

Lys Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Lys Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His 705 710 715 720 705 710 715 720

Ala Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Ala Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu 725 730 735 725 730 735

Page 82 Page 82

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Pro Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Pro Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val 740 745 750 740 745 750

Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly 755 760 765 755 760 765

Asp Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Asp Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe 770 775 780 770 775 780

Leu Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Leu Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr 785 790 795 800 785 790 795 800

Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser 805 810 815 805 810 815

Glu Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Glu Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu 820 825 830 820 825 830

Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val 835 840 845 835 840 845

Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly 850 855 860 850 855 860

Asp Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Asp Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His 865 870 875 880 865 870 875 880

Ala Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Ala Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn 885 890 895 885 890 895

Glu Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Glu Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr 900 905 910 900 905 910

Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr 915 920 925 915 920 925

Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr 930 935 940 930 935 940

Page 83 Page 83

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu 945 950 955 960 945 950 955 960

Arg Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe Arg Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe 965 970 975 965 970 975

His Thr Arg Lys Ser Leu Leu Ala Phe Ile Ala Phe Leu Phe Phe Ala His Thr Arg Lys Ser Leu Leu Ala Phe Ile Ala Phe Leu Phe Phe Ala 980 985 990 980 985 990

Ser Ile Ile Ser Leu Ser Leu Ile Phe Tyr Tyr Ser Lys Lys Gly Arg Ser Ile Ile Ser Leu Ser Leu Ile Phe Tyr Tyr Ser Lys Lys Gly Arg 995 1000 1005 995 1000 1005

Arg Ser Tyr Lys Arg Ser Tyr Lys 1010 1010

<210> 23 <210> 23 <211> 981 <211> 981 <212> PRT <212> PRT <213> Homo sapiens <213> Homo sapiens

<400> 23 <400> 23

Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser 1 5 10 15 1 5 10 15

Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg 20 25 30 20 25 30

Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro 35 40 45 35 40 45

Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly 50 55 60 50 55 60

Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp 65 70 75 80 70 75 80

Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His 85 90 95 85 90 95

Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Page 84 Page 84

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 100 105 110 100 105 110

Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser 115 120 125 115 120 125

Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val 130 135 140 130 135 140

Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly 145 150 155 160 145 150 155 160

Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu 165 170 175 165 170 175

Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr 180 185 190 180 185 190

His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala 195 200 205 195 200 205

Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe 210 215 220 210 215 220

Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro 225 230 235 240 225 230 235 240

Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly 245 250 255 245 250 255

Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu 260 265 270 260 265 270

Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro 275 280 285 275 280 285

Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn 290 295 300 290 295 300

Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Page 85 Page 85

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 305 310 315 320 305 310 315 320

Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp 325 330 335 325 330 335

Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe 340 345 350 340 345 350

Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala 355 360 365 355 360 365

Leu Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Leu Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met 370 375 380 370 375 380

Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp 385 390 395 400 385 390 395 400

Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly 405 410 415 405 410 415

Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr 420 425 430 420 425 430

Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp 435 440 445 435 440 445

Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe 450 455 460 450 455 460

Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp 465 470 475 480 465 470 475 480

Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe 485 490 495 485 490 495

Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn 500 505 510 500 505 510

Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Page 86 Page 86

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 515 520 525 515 520 525

Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu 530 535 540 530 535 540

Asn Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asn Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val 545 550 555 560 545 550 555 560

Asp Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Asp Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala 565 570 575 565 570 575

Ala Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Ala Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His 580 585 590 580 585 590

Phe Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Phe Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln 595 600 605 595 600 605

Ser Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Ser Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser 610 615 620 610 615 620

Glu Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Glu Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro 625 630 635 640 625 630 635 640

Met Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Met Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala 645 650 655 645 650 655

Trp Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Trp Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu 660 665 670 660 665 670

Cys Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Cys Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn 675 680 685 675 680 685

Glu Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Glu Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu 690 695 700 690 695 700

Lys Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Lys Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His 705 710 715 720 705 710 715 720

Ala Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Ala Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Page 87 Page 87

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 725 730 735 725 730 735

Pro Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Pro Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val 740 745 750 740 745 750

Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly 755 760 765 755 760 765

Asp Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Asp Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe 770 775 780 770 775 780

Leu Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Leu Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr 785 790 795 800 785 790 795 800

Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser 805 810 815 805 810 815

Glu Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Glu Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu 820 825 830 820 825 830

Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val 835 840 845 835 840 845

Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly 850 855 860 850 855 860

Asp Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Asp Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His 865 870 875 880 865 870 875 880

Ala Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Ala Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn 885 890 895 885 890 895

Glu Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Glu Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr 900 905 910 900 905 910

Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr 915 920 925 915 920 925

Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Page 88 Page 88

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 930 935 940 930 935 940

Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu 945 950 955 960 945 950 955 960

Arg Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe Arg Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe 965 970 975 965 970 975

His Thr Arg Lys Ser His Thr Arg Lys Ser 980 980

<210> 24 <210> 24 <211> 953 <211> 953 <212> PRT <212> PRT <213> Homo sapiens <213> Homo sapiens

<400> 24 <400> 24

Arg Arg Leu Arg Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Arg Arg Leu Arg Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg 1 5 10 15 1 5 10 15

Val Ser Arg Pro Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Val Ser Arg Pro Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr 20 25 30 20 25 30

Phe Pro Asp Gly Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Phe Pro Asp Gly Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr 35 40 45 35 40 45

Glu Gly Gly Trp Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Glu Gly Gly Trp Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr 50 55 60 50 55 60

Phe Thr His His Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Phe Thr His His Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser 65 70 75 80 70 75 80

Leu Pro Leu Gly Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Leu Pro Leu Gly Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val 85 90 95 85 90 95

Ala Ser Asp Ser Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Ala Ser Asp Ser Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg 100 105 110 100 105 110

Glu Leu Gly Val Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Glu Leu Gly Val Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val 115 120 125 115 120 125

Page 89 Page 89

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Leu Pro Asn Gly Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Leu Pro Asn Gly Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr 130 135 140 130 135 140

Tyr Arg Arg Leu Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Tyr Arg Arg Leu Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val 145 150 155 160 145 150 155 160

Val Thr Leu Tyr His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Val Thr Leu Tyr His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr 165 170 175 165 170 175

Gly Gly Trp Ala Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Gly Gly Trp Ala Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala 180 185 190 180 185 190

Glu Leu Cys Phe Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Glu Leu Cys Phe Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr 195 200 205 195 200 205

Ile Asp Asn Pro Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Ile Asp Asn Pro Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg 210 215 220 210 215 220

Leu Ala Pro Gly Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala Leu Ala Pro Gly Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala 225 230 235 240 225 230 235 240

His Asn Leu Leu Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr His Asn Leu Leu Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr 245 250 255 245 250 255

Ser Phe Arg Pro Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser Ser Phe Arg Pro Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser 260 265 270 260 265 270

His Trp Ile Asn Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys His Trp Ile Asn Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys 275 280 285 275 280 285

Gln Lys Ser Leu Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Gln Lys Ser Leu Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe 290 295 300 290 295 300

Ile Asp Gly Asp Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Ile Asp Gly Asp Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile 305 310 315 320 305 310 315 320

Leu Pro Asp Phe Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Leu Pro Asp Phe Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala 325 330 335 325 330 335 Page 90 Page 90

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Asp Phe Phe Ala Leu Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Phe Phe Ala Leu Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu 340 345 350 340 345 350

Asp Pro His Met Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Asp Pro His Met Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln 355 360 365 355 360 365

Leu Leu Ser Trp Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Leu Leu Ser Trp Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile 370 375 380 370 375 380

Val Glu Asn Gly Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Val Glu Asn Gly Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala 385 390 395 400 385 390 395 400

Lys Tyr Met Tyr Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Lys Tyr Met Tyr Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala 405 410 415 405 410 415

Ile Lys Leu Asp Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Ile Lys Leu Asp Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu 420 425 430 420 425 430

Met Asp Gly Phe Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Met Asp Gly Phe Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu 435 440 445 435 440 445

Phe Tyr Val Asp Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Phe Tyr Val Asp Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser 450 455 460 450 455 460

Ser Ala Leu Phe Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Ser Ala Leu Phe Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro 465 470 475 480 465 470 475 480

Leu Pro Glu Asn Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Leu Pro Glu Asn Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala 485 490 495 485 490 495

Trp Gly Val Val Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Trp Gly Val Val Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln 500 505 510 500 505 510

Phe Thr Asp Leu Asn Val Tyr Leu Trp Asp Val His His Ser Lys Arg Phe Thr Asp Leu Asn Val Tyr Leu Trp Asp Val His His Ser Lys Arg 515 520 525 515 520 525

Leu Ile Lys Val Asp Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Leu Ile Lys Val Asp Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys 530 535 540 530 535 540 Page 91 Page 91

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Val Asp Phe Ala Ala Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met Val Asp Phe Ala Ala Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met 545 550 555 560 545 550 555 560

His Val Thr His Phe Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro His Val Thr His Phe Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro 565 570 575 565 570 575

Leu Gly Asn Gln Ser Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Leu Gly Asn Gln Ser Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg 580 585 590 580 585 590

Cys Met Ala Ser Glu Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Cys Met Ala Ser Glu Leu Val Arg Val Asn Ile Thr Pro Val Val Ala 595 600 605 595 600 605

Leu Trp Gln Pro Met Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Leu Trp Gln Pro Met Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala 610 615 620 610 615 620

Arg Gln Gly Ala Trp Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Arg Gln Gly Ala Trp Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu 625 630 635 640 625 630 635 640

Tyr Ala Arg Leu Cys Phe Gln Glu Leu Gly His His Val Lys Leu Trp Tyr Ala Arg Leu Cys Phe Gln Glu Leu Gly His His Val Lys Leu Trp 645 650 655 645 650 655

Ile Thr Met Asn Glu Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly Ile Thr Met Asn Glu Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly 660 665 670 660 665 670

His Asn Leu Leu Lys Ala His Ala Leu Ala Trp His Val Tyr Asn Glu His Asn Leu Leu Lys Ala His Ala Leu Ala Trp His Val Tyr Asn Glu 675 680 685 675 680 685

Lys Phe Arg His Ala Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Lys Phe Arg His Ala Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala 690 695 700 690 695 700

Asp Trp Ile Glu Pro Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Asp Trp Ile Glu Pro Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val 705 710 715 720 705 710 715 720

Ala Glu Arg Val Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Ala Glu Arg Val Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile 725 730 735 725 730 735

Phe Gly Ser Gly Asp Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Phe Gly Ser Gly Asp Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln 740 745 750 740 745 750 Page 92 Page 92

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Arg Asn Asn Phe Leu Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Arg Asn Asn Phe Leu Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu 755 760 765 755 760 765

Ile Gln Gly Thr Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Ile Gln Gly Thr Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile 770 775 780 770 775 780

Leu Val Asp Ser Glu Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Leu Val Asp Ser Glu Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu 785 790 795 800 785 790 795 800

Glu Val Gln Glu Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Glu Val Gln Glu Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln 805 810 815 805 810 815

Val Ala Val Val Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Val Ala Val Val Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys 820 825 830 820 825 830

Phe Lys Tyr Gly Asp Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Phe Lys Tyr Gly Asp Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp 835 840 845 835 840 845

Asp Gly Leu His Ala Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asp Gly Leu His Ala Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln 850 855 860 850 855 860

Asn Tyr Ile Asn Glu Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Asn Tyr Ile Asn Glu Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn 865 870 875 880 865 870 875 880

Leu Cys Gly Tyr Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Leu Cys Gly Tyr Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg 885 890 895 885 890 895

Phe Gly Leu Tyr Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Phe Gly Leu Tyr Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser 900 905 910 900 905 910

Met Lys His Tyr Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Met Lys His Tyr Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro 915 920 925 915 920 925

Glu Thr Leu Glu Arg Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Glu Thr Leu Glu Arg Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu 930 935 940 930 935 940

Cys Ser Phe Phe His Thr Arg Lys Ser Cys Ser Phe Phe His Thr Arg Lys Ser 945 950 945 950 Page 93 Page 93

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

<210> 25 <210> 25 <211> 948 <211> 948 <212> PRT <212> PRT <213> Homo sapiens <213> Homo sapiens

<400> 25 <400> 25

Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro 1 5 10 15 1 5 10 15

Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe 20 25 30 20 25 30

Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln 35 40 45 35 40 45

Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro 50 55 60 50 55 60

Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala 65 70 75 80 70 75 80

Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr 85 90 95 85 90 95

Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr 100 105 110 100 105 110

His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser 115 120 125 115 120 125

Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu 130 135 140 130 135 140

Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His 145 150 155 160 145 150 155 160

Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn 165 170 175 165 170 175

Page 94 Page 94

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg 180 185 190 180 185 190

His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr 195 200 205 195 200 205

Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile 210 215 220 210 215 220

Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu 225 230 235 240 225 230 235 240

Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr 245 250 255 245 250 255

Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro 260 265 270 260 265 270

Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp 275 280 285 275 280 285

Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr 290 295 300 290 295 300

Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr 305 310 315 320 305 310 315 320

Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu 325 330 335 325 330 335

Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys 340 345 350 340 345 350

Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile 355 360 365 355 360 365

Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp 370 375 380 370 375 380

Page 95 Page 95

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr 385 390 395 400 385 390 395 400

Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly 405 410 415 405 410 415

Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu 420 425 430 420 425 430

Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe 435 440 445 435 440 445

Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr 450 455 460 450 455 460

Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln 465 470 475 480 465 470 475 480

Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp 485 490 495 485 490 495

Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn 500 505 510 500 505 510

Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp 515 520 525 515 520 525

Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala 530 535 540 530 535 540

Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe 545 550 555 560 545 550 555 560

Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser 565 570 575 565 570 575

Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu 580 585 590 580 585 590

Page 96 Page 96

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met 595 600 605 595 600 605

Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp 610 615 620 610 615 620

Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys 625 630 635 640 625 630 635 640

Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu 645 650 655 645 650 655

Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys 660 665 670 660 665 670

Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala 675 680 685 675 680 685

Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro 690 695 700 690 695 700

Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu 705 710 715 720 705 710 715 720

Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp 725 730 735 725 730 735

Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu 740 745 750 740 745 750

Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe 755 760 765 755 760 765

Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu 770 775 780 770 775 780

Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met 785 790 795 800 785 790 795 800

Page 97 Page 97

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro 805 810 815 805 810 815

Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp 820 825 830 820 825 830

Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala 835 840 845 835 840 845

Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu 850 855 860 850 855 860

Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe 865 870 875 880 865 870 875 880

Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg 885 890 895 885 890 895

Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg 900 905 910 900 905 910

Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg 915 920 925 915 920 925

Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His 930 935 940 930 935 940

Thr Arg Lys Ser Thr Arg Lys Ser 945 945

<210> 26 <210> 26 <211> 946 <211> 946 <212> PRT <212> PRT <213> Homo sapiens <213> Homo sapiens

<400> 26 <400> 26

Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro Ala Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro Ala Pro 1 5 10 15 1 5 10 15

Page 98 Page 98

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing TXT Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Leu Trp Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Leu Trp 20 25 30 20 25 30

Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Gln His Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Gln His 35 40 45 35 40 45

Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Leu Ala Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Leu Ala 50 55 60 50 55 60

Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Pro Ser Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Pro Ser 65 70 75 80 70 75 80

Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Asn Asn Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Asn Asn 85 90 95 85 90 95

Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr His Tyr Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr His Tyr 100 105 110 100 105 110

Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala Gly Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala Gly 115 120 125 115 120 125

Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu Arg Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu Arg 130 135 140 130 135 140

Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Trp Asp Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Trp Asp 145 150 155 160 145 150 155 160

Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Arg Ala Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Arg Ala 165 170 175 165 170 175

Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His Phe Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His Phe 180 185 190 180 185 190

Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val Val Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val Val 195 200 205 195 200 205

Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg Gly Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg Gly 210 215 220 210 215 220

Page 99 Page 99

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala His Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala His 225 230 235 240 225 230 235 240

Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln Gly Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln Gly 245 250 255 245 250 255

Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg Arg Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg Arg 260 265 270 260 265 270

Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Val Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Val 275 280 285 275 280 285

Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Pro Glu Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Pro Glu 290 295 300 290 295 300

Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Glu Ser Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Glu Ser 305 310 315 320 305 310 315 320

Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Cys Phe Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Cys Phe 325 330 335 325 330 335

Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Arg Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Arg 340 345 350 340 345 350

Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Asp Leu Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Asp Leu 355 360 365 355 360 365

Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Val Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Val 370 375 380 370 375 380

Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Lys Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Lys 385 390 395 400 385 390 395 400

Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Val Asp Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Val Asp 405 410 415 405 410 415

Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp His Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp His 420 425 430 420 425 430

Page 100 Page 100

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu Ser Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu Ser 435 440 445 435 440 445

Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys 450 455 460 450 455 460

Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu 465 470 475 480 465 470 475 480

Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Tyr Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Tyr 485 490 495 485 490 495

Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Val Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Val Tyr 500 505 510 500 505 510

Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Gly Val Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Gly Val 515 520 525 515 520 525

Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Ile Gln Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Ile Gln 530 535 540 530 535 540

Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe Arg Phe Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe Arg Phe 545 550 555 560 545 550 555 560

Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Gln Val Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Gln Val 565 570 575 565 570 575

Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu Leu Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu Leu Val 580 585 590 580 585 590

Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met Ala Pro Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met Ala Pro 595 600 605 595 600 605

Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp Glu Asn Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp Glu Asn 610 615 620 610 615 620

Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys Phe Gln Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys Phe Gln 625 630 635 640 625 630 635 640

Page 101 Page 101

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu Pro Tyr Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu Pro Tyr 645 650 655 645 650 655

Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Ala His Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Ala His 660 665 670 660 665 670

Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala Gln Asn Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala Gln Asn 675 680 685 675 680 685

Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Ala Cys Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Ala Cys 690 695 700 690 695 700

Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu Glu Phe Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu Glu Phe 705 710 715 720 705 710 715 720

Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Tyr Pro Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Tyr Pro 725 730 735 725 730 735

Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu Leu Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu Leu Pro 740 745 750 740 745 750

Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe Asp Phe Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe Asp Phe 755 760 765 755 760 765

Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu Lys Glu Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu Lys Glu 770 775 780 770 775 780

Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Thr Asp Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Thr Asp 785 790 795 800 785 790 795 800

Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Trp Gly Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Trp Gly 805 810 815 805 810 815

Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp Leu Pro Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp Leu Pro 820 825 830 820 825 830

Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala Glu Asp Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala Glu Asp 835 840 845 835 840 845

Page 102 Page 102

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu Ala Leu Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu Ala Leu 850 855 860 850 855 860

Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe Ala Tyr Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe Ala Tyr 865 870 875 880 865 870 875 880

Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg Tyr Ala Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg Tyr Ala 885 890 895 885 890 895

Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Lys Ile Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Lys Ile 900 905 910 900 905 910

Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Phe Cys Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Phe Cys 915 920 925 915 920 925

Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His Thr Arg Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His Thr Arg 930 935 940 930 935 940

Lys Ser Lys Ser 945 945

<210> 27 <210> 27 <211> 549 <211> 549 <212> PRT <212> PRT <213> Homo sapiens <213> Homo sapiens

<400> 27 <400> 27

Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser 1 5 10 15 1 5 10 15

Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg 20 25 30 20 25 30

Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro 35 40 45 35 40 45

Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly 50 55 60 50 55 60

Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Page 103 Page 103

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 65 70 75 80 70 75 80

Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His 85 90 95 85 90 95

Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly 100 105 110 100 105 110

Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser 115 120 125 115 120 125

Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val 130 135 140 130 135 140

Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly 145 150 155 160 145 150 155 160

Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu 165 170 175 165 170 175

Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr 180 185 190 180 185 190

His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala 195 200 205 195 200 205

Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe 210 215 220 210 215 220

Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro 225 230 235 240 225 230 235 240

Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly 245 250 255 245 250 255

Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu 260 265 270 260 265 270

Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Page 104 Page 104

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 275 280 285 275 280 285

Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn 290 295 300 290 295 300

Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu 305 310 315 320 305 310 315 320

Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp 325 330 335 325 330 335

Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe 340 345 350 340 345 350

Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala 355 360 365 355 360 365

Leu Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Leu Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met 370 375 380 370 375 380

Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp 385 390 395 400 385 390 395 400

Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly 405 410 415 405 410 415

Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr 420 425 430 420 425 430

Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp 435 440 445 435 440 445

Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe 450 455 460 450 455 460

Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp 465 470 475 480 465 470 475 480

Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Page 105 Page 105

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 485 490 495 485 490 495

Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn 500 505 510 500 505 510

Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val 515 520 525 515 520 525

Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu 530 535 540 530 535 540

Asn Val Tyr Leu Trp Asn Val Tyr Leu Trp 545 545

<210> 28 <210> 28 <211> 521 <211> 521 <212> PRT <212> PRT <213> Homo sapiens <213> Homo sapiens

<400> 28 <400> 28

Arg Arg Leu Arg Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Arg Arg Leu Arg Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg 1 5 10 15 1 5 10 15

Val Ser Arg Pro Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Val Ser Arg Pro Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr 20 25 30 20 25 30

Phe Pro Asp Gly Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Phe Pro Asp Gly Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr 35 40 45 35 40 45

Glu Gly Gly Trp Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Glu Gly Gly Trp Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr 50 55 60 50 55 60

Phe Thr His His Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Phe Thr His His Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser 65 70 75 80 70 75 80

Leu Pro Leu Gly Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Leu Pro Leu Gly Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val 85 90 95 85 90 95

Ala Ser Asp Ser Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Ala Ser Asp Ser Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg 100 105 110 100 105 110 Page 106 Page 106

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Glu Leu Gly Val Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Glu Leu Gly Val Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val 115 120 125 115 120 125

Leu Pro Asn Gly Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Leu Pro Asn Gly Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr 130 135 140 130 135 140

Tyr Arg Arg Leu Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Tyr Arg Arg Leu Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val 145 150 155 160 145 150 155 160

Val Thr Leu Tyr His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Val Thr Leu Tyr His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr 165 170 175 165 170 175

Gly Gly Trp Ala Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Gly Gly Trp Ala Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala 180 185 190 180 185 190

Glu Leu Cys Phe Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Glu Leu Cys Phe Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr 195 200 205 195 200 205

Ile Asp Asn Pro Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Ile Asp Asn Pro Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg 210 215 220 210 215 220

Leu Ala Pro Gly Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala Leu Ala Pro Gly Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala 225 230 235 240 225 230 235 240

His Asn Leu Leu Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr His Asn Leu Leu Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr 245 250 255 245 250 255

Ser Phe Arg Pro Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser Ser Phe Arg Pro Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser 260 265 270 260 265 270

His Trp Ile Asn Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys His Trp Ile Asn Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys 275 280 285 275 280 285

Gln Lys Ser Leu Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Gln Lys Ser Leu Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe 290 295 300 290 295 300

Ile Asp Gly Asp Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Ile Asp Gly Asp Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile 305 310 315 320 305 310 315 320 Page 107 Page 107

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Leu Pro Asp Phe Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Leu Pro Asp Phe Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala 325 330 335 325 330 335

Asp Phe Phe Ala Leu Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Phe Phe Ala Leu Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu 340 345 350 340 345 350

Asp Pro His Met Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Asp Pro His Met Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln 355 360 365 355 360 365

Leu Leu Ser Trp Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Leu Leu Ser Trp Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile 370 375 380 370 375 380

Val Glu Asn Gly Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Val Glu Asn Gly Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala 385 390 395 400 385 390 395 400

Lys Tyr Met Tyr Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Lys Tyr Met Tyr Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala 405 410 415 405 410 415

Ile Lys Leu Asp Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Ile Lys Leu Asp Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu 420 425 430 420 425 430

Met Asp Gly Phe Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Met Asp Gly Phe Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu 435 440 445 435 440 445

Phe Tyr Val Asp Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Phe Tyr Val Asp Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser 450 455 460 450 455 460

Ser Ala Leu Phe Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Ser Ala Leu Phe Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro 465 470 475 480 465 470 475 480

Leu Pro Glu Asn Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Leu Pro Glu Asn Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala 485 490 495 485 490 495

Trp Gly Val Val Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Trp Gly Val Val Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln 500 505 510 500 505 510

Phe Thr Asp Leu Asn Val Tyr Leu Trp Phe Thr Asp Leu Asn Val Tyr Leu Trp 515 520 515 520 Page 108 Page 108

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

<210> 29 <210> 29 <211> 516 <211> 516 <212> PRT <212> PRT <213> Homo sapiens <213> Homo sapiens

<400> 29 <400> 29

Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro 1 5 10 15 1 5 10 15

Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe 20 25 30 20 25 30

Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln 35 40 45 35 40 45

Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro 50 55 60 50 55 60

Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala 65 70 75 80 70 75 80

Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr 85 90 95 85 90 95

Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr 100 105 110 100 105 110

His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser 115 120 125 115 120 125

Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu 130 135 140 130 135 140

Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His 145 150 155 160 145 150 155 160

Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn 165 170 175 165 170 175

Page 109 Page 109

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg 180 185 190 180 185 190

His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr 195 200 205 195 200 205

Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile 210 215 220 210 215 220

Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu 225 230 235 240 225 230 235 240

Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr 245 250 255 245 250 255

Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro 260 265 270 260 265 270

Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp 275 280 285 275 280 285

Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr 290 295 300 290 295 300

Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr 305 310 315 320 305 310 315 320

Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu 325 330 335 325 330 335

Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys 340 345 350 340 345 350

Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile 355 360 365 355 360 365

Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp 370 375 380 370 375 380

Page 110 Page 110

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. - TXT

Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr 385 390 395 400 385 390 395 400

Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly 405 410 415 405 410 415

Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu 420 425 430 420 425 430

Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe 435 440 445 435 440 445

Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr 450 455 460 450 455 460

Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln 465 470 475 480 465 470 475 480

Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp 485 490 495 485 490 495

Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn 500 505 510 500 505 510

Val Tyr Leu Trp Val Tyr Leu Trp 515 515

<210> 30 <210> 30 <211> 514 <211> 514 <212> PRT <212> PRT <213> Homo sapiens <213> Homo sapiens

<400> 30 <400> 30

Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro Ala Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro Ala Pro 1 5 10 15 1 5 10 15

Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Leu Trp Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Leu Trp 20 25 30 20 25 30

Page 111 Page 111

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing TXT Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Gln His Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Gln His 35 40 45 35 40 45

Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Leu Ala Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Leu Ala 50 55 60 50 55 60

Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Pro Ser Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Pro Ser 65 70 75 80 70 75 80

Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Asn Asn Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Asn Asn 85 90 95 85 90 95

Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr His Tyr Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr His Tyr 100 105 110 100 105 110

Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala Gly Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala Gly 115 120 125 115 120 125

Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu Arg Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu Arg 130 135 140 130 135 140

Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Trp Asp Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Trp Asp 145 150 155 160 145 150 155 160

Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Arg Ala Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Arg Ala 165 170 175 165 170 175

Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His Phe Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His Phe 180 185 190 180 185 190

Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val Val Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val Val 195 200 205 195 200 205

Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg Gly Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg Gly 210 215 220 210 215 220

Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala His Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala His 225 230 235 240 225 230 235 240

Page 112 Page 112

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln Gly Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln Gly 245 250 255 245 250 255

Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg Arg Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg Arg 260 265 270 260 265 270

Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Val Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Val 275 280 285 275 280 285

Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Pro Glu Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Pro Glu 290 295 300 290 295 300

Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Glu Ser Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Glu Ser 305 310 315 320 305 310 315 320

Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Cys Phe Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Cys Phe 325 330 335 325 330 335

Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Arg Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Arg 340 345 350 340 345 350

Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Asp Leu Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Asp Leu 355 360 365 355 360 365

Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Val Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Val 370 375 380 370 375 380

Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Lys Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Lys 385 390 395 400 385 390 395 400

Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Val Asp Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Val Asp 405 410 415 405 410 415

Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp His Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp His 420 425 430 420 425 430

Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu Ser Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu Ser 435 440 445 435 440 445

Page 113 Page 113

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys 450 455 460 450 455 460

Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu 465 470 475 480 465 470 475 480

Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Tyr Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Tyr 485 490 495 485 490 495

Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Val Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Val Tyr 500 505 510 500 505 510

Leu Trp Leu Trp

<210> 31 <210> 31 <211> 981 <211> 981 <212> PRT <212> PRT <213> Homo sapiens <213> Homo sapiens

<400> 31 <400> 31

Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser 1 5 10 15 1 5 10 15

Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg 20 25 30 20 25 30

Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro 35 40 45 35 40 45

Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly 50 55 60 50 55 60

Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp 65 70 75 80 70 75 80

Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His 85 90 95 85 90 95

Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Page 114 Page 114

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 100 105 110 100 105 110

Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser 115 120 125 115 120 125

Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val 130 135 140 130 135 140

Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly 145 150 155 160 145 150 155 160

Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu 165 170 175 165 170 175

Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr 180 185 190 180 185 190

His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala 195 200 205 195 200 205

Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe 210 215 220 210 215 220

Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro 225 230 235 240 225 230 235 240

Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly 245 250 255 245 250 255

Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu 260 265 270 260 265 270

Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro 275 280 285 275 280 285

Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn 290 295 300 290 295 300

Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Page 115 Page 115

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 305 310 315 320 305 310 315 320

Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp 325 330 335 325 330 335

Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe 340 345 350 340 345 350

Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala 355 360 365 355 360 365

Leu Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Leu Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met 370 375 380 370 375 380

Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp 385 390 395 400 385 390 395 400

Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly 405 410 415 405 410 415

Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr 420 425 430 420 425 430

Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp 435 440 445 435 440 445

Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe 450 455 460 450 455 460

Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp 465 470 475 480 465 470 475 480

Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe 485 490 495 485 490 495

Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn 500 505 510 500 505 510

Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Page 116 Page 116

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 515 520 525 515 520 525

Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu 530 535 540 530 535 540

Asn Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asn Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val 545 550 555 560 545 550 555 560

Asp Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Asp Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala 565 570 575 565 570 575

Ala Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Ala Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His 580 585 590 580 585 590

Phe Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Phe Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln 595 600 605 595 600 605

Ser Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Ser Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser 610 615 620 610 615 620

Glu Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Glu Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro 625 630 635 640 625 630 635 640

Met Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Met Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala 645 650 655 645 650 655

Trp Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Trp Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu 660 665 670 660 665 670

Cys Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Cys Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn 675 680 685 675 680 685

Glu Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Glu Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu 690 695 700 690 695 700

Lys Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Lys Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His 705 710 715 720 705 710 715 720

Ala Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Ala Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Page 117 Page 117

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 725 730 735 725 730 735

Pro Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Pro Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val 740 745 750 740 745 750

Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly 755 760 765 755 760 765

Asp Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Asp Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe 770 775 780 770 775 780

Leu Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Leu Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr 785 790 795 800 785 790 795 800

Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser 805 810 815 805 810 815

Glu Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Glu Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu 820 825 830 820 825 830

Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val 835 840 845 835 840 845

Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly 850 855 860 850 855 860

Asp Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Asp Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His 865 870 875 880 865 870 875 880

Ala Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Ala Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn 885 890 895 885 890 895

Glu Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Glu Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr 900 905 910 900 905 910

Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr 915 920 925 915 920 925

Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Page 118 Page 118

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 930 935 940 930 935 940

Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu 945 950 955 960 945 950 955 960

Arg Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe Arg Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe 965 970 975 965 970 975

His Thr Arg Lys Ser His Thr Arg Lys Ser 980 980

<210> 32 <210> 32 <211> 953 <211> 953 <212> PRT <212> PRT <213> Homo sapiens <213> Homo sapiens

<400> 32 <400> 32

Arg Arg Leu Arg Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Arg Arg Leu Arg Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg 1 5 10 15 1 5 10 15

Val Ser Arg Pro Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Val Ser Arg Pro Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr 20 25 30 20 25 30

Phe Pro Asp Gly Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Phe Pro Asp Gly Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr 35 40 45 35 40 45

Glu Gly Gly Trp Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Glu Gly Gly Trp Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr 50 55 60 50 55 60

Phe Thr His His Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Phe Thr His His Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser 65 70 75 80 70 75 80

Leu Pro Leu Gly Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Leu Pro Leu Gly Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val 85 90 95 85 90 95

Ala Ser Asp Ser Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Ala Ser Asp Ser Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg 100 105 110 100 105 110

Glu Leu Gly Val Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Glu Leu Gly Val Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val 115 120 125 115 120 125

Page 119 Page 119

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Leu Pro Asn Gly Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Leu Pro Asn Gly Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr 130 135 140 130 135 140

Tyr Arg Arg Leu Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Tyr Arg Arg Leu Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val 145 150 155 160 145 150 155 160

Val Thr Leu Tyr His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Val Thr Leu Tyr His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr 165 170 175 165 170 175

Gly Gly Trp Ala Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Gly Gly Trp Ala Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala 180 185 190 180 185 190

Glu Leu Cys Phe Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Glu Leu Cys Phe Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr 195 200 205 195 200 205

Ile Asp Asn Pro Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Ile Asp Asn Pro Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg 210 215 220 210 215 220

Leu Ala Pro Gly Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala Leu Ala Pro Gly Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala 225 230 235 240 225 230 235 240

His Asn Leu Leu Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr His Asn Leu Leu Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr 245 250 255 245 250 255

Ser Phe Arg Pro Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser Ser Phe Arg Pro Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser 260 265 270 260 265 270

His Trp Ile Asn Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys His Trp Ile Asn Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys 275 280 285 275 280 285

Gln Lys Ser Leu Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Gln Lys Ser Leu Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe 290 295 300 290 295 300

Ile Asp Gly Asp Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Ile Asp Gly Asp Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile 305 310 315 320 305 310 315 320

Leu Pro Asp Phe Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Leu Pro Asp Phe Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala 325 330 335 325 330 335 Page 120 Page 120

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Asp Phe Phe Ala Leu Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Phe Phe Ala Leu Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu 340 345 350 340 345 350

Asp Pro His Met Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Asp Pro His Met Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln 355 360 365 355 360 365

Leu Leu Ser Trp Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Leu Leu Ser Trp Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile 370 375 380 370 375 380

Val Glu Asn Gly Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Val Glu Asn Gly Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala 385 390 395 400 385 390 395 400

Lys Tyr Met Tyr Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Lys Tyr Met Tyr Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala 405 410 415 405 410 415

Ile Lys Leu Asp Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Ile Lys Leu Asp Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu 420 425 430 420 425 430

Met Asp Gly Phe Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Met Asp Gly Phe Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu 435 440 445 435 440 445

Phe Tyr Val Asp Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Phe Tyr Val Asp Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser 450 455 460 450 455 460

Ser Ala Leu Phe Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Ser Ala Leu Phe Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro 465 470 475 480 465 470 475 480

Leu Pro Glu Asn Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Leu Pro Glu Asn Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala 485 490 495 485 490 495

Trp Gly Val Val Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Trp Gly Val Val Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln 500 505 510 500 505 510

Phe Thr Asp Leu Asn Val Tyr Leu Trp Asp Val His His Ser Lys Arg Phe Thr Asp Leu Asn Val Tyr Leu Trp Asp Val His His Ser Lys Arg 515 520 525 515 520 525

Leu Ile Lys Val Asp Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Leu Ile Lys Val Asp Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys 530 535 540 530 535 540 Page 121 Page 121

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Val Asp Phe Ala Ala Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met Val Asp Phe Ala Ala Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met 545 550 555 560 545 550 555 560

His Val Thr His Phe Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro His Val Thr His Phe Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro 565 570 575 565 570 575

Leu Gly Asn Gln Ser Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Leu Gly Asn Gln Ser Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg 580 585 590 580 585 590

Cys Met Ala Ser Glu Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Cys Met Ala Ser Glu Leu Val Arg Val Asn Ile Thr Pro Val Val Ala 595 600 605 595 600 605

Leu Trp Gln Pro Met Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Leu Trp Gln Pro Met Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala 610 615 620 610 615 620

Arg Gln Gly Ala Trp Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Arg Gln Gly Ala Trp Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu 625 630 635 640 625 630 635 640

Tyr Ala Arg Leu Cys Phe Gln Glu Leu Gly His His Val Lys Leu Trp Tyr Ala Arg Leu Cys Phe Gln Glu Leu Gly His His Val Lys Leu Trp 645 650 655 645 650 655

Ile Thr Met Asn Glu Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly Ile Thr Met Asn Glu Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly 660 665 670 660 665 670

His Asn Leu Leu Lys Ala His Ala Leu Ala Trp His Val Tyr Asn Glu His Asn Leu Leu Lys Ala His Ala Leu Ala Trp His Val Tyr Asn Glu 675 680 685 675 680 685

Lys Phe Arg His Ala Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Lys Phe Arg His Ala Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala 690 695 700 690 695 700

Asp Trp Ile Glu Pro Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Asp Trp Ile Glu Pro Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val 705 710 715 720 705 710 715 720

Ala Glu Arg Val Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Ala Glu Arg Val Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile 725 730 735 725 730 735

Phe Gly Ser Gly Asp Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Phe Gly Ser Gly Asp Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln 740 745 750 740 745 750 Page 122 Page 122

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Arg Asn Asn Phe Leu Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Arg Asn Asn Phe Leu Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu 755 760 765 755 760 765

Ile Gln Gly Thr Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Ile Gln Gly Thr Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile 770 775 780 770 775 780

Leu Val Asp Ser Glu Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Leu Val Asp Ser Glu Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu 785 790 795 800 785 790 795 800

Glu Val Gln Glu Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Glu Val Gln Glu Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln 805 810 815 805 810 815

Val Ala Val Val Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Val Ala Val Val Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys 820 825 830 820 825 830

Phe Lys Tyr Gly Asp Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Phe Lys Tyr Gly Asp Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp 835 840 845 835 840 845

Asp Gly Leu His Ala Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asp Gly Leu His Ala Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln 850 855 860 850 855 860

Asn Tyr Ile Asn Glu Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Asn Tyr Ile Asn Glu Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn 865 870 875 880 865 870 875 880

Leu Cys Gly Tyr Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Leu Cys Gly Tyr Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg 885 890 895 885 890 895

Phe Gly Leu Tyr Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Phe Gly Leu Tyr Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser 900 905 910 900 905 910

Met Lys His Tyr Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Met Lys His Tyr Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro 915 920 925 915 920 925

Glu Thr Leu Glu Arg Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Glu Thr Leu Glu Arg Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu 930 935 940 930 935 940

Cys Ser Phe Phe His Thr Arg Lys Ser Cys Ser Phe Phe His Thr Arg Lys Ser 945 950 945 950 Page 123 Page 123

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

<210> 33 <210> 33 <211> 948 <211> 948 <212> PRT <212> PRT <213> Homo sapiens <213> Homo sapiens

<400> 33 <400> 33

Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro 1 5 10 15 1 5 10 15

Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe 20 25 30 20 25 30

Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln 35 40 45 35 40 45

Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro 50 55 60 50 55 60

Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala 65 70 75 80 70 75 80

Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr 85 90 95 85 90 95

Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr 100 105 110 100 105 110

His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser 115 120 125 115 120 125

Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu 130 135 140 130 135 140

Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His 145 150 155 160 145 150 155 160

Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn 165 170 175 165 170 175

Page 124 Page 124

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg 180 185 190 180 185 190

His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr 195 200 205 195 200 205

Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile 210 215 220 210 215 220

Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu 225 230 235 240 225 230 235 240

Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr 245 250 255 245 250 255

Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro 260 265 270 260 265 270

Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp 275 280 285 275 280 285

Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr 290 295 300 290 295 300

Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr 305 310 315 320 305 310 315 320

Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu 325 330 335 325 330 335

Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys 340 345 350 340 345 350

Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile 355 360 365 355 360 365

Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp 370 375 380 370 375 380

Page 125 Page 125

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr 385 390 395 400 385 390 395 400

Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly 405 410 415 405 410 415

Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu 420 425 430 420 425 430

Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe 435 440 445 435 440 445

Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr 450 455 460 450 455 460

Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln 465 470 475 480 465 470 475 480

Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp 485 490 495 485 490 495

Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn 500 505 510 500 505 510

Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp 515 520 525 515 520 525

Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala 530 535 540 530 535 540

Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe 545 550 555 560 545 550 555 560

Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser 565 570 575 565 570 575

Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu 580 585 590 580 585 590

Page 126 Page 126

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met 595 600 605 595 600 605

Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp 610 615 620 610 615 620

Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys 625 630 635 640 625 630 635 640

Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu 645 650 655 645 650 655

Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys 660 665 670 660 665 670

Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala 675 680 685 675 680 685

Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro 690 695 700 690 695 700

Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu 705 710 715 720 705 710 715 720

Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp 725 730 735 725 730 735

Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu 740 745 750 740 745 750

Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe 755 760 765 755 760 765

Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu 770 775 780 770 775 780

Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met 785 790 795 800 785 790 795 800

Page 127 Page 127

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro 805 810 815 805 810 815

Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp 820 825 830 820 825 830

Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala 835 840 845 835 840 845

Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu 850 855 860 850 855 860

Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe 865 870 875 880 865 870 875 880

Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg 885 890 895 885 890 895

Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg 900 905 910 900 905 910

Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg 915 920 925 915 920 925

Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His 930 935 940 930 935 940

Thr Arg Lys Ser Thr Arg Lys Ser 945 945

<210> 34 <210> 34 <211> 946 <211> 946 <212> PRT <212> PRT <213> Homo sapiens <213> Homo sapiens

<400> 34 <400> 34

Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro Ala Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro Ala Pro 1 5 10 15 1 5 10 15

Page 128 Page 128

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing TXT Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Leu Trp Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Leu Trp 20 25 30 20 25 30

Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Gln His Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Gln His 35 40 45 35 40 45

Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Leu Ala Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Leu Ala 50 55 60 50 55 60

Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Pro Ser Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Pro Ser 65 70 75 80 70 75 80

Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Asn Asn Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Asn Asn 85 90 95 85 90 95

Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr His Tyr Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr His Tyr 100 105 110 100 105 110

Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala Gly Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala Gly 115 120 125 115 120 125

Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu Arg Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu Arg 130 135 140 130 135 140

Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Trp Asp Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Trp Asp 145 150 155 160 145 150 155 160

Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Arg Ala Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Arg Ala 165 170 175 165 170 175

Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His Phe Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His Phe 180 185 190 180 185 190

Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val Val Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val Val 195 200 205 195 200 205

Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg Gly Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg Gly 210 215 220 210 215 220

Page 129 Page 129

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala His Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala His 225 230 235 240 225 230 235 240

Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln Gly Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln Gly 245 250 255 245 250 255

Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg Arg Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg Arg 260 265 270 260 265 270

Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Val Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Val 275 280 285 275 280 285

Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Pro Glu Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Pro Glu 290 295 300 290 295 300

Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Glu Ser Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Glu Ser 305 310 315 320 305 310 315 320

Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Ser Phe Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Ser Phe 325 330 335 325 330 335

Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Arg Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Arg 340 345 350 340 345 350

Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Asp Leu Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Asp Leu 355 360 365 355 360 365

Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Val Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Val 370 375 380 370 375 380

Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Lys Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Lys 385 390 395 400 385 390 395 400

Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Val Asp Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Val Asp 405 410 415 405 410 415

Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp His Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp His 420 425 430 420 425 430

Page 130 Page 130

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu Ser Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu Ser 435 440 445 435 440 445

Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys 450 455 460 450 455 460

Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu 465 470 475 480 465 470 475 480

Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Tyr Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Tyr 485 490 495 485 490 495

Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Val Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Val Tyr 500 505 510 500 505 510

Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Gly Val Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Gly Val 515 520 525 515 520 525

Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Ile Gln Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Ile Gln 530 535 540 530 535 540

Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe Arg Phe Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe Arg Phe 545 550 555 560 545 550 555 560

Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Gln Val Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Gln Val 565 570 575 565 570 575

Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu Leu Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu Leu Val 580 585 590 580 585 590

Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met Ala Pro Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met Ala Pro 595 600 605 595 600 605

Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp Glu Asn Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp Glu Asn 610 615 620 610 615 620

Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys Phe Gln Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys Phe Gln 625 630 635 640 625 630 635 640

Page 131 Page 131

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu Pro Tyr Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu Pro Tyr 645 650 655 645 650 655

Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Ala His Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Ala His 660 665 670 660 665 670

Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala Gln Asn Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala Gln Asn 675 680 685 675 680 685

Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Ala Cys Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Ala Cys 690 695 700 690 695 700

Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu Glu Phe Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu Glu Phe 705 710 715 720 705 710 715 720

Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Tyr Pro Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Tyr Pro 725 730 735 725 730 735

Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu Leu Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu Leu Pro 740 745 750 740 745 750

Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe Asp Phe Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe Asp Phe 755 760 765 755 760 765

Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu Lys Glu Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu Lys Glu 770 775 780 770 775 780

Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Thr Asp Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Thr Asp 785 790 795 800 785 790 795 800

Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Trp Gly Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Trp Gly 805 810 815 805 810 815

Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp Leu Pro Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp Leu Pro 820 825 830 820 825 830

Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala Glu Asp Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala Glu Asp 835 840 845 835 840 845

Page 132 Page 132

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu Ala Leu Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu Ala Leu 850 855 860 850 855 860

Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe Ala Tyr Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe Ala Tyr 865 870 875 880 865 870 875 880

Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg Tyr Ala Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg Tyr Ala 885 890 895 885 890 895

Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Lys Ile Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Lys Ile 900 905 910 900 905 910

Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Phe Cys Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Phe Cys 915 920 925 915 920 925

Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His Thr Arg Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His Thr Arg 930 935 940 930 935 940

Lys Ser Lys Ser 945 945

<210> 35 <210> 35 <211> 549 <211> 549 <212> PRT <212> PRT <213> Homo sapiens <213> Homo sapiens

<400> 35 <400> 35

Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser 1 5 10 15 1 5 10 15

Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg 20 25 30 20 25 30

Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro 35 40 45 35 40 45

Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly 50 55 60 50 55 60

Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Page 133 Page 133

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 65 70 75 80 70 75 80

Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His 85 90 95 85 90 95

Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly 100 105 110 100 105 110

Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser 115 120 125 115 120 125

Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val 130 135 140 130 135 140

Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly 145 150 155 160 145 150 155 160

Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu 165 170 175 165 170 175

Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr 180 185 190 180 185 190

His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala 195 200 205 195 200 205

Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe 210 215 220 210 215 220

Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro 225 230 235 240 225 230 235 240

Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly 245 250 255 245 250 255

Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu 260 265 270 260 265 270

Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Page 134 Page 134

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 275 280 285 275 280 285

Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn 290 295 300 290 295 300

Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu 305 310 315 320 305 310 315 320

Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp 325 330 335 325 330 335

Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe 340 345 350 340 345 350

Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala 355 360 365 355 360 365

Leu Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Leu Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met 370 375 380 370 375 380

Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp 385 390 395 400 385 390 395 400

Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly 405 410 415 405 410 415

Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr 420 425 430 420 425 430

Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp 435 440 445 435 440 445

Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe 450 455 460 450 455 460

Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp 465 470 475 480 465 470 475 480

Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Page 135 Page 135

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 485 490 495 485 490 495

Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn 500 505 510 500 505 510

Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val 515 520 525 515 520 525

Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu 530 535 540 530 535 540

Asn Val Tyr Leu Trp Asn Val Tyr Leu Trp 545 545

<210> 36 <210> 36 <211> 521 <211> 521 <212> PRT <212> PRT <213> Homo sapiens <213> Homo sapiens

<400> 36 <400> 36

Arg Arg Leu Arg Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Arg Arg Leu Arg Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg 1 5 10 15 1 5 10 15

Val Ser Arg Pro Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Val Ser Arg Pro Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr 20 25 30 20 25 30

Phe Pro Asp Gly Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Phe Pro Asp Gly Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr 35 40 45 35 40 45

Glu Gly Gly Trp Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Glu Gly Gly Trp Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr 50 55 60 50 55 60

Phe Thr His His Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Phe Thr His His Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser 65 70 75 80 70 75 80

Leu Pro Leu Gly Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Leu Pro Leu Gly Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val 85 90 95 85 90 95

Ala Ser Asp Ser Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Ala Ser Asp Ser Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg 100 105 110 100 105 110 Page 136 Page 136

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Glu Leu Gly Val Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Glu Leu Gly Val Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val 115 120 125 115 120 125

Leu Pro Asn Gly Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Leu Pro Asn Gly Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr 130 135 140 130 135 140

Tyr Arg Arg Leu Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Tyr Arg Arg Leu Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val 145 150 155 160 145 150 155 160

Val Thr Leu Tyr His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Val Thr Leu Tyr His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr 165 170 175 165 170 175

Gly Gly Trp Ala Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Gly Gly Trp Ala Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala 180 185 190 180 185 190

Glu Leu Cys Phe Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Glu Leu Cys Phe Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr 195 200 205 195 200 205

Ile Asp Asn Pro Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Ile Asp Asn Pro Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg 210 215 220 210 215 220

Leu Ala Pro Gly Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala Leu Ala Pro Gly Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala 225 230 235 240 225 230 235 240

His Asn Leu Leu Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr His Asn Leu Leu Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr 245 250 255 245 250 255

Ser Phe Arg Pro Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser Ser Phe Arg Pro Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser 260 265 270 260 265 270

His Trp Ile Asn Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys His Trp Ile Asn Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys 275 280 285 275 280 285

Gln Lys Ser Leu Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Gln Lys Ser Leu Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe 290 295 300 290 295 300

Ile Asp Gly Asp Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Ile Asp Gly Asp Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile 305 310 315 320 305 310 315 320 Page 137 Page 137

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Leu Pro Asp Phe Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Leu Pro Asp Phe Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala 325 330 335 325 330 335

Asp Phe Phe Ala Leu Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Phe Phe Ala Leu Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu 340 345 350 340 345 350

Asp Pro His Met Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Asp Pro His Met Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln 355 360 365 355 360 365

Leu Leu Ser Trp Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Leu Leu Ser Trp Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile 370 375 380 370 375 380

Val Glu Asn Gly Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Val Glu Asn Gly Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala 385 390 395 400 385 390 395 400

Lys Tyr Met Tyr Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Lys Tyr Met Tyr Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala 405 410 415 405 410 415

Ile Lys Leu Asp Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Ile Lys Leu Asp Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu 420 425 430 420 425 430

Met Asp Gly Phe Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Met Asp Gly Phe Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu 435 440 445 435 440 445

Phe Tyr Val Asp Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Phe Tyr Val Asp Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser 450 455 460 450 455 460

Ser Ala Leu Phe Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Ser Ala Leu Phe Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro 465 470 475 480 465 470 475 480

Leu Pro Glu Asn Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Leu Pro Glu Asn Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala 485 490 495 485 490 495

Trp Gly Val Val Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Trp Gly Val Val Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln 500 505 510 500 505 510

Phe Thr Asp Leu Asn Val Tyr Leu Trp Phe Thr Asp Leu Asn Val Tyr Leu Trp 515 520 515 520 Page 138 Page 138

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

<210> 37 <210> 37 <211> 516 <211> 516 <212> PRT <212> PRT <213> Homo sapiens <213> Homo sapiens

<400> 37 <400> 37

Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro 1 5 10 15 1 5 10 15

Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe 20 25 30 20 25 30

Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln 35 40 45 35 40 45

Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro 50 55 60 50 55 60

Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala 65 70 75 80 70 75 80

Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr 85 90 95 85 90 95

Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr 100 105 110 100 105 110

His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser 115 120 125 115 120 125

Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu 130 135 140 130 135 140

Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His 145 150 155 160 145 150 155 160

Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn 165 170 175 165 170 175

Page 139 Page 139

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg 180 185 190 180 185 190

His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr 195 200 205 195 200 205

Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile 210 215 220 210 215 220

Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu 225 230 235 240 225 230 235 240

Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr 245 250 255 245 250 255

Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro 260 265 270 260 265 270

Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp 275 280 285 275 280 285

Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr 290 295 300 290 295 300

Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr 305 310 315 320 305 310 315 320

Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu 325 330 335 325 330 335

Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys 340 345 350 340 345 350

Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile 355 360 365 355 360 365

Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp 370 375 380 370 375 380

Page 140 Page 140

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr 385 390 395 400 385 390 395 400

Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly 405 410 415 405 410 415

Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu 420 425 430 420 425 430

Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe 435 440 445 435 440 445

Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr 450 455 460 450 455 460

Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln 465 470 475 480 465 470 475 480

Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp 485 490 495 485 490 495

Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn 500 505 510 500 505 510

Val Tyr Leu Trp Val Tyr Leu Trp 515 515

<210> 38 <210> 38 <211> 514 <211> 514 <212> PRT <212> PRT <213> Homo sapiens <213> Homo sapiens

<400> 38 <400> 38

Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro Ala Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro Ala Pro 1 5 10 15 1 5 10 15

Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Leu Trp Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Leu Trp 20 25 30 20 25 30

Page 141 Page 141

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing TXT Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Gln His Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Gln His 35 40 45 35 40 45

Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Leu Ala Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Leu Ala 50 55 60 50 55 60

Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Pro Ser Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Pro Ser 65 70 75 80 70 75 80

Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Asn Asn Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Asn Asn 85 90 95 85 90 95

Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr His Tyr Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr His Tyr 100 105 110 100 105 110

Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala Gly Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala Gly 115 120 125 115 120 125

Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu Arg Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu Arg 130 135 140 130 135 140

Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Trp Asp Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Trp Asp 145 150 155 160 145 150 155 160

Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Arg Ala Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Arg Ala 165 170 175 165 170 175

Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His Phe Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His Phe 180 185 190 180 185 190

Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val Val Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val Val 195 200 205 195 200 205

Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg Gly Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg Gly 210 215 220 210 215 220

Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala His Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala His 225 230 235 240 225 230 235 240

Page 142 Page 142

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln Gly Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln Gly 245 250 255 245 250 255

Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg Arg Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg Arg 260 265 270 260 265 270

Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Val Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Val 275 280 285 275 280 285

Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Pro Glu Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Pro Glu 290 295 300 290 295 300

Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Glu Ser Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Glu Ser 305 310 315 320 305 310 315 320

Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Ser Phe Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Ser Phe 325 330 335 325 330 335

Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Arg Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Arg 340 345 350 340 345 350

Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Asp Leu Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Asp Leu 355 360 365 355 360 365

Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Val Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Val 370 375 380 370 375 380

Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Lys Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Lys 385 390 395 400 385 390 395 400

Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Val Asp Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Val Asp 405 410 415 405 410 415

Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp His Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp His 420 425 430 420 425 430

Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu Ser Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu Ser 435 440 445 435 440 445

Page 143 Page 143

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys 450 455 460 450 455 460

Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu 465 470 475 480 465 470 475 480

Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Tyr Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Tyr 485 490 495 485 490 495

Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Val Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Val Tyr 500 505 510 500 505 510

Leu Trp Leu Trp

<210> 39 <210> 39 <211> 1218 <211> 1218 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> Protein_Native_SS_34_981V_GS_IgG1_noCH1_Fc_Fusion <223> Protein_Native_SS_34_981V_GS_IgG1_noCH1_Fc_Fusion

<400> 39 <400> 39

Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser 1 5 10 15 1 5 10 15

Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg 20 25 30 20 25 30

Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro 35 40 45 35 40 45

Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly 50 55 60 50 55 60

Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp 65 70 75 80 70 75 80

Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His 85 90 95 85 90 95 Page 144 Page 144

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly 100 105 110 100 105 110

Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser 115 120 125 115 120 125

Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val 130 135 140 130 135 140

Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly 145 150 155 160 145 150 155 160

Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu 165 170 175 165 170 175

Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr 180 185 190 180 185 190

His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala 195 200 205 195 200 205

Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe 210 215 220 210 215 220

Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro 225 230 235 240 225 230 235 240

Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly 245 250 255 245 250 255

Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu 260 265 270 260 265 270

Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro 275 280 285 275 280 285

Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn 290 295 300 290 295 300 Page 145 Page 145

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu 305 310 315 320 305 310 315 320

Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp 325 330 335 325 330 335

Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe 340 345 350 340 345 350

Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala 355 360 365 355 360 365

Leu Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Leu Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met 370 375 380 370 375 380

Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp 385 390 395 400 385 390 395 400

Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly 405 410 415 405 410 415

Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr 420 425 430 420 425 430

Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp 435 440 445 435 440 445

Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe 450 455 460 450 455 460

Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp 465 470 475 480 465 470 475 480

Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe 485 490 495 485 490 495

Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn 500 505 510 500 505 510

Page 146 Page 146

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val 515 520 525 515 520 525

Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu 530 535 540 530 535 540

Asn Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asn Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val 545 550 555 560 545 550 555 560

Asp Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Asp Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala 565 570 575 565 570 575

Ala Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Ala Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His 580 585 590 580 585 590

Phe Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Phe Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln 595 600 605 595 600 605

Ser Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Ser Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser 610 615 620 610 615 620

Glu Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Glu Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro 625 630 635 640 625 630 635 640

Met Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Met Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala 645 650 655 645 650 655

Trp Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Trp Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu 660 665 670 660 665 670

Cys Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Cys Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn 675 680 685 675 680 685

Glu Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Glu Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu 690 695 700 690 695 700

Lys Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Lys Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His 705 710 715 720 705 710 715 720 Page 147 Page 147

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Ala Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Ala Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu 725 730 735 725 730 735

Pro Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Pro Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val 740 745 750 740 745 750

Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly 755 760 765 755 760 765

Asp Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Asp Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe 770 775 780 770 775 780

Leu Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Leu Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr 785 790 795 800 785 790 795 800

Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser 805 810 815 805 810 815

Glu Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Glu Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu 820 825 830 820 825 830

Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val 835 840 845 835 840 845

Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly 850 855 860 850 855 860

Asp Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Asp Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His 865 870 875 880 865 870 875 880

Ala Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Ala Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn 885 890 895 885 890 895

Glu Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Glu Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr 900 905 910 900 905 910

Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr 915 920 925 915 920 925 Page 148 Page 148

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr 930 935 940 930 935 940

Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu 945 950 955 960 945 950 955 960

Arg Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe Arg Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe 965 970 975 965 970 975

His Thr Arg Lys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp His Thr Arg Lys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp 980 985 990 980 985 990

Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 995 1000 1005 995 1000 1005

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 1010 1015 1020 1010 1015 1020

Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 1025 1030 1035 1025 1030 1035

His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val 1040 1045 1050 1040 1045 1050

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn 1055 1060 1065 1055 1060 1065

Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 1070 1075 1080 1070 1075 1080

Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala 1085 1090 1095 1085 1090 1095

Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 1100 1105 1110 1100 1105 1110

Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 1115 1120 1125 1115 1120 1125 Page 149 Page 149

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe 1130 1135 1140 1130 1135 1140

Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 1145 1150 1155 1145 1150 1155

Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly 1160 1165 1170 1160 1165 1170

Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp 1175 1180 1185 1175 1180 1185

Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 1190 1195 1200 1190 1195 1200

His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 1205 1210 1215 1205 1210 1215

<210> 40 <210> 40 <211> 1185 <211> 1185 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> Protein_34_981V_GS_IgG1_noCH1_Fc_Fusion <223> Protein_34_981V_GS_IgG1_noCH1_Fc_Fusion

<400> 40 <400> 40

Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro 1 5 10 15 1 5 10 15

Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe 20 25 30 20 25 30

Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln 35 40 45 35 40 45

Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro 50 55 60 50 55 60

Page 150 Page 150

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala 65 70 75 80 70 75 80

Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr 85 90 95 85 90 95

Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr 100 105 110 100 105 110

His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser 115 120 125 115 120 125

Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu 130 135 140 130 135 140

Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His 145 150 155 160 145 150 155 160

Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn 165 170 175 165 170 175

Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg 180 185 190 180 185 190

His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr 195 200 205 195 200 205

Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile 210 215 220 210 215 220

Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu 225 230 235 240 225 230 235 240

Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr 245 250 255 245 250 255

Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro 260 265 270 260 265 270

Page 151 Page 151

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp 275 280 285 275 280 285

Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr 290 295 300 290 295 300

Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr 305 310 315 320 305 310 315 320

Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu 325 330 335 325 330 335

Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys 340 345 350 340 345 350

Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile 355 360 365 355 360 365

Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp 370 375 380 370 375 380

Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr 385 390 395 400 385 390 395 400

Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly 405 410 415 405 410 415

Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu 420 425 430 420 425 430

Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe 435 440 445 435 440 445

Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr 450 455 460 450 455 460

Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln 465 470 475 480 465 470 475 480

Page 152 Page 152

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp 485 490 495 485 490 495

Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn 500 505 510 500 505 510

Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp 515 520 525 515 520 525

Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala 530 535 540 530 535 540

Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe 545 550 555 560 545 550 555 560

Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser 565 570 575 565 570 575

Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu 580 585 590 580 585 590

Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met 595 600 605 595 600 605

Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp 610 615 620 610 615 620

Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys 625 630 635 640 625 630 635 640

Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu 645 650 655 645 650 655

Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys 660 665 670 660 665 670

Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala 675 680 685 675 680 685

Page 153 Page 153

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro 690 695 700 690 695 700

Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu 705 710 715 720 705 710 715 720

Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp 725 730 735 725 730 735

Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu 740 745 750 740 745 750

Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe 755 760 765 755 760 765

Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu 770 775 780 770 775 780

Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met 785 790 795 800 785 790 795 800

Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro 805 810 815 805 810 815

Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp 820 825 830 820 825 830

Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala 835 840 845 835 840 845

Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu 850 855 860 850 855 860

Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe 865 870 875 880 865 870 875 880

Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg 885 890 895 885 890 895

Page 154 Page 154

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg 900 905 910 900 905 910

Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg 915 920 925 915 920 925

Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His 930 935 940 930 935 940

Thr Arg Lys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr Arg Lys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys 945 950 955 960 945 950 955 960

Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro 965 970 975 965 970 975

Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 980 985 990 980 985 990

Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp 995 1000 1005 995 1000 1005

Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 1010 1015 1020 1010 1015 1020

Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 1025 1030 1035 1025 1030 1035

Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 1040 1045 1050 1040 1045 1050

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala 1055 1060 1065 1055 1060 1065

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 1070 1075 1080 1070 1075 1080

Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys 1085 1090 1095 1085 1090 1095

Page 155 Page 155

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser 1100 1105 1110 1100 1105 1110

Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 1115 1120 1125 1115 1120 1125

Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 1130 1135 1140 1130 1135 1140

Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly 1145 1150 1155 1145 1150 1155

Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 1160 1165 1170 1160 1165 1170

Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 1175 1180 1185 1175 1180 1185

<210> 41 <210> 41 <211> 786 <211> 786 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> Protein_Native_SS_34_549V_GS_IgG1_noCH1_Fc_Fusion <223> Protein_Native_SS_34_549V_GS_IgG1_noCH1_Fc_Fusion

<400> 41 <400> 41

Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser 1 5 10 15 1 5 10 15

Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg 20 25 30 20 25 30

Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro 35 40 45 35 40 45

Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly 50 55 60 50 55 60

Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp 65 70 75 80 70 75 80 Page 156 Page 156

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His 85 90 95 85 90 95

Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly 100 105 110 100 105 110

Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser 115 120 125 115 120 125

Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val 130 135 140 130 135 140

Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly 145 150 155 160 145 150 155 160

Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu 165 170 175 165 170 175

Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr 180 185 190 180 185 190

His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala 195 200 205 195 200 205

Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe 210 215 220 210 215 220

Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro 225 230 235 240 225 230 235 240

Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly 245 250 255 245 250 255

Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu 260 265 270 260 265 270

Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro 275 280 285 275 280 285 Page 157 Page 157

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn 290 295 300 290 295 300

Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu 305 310 315 320 305 310 315 320

Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp 325 330 335 325 330 335

Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe 340 345 350 340 345 350

Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala 355 360 365 355 360 365

Leu Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Leu Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met 370 375 380 370 375 380

Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp 385 390 395 400 385 390 395 400

Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly 405 410 415 405 410 415

Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr 420 425 430 420 425 430

Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp 435 440 445 435 440 445

Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe 450 455 460 450 455 460

Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp 465 470 475 480 465 470 475 480

Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe 485 490 495 485 490 495 Page 158 Page 158

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn 500 505 510 500 505 510

Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val 515 520 525 515 520 525

Asp Asn Tyr Ile Gln Val Ser Gln Leu Thr Lys Pro Ile Ser Ser Leu Asp Asn Tyr Ile Gln Val Ser Gln Leu Thr Lys Pro Ile Ser Ser Leu 530 535 540 530 535 540

Thr Lys Pro Tyr His Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Thr Lys Pro Tyr His Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp 545 550 555 560 545 550 555 560

Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 565 570 575 565 570 575

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 580 585 590 580 585 590

Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 595 600 605 595 600 605

Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 610 615 620 610 615 620

Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg 625 630 635 640 625 630 635 640

Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 645 650 655 645 650 655

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 660 665 670 660 665 670

Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 675 680 685 675 680 685

Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu 690 695 700 690 695 700 Page 159 Page 159

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 705 710 715 720 705 710 715 720

Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 725 730 735 725 730 735

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 740 745 750 740 745 750

Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 755 760 765 755 760 765

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 770 775 780 770 775 780

Gly Lys Gly Lys 785 785

<210> 42 <210> 42 <211> 753 <211> 753 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> Protein_34_549V_GS_IgG1_noCH1_Fc_Fusion <223> Protein_34_549V_GS_IgG1_noCH1_Fc_Fusion

<400> 42 <400> 42

Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro 1 5 10 15 1 5 10 15

Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe 20 25 30 20 25 30

Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln 35 40 45 35 40 45

Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro 50 55 60 50 55 60

Page 160 Page 160

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala 65 70 75 80 70 75 80

Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr 85 90 95 85 90 95

Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr 100 105 110 100 105 110

His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser 115 120 125 115 120 125

Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu 130 135 140 130 135 140

Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His 145 150 155 160 145 150 155 160

Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn 165 170 175 165 170 175

Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg 180 185 190 180 185 190

His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr 195 200 205 195 200 205

Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile 210 215 220 210 215 220

Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu 225 230 235 240 225 230 235 240

Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr 245 250 255 245 250 255

Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro 260 265 270 260 265 270

Page 161 Page 161

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp 275 280 285 275 280 285

Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr 290 295 300 290 295 300

Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr 305 310 315 320 305 310 315 320

Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu 325 330 335 325 330 335

Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys 340 345 350 340 345 350

Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile 355 360 365 355 360 365

Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp 370 375 380 370 375 380

Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr 385 390 395 400 385 390 395 400

Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly 405 410 415 405 410 415

Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu 420 425 430 420 425 430

Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe 435 440 445 435 440 445

Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr 450 455 460 450 455 460

Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln 465 470 475 480 465 470 475 480

Page 162 Page 162

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp 485 490 495 485 490 495

Asn Tyr Ile Gln Val Ser Gln Leu Thr Lys Pro Ile Ser Ser Leu Thr Asn Tyr Ile Gln Val Ser Gln Leu Thr Lys Pro Ile Ser Ser Leu Thr 500 505 510 500 505 510

Lys Pro Tyr His Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Lys Pro Tyr His Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys 515 520 525 515 520 525

Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro 530 535 540 530 535 540

Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 545 550 555 560 545 550 555 560

Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp 565 570 575 565 570 575

Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 580 585 590 580 585 590

Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val 595 600 605 595 600 605

Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu 610 615 620 610 615 620

Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys 625 630 635 640 625 630 635 640

Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 645 650 655 645 650 655

Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr 660 665 670 660 665 670

Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 675 680 685 675 680 685

Page 163 Page 163

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 690 695 700 690 695 700

Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys 705 710 715 720 705 710 715 720

Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu 725 730 735 725 730 735

Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 740 745 750 740 745 750

Lys Lys

<210> 43 <210> 43 <211> 1218 <211> 1218 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> Protein_Native_SS_34_981V_C370S_GS_IgG1_noCH1_Fc_Fusion <223> Protein_Native_SS_34_981V_C370S_GS_IgG1_noCH1_Fc_Fusion

<400> 43 <400> 43

Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser 1 5 10 15 1 5 10 15

Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg 20 25 30 20 25 30

Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro 35 40 45 35 40 45

Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly 50 55 60 50 55 60

Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp 65 70 75 80 70 75 80

Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His 85 90 95 85 90 95 Page 164 Page 164

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly 100 105 110 100 105 110

Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser 115 120 125 115 120 125

Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val 130 135 140 130 135 140

Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly 145 150 155 160 145 150 155 160

Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu 165 170 175 165 170 175

Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr 180 185 190 180 185 190

His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala 195 200 205 195 200 205

Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe 210 215 220 210 215 220

Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro 225 230 235 240 225 230 235 240

Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly 245 250 255 245 250 255

Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu 260 265 270 260 265 270

Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro 275 280 285 275 280 285

Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn 290 295 300 290 295 300 Page 165 Page 165

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu 305 310 315 320 305 310 315 320

Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp 325 330 335 325 330 335

Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe 340 345 350 340 345 350

Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala 355 360 365 355 360 365

Leu Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Leu Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met 370 375 380 370 375 380

Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp 385 390 395 400 385 390 395 400

Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly 405 410 415 405 410 415

Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr 420 425 430 420 425 430

Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp 435 440 445 435 440 445

Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe 450 455 460 450 455 460

Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp 465 470 475 480 465 470 475 480

Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe 485 490 495 485 490 495

Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn 500 505 510 500 505 510

Page 166 Page 166

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val 515 520 525 515 520 525

Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu 530 535 540 530 535 540

Asn Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asn Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val 545 550 555 560 545 550 555 560

Asp Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Asp Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala 565 570 575 565 570 575

Ala Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Ala Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His 580 585 590 580 585 590

Phe Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Phe Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln 595 600 605 595 600 605

Ser Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Ser Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser 610 615 620 610 615 620

Glu Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Glu Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro 625 630 635 640 625 630 635 640

Met Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Met Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala 645 650 655 645 650 655

Trp Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Trp Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu 660 665 670 660 665 670

Cys Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Cys Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn 675 680 685 675 680 685

Glu Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Glu Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu 690 695 700 690 695 700

Lys Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Lys Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His 705 710 715 720 705 710 715 720 Page 167 Page 167

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Ala Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Ala Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu 725 730 735 725 730 735

Pro Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Pro Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val 740 745 750 740 745 750

Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly 755 760 765 755 760 765

Asp Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Asp Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe 770 775 780 770 775 780

Leu Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Leu Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr 785 790 795 800 785 790 795 800

Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser 805 810 815 805 810 815

Glu Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Glu Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu 820 825 830 820 825 830

Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val 835 840 845 835 840 845

Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly 850 855 860 850 855 860

Asp Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Asp Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His 865 870 875 880 865 870 875 880

Ala Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Ala Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn 885 890 895 885 890 895

Glu Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Glu Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr 900 905 910 900 905 910

Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr 915 920 925 915 920 925 Page 168 Page 168

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr 930 935 940 930 935 940

Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu 945 950 955 960 945 950 955 960

Arg Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe Arg Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe 965 970 975 965 970 975

His Thr Arg Lys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp His Thr Arg Lys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp 980 985 990 980 985 990

Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 995 1000 1005 995 1000 1005

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 1010 1015 1020 1010 1015 1020

Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 1025 1030 1035 1025 1030 1035

His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val 1040 1045 1050 1040 1045 1050

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn 1055 1060 1065 1055 1060 1065

Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 1070 1075 1080 1070 1075 1080

Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala 1085 1090 1095 1085 1090 1095

Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 1100 1105 1110 1100 1105 1110

Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 1115 1120 1125 1115 1120 1125 Page 169 Page 169

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe 1130 1135 1140 1130 1135 1140

Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 1145 1150 1155 1145 1150 1155

Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly 1160 1165 1170 1160 1165 1170

Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp 1175 1180 1185 1175 1180 1185

Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 1190 1195 1200 1190 1195 1200

His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 1205 1210 1215 1205 1210 1215

<210> 44 <210> 44 <211> 1185 <211> 1185 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> Protein_34_981V_C370S_GS_IgG1_noCH1_Fc_Fusion <223> Protein_34_981V_C370S_GS_IgG1_noCH1_Fc_Fusion

<400> 44 <400> 44

Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro 1 5 10 15 1 5 10 15

Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe 20 25 30 20 25 30

Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln 35 40 45 35 40 45

Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro 50 55 60 50 55 60

Page 170 Page 170

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala 65 70 75 80 70 75 80

Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr 85 90 95 85 90 95

Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr 100 105 110 100 105 110

His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser 115 120 125 115 120 125

Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu 130 135 140 130 135 140

Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His 145 150 155 160 145 150 155 160

Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn 165 170 175 165 170 175

Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg 180 185 190 180 185 190

His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr 195 200 205 195 200 205

Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile 210 215 220 210 215 220

Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu 225 230 235 240 225 230 235 240

Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr 245 250 255 245 250 255

Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro 260 265 270 260 265 270

Page 171 Page 171

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp 275 280 285 275 280 285

Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr 290 295 300 290 295 300

Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr 305 310 315 320 305 310 315 320

Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu 325 330 335 325 330 335

Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys 340 345 350 340 345 350

Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile 355 360 365 355 360 365

Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp 370 375 380 370 375 380

Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr 385 390 395 400 385 390 395 400

Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly 405 410 415 405 410 415

Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu 420 425 430 420 425 430

Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe 435 440 445 435 440 445

Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr 450 455 460 450 455 460

Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln 465 470 475 480 465 470 475 480

Page 172 Page 172

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp 485 490 495 485 490 495

Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn 500 505 510 500 505 510

Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp 515 520 525 515 520 525

Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala 530 535 540 530 535 540

Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe 545 550 555 560 545 550 555 560

Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser 565 570 575 565 570 575

Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu 580 585 590 580 585 590

Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met 595 600 605 595 600 605

Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp 610 615 620 610 615 620

Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys 625 630 635 640 625 630 635 640

Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu 645 650 655 645 650 655

Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys 660 665 670 660 665 670

Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala 675 680 685 675 680 685

Page 173 Page 173

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro 690 695 700 690 695 700

Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu 705 710 715 720 705 710 715 720

Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp 725 730 735 725 730 735

Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu 740 745 750 740 745 750

Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe 755 760 765 755 760 765

Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu 770 775 780 770 775 780

Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met 785 790 795 800 785 790 795 800

Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro 805 810 815 805 810 815

Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp 820 825 830 820 825 830

Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala 835 840 845 835 840 845

Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu 850 855 860 850 855 860

Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe 865 870 875 880 865 870 875 880

Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg 885 890 895 885 890 895

Page 174 Page 174

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg 900 905 910 900 905 910

Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg 915 920 925 915 920 925

Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His 930 935 940 930 935 940

Thr Arg Lys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr Arg Lys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys 945 950 955 960 945 950 955 960

Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro 965 970 975 965 970 975

Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 980 985 990 980 985 990

Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp 995 1000 1005 995 1000 1005

Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 1010 1015 1020 1010 1015 1020

Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 1025 1030 1035 1025 1030 1035

Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 1040 1045 1050 1040 1045 1050

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala 1055 1060 1065 1055 1060 1065

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 1070 1075 1080 1070 1075 1080

Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys 1085 1090 1095 1085 1090 1095

Page 175 Page 175

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing.1 TXT Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser 1100 1105 1110 1100 1105 1110

Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 1115 1120 1125 1115 1120 1125

Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 1130 1135 1140 1130 1135 1140

Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly 1145 1150 1155 1145 1150 1155

Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 1160 1165 1170 1160 1165 1170

Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 1175 1180 1185 1175 1180 1185

<210> 45 <210> 45 <211> 786 <211> 786 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> Protein_Native_SS_34_549V_C370S_GS_IgG1_noCH1_Fc_Fusion <223> Protein_Native_SS_34_549V_C370S_GS_IgG1_noCH1_Fc_Fusion

<400> 45 <400> 45

Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser 1 5 10 15 1 5 10 15

Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg 20 25 30 20 25 30

Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro 35 40 45 35 40 45

Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly 50 55 60 50 55 60

Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp 65 70 75 80 70 75 80 Page 176 Page 176

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His 85 90 95 85 90 95

Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly 100 105 110 100 105 110

Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser 115 120 125 115 120 125

Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val 130 135 140 130 135 140

Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly 145 150 155 160 145 150 155 160

Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu 165 170 175 165 170 175

Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr 180 185 190 180 185 190

His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala 195 200 205 195 200 205

Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe 210 215 220 210 215 220

Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro 225 230 235 240 225 230 235 240

Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly 245 250 255 245 250 255

Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu 260 265 270 260 265 270

Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro 275 280 285 275 280 285 Page 177 Page 177

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn 290 295 300 290 295 300

Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu 305 310 315 320 305 310 315 320

Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp 325 330 335 325 330 335

Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe 340 345 350 340 345 350

Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala 355 360 365 355 360 365

Leu Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Leu Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met 370 375 380 370 375 380

Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp 385 390 395 400 385 390 395 400

Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly 405 410 415 405 410 415

Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr 420 425 430 420 425 430

Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp 435 440 445 435 440 445

Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe 450 455 460 450 455 460

Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp 465 470 475 480 465 470 475 480

Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe 485 490 495 485 490 495 Page 178 Page 178

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn 500 505 510 500 505 510

Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val 515 520 525 515 520 525

Asp Asn Tyr Ile Gln Val Ser Gln Leu Thr Lys Pro Ile Ser Ser Leu Asp Asn Tyr Ile Gln Val Ser Gln Leu Thr Lys Pro Ile Ser Ser Leu 530 535 540 530 535 540

Thr Lys Pro Tyr His Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Thr Lys Pro Tyr His Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp 545 550 555 560 545 550 555 560

Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 565 570 575 565 570 575

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 580 585 590 580 585 590

Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 595 600 605 595 600 605

Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 610 615 620 610 615 620

Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg 625 630 635 640 625 630 635 640

Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 645 650 655 645 650 655

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 660 665 670 660 665 670

Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 675 680 685 675 680 685

Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu 690 695 700 690 695 700 Page 179 Page 179

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 705 710 715 720 705 710 715 720

Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 725 730 735 725 730 735

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 740 745 750 740 745 750

Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 755 760 765 755 760 765

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 770 775 780 770 775 780

Gly Lys Gly Lys 785 785

<210> 46 <210> 46 <211> 753 <211> 753 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> Protein_34_549V_C370S_GS_IgG1_noCH1_Fc_Fusion <223> Protein_34_549V_C370S_GS_IgG1_noCH1_Fc_Fusion

<400> 46 <400> 46

Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro 1 5 10 15 1 5 10 15

Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe 20 25 30 20 25 30

Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln 35 40 45 35 40 45

Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro 50 55 60 50 55 60

Page 180 Page 180

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala 65 70 75 80 70 75 80

Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr 85 90 95 85 90 95

Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr 100 105 110 100 105 110

His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser 115 120 125 115 120 125

Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu 130 135 140 130 135 140

Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His 145 150 155 160 145 150 155 160

Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn 165 170 175 165 170 175

Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg 180 185 190 180 185 190

His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr 195 200 205 195 200 205

Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile 210 215 220 210 215 220

Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu 225 230 235 240 225 230 235 240

Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr 245 250 255 245 250 255

Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro 260 265 270 260 265 270

Page 181 Page 181

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp 275 280 285 275 280 285

Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr 290 295 300 290 295 300

Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr 305 310 315 320 305 310 315 320

Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu 325 330 335 325 330 335

Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys 340 345 350 340 345 350

Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile 355 360 365 355 360 365

Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp 370 375 380 370 375 380

Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr 385 390 395 400 385 390 395 400

Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly 405 410 415 405 410 415

Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu 420 425 430 420 425 430

Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe 435 440 445 435 440 445

Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr 450 455 460 450 455 460

Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln 465 470 475 480 465 470 475 480

Page 182 Page 182

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp 485 490 495 485 490 495

Asn Tyr Ile Gln Val Ser Gln Leu Thr Lys Pro Ile Ser Ser Leu Thr Asn Tyr Ile Gln Val Ser Gln Leu Thr Lys Pro Ile Ser Ser Leu Thr 500 505 510 500 505 510

Lys Pro Tyr His Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Lys Pro Tyr His Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys 515 520 525 515 520 525

Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro 530 535 540 530 535 540

Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 545 550 555 560 545 550 555 560

Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp 565 570 575 565 570 575

Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 580 585 590 580 585 590

Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val 595 600 605 595 600 605

Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu 610 615 620 610 615 620

Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys 625 630 635 640 625 630 635 640

Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 645 650 655 645 650 655

Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr 660 665 670 660 665 670

Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 675 680 685 675 680 685

Page 183 Page 183

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 690 695 700 690 695 700

Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys 705 710 715 720 705 710 715 720

Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu 725 730 735 725 730 735

Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 740 745 750 740 745 750

Lys Lys

<210> 47 <210> 47 <211> 1183 <211> 1183 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> Protein_36_981V_GS_IgG1_noCH1_Fc_Fusion <223> Protein_36_981V_GS_IgG1_noCH1_Fc_Fusio

<400> 47 <400> 47

Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro Ala Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro Ala Pro 1 5 10 15 1 5 10 15

Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Leu Trp Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Leu Trp 20 25 30 20 25 30

Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Gln His Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Gln His 35 40 45 35 40 45

Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Leu Ala Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Leu Ala 50 55 60 50 55 60

Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Pro Ser Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Pro Ser 65 70 75 80 70 75 80

Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Asn Asn Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Asn Asn 85 90 95 85 90 95 Page 184 Page 184

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr His Tyr Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr His Tyr 100 105 110 100 105 110

Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala Gly Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala Gly 115 120 125 115 120 125

Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu Arg Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu Arg 130 135 140 130 135 140

Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Trp Asp Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Trp Asp 145 150 155 160 145 150 155 160

Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Arg Ala Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Arg Ala 165 170 175 165 170 175

Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His Phe Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His Phe 180 185 190 180 185 190

Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val Val Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val Val 195 200 205 195 200 205

Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg Gly Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg Gly 210 215 220 210 215 220

Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala His Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala His 225 230 235 240 225 230 235 240

Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln Gly Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln Gly 245 250 255 245 250 255

Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg Arg Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg Arg 260 265 270 260 265 270

Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Val Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Val 275 280 285 275 280 285

Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Pro Glu Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Pro Glu 290 295 300 290 295 300 Page 185 Page 185

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Glu Ser Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Glu Ser 305 310 315 320 305 310 315 320

Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Cys Phe Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Cys Phe 325 330 335 325 330 335

Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Arg Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Arg 340 345 350 340 345 350

Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Asp Leu Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Asp Leu 355 360 365 355 360 365

Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Val Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Val 370 375 380 370 375 380

Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Lys Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Lys 385 390 395 400 385 390 395 400

Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Val Asp Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Val Asp 405 410 415 405 410 415

Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp His Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp His 420 425 430 420 425 430

Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu Ser Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu Ser 435 440 445 435 440 445

Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys 450 455 460 450 455 460

Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu 465 470 475 480 465 470 475 480

Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Tyr Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Tyr 485 490 495 485 490 495

Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Val Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Val Tyr 500 505 510 500 505 510 Page 186 Page 186

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Gly Val Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Gly Val 515 520 525 515 520 525

Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Ile Gln Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Ile Gln 530 535 540 530 535 540

Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe Arg Phe Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe Arg Phe 545 550 555 560 545 550 555 560

Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Gln Val Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Gln Val 565 570 575 565 570 575

Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu Leu Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu Leu Val 580 585 590 580 585 590

Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met Ala Pro Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met Ala Pro 595 600 605 595 600 605

Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp Glu Asn Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp Glu Asn 610 615 620 610 615 620

Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys Phe Gln Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys Phe Gln 625 630 635 640 625 630 635 640

Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu Pro Tyr Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu Pro Tyr 645 650 655 645 650 655

Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Ala His Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Ala His 660 665 670 660 665 670

Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala Gln Asn Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala Gln Asn 675 680 685 675 680 685

Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Ala Cys Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Ala Cys 690 695 700 690 695 700

Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu Glu Phe Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu Glu Phe 705 710 715 720 705 710 715 720 Page 187 Page 187

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Tyr Pro Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Tyr Pro 725 730 735 725 730 735

Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu Leu Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu Leu Pro 740 745 750 740 745 750

Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe Asp Phe Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe Asp Phe 755 760 765 755 760 765

Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu Lys Glu Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu Lys Glu 770 775 780 770 775 780

Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Thr Asp Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Thr Asp 785 790 795 800 785 790 795 800

Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Trp Gly Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Trp Gly 805 810 815 805 810 815

Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp Leu Pro Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp Leu Pro 820 825 830 820 825 830

Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala Glu Asp Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala Glu Asp 835 840 845 835 840 845

Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu Ala Leu Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu Ala Leu 850 855 860 850 855 860

Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe Ala Tyr Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe Ala Tyr 865 870 875 880 865 870 875 880

Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg Tyr Ala Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg Tyr Ala 885 890 895 885 890 895

Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Lys Ile Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Lys Ile 900 905 910 900 905 910

Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Phe Cys Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Phe Cys 915 920 925 915 920 925

Page 188 Page 188

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His Thr Arg Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His Thr Arg 930 935 940 930 935 940

Lys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr His Lys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr His 945 950 955 960 945 950 955 960

Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val 965 970 975 965 970 975

Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 980 985 990 980 985 990

Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 995 1000 1005 995 1000 1005

Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 1010 1015 1020 1010 1015 1020

Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val 1025 1030 1035 1025 1030 1035

Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 1040 1045 1050 1040 1045 1050

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 1055 1060 1065 1055 1060 1065

Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 1070 1075 1080 1070 1075 1080

Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln 1085 1090 1095 1085 1090 1095

Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 1100 1105 1110 1100 1105 1110

Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 1115 1120 1125 1115 1120 1125 Page 189 Page 189

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 1130 1135 1140 1130 1135 1140

Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 1145 1150 1155 1145 1150 1155

Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 1160 1165 1170 1160 1165 1170

Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 1175 1180 1175 1180

<210> 48 <210> 48 <211> 1183 <211> 1183 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> Protein_36_981V_C370S_GS_IgG1_noCH1_Fc_Fusion <223> Protein_36_981V_C370S_GS_IgG1_noCH1_Fc_Fusion

<400> 48 <400> 48

Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro Ala Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro Ala Pro 1 5 10 15 1 5 10 15

Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Leu Trp Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Leu Trp 20 25 30 20 25 30

Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Gln His Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Gln His 35 40 45 35 40 45

Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Leu Ala Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Leu Ala 50 55 60 50 55 60

Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Pro Ser Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Pro Ser 65 70 75 80 70 75 80

Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Asn Asn Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Asn Asn 85 90 95 85 90 95

Page 190 Page 190

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing - TXT Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr His Tyr Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr His Tyr 100 105 110 100 105 110

Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala Gly Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala Gly 115 120 125 115 120 125

Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu Arg Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu Arg 130 135 140 130 135 140

Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Trp Asp Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Trp Asp 145 150 155 160 145 150 155 160

Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Arg Ala Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Arg Ala 165 170 175 165 170 175

Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His Phe Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His Phe 180 185 190 180 185 190

Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val Val Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val Val 195 200 205 195 200 205

Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg Gly Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg Gly 210 215 220 210 215 220

Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala His Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala His 225 230 235 240 225 230 235 240

Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln Gly Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln Gly 245 250 255 245 250 255

Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg Arg Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg Arg 260 265 270 260 265 270

Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Val Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Val 275 280 285 275 280 285

Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Pro Glu Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Pro Glu 290 295 300 290 295 300

Page 191 Page 191

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Glu Ser Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Glu Ser 305 310 315 320 305 310 315 320

Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Ser Phe Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Ser Phe 325 330 335 325 330 335

Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Arg Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Arg 340 345 350 340 345 350

Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Asp Leu Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Asp Leu 355 360 365 355 360 365

Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Val Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Val 370 375 380 370 375 380

Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Lys Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Lys 385 390 395 400 385 390 395 400

Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Val Asp Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Val Asp 405 410 415 405 410 415

Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp His Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp His 420 425 430 420 425 430

Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu Ser Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu Ser 435 440 445 435 440 445

Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys 450 455 460 450 455 460

Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu 465 470 475 480 465 470 475 480

Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Tyr Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Tyr 485 490 495 485 490 495

Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Val Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Val Tyr 500 505 510 500 505 510

Page 192 Page 192

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Gly Val Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Gly Val 515 520 525 515 520 525

Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Ile Gln Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Ile Gln 530 535 540 530 535 540

Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe Arg Phe Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe Arg Phe 545 550 555 560 545 550 555 560

Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Gln Val Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Gln Val 565 570 575 565 570 575

Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu Leu Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu Leu Val 580 585 590 580 585 590

Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met Ala Pro Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met Ala Pro 595 600 605 595 600 605

Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp Glu Asn Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp Glu Asn 610 615 620 610 615 620

Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys Phe Gln Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys Phe Gln 625 630 635 640 625 630 635 640

Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu Pro Tyr Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu Pro Tyr 645 650 655 645 650 655

Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Ala His Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Ala His 660 665 670 660 665 670

Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala Gln Asn Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala Gln Asn 675 680 685 675 680 685

Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Ala Cys Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Ala Cys 690 695 700 690 695 700

Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu Glu Phe Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu Glu Phe 705 710 715 720 705 710 715 720

Page 193 Page 193

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing TXT Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Tyr Pro Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Tyr Pro 725 730 735 725 730 735

Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu Leu Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu Leu Pro 740 745 750 740 745 750

Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe Asp Phe Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe Asp Phe 755 760 765 755 760 765

Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu Lys Glu Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu Lys Glu 770 775 780 770 775 780

Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Thr Asp Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Thr Asp 785 790 795 800 785 790 795 800

Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Trp Gly Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Trp Gly 805 810 815 805 810 815

Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp Leu Pro Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp Leu Pro 820 825 830 820 825 830

Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala Glu Asp Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala Glu Asp 835 840 845 835 840 845

Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu Ala Leu Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu Ala Leu 850 855 860 850 855 860

Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe Ala Tyr Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe Ala Tyr 865 870 875 880 865 870 875 880

Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg Tyr Ala Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg Tyr Ala 885 890 895 885 890 895

Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Lys Ile Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Lys Ile 900 905 910 900 905 910

Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Phe Cys Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Phe Cys 915 920 925 915 920 925

Page 194 Page 194

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His Thr Arg Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His Thr Arg 930 935 940 930 935 940

Lys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr His Lys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr His 945 950 955 960 945 950 955 960

Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val 965 970 975 965 970 975

Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 980 985 990 980 985 990

Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 995 1000 1005 995 1000 1005

Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 1010 1015 1020 1010 1015 1020

Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val 1025 1030 1035 1025 1030 1035

Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 1040 1045 1050 1040 1045 1050

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 1055 1060 1065 1055 1060 1065

Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 1070 1075 1080 1070 1075 1080

Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln 1085 1090 1095 1085 1090 1095

Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 1100 1105 1110 1100 1105 1110

Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 1115 1120 1125 1115 1120 1125

Page 195 Page 195

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 1130 1135 1140 1130 1135 1140

Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 1145 1150 1155 1145 1150 1155

Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 1160 1165 1170 1160 1165 1170

Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 1175 1180 1175 1180

<210> 49 <210> 49 <211> 751 <211> 751 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> Protein_36_549V_GS_IgG1_noCH1_Fc_Fusion <223> Protein_36_549V_GS_IgG1_noCH1_Fc_Fusio

<400> 49 <400> 49

Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro Ala Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro Ala Pro 1 5 10 15 1 5 10 15

Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Leu Trp Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Leu Trp 20 25 30 20 25 30

Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Gln His Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Gln His 35 40 45 35 40 45

Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Leu Ala Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Leu Ala 50 55 60 50 55 60

Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Pro Ser Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Pro Ser 65 70 75 80 70 75 80

Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Asn Asn Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Asn Asn 85 90 95 85 90 95

Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr His Tyr Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr His Tyr 100 105 110 100 105 110 Page 196 Page 196

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala Gly Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala Gly 115 120 125 115 120 125

Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu Arg Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu Arg 130 135 140 130 135 140

Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Trp Asp Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Trp Asp 145 150 155 160 145 150 155 160

Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Arg Ala Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Arg Ala 165 170 175 165 170 175

Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His Phe Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His Phe 180 185 190 180 185 190

Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val Val Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val Val 195 200 205 195 200 205

Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg Gly Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg Gly 210 215 220 210 215 220

Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala His Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala His 225 230 235 240 225 230 235 240

Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln Gly Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln Gly 245 250 255 245 250 255

Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg Arg Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg Arg 260 265 270 260 265 270

Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Val Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Val 275 280 285 275 280 285

Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Pro Glu Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Pro Glu 290 295 300 290 295 300

Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Glu Ser Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Glu Ser 305 310 315 320 305 310 315 320 Page 197 Page 197

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Cys Phe Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Cys Phe 325 330 335 325 330 335

Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Arg Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Arg 340 345 350 340 345 350

Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Asp Leu Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Asp Leu 355 360 365 355 360 365

Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Val Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Val 370 375 380 370 375 380

Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Lys Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Lys 385 390 395 400 385 390 395 400

Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Val Asp Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Val Asp 405 410 415 405 410 415

Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp His Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp His 420 425 430 420 425 430

Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu Ser Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu Ser 435 440 445 435 440 445

Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys 450 455 460 450 455 460

Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu 465 470 475 480 465 470 475 480

Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Tyr Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Tyr 485 490 495 485 490 495

Ile Gln Val Ser Gln Leu Thr Lys Pro Ile Ser Ser Leu Thr Lys Pro Ile Gln Val Ser Gln Leu Thr Lys Pro Ile Ser Ser Leu Thr Lys Pro 500 505 510 500 505 510

Tyr His Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr His Tyr His Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr His 515 520 525 515 520 525

Page 198 Page 198

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val 530 535 540 530 535 540

Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 545 550 555 560 545 550 555 560

Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 565 570 575 565 570 575

Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 580 585 590 580 585 590

Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 595 600 605 595 600 605

Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 610 615 620 610 615 620

Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 625 630 635 640 625 630 635 640

Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 645 650 655 645 650 655

Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu 660 665 670 660 665 670

Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 675 680 685 675 680 685

Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 690 695 700 690 695 700

Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 705 710 715 720 705 710 715 720

Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 725 730 735 725 730 735 Page 199 Page 199

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 740 745 750 740 745 750

<210> 50 <210> 50 <211> 751 <211> 751 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> Protein_36_549V_C370S_GS_IgG1_noCH1_Fc_Fusion <223> Protein_36_549V_C370S_GS_IgG1_noCH1_Fc_Fusion

<400> 50 <400> 50

Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro Ala Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro Ala Pro 1 5 10 15 1 5 10 15

Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Leu Trp Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Leu Trp 20 25 30 20 25 30

Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Gln His Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Gln His 35 40 45 35 40 45

Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Leu Ala Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Leu Ala 50 55 60 50 55 60

Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Pro Ser Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Pro Ser 65 70 75 80 70 75 80

Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Asn Asn Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Asn Asn 85 90 95 85 90 95

Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr His Tyr Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr His Tyr 100 105 110 100 105 110

Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala Gly Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala Gly 115 120 125 115 120 125

Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu Arg Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu Arg 130 135 140 130 135 140

Page 200 Page 200

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing TXT Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Trp Asp Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Trp Asp 145 150 155 160 145 150 155 160

Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Arg Ala Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Arg Ala 165 170 175 165 170 175

Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His Phe Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His Phe 180 185 190 180 185 190

Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val Val Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val Val 195 200 205 195 200 205

Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg Gly Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg Gly 210 215 220 210 215 220

Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala His Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala His 225 230 235 240 225 230 235 240

Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln Gly Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln Gly 245 250 255 245 250 255

Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg Arg Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg Arg 260 265 270 260 265 270

Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Val Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Val 275 280 285 275 280 285

Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Pro Glu Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Pro Glu 290 295 300 290 295 300

Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Glu Ser Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Glu Ser 305 310 315 320 305 310 315 320

Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Ser Phe Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Ser Phe 325 330 335 325 330 335

Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Arg Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Arg 340 345 350 340 345 350

Page 201 Page 201

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Asp Leu Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Asp Leu 355 360 365 355 360 365

Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Val Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Val 370 375 380 370 375 380

Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Lys Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Lys 385 390 395 400 385 390 395 400

Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Val Asp Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Val Asp 405 410 415 405 410 415

Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp His Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp His 420 425 430 420 425 430

Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu Ser Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu Ser 435 440 445 435 440 445

Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys 450 455 460 450 455 460

Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu 465 470 475 480 465 470 475 480

Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Tyr Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Tyr 485 490 495 485 490 495

Ile Gln Val Ser Gln Leu Thr Lys Pro Ile Ser Ser Leu Thr Lys Pro Ile Gln Val Ser Gln Leu Thr Lys Pro Ile Ser Ser Leu Thr Lys Pro 500 505 510 500 505 510

Tyr His Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr His Tyr His Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr His 515 520 525 515 520 525

Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val 530 535 540 530 535 540

Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 545 550 555 560 545 550 555 560

Page 202 Page 202

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 565 570 575 565 570 575

Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 580 585 590 580 585 590

Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 595 600 605 595 600 605

Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 610 615 620 610 615 620

Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 625 630 635 640 625 630 635 640

Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 645 650 655 645 650 655

Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu 660 665 670 660 665 670

Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 675 680 685 675 680 685

Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 690 695 700 690 695 700

Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 705 710 715 720 705 710 715 720

Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 725 730 735 725 730 735

His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 740 745 750 740 745 750

<210> 51 <210> 51 <211> 1218 <211> 1218 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence Page 203 Page 203

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

<220> <220> <223> Protein_Native_SS_34_981F_GS_IgG1_noCH1_Fc_Fusion <223> otein_Native_SS_34_981F_GS_IgG1_noCH1_Fc_Fusion

<400> 51 <400> 51

Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser 1 5 10 15 1 5 10 15

Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg 20 25 30 20 25 30

Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro 35 40 45 35 40 45

Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly 50 55 60 50 55 60

Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp 65 70 75 80 70 75 80

Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His 85 90 95 85 90 95

Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly 100 105 110 100 105 110

Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser 115 120 125 115 120 125

Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val 130 135 140 130 135 140

Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly 145 150 155 160 145 150 155 160

Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu 165 170 175 165 170 175

Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr 180 185 190 180 185 190 Page 204 Page 204

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala 195 200 205 195 200 205

Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe 210 215 220 210 215 220

Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro 225 230 235 240 225 230 235 240

Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly 245 250 255 245 250 255

Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu 260 265 270 260 265 270

Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro 275 280 285 275 280 285

Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn 290 295 300 290 295 300

Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu 305 310 315 320 305 310 315 320

Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp 325 330 335 325 330 335

Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe 340 345 350 340 345 350

Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala 355 360 365 355 360 365

Leu Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Leu Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met 370 375 380 370 375 380

Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp 385 390 395 400 385 390 395 400 Page 205 Page 205

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly 405 410 415 405 410 415

Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr 420 425 430 420 425 430

Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp 435 440 445 435 440 445

Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe 450 455 460 450 455 460

Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp 465 470 475 480 465 470 475 480

Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe 485 490 495 485 490 495

Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn 500 505 510 500 505 510

Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val 515 520 525 515 520 525

Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu 530 535 540 530 535 540

Asn Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asn Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val 545 550 555 560 545 550 555 560

Asp Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Asp Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala 565 570 575 565 570 575

Ala Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Ala Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His 580 585 590 580 585 590

Phe Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Phe Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln 595 600 605 595 600 605 Page 206 Page 206

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Ser Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Ser Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser 610 615 620 610 615 620

Glu Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Glu Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro 625 630 635 640 625 630 635 640

Met Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Met Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala 645 650 655 645 650 655

Trp Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Trp Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu 660 665 670 660 665 670

Cys Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Cys Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn 675 680 685 675 680 685

Glu Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Glu Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu 690 695 700 690 695 700

Lys Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Lys Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His 705 710 715 720 705 710 715 720

Ala Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Ala Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu 725 730 735 725 730 735

Pro Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Pro Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val 740 745 750 740 745 750

Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly 755 760 765 755 760 765

Asp Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Asp Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe 770 775 780 770 775 780

Leu Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Leu Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr 785 790 795 800 785 790 795 800

Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser 805 810 815 805 810 815 Page 207 Page 207

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Glu Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Glu Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu 820 825 830 820 825 830

Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val 835 840 845 835 840 845

Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly 850 855 860 850 855 860

Asp Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Asp Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His 865 870 875 880 865 870 875 880

Ala Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Ala Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn 885 890 895 885 890 895

Glu Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Glu Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr 900 905 910 900 905 910

Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr 915 920 925 915 920 925

Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr 930 935 940 930 935 940

Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu 945 950 955 960 945 950 955 960

Arg Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe Arg Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe 965 970 975 965 970 975

His Thr Arg Lys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp His Thr Arg Lys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp 980 985 990 980 985 990

Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 995 1000 1005 995 1000 1005

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 1010 1015 1020 1010 1015 1020 Page 208 Page 208

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 1025 1030 1035 1025 1030 1035

His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val 1040 1045 1050 1040 1045 1050

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn 1055 1060 1065 1055 1060 1065

Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 1070 1075 1080 1070 1075 1080

Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala 1085 1090 1095 1085 1090 1095

Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 1100 1105 1110 1100 1105 1110

Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 1115 1120 1125 1115 1120 1125

Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe 1130 1135 1140 1130 1135 1140

Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 1145 1150 1155 1145 1150 1155

Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly 1160 1165 1170 1160 1165 1170

Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp 1175 1180 1185 1175 1180 1185

Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 1190 1195 1200 1190 1195 1200

His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 1205 1210 1215 1205 1210 1215 Page 209 Page 209

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

<210> 52 <210> 52 <211> 1185 <211> 1185 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> Protein_34_981F_GS_IgG1_noCH1_Fc_Fusion <223> Protein_34_981F_GS_IgG1_noCH1_Fc_Fusion

<400> 52 <400> 52

Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro 1 5 10 15 1 5 10 15

Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe 20 25 30 20 25 30

Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln 35 40 45 35 40 45

Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro 50 55 60 50 55 60

Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala 65 70 75 80 70 75 80

Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr 85 90 95 85 90 95

Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr 100 105 110 100 105 110

His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser 115 120 125 115 120 125

Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu 130 135 140 130 135 140

Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His 145 150 155 160 145 150 155 160

Page 210 Page 210

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn 165 170 175 165 170 175

Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg 180 185 190 180 185 190

His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr 195 200 205 195 200 205

Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile 210 215 220 210 215 220

Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu 225 230 235 240 225 230 235 240

Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr 245 250 255 245 250 255

Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro 260 265 270 260 265 270

Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp 275 280 285 275 280 285

Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr 290 295 300 290 295 300

Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr 305 310 315 320 305 310 315 320

Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu 325 330 335 325 330 335

Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys 340 345 350 340 345 350

Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile 355 360 365 355 360 365

Page 211 Page 211

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp 370 375 380 370 375 380

Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr 385 390 395 400 385 390 395 400

Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly 405 410 415 405 410 415

Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu 420 425 430 420 425 430

Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe 435 440 445 435 440 445

Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr 450 455 460 450 455 460

Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln 465 470 475 480 465 470 475 480

Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp 485 490 495 485 490 495

Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn 500 505 510 500 505 510

Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp 515 520 525 515 520 525

Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala 530 535 540 530 535 540

Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe 545 550 555 560 545 550 555 560

Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser 565 570 575 565 570 575

Page 212 Page 212

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu 580 585 590 580 585 590

Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met 595 600 605 595 600 605

Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp 610 615 620 610 615 620

Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys 625 630 635 640 625 630 635 640

Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu 645 650 655 645 650 655

Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys 660 665 670 660 665 670

Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala 675 680 685 675 680 685

Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro 690 695 700 690 695 700

Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu 705 710 715 720 705 710 715 720

Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp 725 730 735 725 730 735

Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu 740 745 750 740 745 750

Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe 755 760 765 755 760 765

Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu 770 775 780 770 775 780

Page 213 Page 213

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met 785 790 795 800 785 790 795 800

Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro 805 810 815 805 810 815

Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp 820 825 830 820 825 830

Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala 835 840 845 835 840 845

Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu 850 855 860 850 855 860

Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe 865 870 875 880 865 870 875 880

Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg 885 890 895 885 890 895

Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg 900 905 910 900 905 910

Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg 915 920 925 915 920 925

Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His 930 935 940 930 935 940

Thr Arg Lys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr Arg Lys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys 945 950 955 960 945 950 955 960

Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro 965 970 975 965 970 975

Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 980 985 990 980 985 990

Page 214 Page 214

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp 995 1000 1005 995 1000 1005

Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 1010 1015 1020 1010 1015 1020

Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 1025 1030 1035 1025 1030 1035

Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 1040 1045 1050 1040 1045 1050

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala 1055 1060 1065 1055 1060 1065

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 1070 1075 1080 1070 1075 1080

Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys 1085 1090 1095 1085 1090 1095

Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser 1100 1105 1110 1100 1105 1110

Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 1115 1120 1125 1115 1120 1125

Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 1130 1135 1140 1130 1135 1140

Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly 1145 1150 1155 1145 1150 1155

Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 1160 1165 1170 1160 1165 1170

Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 1175 1180 1185 1175 1180 1185

Page 215 Page 215

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT <210> 53 <210> 53 <211> 786 <211> 786 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> Protein_Native_SS_34_549F_GS_IgG1_noCH1_Fc_Fusion <223> Protein_Native_SS_34_549F_GS_IgG1_noCH1_Fc_Fusion

<400> 53 <400> 53

Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser 1 5 10 15 1 5 10 15

Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg 20 25 30 20 25 30

Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro 35 40 45 35 40 45

Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly 50 55 60 50 55 60

Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp 65 70 75 80 70 75 80

Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His 85 90 95 85 90 95

Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly 100 105 110 100 105 110

Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser 115 120 125 115 120 125

Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val 130 135 140 130 135 140

Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly 145 150 155 160 145 150 155 160

Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu 165 170 175 165 170 175 Page 216 Page 216

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr 180 185 190 180 185 190

His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala 195 200 205 195 200 205

Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe 210 215 220 210 215 220

Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro 225 230 235 240 225 230 235 240

Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly 245 250 255 245 250 255

Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu 260 265 270 260 265 270

Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro 275 280 285 275 280 285

Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn 290 295 300 290 295 300

Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu 305 310 315 320 305 310 315 320

Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp 325 330 335 325 330 335

Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe 340 345 350 340 345 350

Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala 355 360 365 355 360 365

Leu Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Leu Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met 370 375 380 370 375 380 Page 217 Page 217

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp 385 390 395 400 385 390 395 400

Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly 405 410 415 405 410 415

Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr 420 425 430 420 425 430

Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp 435 440 445 435 440 445

Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe 450 455 460 450 455 460

Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp 465 470 475 480 465 470 475 480

Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe 485 490 495 485 490 495

Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn 500 505 510 500 505 510

Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val 515 520 525 515 520 525

Asp Asn Tyr Ile Gln Val Ser Gln Leu Thr Lys Pro Ile Ser Ser Leu Asp Asn Tyr Ile Gln Val Ser Gln Leu Thr Lys Pro Ile Ser Ser Leu 530 535 540 530 535 540

Thr Lys Pro Tyr His Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Thr Lys Pro Tyr His Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp 545 550 555 560 545 550 555 560

Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 565 570 575 565 570 575

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 580 585 590 580 585 590 Page 218 Page 218

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 595 600 605 595 600 605

Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 610 615 620 610 615 620

Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg 625 630 635 640 625 630 635 640

Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 645 650 655 645 650 655

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 660 665 670 660 665 670

Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 675 680 685 675 680 685

Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu 690 695 700 690 695 700

Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 705 710 715 720 705 710 715 720

Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 725 730 735 725 730 735

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 740 745 750 740 745 750

Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 755 760 765 755 760 765

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 770 775 780 770 775 780

Gly Lys Gly Lys 785 785 Page 219 Page 219

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

<210> 54 <210> 54 <211> 753 <211> 753 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> Protein_34_549F_GS_IgG1_noCH1_Fc_Fusion <223> Protein_34_549F_GS_IgG1_noCH1_Fc_Fusion

<400> 54 <400> 54

Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro 1 5 10 15 1 5 10 15

Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe 20 25 30 20 25 30

Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln 35 40 45 35 40 45

Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro 50 55 60 50 55 60

Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala 65 70 75 80 70 75 80

Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr 85 90 95 85 90 95

Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr 100 105 110 100 105 110

His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser 115 120 125 115 120 125

Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu 130 135 140 130 135 140

Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His 145 150 155 160 145 150 155 160

Page 220 Page 220

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn 165 170 175 165 170 175

Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg 180 185 190 180 185 190

His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr 195 200 205 195 200 205

Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile 210 215 220 210 215 220

Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu 225 230 235 240 225 230 235 240

Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr 245 250 255 245 250 255

Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro 260 265 270 260 265 270

Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp 275 280 285 275 280 285

Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr 290 295 300 290 295 300

Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr 305 310 315 320 305 310 315 320

Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu 325 330 335 325 330 335

Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys 340 345 350 340 345 350

Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile 355 360 365 355 360 365

Page 221 Page 221

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp 370 375 380 370 375 380

Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr 385 390 395 400 385 390 395 400

Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly 405 410 415 405 410 415

Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu 420 425 430 420 425 430

Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe 435 440 445 435 440 445

Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr 450 455 460 450 455 460

Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln 465 470 475 480 465 470 475 480

Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp 485 490 495 485 490 495

Asn Tyr Ile Gln Val Ser Gln Leu Thr Lys Pro Ile Ser Ser Leu Thr Asn Tyr Ile Gln Val Ser Gln Leu Thr Lys Pro Ile Ser Ser Leu Thr 500 505 510 500 505 510

Lys Pro Tyr His Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Lys Pro Tyr His Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys 515 520 525 515 520 525

Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro 530 535 540 530 535 540

Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 545 550 555 560 545 550 555 560

Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp 565 570 575 565 570 575

Page 222 Page 222

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 580 585 590 580 585 590

Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val 595 600 605 595 600 605

Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu 610 615 620 610 615 620

Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys 625 630 635 640 625 630 635 640

Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 645 650 655 645 650 655

Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr 660 665 670 660 665 670

Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 675 680 685 675 680 685

Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 690 695 700 690 695 700

Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys 705 710 715 720 705 710 715 720

Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu 725 730 735 725 730 735

Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 740 745 750 740 745 750

Lys Lys

<210> 55 <210> 55 <211> 1218 <211> 1218 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence Page 223 Page 223

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

<220> <220> <223> Protein_Native_SS_34_981F_C370S_GS_IgG1_noCH1_Fc_Fusion <223> Protein_Native_SS_34_981F_C370S_GS_IgG1_noCH1_Fc_Fusion

<400> 55 <400> 55

Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser 1 5 10 15 1 5 10 15

Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg 20 25 30 20 25 30

Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro 35 40 45 35 40 45

Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly 50 55 60 50 55 60

Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp 65 70 75 80 70 75 80

Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His 85 90 95 85 90 95

Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly 100 105 110 100 105 110

Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser 115 120 125 115 120 125

Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val 130 135 140 130 135 140

Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly 145 150 155 160 145 150 155 160

Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu 165 170 175 165 170 175

Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr 180 185 190 180 185 190 Page 224 Page 224

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala 195 200 205 195 200 205

Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe 210 215 220 210 215 220

Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro 225 230 235 240 225 230 235 240

Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly 245 250 255 245 250 255

Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu 260 265 270 260 265 270

Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro 275 280 285 275 280 285

Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn 290 295 300 290 295 300

Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu 305 310 315 320 305 310 315 320

Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp 325 330 335 325 330 335

Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe 340 345 350 340 345 350

Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala 355 360 365 355 360 365

Leu Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Leu Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met 370 375 380 370 375 380

Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp 385 390 395 400 385 390 395 400 Page 225 Page 225

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly 405 410 415 405 410 415

Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr 420 425 430 420 425 430

Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp 435 440 445 435 440 445

Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe 450 455 460 450 455 460

Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp 465 470 475 480 465 470 475 480

Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe 485 490 495 485 490 495

Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn 500 505 510 500 505 510

Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val 515 520 525 515 520 525

Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu 530 535 540 530 535 540

Asn Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asn Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val 545 550 555 560 545 550 555 560

Asp Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Asp Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala 565 570 575 565 570 575

Ala Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Ala Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His 580 585 590 580 585 590

Phe Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Phe Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln 595 600 605 595 600 605 Page 226 Page 226

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Ser Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Ser Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser 610 615 620 610 615 620

Glu Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Glu Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro 625 630 635 640 625 630 635 640

Met Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Met Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala 645 650 655 645 650 655

Trp Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Trp Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu 660 665 670 660 665 670

Cys Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Cys Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn 675 680 685 675 680 685

Glu Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Glu Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu 690 695 700 690 695 700

Lys Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Lys Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His 705 710 715 720 705 710 715 720

Ala Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Ala Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu 725 730 735 725 730 735

Pro Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Pro Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val 740 745 750 740 745 750

Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly 755 760 765 755 760 765

Asp Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Asp Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe 770 775 780 770 775 780

Leu Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Leu Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr 785 790 795 800 785 790 795 800

Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser 805 810 815 805 810 815 Page 227 Page 227

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Glu Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Glu Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu 820 825 830 820 825 830

Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val 835 840 845 835 840 845

Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly 850 855 860 850 855 860

Asp Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Asp Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His 865 870 875 880 865 870 875 880

Ala Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Ala Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn 885 890 895 885 890 895

Glu Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Glu Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr 900 905 910 900 905 910

Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr 915 920 925 915 920 925

Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr 930 935 940 930 935 940

Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu 945 950 955 960 945 950 955 960

Arg Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe Arg Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe 965 970 975 965 970 975

His Thr Arg Lys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp His Thr Arg Lys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp 980 985 990 980 985 990

Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 995 1000 1005 995 1000 1005

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 1010 1015 1020 1010 1015 1020 Page 228 Page 228

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 1025 1030 1035 1025 1030 1035

His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val 1040 1045 1050 1040 1045 1050

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn 1055 1060 1065 1055 1060 1065

Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 1070 1075 1080 1070 1075 1080

Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala 1085 1090 1095 1085 1090 1095

Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 1100 1105 1110 1100 1105 1110

Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 1115 1120 1125 1115 1120 1125

Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe 1130 1135 1140 1130 1135 1140

Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 1145 1150 1155 1145 1150 1155

Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly 1160 1165 1170 1160 1165 1170

Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp 1175 1180 1185 1175 1180 1185

Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 1190 1195 1200 1190 1195 1200

His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 1205 1210 1215 1205 1210 1215 Page 229 Page 229

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

<210> 56 <210> 56 <211> 1185 <211> 1185 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> Protein_34_981F_C370S_GS_IgG1_noCH1_Fc_Fusion <223> rotein_34_981F_C370S_GS_IgG1_noCH1_Fc_Fusion

<400> 56 <400> 56

Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro 1 5 10 15 1 5 10 15

Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe 20 25 30 20 25 30

Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln 35 40 45 35 40 45

Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro 50 55 60 50 55 60

Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala 65 70 75 80 70 75 80

Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr 85 90 95 85 90 95

Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr 100 105 110 100 105 110

His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser 115 120 125 115 120 125

Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu 130 135 140 130 135 140

Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His 145 150 155 160 145 150 155 160

Page 230 Page 230

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing TXT Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn 165 170 175 165 170 175

Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg 180 185 190 180 185 190

His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr 195 200 205 195 200 205

Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile 210 215 220 210 215 220

Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu 225 230 235 240 225 230 235 240

Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr 245 250 255 245 250 255

Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro 260 265 270 260 265 270

Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp 275 280 285 275 280 285

Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr 290 295 300 290 295 300

Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr 305 310 315 320 305 310 315 320

Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu 325 330 335 325 330 335

Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys 340 345 350 340 345 350

Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile 355 360 365 355 360 365

Page 231 Page 231

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp 370 375 380 370 375 380

Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr 385 390 395 400 385 390 395 400

Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly 405 410 415 405 410 415

Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu 420 425 430 420 425 430

Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe 435 440 445 435 440 445

Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr 450 455 460 450 455 460

Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln 465 470 475 480 465 470 475 480

Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp 485 490 495 485 490 495

Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn 500 505 510 500 505 510

Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp 515 520 525 515 520 525

Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala 530 535 540 530 535 540

Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe 545 550 555 560 545 550 555 560

Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser 565 570 575 565 570 575

Page 232 Page 232

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu 580 585 590 580 585 590

Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met 595 600 605 595 600 605

Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp 610 615 620 610 615 620

Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys 625 630 635 640 625 630 635 640

Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu 645 650 655 645 650 655

Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys 660 665 670 660 665 670

Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala 675 680 685 675 680 685

Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro 690 695 700 690 695 700

Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu 705 710 715 720 705 710 715 720

Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp 725 730 735 725 730 735

Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu 740 745 750 740 745 750

Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe 755 760 765 755 760 765

Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu 770 775 780 770 775 780

Page 233 Page 233

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met 785 790 795 800 785 790 795 800

Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro 805 810 815 805 810 815

Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp 820 825 830 820 825 830

Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala 835 840 845 835 840 845

Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu 850 855 860 850 855 860

Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe 865 870 875 880 865 870 875 880

Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg 885 890 895 885 890 895

Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg 900 905 910 900 905 910

Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg 915 920 925 915 920 925

Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His 930 935 940 930 935 940

Thr Arg Lys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr Arg Lys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys 945 950 955 960 945 950 955 960

Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro 965 970 975 965 970 975

Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 980 985 990 980 985 990

Page 234 Page 234

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp 995 1000 1005 995 1000 1005

Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 1010 1015 1020 1010 1015 1020

Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 1025 1030 1035 1025 1030 1035

Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 1040 1045 1050 1040 1045 1050

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala 1055 1060 1065 1055 1060 1065

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 1070 1075 1080 1070 1075 1080

Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys 1085 1090 1095 1085 1090 1095

Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser 1100 1105 1110 1100 1105 1110

Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 1115 1120 1125 1115 1120 1125

Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 1130 1135 1140 1130 1135 1140

Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly 1145 1150 1155 1145 1150 1155

Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 1160 1165 1170 1160 1165 1170

Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 1175 1180 1185 1175 1180 1185

Page 235 Page 235

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT <210> 57 <210> 57 <211> 786 <211> 786 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> Protein_Native_SS_34_549F_C370S_GS_IgG1_noCH1_Fc_Fusion <223> Protein_Native_SS_34_549F_C370S_GS_IgG1_noCH1_Fc_Fusion

<400> 57 <400> 57

Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser 1 5 10 15 1 5 10 15

Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg 20 25 30 20 25 30

Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro 35 40 45 35 40 45

Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly 50 55 60 50 55 60

Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp 65 70 75 80 70 75 80

Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His 85 90 95 85 90 95

Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly 100 105 110 100 105 110

Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser 115 120 125 115 120 125

Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val 130 135 140 130 135 140

Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly 145 150 155 160 145 150 155 160

Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu 165 170 175 165 170 175 Page 236 Page 236

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr 180 185 190 180 185 190

His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala 195 200 205 195 200 205

Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe 210 215 220 210 215 220

Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro 225 230 235 240 225 230 235 240

Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly 245 250 255 245 250 255

Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu 260 265 270 260 265 270

Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro 275 280 285 275 280 285

Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn 290 295 300 290 295 300

Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu 305 310 315 320 305 310 315 320

Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp 325 330 335 325 330 335

Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe 340 345 350 340 345 350

Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala 355 360 365 355 360 365

Leu Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Leu Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met 370 375 380 370 375 380 Page 237 Page 237

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp 385 390 395 400 385 390 395 400

Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly 405 410 415 405 410 415

Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr 420 425 430 420 425 430

Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp 435 440 445 435 440 445

Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe 450 455 460 450 455 460

Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp 465 470 475 480 465 470 475 480

Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe 485 490 495 485 490 495

Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn 500 505 510 500 505 510

Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val 515 520 525 515 520 525

Asp Asn Tyr Ile Gln Val Ser Gln Leu Thr Lys Pro Ile Ser Ser Leu Asp Asn Tyr Ile Gln Val Ser Gln Leu Thr Lys Pro Ile Ser Ser Leu 530 535 540 530 535 540

Thr Lys Pro Tyr His Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Thr Lys Pro Tyr His Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp 545 550 555 560 545 550 555 560

Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 565 570 575 565 570 575

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 580 585 590 580 585 590 Page 238 Page 238

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 595 600 605 595 600 605

Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 610 615 620 610 615 620

Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg 625 630 635 640 625 630 635 640

Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 645 650 655 645 650 655

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 660 665 670 660 665 670

Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 675 680 685 675 680 685

Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu 690 695 700 690 695 700

Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 705 710 715 720 705 710 715 720

Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 725 730 735 725 730 735

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 740 745 750 740 745 750

Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 755 760 765 755 760 765

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 770 775 780 770 775 780

Gly Lys Gly Lys 785 785 Page 239 Page 239

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

<210> 58 <210> 58 <211> 753 <211> 753 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> Protein_34_549F_C370S_GS_IgG1_noCH1_Fc_Fusion <223> rotein_34_549F_C370S_GS_IgG1_noCH1_Fc_Fusion

<400> 58 <400> 58

Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro 1 5 10 15 1 5 10 15

Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe 20 25 30 20 25 30

Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln 35 40 45 35 40 45

Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro 50 55 60 50 55 60

Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala 65 70 75 80 70 75 80

Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr 85 90 95 85 90 95

Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr 100 105 110 100 105 110

His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser 115 120 125 115 120 125

Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu 130 135 140 130 135 140

Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His 145 150 155 160 145 150 155 160

Page 240 Page 240

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing TXT Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn 165 170 175 165 170 175

Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg 180 185 190 180 185 190

His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr 195 200 205 195 200 205

Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile 210 215 220 210 215 220

Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu 225 230 235 240 225 230 235 240

Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr 245 250 255 245 250 255

Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro 260 265 270 260 265 270

Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp 275 280 285 275 280 285

Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr 290 295 300 290 295 300

Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr 305 310 315 320 305 310 315 320

Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu 325 330 335 325 330 335

Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys 340 345 350 340 345 350

Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile 355 360 365 355 360 365

Page 241 Page 241

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp 370 375 380 370 375 380

Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr 385 390 395 400 385 390 395 400

Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly 405 410 415 405 410 415

Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu 420 425 430 420 425 430

Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe 435 440 445 435 440 445

Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr 450 455 460 450 455 460

Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln 465 470 475 480 465 470 475 480

Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp 485 490 495 485 490 495

Asn Tyr Ile Gln Val Ser Gln Leu Thr Lys Pro Ile Ser Ser Leu Thr Asn Tyr Ile Gln Val Ser Gln Leu Thr Lys Pro Ile Ser Ser Leu Thr 500 505 510 500 505 510

Lys Pro Tyr His Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Lys Pro Tyr His Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys 515 520 525 515 520 525

Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro 530 535 540 530 535 540

Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 545 550 555 560 545 550 555 560

Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp 565 570 575 565 570 575

Page 242 Page 242

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 580 585 590 580 585 590

Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val 595 600 605 595 600 605

Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu 610 615 620 610 615 620

Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys 625 630 635 640 625 630 635 640

Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 645 650 655 645 650 655

Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr 660 665 670 660 665 670

Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 675 680 685 675 680 685

Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 690 695 700 690 695 700

Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys 705 710 715 720 705 710 715 720

Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu 725 730 735 725 730 735

Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 740 745 750 740 745 750

Lys Lys

<210> 59 <210> 59 <211> 1183 <211> 1183 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence Page 243 Page 243

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

<220> <220> <223> Protein_36_981F_GS_IgG1_noCH1_Fc_Fusion <223> Protein_36_981F_GS_IgG1_noCH1_Fc_Fusion

<400> 59 <400> 59

Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro Ala Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro Ala Pro 1 5 10 15 1 5 10 15

Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Leu Trp Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Leu Trp 20 25 30 20 25 30

Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Gln His Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Gln His 35 40 45 35 40 45

Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Leu Ala Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Leu Ala 50 55 60 50 55 60

Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Pro Ser Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Pro Ser 65 70 75 80 70 75 80

Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Asn Asn Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Asn Asn 85 90 95 85 90 95

Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr His Tyr Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr His Tyr 100 105 110 100 105 110

Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala Gly Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala Gly 115 120 125 115 120 125

Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu Arg Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu Arg 130 135 140 130 135 140

Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Trp Asp Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Trp Asp 145 150 155 160 145 150 155 160

Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Arg Ala Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Arg Ala 165 170 175 165 170 175

Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His Phe Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His Phe 180 185 190 180 185 190

Page 244 Page 244

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val Val Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val Val 195 200 205 195 200 205

Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg Gly Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg Gly 210 215 220 210 215 220

Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala His Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala His 225 230 235 240 225 230 235 240

Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln Gly Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln Gly 245 250 255 245 250 255

Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg Arg Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg Arg 260 265 270 260 265 270

Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Val Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Val 275 280 285 275 280 285

Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Pro Glu Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Pro Glu 290 295 300 290 295 300

Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Glu Ser Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Glu Ser 305 310 315 320 305 310 315 320

Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Cys Phe Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Cys Phe 325 330 335 325 330 335

Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Arg Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Arg 340 345 350 340 345 350

Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Asp Leu Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Asp Leu 355 360 365 355 360 365

Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Val Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Val 370 375 380 370 375 380

Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Lys Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Lys 385 390 395 400 385 390 395 400

Page 245 Page 245

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Val Asp Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Val Asp 405 410 415 405 410 415

Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp His Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp His 420 425 430 420 425 430

Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu Ser Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu Ser 435 440 445 435 440 445

Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys 450 455 460 450 455 460

Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu 465 470 475 480 465 470 475 480

Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Tyr Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Tyr 485 490 495 485 490 495

Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Val Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Val Tyr 500 505 510 500 505 510

Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Gly Val Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Gly Val 515 520 525 515 520 525

Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Ile Gln Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Ile Gln 530 535 540 530 535 540

Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe Arg Phe Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe Arg Phe 545 550 555 560 545 550 555 560

Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Gln Val Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Gln Val 565 570 575 565 570 575

Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu Leu Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu Leu Val 580 585 590 580 585 590

Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met Ala Pro Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met Ala Pro 595 600 605 595 600 605 Page 246 Page 246

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp Glu Asn Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp Glu Asn 610 615 620 610 615 620

Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys Phe Gln Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys Phe Gln 625 630 635 640 625 630 635 640

Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu Pro Tyr Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu Pro Tyr 645 650 655 645 650 655

Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Ala His Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Ala His 660 665 670 660 665 670

Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala Gln Asn Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala Gln Asn 675 680 685 675 680 685

Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Ala Cys Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Ala Cys 690 695 700 690 695 700

Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu Glu Phe Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu Glu Phe 705 710 715 720 705 710 715 720

Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Tyr Pro Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Tyr Pro 725 730 735 725 730 735

Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu Leu Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu Leu Pro 740 745 750 740 745 750

Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe Asp Phe Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe Asp Phe 755 760 765 755 760 765

Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu Lys Glu Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu Lys Glu 770 775 780 770 775 780

Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Thr Asp Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Thr Asp 785 790 795 800 785 790 795 800

Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Trp Gly Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Trp Gly 805 810 815 805 810 815 Page 247 Page 247

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp Leu Pro Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp Leu Pro 820 825 830 820 825 830

Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala Glu Asp Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala Glu Asp 835 840 845 835 840 845

Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu Ala Leu Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu Ala Leu 850 855 860 850 855 860

Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe Ala Tyr Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe Ala Tyr 865 870 875 880 865 870 875 880

Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg Tyr Ala Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg Tyr Ala 885 890 895 885 890 895

Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Lys Ile Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Lys Ile 900 905 910 900 905 910

Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Phe Cys Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Phe Cys 915 920 925 915 920 925

Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His Thr Arg Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His Thr Arg 930 935 940 930 935 940

Lys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr His Lys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr His 945 950 955 960 945 950 955 960

Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val 965 970 975 965 970 975

Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 980 985 990 980 985 990

Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 995 1000 1005 995 1000 1005

Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 1010 1015 1020 1010 1015 1020 Page 248 Page 248

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val 1025 1030 1035 1025 1030 1035

Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 1040 1045 1050 1040 1045 1050

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 1055 1060 1065 1055 1060 1065

Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 1070 1075 1080 1070 1075 1080

Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln 1085 1090 1095 1085 1090 1095

Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 1100 1105 1110 1100 1105 1110

Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 1115 1120 1125 1115 1120 1125

Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 1130 1135 1140 1130 1135 1140

Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 1145 1150 1155 1145 1150 1155

Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 1160 1165 1170 1160 1165 1170

Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 1175 1180 1175 1180

<210> 60 <210> 60 <211> 1183 <211> 1183 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> Page 249 Page 249

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT <223> Protein_36_981F_C370S_GS_IgG1_noCH1_Fc_Fusion <223> Protein_36_981F_C370S_GS_IgG1_noCH1_Fc_Fusion

<400> 60 <400> 60

Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro Ala Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro Ala Pro 1 5 10 15 1 5 10 15

Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Leu Trp Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Leu Trp 20 25 30 20 25 30

Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Gln His Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Gln His 35 40 45 35 40 45

Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Leu Ala Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Leu Ala 50 55 60 50 55 60

Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Pro Ser Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Pro Ser 65 70 75 80 70 75 80

Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Asn Asn Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Asn Asn 85 90 95 85 90 95

Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr His Tyr Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr His Tyr 100 105 110 100 105 110

Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala Gly Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala Gly 115 120 125 115 120 125

Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu Arg Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu Arg 130 135 140 130 135 140

Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Trp Asp Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Trp Asp 145 150 155 160 145 150 155 160

Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Arg Ala Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Arg Ala 165 170 175 165 170 175

Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His Phe Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His Phe 180 185 190 180 185 190

Page 250 Page 250

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val Val Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val Val 195 200 205 195 200 205

Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg Gly Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg Gly 210 215 220 210 215 220

Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala His Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala His 225 230 235 240 225 230 235 240

Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln Gly Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln Gly 245 250 255 245 250 255

Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg Arg Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg Arg 260 265 270 260 265 270

Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Val Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Val 275 280 285 275 280 285

Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Pro Glu Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Pro Glu 290 295 300 290 295 300

Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Glu Ser Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Glu Ser 305 310 315 320 305 310 315 320

Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Ser Phe Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Ser Phe 325 330 335 325 330 335

Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Arg Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Arg 340 345 350 340 345 350

Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Asp Leu Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Asp Leu 355 360 365 355 360 365

Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Val Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Val 370 375 380 370 375 380

Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Lys Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Lys 385 390 395 400 385 390 395 400

Page 251 Page 251

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Val Asp Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Val Asp 405 410 415 405 410 415

Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp His Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp His 420 425 430 420 425 430

Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu Ser Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu Ser 435 440 445 435 440 445

Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys 450 455 460 450 455 460

Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu 465 470 475 480 465 470 475 480

Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Tyr Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Tyr 485 490 495 485 490 495

Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Val Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Val Tyr 500 505 510 500 505 510

Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Gly Val Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Gly Val 515 520 525 515 520 525

Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Ile Gln Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Ile Gln 530 535 540 530 535 540

Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe Arg Phe Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe Arg Phe 545 550 555 560 545 550 555 560

Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Gln Val Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Gln Val 565 570 575 565 570 575

Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu Leu Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu Leu Val 580 585 590 580 585 590

Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met Ala Pro Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met Ala Pro 595 600 605 595 600 605

Page 252 Page 252

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp Glu Asn Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp Glu Asn 610 615 620 610 615 620

Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys Phe Gln Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys Phe Gln 625 630 635 640 625 630 635 640

Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu Pro Tyr Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu Pro Tyr 645 650 655 645 650 655

Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Ala His Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Ala His 660 665 670 660 665 670

Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala Gln Asn Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala Gln Asn 675 680 685 675 680 685

Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Ala Cys Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Ala Cys 690 695 700 690 695 700

Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu Glu Phe Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu Glu Phe 705 710 715 720 705 710 715 720

Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Tyr Pro Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Tyr Pro 725 730 735 725 730 735

Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu Leu Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu Leu Pro 740 745 750 740 745 750

Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe Asp Phe Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe Asp Phe 755 760 765 755 760 765

Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu Lys Glu Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu Lys Glu 770 775 780 770 775 780

Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Thr Asp Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Thr Asp 785 790 795 800 785 790 795 800

Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Trp Gly Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Trp Gly 805 810 815 805 810 815

Page 253 Page 253

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing TXT Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp Leu Pro Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp Leu Pro 820 825 830 820 825 830

Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala Glu Asp Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala Glu Asp 835 840 845 835 840 845

Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu Ala Leu Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu Ala Leu 850 855 860 850 855 860

Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe Ala Tyr Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe Ala Tyr 865 870 875 880 865 870 875 880

Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg Tyr Ala Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg Tyr Ala 885 890 895 885 890 895

Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Lys Ile Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Lys Ile 900 905 910 900 905 910

Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Phe Cys Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Phe Cys 915 920 925 915 920 925

Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His Thr Arg Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His Thr Arg 930 935 940 930 935 940

Lys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr His Lys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr His 945 950 955 960 945 950 955 960

Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val 965 970 975 965 970 975

Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 980 985 990 980 985 990

Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 995 1000 1005 995 1000 1005

Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 1010 1015 1020 1010 1015 1020

Page 254 Page 254

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val 1025 1030 1035 1025 1030 1035

Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 1040 1045 1050 1040 1045 1050

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 1055 1060 1065 1055 1060 1065

Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 1070 1075 1080 1070 1075 1080

Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln 1085 1090 1095 1085 1090 1095

Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 1100 1105 1110 1100 1105 1110

Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 1115 1120 1125 1115 1120 1125

Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 1130 1135 1140 1130 1135 1140

Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 1145 1150 1155 1145 1150 1155

Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 1160 1165 1170 1160 1165 1170

Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 1175 1180 1175 1180

<210> 61 <210> 61 <211> 751 <211> 751 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> Protein_36_549F_GS_IgG1_noCH1_Fc_Fusion <223> Protein_36_549F_GS_IgG1_noCH1_Fc_Fusion

Page 255 Page 255

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT <400> 61 <400> 61

Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro Ala Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro Ala Pro 1 5 10 15 1 5 10 15

Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Leu Trp Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Leu Trp 20 25 30 20 25 30

Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Gln His Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Gln His 35 40 45 35 40 45

Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Leu Ala Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Leu Ala 50 55 60 50 55 60

Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Pro Ser Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Pro Ser 65 70 75 80 70 75 80

Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Asn Asn Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Asn Asn 85 90 95 85 90 95

Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr His Tyr Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr His Tyr 100 105 110 100 105 110

Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala Gly Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala Gly 115 120 125 115 120 125

Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu Arg Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu Arg 130 135 140 130 135 140

Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Trp Asp Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Trp Asp 145 150 155 160 145 150 155 160

Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Arg Ala Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Arg Ala 165 170 175 165 170 175

Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His Phe Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His Phe 180 185 190 180 185 190

Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val Val Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val Val 195 200 205 195 200 205 Page 256 Page 256

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg Gly Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg Gly 210 215 220 210 215 220

Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala His Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala His 225 230 235 240 225 230 235 240

Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln Gly Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln Gly 245 250 255 245 250 255

Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg Arg Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg Arg 260 265 270 260 265 270

Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Val Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Val 275 280 285 275 280 285

Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Pro Glu Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Pro Glu 290 295 300 290 295 300

Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Glu Ser Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Glu Ser 305 310 315 320 305 310 315 320

Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Cys Phe Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Cys Phe 325 330 335 325 330 335

Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Arg Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Arg 340 345 350 340 345 350

Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Asp Leu Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Asp Leu 355 360 365 355 360 365

Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Val Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Val 370 375 380 370 375 380

Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Lys Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Lys 385 390 395 400 385 390 395 400

Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Val Asp Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Val Asp 405 410 415 405 410 415 Page 257 Page 257

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp His Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp His 420 425 430 420 425 430

Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu Ser Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu Ser 435 440 445 435 440 445

Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys 450 455 460 450 455 460

Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu 465 470 475 480 465 470 475 480

Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Tyr Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Tyr 485 490 495 485 490 495

Ile Gln Val Ser Gln Leu Thr Lys Pro Ile Ser Ser Leu Thr Lys Pro Ile Gln Val Ser Gln Leu Thr Lys Pro Ile Ser Ser Leu Thr Lys Pro 500 505 510 500 505 510

Tyr His Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr His Tyr His Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr His 515 520 525 515 520 525

Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val 530 535 540 530 535 540

Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 545 550 555 560 545 550 555 560

Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 565 570 575 565 570 575

Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 580 585 590 580 585 590

Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 595 600 605 595 600 605

Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 610 615 620 610 615 620 Page 258 Page 258

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 625 630 635 640 625 630 635 640

Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 645 650 655 645 650 655

Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu 660 665 670 660 665 670

Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 675 680 685 675 680 685

Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 690 695 700 690 695 700

Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 705 710 715 720 705 710 715 720

Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 725 730 735 725 730 735

His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 740 745 750 740 745 750

<210> 62 <210> 62 <211> 751 <211> 751 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> Protein_36_549F_C370S_GS_IgG1_noCH1_Fc_Fusion <223> rotein_36_549F_C370S_GS_IgG1_noCH1_Fc_Fusion

<400> 62 <400> 62

Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro Ala Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro Ala Pro 1 5 10 15 1 5 10 15

Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Leu Trp Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Leu Trp 20 25 30 20 25 30

Page 259 Page 259

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Gln His Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Gln His 35 40 45 35 40 45

Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Leu Ala Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Leu Ala 50 55 60 50 55 60

Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Pro Ser Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Pro Ser 65 70 75 80 70 75 80

Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Asn Asn Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Asn Asn 85 90 95 85 90 95

Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr His Tyr Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr His Tyr 100 105 110 100 105 110

Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala Gly Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala Gly 115 120 125 115 120 125

Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu Arg Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu Arg 130 135 140 130 135 140

Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Trp Asp Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Trp Asp 145 150 155 160 145 150 155 160

Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Arg Ala Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Arg Ala 165 170 175 165 170 175

Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His Phe Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His Phe 180 185 190 180 185 190

Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val Val Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val Val 195 200 205 195 200 205

Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg Gly Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg Gly 210 215 220 210 215 220

Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala His Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala His 225 230 235 240 225 230 235 240

Page 260 Page 260

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln Gly Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln Gly 245 250 255 245 250 255

Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg Arg Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg Arg 260 265 270 260 265 270

Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Val Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Val 275 280 285 275 280 285

Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Pro Glu Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Pro Glu 290 295 300 290 295 300

Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Glu Ser Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Glu Ser 305 310 315 320 305 310 315 320

Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Ser Phe Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Ser Phe 325 330 335 325 330 335

Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Arg Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Arg 340 345 350 340 345 350

Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Asp Leu Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Asp Leu 355 360 365 355 360 365

Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Val Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Val 370 375 380 370 375 380

Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Lys Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Lys 385 390 395 400 385 390 395 400

Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Val Asp Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Val Asp 405 410 415 405 410 415

Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp His Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp His 420 425 430 420 425 430

Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu Ser Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu Ser 435 440 445 435 440 445

Page 261 Page 261

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys 450 455 460 450 455 460

Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu 465 470 475 480 465 470 475 480

Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Tyr Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Tyr 485 490 495 485 490 495

Ile Gln Val Ser Gln Leu Thr Lys Pro Ile Ser Ser Leu Thr Lys Pro Ile Gln Val Ser Gln Leu Thr Lys Pro Ile Ser Ser Leu Thr Lys Pro 500 505 510 500 505 510

Tyr His Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr His Tyr His Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr His 515 520 525 515 520 525

Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val 530 535 540 530 535 540

Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 545 550 555 560 545 550 555 560

Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 565 570 575 565 570 575

Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 580 585 590 580 585 590

Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 595 600 605 595 600 605

Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 610 615 620 610 615 620

Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 625 630 635 640 625 630 635 640

Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 645 650 655 645 650 655

Page 262 Page 262

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. - TXT Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu 660 665 670 660 665 670

Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 675 680 685 675 680 685

Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 690 695 700 690 695 700

Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 705 710 715 720 705 710 715 720

Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 725 730 735 725 730 735

His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 740 745 750 740 745 750

<210> 63 <210> 63 <211> 988 <211> 988 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> Protein_34_981V_TEV_TwinStrep <223> Protein_34_981V_TEV_TwinStrep

<400> 63 <400> 63

Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro 1 5 10 15 1 5 10 15

Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe 20 25 30 20 25 30

Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln 35 40 45 35 40 45

Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro 50 55 60 50 55 60

Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala 65 70 75 80 70 75 80 Page 263 Page 263

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr 85 90 95 85 90 95

Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr 100 105 110 100 105 110

His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser 115 120 125 115 120 125

Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu 130 135 140 130 135 140

Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His 145 150 155 160 145 150 155 160

Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn 165 170 175 165 170 175

Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg 180 185 190 180 185 190

His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr 195 200 205 195 200 205

Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile 210 215 220 210 215 220

Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu 225 230 235 240 225 230 235 240

Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr 245 250 255 245 250 255

Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro 260 265 270 260 265 270

Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp 275 280 285 275 280 285

Page 264 Page 264

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr 290 295 300 290 295 300

Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr 305 310 315 320 305 310 315 320

Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu 325 330 335 325 330 335

Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys 340 345 350 340 345 350

Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile 355 360 365 355 360 365

Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp 370 375 380 370 375 380

Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr 385 390 395 400 385 390 395 400

Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly 405 410 415 405 410 415

Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu 420 425 430 420 425 430

Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe 435 440 445 435 440 445

Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr 450 455 460 450 455 460

Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln 465 470 475 480 465 470 475 480

Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp 485 490 495 485 490 495 Page 265 Page 265

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn 500 505 510 500 505 510

Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp 515 520 525 515 520 525

Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala 530 535 540 530 535 540

Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe 545 550 555 560 545 550 555 560

Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser 565 570 575 565 570 575

Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu 580 585 590 580 585 590

Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met 595 600 605 595 600 605

Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp 610 615 620 610 615 620

Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys 625 630 635 640 625 630 635 640

Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu 645 650 655 645 650 655

Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys 660 665 670 660 665 670

Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala 675 680 685 675 680 685

Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro 690 695 700 690 695 700 Page 266 Page 266

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu 705 710 715 720 705 710 715 720

Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp 725 730 735 725 730 735

Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu 740 745 750 740 745 750

Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe 755 760 765 755 760 765

Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu 770 775 780 770 775 780

Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met 785 790 795 800 785 790 795 800

Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro 805 810 815 805 810 815

Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp 820 825 830 820 825 830

Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala 835 840 845 835 840 845

Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu 850 855 860 850 855 860

Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe 865 870 875 880 865 870 875 880

Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg 885 890 895 885 890 895

Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg 900 905 910 900 905 910 Page 267 Page 267

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg 915 920 925 915 920 925

Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His 930 935 940 930 935 940

Thr Arg Lys Ser Gly Gly Glu Asn Leu Tyr Phe Gln Ser Ser Ala Trp Thr Arg Lys Ser Gly Gly Glu Asn Leu Tyr Phe Gln Ser Ser Ala Trp 945 950 955 960 945 950 955 960

Ser His Pro Gln Phe Glu Lys Gly Gly Gly Ser Gly Gly Gly Ser Gly Ser His Pro Gln Phe Glu Lys Gly Gly Gly Ser Gly Gly Gly Ser Gly 965 970 975 965 970 975

Gly Ser Ser Ala Trp Ser His Pro Gln Phe Glu Lys Gly Ser Ser Ala Trp Ser His Pro Gln Phe Glu Lys 980 985 980 985

<210> 64 <210> 64 <211> 956 <211> 956 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> Protein_34_981V_minus_TEV_TwinStrep <223> Protein_34_981V_minus_TEV_TwinStrep

<400> 64 <400> 64

Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro 1 5 10 15 1 5 10 15

Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe 20 25 30 20 25 30

Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln 35 40 45 35 40 45

Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro 50 55 60 50 55 60

Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala 65 70 75 80 70 75 80

Page 268 Page 268

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr 85 90 95 85 90 95

Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr 100 105 110 100 105 110

His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser 115 120 125 115 120 125

Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu 130 135 140 130 135 140

Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His 145 150 155 160 145 150 155 160

Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn 165 170 175 165 170 175

Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg 180 185 190 180 185 190

His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr 195 200 205 195 200 205

Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile 210 215 220 210 215 220

Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu 225 230 235 240 225 230 235 240

Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr 245 250 255 245 250 255

Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro 260 265 270 260 265 270

Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp 275 280 285 275 280 285

Page 269 Page 269

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr 290 295 300 290 295 300

Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr 305 310 315 320 305 310 315 320

Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu 325 330 335 325 330 335

Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys 340 345 350 340 345 350

Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile 355 360 365 355 360 365

Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp 370 375 380 370 375 380

Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr 385 390 395 400 385 390 395 400

Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly 405 410 415 405 410 415

Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu 420 425 430 420 425 430

Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe 435 440 445 435 440 445

Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr 450 455 460 450 455 460

Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln 465 470 475 480 465 470 475 480

Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp 485 490 495 485 490 495

Page 270 Page 270

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn 500 505 510 500 505 510

Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp 515 520 525 515 520 525

Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala 530 535 540 530 535 540

Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe 545 550 555 560 545 550 555 560

Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser 565 570 575 565 570 575

Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu 580 585 590 580 585 590

Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met 595 600 605 595 600 605

Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp 610 615 620 610 615 620

Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys 625 630 635 640 625 630 635 640

Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu 645 650 655 645 650 655

Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys 660 665 670 660 665 670

Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala 675 680 685 675 680 685

Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro 690 695 700 690 695 700

Page 271 Page 271

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu 705 710 715 720 705 710 715 720

Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp 725 730 735 725 730 735

Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu 740 745 750 740 745 750

Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe 755 760 765 755 760 765

Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu 770 775 780 770 775 780

Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met 785 790 795 800 785 790 795 800

Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro 805 810 815 805 810 815

Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp 820 825 830 820 825 830

Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala 835 840 845 835 840 845

Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu 850 855 860 850 855 860

Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe 865 870 875 880 865 870 875 880

Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg 885 890 895 885 890 895

Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg 900 905 910 900 905 910

Page 272 Page 272

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg 915 920 925 915 920 925

Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His 930 935 940 930 935 940

Thr Arg Lys Ser Gly Gly Glu Asn Leu Tyr Phe Gln Thr Arg Lys Ser Gly Gly Glu Asn Leu Tyr Phe Gln 945 950 955 945 950 955

<210> 65 <210> 65 <211> 988 <211> 988 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> Protein_34_981F_TEV_TwinStrep <223> Protein_34_981F_TEV_TwinStrep

<400> 65 <400> 65

Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro 1 5 10 15 1 5 10 15

Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe 20 25 30 20 25 30

Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln 35 40 45 35 40 45

Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro 50 55 60 50 55 60

Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala 65 70 75 80 70 75 80

Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr 85 90 95 85 90 95

Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr 100 105 110 100 105 110

His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser 115 120 125 115 120 125

Page 273 Page 273

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu 130 135 140 130 135 140

Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His 145 150 155 160 145 150 155 160

Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn 165 170 175 165 170 175

Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg 180 185 190 180 185 190

His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr 195 200 205 195 200 205

Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile 210 215 220 210 215 220

Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu 225 230 235 240 225 230 235 240

Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr 245 250 255 245 250 255

Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro 260 265 270 260 265 270

Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp 275 280 285 275 280 285

Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr 290 295 300 290 295 300

Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr 305 310 315 320 305 310 315 320

Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu 325 330 335 325 330 335

Page 274 Page 274

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys 340 345 350 340 345 350

Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile 355 360 365 355 360 365

Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp 370 375 380 370 375 380

Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr 385 390 395 400 385 390 395 400

Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly 405 410 415 405 410 415

Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu 420 425 430 420 425 430

Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe 435 440 445 435 440 445

Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr 450 455 460 450 455 460

Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln 465 470 475 480 465 470 475 480

Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp 485 490 495 485 490 495

Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn 500 505 510 500 505 510

Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp 515 520 525 515 520 525

Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala 530 535 540 530 535 540

Page 275 Page 275

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe 545 550 555 560 545 550 555 560

Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser 565 570 575 565 570 575

Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu 580 585 590 580 585 590

Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met 595 600 605 595 600 605

Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp 610 615 620 610 615 620

Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys 625 630 635 640 625 630 635 640

Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu 645 650 655 645 650 655

Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys 660 665 670 660 665 670

Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala 675 680 685 675 680 685

Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro 690 695 700 690 695 700

Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu 705 710 715 720 705 710 715 720

Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp 725 730 735 725 730 735

Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu 740 745 750 740 745 750 Page 276 Page 276

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe 755 760 765 755 760 765

Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu 770 775 780 770 775 780

Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met 785 790 795 800 785 790 795 800

Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro 805 810 815 805 810 815

Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp 820 825 830 820 825 830

Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala 835 840 845 835 840 845

Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu 850 855 860 850 855 860

Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe 865 870 875 880 865 870 875 880

Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg 885 890 895 885 890 895

Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg 900 905 910 900 905 910

Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg 915 920 925 915 920 925

Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His 930 935 940 930 935 940

Thr Arg Lys Ser Gly Gly Glu Asn Leu Tyr Phe Gln Ser Ser Ala Trp Thr Arg Lys Ser Gly Gly Glu Asn Leu Tyr Phe Gln Ser Ser Ala Trp 945 950 955 960 945 950 955 960 Page 277 Page 277

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Ser His Pro Gln Phe Glu Lys Gly Gly Gly Ser Gly Gly Gly Ser Gly Ser His Pro Gln Phe Glu Lys Gly Gly Gly Ser Gly Gly Gly Ser Gly 965 970 975 965 970 975

Gly Ser Ser Ala Trp Ser His Pro Gln Phe Glu Lys Gly Ser Ser Ala Trp Ser His Pro Gln Phe Glu Lys 980 985 980 985

<210> 66 <210> 66 <211> 956 <211> 956 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> Protein_34_981F_minus_TEV_TwinStrep <223> Protein_34_981F_minus_TEV_TwinStrep

<400> 66 <400> 66

Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro 1 5 10 15 1 5 10 15

Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe 20 25 30 20 25 30

Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln 35 40 45 35 40 45

Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro 50 55 60 50 55 60

Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala 65 70 75 80 70 75 80

Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr 85 90 95 85 90 95

Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr 100 105 110 100 105 110

His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser 115 120 125 115 120 125

Page 278 Page 278

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu 130 135 140 130 135 140

Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His 145 150 155 160 145 150 155 160

Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn 165 170 175 165 170 175

Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg 180 185 190 180 185 190

His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr 195 200 205 195 200 205

Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile 210 215 220 210 215 220

Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu 225 230 235 240 225 230 235 240

Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr 245 250 255 245 250 255

Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro 260 265 270 260 265 270

Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp 275 280 285 275 280 285

Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr 290 295 300 290 295 300

Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr 305 310 315 320 305 310 315 320

Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu 325 330 335 325 330 335

Page 279 Page 279

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys 340 345 350 340 345 350

Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile 355 360 365 355 360 365

Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp 370 375 380 370 375 380

Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr 385 390 395 400 385 390 395 400

Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly 405 410 415 405 410 415

Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu 420 425 430 420 425 430

Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe 435 440 445 435 440 445

Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr 450 455 460 450 455 460

Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln 465 470 475 480 465 470 475 480

Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp 485 490 495 485 490 495

Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn 500 505 510 500 505 510

Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp 515 520 525 515 520 525

Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala 530 535 540 530 535 540

Page 280 Page 280

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. - TXT Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe 545 550 555 560 545 550 555 560

Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser 565 570 575 565 570 575

Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu 580 585 590 580 585 590

Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met 595 600 605 595 600 605

Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp 610 615 620 610 615 620

Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys 625 630 635 640 625 630 635 640

Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu 645 650 655 645 650 655

Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys 660 665 670 660 665 670

Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala 675 680 685 675 680 685

Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro 690 695 700 690 695 700

Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu 705 710 715 720 705 710 715 720

Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp 725 730 735 725 730 735

Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu 740 745 750 740 745 750

Page 281 Page 281

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe 755 760 765 755 760 765

Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu 770 775 780 770 775 780

Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met 785 790 795 800 785 790 795 800

Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro 805 810 815 805 810 815

Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp 820 825 830 820 825 830

Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala 835 840 845 835 840 845

Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu 850 855 860 850 855 860

Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe 865 870 875 880 865 870 875 880

Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg 885 890 895 885 890 895

Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg 900 905 910 900 905 910

Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg 915 920 925 915 920 925

Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His 930 935 940 930 935 940

Thr Arg Lys Ser Gly Gly Glu Asn Leu Tyr Phe Gln Thr Arg Lys Ser Gly Gly Glu Asn Leu Tyr Phe Gln 945 950 955 945 950 955

Page 282 Page 282

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT <210> 67 <210> 67 <211> 988 <211> 988 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> Protein_34_981V_C370S_TEV_TwinStrep <223> Protein_34_981V_C370S_TEV_TwinStrep

<400> 67 <400> 67

Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro 1 5 10 15 1 5 10 15

Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe 20 25 30 20 25 30

Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln 35 40 45 35 40 45

Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro 50 55 60 50 55 60

Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala 65 70 75 80 70 75 80

Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr 85 90 95 85 90 95

Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr 100 105 110 100 105 110

His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser 115 120 125 115 120 125

Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu 130 135 140 130 135 140

Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His 145 150 155 160 145 150 155 160

Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn 165 170 175 165 170 175 Page 283 Page 283

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg 180 185 190 180 185 190

His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr 195 200 205 195 200 205

Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile 210 215 220 210 215 220

Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu 225 230 235 240 225 230 235 240

Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr 245 250 255 245 250 255

Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro 260 265 270 260 265 270

Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp 275 280 285 275 280 285

Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr 290 295 300 290 295 300

Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr 305 310 315 320 305 310 315 320

Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu 325 330 335 325 330 335

Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys 340 345 350 340 345 350

Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile 355 360 365 355 360 365

Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp 370 375 380 370 375 380 Page 284 Page 284

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr 385 390 395 400 385 390 395 400

Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly 405 410 415 405 410 415

Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu 420 425 430 420 425 430

Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe 435 440 445 435 440 445

Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr 450 455 460 450 455 460

Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln 465 470 475 480 465 470 475 480

Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp 485 490 495 485 490 495

Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn 500 505 510 500 505 510

Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp 515 520 525 515 520 525

Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala 530 535 540 530 535 540

Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe 545 550 555 560 545 550 555 560

Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser 565 570 575 565 570 575

Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu 580 585 590 580 585 590 Page 285 Page 285

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met 595 600 605 595 600 605

Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp 610 615 620 610 615 620

Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys 625 630 635 640 625 630 635 640

Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu 645 650 655 645 650 655

Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys 660 665 670 660 665 670

Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala 675 680 685 675 680 685

Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro 690 695 700 690 695 700

Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu 705 710 715 720 705 710 715 720

Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp 725 730 735 725 730 735

Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu 740 745 750 740 745 750

Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe 755 760 765 755 760 765

Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu 770 775 780 770 775 780

Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met 785 790 795 800 785 790 795 800 Page 286 Page 286

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro 805 810 815 805 810 815

Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp 820 825 830 820 825 830

Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala 835 840 845 835 840 845

Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu 850 855 860 850 855 860

Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe 865 870 875 880 865 870 875 880

Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg 885 890 895 885 890 895

Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg 900 905 910 900 905 910

Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg 915 920 925 915 920 925

Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His 930 935 940 930 935 940

Thr Arg Lys Ser Gly Gly Glu Asn Leu Tyr Phe Gln Ser Ser Ala Trp Thr Arg Lys Ser Gly Gly Glu Asn Leu Tyr Phe Gln Ser Ser Ala Trp 945 950 955 960 945 950 955 960

Ser His Pro Gln Phe Glu Lys Gly Gly Gly Ser Gly Gly Gly Ser Gly Ser His Pro Gln Phe Glu Lys Gly Gly Gly Ser Gly Gly Gly Ser Gly 965 970 975 965 970 975

Gly Ser Ser Ala Trp Ser His Pro Gln Phe Glu Lys Gly Ser Ser Ala Trp Ser His Pro Gln Phe Glu Lys 980 985 980 985

<210> 68 <210> 68 <211> 956 <211> 956 Page 287 Page 287

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> Protein_34_981V_C370S_minus_TEV_TwinStrep <223> Protein_34_981V_C370S_minus_TEV_TwinStrep

<400> 68 <400> 68

Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro 1 5 10 15 1 5 10 15

Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe 20 25 30 20 25 30

Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln 35 40 45 35 40 45

Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro 50 55 60 50 55 60

Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala 65 70 75 80 70 75 80

Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr 85 90 95 85 90 95

Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr 100 105 110 100 105 110

His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser 115 120 125 115 120 125

Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu 130 135 140 130 135 140

Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His 145 150 155 160 145 150 155 160

Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn 165 170 175 165 170 175

Page 288 Page 288

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg 180 185 190 180 185 190

His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr 195 200 205 195 200 205

Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile 210 215 220 210 215 220

Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu 225 230 235 240 225 230 235 240

Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr 245 250 255 245 250 255

Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro 260 265 270 260 265 270

Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp 275 280 285 275 280 285

Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr 290 295 300 290 295 300

Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr 305 310 315 320 305 310 315 320

Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu 325 330 335 325 330 335

Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys 340 345 350 340 345 350

Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile 355 360 365 355 360 365

Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp 370 375 380 370 375 380

Page 289 Page 289

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr 385 390 395 400 385 390 395 400

Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly 405 410 415 405 410 415

Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu 420 425 430 420 425 430

Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe 435 440 445 435 440 445

Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr 450 455 460 450 455 460

Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln 465 470 475 480 465 470 475 480

Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp 485 490 495 485 490 495

Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn 500 505 510 500 505 510

Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp 515 520 525 515 520 525

Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala 530 535 540 530 535 540

Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe 545 550 555 560 545 550 555 560

Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser 565 570 575 565 570 575

Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu 580 585 590 580 585 590

Page 290 Page 290

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met 595 600 605 595 600 605

Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp 610 615 620 610 615 620

Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys 625 630 635 640 625 630 635 640

Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu 645 650 655 645 650 655

Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys 660 665 670 660 665 670

Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala 675 680 685 675 680 685

Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro 690 695 700 690 695 700

Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu 705 710 715 720 705 710 715 720

Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp 725 730 735 725 730 735

Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu 740 745 750 740 745 750

Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe 755 760 765 755 760 765

Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu 770 775 780 770 775 780

Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met 785 790 795 800 785 790 795 800

Page 291 Page 291

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. - TXT Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro 805 810 815 805 810 815

Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp 820 825 830 820 825 830

Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala 835 840 845 835 840 845

Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu 850 855 860 850 855 860

Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe 865 870 875 880 865 870 875 880

Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg 885 890 895 885 890 895

Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg 900 905 910 900 905 910

Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg 915 920 925 915 920 925

Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His 930 935 940 930 935 940

Thr Arg Lys Ser Gly Gly Glu Asn Leu Tyr Phe Gln Thr Arg Lys Ser Gly Gly Glu Asn Leu Tyr Phe Gln 945 950 955 945 950 955

<210> 69 <210> 69 <211> 988 <211> 988 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> Protein_34_981F_C370S_TEV_TwinStrep <223> Protein_34_981F_C370S_TEV_TwinStrep

<400> 69 <400> 69

Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro 1 5 10 15 1 5 10 15 Page 292 Page 292

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe 20 25 30 20 25 30

Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln 35 40 45 35 40 45

Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro 50 55 60 50 55 60

Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala 65 70 75 80 70 75 80

Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr 85 90 95 85 90 95

Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr 100 105 110 100 105 110

His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser 115 120 125 115 120 125

Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu 130 135 140 130 135 140

Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His 145 150 155 160 145 150 155 160

Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn 165 170 175 165 170 175

Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg 180 185 190 180 185 190

His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr 195 200 205 195 200 205

Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile 210 215 220 210 215 220 Page 293 Page 293

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu 225 230 235 240 225 230 235 240

Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr 245 250 255 245 250 255

Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro 260 265 270 260 265 270

Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp 275 280 285 275 280 285

Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr 290 295 300 290 295 300

Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr 305 310 315 320 305 310 315 320

Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu 325 330 335 325 330 335

Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys 340 345 350 340 345 350

Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile 355 360 365 355 360 365

Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp 370 375 380 370 375 380

Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr 385 390 395 400 385 390 395 400

Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly 405 410 415 405 410 415

Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu 420 425 430 420 425 430

Page 294 Page 294

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe 435 440 445 435 440 445

Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr 450 455 460 450 455 460

Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln 465 470 475 480 465 470 475 480

Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp 485 490 495 485 490 495

Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn 500 505 510 500 505 510

Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp 515 520 525 515 520 525

Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala 530 535 540 530 535 540

Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe 545 550 555 560 545 550 555 560

Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser 565 570 575 565 570 575

Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu 580 585 590 580 585 590

Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met 595 600 605 595 600 605

Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp 610 615 620 610 615 620

Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys 625 630 635 640 625 630 635 640 Page 295 Page 295

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu 645 650 655 645 650 655

Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys 660 665 670 660 665 670

Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala 675 680 685 675 680 685

Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro 690 695 700 690 695 700

Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu 705 710 715 720 705 710 715 720

Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp 725 730 735 725 730 735

Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu 740 745 750 740 745 750

Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe 755 760 765 755 760 765

Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu 770 775 780 770 775 780

Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met 785 790 795 800 785 790 795 800

Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro 805 810 815 805 810 815

Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp 820 825 830 820 825 830

Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala 835 840 845 835 840 845 Page 296 Page 296

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu 850 855 860 850 855 860

Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe 865 870 875 880 865 870 875 880

Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg 885 890 895 885 890 895

Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg 900 905 910 900 905 910

Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg 915 920 925 915 920 925

Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His 930 935 940 930 935 940

Thr Arg Lys Ser Gly Gly Glu Asn Leu Tyr Phe Gln Ser Ser Ala Trp Thr Arg Lys Ser Gly Gly Glu Asn Leu Tyr Phe Gln Ser Ser Ala Trp 945 950 955 960 945 950 955 960

Ser His Pro Gln Phe Glu Lys Gly Gly Gly Ser Gly Gly Gly Ser Gly Ser His Pro Gln Phe Glu Lys Gly Gly Gly Ser Gly Gly Gly Ser Gly 965 970 975 965 970 975

Gly Ser Ser Ala Trp Ser His Pro Gln Phe Glu Lys Gly Ser Ser Ala Trp Ser His Pro Gln Phe Glu Lys 980 985 980 985

<210> 70 <210> 70 <211> 956 <211> 956 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> Protein_34_981F_C370S_minus_TEV_TwinStrep <223> Protein_34_981F_C370S_minus_TEV_TwinStrep

<400> 70 <400> 70

Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro 1 5 10 15 1 5 10 15

Page 297 Page 297

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe 20 25 30 20 25 30

Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln 35 40 45 35 40 45

Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro 50 55 60 50 55 60

Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala 65 70 75 80 70 75 80

Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr 85 90 95 85 90 95

Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr 100 105 110 100 105 110

His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser 115 120 125 115 120 125

Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu 130 135 140 130 135 140

Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His 145 150 155 160 145 150 155 160

Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn 165 170 175 165 170 175

Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg 180 185 190 180 185 190

His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr 195 200 205 195 200 205

Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile 210 215 220 210 215 220

Page 298 Page 298

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu 225 230 235 240 225 230 235 240

Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr 245 250 255 245 250 255

Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro 260 265 270 260 265 270

Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp 275 280 285 275 280 285

Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr 290 295 300 290 295 300

Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr 305 310 315 320 305 310 315 320

Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu 325 330 335 325 330 335

Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys 340 345 350 340 345 350

Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile 355 360 365 355 360 365

Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp 370 375 380 370 375 380

Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr 385 390 395 400 385 390 395 400

Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly 405 410 415 405 410 415

Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu 420 425 430 420 425 430

Page 299 Page 299

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe 435 440 445 435 440 445

Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr 450 455 460 450 455 460

Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln 465 470 475 480 465 470 475 480

Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp 485 490 495 485 490 495

Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asn 500 505 510 500 505 510

Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp 515 520 525 515 520 525

Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala 530 535 540 530 535 540

Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe 545 550 555 560 545 550 555 560

Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser 565 570 575 565 570 575

Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu 580 585 590 580 585 590

Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met 595 600 605 595 600 605

Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp 610 615 620 610 615 620

Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys 625 630 635 640 625 630 635 640

Page 300 Page 300

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Glu 645 650 655 645 650 655

Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys 660 665 670 660 665 670

Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Ala 675 680 685 675 680 685

Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro 690 695 700 690 695 700

Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu 705 710 715 720 705 710 715 720

Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp 725 730 735 725 730 735

Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu 740 745 750 740 745 750

Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Phe 755 760 765 755 760 765

Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Glu 770 775 780 770 775 780

Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met 785 790 795 800 785 790 795 800

Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro 805 810 815 805 810 815

Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp 820 825 830 820 825 830

Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala 835 840 845 835 840 845

Page 301 Page 301

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu 850 855 860 850 855 860

Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe 865 870 875 880 865 870 875 880

Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Arg 885 890 895 885 890 895

Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg 900 905 910 900 905 910

Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg 915 920 925 915 920 925

Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe His 930 935 940 930 935 940

Thr Arg Lys Ser Gly Gly Glu Asn Leu Tyr Phe Gln Thr Arg Lys Ser Gly Gly Glu Asn Leu Tyr Phe Gln 945 950 955 945 950 955

<210> 71 <210> 71 <211> 33 <211> 33 <212> PRT <212> PRT <213> Homo sapiens <213> Homo sapiens

<400> 71 <400> 71

Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser 1 5 10 15 1 5 10 15

Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg 20 25 30 20 25 30

Ala Ala

<210> 72 <210> 72 <211> 19 <211> 19 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

Page 302 Page 302

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT <220> <220> <223> Protein_Synthetic_Signal_Peptide <223> Protein_Synthetic_Signal_Peptide

<400> 72 <400> 72

Met Ala Arg Leu Thr Val Leu Ala Leu Leu Ala Gly Leu Leu Ala Ser Met Ala Arg Leu Thr Val Leu Ala Leu Leu Ala Gly Leu Leu Ala Ser 1 5 10 15 1 5 10 15

Ser Arg Ala Ser Arg Ala

<210> 73 <210> 73 <211> 10 <211> 10 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> Protein_GS_linker <223> Protein_GS_linken

<400> 73 <400> 73

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 1 5 10 1 5 10

<210> 74 <210> 74 <211> 227 <211> 227 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> Protein_ IgG1_noCH1_Fc_Fusion <223> Protein IgG1_noCH1_Fc_Fusion

<400> 74 <400> 74

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 1 5 10 15 1 5 10 15

Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 20 25 30 20 25 30

Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 35 40 45 35 40 45

Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 50 55 60 50 55 60

Page 303 Page 303

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 65 70 75 80 70 75 80

Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 85 90 95 85 90 95

Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 100 105 110 100 105 110

Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 115 120 125 115 120 125

Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 130 135 140 130 135 140

Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 145 150 155 160 145 150 155 160

Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 165 170 175 165 170 175

Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 180 185 190 180 185 190

Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 195 200 205 195 200 205

His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 210 215 220 210 215 220

Pro Gly Lys Pro Gly Lys 225 225

<210> 75 <210> 75 <211> 40 <211> 40 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> Protein_TwinStrep <223> Protein_TwinStrep Page 304 Page 304

20780-15A_SequenceListing.TXT 20780‐15A_SequenceListing.TXT

<400> 75 <400> 75 Gly 1 Gly Glu Asn Leu Tyr Phe Gln Ser Ser Ala Trp Ser His Pro Gln Gly Gly Glu Asn Leu Tyr Phe Gln Ser Ser Ala Trp Ser His Pro Gln 1 5 10 15 5 10 15

Phe Glu Lys Gly 20 Gly Gly Ser Gly Gly Gly Ser Gly Gly Ser Ser Ala Phe Glu Lys Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Ser Ser Ala 20 25 30 25 30

Trp Ser His Pro Gln Phe Glu Lys Trp Ser His Pro Gln Phe Glu Lys 35 40 35 40

<210> 76 <210> 76 <211> 3036 <211> 3036 <212> DNA <212> DNA <213> Homo sapiens <213> Homo sapiens

<400> 76 atgcccgcca <400> 76 gcgccccgcc gcgccgcccg cggccgccgc cgccgtcgct gtcgctgctg atgcccgcca gcgccccgcc gcgccgcccg cggccgccgc cgccgtcgct gtcgctgctg 60 60 ctggtgctgc tgggcctggg cggccgccgc ctgcgtgcgg agccgggcga cggcgcgcag ctggtgctgc tgggcctggg cggccgccgc ctgcgtgcgg agccgggcga cggcgcgcag 120 120 acctgggcco gtgtctcgcg gcctcctgcc cccgaggccg cgggcctctt ccagggcaco acctgggccc gtgtctcgcg gcctcctgcc cccgaggccg cgggcctctt ccagggcacc 180 180 ttccccgacg gcttcctctg ggccgtgggo agcgccgcct accagaccga gggcggctgg ttccccgacg gcttcctctg ggccgtgggc agcgccgcct accagaccga gggcggctgg 240 240 cagcagcacg gcaagggtgc gtccatctgg gacacgttca cccaccaccc cctggcaccc cagcagcacg gcaagggtgc gtccatctgg gacacgttca cccaccaccc cctggcaccc 300 300 ccgggagact cccggaacgc cagtctgccg ttgggcgccc cgtcgccgct gcagcccgcc ccgggagact cccggaacgc cagtctgccg ttgggcgccc cgtcgccgct gcagcccgcc 360 360 accggggacg tagccagcga cagctacaac aacgtcttcc gcgacacgga ggcgctgcgc accggggacg tagccagcga cagctacaac aacgtcttcc gcgacacgga ggcgctgcgc 420 420 gagctcgggg tcactcacta ccgcttctcc atctcgtggg cgcgagtgct ccccaatggc gagctcgggg tcactcacta ccgcttctcc atctcgtggg cgcgagtgct ccccaatggc 480 480 agcgcgggcg tccccaaccg cgaggggctg cgctactacc ggcgcctgct ggagcggctg agcgcgggcg tccccaaccg cgaggggctg cgctactacc ggcgcctgct ggagcggctg 540 540 cgggagctgg gcgtgcagcc cgtggtcacc ctgtaccact gggacctgcc ccagcgcctg cgggagctgg gcgtgcagcc cgtggtcacc ctgtaccact gggacctgcc ccagcgcctg 600 600 caggacgcct acggcggctg ggccaaccgc gccctggccg accacttcag ggattacgcg caggacgcct acggcggctg ggccaaccgc gccctggccg accacttcag ggattacgcg 660 660 gagctctgct tccgccactt cggcggtcag gtcaagtact ggatcaccat cgacaacccc gagctctgct tccgccactt cggcggtcag gtcaagtact ggatcaccat cgacaacccc 720 720 tacgtggtgg cctggcacgg ctacgccacc gggcgcctgg cccccggcat ccggggcago tacgtggtgg cctggcacgg ctacgccacc gggcgcctgg cccccggcat ccggggcagc 780 780 ccgcggctcg ggtacctggt ggcgcacaac ctcctcctgg ctcatgccaa agtctggcat ccgcggctcg ggtacctggt ggcgcacaac ctcctcctgg ctcatgccaa agtctggcat 840 840 ctctacaata cttctttccg tcccactcag ggaggtcagg tgtccattgc cctaagctct ctctacaata cttctttccg tcccactcag ggaggtcagg tgtccattgc cctaagctct 900 900 cactggatca atcctcgaag aatgaccgac cacagcatca aagaatgtca aaaatctctg cactggatca atcctcgaag aatgaccgac cacagcatca aagaatgtca aaaatctctg 960 960 Page 305 Page 305

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

gactttgtac taggttggtt tgccaaaccc gtatttattg atggtgacta tcccgagagc 1020 gactttgtac taggttggtt tgccaaaccc gtatttattg atggtgacta tcccgagagc 1020

atgaagaata acctttcatc tattctgcct gattttactg aatctgagaa aaagttcatc 1080 atgaagaata acctttcatc tattctgcct gattttactg aatctgagaa aaagttcatc 1080

aaaggaactg ctgacttttt tgctctttgc tttggaccca ccttgagttt tcaacttttg 1140 aaaggaactg ctgacttttt tgctctttgc tttggaccca ccttgagttt tcaacttttg 1140

gaccctcaca tgaagttccg ccaattggaa tctcccaacc tgaggcaact gctttcctgg 1200 gaccctcaca tgaagttccg ccaattggaa tctcccaacc tgaggcaact gctttcctgg 1200

attgaccttg aatttaacca tcctcaaata tttattgtgg aaaatggctg gtttgtctca 1260 attgaccttg aatttaacca tcctcaaata tttattgtgg aaaatggctg gtttgtctca 1260

gggaccacca agagagatga tgccaaatat atgtattacc tcaaaaagtt catcatggaa 1320 gggaccacca agagagatga tgccaaatat atgtattacc tcaaaaagtt catcatggaa 1320

accttaaaag ccatcaagct ggatggggtg gatgtcatcg ggtataccgc atggtccctc 1380 accttaaaag ccatcaagct ggatggggtg gatgtcatcg ggtataccgc atggtccctc 1380

atggatggtt tcgagtggca cagaggttac agcatcaggc gtggactctt ctatgttgac 1440 atggatggtt tcgagtggca cagaggttac agcatcaggc gtggactctt ctatgttgac 1440

tttctaagcc aggacaagat gttgttgcca aagtcttcag ccttgttcta ccaaaagctg 1500 tttctaagcc aggacaagat gttgttgcca aagtcttcag ccttgttcta ccaaaagctg 1500

atagagaaaa atggcttccc tcctttacct gaaaatcagc ccctagaagg gacatttccc 1560 atagagaaaa atggcttccc tcctttacct gaaaatcagc ccctagaagg gacatttccc 1560

tgtgactttg cttggggagt tgttgacaac tacattcaag tagataccac tctgtctcag 1620 tgtgactttg cttggggagt tgttgacaac tacattcaag tagataccac tctgtctcag 1620

tttaccgacc tgaatgttta cctgtgggat gtccaccaca gtaaaaggct tattaaagtg 1680 tttaccgacc tgaatgttta cctgtgggat gtccaccaca gtaaaaggct tattaaagtg 1680

gatggggttg tgaccaagaa gaggaaatcc tactgtgttg actttgctgc catccagccc 1740 gatggggttg tgaccaagaa gaggaaatcc tactgtgttg actttgctgc catccagccc 1740

cagatcgctt tactccagga aatgcacgtt acacattttc gcttctccct ggactgggcc 1800 cagatcgctt tactccagga aatgcacgtt acacattttc gcttctccct ggactgggcc 1800

ctgattctcc ctctgggtaa ccagtcccag gtgaaccaca ccatcctgca gtactatcgc 1860 ctgattctcc ctctgggtaa ccagtcccag gtgaaccaca ccatcctgca gtactatcgc 1860

tgcatggcca gcgagcttgt ccgtgtcaac atcaccccag tggtggccct gtggcagcct 1920 tgcatggcca gcgagcttgt ccgtgtcaac atcaccccag tggtggccct gtggcagcct 1920

atggccccga accaaggact gccgcgcctc ctggccaggc agggcgcctg ggagaacccc 1980 atggccccga accaaggact gccgcgcctc ctggccaggc agggcgcctg ggagaacccc 1980

tacactgccc tggcctttgc agagtatgcc cgactgtgct ttcaagagct cggccatcac 2040 tacactgccc tggcctttgc agagtatgcc cgactgtgct ttcaagagct cggccatcac 2040

gtcaagcttt ggataacgat gaatgagccg tatacaagga atatgacata cagtgctggc 2100 gtcaagcttt ggataacgat gaatgagccg tatacaagga atatgacata cagtgctggc 2100

cacaaccttc tgaaggccca tgccctggct tggcatgtgt acaatgaaaa gtttaggcat 2160 cacaaccttc tgaaggccca tgccctggct tggcatgtgt acaatgaaaa gtttaggcat 2160

gctcagaatg ggaaaatatc catagccttg caggctgatt ggatagaacc tgcctgccct 2220 gctcagaatg ggaaaatatc catagccttg caggctgatt ggatagaacc tgcctgccct 2220

ttctcccaaa aggacaaaga ggtggccgag agagttttgg aatttgacat tggctggctg 2280 ttctcccaaa aggacaaaga ggtggccgag agagttttgg aatttgacat tggctggctg 2280

gctgagccca ttttcggctc tggagattat ccatgggtga tgagggactg gctgaaccaa 2340 gctgagccca ttttcggctc tggagattat ccatgggtga tgagggactg gctgaaccaa 2340

agaaacaatt ttcttcttcc ttatttcact gaagatgaaa aaaagctaat ccagggtacc 2400 agaaacaatt ttcttcttcc ttatttcact gaagatgaaa aaaagctaat ccagggtacc 2400

tttgactttt tggctttaag ccattatacc accatccttg tagactcaga aaaagaagat 2460 tttgactttt tggctttaag ccattatacc accatccttg tagactcaga aaaagaagat 2460

ccaataaaat acaatgatta cctagaagtg caagaaatga ccgacatcac gtggctcaac 2520 ccaataaaat acaatgatta cctagaagtg caagaaatga ccgacatcad gtggctcaac 2520

Page 306 Page 306

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

tcccccagtc aggtggcggt agtgccctgg gggttgcgca aagtgctgaa ctggctgaag 2580 tcccccagtc aggtggcggt agtgccctgg gggttgcgca aagtgctgaa ctggctgaag 2580

ttcaagtacg gagacctccc catgtacata atatccaacg gaatcgatga cgggctgcat 2640 ttcaagtacg gagacctccc catgtacata atatccaacg gaatcgatga cgggctgcat 2640

gctgaggacg accagctgag ggtgtattat atgcagaatt acataaacga agctctcaaa 2700 gctgaggacg accagctgag ggtgtattat atgcagaatt acataaacga agctctcaaa 2700

gcccacatac tggatggtat caatctttgc ggatactttg cttattcgtt taacgaccgc 2760 gcccacatac tggatggtat caatctttgc ggatactttg cttattcgtt taacgaccgc 2760

acagctccga ggtttggcct ctatcgttat gctgcagatc agtttgagcc caaggcatcc 2820 acagctccga ggtttggcct ctatcgttat gctgcagatc agtttgagcc caaggcatcc 2820

atgaaacatt acaggaaaat tattgacagc aatggtttcc cgggcccaga aactctggaa 2880 atgaaacatt acaggaaaat tattgacagc aatggtttcc cgggcccaga aactctggaa 2880

agattttgtc cagaagaatt caccgtgtgt actgagtgca gtttttttca cacccgaaag 2940 agattttgtc cagaagaatt caccgtgtgt actgagtgca gtttttttca cacccgaaag 2940

tctttactgg ctttcatagc ttttctattt tttgcttcta ttatttctct ctcccttata 3000 tctttactgg ctttcatagc ttttctattt tttgcttcta ttatttctct ctcccttata 3000

ttttactact cgaagaaagg cagaagaagt tacaaa 3036 ttttactact cgaagaaagg cagaagaagt tacaaa 3036

<210> 77 <210> 77 <211> 2943 <211> 2943 <212> DNA <212> DNA <213> Homo sapiens <213> Homo sapiens

<400> 77 <400> 77 atgcccgcca gcgccccgcc gcgccgcccg cggccgccgc cgccgtcgct gtcgctgctg 60 atgcccgcca gcgccccgcc gcgccgcccg cggccgccgc cgccgtcgct gtcgctgctg 60

ctggtgctgc tgggcctggg cggccgccgc ctgcgtgcgg agccgggcga cggcgcgcag 120 ctggtgctgc tgggcctggg cggccgccgc ctgcgtgcgg agccgggcga cggcgcgcag 120

acctgggccc gtgtctcgcg gcctcctgcc cccgaggccg cgggcctctt ccagggcacc 180 acctgggccc gtgtctcgcg gcctcctgcc cccgaggccg cgggcctctt ccagggcacc 180

ttccccgacg gcttcctctg ggccgtgggc agcgccgcct accagaccga gggcggctgg 240 ttccccgacg gcttcctctg ggccgtgggc agcgccgcct accagaccga gggcggctgg 240

cagcagcacg gcaagggtgc gtccatctgg gacacgttca cccaccaccc cctggcaccc 300 cagcagcacg gcaagggtgc gtccatctgg gacacgttca cccaccaccc cctggcaccc 300

ccgggagact cccggaacgc cagtctgccg ttgggcgccc cgtcgccgct gcagcccgcc 360 ccgggagact cccggaacgc cagtctgccg ttgggcgccc cgtcgccgct gcagcccgcc 360

accggggacg tagccagcga cagctacaac aacgtcttcc gcgacacgga ggcgctgcgc 420 accggggacg tagccagcga cagctacaac aacgtcttcc gcgacacgga ggcgctgcgc 420

gagctcgggg tcactcacta ccgcttctcc atctcgtggg cgcgagtgct ccccaatggc 480 gagctcgggg tcactcacta ccgcttctcc atctcgtggg cgcgagtgct ccccaatggc 480

agcgcgggcg tccccaaccg cgaggggctg cgctactacc ggcgcctgct ggagcggctg 540 agcgcgggcg tccccaaccg cgaggggctg cgctactacc ggcgcctgct ggagcggctg 540

cgggagctgg gcgtgcagcc cgtggtcacc ctgtaccact gggacctgcc ccagcgcctg 600 cgggagctgg gcgtgcagcc cgtggtcacc ctgtaccact gggacctgcc ccagcgcctg 600

caggacgcct acggcggctg ggccaaccgc gccctggccg accacttcag ggattacgcg 660 caggacgcct acggcggctg ggccaaccgc gccctggccg accacttcag ggattacgcg 660

gagctctgct tccgccactt cggcggtcag gtcaagtact ggatcaccat cgacaacccc 720 gagctctgct tccgccactt cggcggtcag gtcaagtact ggatcaccat cgacaacccc 720

tacgtggtgg cctggcacgg ctacgccacc gggcgcctgg cccccggcat ccggggcagc 780 tacgtggtgg cctggcacgg ctacgccacc gggcgcctgg cccccggcat ccggggcagc 780

Page 307 Page 307

20780‐15A_SequenceListing.TXT ccgcggctcg ggtacctggt ggcgcacaac ctcctcctgg ctcatgccaa agtctggcat 840

ctctacaata cttctttccg tcccactcag ggaggtcagg tgtccattgc cctaagctct 900 006

cactggatca atcctcgaag aatgaccgac cacagcatca aagaatgtca aaaatctctg 960 096

the gactttgtac taggttggtt tgccaaaccc gtatttattg atggtgacta tcccgagagc 1020 0201

atgaagaata acctttcatc tattctgcct gattttactg aatctgagaa aaagttcatc 1080 080T

the aaaggaactg ctgacttttt tgctctttgc tttggaccca ccttgagttt tcaacttttg 1140

gaccctcaca tgaagttccg ccaattggaa tctcccaacc tgaggcaact gctttcctgg 1200

attgaccttg aatttaacca tcctcaaata tttattgtgg aaaatggctg gtttgtctca 1260 092I

the e gggaccacca agagagatga tgccaaatat atgtattacc tcaaaaagtt catcatggaa 1320 OZET

accttaaaag ccatcaagct ggatggggtg gatgtcatcg ggtataccgc atggtccctc 1380 08EI

atggatggtt tcgagtggca cagaggttac agcatcaggc gtggactctt ctatgttgac 1440

tttctaagcc aggacaagat gttgttgcca aagtcttcag ccttgttcta ccaaaagctg 1500 00ST

atagagaaaa atggcttccc tcctttacct gaaaatcagc ccctagaagg gacatttccc 1560 09ST

tgtgactttg cttggggagt tgttgacaac tacattcaag tagataccac tctgtctcag 1620 029T

tttaccgacc tgaatgttta cctgtgggat gtccaccaca gtaaaaggct tattaaagtg 1680 089T

gatggggttg tgaccaagaa gaggaaatcc tactgtgttg actttgctgc catccagccc 1740 97789991e8

cagatcgctt tactccagga aatgcacgtt acacattttc gcttctccct ggactgggcc 1800 008T

the ctgattctcc ctctgggtaa ccagtcccag gtgaaccaca ccatcctgca gtactatcgc 1860 098T

tgcatggcca gcgagcttgt ccgtgtcaac atcaccccag tggtggccct gtggcagcct 1920 026T

atggccccga accaaggact gccgcgcctc ctggccaggc agggcgcctg ggagaacccc 1980 086T

tacactgccc tggcctttgc agagtatgcc cgactgtgct ttcaagagct cggccatcac 2040 9702

gtcaagcttt ggataacgat gaatgagccg tatacaagga atatgacata cagtgctggc 2100 00I2

cacaaccttc tgaaggccca tgccctggct tggcatgtgt acaatgaaaa gtttaggcat 2160 09T2

gctcagaatg ggaaaatatc catagccttg caggctgatt ggatagaacc tgcctgccct 2220 0222

ttctcccaaa aggacaaaga ggtggccgag agagttttgg aatttgacat tggctggctg 2280 0822 9977778e8e e gctgagccca ttttcggctc tggagattat ccatgggtga tgagggactg gctgaaccaa 2340 OTEL

Page 308 80E

20780‐15A_SequenceListing.TXT agaaacaatt ttcttcttcc ttatttcact gaagatgaaa aaaagctaat ccagggtacc 2400

tttgactttt tggctttaag ccattatacc accatccttg tagactcaga aaaagaagat 2460

ccaataaaat acaatgatta cctagaagtg caagaaatga ccgacatcac gtggctcaac 2520 0252

tcccccagtc aggtggcggt agtgccctgg gggttgcgca aagtgctgaa ctggctgaag 2580 0852

ttcaagtacg gagacctccc catgtacata atatccaacg gaatcgatga cgggctgcat 2640

gctgaggacg accagctgag ggtgtattat atgcagaatt acataaacga agctctcaaa 2700 00/2

gcccacatac tggatggtat caatctttgc ggatactttg cttattcgtt taacgaccgc 2760 09/2

e acagctccga ggtttggcct ctatcgttat gctgcagatc agtttgagcc caaggcatcc 2820 0282

atgaaacatt acaggaaaat tattgacagc aatggtttcc cgggcccaga aactctggaa 2880 0887

agattttgtc cagaagaatt caccgtgtgt actgagtgca gtttttttca cacccgaaag 2940

the 9762

tct 2943 707 8762

<210> 78 <0TZ> 8L <211> 2859 <IIZ> 6982 <212> DNA <ZIZ> ANC <213> Homo sapiens <ETZ>

<400> 78 8L <00 cgccgcctgc gtgcggagcc gggcgacggc gcgcagacct gggcccgtgt ctcgcggcct 60 09

cctgcccccg aggccgcggg cctcttccag ggcaccttcc ccgacggctt cctctgggcc 120

gtgggcagcg ccgcctacca gaccgagggc ggctggcagc agcacggcaa gggtgcgtcc 180 08T

atctgggaca cgttcaccca ccaccccctg gcacccccgg gagactcccg gaacgccagt 240

the ctgccgttgg gcgccccgtc gccgctgcag cccgccaccg gggacgtagc cagcgacagc 300 00E

tacaacaacg tcttccgcga cacggaggcg ctgcgcgagc tcggggtcac tcactaccgc 360 09E

ttctccatct cgtgggcgcg agtgctcccc aatggcagcg cgggcgtccc caaccgcgag 420

gggctgcgct actaccggcg cctgctggag cggctgcggg agctgggcgt gcagcccgtg 480 08/7

gtcaccctgt accactggga cctgccccag cgcctgcagg acgcctacgg cggctgggcc 540 STS

aaccgcgccc tggccgacca cttcagggat tacgcggagc tctgcttccg ccacttcggc 600 009

ggtcaggtca agtactggat caccatcgac aacccctacg tggtggcctg gcacggctac 660 099

gccaccgggc gcctggcccc cggcatccgg ggcagcccgc ggctcgggta cctggtggcg 720 02L Page 309 60E anded

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

cacaacctcc tcctggctca tgccaaagtc tggcatctct acaatacttc tttccgtccc 780 cacaacctcc tcctggctca tgccaaagtc tggcatctct acaatacttc tttccgtccc 780

actcagggag gtcaggtgtc cattgcccta agctctcact ggatcaatcc tcgaagaatg 840 actcagggag gtcaggtgtc cattgcccta agctctcact ggatcaatcc tcgaagaatg 840

accgaccaca gcatcaaaga atgtcaaaaa tctctggact ttgtactagg ttggtttgcc 900 accgaccaca gcatcaaaga atgtcaaaaa tctctggact ttgtactagg ttggtttgcc 900

aaacccgtat ttattgatgg tgactatccc gagagcatga agaataacct ttcatctatt 960 aaacccgtat ttattgatgg tgactatccc gagagcatga agaataacct ttcatctatt 960

ctgcctgatt ttactgaatc tgagaaaaag ttcatcaaag gaactgctga cttttttgct 1020 ctgcctgatt ttactgaatc tgagaaaaag ttcatcaaag gaactgctga cttttttgct 1020

ctttgctttg gacccacctt gagttttcaa cttttggacc ctcacatgaa gttccgccaa 1080 ctttgctttg gacccacctt gagttttcaa cttttggacc ctcacatgaa gttccgccaa 1080

ttggaatctc ccaacctgag gcaactgctt tcctggattg accttgaatt taaccatcct 1140 ttggaatctc ccaacctgag gcaactgctt tcctggattg accttgaatt taaccatcct 1140

caaatattta ttgtggaaaa tggctggttt gtctcaggga ccaccaagag agatgatgcc 1200 caaatattta ttgtggaaaa tggctggttt gtctcaggga ccaccaagag agatgatgcc 1200

aaatatatgt attacctcaa aaagttcatc atggaaacct taaaagccat caagctggat 1260 aaatatatgt attacctcaa aaagttcatc atggaaacct taaaagccat caagctggat 1260

ggggtggatg tcatcgggta taccgcatgg tccctcatgg atggtttcga gtggcacaga 1320 ggggtggatg tcatcgggta taccgcatgg tccctcatgg atggtttcga gtggcacaga 1320

ggttacagca tcaggcgtgg actcttctat gttgactttc taagccagga caagatgttg 1380 ggttacagca tcaggcgtgg actcttctat gttgactttc taagccagga caagatgttg 1380

ttgccaaagt cttcagcctt gttctaccaa aagctgatag agaaaaatgg cttccctcct 1440 ttgccaaagt cttcagcctt gttctaccaa aagctgatag agaaaaatgg cttccctcct 1440

ttacctgaaa atcagcccct agaagggaca tttccctgtg actttgcttg gggagttgtt 1500 ttacctgaaa atcagcccct agaagggaca tttccctgtg actttgcttg gggagttgtt 1500

gacaactaca ttcaagtaga taccactctg tctcagttta ccgacctgaa tgtttacctg 1560 gacaactaca ttcaagtaga taccactctg tctcagttta ccgacctgaa tgtttacctg 1560

tgggatgtcc accacagtaa aaggcttatt aaagtggatg gggttgtgac caagaagagg 1620 tgggatgtcc accacagtaa aaggcttatt aaagtggatg gggttgtgac caagaagagg 1620

aaatcctact gtgttgactt tgctgccatc cagccccaga tcgctttact ccaggaaatg 1680 aaatcctact gtgttgactt tgctgccatc cagccccaga tcgctttact ccaggaaatg 1680

cacgttacac attttcgctt ctccctggac tgggccctga ttctccctct gggtaaccag 1740 cacgttacac attttcgctt ctccctggac tgggccctga ttctccctct gggtaaccag 1740

tcccaggtga accacaccat cctgcagtac tatcgctgca tggccagcga gcttgtccgt 1800 tcccaggtga accacaccat cctgcagtac tatcgctgca tggccagcga gcttgtccgt 1800

gtcaacatca ccccagtggt ggccctgtgg cagcctatgg ccccgaacca aggactgccg 1860 gtcaacatca ccccagtggt ggccctgtgg cagcctatgg ccccgaacca aggactgccg 1860

cgcctcctgg ccaggcaggg cgcctgggag aacccctaca ctgccctggc ctttgcagag 1920 cgcctcctgg ccaggcaggg cgcctgggag aacccctaca ctgccctggc ctttgcagag 1920

tatgcccgac tgtgctttca agagctcggc catcacgtca agctttggat aacgatgaat 1980 tatgcccgac tgtgctttca agagctcggc catcacgtca agctttggat aacgatgaat 1980

gagccgtata caaggaatat gacatacagt gctggccaca accttctgaa ggcccatgcc 2040 gagccgtata caaggaatat gacatacagt gctggccaca accttctgaa ggcccatgcc 2040

ctggcttggc atgtgtacaa tgaaaagttt aggcatgctc agaatgggaa aatatccata 2100 ctggcttggc atgtgtacaa tgaaaagttt aggcatgctc agaatgggaa aatatccata 2100

gccttgcagg ctgattggat agaacctgcc tgccctttct cccaaaagga caaagaggtg 2160 gccttgcagg ctgattggat agaacctgcc tgccctttct cccaaaagga caaagaggtg 2160

gccgagagag ttttggaatt tgacattggc tggctggctg agcccatttt cggctctgga 2220 gccgagagag ttttggaatt tgacattggc tggctggctg agcccatttt cggctctgga 2220

gattatccat gggtgatgag ggactggctg aaccaaagaa acaattttct tcttccttat 2280 gattatccat gggtgatgag ggactggctg aaccaaagaa acaattttct tcttccttat 2280

Page 310 Page 310

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

ttcactgaag atgaaaaaaa gctaatccag ggtacctttg actttttggc tttaagccat 2340 ttcactgaag atgaaaaaaa gctaatccag ggtacctttg actttttggc tttaagccat 2340

tataccacca tccttgtaga ctcagaaaaa gaagatccaa taaaatacaa tgattaccta 2400 tataccacca tccttgtaga ctcagaaaaa gaagatccaa taaaatacaa tgattaccta 2400

gaagtgcaag aaatgaccga catcacgtgg ctcaactccc ccagtcaggt ggcggtagtg 2460 gaagtgcaag aaatgaccga catcacgtgg ctcaactccc ccagtcaggt ggcggtagtg 2460

ccctgggggt tgcgcaaagt gctgaactgg ctgaagttca agtacggaga cctccccatg 2520 ccctgggggt tgcgcaaagt gctgaactgg ctgaagttca agtacggaga cctccccatg 2520

tacataatat ccaacggaat cgatgacggg ctgcatgctg aggacgacca gctgagggtg 2580 tacataatat ccaacggaat cgatgacggg ctgcatgctg aggacgacca gctgagggtg 2580

tattatatgc agaattacat aaacgaagct ctcaaagccc acatactgga tggtatcaat 2640 tattatatgc agaattacat aaacgaagct ctcaaagccc acatactgga tggtatcaat 2640

ctttgcggat actttgctta ttcgtttaac gaccgcacag ctccgaggtt tggcctctat 2700 ctttgcggat actttgctta ttcgtttaac gaccgcacag ctccgaggtt tggcctctat 2700

cgttatgctg cagatcagtt tgagcccaag gcatccatga aacattacag gaaaattatt 2760 cgttatgctg cagatcagtt tgagcccaag gcatccatga aacattacag gaaaattatt 2760

gacagcaatg gtttcccggg cccagaaact ctggaaagat tttgtccaga agaattcacc 2820 gacagcaatg gtttcccggg cccagaaact ctggaaagat tttgtccaga agaattcacc 2820

gtgtgtactg agtgcagttt ttttcacacc cgaaagtct 2859 gtgtgtactg agtgcagttt ttttcacacc cgaaagtct 2859

<210> 79 <210> 79 <211> 2844 <211> 2844 <212> DNA <212> DNA <213> Homo sapiens <213> Homo sapiens

<400> 79 <400> 79 gagccgggcg acggcgcgca gacctgggcc cgtgtctcgc ggcctcctgc ccccgaggcc 60 gagccgggcg acggcgcgca gacctgggcc cgtgtctcgc ggcctcctgc ccccgaggcc 60

gcgggcctct tccagggcac cttccccgac ggcttcctct gggccgtggg cagcgccgcc 120 gcgggcctct tccagggcac cttccccgac ggcttcctct gggccgtggg cagcgccgcc 120

taccagaccg agggcggctg gcagcagcac ggcaagggtg cgtccatctg ggacacgttc 180 taccagaccg agggcggctg gcagcagcaa ggcaagggtg cgtccatctg ggacacgttc 180

acccaccacc ccctggcacc cccgggagac tcccggaacg ccagtctgcc gttgggcgcc 240 acccaccacc ccctggcacc cccgggagac tcccggaacg ccagtctgcc gttgggcgcc 240

ccgtcgccgc tgcagcccgc caccggggac gtagccagcg acagctacaa caacgtcttc 300 ccgtcgccgc tgcagcccgc caccggggac gtagccagcg acagctacaa caacgtcttc 300

cgcgacacgg aggcgctgcg cgagctcggg gtcactcact accgcttctc catctcgtgg 360 cgcgacacgg aggcgctgcg cgagctcggg gtcactcact accgcttctc catctcgtgg 360

gcgcgagtgc tccccaatgg cagcgcgggc gtccccaacc gcgaggggct gcgctactac 420 gcgcgagtgc tccccaatgg cagcgcgggo gtccccaacc gcgaggggct gcgctactac 420

cggcgcctgc tggagcggct gcgggagctg ggcgtgcagc ccgtggtcac cctgtaccac 480 cggcgcctgc tggagcggct gcgggagctg ggcgtgcagc ccgtggtcac cctgtaccac 480

tgggacctgc cccagcgcct gcaggacgcc tacggcggct gggccaaccg cgccctggcc 540 tgggacctgc cccagcgcct gcaggacgcc tacggcggct gggccaaccg cgccctggcc 540

gaccacttca gggattacgc ggagctctgc ttccgccact tcggcggtca ggtcaagtac 600 gaccacttca gggattacgc ggagctctgc ttccgccact tcggcggtca ggtcaagtac 600

tggatcacca tcgacaaccc ctacgtggtg gcctggcacg gctacgccac cgggcgcctg 660 tggatcacca tcgacaaccc ctacgtggtg gcctggcacg gctacgccac cgggcgcctg 660

gcccccggca tccggggcag cccgcggctc gggtacctgg tggcgcacaa cctcctcctg 720 gccccccggca tccggggcag cccgcggctc gggtacctgg tggcgcacaa cctcctcctg 720

Page 311 Page 311

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT gctcatgcca aagtctggca tctctacaat acttctttcc gtcccactca gggaggtcag gctcatgcca aagtctggca tctctacaat acttctttcc gtcccactca gggaggtcag 780 780

gtgtccattg ccctaagctc tcactggatc aatcctcgaa gaatgaccga ccacagcato gtgtccattg ccctaagctc tcactggatc aatcctcgaa gaatgaccga ccacagcatc 840 840

aaagaatgtc aaaaatctct ggactttgta ctaggttggt ttgccaaacc cgtatttatt aaagaatgtc aaaaatctct ggactttgta ctaggttggt ttgccaaacc cgtatttatt 900 900

gatggtgact atcccgagag catgaagaat aacctttcat ctattctgcc tgattttact gatggtgact atcccgagag catgaagaat aacctttcat ctattctgcc tgattttact 960 960

gaatctgaga aaaagttcat caaaggaact gctgactttt ttgctctttg ctttggaccc 1020 gaatctgaga aaaagttcat caaaggaact gctgactttt ttgctctttg ctttggacco 1020

accttgagtt ttcaactttt ggaccctcac atgaagttcc gccaattgga atctcccaac 1080 accttgagtt ttcaactttt ggaccctcac atgaagttcc gccaattgga atctcccaac 1080

ctgaggcaac tgctttcctg gattgacctt gaatttaacc atcctcaaat atttattgtg ctgaggcaac tgctttcctg gattgacctt gaatttaacc atcctcaaat atttattgtg 1140 1140

gaaaatggct ggtttgtctc agggaccacc aagagagatg atgccaaata tatgtattac gaaaatggct ggtttgtctc agggaccacc aagagagatg atgccaaata tatgtattac 1200 1200

ctcaaaaagt tcatcatgga aaccttaaaa gccatcaagc tggatggggt ggatgtcatc ctcaaaaagt tcatcatgga aaccttaaaa gccatcaagc tggatggggt ggatgtcatc 1260 1260

gggtataccg catggtccct catggatggt ttcgagtggc acagaggtta cagcatcagg 1320 gggtataccg catggtccct catggatggt ttcgagtggc acagaggtta cagcatcagg 1320

cgtggactct tctatgttga ctttctaago caggacaaga tgttgttgcc aaagtcttca cgtggactct tctatgttga ctttctaagc caggacaaga tgttgttgcc aaagtcttca 1380 1380

gccttgttct accaaaagct gatagagaaa aatggcttcc ctcctttacc tgaaaatcag gccttgttct accaaaagct gatagagaaa aatggcttcc ctcctttacc tgaaaatcag 1440 1440

cccctagaag ggacatttcc ctgtgacttt gcttggggag ttgttgacaa ctacattcaa cccctagaag ggacatttcc ctgtgacttt gcttggggag ttgttgacaa ctacattcaa 1500 1500

gtagatacca ctctgtctca gtttaccgac ctgaatgttt acctgtggga tgtccaccac 1560 gtagatacca ctctgtctca gtttaccgac ctgaatgttt acctgtggga tgtccaccao 1560

agtaaaaggc ttattaaagt ggatggggtt gtgaccaaga agaggaaatc ctactgtgtt agtaaaaggc ttattaaagt ggatggggtt gtgaccaaga agaggaaatc ctactgtgtt 1620 1620

gactttgctg ccatccagcc ccagatcgct ttactccagg aaatgcacgt tacacatttt gactttgctg ccatccagcc ccagatcgct ttactccagg aaatgcacgt tacacatttt 1680 1680

cgcttctccc tggactgggc cctgattctc cctctgggta accagtccca ggtgaaccac 1740 cgcttctccc tggactgggc cctgattctc cctctgggta accagtccca ggtgaaccad 1740

accatcctgc agtactatcg ctgcatggcc agcgagcttg tccgtgtcaa catcacccca 1800 accatcctgc agtactatcg ctgcatggcc agcgagcttg tccgtgtcaa catcacccca 1800

gtggtggccc tgtggcagcc tatggccccg aaccaaggac tgccgcgcct cctggccagg 1860 gtggtggccc tgtggcagcc tatggccccg aaccaaggac tgccgcgcct cctggccagg 1860

cagggcgcct gggagaaccc ctacactgcc ctggcctttg cagagtatgc ccgactgtgc 1920 cagggcgcct gggagaaccc ctacactgcc ctggcctttg cagagtatgo ccgactgtgc 1920

tttcaagagc tcggccatca cgtcaagctt tggataacga tgaatgagcc gtatacaagg 1980 tttcaagagc tcggccatca cgtcaagctt tggataacga tgaatgagcc gtatacaagg 1980

aatatgacat acagtgctgg ccacaacctt ctgaaggccc atgccctggc ttggcatgtg aatatgacat acagtgctgg ccacaacctt ctgaaggccc atgccctggc ttggcatgtg 2040 2040

tacaatgaaa agtttaggca tgctcagaat gggaaaatat ccatagcctt gcaggctgat tacaatgaaa agtttaggca tgctcagaat gggaaaatat ccatagcctt gcaggctgat 2100 2100

tggatagaac ctgcctgccc tttctcccaa aaggacaaag aggtggccga gagagttttg tggatagaac ctgcctgccc tttctcccaa aaggacaaag aggtggccga gagagttttg 2160 2160

gaatttgaca ttggctggct ggctgagccc attttcggct ctggagatta tccatgggtg gaatttgaca ttggctggct ggctgagccc attttcggct ctggagatta tccatgggtg 2220 2220

atgagggact ggctgaacca aagaaacaat tttcttcttc cttatttcac tgaagatgaa atgagggact ggctgaacca aagaaacaat tttcttcttc cttatttcac tgaagatgaa 2280 2280

Page 312 Page 312

20780‐15A_SequenceListing.TXT aaaaagctaa tccagggtac ctttgacttt ttggctttaa gccattatac caccatcctt 2340 OTEL

gtagactcag aaaaagaaga tccaataaaa tacaatgatt acctagaagt gcaagaaatg 2400

accgacatca cgtggctcaa ctcccccagt caggtggcgg tagtgccctg ggggttgcgc 2460

e aaagtgctga actggctgaa gttcaagtac ggagacctcc ccatgtacat aatatccaac 2520

the 0252

ggaatcgatg acgggctgca tgctgaggac gaccagctga gggtgtatta tatgcagaat 2580 0852

tacataaacg aagctctcaa agcccacata ctggatggta tcaatctttg cggatacttt 2640 797 gcttattcgt ttaacgaccg cacagctccg aggtttggcc tctatcgtta tgctgcagat 2700 00L2

cagtttgagc ccaaggcatc catgaaacat tacaggaaaa ttattgacag caatggtttc 2760 09/2

ccgggcccag aaactctgga aagattttgt ccagaagaat tcaccgtgtg tactgagtgc 2820 787777e8ee 0782

7078 277777778e agtttttttc acacccgaaa gtct 2844

<210> 80 <0TZ> 08 <211> 2838 <IIZ> 8882 <212> DNA <ZIZ> ANC <213> Homo sapiens <EIZ>

<400> 80 08 <00 ggcgacggcg cgcagacctg ggcccgtgtc tcgcggcctc ctgcccccga ggccgcgggc 60 09

ctcttccagg gcaccttccc cgacggcttc ctctgggccg tgggcagcgc cgcctaccag 120

accgagggcg gctggcagca gcacggcaag ggtgcgtcca tctgggacac gttcacccac 180 08T

caccccctgg cacccccggg agactcccgg aacgccagtc tgccgttggg cgccccgtcg 240

ccgctgcagc ccgccaccgg ggacgtagcc agcgacagct acaacaacgt cttccgcgac 300 00E

acggaggcgc tgcgcgagct cggggtcact cactaccgct tctccatctc gtgggcgcga 360 09E

gtgctcccca atggcagcgc gggcgtcccc aaccgcgagg ggctgcgcta ctaccggcgc 420

7 ctgctggagc ggctgcggga gctgggcgtg cagcccgtgg tcaccctgta ccactgggac 480 08/

ctgccccagc gcctgcagga cgcctacggc ggctgggcca accgcgccct ggccgaccac 540

ttcagggatt acgcggagct ctgcttccgc cacttcggcg gtcaggtcaa gtactggatc 600 009

accatcgaca acccctacgt ggtggcctgg cacggctacg ccaccgggcg cctggccccc 660 9970088188 099

ggcatccggg gcagcccgcg gctcgggtac ctggtggcgc acaacctcct cctggctcat 720 OZL

gccaaagtct ggcatctcta caatacttct ttccgtccca ctcagggagg tcaggtgtcc 780 08L Page 313 ETE aged

20780‐15A_SequenceListing.TXT

attgccctaa gctctcactg gatcaatcct cgaagaatga ccgaccacag catcaaagaa 840

tgtcaaaaat ctctggactt tgtactaggt tggtttgcca aacccgtatt tattgatggt 900 006

gactatcccg agagcatgaa gaataacctt tcatctattc tgcctgattt tactgaatct 960 096 9877708777 9708777777 gagaaaaagt tcatcaaagg aactgctgac ttttttgctc tttgctttgg acccaccttg 1020 0201

agttttcaac ttttggaccc tcacatgaag ttccgccaat tggaatctcc caacctgagg 1080 080I

caactgcttt cctggattga ccttgaattt aaccatcctc aaatatttat tgtggaaaat 1140

ggctggtttg tctcagggac caccaagaga gatgatgcca aatatatgta ttacctcaaa 1200

the aagttcatca tggaaacctt aaaagccatc aagctggatg gggtggatgt catcgggtat 1260 The accgcatggt ccctcatgga tggtttcgag tggcacagag gttacagcat caggcgtgga 1320 OZET

ctcttctatg ttgactttct aagccaggac aagatgttgt tgccaaagtc ttcagccttg 1380 08EI

ttctaccaaa agctgataga gaaaaatggc ttccctcctt tacctgaaaa tcagccccta 1440

the gaagggacat ttccctgtga ctttgcttgg ggagttgttg acaactacat tcaagtagat 1500 00ST

accactctgt ctcagtttac cgacctgaat gtttacctgt gggatgtcca ccacagtaaa 1560 09ST

aggcttatta aagtggatgg ggttgtgacc aagaagagga aatcctactg tgttgacttt 1620 The 2770807777 gctgccatcc agccccagat cgctttactc caggaaatgc acgttacaca ttttcgcttc 1680 089T

e tccctggact gggccctgat tctccctctg ggtaaccagt cccaggtgaa ccacaccatc 1740

ctgcagtact atcgctgcat ggccagcgag cttgtccgtg tcaacatcac cccagtggtg 1800 008T

gccctgtggc agcctatggc cccgaaccaa ggactgccgc gcctcctggc caggcagggc 1860 098T

gcctgggaga acccctacac tgccctggcc tttgcagagt atgcccgact gtgctttcaa 1920 0261

gagctcggcc atcacgtcaa gctttggata acgatgaatg agccgtatac aaggaatatg 1980 086T

the acatacagtg ctggccacaa ccttctgaag gcccatgccc tggcttggca tgtgtacaat 2040

gaaaagttta ggcatgctca gaatgggaaa atatccatag ccttgcaggc tgattggata 2100 0012

the gaacctgcct gccctttctc ccaaaaggac aaagaggtgg ccgagagagt tttggaattt 2160

gacattggct ggctggctga gcccattttc ggctctggag attatccatg ggtgatgagg 2220 0222

the gactggctga accaaagaaa caattttctt cttccttatt tcactgaaga tgaaaaaaag 2280 0822

eee ctaatccagg gtacctttga ctttttggct ttaagccatt ataccaccat ccttgtagac 2340 OTEL Page 314 DIE aged

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

tcagaaaaag aagatccaat aaaatacaat gattacctag aagtgcaaga aatgaccgac 2400 tcagaaaaag aagatccaat aaaatacaat gattacctag aagtgcaaga aatgaccgac 2400

atcacgtggc tcaactcccc cagtcaggtg gcggtagtgc cctgggggtt gcgcaaagtg 2460 atcacgtggc tcaactcccc cagtcaggtg gcggtagtgc cctgggggtt gcgcaaagtg 2460

ctgaactggc tgaagttcaa gtacggagac ctccccatgt acataatatc caacggaatc 2520 ctgaactggc tgaagttcaa gtacggagac ctccccatgt acataatatc caacggaatc 2520

gatgacgggc tgcatgctga ggacgaccag ctgagggtgt attatatgca gaattacata 2580 gatgacgggc tgcatgctga ggacgaccag ctgagggtgt attatatgca gaattacata 2580

aacgaagctc tcaaagccca catactggat ggtatcaatc tttgcggata ctttgcttat 2640 aacgaagctc tcaaagccca catactggat ggtatcaatc tttgcggata ctttgcttat 2640

tcgtttaacg accgcacagc tccgaggttt ggcctctatc gttatgctgc agatcagttt 2700 tcgtttaacg accgcacago tccgaggttt ggcctctatc gttatgctgc agatcagttt 2700

gagcccaagg catccatgaa acattacagg aaaattattg acagcaatgg tttcccgggc 2760 gagcccaagg catccatgaa acattacagg aaaattattg acagcaatgg tttcccgggc 2760

ccagaaactc tggaaagatt ttgtccagaa gaattcaccg tgtgtactga gtgcagtttt 2820 ccagaaactc tggaaagatt ttgtccagaa gaattcaccg tgtgtactga gtgcagtttt 2820

tttcacaccc gaaagtct 2838 tttcacaccc gaaagtct 2838

<210> 81 <210> 81 <211> 2553 <211> 2553 <212> DNA <212> DNA <213> Homo sapiens <213> Homo sapiens

<400> 81 <400> 81 aacgtcttcc gcgacacgga ggcgctgcgc gagctcgggg tcactcacta ccgcttctcc 60 aacgtcttcc gcgacacgga ggcgctgcgc gagctcgggg tcactcacta ccgcttctcc 60

atctcgtggg cgcgagtgct ccccaatggc agcgcgggcg tccccaaccg cgaggggctg 120 atctcgtggg cgcgagtgct ccccaatggc agcgcgggcg tccccaaccg cgaggggctg 120

cgctactacc ggcgcctgct ggagcggctg cgggagctgg gcgtgcagcc cgtggtcacc 180 cgctactacc ggcgcctgct ggagcggctg cgggagctgg gcgtgcagcc cgtggtcacc 180

ctgtaccact gggacctgcc ccagcgcctg caggacgcct acggcggctg ggccaaccgc 240 ctgtaccact gggacctgcc ccagcgcctg caggacgcct acggcggctg ggccaaccgc 240

gccctggccg accacttcag ggattacgcg gagctctgct tccgccactt cggcggtcag 300 gccctggccg accacttcag ggattacgcg gagctctgct tccgccactt cggcggtcag 300

gtcaagtact ggatcaccat cgacaacccc tacgtggtgg cctggcacgg ctacgccacc 360 gtcaagtact ggatcaccat cgacaacccc tacgtggtgg cctggcacgg ctacgccacc 360

gggcgcctgg cccccggcat ccggggcagc ccgcggctcg ggtacctggt ggcgcacaac 420 gggcgcctgg cccccggcat ccggggcagc ccgcggctcg ggtacctggt ggcgcacaac 420

ctcctcctgg ctcatgccaa agtctggcat ctctacaata cttctttccg tcccactcag 480 ctcctcctgg ctcatgccaa agtctggcat ctctacaata cttctttccg tcccactcag 480

ggaggtcagg tgtccattgc cctaagctct cactggatca atcctcgaag aatgaccgac 540 ggaggtcagg tgtccattgc cctaagctct cactggatca atcctcgaag aatgaccgac 540

cacagcatca aagaatgtca aaaatctctg gactttgtac taggttggtt tgccaaaccc 600 cacagcatca aagaatgtca aaaatctctg gactttgtac taggttggtt tgccaaaccc 600

gtatttattg atggtgacta tcccgagagc atgaagaata acctttcatc tattctgcct 660 gtatttattg atggtgacta tcccgagagc atgaagaata acctttcatc tattctgcct 660

gattttactg aatctgagaa aaagttcatc aaaggaactg ctgacttttt tgctctttgc 720 gattttactg aatctgagaa aaagttcatc aaaggaactg ctgacttttt tgctctttgc 720

tttggaccca ccttgagttt tcaacttttg gaccctcaca tgaagttccg ccaattggaa 780 tttggaccca ccttgagttt tcaacttttg gaccctcaca tgaagttccg ccaattggaa 780

Page 315 Page 315

20780‐15A_SequenceListing.TXT tctcccaacc tgaggcaact gctttcctgg attgaccttg aatttaacca tcctcaaata 840

1189 tttattgtgg aaaatggctg gtttgtctca gggaccacca agagagatga tgccaaatat 900 006

the the e atgtattacc tcaaaaagtt catcatggaa accttaaaag ccatcaagct ggatggggtg 960 096

gatgtcatcg ggtataccgc atggtccctc atggatggtt tcgagtggca cagaggttac 1020

agcatcaggc gtggactctt ctatgttgac tttctaagcc aggacaagat gttgttgcca 1080 080I

aagtcttcag ccttgttcta ccaaaagctg atagagaaaa atggcttccc tcctttacct 1140

gaaaatcagc ccctagaagg gacatttccc tgtgactttg cttggggagt tgttgacaac 1200

the tacattcaag tagataccac tctgtctcag tttaccgacc tgaatgttta cctgtgggat 1260 0921

gtccaccaca gtaaaaggct tattaaagtg gatggggttg tgaccaagaa gaggaaatcc 1320 OZET

tactgtgttg actttgctgc catccagccc cagatcgctt tactccagga aatgcacgtt 1380 08ET

acacattttc gcttctccct ggactgggcc ctgattctcc ctctgggtaa ccagtcccag 1440

gtgaaccaca ccatcctgca gtactatcgc tgcatggcca gcgagcttgt ccgtgtcaac 1500 00ST

atcaccccag tggtggccct gtggcagcct atggccccga accaaggact gccgcgcctc 1560 09ST

ctggccaggc agggcgcctg ggagaacccc tacactgccc tggcctttgc agagtatgcc 1620 029T

e cgactgtgct ttcaagagct cggccatcac gtcaagcttt ggataacgat gaatgagccg 1680 089T

tatacaagga atatgacata cagtgctggc cacaaccttc tgaaggccca tgccctggct 1740

tggcatgtgt acaatgaaaa gtttaggcat gctcagaatg ggaaaatatc catagccttg 1800 008T

caggctgatt ggatagaacc tgcctgccct ttctcccaaa aggacaaaga ggtggccgag 1860 098T

agagttttgg aatttgacat tggctggctg gctgagccca ttttcggctc tggagattat 1920 026T

the e ccatgggtga tgagggactg gctgaaccaa agaaacaatt ttcttcttcc ttatttcact 1980 086T

gaagatgaaa aaaagctaat ccagggtacc tttgactttt tggctttaag ccattatacc 2040 9702

accatccttg tagactcaga aaaagaagat ccaataaaat acaatgatta cctagaagtg 2100 0012

caagaaatga ccgacatcac gtggctcaac tcccccagtc aggtggcggt agtgccctgg 2160 0912

gggttgcgca aagtgctgaa ctggctgaag ttcaagtacg gagacctccc catgtacata 2220 0222

atatccaacg gaatcgatga cgggctgcat gctgaggacg accagctgag ggtgtattat 2280 0822

the atgcagaatt acataaacga agctctcaaa gcccacatac tggatggtat caatctttgc 2340 OTEL

Page 316 9TE aged

e

20780‐15A_SequenceListing.TXT ggatactttg cttattcgtt taacgaccgc acagctccga ggtttggcct ctatcgttat 2400

gctgcagatc agtttgagcc caaggcatcc atgaaacatt acaggaaaat tattgacagc 2460

aatggtttcc cgggcccaga aactctggaa agattttgtc cagaagaatt caccgtgtgt 2520 0252

actgagtgca gtttttttca cacccgaaag tct 2553 707 ESSE

<210> 82 <0IZ> 28 <211> 1648 <IIZ> <212> DNA <ZIZ> ANC <213> Homo sapiens <ETZ>

<400> 82 28 <00 atgcccgcca gcgccccgcc gcgccgcccg cggccgccgc cgccgtcgct gtcgctgctg 60 09

ctggtgctgc tgggcctggg cggccgccgc ctgcgtgcgg agccgggcga cggcgcgcag 120 OZI

acctgggccc gtgtctcgcg gcctcctgcc cccgaggccg cgggcctctt ccagggcacc 180 08T

ttccccgacg gcttcctctg ggccgtgggc agcgccgcct accagaccga gggcggctgg 240

cagcagcacg gcaagggtgc gtccatctgg gacacgttca cccaccaccc cctggcaccc 300 00E

ccgggagact cccggaacgc cagtctgccg ttgggcgccc cgtcgccgct gcagcccgcc 360 09E

accggggacg tagccagcga cagctacaac aacgtcttcc gcgacacgga ggcgctgcgc 420

7 gagctcgggg tcactcacta ccgcttctcc atctcgtggg cgcgagtgct ccccaatggc 480 08/

agcgcgggcg tccccaaccg cgaggggctg cgctactacc ggcgcctgct ggagcggctg 540

cgggagctgg gcgtgcagcc cgtggtcacc ctgtaccact gggacctgcc ccagcgcctg 600 009

caggacgcct acggcggctg ggccaaccgc gccctggccg accacttcag ggattacgcg 660 099

gagctctgct tccgccactt cggcggtcag gtcaagtact ggatcaccat cgacaacccc 720 OZL

tacgtggtgg cctggcacgg ctacgccacc gggcgcctgg cccccggcat ccggggcagc 780 08L

ccgcggctcg ggtacctggt ggcgcacaac ctcctcctgg ctcatgccaa agtctggcat 840 778

ctctacaata cttctttccg tcccactcag ggaggtcagg tgtccattgc cctaagctct 900 006

cactggatca atcctcgaag aatgaccgac cacagcatca aagaatgtca aaaatctctg 960 096

the gactttgtac taggttggtt tgccaaaccc gtatttattg atggtgacta tcccgagagc 1020 0201

atgaagaata acctttcatc tattctgcct gattttactg aatctgagaa aaagttcatc 1080 080I the the aaaggaactg ctgacttttt tgctctttgc tttggaccca ccttgagttt tcaacttttg 1140 Page 317 LTE

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

gaccctcaca tgaagttccg ccaattggaa tctcccaacc tgaggcaact gctttcctgg 1200 gaccctcaca tgaagttccg ccaattggaa tctcccaacc tgaggcaact gctttcctgg 1200

attgaccttg aatttaacca tcctcaaata tttattgtgg aaaatggctg gtttgtctca 1260 attgaccttg aatttaacca tcctcaaata tttattgtgg aaaatggctg gtttgtctca 1260

gggaccacca agagagatga tgccaaatat atgtattacc tcaaaaagtt catcatggaa 1320 gggaccacca agagagatga tgccaaatat atgtattacc tcaaaaagtt catcatggaa 1320

accttaaaag ccatcaagct ggatggggtg gatgtcatcg ggtataccgc atggtccctc 1380 accttaaaag ccatcaagct ggatggggtg gatgtcatcg ggtataccgc atggtccctc 1380

atggatggtt tcgagtggca cagaggttac agcatcaggc gtggactctt ctatgttgac 1440 atggatggtt tcgagtggca cagaggttac agcatcaggc gtggactctt ctatgttgac 1440

tttctaagcc aggacaagat gttgttgcca aagtcttcag ccttgttcta ccaaaagctg 1500 tttctaagcc aggacaagat gttgttgcca aagtcttcag ccttgttcta ccaaaagctg 1500

atagagaaaa atggcttccc tcctttacct gaaaatcagc ccctagaagg gacatttccc 1560 atagagaaaa atggcttccc tcctttacct gaaaatcagc ccctagaagg gacatttccc 1560

tgtgactttg cttggggagt tgttgacaac tacattcaag tagataccac tctgtctcag 1620 tgtgactttg cttggggagt tgttgacaac tacattcaag tagataccac tctgtctcag 1620

tttaccgacc tgaatgttta cctgtggg 1648 tttaccgacc tgaatgttta cctgtggg 1648

<210> 83 <210> 83 <211> 1564 <211> 1564 <212> DNA <212> DNA <213> Homo sapiens <213> Homo sapiens

<400> 83 <400> 83 cgccgcctgc gtgcggagcc gggcgacggc gcgcagacct gggcccgtgt ctcgcggcct 60 cgccgcctgc gtgcggagcc gggcgacggc gcgcagacct gggcccgtgt ctcgcggcct 60

cctgcccccg aggccgcggg cctcttccag ggcaccttcc ccgacggctt cctctgggcc 120 cctgcccccg aggccgcggg cctcttccag ggcaccttcc ccgacggctt cctctgggcc 120

gtgggcagcg ccgcctacca gaccgagggc ggctggcagc agcacggcaa gggtgcgtcc 180 gtgggcagcg ccgcctacca gaccgagggc ggctggcagc agcacggcaa gggtgcgtcc 180

atctgggaca cgttcaccca ccaccccctg gcacccccgg gagactcccg gaacgccagt 240 atctgggaca cgttcaccca ccaccccctg gcacccccgg gagactcccg gaacgccagt 240

ctgccgttgg gcgccccgtc gccgctgcag cccgccaccg gggacgtagc cagcgacagc 300 ctgccgttgg gcgccccgtc gccgctgcag cccgccaccg gggacgtagc cagcgacagc 300

tacaacaacg tcttccgcga cacggaggcg ctgcgcgagc tcggggtcac tcactaccgc 360 tacaacaacg tcttccgcga cacggaggcg ctgcgcgagc tcggggtcac tcactaccgc 360

ttctccatct cgtgggcgcg agtgctcccc aatggcagcg cgggcgtccc caaccgcgag 420 ttctccatct cgtgggcgcg agtgctcccc aatggcagcg cgggcgtccc caaccgcgag 420

gggctgcgct actaccggcg cctgctggag cggctgcggg agctgggcgt gcagcccgtg 480 gggctgcgct actaccggcg cctgctggag cggctgcggg agctgggcgt gcagcccgtg 480

gtcaccctgt accactggga cctgccccag cgcctgcagg acgcctacgg cggctgggcc 540 gtcaccctgt accactggga cctgccccag cgcctgcagg acgcctacgg cggctgggcc 540

aaccgcgccc tggccgacca cttcagggat tacgcggagc tctgcttccg ccacttcggc 600 aaccgcgccc tggccgacca cttcagggat tacgcggagc tctgcttccg ccacttcggc 600

ggtcaggtca agtactggat caccatcgac aacccctacg tggtggcctg gcacggctac 660 ggtcaggtca agtactggat caccatogac aacccctacg tggtggcctg gcacggctac 660

gccaccgggc gcctggcccc cggcatccgg ggcagcccgc ggctcgggta cctggtggcg 720 gccaccgggc gcctggcccc cggcatccgg ggcagcccgc ggctcgggta cctggtggcg 720

cacaacctcc tcctggctca tgccaaagtc tggcatctct acaatacttc tttccgtccc 780 cacaacctcc tcctggctca tgccaaagtc tggcatctct acaatacttc tttccgtccc 780

Page 318 Page 318

20780‐15A_SequenceListing.TXT actcagggag gtcaggtgtc cattgcccta agctctcact ggatcaatcc tcgaagaatg 840

1108 accgaccaca gcatcaaaga atgtcaaaaa tctctggact ttgtactagg ttggtttgcc 900 0087778877 006

aaacccgtat ttattgatgg tgactatccc gagagcatga agaataacct ttcatctatt 960 096

ctgcctgatt ttactgaatc tgagaaaaag ttcatcaaag gaactgctga cttttttgct 1020 0201

ctttgctttg gacccacctt gagttttcaa cttttggacc ctcacatgaa gttccgccaa 1080 9777087770 080I

ttggaatctc ccaacctgag gcaactgctt tcctggattg accttgaatt taaccatcct 1140

caaatattta ttgtggaaaa tggctggttt gtctcaggga ccaccaagag agatgatgcc 1200

aaatatatgt attacctcaa aaagttcatc atggaaacct taaaagccat caagctggat 1260 0921

the ggggtggatg tcatcgggta taccgcatgg tccctcatgg atggtttcga gtggcacaga 1320 OZET

ggttacagca tcaggcgtgg actcttctat gttgactttc taagccagga caagatgttg 1380 08ET

ttgccaaagt cttcagcctt gttctaccaa aagctgatag agaaaaatgg cttccctcct 1440

ttacctgaaa atcagcccct agaagggaca tttccctgtg actttgcttg gggagttgtt 1500 00ST

gacaactaca ttcaagtaga taccactctg tctcagttta ccgacctgaa tgtttacctg 1560 09ST

tggg 1564 9997

<210> 84 <0IZ> 98 <211> 1549 <IIZ> <212> DNA <<IZ> ANC <213> Homo sapiens <ETZ>

<400> 84 <00 98 gagccgggcg acggcgcgca gacctgggcc cgtgtctcgc ggcctcctgc ccccgaggcc 60 09

gcgggcctct tccagggcac cttccccgac ggcttcctct gggccgtggg cagcgccgcc 120

taccagaccg agggcggctg gcagcagcac ggcaagggtg cgtccatctg ggacacgttc 180 08T

acccaccacc ccctggcacc cccgggagac tcccggaacg ccagtctgcc gttgggcgcc 240

ccgtcgccgc tgcagcccgc caccggggac gtagccagcg acagctacaa caacgtcttc 300 00E

cgcgacacgg aggcgctgcg cgagctcggg gtcactcact accgcttctc catctcgtgg 360 09E

e gcgcgagtgc tccccaatgg cagcgcgggc gtccccaacc gcgaggggct gcgctactac 420

Page 319 6TE aged 7 cggcgcctgc tggagcggct gcgggagctg ggcgtgcagc ccgtggtcac cctgtaccac 480 08/7

tgggacctgc cccagcgcct gcaggacgcc tacggcggct gggccaaccg cgccctggcc 540

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

gaccacttca gggattacgc ggagctctgc ttccgccact tcggcggtca ggtcaagtac 600 gaccacttca gggattacgc ggagctctgc ttccgccact tcggcggtca ggtcaagtac 600

tggatcacca tcgacaaccc ctacgtggtg gcctggcacg gctacgccac cgggcgcctg 660 tggatcacca tcgacaaccc ctacgtggtg gcctggcacg gctacgccac cgggcgcctg 660

gcccccggca tccggggcag cccgcggctc gggtacctgg tggcgcacaa cctcctcctg 720 gccccccggca tccggggcag cccgcggctc gggtacctgg tggcgcacaa cctcctcctg 720

gctcatgcca aagtctggca tctctacaat acttctttcc gtcccactca gggaggtcag 780 gctcatgcca aagtctggca tctctacaat acttctttcc gtcccactca gggaggtcag 780

gtgtccattg ccctaagctc tcactggatc aatcctcgaa gaatgaccga ccacagcatc 840 gtgtccattg ccctaagctc tcactggatc aatcctcgaa gaatgaccga ccacagcato 840

aaagaatgtc aaaaatctct ggactttgta ctaggttggt ttgccaaacc cgtatttatt 900 aaagaatgtc aaaaatctct ggactttgta ctaggttggt ttgccaaacc cgtatttatt 900

gatggtgact atcccgagag catgaagaat aacctttcat ctattctgcc tgattttact 960 gatggtgact atcccgagag catgaagaat aacctttcat ctattctgcc tgattttact 960

gaatctgaga aaaagttcat caaaggaact gctgactttt ttgctctttg ctttggaccc 1020 gaatctgaga aaaagttcat caaaggaact gctgactttt ttgctctttg ctttggaccc 1020

accttgagtt ttcaactttt ggaccctcac atgaagttcc gccaattgga atctcccaac 1080 accttgagtt ttcaactttt ggaccctcac atgaagttcc gccaattgga atctcccaac 1080

ctgaggcaac tgctttcctg gattgacctt gaatttaacc atcctcaaat atttattgtg 1140 ctgaggcaac tgctttcctg gattgacctt gaatttaacc atcctcaaat atttattgtg 1140

gaaaatggct ggtttgtctc agggaccacc aagagagatg atgccaaata tatgtattac 1200 gaaaatggct ggtttgtctc agggaccaco aagagagatg atgccaaata tatgtattac 1200

ctcaaaaagt tcatcatgga aaccttaaaa gccatcaagc tggatggggt ggatgtcatc 1260 ctcaaaaagt tcatcatgga aaccttaaaa gccatcaagc tggatggggt ggatgtcatc 1260

gggtataccg catggtccct catggatggt ttcgagtggc acagaggtta cagcatcagg 1320 gggtataccg catggtccct catggatggt ttcgagtggc acagaggtta cagcatcagg 1320

cgtggactct tctatgttga ctttctaagc caggacaaga tgttgttgcc aaagtcttca 1380 cgtggactct tctatgttga ctttctaagc caggacaaga tgttgttgcc aaagtcttca 1380

gccttgttct accaaaagct gatagagaaa aatggcttcc ctcctttacc tgaaaatcag 1440 gccttgttct accaaaagct gatagagaaa aatggcttcc ctcctttacc tgaaaatcag 1440

cccctagaag ggacatttcc ctgtgacttt gcttggggag ttgttgacaa ctacattcaa 1500 cccctagaag ggacatttcc ctgtgacttt gcttggggag ttgttgacaa ctacattcaa 1500

gtagatacca ctctgtctca gtttaccgac ctgaatgttt acctgtggg 1549 gtagatacca ctctgtctca gtttaccgac ctgaatgttt acctgtggg 1549

<210> 85 <210> 85 <211> 1543 <211> 1543 <212> DNA <212> DNA <213> Homo sapiens <213> Homo sapiens

<400> 85 <400> 85 ggcgacggcg cgcagacctg ggcccgtgtc tcgcggcctc ctgcccccga ggccgcgggc 60 ggcgacggcg cgcagacctg ggcccgtgtc tcgcggcctc ctgcccccga ggccgcgggc 60

ctcttccagg gcaccttccc cgacggcttc ctctgggccg tgggcagcgc cgcctaccag 120 ctcttccagg gcaccttccc cgacggcttc ctctgggccg tgggcagcgc cgcctaccag 120

accgagggcg gctggcagca gcacggcaag ggtgcgtcca tctgggacac gttcacccac 180 accgagggcg gctggcagca gcacggcaag ggtgcgtcca tctgggacac gttcacccac 180

caccccctgg cacccccggg agactcccgg aacgccagtc tgccgttggg cgccccgtcg 240 caccccctgg cacccccggg agactcccgg aacgccagtc tgccgttggg cgccccgtcg 240

ccgctgcagc ccgccaccgg ggacgtagcc agcgacagct acaacaacgt cttccgcgac 300 ccgctgcagc ccgccaccgg ggacgtagcc agcgacagct acaacaacgt cttccgcgac 300

Page 320 Page 320

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT acggaggcgc tgcgcgagct cggggtcact cactaccgct tctccatctc gtgggcgcga 360 acggaggcgc tgcgcgagct cggggtcact cactaccgct tctccatctc gtgggcgcga 360

gtgctcccca atggcagcgc gggcgtcccc aaccgcgagg ggctgcgcta ctaccggcgc 420 gtgctcccca atggcagcgc gggcgtcccc aaccgcgagg ggctgcgcta ctaccggcgc 420

ctgctggagc ggctgcggga gctgggcgtg cagcccgtgg tcaccctgta ccactgggac 480 ctgctggagc ggctgcggga gctgggcgtg cagcccgtgg tcaccctgta ccactgggad 480

ctgccccagc gcctgcagga cgcctacggc ggctgggcca accgcgccct ggccgaccac 540 ctgccccagc gcctgcagga cgcctacggo ggctgggcca accgcgccct ggccgaccao 540

ttcagggatt acgcggagct ctgcttccgc cacttcggcg gtcaggtcaa gtactggatc 600 ttcagggatt acgcggagct ctgcttccgc cacttcggcg gtcaggtcaa gtactggatc 600

accatcgaca acccctacgt ggtggcctgg cacggctacg ccaccgggcg cctggccccc 660 accatcgaca acccctacgt ggtggcctgg cacggctacg ccaccgggcg cctggccccc 660

ggcatccggg gcagcccgcg gctcgggtac ctggtggcgc acaacctcct cctggctcat 720 ggcatccggg gcagcccgcg gctcgggtac ctggtggcgc acaacctcct cctggctcat 720

gccaaagtct ggcatctcta caatacttct ttccgtccca ctcagggagg tcaggtgtcc 780 gccaaaattct ggcatctcta caatacttct ttccgtccca ctcagggagg tcaggtgtcc 780

attgccctaa gctctcactg gatcaatcct cgaagaatga ccgaccacag catcaaagaa 840 attgccctaa gctctcactg gatcaatcct cgaagaatga ccgaccacag catcaaagaa 840

tgtcaaaaat ctctggactt tgtactaggt tggtttgcca aacccgtatt tattgatggt 900 tgtcaaaaat ctctggactt tgtactaggt tggtttgcca aacccgtatt tattgatggt 900

gactatcccg agagcatgaa gaataacctt tcatctattc tgcctgattt tactgaatct 960 gactatcccg agagcatgaa gaataacctt tcatctatto tgcctgattt tactgaatct 960

gagaaaaagt tcatcaaagg aactgctgac ttttttgctc tttgctttgg acccaccttg 1020 gagaaaaagt tcatcaaagg aactgctgac ttttttgctc tttgctttgg acccaccttg 1020

agttttcaac ttttggaccc tcacatgaag ttccgccaat tggaatctcc caacctgagg 1080 agttttcaac ttttggaccc tcacatgaag ttccgccaat tggaatctcc caacctgagg 1080

caactgcttt cctggattga ccttgaattt aaccatcctc aaatatttat tgtggaaaat 1140 caactgcttt cctggattga ccttgaattt aaccatcctc aaatatttat tgtggaaaat 1140

ggctggtttg tctcagggac caccaagaga gatgatgcca aatatatgta ttacctcaaa 1200 ggctggtttg tctcagggad caccaagaga gatgatgcca aatatatgta ttacctcaaa 1200

aagttcatca tggaaacctt aaaagccatc aagctggatg gggtggatgt catcgggtat 1260 aagttcatca tggaaacctt aaaagccatc aagctggatg gggtggatgt catcgggtat 1260

accgcatggt ccctcatgga tggtttcgag tggcacagag gttacagcat caggcgtgga 1320 accgcatggt ccctcatgga tggtttcgag tggcacagag gttacagcat caggcgtgga 1320

ctcttctatg ttgactttct aagccaggac aagatgttgt tgccaaagtc ttcagccttg 1380 ctcttctatg ttgactttct aagccaggac aagatgttgt tgccaaagtc ttcagccttg 1380

ttctaccaaa agctgataga gaaaaatggc ttccctcctt tacctgaaaa tcagccccta 1440 ttctaccaaa agctgataga gaaaaatggc ttccctcctt tacctgaaaa tcagccccta 1440

gaagggacat ttccctgtga ctttgcttgg ggagttgttg acaactacat tcaagtagat 1500 gaagggacat ttccctgtga ctttgcttgg ggagttgttg acaactacat tcaagtagat 1500

accactctgt ctcagtttac cgacctgaat gtttacctgt ggg 1543 accactctgt ctcagtttac cgacctgaat gtttacctgt ggg 1543

<210> 86 <210> 86 <211> 1258 <211> 1258 <212> DNA <212> DNA <213> Homo sapiens <213> Homo sapiens

<400> 86 <400> 86 aacgtcttcc gcgacacgga ggcgctgcgc gagctcgggg tcactcacta ccgcttctcc 60 aacgtcttcc gcgacacgga ggcgctgcgc gagctcgggg tcactcacta ccgcttctcc 60

atctcgtggg cgcgagtgct ccccaatggc agcgcgggcg tccccaaccg cgaggggctg 120 atctcgtggg cgcgagtgct ccccaatggc agcgcgggcg tccccaaccg cgaggggctg 120 Page 321 Page 321

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing.7 TXT

cgctactacc ggcgcctgct ggagcggctg cgggagctgg gcgtgcagcc cgtggtcacc 180 cgctactacc ggcgcctgct ggagcggctg cgggagctgg gcgtgcagcc cgtggtcacc 180

ctgtaccact gggacctgcc ccagcgcctg caggacgcct acggcggctg ggccaaccgc 240 ctgtaccact gggacctgcc ccagcgcctg caggacgcct acggcggctg ggccaaccgc 240

gccctggccg accacttcag ggattacgcg gagctctgct tccgccactt cggcggtcag 300 gccctggccg accacttcag ggattacgcg gagctctgct tccgccactt cggcggtcag 300

gtcaagtact ggatcaccat cgacaacccc tacgtggtgg cctggcacgg ctacgccacc 360 gtcaagtact ggatcaccat cgacaacccc tacgtggtgg cctggcacgg ctacgccacc 360

gggcgcctgg cccccggcat ccggggcagc ccgcggctcg ggtacctggt ggcgcacaac 420 gggcgcctgg cccccggcat ccggggcago ccgcggctcg ggtacctggt ggcgcacaac 420

ctcctcctgg ctcatgccaa agtctggcat ctctacaata cttctttccg tcccactcag 480 ctcctcctgg ctcatgccaa agtctggcat ctctacaata cttctttccg tcccactcag 480

ggaggtcagg tgtccattgc cctaagctct cactggatca atcctcgaag aatgaccgac 540 ggaggtcagg tgtccattgo cctaagctct cactggatca atcctcgaag aatgaccgac 540

cacagcatca aagaatgtca aaaatctctg gactttgtac taggttggtt tgccaaaccc 600 cacagcatca aagaatgtca aaaatctctg gactttgtac taggttggtt tgccaaaccc 600

gtatttattg atggtgacta tcccgagagc atgaagaata acctttcatc tattctgcct 660 gtatttattg atggtgacta tcccgagagc atgaagaata acctttcatc tattctgcct 660

gattttactg aatctgagaa aaagttcatc aaaggaactg ctgacttttt tgctctttgc 720 gattttactg aatctgagaa aaagttcatc aaaggaactg ctgacttttt tgctctttgc 720

tttggaccca ccttgagttt tcaacttttg gaccctcaca tgaagttccg ccaattggaa 780 tttggaccca ccttgagttt tcaacttttg gaccctcaca tgaagttccg ccaattggaa 780

tctcccaacc tgaggcaact gctttcctgg attgaccttg aatttaacca tcctcaaata 840 tctcccaacc tgaggcaact gctttcctgg attgaccttg aatttaacca tcctcaaata 840

tttattgtgg aaaatggctg gtttgtctca gggaccacca agagagatga tgccaaatat 900 tttattgtgg aaaatggctg gtttgtctca gggaccacca agagagatga tgccaaatat 900

atgtattacc tcaaaaagtt catcatggaa accttaaaag ccatcaagct ggatggggtg 960 atgtattacc tcaaaaagtt catcatggaa accttaaaag ccatcaagct ggatggggtg 960

gatgtcatcg ggtataccgc atggtccctc atggatggtt tcgagtggca cagaggttac 1020 gatgtcatcg ggtataccgc atggtccctc atggatggtt tcgagtggca cagaggttad 1020

agcatcaggc gtggactctt ctatgttgac tttctaagcc aggacaagat gttgttgcca 1080 agcatcaggc gtggactctt ctatgttgac tttctaagcc aggacaagat gttgttgcca 1080

aagtcttcag ccttgttcta ccaaaagctg atagagaaaa atggcttccc tcctttacct 1140 aagtcttcag ccttgttcta ccaaaagctg atagagaaaa atggcttccc tcctttacct 1140

gaaaatcagc ccctagaagg gacatttccc tgtgactttg cttggggagt tgttgacaac 1200 gaaaatcagc ccctagaagg gacatttccc tgtgactttg cttggggagt tgttgacaac 1200

tacattcaag tagataccac tctgtctcag tttaccgacc tgaatgttta cctgtggg 1258 tacattcaag tagataccao tctgtctcag tttaccgaco tgaatgttta cctgtggg 1258

<210> 87 <210> 87 <211> 3654 <211> 3654 <212> DNA <212> DNA <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> DNA_Native_SS_34_981_GS_IgG1_noCH1_Fc_Fusion <223> DNA_Native_SS_34_981_GS_IgG1_noCH1_Fc_Fusion

<400> 87 <400> 87 atgcctgctt ccgccccgcc tagaaggcct cggcctcctc cccccagcct gtctctgctc 60 atgcctgctt ccgccccgcc tagaaggcct cggcctcctc cccccagcct gtctctgctc 60

ttggtgctgc tgggactggg tggacggcgc cttcgcgcag agcctggcga cggcgcccag 120 ttggtgctgc tgggactggg tggacggcgc cttcgcgcag agcctggcga cggcgcccag 120 Page 322 Page 322

20780‐15A_SequenceListing.TXT

acctgggccc gggtgtcgag gccgccagcg cccgaggccg ccggactgtt ccagggaacc 180 08T

ttccctgatg ggttcctctg ggccgtgggc tcagccgcat accagaccga ggggggctgg 240

cagcagcacg gaaagggcgc cagcatatgg gacacgttca cccaccaccc gctggctccg 300 00E

cccggggact ccagaaacgc ctccttgccc ctcggtgctc cttcgccact gcaacccgca 360 09E

accggcgacg tggccagcga ttcatacaac aacgtgttcc gggacaccga ggccctgagg 420 0077878000

7 gaactgggag tgactcacta ccgcttttcg atctcctggg cacgcgtgct cccgaacgga 480 08/

tcggcgggag tgccgaatcg cgagggcctg cggtactacc gacggctgct ggaaaggctc 540 STS 9999 agagaactgg gcgtgcagcc tgtcgtgact ctttaccact gggatctgcc ccaacggctg 600 009

caggatgctt acgggggatg ggccaataga gccctggctg atcacttccg cgactacgcc 660 099

gaattgtgct tccggcactt cggtggccaa gtcaagtact ggattaccat cgacaaccca 720 OZL

tacgtcgtgg cgtggcacgg atacgcaacc ggtcggctgg cccctggtat tcgcgggtcc 780 08L

ccgcggcttg gatacctggt ggcccacaac ctgttgctcg cgcatgccaa agtctggcac 840

ctgtacaaca cctcgttccg gccgacccag ggtggacaag tgtccatcgc cctgtcgtca 900 006

cactggatca acccgcggag aatgaccgac cactccatca aggaatgcca gaagtccctc 960 096

gatttcgtgt tgggctggtt tgccaagcct gtgtttattg acggagacta ccccgagtcc 1020 020T

atgaagaaca acctgtcgtc tatcctgccc gatttcactg aatccgagaa aaagtttatc 1080 080T

aagggaaccg ctgacttctt cgccctctgt ttcggcccga ccttgtcctt ccaactgctc 1140

gatcctcata tgaagttccg gcagctggaa tcccctaacc ttcgccagct gctgtcctgg 1200

atcgacttgg aattcaacca cccgcagatc ttcattgtcg agaacggctg gttcgtgtcc 1260 097T

gggaccacca agcgcgacga cgccaagtac atgtattatc tcaaaaagtt catcatggaa 1320 OZET

e accctcaagg ccatcaaatt ggatggcgtg gacgtgatcg gatatacggc gtggagcctg 1380 08ET

atggacggtt tcgagtggca ccgcggatac agcatccgca gaggactctt ctacgtggac 1440

ttcctgtcgc aagacaagat gctgctgcct aagagcagcg cgctgttcta ccaaaagctc 1500 00ST

attgagaaga acgggttccc gcccctgccg gagaaccagc ctctggaagg gaccttccct 1560 09ST

tgcgacttcg cctggggagt ggtggacaac tacatccagg tcgataccac tctgagccag 1620 029T

ttcaccgacc tgaacgtgta cctgtgggac gtgcatcaca gcaagaggct cattaaggtc 1680 089T

Page 323 EZE aged

20780‐15A_SequenceListing.TXT

gacggagtgg tcaccaagaa gagaaagtcg tactgcgtgg atttcgccgc aatccagcca 1740

1148 cagatcgccc tgctgcaaga gatgcacgtg acccatttcc gcttctccct ggattgggcc 1800 008T

ctgattctcc cgctggggaa ccagtcgcaa gtgaaccaca ctatcctgca atactaccgg 1860 098T

tgcatggctt ccgagctcgt ccgcgtgaat atcacccccg tggtggcgct ctggcagcct 1920 026T

atggccccga accagggact gccacgactg ctggccagac agggagcgtg ggaaaacccg 1980 086T

tacacagcac tggcctttgc ggagtacgcc cggctgtgct tccaggaact tgggcatcac 2040 9702

I gtcaagcttt ggattactat gaacgaaccc tacactagga acatgactta ctcagccgga 2100 0012

cataaccttc tgaaggcaca cgccctcgct tggcacgtgt acaacgaaaa gttcagacac 2160 09T2

gctcagaacg gaaagatttc catcgcgctg caagcagact ggatcgagcc cgcctgccct 2220 0222

ttctcccaaa aagacaagga agtggccgaa cgggtgctgg aattcgacat cggatggctg 2280 0877

gccgaaccca tcttcggctc cggcgattat ccatgggtca tgcgggactg gctcaaccag 2340 OTEC

e cgcaacaact ttttgctgcc atacttcacc gaagatgaga agaagctgat ccagggcacc 2400

tttgatttcc tggcgctgag ccactacact acgattctgg tggacagcga aaaggaggac 2460

the ccgattaagt acaacgacta cctggaagtc caggaaatga ccgatattac ttggctgaac 2520 0252

tcacctagcc aagtggcggt ggtgccttgg ggactgagaa aggtcctcaa ctggctcaaa 2580 0852

ttcaaatacg gagatctgcc catgtacatc atctccaatg ggatcgacga cggcctgcat 2640

gctgaggacg atcagctccg cgtgtactat atgcagaact acattaacga ggcactgaag 2700 00L2

gcccatattc tggacggcat taacctctgc ggttattttg cctactcgtt caacgaccgg 2760 09/2

e actgcccccc gcttcgggtt gtaccgctac gccgcggatc agtttgagcc aaaggcctcc 2820 0782

atgaagcatt accgcaagat cattgattcc aatggatttc cgggccccga aaccctcgaa 2880 0887

cggttctgtc cggaagagtt caccgtgtgt accgagtgct ccttctttca cacccgcaag 2940 9767

agcgggggtg gcggaagcgg tggcggagga agcgacaaaa ctcacacatg cccaccgtgc 3000 000E

ccagcacctg aactcctggg gggaccgtca gtcttcctct tccccccaaa acccaaggac 3060 090E

accctcatga tctcccggac ccctgaggtc acatgcgtgg tggtggacgt gagccacgaa 3120 OTTE

gaccctgagg tcaagttcaa ctggtacgtg gacggcgtgg aggtgcataa tgccaagaca 3180 08IE

aagccgcggg aggagcagta caacagcacg taccgggtgg tcagcgtcct caccgtcctg 3240 Page 324 aged

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

caccaggact ggctgaatgg caaggagtac aagtgcaagg tcagcaacaa agccctccca 3300 caccaggact ggctgaatgg caaggagtac aagtgcaagg tcagcaacaa agccctccca 3300

gcccccatcg agaaaaccat ctccaaagcc aaagggcagc cccgagaacc acaggtgtac 3360 gcccccatcg agaaaaccat ctccaaagcc aaagggcagc cccgagaacc acaggtgtac 3360

accctgcccc catcccggga tgagctgacc aagaaccagg tcagcctgac ctgcctggtc 3420 accctgcccc catcccggga tgagctgacc aagaaccagg tcagcctgac ctgcctggtc 3420

aaaggcttct atcccagcga catcgccgtg gagtgggaga gcaatgggca gccggagaac 3480 aaaggcttct atcccagcga catcgccgtg gagtgggaga gcaatgggca gccggagaac 3480

aactacaaga ccacgcctcc cgtgctggac tccgacggct ccttcttcct ctacagcaag 3540 aactacaaga ccacgcctcc cgtgctggac tccgacggct ccttcttcct ctacagcaag 3540

ctcaccgtgg acaagagcag gtggcagcag gggaacgtct tctcatgctc cgtgatgcat 3600 ctcaccgtgg acaagagcag gtggcagcag gggaacgtct tctcatgctc cgtgatgcat 3600

gaggctctgc acaaccacta cacgcagaag tccctctccc tgtctccggg taaa 3654 gaggctctgc acaaccacta cacgcagaag tccctctccc tgtctccggg taaa 3654

<210> 88 <210> 88 <211> 2358 <211> 2358 <212> DNA <212> DNA <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> DNA_Native_Secreted_Iso2_SS_34_549_GS_IgG1_noCH1_Fc_Fusion <223> DNA_Native_Secreted_Iso2_SS_34_549_GS_IgG1_noCH1_Fc_Fusion

<400> 88 <400> 88 atgccagctt ccgccccccc tcggcggcct agacccccac ctccctccct gtcgctgctg 60 atgccagctt ccgccccccc tcggcggcct agacccccac ctccctccct gtcgctgctg 60

ctggtgctgc tcggtctggg cggacggaga ctcagggccg agcctggcga cggcgcacag 120 ctggtgctgc tcggtctggg cggacggaga ctcagggccg agcctggcga cggcgcacag 120

acctgggccc ggttctcacg ccccccggcc ccggaagccg ccggactgtt tcagggaacc 180 acctgggccc ggttctcacg ccccccggcc ccggaagccg ccggactgtt tcagggaacc 180

ttccccgacg gattcctgtg ggccgtgggt agcgcggcgt accagactga gggcggatgg 240 ttccccgacg gattcctgtg ggccgtgggt agcgcggcgt accagactga gggcggatgg 240

cagcagcacg gaaagggagc ctcaatttgg gatactttca ctcatcatcc cctcgccccg 300 cagcagcacg gaaagggage ctcaatttgg gatactttca ctcatcatcc cctcgccccg 300

ccgggggatt cgcggaacgc ctccctcccc ctgggtgctc ctagcccgct gcagccagcc 360 ccgggggatt cgcggaacgc ctccctcccc ctgggtgctc ctagcccgct gcagccagcc 360

accggcgacg tggcatccga cagctacaac aacgtgttcc gggacaccga ggccctgagg 420 accggcgacg tggcatccga cagctacaac aacgtgttcc gggacaccga ggccctgagg 420

gaactgggag tgactcacta ccgcttttcg atctcctggg cacgcgtgct cccgaacgga 480 gaactgggag tgactcacta ccgcttttcg atctcctggg cacgcgtgct cccgaacgga 480

tcggcgggag tgccgaatcg cgagggcctg cggtactacc gacggctgct ggaaaggctc 540 tcggcgggag tgccgaatcg cgagggcctg cggtactacc gacggctgct ggaaaggctc 540

agagaactgg gcgtgcagcc tgtcgtgact ctttaccact gggatctgcc ccaacggctg 600 agagaactgg gcgtgcagcc tgtcgtgact ctttaccact gggatctgcc ccaacggctg 600

caggatgctt acgggggatg ggccaataga gccctggctg atcacttccg cgactacgcc 660 caggatgctt acgggggatg ggccaataga gccctggctg atcacttccg cgactacgcc 660

gaattgtgct tccggcactt cggtggccaa gtcaagtact ggattaccat cgacaaccca 720 gaattgtgct tccggcactt cggtggccaa gtcaagtact ggattaccat cgacaaccca 720

tacgtcgtgg cgtggcacgg atacgcaacc ggtcggctgg cccctggtat tcgcgggtcc 780 tacgtcgtgg cgtggcacgg atacgcaacc ggtcggctgg cccctggtat tcgcgggtcc 780

ccgcggcttg gatacctggt ggcccacaac ctgttgctcg cgcatgccaa agtctggcac 840 ccgcggcttg gatacctggt ggcccacaac ctgttgctcg cgcatgccaa agtctggcac 840

Page 325 Page 325

20780‐15A_SequenceListing.TXT

ctgtacaaca cctcgttccg gccgacccag ggtggacaag tgtccatcgc cctgtcgtca 900 006

118 cactggatca acccgcggag aatgaccgac cactccatca aggaatgcca gaagtccctc 960

9778777878 096

gatttcgtgt tgggctggtt tgccaagcct gtgtttattg acggagacta ccccgagtcc 1020 0201

atgaagaaca acctgtcgtc tatcctgccc gatttcactg aatccgagaa aaagtttatc 1080 080T

aagggaaccg ctgacttctt cgccctctgt ttcggcccga ccttgtcctt ccaactgctc 1140

gatcctcata tgaagttccg gcagctggaa tcccctaacc ttcgccagct gctgtcctgg 1200

atcgacttgg aattcaacca cccgcagatc ttcattgtcg agaacggctg gttcgtgtcc 1260

gggaccacca agcgcgacga cgccaagtac atgtattatc tcaaaaagtt catcatggaa 1320 OZET

e accctcaagg ccatcaaatt ggatggcgtg gacgtgatcg gatatacggc gtggagcctg 1380 08ET

atggacggtt tcgagtggca ccgcggatac agcatccgca gaggactctt ctacgtggac 1440

ttcctgtcgc aagacaagat gctgctgcct aagagcagcg cgctgttcta ccaaaagctc 1500 00ST

attgagaaga acgggttccc gcccctgccg gagaaccagc ctctggaagg gaccttccct 1560 09ST

tgcgacttcg cctggggagt ggtcgacaac tacattcaag tgtcccagct tactaagcca 1620 029D

e atcagcagcc tgactaagcc ataccacggc gggggagggt cgggcggagg cggatccgac 1680 089T

aaaactcaca catgcccacc gtgcccagca cctgaactcc tggggggacc gtcagtcttc 1740

ctcttccccc caaaacccaa ggacaccctc atgatctccc ggacccctga ggtcacatgc 1800 008T

gtggtggtgg acgtgagcca cgaagaccct gaggtcaagt tcaactggta cgtggacggc 1860 098T

the 9978878878 gtggaggtgc ataatgccaa gacaaagccg cgggaggagc agtacaacag cacgtaccgg 1920 026T

gtggtcagcg tcctcaccgt cctgcaccag gactggctga atggcaagga gtacaagtgc 1980 086T

aaggtcagca acaaagccct cccagccccc atcgagaaaa ccatctccaa agccaaaggg 2040

cagccccgag aaccacaggt gtacaccctg cccccatccc gggatgagct gaccaagaac 2100 00I2 been caggtcagcc tgacctgcct ggtcaaaggc ttctatccca gcgacatcgc cgtggagtgg 2160 09T2

gagagcaatg ggcagccgga gaacaactac aagaccacgc ctcccgtgct ggactccgac 2220 0222

ggctccttct tcctctacag caagctcacc gtggacaaga gcaggtggca gcaggggaac 2280 0822

gtcttctcat gctccgtgat gcatgaggct ctgcacaacc actacacgca gaagtccctc 2340 OTEC

e tccctgtctc cgggtaaa 2358 Page 326 978 aged

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing TXT

<210> 89 <210> 89 <211> 99 <211> 99 <212> DNA <212> DNA <213> Homo sapiens <213> Homo sapiens

<400> 89 <400> 89 atgcctgctt ccgccccgcc tagaaggcct cggcctcctc cccccagcct gtctctgctc 60 atgcctgctt ccgccccgcc tagaaggcct cggcctcctc cccccagcct gtctctgctc 60

ttggtgctgc tgggactggg tggacggcgc cttcgcgca 99 ttggtgctgc tgggactggg tggacggcgc cttcgcgca 99

<210> 90 <210> 90 <211> 99 <211> 99 <212> DNA <212> DNA <213> Homo sapiens <213> Homo sapiens

<400> 90 <400> 90 atgccagctt ccgccccccc tcggcggcct agacccccac ctccctccct gtcgctgctg 60 atgccagctt ccgccccccc tcggcggcct agacccccac ctccctccct gtcgctgctg 60

ctggtgctgc tcggtctggg cggacggaga ctcagggcc 99 ctggtgctgc tcggtctggg cggacggaga ctcagggcc 99

<210> 91 <210> 91 <211> 2844 <211> 2844 <212> DNA <212> DNA <213> Homo sapiens <213> Homo sapiens

<400> 91 <400> 91 gagcctggcg acggcgccca gacctgggcc cgggtgtcga ggccgccagc gcccgaggcc 60 gagcctggcg acggcgccca gacctgggcc cgggtgtcga ggccgccagc gcccgaggcc 60

gccggactgt tccagggaac cttccctgat gggttcctct gggccgtggg ctcagccgca 120 gccggactgt tccagggaac cttccctgat gggttcctct gggccgtggg ctcagccgca 120

taccagaccg aggggggctg gcagcagcac ggaaagggcg ccagcatatg ggacacgttc 180 taccagaccg aggggggctg gcagcagcaa ggaaagggcg ccagcatatg ggacacgttc 180

acccaccacc cgctggctcc gcccggggac tccagaaacg cctccttgcc cctcggtgct 240 acccaccacc cgctggctcc gcccggggac tccagaaacg cctccttgcc cctcggtgct 240

ccttcgccac tgcaacccgc aaccggcgac gtggccagcg attcatacaa caacgtgttc 300 ccttcgcccac tgcaacccgc aaccggcgac gtggccagcg attcatacaa caacgtgttc 300

cgggacaccg aggccctgag ggaactggga gtgactcact accgcttttc gatctcctgg 360 cgggacaccg aggccctgag ggaactggga gtgactcact accgcttttc gatctcctgg 360

gcacgcgtgc tcccgaacgg atcggcggga gtgccgaatc gcgagggcct gcggtactac 420 gcacgcgtgc tcccgaacgg atcggcggga gtgccgaatc gcgagggcct gcggtactad 420

cgacggctgc tggaaaggct cagagaactg ggcgtgcagc ctgtcgtgac tctttaccac 480 cgacggctgc tggaaaggct cagagaactg ggcgtgcagc ctgtcgtgac tctttaccac 480

tgggatctgc cccaaccggct gcaggatgct tacgggggat gggccaatag agccctggct tgggatctgc cccaacggct gcaggatgct tacgggggat gggccaatag agccctggct 540 540

gatcacttcc gcgactacgc cgaattgtgc ttccggcact tcggtggcca agtcaagtac 600 gatcacttcc gcgactacgc cgaattgtgc ttccggcact tcggtggcca agtcaagtac 600

tggattacca tcgacaaccc atacgtcgtg gcgtggcacg gatacgcaac cggtcggctg 660 tggattacca tcgacaaccc atacgtcgtg gcgtggcacg gatacgcaac cggtcggctg 660

Page 327 Page 327

20780‐15A_SequenceListing.TXT gcccctggta ttcgcgggtc cccgcggctt ggatacctgg tggcccacaa cctgttgctc 720

1X14s80 07L

gcgcatgcca aagtctggca cctgtacaac acctcgttcc ggccgaccca gggtggacaa 780 08L

gtgtccatcg ccctgtcgtc acactggatc aacccgcgga gaatgaccga ccactccatc 840

eee aaggaatgcc agaagtccct cgatttcgtg ttgggctggt ttgccaagcc tgtgtttatt 900 7787778787 006

gacggagact accccgagtc catgaagaac aacctgtcgt ctatcctgcc cgatttcact 960 096

gaatccgaga aaaagtttat caagggaacc gctgacttct tcgccctctg tttcggcccg 1020

accttgtcct tccaactgct cgatcctcat atgaagttcc ggcagctgga atcccctaac 1080 080T

cttcgccagc tgctgtcctg gatcgacttg gaattcaacc acccgcagat cttcattgtc 1140

gagaacggct ggttcgtgtc cgggaccacc aagcgcgacg acgccaagta catgtattat 1200 0021

ctcaaaaagt tcatcatgga aaccctcaag gccatcaaat tggatggcgt ggacgtgatc 1260 092T

ggatatacgg cgtggagcct gatggacggt ttcgagtggc accgcggata cagcatccgc 1320 OZET

agaggactct tctacgtgga cttcctgtcg caagacaaga tgctgctgcc taagagcagc 1380 08ET

gcgctgttct accaaaagct cattgagaag aacgggttcc cgcccctgcc ggagaaccag 1440

cctctggaag ggaccttccc ttgcgacttc gcctggggag tggtggacaa ctacatccag 1500 00ST

gtcgatacca ctctgagcca gttcaccgac ctgaacgtgt acctgtggga cgtgcatcac 1560 09ST

agcaagaggc tcattaaggt cgacggagtg gtcaccaaga agagaaagtc gtactgcgtg 1620 029T

e e gatttcgccg caatccagcc acagatcgcc ctgctgcaag agatgcacgt gacccatttc 1680 089T

cgcttctccc tggattgggc cctgattctc ccgctgggga accagtcgca agtgaaccac 1740

actatcctgc aatactaccg gtgcatggct tccgagctcg tccgcgtgaa tatcaccccc 1800 008T

e gtggtggcgc tctggcagcc tatggccccg aaccagggac tgccacgact gctggccaga 1860

ee 0878708800 098T

cagggagcgt gggaaaaccc gtacacagca ctggcctttg cggagtacgc ccggctgtgc 1920 026T

ttccaggaac ttgggcatca cgtcaagctt tggattacta tgaacgaacc ctacactagg 1980 086T

aacatgactt actcagccgg acataacctt ctgaaggcac acgccctcgc ttggcacgtg 2040

tacaacgaaa agttcagaca cgctcagaac ggaaagattt ccatcgcgct gcaagcagac 2100 0012

been tggatcgagc ccgcctgccc tttctcccaa aaagacaagg aagtggccga acgggtgctg 2160 0912

gaattcgaca tcggatggct ggccgaaccc atcttcggct ccggcgatta tccatgggtc 2220 0222

Page 328 878 aged

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT atgcgggact ggctcaacca gcgcaacaac tttttgctgc catacttcac cgaagatgag 2280 atgcgggact ggctcaacca gcgcaacaac tttttgctgc catacttcac cgaagatgag 2280

aagaagctga tccagggcac ctttgatttc ctggcgctga gccactacac tacgattctg 2340 aagaagctga tccagggcac ctttgatttc ctggcgctga gccactacac tacgattctg 2340

gtggacagcg aaaaggagga cccgattaag tacaacgact acctggaagt ccaggaaatg 2400 gtggacagcg aaaaggagga cccgattaag tacaacgact acctggaagt ccaggaaatg 2400

accgatatta cttggctgaa ctcacctagc caagtggcgg tggtgccttg gggactgaga 2460 accgatatta cttggctgaa ctcacctago caagtggcgg tggtgccttg gggactgaga 2460

aaggtcctca actggctcaa attcaaatac ggagatctgc ccatgtacat catctccaat 2520 aaggtcctca actggctcaa attcaaatac ggagatctgc ccatgtacat catctccaat 2520

gggatcgacg acggcctgca tgctgaggac gatcagctcc gcgtgtacta tatgcagaac 2580 gggatcgacg acggcctgca tgctgaggac gatcagctcc gcgtgtacta tatgcagaac 2580

tacattaacg aggcactgaa ggcccatatt ctggacggca ttaacctctg cggttatttt 2640 tacattaacg aggcactgaa ggcccatatt ctggacggca ttaacctctg cggttatttt 2640

gcctactcgt tcaacgaccg gactgccccc cgcttcgggt tgtaccgcta cgccgcggat 2700 gcctactcgt tcaacgaccg gactgccccc cgcttcgggt tgtaccgcta cgccgcggat 2700

cagtttgagc caaaggcctc catgaagcat taccgcaaga tcattgattc caatggattt 2760 cagtttgagc caaaggcctc catgaagcat taccgcaaga tcattgattc caatggattt 2760

ccgggccccg aaaccctcga acggttctgt ccggaagagt tcaccgtgtg taccgagtgc 2820 ccgggccccg aaaccctcga acggttctgt ccggaagagt tcaccgtgtg taccgagtgc 2820

tccttctttc acacccgcaa gagc 2844 tccttctttc acacccgcaa gagc 2844

<210> 92 <210> 92 <211> 1548 <211> 1548 <212> DNA <212> DNA <213> Homo sapiens <213> Homo sapiens

<400> 92 <400> 92 gagcctggcg acggcgcaca gacctgggcc cggttctcac gccccccggc cccggaagcc 60 gagcctggcg acggcgcaca gacctgggcc cggttctcac gccccccggc cccggaagcc 60

gccggactgt ttcagggaac cttccccgac ggattcctgt gggccgtggg tagcgcggcg 120 gccggactgt ttcagggaac cttccccgac ggattcctgt gggccgtggg tagcgcggcg 120

taccagactg agggcggatg gcagcagcac ggaaagggag cctcaatttg ggatactttc 180 taccagactg agggcggatg gcagcagcad ggaaagggag cctcaatttg ggatactttc 180

actcatcatc ccctcgcccc gccgggggat tcgcggaacg cctccctccc cctgggtgct 240 actcatcatc ccctcgcccc gccgggggat tcgcggaacg cctccctccc cctgggtgct 240

cctagcccgc tgcagccagc caccggcgac gtggcatccg acagctacaa caacgtgttc 300 cctagcccgc tgcagccagc caccggcgac gtggcatccg acagctacaa caacgtgttc 300

cgggacaccg aggccctgag ggaactggga gtgactcact accgcttttc gatctcctgg 360 cgggacaccg aggccctgag ggaactggga gtgactcact accgcttttc gatctcctgg 360

gcacgcgtgc tcccgaacgg atcggcggga gtgccgaatc gcgagggcct gcggtactac 420 gcacgcgtgc tcccgaacgg atcggcggga gtgccgaatc gcgagggcct gcggtactac 420

cgacggctgc tggaaaggct cagagaactg ggcgtgcagc ctgtcgtgac tctttaccac 480 cgacggctgc tggaaaggct cagagaactg ggcgtgcagc ctgtcgtgac tctttaccac 480

tgggatctgc cccaacggct gcaggatgct tacgggggat gggccaatag agccctggct 540 tgggatctgc cccaaccggct gcaggatgct tacgggggat gggccaatag agccctggct 540

gatcacttcc gcgactacgc cgaattgtgc ttccggcact tcggtggcca agtcaagtac 600 gatcacttcc gcgactacgc cgaattgtgc ttccggcact tcggtggcca agtcaagtac 600

tggattacca tcgacaaccc atacgtcgtg gcgtggcacg gatacgcaac cggtcggctg 660 tggattacca tcgacaaccc atacgtcgtg gcgtggcacg gatacgcaac cggtcggctg 660

gcccctggta ttcgcgggtc cccgcggctt ggatacctgg tggcccacaa cctgttgctc 720 gcccctggta ttcgcgggtc cccgcggctt ggatacctgg tggcccacaa cctgttgctc 720 Page 329 Page 329

20780‐15A_SequenceListing.TXT

gcgcatgcca aagtctggca cctgtacaac acctcgttcc ggccgaccca gggtggacaa 780 08/

gtgtccatcg ccctgtcgtc acactggatc aacccgcgga gaatgaccga ccactccatc 840

aaggaatgcc agaagtccct cgatttcgtg ttgggctggt ttgccaagcc tgtgtttatt 900 7787778787 006

gacggagact accccgagtc catgaagaac aacctgtcgt ctatcctgcc cgatttcact 960 096

gaatccgaga aaaagtttat caagggaacc gctgacttct tcgccctctg tttcggcccg 1020 0201

accttgtcct tccaactgct cgatcctcat atgaagttcc ggcagctgga atcccctaac 1080 080I

cttcgccagc tgctgtcctg gatcgacttg gaattcaacc acccgcagat cttcattgtc 1140

gagaacggct ggttcgtgtc cgggaccacc aagcgcgacg acgccaagta catgtattat 1200

ctcaaaaagt tcatcatgga aaccctcaag gccatcaaat tggatggcgt ggacgtgatc 1260 The ggatatacgg cgtggagcct gatggacggt ttcgagtggc accgcggata cagcatccgc 1320 OZET

agaggactct tctacgtgga cttcctgtcg caagacaaga tgctgctgcc taagagcagc 1380 08EI

gcgctgttct accaaaagct cattgagaag aacgggttcc cgcccctgcc ggagaaccag 1440 DATE

cctctggaag ggaccttccc ttgcgacttc gcctggggag tggtcgacaa ctacattcaa 1500 00ST

gtgtcccagc ttactaagcc aatcagcagc ctgactaagc cataccac 1548 STATE

<210> 93 <0IZ> E6 <211> 2838 <IIZ> 8882 <212> DNA <ZIZ> AND <213> Homo sapiens <EIZ> OWOH subides

<400> 93 E6 <00 ggcgacggcg cccagacctg ggcccgggtg tcgaggccgc cagcgcccga ggccgccgga 60 09

ctgttccagg gaaccttccc tgatgggttc ctctgggccg tgggctcagc cgcataccag 120 OZI

accgaggggg gctggcagca gcacggaaag ggcgccagca tatgggacac gttcacccac 180 08T

cacccgctgg ctccgcccgg ggactccaga aacgcctcct tgcccctcgg tgctccttcg 240

ccactgcaac ccgcaaccgg cgacgtggcc agcgattcat acaacaacgt gttccgggac 300 00E

accgaggccc tgagggaact gggagtgact cactaccgct tttcgatctc ctgggcacgc 360 09E

gtgctcccga acggatcggc gggagtgccg aatcgcgagg gcctgcggta ctaccgacgg 420

7 ctgctggaaa ggctcagaga actgggcgtg cagcctgtcg tgactcttta ccactgggat 480 08/

Page 330 0EE

20780‐15A_SequenceListing.TXT ctgccccaac ggctgcagga tgcttacggg ggatgggcca atagagccct ggctgatcac 540

1148 ttccgcgact acgccgaatt gtgcttccgg cacttcggtg gccaagtcaa gtactggatt 600 009

accatcgaca acccatacgt cgtggcgtgg cacggatacg caaccggtcg gctggcccct 660 099

ggtattcgcg ggtccccgcg gcttggatac ctggtggccc acaacctgtt gctcgcgcat 720 02L

gccaaagtct ggcacctgta caacacctcg ttccggccga cccagggtgg acaagtgtcc 780 08L

atcgccctgt cgtcacactg gatcaacccg cggagaatga ccgaccactc catcaaggaa 840

tgccagaagt ccctcgattt cgtgttgggc tggtttgcca agcctgtgtt tattgacgga 900 006

gactaccccg agtccatgaa gaacaacctg tcgtctatcc tgcccgattt cactgaatcc 960 096

gagaaaaagt ttatcaaggg aaccgctgac ttcttcgccc tctgtttcgg cccgaccttg 1020

tccttccaac tgctcgatcc tcatatgaag ttccggcagc tggaatcccc taaccttcgc 1080 080T

cagctgctgt cctggatcga cttggaattc aaccacccgc agatcttcat tgtcgagaac 1140

ggctggttcg tgtccgggac caccaagcgc gacgacgcca agtacatgta ttatctcaaa 1200

the aagttcatca tggaaaccct caaggccatc aaattggatg gcgtggacgt gatcggatat 1260 092T

acggcgtgga gcctgatgga cggtttcgag tggcaccgcg gatacagcat ccgcagagga 1320 OZET

ctcttctacg tggacttcct gtcgcaagac aagatgctgc tgcctaagag cagcgcgctg 1380 08ET

ttctaccaaa agctcattga gaagaacggg ttcccgcccc tgccggagaa ccagcctctg 1440

gaagggacct tcccttgcga cttcgcctgg ggagtggtgg acaactacat ccaggtcgat 1500 00ST

accactctga gccagttcac cgacctgaac gtgtacctgt gggacgtgca tcacagcaag 1560 09ST

aggctcatta aggtcgacgg agtggtcacc aagaagagaa agtcgtactg cgtggatttc 1620 The gccgcaatcc agccacagat cgccctgctg caagagatgc acgtgaccca tttccgcttc 1680 089T

tccctggatt gggccctgat tctcccgctg gggaaccagt cgcaagtgaa ccacactatc 1740 DATE

ctgcaatact accggtgcat ggcttccgag ctcgtccgcg tgaatatcac ccccgtggtg 1800 9799780000 008T

gcgctctggc agcctatggc cccgaaccag ggactgccac gactgctggc cagacaggga 1860 098T

gcgtgggaaa acccgtacac agcactggcc tttgcggagt acgcccggct gtgcttccag 1920 026T

e gaacttgggc atcacgtcaa gctttggatt actatgaacg aaccctacac taggaacatg 1980 086T

acttactcag ccggacataa ccttctgaag gcacacgccc tcgcttggca cgtgtacaac 2040

Page 331 IEE aged

20780‐15A_SequenceListing.TXT gaaaagttca gacacgctca gaacggaaag atttccatcg cgctgcaagc agactggatc 2100 0012

the gagcccgcct gccctttctc ccaaaaagac aaggaagtgg ccgaacgggt gctggaattc 2160

gacatcggat ggctggccga acccatcttc ggctccggcg attatccatg ggtcatgcgg 2220 0222

gactggctca accagcgcaa caactttttg ctgccatact tcaccgaaga tgagaagaag 2280 0822

ctgatccagg gcacctttga tttcctggcg ctgagccact acactacgat tctggtggac 2340 OTEL

agcgaaaagg aggacccgat taagtacaac gactacctgg aagtccagga aatgaccgat 2400

the attacttggc tgaactcacc tagccaagtg gcggtggtgc cttggggact gagaaaggtc 2460

ctcaactggc tcaaattcaa atacggagat ctgcccatgt acatcatctc caatgggatc 2520 0252

the gacgacggcc tgcatgctga ggacgatcag ctccgcgtgt actatatgca gaactacatt 2580 0852

aacgaggcac tgaaggccca tattctggac ggcattaacc tctgcggtta ttttgcctac 2640

tcgttcaacg accggactgc cccccgcttc gggttgtacc gctacgccgc ggatcagttt 2700 00L2

gagccaaagg cctccatgaa gcattaccgc aagatcattg attccaatgg atttccgggc 2760 09/2

the cccgaaaccc tcgaacggtt ctgtccggaa gagttcaccg tgtgtaccga gtgctccttc 2820 0282

tttcacaccc gcaagagc 2838 8882

<210> 94 <0IZ> 16 <211> 1542 <IIZ> COST <212> DNA <ZIZ> ANC <213> Homo sapiens <ETZ>

<400> 94 <00 16 ggcgacggcg cacagacctg ggcccggttc tcacgccccc cggccccgga agccgccgga 60 09

ctgtttcagg gaaccttccc cgacggattc ctgtgggccg tgggtagcgc ggcgtaccag 120 OZI

actgagggcg gatggcagca gcacggaaag ggagcctcaa tttgggatac tttcactcat 180 08T

catcccctcg ccccgccggg ggattcgcgg aacgcctccc tccccctggg tgctcctagc 240

ccgctgcagc cagccaccgg cgacgtggca tccgacagct acaacaacgt gttccgggac 300 00E

accgaggccc tgagggaact gggagtgact cactaccgct tttcgatctc ctgggcacgc 360 09E

gtgctcccga acggatcggc gggagtgccg aatcgcgagg gcctgcggta ctaccgacgg 420

the 7 ctgctggaaa ggctcagaga actgggcgtg cagcctgtcg tgactcttta ccactgggat 480 08/

ctgccccaac ggctgcagga tgcttacggg ggatgggcca atagagccct ggctgatcac 540 Page 332 ZEE aged

20780‐15A_SequenceListing.TXT

ttccgcgact acgccgaatt gtgcttccgg cacttcggtg gccaagtcaa gtactggatt 600 009

accatcgaca acccatacgt cgtggcgtgg cacggatacg caaccggtcg gctggcccct 660 099

ggtattcgcg ggtccccgcg gcttggatac ctggtggccc acaacctgtt gctcgcgcat 720 OZL

gccaaagtct ggcacctgta caacacctcg ttccggccga cccagggtgg acaagtgtcc 780 08L

atcgccctgt cgtcacactg gatcaacccg cggagaatga ccgaccactc catcaaggaa 840

tgccagaagt ccctcgattt cgtgttgggc tggtttgcca agcctgtgtt tattgacgga 900 006

gactaccccg agtccatgaa gaacaacctg tcgtctatcc tgcccgattt cactgaatcc 960 096

gagaaaaagt ttatcaaggg aaccgctgac ttcttcgccc tctgtttcgg cccgaccttg 1020 020T

tccttccaac tgctcgatcc tcatatgaag ttccggcagc tggaatcccc taaccttcgc 1080 080I

cagctgctgt cctggatcga cttggaattc aaccacccgc agatcttcat tgtcgagaac 1140

ggctggttcg tgtccgggac caccaagcgc gacgacgcca agtacatgta ttatctcaaa 1200

aagttcatca tggaaaccct caaggccatc aaattggatg gcgtggacgt gatcggatat 1260 The acggcgtgga gcctgatgga cggtttcgag tggcaccgcg gatacagcat ccgcagagga 1320 OZET

ctcttctacg tggacttcct gtcgcaagac aagatgctgc tgcctaagag cagcgcgctg 1380 08ET

ttctaccaaa agctcattga gaagaacggg ttcccgcccc tgccggagaa ccagcctctg 1440

gaagggacct tcccttgcga cttcgcctgg ggagtggtcg acaactacat tcaagtgtcc 1500 00ST

cagcttacta agccaatcag cagcctgact aagccatacc ac 1542 be COST

<210> 95 S6 <0IZ> <211> 2553 <IIZ> ESSE <212> DNA <ZIZ> ANC <213> Homo sapiens <ETZ>

<400> 95 S6 <00 aacgtgttcc gggacaccga ggccctgagg gaactgggag tgactcacta ccgcttttcg 60 09

atctcctggg cacgcgtgct cccgaacgga tcggcgggag tgccgaatcg cgagggcctg 120 OZI

cggtactacc gacggctgct ggaaaggctc agagaactgg gcgtgcagcc tgtcgtgact 180 08T

ctttaccact gggatctgcc ccaacggctg caggatgctt acgggggatg ggccaataga 240

gccctggctg atcacttccg cgactacgcc gaattgtgct tccggcactt cggtggccaa 300 00E

Page 333 EEE

20780‐15A_SequenceListing.TXT gtcaagtact ggattaccat cgacaaccca tacgtcgtgg cgtggcacgg atacgcaacc 360 09E

887088788 1X180 ggtcggctgg cccctggtat tcgcgggtcc ccgcggcttg gatacctggt ggcccacaac 420

ctgttgctcg cgcatgccaa agtctggcac ctgtacaaca cctcgttccg gccgacccag 480 08/

ggtggacaag tgtccatcgc cctgtcgtca cactggatca acccgcggag aatgaccgac 540

cactccatca aggaatgcca gaagtccctc gatttcgtgt tgggctggtt tgccaagcct 600 009

gtgtttattg acggagacta ccccgagtcc atgaagaaca acctgtcgtc tatcctgccc 660 099

gatttcactg aatccgagaa aaagtttatc aagggaaccg ctgacttctt cgccctctgt 720 07L

ttcggcccga ccttgtcctt ccaactgctc gatcctcata tgaagttccg gcagctggaa 780 08L

tcccctaacc ttcgccagct gctgtcctgg atcgacttgg aattcaacca cccgcagatc 840 798

ttcattgtcg agaacggctg gttcgtgtcc gggaccacca agcgcgacga cgccaagtac 900 006

e e atgtattatc tcaaaaagtt catcatggaa accctcaagg ccatcaaatt ggatggcgtg 960 096

gacgtgatcg gatatacggc gtggagcctg atggacggtt tcgagtggca ccgcggatac 1020 0201

agcatccgca gaggactctt ctacgtggac ttcctgtcgc aagacaagat gctgctgcct 1080 080T

aagagcagcg cgctgttcta ccaaaagctc attgagaaga acgggttccc gcccctgccg 1140

gagaaccagc ctctggaagg gaccttccct tgcgacttcg cctggggagt ggtggacaac 1200

e tacatccagg tcgataccac tctgagccag ttcaccgacc tgaacgtgta cctgtgggac 1260 092T

gtgcatcaca gcaagaggct cattaaggtc gacggagtgg tcaccaagaa gagaaagtcg 1320 OZET

tactgcgtgg atttcgccgc aatccagcca cagatcgccc tgctgcaaga gatgcacgtg 1380 08ET

acccatttcc gcttctccct ggattgggcc ctgattctcc cgctggggaa ccagtcgcaa 1440

gtgaaccaca ctatcctgca atactaccgg tgcatggctt ccgagctcgt ccgcgtgaat 1500 00ST

atcacccccg tggtggcgct ctggcagcct atggccccga accagggact gccacgactg 1560 09ST

ctggccagac agggagcgtg ggaaaacccg tacacagcac tggcctttgc ggagtacgcc 1620 029T

cggctgtgct tccaggaact tgggcatcac gtcaagcttt ggattactat gaacgaaccc 1680 089T

tacactagga acatgactta ctcagccgga cataaccttc tgaaggcaca cgccctcgct 1740

tggcacgtgt acaacgaaaa gttcagacac gctcagaacg gaaagatttc catcgcgctg 1800 008T been

e caagcagact ggatcgagcc cgcctgccct ttctcccaaa aagacaagga agtggccgaa 1860

Page 334 DEE aged 098T

e

20780‐15A_SequenceListing.TXT cgggtgctgg aattcgacat cggatggctg gccgaaccca tcttcggctc cggcgattat 1920

118080 026T

ccatgggtca tgcgggactg gctcaaccag cgcaacaact ttttgctgcc atacttcacc 1980 086T

gaagatgaga agaagctgat ccagggcacc tttgatttcc tggcgctgag ccactacact 2040

acgattctgg tggacagcga aaaggaggac ccgattaagt acaacgacta cctggaagtc 2100 00I2

caggaaatga ccgatattac ttggctgaac tcacctagcc aagtggcggt ggtgccttgg 2160 0912

ggactgagaa aggtcctcaa ctggctcaaa ttcaaatacg gagatctgcc catgtacatc 2220 0222

atctccaatg ggatcgacga cggcctgcat gctgaggacg atcagctccg cgtgtactat 2280 0822

atgcagaact acattaacga ggcactgaag gcccatattc tggacggcat taacctctgc 2340 OTEC

ggttattttg cctactcgtt caacgaccgg actgcccccc gcttcgggtt gtaccgctac 2400

gccgcggatc agtttgagcc aaaggcctcc atgaagcatt accgcaagat cattgattcc 2460

aatggatttc cgggccccga aaccctcgaa cggttctgtc cggaagagtt caccgtgtgt 2520 0252

accgagtgct ccttctttca cacccgcaag agc 2553 age ESSE

<210> 96 96 <0IZ> <211> 1257 <IIZ> <212> DNA <ZIZ> <ETZ> ANC e <213> Homo sapiens

<400> 96 96 <00 suisides

aacgtgttcc gggacaccga ggccctgagg gaactgggag tgactcacta ccgcttttcg 60 09

atctcctggg cacgcgtgct cccgaacgga tcggcgggag tgccgaatcg cgagggcctg 120

cggtactacc gacggctgct ggaaaggctc agagaactgg gcgtgcagcc tgtcgtgact 180 08T

ctttaccact gggatctgcc ccaacggctg caggatgctt acgggggatg ggccaataga 240

gccctggctg atcacttccg cgactacgcc gaattgtgct tccggcactt cggtggccaa 300 00E

gtcaagtact ggattaccat cgacaaccca tacgtcgtgg cgtggcacgg atacgcaacc 360 09E

ggtcggctgg cccctggtat tcgcgggtcc ccgcggcttg gatacctggt ggcccacaac 420 9770880800

ctgttgctcg cgcatgccaa agtctggcac ctgtacaaca cctcgttccg gccgacccag 480 08/7

ggtggacaag tgtccatcgc cctgtcgtca cactggatca acccgcggag aatgaccgac 540

cactccatca aggaatgcca gaagtccctc gatttcgtgt tgggctggtt tgccaagcct 600 009

gtgtttattg acggagacta ccccgagtcc atgaagaaca acctgtcgtc tatcctgccc 660 9778777878 099 Page 335 SEE ested

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

gatttcactg aatccgagaa aaagtttatc aagggaaccg ctgacttctt cgccctctgt 720 gatttcactg aatccgagaa aaagtttatc aagggaaccg ctgacttctt cgccctctgt 720

ttcggcccga ccttgtcctt ccaactgctc gatcctcata tgaagttccg gcagctggaa 780 ttcggcccga ccttgtcctt ccaactgctc gatcctcata tgaagttccg gcagctggaa 780

tcccctaacc ttcgccagct gctgtcctgg atcgacttgg aattcaacca cccgcagatc 840 tcccctaacc ttcgccagct gctgtcctgg atcgacttgg aattcaacca cccgcagato 840

ttcattgtcg agaacggctg gttcgtgtcc gggaccacca agcgcgacga cgccaagtac 900 ttcattgtcg agaacggctg gttcgtgtcc gggaccacca agcgcgacga cgccaagtac 900

atgtattatc tcaaaaagtt catcatggaa accctcaagg ccatcaaatt ggatggcgtg 960 atgtattatc tcaaaaagtt catcatggaa accctcaagg ccatcaaatt ggatggcgtg 960

gacgtgatcg gatatacggc gtggagcctg atggacggtt tcgagtggca ccgcggatac 1020 gacgtgatcg gatatacggc gtggagcctg atggacggtt tcgagtggca ccgcggatad 1020

agcatccgca gaggactctt ctacgtggac ttcctgtcgc aagacaagat gctgctgcct 1080 agcatccgca gaggactctt ctacgtggac ttcctgtcgc aagacaagat gctgctgcct 1080

aagagcagcg cgctgttcta ccaaaagctc attgagaaga acgggttccc gcccctgccg 1140 aagagcagcg cgctgttcta ccaaaagctc attgagaaga acgggttccc gccccctgccg 1140

gagaaccagc ctctggaagg gaccttccct tgcgacttcg cctggggagt ggtcgacaac 1200 gagaaccago ctctggaagg gaccttccct tgcgacttcg cctggggagt ggtcgacaac 1200

tacattcaag tgtcccagct tactaagcca atcagcagcc tgactaagcc ataccac 1257 tacattcaag tgtcccagct tactaagcca atcagcagcc tgactaagcc ataccao 1257

<210> 97 <210> 97 <211> 30 <211> 30 <212> DNA <212> DNA <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> DNA_GS_linker1 <223> DNA_GS_linker1

<400> 97 <400> 97 gggggtggcg gaagcggtgg cggaggaagc 30 gggggtggcg gaagcggtgg cggaggaago 30

<210> 98 <210> 98 <211> 30 <211> 30 <212> DNA <212> DNA <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> DNA_GS_Linker_iso2 <223> DNA_GS_Linker_iso2

<400> 98 <400> 98 ggcgggggag ggtcgggcgg aggcggatcc 30 ggcgggggag ggtcgggcgg aggcggatco 30

<210> 99 <210> 99 <211> 681 <211> 681 <212> DNA <212> DNA <213> Artificial Sequence <213> Artificial Sequence

<220> <220> Page 336 Page 336

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT <223> DNA_ IgG1_noCH1_Fc_Fusion <223> DNA_ IgG1_noCH1_Fc_Fusion

<400> 99 <400> 99 gacaaaactc acacatgccc accgtgccca gcacctgaac tcctgggggg accgtcagtc 60 gacaaaactc acacatgccc accgtgccca gcacctgaac tcctgggggg accgtcagtc 60

ttcctcttcc ccccaaaacc caaggacacc ctcatgatct cccggacccc tgaggtcaca 120 ttcctcttcc ccccaaaacc caaggacacc ctcatgatct cccggacccc tgaggtcaca 120

tgcgtggtgg tggacgtgag ccacgaagac cctgaggtca agttcaactg gtacgtggac 180 tgcgtggtgg tggacgtgag ccacgaagac cctgaggtca agttcaactg gtacgtggac 180

ggcgtggagg tgcataatgc caagacaaag ccgcgggagg agcagtacaa cagcacgtac 240 ggcgtggagg tgcataatgc caagacaaag ccgcgggagg agcagtacaa cagcacgtad 240

cgggtggtca gcgtcctcac cgtcctgcac caggactggc tgaatggcaa ggagtacaag 300 cgggtggtca gcgtcctcac cgtcctgcac caggactggc tgaatggcaa ggagtacaag 300

tgcaaggtca gcaacaaagc cctcccagcc cccatcgaga aaaccatctc caaagccaaa 360 tgcaaggtca gcaacaaagc cctcccagcc cccatcgaga aaaccatctc caaagccaaa 360

gggcagcccc gagaaccaca ggtgtacacc ctgcccccat cccgggatga gctgaccaag 420 gggcagcccc gagaaccaca ggtgtacacc ctgcccccat cccgggatga gctgaccaag 420

aaccaggtca gcctgacctg cctggtcaaa ggcttctatc ccagcgacat cgccgtggag 480 aaccaggtca gcctgacctg cctggtcaaa ggcttctatc ccagcgacat cgccgtggag 480

tgggagagca atgggcagcc ggagaacaac tacaagacca cgcctcccgt gctggactcc 540 tgggagagca atgggcagcc ggagaacaac tacaagacca cgcctcccgt gctggactcc 540

gacggctcct tcttcctcta cagcaagctc accgtggaca agagcaggtg gcagcagggg 600 gacggctcct tcttcctcta cagcaagctc accgtggaca agagcaggtg gcagcagggg 600

aacgtcttct catgctccgt gatgcatgag gctctgcaca accactacac gcagaagtcc 660 aacgtcttct catgctccgt gatgcatgag gctctgcaca accactacad gcagaagtcc 660

ctctccctgt ctccgggtaa a 681 ctctccctgt ctccgggtaa a 681

<210> 100 <210> 100 <211> 57 <211> 57 <212> DNA <212> DNA <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> DNA_Synthetic_SS <223> DNA_Synthetic_SS

<400> 100 <400> 100 atggctcggc tgacagtcct ggccctgctg gctggtctgc tggcgtcctc gagggcc 57 atggctcggc tgacagtcct ggccctgctg gctggtctgc tggcgtcctc gagggcc 57

<210> 101 <210> 101 <211> 120 <211> 120 <212> DNA <212> DNA <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> DNA_TwinStrep_tag <223> DNA_TwinStrep_tag

<400> 101 <400> 101 ggcggagaaa acctttactt ccaatcctct gcctggagcc acccccagtt tgaaaagggc 60 ggcggagaaa acctttactt ccaatcctct gcctggagcc acccccagtt tgaaaagggc 60

ggcggctcag ggggcggatc cgggggatca tccgcctggt cccatccgca attcgagaag 120 ggcggctcag ggggcggatc cgggggatca tccgcctggt cccatccgca attcgagaag 120 Page 337 Page 337

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

<210> 102 <210> 102 <211> 32 <211> 32 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> Protein_TwinStrep_Tag_2 <223> Protein_TwinStrep_Tag_2

<400> 102 <400> 102

Ser Ser Ala Trp Ser His Pro Gln Phe Glu Lys Gly Gly Gly Ser Gly Ser Ser Ala Trp Ser His Pro Gln Phe Glu Lys Gly Gly Gly Ser Gly 1 5 10 15 1 5 10 15

Gly Gly Ser Gly Gly Ser Ser Ala Trp Ser His Pro Gln Phe Glu Lys Gly Gly Ser Gly Gly Ser Ser Ala Trp Ser His Pro Gln Phe Glu Lys 20 25 30 20 25 30

<210> 103 <210> 103 <211> 29 <211> 29 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> Protein_TwinStrep_Tag_3 <223> Protein_TwinStrep_Tag_3

<400> 103 <400> 103

Trp Ser His Pro Gln Phe Glu Lys Gly Gly Gly Ser Gly Gly Gly Ser Trp Ser His Pro Gln Phe Glu Lys Gly Gly Gly Ser Gly Gly Gly Ser 1 5 10 15 1 5 10 15

Gly Gly Ser Ser Ala Trp Ser His Pro Gln Phe Glu Lys Gly Gly Ser Ser Ala Trp Ser His Pro Gln Phe Glu Lys 20 25 20 25

<210> 104 <210> 104 <211> 8 <211> 8 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> Strep_Tag <223> Strep_Tag

<400> 104 <400> 104

Trp Ser His Pro Gln Phe Glu Lys Trp Ser His Pro Gln Phe Glu Lys 1 5 1 5

Page 338 Page 338

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. - TXT <210> 105 <210> 105 <211> 11 <211> 11 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> Protein_Strep_Tag_Linker <223> Protein_Strep_Tag_Linker

<400> 105 <400> 105

Gly Gly Glu Asn Leu Tyr Phe Gln Ser Ser Ala Gly Gly Glu Asn Leu Tyr Phe Gln Ser Ser Ala 1 5 10 1 5 10

<210> 106 <210> 106 <211> 8 <211> 8 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> Protein_Strep_Tag_Linker_2 <223> Protein_Strep_Tag_Linker_2

<400> 106 <400> 106

Gly Gly Glu Asn Leu Tyr Phe Gln Gly Gly Glu Asn Leu Tyr Phe Gln 1 5 1 5

<210> 107 <210> 107 <211> 516 <211> 516 <212> PRT <212> PRT <213> Homo sapiens <213> Homo sapiens

<400> 107 <400> 107

Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro 1 5 10 15 1 5 10 15

Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe 20 25 30 20 25 30

Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln 35 40 45 35 40 45

Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro 50 55 60 50 55 60

Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Page 339 Page 339

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 65 70 75 80 70 75 80

Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr 85 90 95 85 90 95

Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr 100 105 110 100 105 110

His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser 115 120 125 115 120 125

Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu 130 135 140 130 135 140

Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His 145 150 155 160 145 150 155 160

Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn 165 170 175 165 170 175

Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg 180 185 190 180 185 190

His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr 195 200 205 195 200 205

Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile 210 215 220 210 215 220

Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu 225 230 235 240 225 230 235 240

Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr 245 250 255 245 250 255

Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro 260 265 270 260 265 270

Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Page 340 Page 340

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 275 280 285 275 280 285

Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr 290 295 300 290 295 300

Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr 305 310 315 320 305 310 315 320

Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu 325 330 335 325 330 335

Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys 340 345 350 340 345 350

Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile 355 360 365 355 360 365

Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp 370 375 380 370 375 380

Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr 385 390 395 400 385 390 395 400

Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly 405 410 415 405 410 415

Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu 420 425 430 420 425 430

Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe 435 440 445 435 440 445

Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr 450 455 460 450 455 460

Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln 465 470 475 480 465 470 475 480

Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Page 341 Page 341

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing TXT 485 490 495 485 490 495

Asn Tyr Ile Gln Val Ser Gln Leu Thr Lys Pro Ile Ser Ser Leu Thr Asn Tyr Ile Gln Val Ser Gln Leu Thr Lys Pro Ile Ser Ser Leu Thr 500 505 510 500 505 510

Lys Pro Tyr His Lys Pro Tyr His 515 515

<210> 108 <210> 108 <211> 516 <211> 516 <212> PRT <212> PRT <213> Homo sapiens <213> Homo sapiens

<400> 108 <400> 108

Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Arg Pro Pro 1 5 10 15 1 5 10 15

Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe 20 25 30 20 25 30

Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln 35 40 45 35 40 45

Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro 50 55 60 50 55 60

Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala 65 70 75 80 70 75 80

Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr 85 90 95 85 90 95

Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr 100 105 110 100 105 110

His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser 115 120 125 115 120 125

Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu 130 135 140 130 135 140 Page 342 Page 342

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His 145 150 155 160 145 150 155 160

Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn 165 170 175 165 170 175

Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg 180 185 190 180 185 190

His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr 195 200 205 195 200 205

Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile 210 215 220 210 215 220

Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu 225 230 235 240 225 230 235 240

Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr 245 250 255 245 250 255

Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro 260 265 270 260 265 270

Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp 275 280 285 275 280 285

Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr 290 295 300 290 295 300

Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr 305 310 315 320 305 310 315 320

Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu 325 330 335 325 330 335

Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys 340 345 350 340 345 350 Page 343 Page 343

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile 355 360 365 355 360 365

Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp 370 375 380 370 375 380

Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr 385 390 395 400 385 390 395 400

Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly 405 410 415 405 410 415

Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu 420 425 430 420 425 430

Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe 435 440 445 435 440 445

Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr 450 455 460 450 455 460

Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln 465 470 475 480 465 470 475 480

Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp 485 490 495 485 490 495

Asn Tyr Ile Gln Val Ser Gln Leu Thr Lys Pro Ile Ser Ser Leu Thr Asn Tyr Ile Gln Val Ser Gln Leu Thr Lys Pro Ile Ser Ser Leu Thr 500 505 510 500 505 510

Lys Pro Tyr His Lys Pro Tyr His 515 515

<210> 109 <210> 109 <211> 516 <211> 516 <212> PRT <212> PRT <213> Homo sapiens <213> Homo sapiens

<400> 109 <400> 109 Page 344 Page 344

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro 1 5 10 15 1 5 10 15

Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe 20 25 30 20 25 30

Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln 35 40 45 35 40 45

Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro 50 55 60 50 55 60

Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala 65 70 75 80 70 75 80

Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr 85 90 95 85 90 95

Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr 100 105 110 100 105 110

His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser 115 120 125 115 120 125

Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu 130 135 140 130 135 140

Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His 145 150 155 160 145 150 155 160

Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn 165 170 175 165 170 175

Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg 180 185 190 180 185 190

His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr 195 200 205 195 200 205

Page 345 Page 345

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile 210 215 220 210 215 220

Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu 225 230 235 240 225 230 235 240

Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr 245 250 255 245 250 255

Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro 260 265 270 260 265 270

Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp 275 280 285 275 280 285

Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr 290 295 300 290 295 300

Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr 305 310 315 320 305 310 315 320

Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu 325 330 335 325 330 335

Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys 340 345 350 340 345 350

Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile 355 360 365 355 360 365

Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp 370 375 380 370 375 380

Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr 385 390 395 400 385 390 395 400

Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly 405 410 415 405 410 415

Page 346 Page 346

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu 420 425 430 420 425 430

Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe 435 440 445 435 440 445

Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr 450 455 460 450 455 460

Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln 465 470 475 480 465 470 475 480

Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp 485 490 495 485 490 495

Asn Tyr Ile Gln Val Ser Gln Leu Thr Lys Pro Ile Ser Ser Leu Thr Asn Tyr Ile Gln Val Ser Gln Leu Thr Lys Pro Ile Ser Ser Leu Thr 500 505 510 500 505 510

Lys Pro Tyr His Lys Pro Tyr His 515 515

<210> 110 <210> 110 <211> 516 <211> 516 <212> PRT <212> PRT <213> Homo sapiens <213> Homo sapiens

<400> 110 <400> 110

Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro 1 5 10 15 1 5 10 15

Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe 20 25 30 20 25 30

Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln 35 40 45 35 40 45

Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro 50 55 60 50 55 60

Page 347 Page 347

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing TXT Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala 65 70 75 80 70 75 80

Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr 85 90 95 85 90 95

Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr 100 105 110 100 105 110

His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser 115 120 125 115 120 125

Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu 130 135 140 130 135 140

Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His 145 150 155 160 145 150 155 160

Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn 165 170 175 165 170 175

Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg 180 185 190 180 185 190

His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr 195 200 205 195 200 205

Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile 210 215 220 210 215 220

Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu 225 230 235 240 225 230 235 240

Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr 245 250 255 245 250 255

Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro 260 265 270 260 265 270

Page 348 Page 348

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp 275 280 285 275 280 285

Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr 290 295 300 290 295 300

Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr 305 310 315 320 305 310 315 320

Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu 325 330 335 325 330 335

Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys 340 345 350 340 345 350

Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile 355 360 365 355 360 365

Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp 370 375 380 370 375 380

Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr 385 390 395 400 385 390 395 400

Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly 405 410 415 405 410 415

Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu 420 425 430 420 425 430

Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe 435 440 445 435 440 445

Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr 450 455 460 450 455 460

Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln 465 470 475 480 465 470 475 480

Page 349 Page 349

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp 485 490 495 485 490 495

Asn Tyr Ile Gln Val Ser Gln Leu Thr Lys Pro Ile Ser Ser Leu Thr Asn Tyr Ile Gln Val Ser Gln Leu Thr Lys Pro Ile Ser Ser Leu Thr 500 505 510 500 505 510

Lys Pro Tyr His Lys Pro Tyr His 515 515

<210> 111 <210> 111 <211> 864 <211> 864 <212> PRT <212> PRT <213> Canis familiaris <213> Canis familiaris

<400> 111 <400> 111

Met Ala Thr Cys Ile Leu Gln Met Arg Phe Leu Arg Leu Gly Lys Ile Met Ala Thr Cys Ile Leu Gln Met Arg Phe Leu Arg Leu Gly Lys Ile 1 5 10 15 1 5 10 15

Leu Phe His Ser Ser Pro Gln Ser Thr Gly Gly Ser Gly Gly Thr Arg Leu Phe His Ser Ser Pro Gln Ser Thr Gly Gly Ser Gly Gly Thr Arg 20 25 30 20 25 30

Gly Pro Arg Ala Pro Ala Gln Leu Arg Thr Gln Arg Gly Thr Asp Lys Gly Pro Arg Ala Pro Ala Gln Leu Arg Thr Gln Arg Gly Thr Asp Lys 35 40 45 35 40 45

Leu Val Ala Lys Ser Glu Leu Lys Ala Lys Thr Ala His Arg Ala Leu Leu Val Ala Lys Ser Glu Leu Lys Ala Lys Thr Ala His Arg Ala Leu 50 55 60 50 55 60

Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His Phe Cys Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His Phe Cys 65 70 75 80 70 75 80

Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val Val Ala Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val Val Ala 85 90 95 85 90 95

Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Val Arg Gly Ser Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Val Arg Gly Ser 100 105 110 100 105 110

Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala His Ala Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala His Ala 115 120 125 115 120 125

Lys Ile Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln Gly Gly Lys Ile Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln Gly Gly Page 350 Page 350

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 130 135 140 130 135 140

Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg Arg Met Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg Arg Met 145 150 155 160 145 150 155 160

Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Val Leu Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Val Leu 165 170 175 165 170 175

Gly Trp Phe Ala Lys Pro Ile Phe Ile Asp Gly Asp Tyr Pro Glu Ser Gly Trp Phe Ala Lys Pro Ile Phe Ile Asp Gly Asp Tyr Pro Glu Ser 180 185 190 180 185 190

Met Lys Asn Asn Leu Ser Ser Leu Leu Pro Val Phe Thr Glu Ser Glu Met Lys Asn Asn Leu Ser Ser Leu Leu Pro Val Phe Thr Glu Ser Glu 195 200 205 195 200 205

Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Ser Phe Gly Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Ser Phe Gly 210 215 220 210 215 220

Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe His Gln Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe His Gln 225 230 235 240 225 230 235 240

Leu Glu Ser Pro Ser Leu Arg Gln Leu Leu Ser Trp Ile Asp Leu Glu Leu Glu Ser Pro Ser Leu Arg Gln Leu Leu Ser Trp Ile Asp Leu Glu 245 250 255 245 250 255

Tyr Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Val Ser Tyr Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Val Ser 260 265 270 260 265 270

Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Lys Lys Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Lys Lys 275 280 285 275 280 285

Phe Ile Met Glu Thr Leu Lys Ala Ile Arg Leu Asp Gly Val Asp Val Phe Ile Met Glu Thr Leu Lys Ala Ile Arg Leu Asp Gly Val Asp Val 290 295 300 290 295 300

Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp His Arg Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp His Arg 305 310 315 320 305 310 315 320

Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu Ser Gln Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu Ser Gln 325 330 335 325 330 335

Asp Lys Lys Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys Leu Asp Lys Lys Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys Leu Page 351 Page 351

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 340 345 350 340 345 350

Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu Glu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu Glu 355 360 365 355 360 365

Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Ile Val Asp Asn Tyr Ile Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Ile Val Asp Asn Tyr Ile 370 375 380 370 375 380

Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Pro Asn Val Tyr Leu Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Pro Asn Val Tyr Leu 385 390 395 400 385 390 395 400

Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Gly Leu Arg Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Gly Leu Arg 405 410 415 405 410 415

Ala Lys Lys Arg Lys Pro Tyr Cys Val Asp Phe Ala Ala Ile Gly Pro Ala Lys Lys Arg Lys Pro Tyr Cys Val Asp Phe Ala Ala Ile Gly Pro 420 425 430 420 425 430

Gln Val Ala Leu Leu Gln Glu Met His Val Ser His Phe His Phe Ser Gln Val Ala Leu Leu Gln Glu Met His Val Ser His Phe His Phe Ser 435 440 445 435 440 445

Leu Asp Trp Ala Leu Leu Leu Pro Leu Gly Asn Gln Ser Arg Val Asn Leu Asp Trp Ala Leu Leu Leu Pro Leu Gly Asn Gln Ser Arg Val Asn 450 455 460 450 455 460

His Ala Ala Leu His Tyr Tyr Gly Cys Val Ala Ser Glu Leu Leu Arg His Ala Ala Leu His Tyr Tyr Gly Cys Val Ala Ser Glu Leu Leu Arg 465 470 475 480 465 470 475 480

Ala Asn Ile Thr Pro Val Val Ala Leu Trp Arg Pro Ala Ala Ala His Ala Asn Ile Thr Pro Val Val Ala Leu Trp Arg Pro Ala Ala Ala His 485 490 495 485 490 495

Gln Gly Leu Pro Gly Pro Leu Ala Gln Arg Gly Ala Trp Glu Asn Pro Gln Gly Leu Pro Gly Pro Leu Ala Gln Arg Gly Ala Trp Glu Asn Pro 500 505 510 500 505 510

Arg Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys Phe Arg Ala Arg Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Cys Phe Arg Ala 515 520 525 515 520 525

Leu Gly Arg His Val Lys Val Trp Ile Thr Leu Arg Glu Pro Pro Thr Leu Gly Arg His Val Lys Val Trp Ile Thr Leu Arg Glu Pro Pro Thr 530 535 540 530 535 540

Arg Asn Leu Thr Leu Arg Ala Gly His Asn Leu Leu Arg Ala His Ala Arg Asn Leu Thr Leu Arg Ala Gly His Asn Leu Leu Arg Ala His Ala Page 352 Page 352

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 545 550 555 560 545 550 555 560

Leu Ala Trp Arg Val Tyr Asp Glu Gln Phe Arg Gly Ser Gln Gln Gly Leu Ala Trp Arg Val Tyr Asp Glu Gln Phe Arg Gly Ser Gln Gln Gly 565 570 575 565 570 575

Lys Val Ser Ile Ala Leu Gln Ala Asp Trp Val Glu Pro Ala Cys Pro Lys Val Ser Ile Ala Leu Gln Ala Asp Trp Val Glu Pro Ala Cys Pro 580 585 590 580 585 590

Ser Ser Gln Lys Asp Arg Glu Val Ala Glu Arg Val Leu Glu Phe Asp Ser Ser Gln Lys Asp Arg Glu Val Ala Glu Arg Val Leu Glu Phe Asp 595 600 605 595 600 605

Val Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Tyr Pro Arg Val Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Tyr Pro Arg 610 615 620 610 615 620

Leu Met Arg Asp Trp Leu Thr Arg Arg Asp His Ser Leu Leu Pro Tyr Leu Met Arg Asp Trp Leu Thr Arg Arg Asp His Ser Leu Leu Pro Tyr 625 630 635 640 625 630 635 640

Phe Thr Asp Glu Glu Lys Arg Leu Ile Arg Gly Ser Phe Asp Phe Leu Phe Thr Asp Glu Glu Lys Arg Leu Ile Arg Gly Ser Phe Asp Phe Leu 645 650 655 645 650 655

Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Trp Glu Lys Glu Asp Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Trp Glu Lys Glu Asp 660 665 670 660 665 670

Pro Val Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Thr Asp Ile Pro Val Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Thr Asp Ile 675 680 685 675 680 685

Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Trp Gly Leu Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Trp Gly Leu 690 695 700 690 695 700

Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp Leu Pro Met Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp Leu Pro Met 705 710 715 720 705 710 715 720

Tyr Ile Val Ser Asn Gly Ile Asp Asp Asp Pro Arg Ala Ala Gln Asp Tyr Ile Val Ser Asn Gly Ile Asp Asp Asp Pro Arg Ala Ala Gln Asp 725 730 735 725 730 735

Ser Leu Arg Val Tyr Tyr Met Gln Asn Tyr Val Asn Glu Ala Leu Lys Ser Leu Arg Val Tyr Tyr Met Gln Asn Tyr Val Asn Glu Ala Leu Lys 740 745 750 740 745 750

Ala Tyr Val Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe Ala Tyr Ser Ala Tyr Val Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe Ala Tyr Ser Page 353 Page 353

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 755 760 765 755 760 765

Phe Asn Asp Arg Thr Ala Pro Lys Phe Gly Leu Tyr His Tyr Ala Ala Phe Asn Asp Arg Thr Ala Pro Lys Phe Gly Leu Tyr His Tyr Ala Ala 770 775 780 770 775 780

Asn Gln Phe Glu Pro Lys Pro Ser Val Lys His Tyr Arg Lys Ile Ile Asn Gln Phe Glu Pro Lys Pro Ser Val Lys His Tyr Arg Lys Ile Ile 785 790 795 800 785 790 795 800

Asp Asn Asn Gly Phe Pro Gly Pro Glu Thr Leu Gly Arg Phe Cys Pro Asp Asn Asn Gly Phe Pro Gly Pro Glu Thr Leu Gly Arg Phe Cys Pro 805 810 815 805 810 815

Glu Glu Phe Thr Leu Cys Thr Glu Cys Ser Phe Phe His Thr Arg Lys Glu Glu Phe Thr Leu Cys Thr Glu Cys Ser Phe Phe His Thr Arg Lys 820 825 830 820 825 830

Ser Leu Leu Ala Phe Ile Ala Phe Leu Leu Phe Ala Phe Ile Ile Ser Ser Leu Leu Ala Phe Ile Ala Phe Leu Leu Phe Ala Phe Ile Ile Ser 835 840 845 835 840 845

Leu Ser Leu Ile Phe Tyr Tyr Ser Arg Lys Gly Arg Arg Ser Tyr Lys Leu Ser Leu Ile Phe Tyr Tyr Ser Arg Lys Gly Arg Arg Ser Tyr Lys 850 855 860 850 855 860

<210> 112 <210> 112 <211> 705 <211> 705 <212> PRT <212> PRT <213> Felis catus <213> Felis catus

<400> 112 <400> 112

Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Val Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Val 1 5 10 15 1 5 10 15

Leu Gly Trp Phe Ala Lys Pro Ile Phe Ile Asp Gly Asp Tyr Pro Glu Leu Gly Trp Phe Ala Lys Pro Ile Phe Ile Asp Gly Asp Tyr Pro Glu 20 25 30 20 25 30

Ser Met Lys Asn Asn Leu Ser His Leu Leu Pro Asp Phe Thr Glu Ala Ser Met Lys Asn Asn Leu Ser His Leu Leu Pro Asp Phe Thr Glu Ala 35 40 45 35 40 45

Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Ser Phe Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Ser Phe 50 55 60 50 55 60

Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Arg Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Arg 65 70 75 80 70 75 80 Page 354 Page 354

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Gln Leu Glu Ser Pro Ser Leu Arg Gln Leu Leu Ser Trp Ile Asp Leu Gln Leu Glu Ser Pro Ser Leu Arg Gln Leu Leu Ser Trp Ile Asp Leu 85 90 95 85 90 95

Glu Tyr Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Val Glu Tyr Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Val 100 105 110 100 105 110

Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Lys Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Lys 115 120 125 115 120 125

Lys Phe Val Met Glu Thr Leu Lys Ala Ile Arg Leu Asp Gly Val Asp Lys Phe Val Met Glu Thr Leu Lys Ala Ile Arg Leu Asp Gly Val Asp 130 135 140 130 135 140

Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp His Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp His 145 150 155 160 145 150 155 160

Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu Ser Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu Ser 165 170 175 165 170 175

Gln Asp Lys Lys Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys Gln Asp Lys Lys Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys 180 185 190 180 185 190

Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu 195 200 205 195 200 205

Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Ile Val Asp Asn Tyr Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Ile Val Asp Asn Tyr 210 215 220 210 215 220

Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Pro Asn Val Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Pro Asn Val Tyr 225 230 235 240 225 230 235 240

Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Gly Val Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Gly Val 245 250 255 245 250 255

Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Ile Arg Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Ile Arg 260 265 270 260 265 270

Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Ser His Phe His Phe Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Ser His Phe His Phe 275 280 285 275 280 285 Page 355 Page 355

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Gln Val Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Gln Val 290 295 300 290 295 300

Asn His Thr Val Leu Asp Tyr Tyr Arg Cys Val Val Ser Glu Leu Val Asn His Thr Val Leu Asp Tyr Tyr Arg Cys Val Val Ser Glu Leu Val 305 310 315 320 305 310 315 320

Arg Ala Asn Ile Thr Pro Val Val Ala Leu Trp Arg Pro Ala Ala Pro Arg Ala Asn Ile Thr Pro Val Val Ala Leu Trp Arg Pro Ala Ala Pro 325 330 335 325 330 335

His Gln Gly Leu Pro Arg Pro Leu Ala Lys His Gly Ala Trp Glu Asn His Gln Gly Leu Pro Arg Pro Leu Ala Lys His Gly Ala Trp Glu Asn 340 345 350 340 345 350

Pro His Thr Ala Ser Ala Phe Ala Glu Tyr Ala Arg Leu Cys Phe Lys Pro His Thr Ala Ser Ala Phe Ala Glu Tyr Ala Arg Leu Cys Phe Lys 355 360 365 355 360 365

Asp Leu Gly His His Val Lys Phe Trp Ile Thr Met Gly Glu Pro Tyr Asp Leu Gly His His Val Lys Phe Trp Ile Thr Met Gly Glu Pro Tyr 370 375 380 370 375 380

Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Ala His Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Ala His 385 390 395 400 385 390 395 400

Ala Leu Ala Trp Arg Val Tyr Asp Glu Asn Phe Arg Gly Ser Gln Lys Ala Leu Ala Trp Arg Val Tyr Asp Glu Asn Phe Arg Gly Ser Gln Lys 405 410 415 405 410 415

Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Ala Cys Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Ala Cys 420 425 430 420 425 430

Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu Glu Phe Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu Glu Phe 435 440 445 435 440 445

Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Tyr Pro Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Tyr Pro 450 455 460 450 455 460

Arg Val Met Arg Asp Trp Leu Thr Gln Arg Asn Asn Phe Leu Leu Pro Arg Val Met Arg Asp Trp Leu Thr Gln Arg Asn Asn Phe Leu Leu Pro 465 470 475 480 465 470 475 480

Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Arg Gly Ser Phe Asp Phe Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Arg Gly Ser Phe Asp Phe 485 490 495 485 490 495 Page 356 Page 356

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Leu Ala Val Ser His Tyr Thr Thr Ile Leu Val Asp Trp Glu Lys Glu Leu Ala Val Ser His Tyr Thr Thr Ile Leu Val Asp Trp Glu Lys Glu 500 505 510 500 505 510

Asp Pro Met Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Thr Asp Asp Pro Met Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Thr Asp 515 520 525 515 520 525

Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Trp Gly Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Trp Gly 530 535 540 530 535 540

Leu Arg Lys Ile Leu Asn Trp Leu Lys Leu Lys Tyr Gly Asp Leu Pro Leu Arg Lys Ile Leu Asn Trp Leu Lys Leu Lys Tyr Gly Asp Leu Pro 545 550 555 560 545 550 555 560

Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Asp Pro Gln Ala Ala Gln Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Asp Pro Gln Ala Ala Gln 565 570 575 565 570 575

Asp Lys Leu Arg Val Tyr Tyr Met Gln Asn Tyr Val Asn Glu Ala Leu Asp Lys Leu Arg Val Tyr Tyr Met Gln Asn Tyr Val Asn Glu Ala Leu 580 585 590 580 585 590

Lys Ala Tyr Val Leu Asp Gly Val Asn Leu Cys Gly Tyr Phe Ala Tyr Lys Ala Tyr Val Leu Asp Gly Val Asn Leu Cys Gly Tyr Phe Ala Tyr 595 600 605 595 600 605

Ser Phe Asn Asp Arg Thr Ala Pro Lys Phe Gly Phe Tyr His Tyr Ala Ser Phe Asn Asp Arg Thr Ala Pro Lys Phe Gly Phe Tyr His Tyr Ala 610 615 620 610 615 620

Ala Asn Gln Phe Glu Pro Lys Pro Ser Met Lys His Tyr Arg Lys Met Ala Asn Gln Phe Glu Pro Lys Pro Ser Met Lys His Tyr Arg Lys Met 625 630 635 640 625 630 635 640

Ile Asp Ser Asn Gly Phe Ser Gly Pro Asp Thr Leu Gly Arg Phe Cys Ile Asp Ser Asn Gly Phe Ser Gly Pro Asp Thr Leu Gly Arg Phe Cys 645 650 655 645 650 655

Pro Glu Glu Phe Thr Leu Cys Thr Glu Cys Gly Phe Phe His Thr Arg Pro Glu Glu Phe Thr Leu Cys Thr Glu Cys Gly Phe Phe His Thr Arg 660 665 670 660 665 670

Lys Ser Leu Leu Ala Phe Ile Ala Phe Leu Leu Phe Ala Phe Ile Ile Lys Ser Leu Leu Ala Phe Ile Ala Phe Leu Leu Phe Ala Phe Ile Ile 675 680 685 675 680 685

Ser Leu Ser Leu Ile Phe Tyr Tyr Ser Lys Lys Gly Lys Arg Ser Tyr Ser Leu Ser Leu Ile Phe Tyr Tyr Ser Lys Lys Gly Lys Arg Ser Tyr 690 695 700 690 695 700 Page 357 Page 357

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Lys Lys 705 705

<210> 113 <210> 113 <211> 705 <211> 705 <212> PRT <212> PRT <213> Felis catus <213> Felis catus

<400> 113 <400> 113

Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Val Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Val 1 5 10 15 1 5 10 15

Leu Gly Trp Phe Ala Lys Pro Ile Phe Ile Asp Gly Asp Tyr Pro Glu Leu Gly Trp Phe Ala Lys Pro Ile Phe Ile Asp Gly Asp Tyr Pro Glu 20 25 30 20 25 30

Ser Met Lys Asn Asn Leu Ser His Leu Leu Pro Asp Phe Thr Glu Ala Ser Met Lys Asn Asn Leu Ser His Leu Leu Pro Asp Phe Thr Glu Ala 35 40 45 35 40 45

Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Ser Phe Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Ser Phe 50 55 60 50 55 60

Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Arg Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Arg 65 70 75 80 70 75 80

Gln Leu Glu Ser Pro Ser Leu Arg Gln Leu Leu Ser Trp Ile Asp Leu Gln Leu Glu Ser Pro Ser Leu Arg Gln Leu Leu Ser Trp Ile Asp Leu 85 90 95 85 90 95

Glu Tyr Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Val Glu Tyr Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Val 100 105 110 100 105 110

Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Lys Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Lys 115 120 125 115 120 125

Lys Phe Val Met Glu Thr Leu Lys Ala Ile Arg Leu Asp Gly Val Asp Lys Phe Val Met Glu Thr Leu Lys Ala Ile Arg Leu Asp Gly Val Asp 130 135 140 130 135 140

Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp His Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp His 145 150 155 160 145 150 155 160

Page 358 Page 358

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu Ser Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu Ser 165 170 175 165 170 175

Gln Asp Lys Lys Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys Gln Asp Lys Lys Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys 180 185 190 180 185 190

Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu 195 200 205 195 200 205

Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Ile Val Asp Asn Tyr Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Ile Val Asp Asn Tyr 210 215 220 210 215 220

Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Pro Asn Val Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Pro Asn Val Tyr 225 230 235 240 225 230 235 240

Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Gly Val Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Gly Val 245 250 255 245 250 255

Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Ile Arg Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Ile Arg 260 265 270 260 265 270

Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Ser His Phe His Phe Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Ser His Phe His Phe 275 280 285 275 280 285

Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Gln Val Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Gln Val 290 295 300 290 295 300

Asn His Thr Val Leu Asp Tyr Tyr Arg Cys Val Val Ser Glu Leu Val Asn His Thr Val Leu Asp Tyr Tyr Arg Cys Val Val Ser Glu Leu Val 305 310 315 320 305 310 315 320

Arg Ala Asn Ile Thr Pro Val Val Ala Leu Trp Arg Pro Ala Ala Pro Arg Ala Asn Ile Thr Pro Val Val Ala Leu Trp Arg Pro Ala Ala Pro 325 330 335 325 330 335

His Gln Gly Leu Pro Arg Pro Leu Ala Lys His Gly Ala Trp Glu Asn His Gln Gly Leu Pro Arg Pro Leu Ala Lys His Gly Ala Trp Glu Asn 340 345 350 340 345 350

Pro His Thr Ala Ser Ala Phe Ala Glu Tyr Ala Arg Leu Cys Phe Lys Pro His Thr Ala Ser Ala Phe Ala Glu Tyr Ala Arg Leu Cys Phe Lys 355 360 365 355 360 365

Page 359 Page 359

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Asp Leu Gly His His Val Lys Phe Trp Ile Thr Met Gly Glu Pro Tyr Asp Leu Gly His His Val Lys Phe Trp Ile Thr Met Gly Glu Pro Tyr 370 375 380 370 375 380

Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Ala His Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Ala His 385 390 395 400 385 390 395 400

Ala Leu Ala Trp Arg Val Tyr Asp Glu Asn Phe Arg Gly Ser Gln Lys Ala Leu Ala Trp Arg Val Tyr Asp Glu Asn Phe Arg Gly Ser Gln Lys 405 410 415 405 410 415

Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Ala Cys Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Ala Cys 420 425 430 420 425 430

Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu Glu Phe Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu Glu Phe 435 440 445 435 440 445

Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Tyr Pro Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Tyr Pro 450 455 460 450 455 460

Arg Val Met Arg Asp Trp Leu Thr Gln Arg Asn Asn Phe Leu Leu Pro Arg Val Met Arg Asp Trp Leu Thr Gln Arg Asn Asn Phe Leu Leu Pro 465 470 475 480 465 470 475 480

Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Arg Gly Ser Phe Asp Phe Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Arg Gly Ser Phe Asp Phe 485 490 495 485 490 495

Leu Ala Val Ser His Tyr Thr Thr Ile Leu Val Asp Trp Glu Lys Glu Leu Ala Val Ser His Tyr Thr Thr Ile Leu Val Asp Trp Glu Lys Glu 500 505 510 500 505 510

Asp Pro Met Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Thr Asp Asp Pro Met Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Thr Asp 515 520 525 515 520 525

Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Trp Gly Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Trp Gly 530 535 540 530 535 540

Leu Arg Lys Ile Leu Asn Trp Leu Lys Leu Lys Tyr Gly Asp Leu Pro Leu Arg Lys Ile Leu Asn Trp Leu Lys Leu Lys Tyr Gly Asp Leu Pro 545 550 555 560 545 550 555 560

Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Asp Pro Gln Ala Ala Gln Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Asp Pro Gln Ala Ala Gln 565 570 575 565 570 575

Page 360 Page 360

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Asp Lys Leu Arg Val Tyr Tyr Met Gln Asn Tyr Val Asn Glu Ala Leu Asp Lys Leu Arg Val Tyr Tyr Met Gln Asn Tyr Val Asn Glu Ala Leu 580 585 590 580 585 590

Lys Ala Tyr Val Leu Asp Gly Val Asn Leu Cys Gly Tyr Phe Ala Tyr Lys Ala Tyr Val Leu Asp Gly Val Asn Leu Cys Gly Tyr Phe Ala Tyr 595 600 605 595 600 605

Ser Phe Asn Asp Arg Thr Ala Pro Lys Phe Gly Phe Tyr His Tyr Ala Ser Phe Asn Asp Arg Thr Ala Pro Lys Phe Gly Phe Tyr His Tyr Ala 610 615 620 610 615 620

Ala Asn Gln Phe Glu Pro Lys Pro Ser Met Lys His Tyr Arg Lys Met Ala Asn Gln Phe Glu Pro Lys Pro Ser Met Lys His Tyr Arg Lys Met 625 630 635 640 625 630 635 640

Ile Asp Ser Asn Gly Phe Ser Gly Pro Asp Thr Leu Gly Arg Phe Cys Ile Asp Ser Asn Gly Phe Ser Gly Pro Asp Thr Leu Gly Arg Phe Cys 645 650 655 645 650 655

Pro Glu Glu Phe Thr Leu Cys Thr Glu Cys Gly Phe Phe His Thr Arg Pro Glu Glu Phe Thr Leu Cys Thr Glu Cys Gly Phe Phe His Thr Arg 660 665 670 660 665 670

Lys Ser Leu Leu Ala Phe Ile Ala Phe Leu Leu Phe Ala Phe Ile Ile Lys Ser Leu Leu Ala Phe Ile Ala Phe Leu Leu Phe Ala Phe Ile Ile 675 680 685 675 680 685

Ser Leu Ser Leu Ile Phe Tyr Tyr Ser Lys Lys Gly Lys Arg Ser Tyr Ser Leu Ser Leu Ile Phe Tyr Tyr Ser Lys Lys Gly Lys Arg Ser Tyr 690 695 700 690 695 700

Lys Lys 705 705

<210> 114 <210> 114 <211> 754 <211> 754 <212> PRT <212> PRT <213> Felis catus <213> Felis catus

<400> 114 <400> 114

Met Arg Asp Leu Cys Tyr Ile Thr Trp Ser Arg Gly Thr Val Gln Ala Met Arg Asp Leu Cys Tyr Ile Thr Trp Ser Arg Gly Thr Val Gln Ala 1 5 10 15 1 5 10 15

His Ala Lys Ile Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln His Ala Lys Ile Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln 20 25 30 20 25 30

Page 361 Page 361

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg 35 40 45 35 40 45

Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe 50 55 60 50 55 60

Val Leu Gly Trp Phe Ala Lys Pro Ile Phe Ile Asp Gly Asp Tyr Pro Val Leu Gly Trp Phe Ala Lys Pro Ile Phe Ile Asp Gly Asp Tyr Pro 65 70 75 80 70 75 80

Glu Ser Met Lys Asn Asn Leu Ser His Leu Leu Pro Asp Phe Thr Glu Glu Ser Met Lys Asn Asn Leu Ser His Leu Leu Pro Asp Phe Thr Glu 85 90 95 85 90 95

Ala Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Ser Ala Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Ser 100 105 110 100 105 110

Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe 115 120 125 115 120 125

Arg Gln Leu Glu Ser Pro Ser Leu Arg Gln Leu Leu Ser Trp Ile Asp Arg Gln Leu Glu Ser Pro Ser Leu Arg Gln Leu Leu Ser Trp Ile Asp 130 135 140 130 135 140

Leu Glu Tyr Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Leu Glu Tyr Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe 145 150 155 160 145 150 155 160

Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu 165 170 175 165 170 175

Lys Lys Phe Val Met Glu Thr Leu Lys Ala Ile Arg Leu Asp Gly Val Lys Lys Phe Val Met Glu Thr Leu Lys Ala Ile Arg Leu Asp Gly Val 180 185 190 180 185 190

Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp 195 200 205 195 200 205

His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu 210 215 220 210 215 220

Ser Gln Asp Lys Lys Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Ser Gln Asp Lys Lys Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln 225 230 235 240 225 230 235 240

Page 362 Page 362

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro 245 250 255 245 250 255

Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Ile Val Asp Asn Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Ile Val Asp Asn 260 265 270 260 265 270

Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Pro Asn Val Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Pro Asn Val 275 280 285 275 280 285

Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Gly Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asp Gly 290 295 300 290 295 300

Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Ile Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Ile 305 310 315 320 305 310 315 320

Arg Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Ser His Phe His Arg Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Ser His Phe His 325 330 335 325 330 335

Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Gln Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Gln 340 345 350 340 345 350

Val Asn His Thr Val Leu Asp Tyr Tyr Arg Cys Val Val Ser Glu Leu Val Asn His Thr Val Leu Asp Tyr Tyr Arg Cys Val Val Ser Glu Leu 355 360 365 355 360 365

Val Arg Ala Asn Ile Thr Pro Val Val Ala Leu Trp Arg Pro Ala Ala Val Arg Ala Asn Ile Thr Pro Val Val Ala Leu Trp Arg Pro Ala Ala 370 375 380 370 375 380

Pro His Gln Gly Leu Pro Arg Pro Leu Ala Lys His Gly Ala Trp Glu Pro His Gln Gly Leu Pro Arg Pro Leu Ala Lys His Gly Ala Trp Glu 385 390 395 400 385 390 395 400

Asn Pro His Thr Ala Ser Ala Phe Ala Glu Tyr Ala Arg Leu Cys Phe Asn Pro His Thr Ala Ser Ala Phe Ala Glu Tyr Ala Arg Leu Cys Phe 405 410 415 405 410 415

Lys Asp Leu Gly His His Val Lys Phe Trp Ile Thr Met Gly Glu Pro Lys Asp Leu Gly His His Val Lys Phe Trp Ile Thr Met Gly Glu Pro 420 425 430 420 425 430

Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Ala Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Ala 435 440 445 435 440 445

Page 363 Page 363

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT His Ala Leu Ala Trp Arg Val Tyr Asp Glu Asn Phe Arg Gly Ser Gln His Ala Leu Ala Trp Arg Val Tyr Asp Glu Asn Phe Arg Gly Ser Gln 450 455 460 450 455 460

Lys Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Ala Lys Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Ala 465 470 475 480 465 470 475 480

Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu Glu Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Leu Glu 485 490 495 485 490 495

Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Tyr Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Tyr 500 505 510 500 505 510

Pro Arg Val Met Arg Asp Trp Leu Thr Gln Arg Asn Asn Phe Leu Leu Pro Arg Val Met Arg Asp Trp Leu Thr Gln Arg Asn Asn Phe Leu Leu 515 520 525 515 520 525

Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Arg Gly Ser Phe Asp Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Arg Gly Ser Phe Asp 530 535 540 530 535 540

Phe Leu Ala Val Ser His Tyr Thr Thr Ile Leu Val Asp Trp Glu Lys Phe Leu Ala Val Ser His Tyr Thr Thr Ile Leu Val Asp Trp Glu Lys 545 550 555 560 545 550 555 560

Glu Asp Pro Met Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Thr Glu Asp Pro Met Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Thr 565 570 575 565 570 575

Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Trp Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Trp 580 585 590 580 585 590

Gly Leu Arg Lys Ile Leu Asn Trp Leu Lys Leu Lys Tyr Gly Asp Leu Gly Leu Arg Lys Ile Leu Asn Trp Leu Lys Leu Lys Tyr Gly Asp Leu 595 600 605 595 600 605

Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Asp Pro Gln Ala Ala Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Asp Pro Gln Ala Ala 610 615 620 610 615 620

Gln Asp Lys Leu Arg Val Tyr Tyr Met Gln Asn Tyr Val Asn Glu Ala Gln Asp Lys Leu Arg Val Tyr Tyr Met Gln Asn Tyr Val Asn Glu Ala 625 630 635 640 625 630 635 640

Leu Lys Ala Tyr Val Leu Asp Gly Val Asn Leu Cys Gly Tyr Phe Ala Leu Lys Ala Tyr Val Leu Asp Gly Val Asn Leu Cys Gly Tyr Phe Ala 645 650 655 645 650 655

Page 364 Page 364

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. - TXT Tyr Ser Phe Asn Asp Arg Thr Ala Pro Lys Phe Gly Phe Tyr His Tyr Tyr Ser Phe Asn Asp Arg Thr Ala Pro Lys Phe Gly Phe Tyr His Tyr 660 665 670 660 665 670

Ala Ala Asn Gln Phe Glu Pro Lys Pro Ser Met Lys His Tyr Arg Lys Ala Ala Asn Gln Phe Glu Pro Lys Pro Ser Met Lys His Tyr Arg Lys 675 680 685 675 680 685

Met Ile Asp Ser Asn Gly Phe Ser Gly Pro Asp Thr Leu Gly Arg Phe Met Ile Asp Ser Asn Gly Phe Ser Gly Pro Asp Thr Leu Gly Arg Phe 690 695 700 690 695 700

Cys Pro Glu Glu Phe Thr Leu Cys Thr Glu Cys Gly Phe Phe His Thr Cys Pro Glu Glu Phe Thr Leu Cys Thr Glu Cys Gly Phe Phe His Thr 705 710 715 720 705 710 715 720

Arg Lys Ser Leu Leu Ala Phe Ile Ala Phe Leu Leu Phe Ala Phe Ile Arg Lys Ser Leu Leu Ala Phe Ile Ala Phe Leu Leu Phe Ala Phe Ile 725 730 735 725 730 735

Ile Ser Leu Ser Leu Ile Phe Tyr Tyr Ser Lys Lys Gly Lys Arg Ser Ile Ser Leu Ser Leu Ile Phe Tyr Tyr Ser Lys Lys Gly Lys Arg Ser 740 745 750 740 745 750

Tyr Lys Tyr Lys

<210> 115 <210> 115 <211> 1012 <211> 1012 <212> PRT <212> PRT <213> Sus scrofa <213> Sus scrofa

<400> 115 <400> 115

Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser 1 5 10 15 1 5 10 15

Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg 20 25 30 20 25 30

Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro 35 40 45 35 40 45

Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly 50 55 60 50 55 60

Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Page 365 Page 365

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 65 70 75 80 70 75 80

Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His 85 90 95 85 90 95

Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly 100 105 110 100 105 110

Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser 115 120 125 115 120 125

Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val 130 135 140 130 135 140

Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly 145 150 155 160 145 150 155 160

Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu 165 170 175 165 170 175

Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr 180 185 190 180 185 190

His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala 195 200 205 195 200 205

Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe 210 215 220 210 215 220

Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro 225 230 235 240 225 230 235 240

Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly 245 250 255 245 250 255

Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu 260 265 270 260 265 270

Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Page 366 Page 366

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 275 280 285 275 280 285

Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn 290 295 300 290 295 300

Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu 305 310 315 320 305 310 315 320

Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp 325 330 335 325 330 335

Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe 340 345 350 340 345 350

Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala 355 360 365 355 360 365

Leu Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Leu Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met 370 375 380 370 375 380

Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp 385 390 395 400 385 390 395 400

Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly 405 410 415 405 410 415

Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr 420 425 430 420 425 430

Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp 435 440 445 435 440 445

Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe 450 455 460 450 455 460

Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp 465 470 475 480 465 470 475 480

Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Page 367 Page 367

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 485 490 495 485 490 495

Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn 500 505 510 500 505 510

Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val 515 520 525 515 520 525

Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu 530 535 540 530 535 540

Asn Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asn Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val 545 550 555 560 545 550 555 560

Asp Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Asp Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala 565 570 575 565 570 575

Ala Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Ala Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His 580 585 590 580 585 590

Phe Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Phe Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln 595 600 605 595 600 605

Ser Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Ser Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser 610 615 620 610 615 620

Glu Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Glu Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro 625 630 635 640 625 630 635 640

Met Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Met Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala 645 650 655 645 650 655

Trp Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Trp Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu 660 665 670 660 665 670

Cys Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Cys Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn 675 680 685 675 680 685

Glu Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Glu Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Page 368 Page 368

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 690 695 700 690 695 700

Lys Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Lys Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His 705 710 715 720 705 710 715 720

Ala Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Ala Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu 725 730 735 725 730 735

Pro Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Pro Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val 740 745 750 740 745 750

Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly 755 760 765 755 760 765

Asp Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Asp Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe 770 775 780 770 775 780

Leu Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Leu Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr 785 790 795 800 785 790 795 800

Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser 805 810 815 805 810 815

Glu Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Glu Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu 820 825 830 820 825 830

Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val 835 840 845 835 840 845

Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly 850 855 860 850 855 860

Asp Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Asp Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His 865 870 875 880 865 870 875 880

Ala Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Ala Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn 885 890 895 885 890 895

Glu Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Glu Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Page 369 Page 369

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. - TXT 900 905 910 900 905 910

Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr 915 920 925 915 920 925

Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr 930 935 940 930 935 940

Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu 945 950 955 960 945 950 955 960

Arg Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe Arg Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe 965 970 975 965 970 975

His Thr Arg Lys Ser Leu Leu Ala Phe Ile Ala Phe Leu Phe Phe Ala His Thr Arg Lys Ser Leu Leu Ala Phe Ile Ala Phe Leu Phe Phe Ala 980 985 990 980 985 990

Ser Ile Ile Ser Leu Ser Leu Ile Phe Tyr Tyr Ser Lys Lys Gly Arg Ser Ile Ile Ser Leu Ser Leu Ile Phe Tyr Tyr Ser Lys Lys Gly Arg 995 1000 1005 995 1000 1005

Arg Ser Tyr Lys Arg Ser Tyr Lys 1010 1010

<210> 116 <210> 116 <211> 1013 <211> 1013 <212> PRT <212> PRT <213> Bos taurus <213> Bos taurus

<400> 116 <400> 116

Met Pro Ala Arg Ala Pro Pro Arg Arg Leu Arg Ala Phe Pro Pro Pro Met Pro Ala Arg Ala Pro Pro Arg Arg Leu Arg Ala Phe Pro Pro Pro 1 5 10 15 1 5 10 15

Pro Pro Pro Leu Trp Leu Leu Leu Leu Ala Leu Gly Gly Arg Pro Leu Pro Pro Pro Leu Trp Leu Leu Leu Leu Ala Leu Gly Gly Arg Pro Leu 20 25 30 20 25 30

Arg Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ala Arg Arg Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ala Arg 35 40 45 35 40 45

Pro Pro Thr Pro Glu Ala Ala Gly Leu Leu His Asp Thr Phe Pro Asp Pro Pro Thr Pro Glu Ala Ala Gly Leu Leu His Asp Thr Phe Pro Asp 50 55 60 50 55 60 Page 370 Page 370

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Gly Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Gly Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly 65 70 75 80 70 75 80

Trp Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His Trp Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His 85 90 95 85 90 95

Arg Pro Pro Ala Pro Pro Gly Asp Pro Ser Ala Ala Gly Trp Pro Ser Arg Pro Pro Ala Pro Pro Gly Asp Pro Ser Ala Ala Gly Trp Pro Ser 100 105 110 100 105 110

Gly Ala Pro Ser Pro Pro Pro Pro Ala Thr Gly Asp Val Ala Ser Asp Gly Ala Pro Ser Pro Pro Pro Pro Ala Thr Gly Asp Val Ala Ser Asp 115 120 125 115 120 125

Gly Tyr Asn Asn Val Phe Arg Asp Thr Glu Gly Leu Arg Glu Leu Gly Gly Tyr Asn Asn Val Phe Arg Asp Thr Glu Gly Leu Arg Glu Leu Gly 130 135 140 130 135 140

Val Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Val Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn 145 150 155 160 145 150 155 160

Gly Ser Ala Ser Ala Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Gly Ser Ala Ser Ala Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg 165 170 175 165 170 175

Leu Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Leu Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu 180 185 190 180 185 190

Tyr His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Tyr His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp 195 200 205 195 200 205

Ala Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Ala Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys 210 215 220 210 215 220

Phe Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Phe Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn 225 230 235 240 225 230 235 240

Pro Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Pro Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro 245 250 255 245 250 255

Gly Val Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Gly Val Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu 260 265 270 260 265 270 Page 371 Page 371

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Leu Leu Ala His Ala Lys Ile Trp His Leu Tyr Asp Thr Ser Phe Arg Leu Leu Ala His Ala Lys Ile Trp His Leu Tyr Asp Thr Ser Phe Arg 275 280 285 275 280 285

Pro Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Pro Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile 290 295 300 290 295 300

Ser Pro Arg Arg Met Thr Glu His Ser Ile Gln Glu Cys Gln Lys Ser Ser Pro Arg Arg Met Thr Glu His Ser Ile Gln Glu Cys Gln Lys Ser 305 310 315 320 305 310 315 320

Leu Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Ile Phe Ile Asp Gly Leu Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Ile Phe Ile Asp Gly 325 330 335 325 330 335

Asp Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Leu Leu Pro Asp Asp Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Leu Leu Pro Asp 340 345 350 340 345 350

Phe Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Phe Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe 355 360 365 355 360 365

Ala Leu Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro Gln Ala Leu Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro Gln 370 375 380 370 375 380

Met Lys Phe Arg Gln Leu Glu Ser Pro Ser Leu Arg Gln Leu Leu Ser Met Lys Phe Arg Gln Leu Glu Ser Pro Ser Leu Arg Gln Leu Leu Ser 385 390 395 400 385 390 395 400

Trp Ile Asp Leu Glu Tyr Asn His Pro Gln Ile Phe Ile Val Glu Asn Trp Ile Asp Leu Glu Tyr Asn His Pro Gln Ile Phe Ile Val Glu Asn 405 410 415 405 410 415

Gly Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Gly Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met 420 425 430 420 425 430

Tyr Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Arg Leu Tyr Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Arg Leu 435 440 445 435 440 445

Asp Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Asp Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly 450 455 460 450 455 460

Phe Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Phe Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val 465 470 475 480 465 470 475 480 Page 372 Page 372

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Asp Phe Leu Ser Gln Asp Lys Lys Leu Leu Pro Lys Ser Ser Ala Leu Asp Phe Leu Ser Gln Asp Lys Lys Leu Leu Pro Lys Ser Ser Ala Leu 485 490 495 485 490 495

Phe Tyr Gln Lys Leu Ile Glu Asn Asn Gly Phe Pro Pro Leu Pro Glu Phe Tyr Gln Lys Leu Ile Glu Asn Asn Gly Phe Pro Pro Leu Pro Glu 500 505 510 500 505 510

Asn Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Asn Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val 515 520 525 515 520 525

Val Asp Asn Cys Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Ile Asp Val Asp Asn Cys Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Ile Asp 530 535 540 530 535 540

Pro Asn Val Tyr Leu Trp Asp Val His Arg Ser Lys Arg Leu Ile Lys Pro Asn Val Tyr Leu Trp Asp Val His Arg Ser Lys Arg Leu Ile Lys 545 550 555 560 545 550 555 560

Val Asp Gly Val Leu Thr Lys Thr Arg Lys Ser Tyr Cys Val Asp Phe Val Asp Gly Val Leu Thr Lys Thr Arg Lys Ser Tyr Cys Val Asp Phe 565 570 575 565 570 575

Ala Ala Ile Arg Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr Ala Ala Ile Arg Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr 580 585 590 580 585 590

His Phe His Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn His Phe His Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn 595 600 605 595 600 605

Arg Ser Gln Val Asn Arg Thr Val Leu Gly Phe Tyr Arg Cys Val Ala Arg Ser Gln Val Asn Arg Thr Val Leu Gly Phe Tyr Arg Cys Val Ala 610 615 620 610 615 620

Ser Glu Leu Val Arg Ala Asn Ile Thr Pro Val Val Ala Leu Trp Arg Ser Glu Leu Val Arg Ala Asn Ile Thr Pro Val Val Ala Leu Trp Arg 625 630 635 640 625 630 635 640

Pro Ala Ala Pro His Gln Gly Leu Pro Ala Pro Leu Ala Arg His Gly Pro Ala Ala Pro His Gln Gly Leu Pro Ala Pro Leu Ala Arg His Gly 645 650 655 645 650 655

Ala Trp Glu Asn Pro His Thr Ala Leu Ala Phe Ala Glu Tyr Ala Ser Ala Trp Glu Asn Pro His Thr Ala Leu Ala Phe Ala Glu Tyr Ala Ser 660 665 670 660 665 670

Leu Cys Phe Gln Asp Leu Gly Arg His Val Lys Phe Trp Ile Thr Met Leu Cys Phe Gln Asp Leu Gly Arg His Val Lys Phe Trp Ile Thr Met 675 680 685 675 680 685

Page 373 Page 373

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

His Glu Pro Ser Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu His Glu Pro Ser Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu 690 695 700 690 695 700

Leu Lys Ala His Ala Leu Ala Trp Arg Thr Tyr Asp Glu Arg Phe Arg Leu Lys Ala His Ala Leu Ala Trp Arg Thr Tyr Asp Glu Arg Phe Arg 705 710 715 720 705 710 715 720

Arg Ser Gln Lys Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Arg Ser Gln Lys Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile 725 730 735 725 730 735

Glu Pro Ala Cys Pro Phe Ser Pro Glu Asp Arg Glu Val Ala Glu Arg Glu Pro Ala Cys Pro Phe Ser Pro Glu Asp Arg Glu Val Ala Glu Arg 740 745 750 740 745 750

Val Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Val Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser 755 760 765 755 760 765

Gly Asp Tyr Pro Arg Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Gly Asp Tyr Pro Arg Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn 770 775 780 770 775 780

Phe Leu Leu Pro Tyr Phe Thr Asp Glu Glu Lys Lys Leu Ile Arg Gly Phe Leu Leu Pro Tyr Phe Thr Asp Glu Glu Lys Lys Leu Ile Arg Gly 785 790 795 800 785 790 795 800

Ser Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp 805 810 815 805 810 815

Trp Glu Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Ala Val Gln Trp Glu Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Ala Val Gln 820 825 830 820 825 830

Glu Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Glu Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val 835 840 845 835 840 845

Val Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Ala Lys Tyr Val Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Ala Lys Tyr 850 855 860 850 855 860

Gly Asp Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Asp Pro Gly Asp Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Asp Pro 865 870 875 880 865 870 875 880

His Ala Ala Gln Asp Asn Leu Arg Val Tyr Tyr Met Gln Thr Tyr Val His Ala Ala Gln Asp Asn Leu Arg Val Tyr Tyr Met Gln Thr Tyr Val 885 890 895 885 890 895 Page 374 Page 374

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Asn Glu Ala Leu Lys Ala Tyr Ile Leu Asp Gly Ile Asn Leu Cys Gly Asn Glu Ala Leu Lys Ala Tyr Ile Leu Asp Gly Ile Asn Leu Cys Gly 900 905 910 900 905 910

Tyr Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Lys Phe Gly Leu Tyr Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Lys Phe Gly Leu 915 920 925 915 920 925

Tyr Arg Tyr Ala Ala Asn Gln Phe Glu Pro Lys Pro Ser Met Lys His Tyr Arg Tyr Ala Ala Asn Gln Phe Glu Pro Lys Pro Ser Met Lys His 930 935 940 930 935 940

Tyr Arg Lys Ile Ile Asp Asn Asn Gly Phe Pro Gly Pro Glu Thr Leu Tyr Arg Lys Ile Ile Asp Asn Asn Gly Phe Pro Gly Pro Glu Thr Leu 945 950 955 960 945 950 955 960

Gly Arg Phe Cys Pro Glu Glu Phe Thr Leu Cys Thr Glu Cys Ser Phe Gly Arg Phe Cys Pro Glu Glu Phe Thr Leu Cys Thr Glu Cys Ser Phe 965 970 975 965 970 975

Phe His Thr Arg Lys Ser Leu Leu Ala Phe Ile Ala Phe Leu Leu Phe Phe His Thr Arg Lys Ser Leu Leu Ala Phe Ile Ala Phe Leu Leu Phe 980 985 990 980 985 990

Ala Phe Val Ile Ser Leu Ser Leu Ile Phe Tyr Tyr Ser Lys Lys Gly Ala Phe Val Ile Ser Leu Ser Leu Ile Phe Tyr Tyr Ser Lys Lys Gly 995 1000 1005 995 1000 1005

Arg Arg Gly Tyr Lys Arg Arg Gly Tyr Lys 1010 1010

<210> 117 <210> 117 <211> 1010 <211> 1010 <212> PRT <212> PRT <213> Ovis aries <213> Ovis aries

<220> <220> <221> misc_feature <221> misc_feature <222> (63)..(63) <222> (63)- (63) <223> Xaa can be any naturally occurring amino acid <223> Xaa can be any naturally occurring amino acid

<400> 117 <400> 117

Met Pro Ala Arg Ala Arg Arg Ala Leu Gly Pro Ser Arg Leu Pro Ala Met Pro Ala Arg Ala Arg Arg Ala Leu Gly Pro Ser Arg Leu Pro Ala 1 5 10 15 1 5 10 15

Ala Ala Ala Arg Leu Trp Leu Leu Leu Pro Gly Leu Gly Arg Pro Ala Ala Ala Ala Arg Leu Trp Leu Leu Leu Pro Gly Leu Gly Arg Pro Ala Page 375 Page 375

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 20 25 30 20 25 30

Leu Arg Ala Arg Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ala Leu Arg Ala Arg Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ala 35 40 45 35 40 45

Arg Pro Pro Asn Pro Arg Gly Arg Gly Leu Leu His Asp Thr Xaa Pro Arg Pro Pro Asn Pro Arg Gly Arg Gly Leu Leu His Asp Thr Xaa Pro 50 55 60 50 55 60

Asp Gly Phe Ser Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Asp Gly Phe Ser Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly 65 70 75 80 70 75 80

Gly Trp Gln Gln His Gly Lys Gly Ala Ser His Leu Gly His Val His Gly Trp Gln Gln His Gly Lys Gly Ala Ser His Leu Gly His Val His 85 90 95 85 90 95

His Arg Pro Pro Ala Pro Pro Gly Asp Pro Ser Arg Pro Gly Trp Pro His Arg Pro Pro Ala Pro Pro Gly Asp Pro Ser Arg Pro Gly Trp Pro 100 105 110 100 105 110

Ser Gly Ala Pro Ser Pro Pro Pro Arg Pro Pro Ser Gly Asp Val Ala Ser Gly Ala Pro Ser Pro Pro Pro Arg Pro Pro Ser Gly Asp Val Ala 115 120 125 115 120 125

Ser Asp Gly Tyr Asn Asn Val Phe Arg Asp Thr Glu Gly Leu Arg Glu Ser Asp Gly Tyr Asn Asn Val Phe Arg Asp Thr Glu Gly Leu Arg Glu 130 135 140 130 135 140

Leu Gly Val Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Leu Gly Val Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu 145 150 155 160 145 150 155 160

Pro Asn Gly Ser Ala Ser Ala Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Pro Asn Gly Ser Ala Ser Ala Pro Asn Arg Glu Gly Leu Arg Tyr Tyr 165 170 175 165 170 175

Arg Arg Leu Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Arg Arg Leu Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val 180 185 190 180 185 190

Thr Leu Ser His Trp Ala Leu Pro Gln Leu Leu Gln Asp Ala Tyr Gly Thr Leu Ser His Trp Ala Leu Pro Gln Leu Leu Gln Asp Ala Tyr Gly 195 200 205 195 200 205

Gly Trp Ala Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Gly Trp Ala Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu 210 215 220 210 215 220

Leu Cys Phe Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Leu Cys Phe Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Page 376 Page 376

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 225 230 235 240 225 230 235 240

Asp Asn Pro Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Asp Asn Pro Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu 245 250 255 245 250 255

Ala Pro Gly Gly Arg Gly Ser Pro Arg Leu His Asn Leu Leu Leu Ala Ala Pro Gly Gly Arg Gly Ser Pro Arg Leu His Asn Leu Leu Leu Ala 260 265 270 260 265 270

His Ala Lys Ile Trp His Leu Tyr Asp Thr Ser Phe Arg Pro Thr Gln His Ala Lys Ile Trp His Leu Tyr Asp Thr Ser Phe Arg Pro Thr Gln 275 280 285 275 280 285

Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Ser Pro Arg Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Ser Pro Arg 290 295 300 290 295 300

Arg Met Thr Glu His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Arg Met Thr Glu His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe 305 310 315 320 305 310 315 320

Val Leu Gly Trp Phe Ala Lys Pro Ile Phe Ile Asp Gly Asp Tyr Pro Val Leu Gly Trp Phe Ala Lys Pro Ile Phe Ile Asp Gly Asp Tyr Pro 325 330 335 325 330 335

Glu Ser Met Lys Asn Asn Leu Ser Ser Leu Leu Pro Asp Phe Thr Glu Glu Ser Met Lys Asn Asn Leu Ser Ser Leu Leu Pro Asp Phe Thr Glu 340 345 350 340 345 350

Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Ser Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Ser 355 360 365 355 360 365

Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro Gln Met Lys Phe Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro Gln Met Lys Phe 370 375 380 370 375 380

Arg Gln Leu Glu Ser Pro Ser Leu Arg Gln Leu Leu Ser Trp Ile Asp Arg Gln Leu Glu Ser Pro Ser Leu Arg Gln Leu Leu Ser Trp Ile Asp 385 390 395 400 385 390 395 400

Leu Glu Tyr Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Leu Glu Tyr Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe 405 410 415 405 410 415

Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu 420 425 430 420 425 430

Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Arg Leu Asp Gly Val Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Arg Leu Asp Gly Val Page 377 Page 377

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 435 440 445 435 440 445

Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp 450 455 460 450 455 460

His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu 465 470 475 480 465 470 475 480

Ser Gln Asp Lys Lys Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Ser Gln Asp Lys Lys Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln 485 490 495 485 490 495

Lys Leu Ile Glu Asn Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Lys Leu Ile Glu Asn Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro 500 505 510 500 505 510

Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn 515 520 525 515 520 525

Cys Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Ile Asp Pro Asn Val Cys Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Ile Asp Pro Asn Val 530 535 540 530 535 540

Tyr Leu Trp Asp Val His Arg Ser Lys Arg Leu Ile Lys Val Asp Gly Tyr Leu Trp Asp Val His Arg Ser Lys Arg Leu Ile Lys Val Asp Gly 545 550 555 560 545 550 555 560

Val Leu Thr Lys Thr Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Ile Val Leu Thr Lys Thr Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Ile 565 570 575 565 570 575

Arg Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe His Arg Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Phe His 580 585 590 580 585 590

Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Arg Ser Gln Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Arg Ser Gln 595 600 605 595 600 605

Val Asn Arg Thr Val Leu Gly Phe Tyr Arg Cys Val Ala Ser Glu Leu Val Asn Arg Thr Val Leu Gly Phe Tyr Arg Cys Val Ala Ser Glu Leu 610 615 620 610 615 620

Val Arg Ala Asn Ile Thr Pro Val Val Ala Leu Trp Arg Pro Ala Ala Val Arg Ala Asn Ile Thr Pro Val Val Ala Leu Trp Arg Pro Ala Ala 625 630 635 640 625 630 635 640

Pro His Gln Gly Leu Pro Ala Pro Leu Ala Arg His Gly Ala Trp Glu Pro His Gln Gly Leu Pro Ala Pro Leu Ala Arg His Gly Ala Trp Glu Page 378 Page 378

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 645 650 655 645 650 655

Asn Pro His Thr Ala Leu Ala Phe Ala Glu Tyr Ala Ser Leu Cys Phe Asn Pro His Thr Ala Leu Ala Phe Ala Glu Tyr Ala Ser Leu Cys Phe 660 665 670 660 665 670

Gln Asp Leu Gly Arg His Val Lys Phe Trp Ile Thr Met His Glu Pro Gln Asp Leu Gly Arg His Val Lys Phe Trp Ile Thr Met His Glu Pro 675 680 685 675 680 685

Ser Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Ala Ser Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Lys Ala 690 695 700 690 695 700

His Ala Leu Ala Trp Arg Thr Tyr Asp Glu Arg Phe Arg Arg Ser Gln His Ala Leu Ala Trp Arg Thr Tyr Asp Glu Arg Phe Arg Arg Ser Gln 705 710 715 720 705 710 715 720

Lys Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Ala Lys Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Ala 725 730 735 725 730 735

Cys Pro Phe Ser Pro Glu Asp Arg Glu Val Ala Glu Arg Val Leu Glu Cys Pro Phe Ser Pro Glu Asp Arg Glu Val Ala Glu Arg Val Leu Glu 740 745 750 740 745 750

Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Tyr Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Tyr 755 760 765 755 760 765

Pro Arg Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu Leu Pro Arg Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu Leu 770 775 780 770 775 780

Pro Tyr Phe Thr Asp Glu Glu Lys Lys Leu Ile Arg Gly Ser Phe Asp Pro Tyr Phe Thr Asp Glu Glu Lys Lys Leu Ile Arg Gly Ser Phe Asp 785 790 795 800 785 790 795 800

Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Trp Glu Lys Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Trp Glu Lys 805 810 815 805 810 815

Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Ala Val Gln Glu Met Thr Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Ala Val Gln Glu Met Thr 820 825 830 820 825 830

Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Trp Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Trp 835 840 845 835 840 845

Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Ala Lys Tyr Gly Asp Leu Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Ala Lys Tyr Gly Asp Leu Page 379 Page 379

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 850 855 860 850 855 860

Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Asp Pro His Ala Ala Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Asp Pro His Ala Ala 865 870 875 880 865 870 875 880

Gln Asp Asn Leu Arg Val Tyr Tyr Met Gln Asn Tyr Val Asn Glu Ala Gln Asp Asn Leu Arg Val Tyr Tyr Met Gln Asn Tyr Val Asn Glu Ala 885 890 895 885 890 895

Leu Lys Ala Tyr Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe Ala Leu Lys Ala Tyr Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe Ala 900 905 910 900 905 910

Tyr Ser Phe Asn Asp Arg Thr Ala Pro Lys Phe Gly Leu Tyr Arg Tyr Tyr Ser Phe Asn Asp Arg Thr Ala Pro Lys Phe Gly Leu Tyr Arg Tyr 915 920 925 915 920 925

Ala Ala Asn Gln Phe Glu Pro Lys Pro Ser Met Lys His Tyr Arg Lys Ala Ala Asn Gln Phe Glu Pro Lys Pro Ser Met Lys His Tyr Arg Lys 930 935 940 930 935 940

Ile Ile Asp Asn Asn Gly Phe Pro Gly Pro Glu Thr Leu Gly Arg Phe Ile Ile Asp Asn Asn Gly Phe Pro Gly Pro Glu Thr Leu Gly Arg Phe 945 950 955 960 945 950 955 960

Cys Pro Glu Glu Phe Thr Leu Cys Thr Glu Cys Ser Phe Phe His Ala Cys Pro Glu Glu Phe Thr Leu Cys Thr Glu Cys Ser Phe Phe His Ala 965 970 975 965 970 975

Arg Lys Ser Leu Leu Ala Phe Ile Ala Phe Leu Leu Phe Ala Phe Val Arg Lys Ser Leu Leu Ala Phe Ile Ala Phe Leu Leu Phe Ala Phe Val 980 985 990 980 985 990

Ile Ser Leu Ser Leu Ile Phe Tyr Tyr Ser Lys Lys Gly Arg Arg Gly Ile Ser Leu Ser Leu Ile Phe Tyr Tyr Ser Lys Lys Gly Arg Arg Gly 995 1000 1005 995 1000 1005

Tyr Lys Tyr Lys 1010 1010

<210> 118 <210> 118 <211> 983 <211> 983 <212> PRT <212> PRT <213> Equus caballus <213> Equus caballus

<220> <220> <221> misc_feature <221> misc_feature <222> (38)..(38) <222> (38)- (38) Page 380 Page 380

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing TXT <223> Xaa can be any naturally occurring amino acid <223> Xaa can be any naturally occurring amino acid

<400> 118 <400> 118

Met Ser Arg Lys Thr Arg Arg Ala Trp Gly Ser Pro Val His Leu Ser Met Ser Arg Lys Thr Arg Arg Ala Trp Gly Ser Pro Val His Leu Ser 1 5 10 15 1 5 10 15

Ala Arg Ser Pro Ala Pro Glu Pro Arg Gly Leu Leu Thr Ala Ser Phe Ala Arg Ser Pro Ala Pro Glu Pro Arg Gly Leu Leu Thr Ala Ser Phe 20 25 30 20 25 30

Pro Asp Gly Phe Leu Xaa Ala Val Ser Ser Ala Ala Tyr Gln Thr Glu Pro Asp Gly Phe Leu Xaa Ala Val Ser Ser Ala Ala Tyr Gln Thr Glu 35 40 45 35 40 45

Gly Gly Trp Arg Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Gly Gly Trp Arg Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe 50 55 60 50 55 60

Thr His His Pro Pro Ala Thr Pro Gly Gly Pro Gln Leu Ser Gly Leu Thr His His Pro Pro Ala Thr Pro Gly Gly Pro Gln Leu Ser Gly Leu 65 70 75 80 70 75 80

Pro Ser Gly Gly Pro Ser Pro Ser Pro Leu Ala Thr Gly Asp Val Ala Pro Ser Gly Gly Pro Ser Pro Ser Pro Leu Ala Thr Gly Asp Val Ala 85 90 95 85 90 95

Ser Asp Gly Tyr Asn Asn Val Phe Arg Asp Thr Glu Gly Leu Arg Glu Ser Asp Gly Tyr Asn Asn Val Phe Arg Asp Thr Glu Gly Leu Arg Glu 100 105 110 100 105 110

Leu Gly Val Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Leu Gly Val Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu 115 120 125 115 120 125

Pro Asn Gly Ser Ala Gly Ala Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Pro Asn Gly Ser Ala Gly Ala Pro Asn Arg Glu Gly Leu Arg Tyr Tyr 130 135 140 130 135 140

Arg Arg Leu Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Arg Arg Leu Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val 145 150 155 160 145 150 155 160

Thr Leu Tyr His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Thr Leu Tyr His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly 165 170 175 165 170 175

Gly Trp Ala Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Gly Trp Ala Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu 180 185 190 180 185 190

Page 381 Page 381

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Leu Cys Phe Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Leu Cys Phe Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile 195 200 205 195 200 205

Asp Asn Pro Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Asp Asn Pro Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu 210 215 220 210 215 220

Ala Pro Gly Val Arg Gly Ser Pro Gln Leu Gly Tyr Leu Val Ala His Ala Pro Gly Val Arg Gly Ser Pro Gln Leu Gly Tyr Leu Val Ala His 225 230 235 240 225 230 235 240

Asn Leu Leu Leu Ala His Ala Lys Ile Trp His Leu Tyr Asn Thr Ser Asn Leu Leu Leu Ala His Ala Lys Ile Trp His Leu Tyr Asn Thr Ser 245 250 255 245 250 255

Phe Arg Pro Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Phe Arg Pro Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His 260 265 270 260 265 270

Trp Ile Asn Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Trp Ile Asn Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln 275 280 285 275 280 285

Lys Ser Leu Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Ile Phe Ile Lys Ser Leu Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Ile Phe Ile 290 295 300 290 295 300

Asp Gly Asp Tyr Pro Glu Thr Met Lys Asn Asn Leu Ser Ser Leu Leu Asp Gly Asp Tyr Pro Glu Thr Met Lys Asn Asn Leu Ser Ser Leu Leu 305 310 315 320 305 310 315 320

Pro Asp Phe Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Pro Asp Phe Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp 325 330 335 325 330 335

Phe Phe Ala Leu Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Phe Phe Ala Leu Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp 340 345 350 340 345 350

Pro His Met Lys Phe Arg Gln Leu Glu Ser Pro Ser Leu Arg Gln Leu Pro His Met Lys Phe Arg Gln Leu Glu Ser Pro Ser Leu Arg Gln Leu 355 360 365 355 360 365

Leu Ser Trp Ile Asp Leu Glu Tyr Asn His Pro Gln Ile Phe Ile Val Leu Ser Trp Ile Asp Leu Glu Tyr Asn His Pro Gln Ile Phe Ile Val 370 375 380 370 375 380

Glu Asn Gly Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Glu Asn Gly Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys 385 390 395 400 385 390 395 400

Page 382 Page 382

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. - TXT Tyr Met Tyr Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Tyr Met Tyr Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile 405 410 415 405 410 415

Arg Leu Asp Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Arg Leu Asp Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met 420 425 430 420 425 430

Asp Gly Phe Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Asp Gly Phe Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe 435 440 445 435 440 445

Tyr Val Asp Phe Leu Ser Gln Asp Lys Lys Leu Leu Pro Lys Ser Ser Tyr Val Asp Phe Leu Ser Gln Asp Lys Lys Leu Leu Pro Lys Ser Ser 450 455 460 450 455 460

Ala Leu Phe Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Ala Leu Phe Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu 465 470 475 480 465 470 475 480

Pro Glu Asn Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Pro Glu Asn Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp 485 490 495 485 490 495

Gly Val Val Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Gly Val Val Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe 500 505 510 500 505 510

Thr Asp Pro Asn Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Thr Asp Pro Asn Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu 515 520 525 515 520 525

Ile Lys Val Asp Gly Leu Val Ala Lys Lys Arg Thr Ser Tyr Cys Val Ile Lys Val Asp Gly Leu Val Ala Lys Lys Arg Thr Ser Tyr Cys Val 530 535 540 530 535 540

Asp Phe Ala Ala Ile Arg Pro Gln Ile Ala Leu Leu Gln Glu Met His Asp Phe Ala Ala Ile Arg Pro Gln Ile Ala Leu Leu Gln Glu Met His 545 550 555 560 545 550 555 560

Val Ser His Phe His Phe Ala Leu Asp Trp Pro Leu Ile Leu Pro Leu Val Ser His Phe His Phe Ala Leu Asp Trp Pro Leu Ile Leu Pro Leu 565 570 575 565 570 575

Gly Asn Gln Ser Gln Val Asn Arg Thr Gly Leu His Tyr Tyr Arg Cys Gly Asn Gln Ser Gln Val Asn Arg Thr Gly Leu His Tyr Tyr Arg Cys 580 585 590 580 585 590

Val Val Ser Glu Leu Val Arg Ala Asn Ile Thr Pro Val Val Ala Leu Val Val Ser Glu Leu Val Arg Ala Asn Ile Thr Pro Val Val Ala Leu 595 600 605 595 600 605

Page 383 Page 383

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Trp Arg Pro Ser Pro Gln His Gln Gly Leu Pro Arg Leu Leu Ala Lys Trp Arg Pro Ser Pro Gln His Gln Gly Leu Pro Arg Leu Leu Ala Lys 610 615 620 610 615 620

His Gly Ala Trp Glu Asn Pro His Thr Ala Leu Ala Phe Ala Glu Tyr His Gly Ala Trp Glu Asn Pro His Thr Ala Leu Ala Phe Ala Glu Tyr 625 630 635 640 625 630 635 640

Ala Arg Leu Cys Phe Gln Glu Leu Gly His His Val Lys Phe Trp Ile Ala Arg Leu Cys Phe Gln Glu Leu Gly His His Val Lys Phe Trp Ile 645 650 655 645 650 655

Thr Met Ser Glu Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Thr Met Ser Glu Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His 660 665 670 660 665 670

Asn Leu Leu Lys Ala His Ala Leu Ala Trp Arg Val Tyr Asp Asp Lys Asn Leu Leu Lys Ala His Ala Leu Ala Trp Arg Val Tyr Asp Asp Lys 675 680 685 675 680 685

Phe Arg His Ala Gln Lys Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Phe Arg His Ala Gln Lys Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp 690 695 700 690 695 700

Trp Ile Glu Pro Ala Cys Pro Phe Ser Gln Gln Asp Lys Glu Gly Ala Trp Ile Glu Pro Ala Cys Pro Phe Ser Gln Gln Asp Lys Glu Gly Ala 705 710 715 720 705 710 715 720

Glu Arg Val Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Glu Arg Val Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe 725 730 735 725 730 735

Gly Ser Gly Asp Tyr Pro Pro Val Met Arg Asp Trp Leu Asn Gln Arg Gly Ser Gly Asp Tyr Pro Pro Val Met Arg Asp Trp Leu Asn Gln Arg 740 745 750 740 745 750

Asn Asn Phe Leu Leu Pro Tyr Phe Ser Glu Glu Glu Lys Lys Leu Ile Asn Asn Phe Leu Leu Pro Tyr Phe Ser Glu Glu Glu Lys Lys Leu Ile 755 760 765 755 760 765

Arg Gly Ser Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Arg Gly Ser Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu 770 775 780 770 775 780

Val Asp Trp Glu Lys Glu Asp Pro Met Lys Tyr Asn Asp Tyr Leu Glu Val Asp Trp Glu Lys Glu Asp Pro Met Lys Tyr Asn Asp Tyr Leu Glu 785 790 795 800 785 790 795 800

Val Gln Glu Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Val Gln Glu Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val 805 810 815 805 810 815

Page 384 Page 384

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Ala Val Val Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Ser Ala Val Val Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Ser 820 825 830 820 825 830

Lys Tyr Gly Asp Leu Pro Met Tyr Ile Ile Ala Asn Gly Ile Asp Asp Lys Tyr Gly Asp Leu Pro Met Tyr Ile Ile Ala Asn Gly Ile Asp Asp 835 840 845 835 840 845

Asp Pro Gln Glu Ala Gln Asp Arg Leu Arg Val Tyr Tyr Met Gln Asn Asp Pro Gln Glu Ala Gln Asp Arg Leu Arg Val Tyr Tyr Met Gln Asn 850 855 860 850 855 860

Tyr Val Asn Glu Ala Leu Lys Ala Tyr Val Leu Asp Gly Ile Asn Leu Tyr Val Asn Glu Ala Leu Lys Ala Tyr Val Leu Asp Gly Ile Asn Leu 865 870 875 880 865 870 875 880

Cys Gly Tyr Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Lys Phe Cys Gly Tyr Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Lys Phe 885 890 895 885 890 895

Gly Leu Tyr Arg Tyr Ala Ala Asn Gln Phe Glu Pro Lys Pro Ser Met Gly Leu Tyr Arg Tyr Ala Ala Asn Gln Phe Glu Pro Lys Pro Ser Met 900 905 910 900 905 910

Lys His Tyr Arg Lys Ile Ile Asp Asn Asn Gly Phe Pro Gly Pro Lys Lys His Tyr Arg Lys Ile Ile Asp Asn Asn Gly Phe Pro Gly Pro Lys 915 920 925 915 920 925

Thr Leu Gly Arg Phe Cys Pro Glu Glu Phe Thr Leu Cys Thr Glu Cys Thr Leu Gly Arg Phe Cys Pro Glu Glu Phe Thr Leu Cys Thr Glu Cys 930 935 940 930 935 940

Ser Phe Phe His Thr Arg Lys Ser Leu Leu Ala Phe Ile Ala Phe Leu Ser Phe Phe His Thr Arg Lys Ser Leu Leu Ala Phe Ile Ala Phe Leu 945 950 955 960 945 950 955 960

Leu Phe Ala Phe Ile Ile Ser Leu Ser Leu Ile Phe Tyr Tyr Ser Lys Leu Phe Ala Phe Ile Ile Ser Leu Ser Leu Ile Phe Tyr Tyr Ser Lys 965 970 975 965 970 975

Lys Gly Arg Arg Asn Tyr Lys Lys Gly Arg Arg Asn Tyr Lys 980 980

<210> 119 <210> 119 <211> 1005 <211> 1005 <212> PRT <212> PRT <213> Oryctolagus cuniculus <213> Oryctolagus cuniculus

<400> 119 <400> 119

Met Pro Val Arg Ala Arg Pro Leu Gln Leu Arg Leu Arg Leu Leu Leu Met Pro Val Arg Ala Arg Pro Leu Gln Leu Arg Leu Arg Leu Leu Leu Page 385 Page 385

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing TXT 1 5 10 15 1 5 10 15

Leu Ala Leu Val Gly Arg Leu Leu Arg Ala Glu Pro Gly Asp Gly Ala Leu Ala Leu Val Gly Arg Leu Leu Arg Ala Glu Pro Gly Asp Gly Ala 20 25 30 20 25 30

Gln Thr Trp Val Arg Phe Ala Arg Pro Pro Val Pro Asp Ala Ala Gly Gln Thr Trp Val Arg Phe Ala Arg Pro Pro Val Pro Asp Ala Ala Gly 35 40 45 35 40 45

Leu Leu His Asp Thr Phe Pro Asp Gly Phe Leu Trp Ala Val Gly Ser Leu Leu His Asp Thr Phe Pro Asp Gly Phe Leu Trp Ala Val Gly Ser 50 55 60 50 55 60

Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Gln His Gly Lys Gly Glu Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Gln His Gly Lys Gly Glu 65 70 75 80 70 75 80

Ser Ile Trp Asp Thr Phe Thr His His Pro Pro Ala Pro Leu Gly Asp Ser Ile Trp Asp Thr Phe Thr His His Pro Pro Ala Pro Leu Gly Asp 85 90 95 85 90 95

Leu Ser Ile Thr Pro Leu Pro Ser Gly Thr Pro Ser Ala Pro Pro Ala Leu Ser Ile Thr Pro Leu Pro Ser Gly Thr Pro Ser Ala Pro Pro Ala 100 105 110 100 105 110

Ala Thr Gly Asp Val Ala Ser Asp Gly Tyr Asn Asn Val Leu Arg Asp Ala Thr Gly Asp Val Ala Ser Asp Gly Tyr Asn Asn Val Leu Arg Asp 115 120 125 115 120 125

Thr Glu Gly Leu Arg Glu Leu Gly Val Thr His Tyr Arg Phe Ser Ile Thr Glu Gly Leu Arg Glu Leu Gly Val Thr His Tyr Arg Phe Ser Ile 130 135 140 130 135 140

Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala Ser Ala Pro Asn Arg Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala Ser Ala Pro Asn Arg 145 150 155 160 145 150 155 160

Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu Arg Leu Arg Glu Leu Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu Arg Leu Arg Glu Leu 165 170 175 165 170 175

Gly Val Gln Pro Val Val Thr Leu Tyr His Trp Asp Leu Pro Gln Arg Gly Val Gln Pro Val Val Thr Leu Tyr His Trp Asp Leu Pro Gln Arg 180 185 190 180 185 190

Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Pro Ser Leu Ala Asp His Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Pro Ser Leu Ala Asp His 195 200 205 195 200 205

Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His Phe Gly Ser Gln Val Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His Phe Gly Ser Gln Val Page 386 Page 386

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 210 215 220 210 215 220

Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val Val Ala Trp His Gly Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val Val Ala Trp His Gly 225 230 235 240 225 230 235 240

Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg Gly Gly Ala Arg Leu Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg Gly Gly Ala Arg Leu 245 250 255 245 250 255

Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala His Ala Lys Ile Trp Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala His Ala Lys Ile Trp 260 265 270 260 265 270

His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln Gly Gly Gln Val Ser His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln Gly Gly Gln Val Ser 275 280 285 275 280 285

Ile Ala Leu Gly Ser His Trp Ile Ile Pro Arg Arg Arg Thr Asp His Ile Ala Leu Gly Ser His Trp Ile Ile Pro Arg Arg Arg Thr Asp His 290 295 300 290 295 300

Asn Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Val Leu Gly Trp Phe Asn Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Val Leu Gly Trp Phe 305 310 315 320 305 310 315 320

Ala Arg Pro Ile Phe Ile Asp Gly Asp Tyr Pro Glu Ser Met Lys Asn Ala Arg Pro Ile Phe Ile Asp Gly Asp Tyr Pro Glu Ser Met Lys Asn 325 330 335 325 330 335

Asn Leu Ser Ser Leu Leu Pro Asp Phe Thr Glu Ala Glu Lys Lys Phe Asn Leu Ser Ser Leu Leu Pro Asp Phe Thr Glu Ala Glu Lys Lys Phe 340 345 350 340 345 350

Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Ser Phe Gly Pro Thr Leu Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Ser Phe Gly Pro Thr Leu 355 360 365 355 360 365

Ser Phe Gln Leu Leu Asp Pro Gln Met Lys Phe Arg Gln Leu Glu Ser Ser Phe Gln Leu Leu Asp Pro Gln Met Lys Phe Arg Gln Leu Glu Ser 370 375 380 370 375 380

Pro Ser Leu Arg Gln Leu Leu Ser Trp Ile Ala Leu Glu Tyr Asn His Pro Ser Leu Arg Gln Leu Leu Ser Trp Ile Ala Leu Glu Tyr Asn His 385 390 395 400 385 390 395 400

Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Val Ser Gly Thr Thr Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Val Ser Gly Thr Thr 405 410 415 405 410 415

Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Lys Lys Phe Ile Met Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Lys Lys Phe Ile Met Page 387 Page 387

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 420 425 430 420 425 430

Glu Thr Leu Lys Ala Ile Arg Leu Asp Gly Val Asp Val Ile Gly Tyr Glu Thr Leu Lys Ala Ile Arg Leu Asp Gly Val Asp Val Ile Gly Tyr 435 440 445 435 440 445

Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp His Arg Gly Tyr Asn Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp His Arg Gly Tyr Asn 450 455 460 450 455 460

Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu Ser Gln Asp Lys Lys Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu Ser Gln Asp Lys Lys 465 470 475 480 465 470 475 480

Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys Leu Ile Glu Lys Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys Leu Ile Glu Lys 485 490 495 485 490 495

Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu Glu Gly Thr Phe Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu Glu Gly Thr Phe 500 505 510 500 505 510

Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Tyr Ile Gln Val Asp Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Tyr Ile Gln Val Asp 515 520 525 515 520 525

Thr Thr Leu Ser Gln Phe Thr Asp Pro Asn Val Tyr Leu Trp Asp Val Thr Thr Leu Ser Gln Phe Thr Asp Pro Asn Val Tyr Leu Trp Asp Val 530 535 540 530 535 540

His His Ser Lys Arg Leu Ile Lys Leu Asp Gly Val Val Ser Arg Lys His His Ser Lys Arg Leu Ile Lys Leu Asp Gly Val Val Ser Arg Lys 545 550 555 560 545 550 555 560

Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Ile Arg Ser Gln Ile Val Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Ile Arg Ser Gln Ile Val 565 570 575 565 570 575

Leu Leu Gln Glu Thr His Val Thr His Phe His Phe Ser Leu Asp Trp Leu Leu Gln Glu Thr His Val Thr His Phe His Phe Ser Leu Asp Trp 580 585 590 580 585 590

Ala Leu Val Leu Pro Leu Gly Asn Gln Ser Gln Val Asn Arg Thr Val Ala Leu Val Leu Pro Leu Gly Asn Gln Ser Gln Val Asn Arg Thr Val 595 600 605 595 600 605

Leu Arg Tyr Tyr Arg Cys Val Val Glu Glu Leu Val Arg Ala Asn Ile Leu Arg Tyr Tyr Arg Cys Val Val Glu Glu Leu Val Arg Ala Asn Ile 610 615 620 610 615 620

Thr Pro Val Val Ala Leu Trp Gln Pro Ala Ala Pro His Gln Gly Leu Thr Pro Val Val Ala Leu Trp Gln Pro Ala Ala Pro His Gln Gly Leu Page 388 Page 388

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 625 630 635 640 625 630 635 640

Pro Gln Pro Leu Ala Gln Gln Gly Ala Trp Glu Asn Pro His Thr Val Pro Gln Pro Leu Ala Gln Gln Gly Ala Trp Glu Asn Pro His Thr Val 645 650 655 645 650 655

Leu Ala Phe Val Glu Tyr Ala Arg Leu Cys Phe Met Glu Leu Gly His Leu Ala Phe Val Glu Tyr Ala Arg Leu Cys Phe Met Glu Leu Gly His 660 665 670 660 665 670

Arg Ile Lys Phe Trp Ile Thr Met Asn Glu Pro Asn Thr Arg Asn Met Arg Ile Lys Phe Trp Ile Thr Met Asn Glu Pro Asn Thr Arg Asn Met 675 680 685 675 680 685

Thr Tyr Arg Ala Gly His His Leu Leu Lys Ala His Ala Leu Val Trp Thr Tyr Arg Ala Gly His His Leu Leu Lys Ala His Ala Leu Val Trp 690 695 700 690 695 700

Arg Glu Tyr Asp Gly Lys Phe Arg Pro Ala Gln Lys Gly Lys Val Ser Arg Glu Tyr Asp Gly Lys Phe Arg Pro Ala Gln Lys Gly Lys Val Ser 705 710 715 720 705 710 715 720

Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Ala Cys Pro Phe Ser Gln Ile Ala Leu Gln Ala Asp Trp Ile Glu Pro Ala Cys Pro Phe Ser Gln 725 730 735 725 730 735

Lys Asp Lys Glu Val Ala Glu Arg Val Leu Glu Phe Asp Ile Gly Trp Lys Asp Lys Glu Val Ala Glu Arg Val Leu Glu Phe Asp Ile Gly Trp 740 745 750 740 745 750

Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Tyr Pro Arg Val Met Arg Leu Ala Glu Pro Ile Phe Gly Ser Gly Asp Tyr Pro Arg Val Met Arg 755 760 765 755 760 765

Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu Leu Pro Tyr Phe Thr Glu Asp Trp Leu Asn Gln Arg Asn Asn Phe Leu Leu Pro Tyr Phe Thr Glu 770 775 780 770 775 780

Glu Glu Arg Gln Leu Val Arg Gly Ser Phe Asp Phe Leu Ala Leu Ser Glu Glu Arg Gln Leu Val Arg Gly Ser Phe Asp Phe Leu Ala Leu Ser 785 790 795 800 785 790 795 800

His Tyr Thr Thr Ile Leu Val Asp Trp Glu Lys Glu Asp Pro Thr Lys His Tyr Thr Thr Ile Leu Val Asp Trp Glu Lys Glu Asp Pro Thr Lys 805 810 815 805 810 815

Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Thr Asp Ile Thr Trp Leu Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Thr Asp Ile Thr Trp Leu 820 825 830 820 825 830

Asn Ser Pro Gly Gln Val Ala Val Val Pro Trp Gly Leu Arg Lys Val Asn Ser Pro Gly Gln Val Ala Val Val Pro Trp Gly Leu Arg Lys Val Page 389 Page 389

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 835 840 845 835 840 845

Leu Asn Trp Leu Arg Leu Lys Tyr Gly Asp Leu Pro Met Tyr Val Ile Leu Asn Trp Leu Arg Leu Lys Tyr Gly Asp Leu Pro Met Tyr Val Ile 850 855 860 850 855 860

Ala Asn Gly Ile Asp Asp Asp Leu Gln Ala Glu Gln Asp Gln Leu Arg Ala Asn Gly Ile Asp Asp Asp Leu Gln Ala Glu Gln Asp Gln Leu Arg 865 870 875 880 865 870 875 880

Val Tyr Tyr Ile Gln Asn Tyr Val Asn Glu Ala Leu Lys Ala Tyr Met Val Tyr Tyr Ile Gln Asn Tyr Val Asn Glu Ala Leu Lys Ala Tyr Met 885 890 895 885 890 895

Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe Ala Tyr Ser Leu Asn Asp Leu Asp Gly Ile Asn Leu Cys Gly Tyr Phe Ala Tyr Ser Leu Asn Asp 900 905 910 900 905 910

Arg Ser Ala Pro Lys Phe Gly Leu Tyr Arg Tyr Ala Ala Asn Gln Phe Arg Ser Ala Pro Lys Phe Gly Leu Tyr Arg Tyr Ala Ala Asn Gln Phe 915 920 925 915 920 925

Glu Pro Lys Pro Ser Met Lys His Tyr Arg Arg Ile Ile Asp Asn Asn Glu Pro Lys Pro Ser Met Lys His Tyr Arg Arg Ile Ile Asp Asn Asn 930 935 940 930 935 940

Gly Phe Pro Ser Ser Glu Thr Leu Glu Glu Phe Cys Pro Glu Glu Leu Gly Phe Pro Ser Ser Glu Thr Leu Glu Glu Phe Cys Pro Glu Glu Leu 945 950 955 960 945 950 955 960

Ser Lys Cys Ile Glu Cys Ser Phe Phe His Lys Arg Lys Ser Leu Leu Ser Lys Cys Ile Glu Cys Ser Phe Phe His Lys Arg Lys Ser Leu Leu 965 970 975 965 970 975

Ala Phe Ile Ala Phe Leu Phe Phe Ala Phe Ile Ile Ser Leu Ser Leu Ala Phe Ile Ala Phe Leu Phe Phe Ala Phe Ile Ile Ser Leu Ser Leu 980 985 990 980 985 990

Ile Phe Tyr Tyr Ser Lys Lys Gly Arg Arg Ser Tyr Lys Ile Phe Tyr Tyr Ser Lys Lys Gly Arg Arg Ser Tyr Lys 995 1000 1005 995 1000 1005

<210> 120 <210> 120 <211> 1013 <211> 1013 <212> PRT <212> PRT <213> Capra aegagrus <213> Capra aegagrus

<400> 120 <400> 120

Met Pro Ala Arg Ala Pro Pro Arg Arg Leu Arg Ala Leu Pro Pro Pro Met Pro Ala Arg Ala Pro Pro Arg Arg Leu Arg Ala Leu Pro Pro Pro 1 5 10 15 1 5 10 15 Page 390 Page 390

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Pro Pro Pro Leu Trp Leu Leu Leu Leu Ala Leu Gly Gly Arg Pro Leu Pro Pro Pro Leu Trp Leu Leu Leu Leu Ala Leu Gly Gly Arg Pro Leu 20 25 30 20 25 30

Arg Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ala Arg Arg Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ala Arg 35 40 45 35 40 45

Pro Pro Thr Pro Glu Ala Ala Gly Leu Leu His Asp Thr Phe Pro Asp Pro Pro Thr Pro Glu Ala Ala Gly Leu Leu His Asp Thr Phe Pro Asp 50 55 60 50 55 60

Gly Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Gly Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly 65 70 75 80 70 75 80

Trp Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His Trp Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His 85 90 95 85 90 95

Arg Pro Pro Ala Pro Pro Gly Asp Pro Ser Ala Ala Gly Trp Pro Ser Arg Pro Pro Ala Pro Pro Gly Asp Pro Ser Ala Ala Gly Trp Pro Ser 100 105 110 100 105 110

Gly Ala Pro Ser Pro Pro Pro Pro Ala Thr Gly Asp Val Ala Ser Asp Gly Ala Pro Ser Pro Pro Pro Pro Ala Thr Gly Asp Val Ala Ser Asp 115 120 125 115 120 125

Gly Tyr Asn Asn Val Phe Arg Asp Thr Glu Gly Leu Arg Glu Leu Gly Gly Tyr Asn Asn Val Phe Arg Asp Thr Glu Gly Leu Arg Glu Leu Gly 130 135 140 130 135 140

Val Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Val Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn 145 150 155 160 145 150 155 160

Gly Ser Ala Ser Ala Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Gly Ser Ala Ser Ala Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg 165 170 175 165 170 175

Leu Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Leu Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu 180 185 190 180 185 190

Tyr His Trp Asp Leu Pro Gln Leu Leu Gln Asp Ala Tyr Gly Gly Trp Tyr His Trp Asp Leu Pro Gln Leu Leu Gln Asp Ala Tyr Gly Gly Trp 195 200 205 195 200 205

Ala Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Ala Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys 210 215 220 210 215 220 Page 391 Page 391

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Phe Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Phe Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn 225 230 235 240 225 230 235 240

Pro Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Pro Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro 245 250 255 245 250 255

Gly Val Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Gly Val Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu 260 265 270 260 265 270

Leu Leu Ala His Ala Lys Ile Trp His Leu Tyr Asp Thr Ser Phe Arg Leu Leu Ala His Ala Lys Ile Trp His Leu Tyr Asp Thr Ser Phe Arg 275 280 285 275 280 285

Pro Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Pro Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile 290 295 300 290 295 300

Ser Pro Arg Arg Met Thr Glu His Ser Ile Lys Glu Cys Gln Lys Ser Ser Pro Arg Arg Met Thr Glu His Ser Ile Lys Glu Cys Gln Lys Ser 305 310 315 320 305 310 315 320

Leu Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Ile Phe Ile Asp Gly Leu Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Ile Phe Ile Asp Gly 325 330 335 325 330 335

Asp Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Leu Leu Pro Asp Asp Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Leu Leu Pro Asp 340 345 350 340 345 350

Phe Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Phe Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe 355 360 365 355 360 365

Ala Leu Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro Gln Ala Leu Ser Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro Gln 370 375 380 370 375 380

Met Lys Phe Arg Gln Leu Glu Ser Pro Ser Leu Arg Gln Leu Leu Ser Met Lys Phe Arg Gln Leu Glu Ser Pro Ser Leu Arg Gln Leu Leu Ser 385 390 395 400 385 390 395 400

Trp Ile Asp Leu Glu Tyr Asn His Pro Gln Ile Phe Ile Val Glu Asn Trp Ile Asp Leu Glu Tyr Asn His Pro Gln Ile Phe Ile Val Glu Asn 405 410 415 405 410 415

Gly Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Gly Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met 420 425 430 420 425 430 Page 392 Page 392

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Tyr Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Arg Leu Tyr Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Arg Leu 435 440 445 435 440 445

Asp Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Asp Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly 450 455 460 450 455 460

Phe Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Phe Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val 465 470 475 480 465 470 475 480

Asp Phe Leu Ser Gln Asp Lys Lys Leu Leu Pro Lys Ser Ser Ala Leu Asp Phe Leu Ser Gln Asp Lys Lys Leu Leu Pro Lys Ser Ser Ala Leu 485 490 495 485 490 495

Phe Tyr Gln Lys Leu Ile Glu Asn Asn Gly Phe Pro Pro Leu Pro Glu Phe Tyr Gln Lys Leu Ile Glu Asn Asn Gly Phe Pro Pro Leu Pro Glu 500 505 510 500 505 510

Asn Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Asn Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val 515 520 525 515 520 525

Val Asp Asn Cys Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Ile Asp Val Asp Asn Cys Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Ile Asp 530 535 540 530 535 540

Pro Asn Val Tyr Leu Trp Asp Val His Arg Ser Lys Arg Leu Ile Lys Pro Asn Val Tyr Leu Trp Asp Val His Arg Ser Lys Arg Leu Ile Lys 545 550 555 560 545 550 555 560

Val Asp Gly Val Leu Thr Lys Thr Arg Lys Ser Tyr Cys Val Asp Phe Val Asp Gly Val Leu Thr Lys Thr Arg Lys Ser Tyr Cys Val Asp Phe 565 570 575 565 570 575

Ala Ala Ile Arg Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr Ala Ala Ile Arg Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr 580 585 590 580 585 590

His Phe His Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn His Phe His Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn 595 600 605 595 600 605

Arg Ser Gln Val Asn Arg Thr Val Leu Gly Phe Tyr Arg Cys Val Ala Arg Ser Gln Val Asn Arg Thr Val Leu Gly Phe Tyr Arg Cys Val Ala 610 615 620 610 615 620

Ser Glu Leu Val Arg Ala Asn Ile Thr Pro Val Val Ala Leu Trp Arg Ser Glu Leu Val Arg Ala Asn Ile Thr Pro Val Val Ala Leu Trp Arg 625 630 635 640 625 630 635 640 Page 393 Page 393

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Pro Ala Ala Pro His Gln Gly Leu Pro Ala Pro Leu Ala Arg His Gly Pro Ala Ala Pro His Gln Gly Leu Pro Ala Pro Leu Ala Arg His Gly 645 650 655 645 650 655

Ala Trp Glu Asn Pro His Thr Ala Leu Ala Phe Ala Glu Tyr Ala Ser Ala Trp Glu Asn Pro His Thr Ala Leu Ala Phe Ala Glu Tyr Ala Ser 660 665 670 660 665 670

Leu Cys Phe Gln Asp Leu Gly Arg His Val Lys Phe Trp Ile Thr Met Leu Cys Phe Gln Asp Leu Gly Arg His Val Lys Phe Trp Ile Thr Met 675 680 685 675 680 685

His Glu Pro Ser Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu His Glu Pro Ser Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu 690 695 700 690 695 700

Leu Lys Ala His Ala Leu Ala Trp Arg Thr Tyr Asp Glu Arg Phe Arg Leu Lys Ala His Ala Leu Ala Trp Arg Thr Tyr Asp Glu Arg Phe Arg 705 710 715 720 705 710 715 720

Arg Ser Gln Lys Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Arg Ser Gln Lys Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile 725 730 735 725 730 735

Glu Pro Ala Cys Pro Phe Ser Pro Glu Asp Arg Glu Val Ala Glu Arg Glu Pro Ala Cys Pro Phe Ser Pro Glu Asp Arg Glu Val Ala Glu Arg 740 745 750 740 745 750

Val Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Val Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser 755 760 765 755 760 765

Gly Asp Tyr Pro Arg Val Met Arg Glu Trp Leu Asn Gln Arg Asn Asn Gly Asp Tyr Pro Arg Val Met Arg Glu Trp Leu Asn Gln Arg Asn Asn 770 775 780 770 775 780

Phe Leu Leu Pro Tyr Phe Thr Asp Glu Glu Lys Lys Leu Ile Arg Gly Phe Leu Leu Pro Tyr Phe Thr Asp Glu Glu Lys Lys Leu Ile Arg Gly 785 790 795 800 785 790 795 800

Ser Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp 805 810 815 805 810 815

Trp Glu Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Ala Val Gln Trp Glu Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Ala Val Gln 820 825 830 820 825 830

Glu Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Glu Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val 835 840 845 835 840 845 Page 394 Page 394

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Val Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Ala Lys Tyr Val Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Ala Lys Tyr 850 855 860 850 855 860

Gly Asp Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Asp Pro Gly Asp Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Asp Pro 865 870 875 880 865 870 875 880

His Thr Ala Gln Asp Asn Leu Arg Val Tyr Tyr Met Gln Asn Tyr Val His Thr Ala Gln Asp Asn Leu Arg Val Tyr Tyr Met Gln Asn Tyr Val 885 890 895 885 890 895

Asn Glu Ala Leu Lys Ala Tyr Ile Leu Asp Gly Ile Asn Leu Cys Gly Asn Glu Ala Leu Lys Ala Tyr Ile Leu Asp Gly Ile Asn Leu Cys Gly 900 905 910 900 905 910

Tyr Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Lys Phe Gly Leu Tyr Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Lys Phe Gly Leu 915 920 925 915 920 925

Tyr Arg Tyr Ala Ala Asn Gln Phe Glu Pro Lys Pro Ser Met Lys His Tyr Arg Tyr Ala Ala Asn Gln Phe Glu Pro Lys Pro Ser Met Lys His 930 935 940 930 935 940

Tyr Arg Lys Ile Ile Asp Asn Asn Gly Phe Pro Gly Pro Glu Thr Leu Tyr Arg Lys Ile Ile Asp Asn Asn Gly Phe Pro Gly Pro Glu Thr Leu 945 950 955 960 945 950 955 960

Gly Arg Phe Cys Pro Glu Glu Phe Thr Leu Cys Thr Glu Cys Ser Phe Gly Arg Phe Cys Pro Glu Glu Phe Thr Leu Cys Thr Glu Cys Ser Phe 965 970 975 965 970 975

Phe His Ala Arg Lys Ser Leu Leu Ala Phe Ile Ala Phe Leu Leu Phe Phe His Ala Arg Lys Ser Leu Leu Ala Phe Ile Ala Phe Leu Leu Phe 980 985 990 980 985 990

Ala Phe Val Ile Ser Leu Ser Leu Ile Phe Tyr Tyr Ser Lys Lys Gly Ala Phe Val Ile Ser Leu Ser Leu Ile Phe Tyr Tyr Ser Lys Lys Gly 995 1000 1005 995 1000 1005

Arg Arg Gly Tyr Lys Arg Arg Gly Tyr Lys 1010 1010

<210> 121 <210> 121 <211> 4570 <211> 4570 <212> PRT <212> PRT <213> Canis familiaris <213> Canis familiaris

<400> 121 <400> 121

Page 395 Page 395

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Ala Thr Gly Gly Cys Cys Ala Cys Cys Thr Gly Cys Ala Thr Thr Thr Ala Thr Gly Gly Cys Cys Ala Cys Cys Thr Gly Cys Ala Thr Thr Thr 1 5 10 15 1 5 10 15

Thr Ala Cys Ala Gly Ala Thr Gly Ala Gly Ala Thr Thr Cys Cys Thr Thr Ala Cys Ala Gly Ala Thr Gly Ala Gly Ala Thr Thr Cys Cys Thr 20 25 30 20 25 30

Ala Ala Gly Gly Cys Thr Gly Gly Gly Gly Ala Ala Gly Ala Thr Ala Ala Ala Gly Gly Cys Thr Gly Gly Gly Gly Ala Ala Gly Ala Thr Ala 35 40 45 35 40 45

Cys Thr Gly Thr Thr Cys Cys Ala Cys Thr Cys Cys Ala Gly Cys Cys Cys Thr Gly Thr Thr Cys Cys Ala Cys Thr Cys Cys Ala Gly Cys Cys 50 55 60 50 55 60

Cys Ala Cys Ala Ala Ala Gly Cys Ala Cys Ala Gly Gly Thr Gly Gly Cys Ala Cys Ala Ala Ala Gly Cys Ala Cys Ala Gly Gly Thr Gly Gly 65 70 75 80 70 75 80

Cys Ala Gly Thr Gly Gly Thr Gly Gly Gly Ala Cys Cys Cys Gly Gly Cys Ala Gly Thr Gly Gly Thr Gly Gly Gly Ala Cys Cys Cys Gly Gly 85 90 95 85 90 95

Gly Gly Ala Cys Cys Thr Cys Gly Ala Gly Cys Thr Cys Cys Gly Gly Gly Gly Ala Cys Cys Thr Cys Gly Ala Gly Cys Thr Cys Cys Gly Gly 100 105 110 100 105 110

Cys Ala Cys Ala Gly Cys Thr Gly Cys Gly Ala Ala Cys Gly Cys Ala Cys Ala Cys Ala Gly Cys Thr Gly Cys Gly Ala Ala Cys Gly Cys Ala 115 120 125 115 120 125

Gly Cys Gly Thr Gly Gly Cys Ala Cys Ala Gly Ala Thr Ala Ala Gly Gly Cys Gly Thr Gly Gly Cys Ala Cys Ala Gly Ala Thr Ala Ala Gly 130 135 140 130 135 140

Thr Thr Ala Gly Thr Thr Gly Cys Thr Ala Ala Gly Thr Cys Ala Gly Thr Thr Ala Gly Thr Thr Gly Cys Thr Ala Ala Gly Thr Cys Ala Gly 145 150 155 160 145 150 155 160

Ala Gly Cys Thr Cys Ala Ala Gly Gly Cys Thr Ala Ala Ala Ala Cys Ala Gly Cys Thr Cys Ala Ala Gly Gly Cys Thr Ala Ala Ala Ala Cys 165 170 175 165 170 175

Gly Gly Cys Cys Cys Ala Cys Cys Gly Cys Gly Cys Gly Cys Thr Gly Gly Gly Cys Cys Cys Ala Cys Cys Gly Cys Gly Cys Gly Cys Thr Gly 180 185 190 180 185 190

Gly Cys Cys Gly Ala Cys Cys Ala Cys Thr Thr Cys Ala Gly Gly Gly Gly Cys Cys Gly Ala Cys Cys Ala Cys Thr Thr Cys Ala Gly Gly Gly 195 200 205 195 200 205

Page 396 Page 396

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Ala Cys Thr Ala Cys Gly Cys Cys Gly Ala Gly Cys Thr Cys Thr Gly Ala Cys Thr Ala Cys Gly Cys Cys Gly Ala Gly Cys Thr Cys Thr Gly 210 215 220 210 215 220

Cys Thr Thr Cys Cys Gly Cys Cys Ala Cys Thr Thr Cys Thr Gly Cys Cys Thr Thr Cys Cys Gly Cys Cys Ala Cys Thr Thr Cys Thr Gly Cys 225 230 235 240 225 230 235 240

Gly Gly Cys Cys Ala Gly Gly Thr Cys Ala Ala Gly Thr Ala Cys Thr Gly Gly Cys Cys Ala Gly Gly Thr Cys Ala Ala Gly Thr Ala Cys Thr 245 250 255 245 250 255

Gly Gly Ala Thr Cys Ala Cys Cys Ala Thr Cys Gly Ala Cys Ala Ala Gly Gly Ala Thr Cys Ala Cys Cys Ala Thr Cys Gly Ala Cys Ala Ala 260 265 270 260 265 270

Cys Cys Cys Cys Thr Ala Cys Gly Thr Gly Gly Thr Gly Gly Cys Cys Cys Cys Cys Cys Thr Ala Cys Gly Thr Gly Gly Thr Gly Gly Cys Cys 275 280 285 275 280 285

Thr Gly Gly Cys Ala Cys Gly Gly Cys Thr Ala Cys Gly Cys Cys Ala Thr Gly Gly Cys Ala Cys Gly Gly Cys Thr Ala Cys Gly Cys Cys Ala 290 295 300 290 295 300

Cys Cys Gly Gly Gly Cys Gly Cys Cys Thr Gly Gly Cys Cys Cys Cys Cys Cys Gly Gly Gly Cys Gly Cys Cys Thr Gly Gly Cys Cys Cys Cys 305 310 315 320 305 310 315 320

Cys Gly Gly Cys Gly Thr Cys Cys Gly Gly Gly Gly Cys Ala Gly Cys Cys Gly Gly Cys Gly Thr Cys Cys Gly Gly Gly Gly Cys Ala Gly Cys 325 330 335 325 330 335

Cys Cys Gly Cys Gly Gly Cys Thr Cys Gly Gly Gly Thr Ala Cys Cys Cys Cys Gly Cys Gly Gly Cys Thr Cys Gly Gly Gly Thr Ala Cys Cys 340 345 350 340 345 350

Thr Gly Gly Thr Gly Gly Cys Gly Cys Ala Cys Ala Ala Cys Cys Thr Thr Gly Gly Thr Gly Gly Cys Gly Cys Ala Cys Ala Ala Cys Cys Thr 355 360 365 355 360 365

Cys Cys Thr Cys Cys Thr Gly Gly Cys Thr Cys Ala Cys Gly Cys Cys Cys Cys Thr Cys Cys Thr Gly Gly Cys Thr Cys Ala Cys Gly Cys Cys 370 375 380 370 375 380

Ala Ala Ala Ala Thr Cys Thr Gly Gly Cys Ala Thr Cys Thr Cys Thr Ala Ala Ala Ala Thr Cys Thr Gly Gly Cys Ala Thr Cys Thr Cys Thr 385 390 395 400 385 390 395 400

Ala Cys Ala Ala Thr Ala Cys Thr Thr Cys Thr Thr Thr Cys Cys Gly Ala Cys Ala Ala Thr Ala Cys Thr Thr Cys Thr Thr Thr Cys Cys Gly 405 410 415 405 410 415

Page 397 Page 397

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Cys Cys Cys Ala Ala Cys Thr Cys Ala Gly Gly Gly Ala Gly Gly Cys Cys Cys Cys Ala Ala Cys Thr Cys Ala Gly Gly Gly Ala Gly Gly Cys 420 425 430 420 425 430

Cys Ala Gly Gly Thr Ala Thr Cys Cys Ala Thr Thr Gly Cys Cys Cys Cys Ala Gly Gly Thr Ala Thr Cys Cys Ala Thr Thr Gly Cys Cys Cys 435 440 445 435 440 445

Thr Ala Ala Gly Cys Thr Cys Cys Cys Ala Cys Thr Gly Gly Ala Thr Thr Ala Ala Gly Cys Thr Cys Cys Cys Ala Cys Thr Gly Gly Ala Thr 450 455 460 450 455 460

Cys Ala Ala Thr Cys Cys Thr Cys Gly Ala Ala Gly Ala Ala Thr Gly Cys Ala Ala Thr Cys Cys Thr Cys Gly Ala Ala Gly Ala Ala Thr Gly 465 470 475 480 465 470 475 480

Ala Cys Cys Gly Ala Cys Cys Ala Thr Ala Gly Cys Ala Thr Cys Ala Ala Cys Cys Gly Ala Cys Cys Ala Thr Ala Gly Cys Ala Thr Cys Ala 485 490 495 485 490 495

Ala Ala Gly Ala Ala Thr Gly Thr Cys Ala Ala Ala Ala Ala Thr Cys Ala Ala Gly Ala Ala Thr Gly Thr Cys Ala Ala Ala Ala Ala Thr Cys 500 505 510 500 505 510

Thr Cys Thr Thr Gly Ala Cys Thr Thr Thr Gly Thr Ala Cys Thr Ala Thr Cys Thr Thr Gly Ala Cys Thr Thr Thr Gly Thr Ala Cys Thr Ala 515 520 525 515 520 525

Gly Gly Cys Thr Gly Gly Thr Thr Thr Gly Cys Cys Ala Ala Gly Cys Gly Gly Cys Thr Gly Gly Thr Thr Thr Gly Cys Cys Ala Ala Gly Cys 530 535 540 530 535 540

Cys Cys Ala Thr Ala Thr Thr Thr Ala Thr Thr Gly Ala Thr Gly Gly Cys Cys Ala Thr Ala Thr Thr Thr Ala Thr Thr Gly Ala Thr Gly Gly 545 550 555 560 545 550 555 560

Thr Gly Ala Cys Thr Ala Thr Cys Cys Thr Gly Ala Gly Ala Gly Cys Thr Gly Ala Cys Thr Ala Thr Cys Cys Thr Gly Ala Gly Ala Gly Cys 565 570 575 565 570 575

Ala Thr Gly Ala Ala Gly Ala Ala Thr Ala Ala Cys Cys Thr Gly Thr Ala Thr Gly Ala Ala Gly Ala Ala Thr Ala Ala Cys Cys Thr Gly Thr 580 585 590 580 585 590

Cys Ala Thr Cys Thr Cys Thr Thr Cys Thr Gly Cys Cys Thr Gly Thr Cys Ala Thr Cys Thr Cys Thr Thr Cys Thr Gly Cys Cys Thr Gly Thr 595 600 605 595 600 605

Thr Thr Thr Thr Ala Cys Thr Gly Ala Ala Thr Cys Thr Gly Ala Gly Thr Thr Thr Thr Ala Cys Thr Gly Ala Ala Thr Cys Thr Gly Ala Gly 610 615 620 610 615 620

Page 398 Page 398

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Ala Ala Ala Ala Ala Gly Thr Thr Cys Ala Thr Cys Ala Ala Gly Gly Ala Ala Ala Ala Ala Gly Thr Thr Cys Ala Thr Cys Ala Ala Gly Gly 625 630 635 640 625 630 635 640

Gly Ala Ala Cys Ala Gly Cys Thr Gly Ala Cys Thr Thr Thr Thr Thr Gly Ala Ala Cys Ala Gly Cys Thr Gly Ala Cys Thr Thr Thr Thr Thr 645 650 655 645 650 655

Thr Gly Cys Thr Cys Thr Thr Thr Cys Thr Thr Thr Thr Gly Gly Ala Thr Gly Cys Thr Cys Thr Thr Thr Cys Thr Thr Thr Thr Gly Gly Ala 660 665 670 660 665 670

Cys Cys Ala Ala Cys Thr Thr Thr Gly Ala Gly Thr Thr Thr Thr Cys Cys Cys Ala Ala Cys Thr Thr Thr Gly Ala Gly Thr Thr Thr Thr Cys 675 680 685 675 680 685

Ala Ala Cys Thr Cys Thr Thr Gly Gly Ala Cys Cys Cys Thr Cys Ala Ala Ala Cys Thr Cys Thr Thr Gly Gly Ala Cys Cys Cys Thr Cys Ala 690 695 700 690 695 700

Thr Ala Thr Gly Ala Ala Gly Thr Thr Cys Cys Ala Cys Cys Ala Ala Thr Ala Thr Gly Ala Ala Gly Thr Thr Cys Cys Ala Cys Cys Ala Ala 705 710 715 720 705 710 715 720

Thr Thr Ala Gly Ala Ala Thr Cys Thr Cys Cys Cys Ala Gly Cys Cys Thr Thr Ala Gly Ala Ala Thr Cys Thr Cys Cys Cys Ala Gly Cys Cys 725 730 735 725 730 735

Thr Gly Ala Gly Gly Cys Ala Ala Cys Thr Cys Cys Thr Thr Thr Cys Thr Gly Ala Gly Gly Cys Ala Ala Cys Thr Cys Cys Thr Thr Thr Cys 740 745 750 740 745 750

Thr Thr Gly Gly Ala Thr Thr Gly Ala Cys Cys Thr Thr Gly Ala Ala Thr Thr Gly Gly Ala Thr Thr Gly Ala Cys Cys Thr Thr Gly Ala Ala 755 760 765 755 760 765

Thr Ala Thr Ala Ala Cys Cys Ala Cys Cys Cys Thr Cys Ala Ala Ala Thr Ala Thr Ala Ala Cys Cys Ala Cys Cys Cys Thr Cys Ala Ala Ala 770 775 780 770 775 780

Thr Ala Thr Thr Thr Ala Thr Thr Gly Thr Gly Gly Ala Ala Ala Ala Thr Ala Thr Thr Thr Ala Thr Thr Gly Thr Gly Gly Ala Ala Ala Ala 785 790 795 800 785 790 795 800

Thr Gly Gly Cys Thr Gly Gly Thr Thr Thr Gly Thr Cys Thr Cys Ala Thr Gly Gly Cys Thr Gly Gly Thr Thr Thr Gly Thr Cys Thr Cys Ala 805 810 815 805 810 815

Gly Gly Gly Ala Cys Cys Ala Cys Cys Ala Ala Gly Ala Gly Ala Gly Gly Gly Gly Ala Cys Cys Ala Cys Cys Ala Ala Gly Ala Gly Ala Gly 820 825 830 820 825 830

Page 399 Page 399

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Ala Thr Gly Ala Thr Gly Cys Cys Ala Ala Ala Thr Ala Thr Ala Thr Ala Thr Gly Ala Thr Gly Cys Cys Ala Ala Ala Thr Ala Thr Ala Thr 835 840 845 835 840 845

Gly Thr Ala Thr Thr Ala Cys Cys Thr Cys Ala Ala Ala Ala Ala Ala Gly Thr Ala Thr Thr Ala Cys Cys Thr Cys Ala Ala Ala Ala Ala Ala 850 855 860 850 855 860

Thr Thr Cys Ala Thr Ala Ala Thr Gly Gly Ala Ala Ala Cys Cys Thr Thr Thr Cys Ala Thr Ala Ala Thr Gly Gly Ala Ala Ala Cys Cys Thr 865 870 875 880 865 870 875 880

Thr Ala Ala Ala Ala Gly Cys Cys Ala Thr Cys Ala Gly Gly Cys Thr Thr Ala Ala Ala Ala Gly Cys Cys Ala Thr Cys Ala Gly Gly Cys Thr 885 890 895 885 890 895

Gly Gly Ala Thr Gly Gly Gly Gly Thr Gly Gly Ala Thr Gly Thr Cys Gly Gly Ala Thr Gly Gly Gly Gly Thr Gly Gly Ala Thr Gly Thr Cys 900 905 910 900 905 910

Ala Thr Ala Gly Gly Ala Thr Ala Cys Ala Cys Ala Gly Cys Gly Thr Ala Thr Ala Gly Gly Ala Thr Ala Cys Ala Cys Ala Gly Cys Gly Thr 915 920 925 915 920 925

Gly Gly Thr Cys Cys Cys Thr Thr Ala Thr Gly Gly Ala Thr Gly Gly Gly Gly Thr Cys Cys Cys Thr Thr Ala Thr Gly Gly Ala Thr Gly Gly 930 935 940 930 935 940

Cys Thr Thr Cys Gly Ala Gly Thr Gly Gly Cys Ala Cys Ala Gly Ala Cys Thr Thr Cys Gly Ala Gly Thr Gly Gly Cys Ala Cys Ala Gly Ala 945 950 955 960 945 950 955 960

Gly Gly Cys Thr Ala Cys Ala Gly Cys Ala Thr Cys Ala Gly Ala Cys Gly Gly Cys Thr Ala Cys Ala Gly Cys Ala Thr Cys Ala Gly Ala Cys 965 970 975 965 970 975

Gly Thr Gly Gly Ala Cys Thr Cys Thr Thr Cys Thr Ala Cys Gly Thr Gly Thr Gly Gly Ala Cys Thr Cys Thr Thr Cys Thr Ala Cys Gly Thr 980 985 990 980 985 990

Gly Gly Ala Cys Thr Thr Thr Cys Thr Ala Ala Gly Cys Cys Ala Gly Gly Gly Ala Cys Thr Thr Thr Cys Thr Ala Ala Gly Cys Cys Ala Gly 995 1000 1005 995 1000 1005

Gly Ala Thr Ala Ala Gly Ala Ala Ala Cys Thr Gly Thr Thr Gly Gly Ala Thr Ala Ala Gly Ala Ala Ala Cys Thr Gly Thr Thr Gly 1010 1015 1020 1010 1015 1020

Cys Cys Ala Ala Ala Gly Thr Cys Thr Thr Cys Ala Gly Cys Cys Cys Cys Ala Ala Ala Gly Thr Cys Thr Thr Cys Ala Gly Cys Cys 1025 1030 1035 1025 1030 1035

Page 400 Page 400

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Thr Thr Gly Thr Thr Cys Thr Ala Cys Cys Ala Ala Ala Ala Gly Thr Thr Gly Thr Thr Cys Thr Ala Cys Cys Ala Ala Ala Ala Gly 1040 1045 1050 1040 1045 1050

Cys Thr Gly Ala Thr Ala Gly Ala Gly Ala Ala Ala Ala Ala Thr Cys Thr Gly Ala Thr Ala Gly Ala Gly Ala Ala Ala Ala Ala Thr 1055 1060 1065 1055 1060 1065

Gly Gly Cys Thr Thr Cys Cys Cys Thr Cys Cys Thr Thr Thr Ala Gly Gly Cys Thr Thr Cys Cys Cys Thr Cys Cys Thr Thr Thr Ala 1070 1075 1080 1070 1075 1080

Cys Cys Thr Gly Ala Ala Ala Ala Thr Cys Ala Gly Cys Cys Cys Cys Cys Thr Gly Ala Ala Ala Ala Thr Cys Ala Gly Cys Cys Cys 1085 1090 1095 1085 1090 1095

Cys Thr Ala Gly Ala Ala Gly Gly Gly Ala Cys Ala Thr Thr Thr Cys Thr Ala Gly Ala Ala Gly Gly Gly Ala Cys Ala Thr Thr Thr 1100 1105 1110 1100 1105 1110

Cys Cys Cys Thr Gly Thr Gly Ala Cys Thr Thr Thr Gly Cys Thr Cys Cys Cys Thr Gly Thr Gly Ala Cys Thr Thr Thr Gly Cys Thr 1115 1120 1125 1115 1120 1125

Thr Gly Gly Gly Gly Ala Ala Thr Thr Gly Thr Thr Gly Ala Cys Thr Gly Gly Gly Gly Ala Ala Thr Thr Gly Thr Thr Gly Ala Cys 1130 1135 1140 1130 1135 1140

Ala Ala Cys Thr Ala Cys Ala Thr Thr Cys Ala Ala Gly Thr Gly Ala Ala Cys Thr Ala Cys Ala Thr Thr Cys Ala Ala Gly Thr Gly 1145 1150 1155 1145 1150 1155

Gly Ala Cys Ala Cys Cys Ala Cys Thr Cys Thr Gly Thr Cys Thr Gly Ala Cys Ala Cys Cys Ala Cys Thr Cys Thr Gly Thr Cys Thr 1160 1165 1170 1160 1165 1170

Cys Ala Gly Thr Thr Thr Ala Cys Cys Gly Ala Cys Cys Cys Gly Cys Ala Gly Thr Thr Thr Ala Cys Cys Gly Ala Cys Cys Cys Gly 1175 1180 1185 1175 1180 1185

Ala Ala Cys Gly Thr Thr Thr Ala Cys Cys Thr Gly Thr Gly Gly Ala Ala Cys Gly Thr Thr Thr Ala Cys Cys Thr Gly Thr Gly Gly 1190 1195 1200 1190 1195 1200

Gly Ala Cys Gly Thr Cys Cys Ala Thr Cys Ala Cys Ala Gly Cys Gly Ala Cys Gly Thr Cys Cys Ala Thr Cys Ala Cys Ala Gly Cys 1205 1210 1215 1205 1210 1215

Ala Ala Gly Ala Gly Gly Cys Thr Gly Ala Thr Thr Ala Ala Gly Ala Ala Gly Ala Gly Gly Cys Thr Gly Ala Thr Thr Ala Ala Gly 1220 1225 1230 1220 1225 1230

Page 401 Page 401

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Gly Thr Gly Gly Ala Cys Gly Gly Gly Cys Thr Gly Cys Gly Gly Gly Thr Gly Gly Ala Cys Gly Gly Gly Cys Thr Gly Cys Gly Gly 1235 1240 1245 1235 1240 1245

Gly Cys Cys Ala Ala Gly Ala Ala Gly Ala Gly Gly Ala Ala Gly Gly Cys Cys Ala Ala Gly Ala Ala Gly Ala Gly Gly Ala Ala Gly 1250 1255 1260 1250 1255 1260

Cys Cys Cys Thr Ala Cys Thr Gly Cys Gly Thr Gly Gly Ala Cys Cys Cys Cys Thr Ala Cys Thr Gly Cys Gly Thr Gly Gly Ala Cys 1265 1270 1275 1265 1270 1275

Thr Thr Thr Gly Cys Cys Gly Cys Cys Ala Thr Cys Gly Gly Gly Thr Thr Thr Gly Cys Cys Gly Cys Cys Ala Thr Cys Gly Gly Gly 1280 1285 1290 1280 1285 1290

Cys Cys Cys Cys Ala Gly Gly Thr Gly Gly Cys Cys Cys Thr Gly Cys Cys Cys Cys Ala Gly Gly Thr Gly Gly Cys Cys Cys Thr Gly 1295 1300 1305 1295 1300 1305

Cys Thr Gly Cys Ala Gly Gly Ala Gly Ala Thr Gly Cys Ala Cys Cys Thr Gly Cys Ala Gly Gly Ala Gly Ala Thr Gly Cys Ala Cys 1310 1315 1320 1310 1315 1320

Gly Thr Cys Thr Cys Gly Cys Ala Thr Thr Thr Thr Cys Ala Cys Gly Thr Cys Thr Cys Gly Cys Ala Thr Thr Thr Thr Cys Ala Cys 1325 1330 1335 1325 1330 1335

Thr Thr Cys Thr Cys Gly Cys Thr Gly Gly Ala Cys Thr Gly Gly Thr Thr Cys Thr Cys Gly Cys Thr Gly Gly Ala Cys Thr Gly Gly 1340 1345 1350 1340 1345 1350

Gly Cys Cys Cys Thr Gly Cys Thr Cys Cys Thr Gly Cys Cys Gly Gly Cys Cys Cys Thr Gly Cys Thr Cys Cys Thr Gly Cys Cys Gly 1355 1360 1365 1355 1360 1365

Cys Thr Gly Gly Gly Cys Ala Ala Cys Cys Ala Gly Thr Cys Cys Cys Thr Gly Gly Gly Cys Ala Ala Cys Cys Ala Gly Thr Cys Cys 1370 1375 1380 1370 1375 1380

Cys Gly Gly Gly Thr Gly Ala Ala Cys Cys Ala Cys Gly Cys Gly Cys Gly Gly Gly Thr Gly Ala Ala Cys Cys Ala Cys Gly Cys Gly 1385 1390 1395 1385 1390 1395

Gly Cys Cys Cys Thr Gly Cys Ala Cys Thr Ala Cys Thr Ala Cys Gly Cys Cys Cys Thr Gly Cys Ala Cys Thr Ala Cys Thr Ala Cys 1400 1405 1410 1400 1405 1410

Gly Gly Cys Thr Gly Cys Gly Thr Gly Gly Cys Cys Ala Gly Cys Gly Gly Cys Thr Gly Cys Gly Thr Gly Gly Cys Cys Ala Gly Cys 1415 1420 1425 1415 1420 1425

Page 402 Page 402

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Gly Ala Gly Cys Thr Cys Cys Thr Gly Cys Gly Cys Gly Cys Cys Gly Ala Gly Cys Thr Cys Cys Thr Gly Cys Gly Cys Gly Cys Cys 1430 1435 1440 1430 1435 1440

Ala Ala Cys Ala Thr Cys Ala Cys Cys Cys Cys Gly Gly Thr Gly Ala Ala Cys Ala Thr Cys Ala Cys Cys Cys Cys Gly Gly Thr Gly 1445 1450 1455 1445 1450 1455

Gly Thr Gly Gly Cys Gly Cys Thr Cys Thr Gly Gly Cys Gly Cys Gly Thr Gly Gly Cys Gly Cys Thr Cys Thr Gly Gly Cys Gly Cys 1460 1465 1470 1460 1465 1470

Cys Cys Cys Gly Cys Cys Gly Cys Cys Gly Cys Gly Cys Ala Cys Cys Cys Cys Gly Cys Cys Gly Cys Cys Gly Cys Gly Cys Ala Cys 1475 1480 1485 1475 1480 1485

Cys Ala Gly Gly Gly Cys Cys Thr Gly Cys Cys Gly Gly Gly Gly Cys Ala Gly Gly Gly Cys Cys Thr Gly Cys Cys Gly Gly Gly Gly 1490 1495 1500 1490 1495 1500

Cys Cys Gly Cys Thr Gly Gly Cys Cys Cys Ala Gly Cys Gly Cys Cys Cys Gly Cys Thr Gly Gly Cys Cys Cys Ala Gly Cys Gly Cys 1505 1510 1515 1505 1510 1515

Gly Gly Cys Gly Cys Cys Thr Gly Gly Gly Ala Gly Ala Ala Cys Gly Gly Cys Gly Cys Cys Thr Gly Gly Gly Ala Gly Ala Ala Cys 1520 1525 1530 1520 1525 1530

Cys Cys Gly Cys Gly Cys Ala Cys Cys Gly Cys Cys Cys Thr Gly Cys Cys Gly Cys Gly Cys Ala Cys Cys Gly Cys Cys Cys Thr Gly 1535 1540 1545 1535 1540 1545

Gly Cys Gly Thr Thr Cys Gly Cys Cys Gly Ala Gly Thr Ala Cys Gly Cys Gly Thr Thr Cys Gly Cys Cys Gly Ala Gly Thr Ala Cys 1550 1555 1560 1550 1555 1560

Gly Cys Gly Cys Gly Cys Cys Thr Gly Thr Gly Cys Thr Thr Cys Gly Cys Gly Cys Gly Cys Cys Thr Gly Thr Gly Cys Thr Thr Cys 1565 1570 1575 1565 1570 1575

Cys Gly Cys Gly Cys Cys Cys Thr Gly Gly Gly Cys Cys Gly Cys Cys Gly Cys Gly Cys Cys Cys Thr Gly Gly Gly Cys Cys Gly Cys 1580 1585 1590 1580 1585 1590

Cys Ala Cys Gly Thr Cys Ala Ala Gly Gly Thr Gly Thr Gly Gly Cys Ala Cys Gly Thr Cys Ala Ala Gly Gly Thr Gly Thr Gly Gly 1595 1600 1605 1595 1600 1605

Ala Thr Cys Ala Cys Gly Cys Thr Gly Cys Gly Cys Gly Ala Gly Ala Thr Cys Ala Cys Gly Cys Thr Gly Cys Gly Cys Gly Ala Gly 1610 1615 1620 1610 1615 1620

Page 403 Page 403

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Cys Cys Gly Cys Cys Cys Ala Cys Gly Cys Gly Gly Ala Ala Cys Cys Cys Gly Cys Cys Cys Ala Cys Gly Cys Gly Gly Ala Ala Cys 1625 1630 1635 1625 1630 1635

Cys Thr Gly Ala Cys Gly Cys Thr Cys Cys Gly Cys Gly Cys Cys Cys Thr Gly Ala Cys Gly Cys Thr Cys Cys Gly Cys Gly Cys Cys 1640 1645 1650 1640 1645 1650

Gly Gly Gly Cys Ala Cys Ala Ala Cys Cys Thr Gly Cys Thr Gly Gly Gly Gly Cys Ala Cys Ala Ala Cys Cys Thr Gly Cys Thr Gly 1655 1660 1665 1655 1660 1665

Cys Gly Gly Gly Cys Gly Cys Ala Cys Gly Cys Gly Cys Thr Gly Cys Gly Gly Gly Cys Gly Cys Ala Cys Gly Cys Gly Cys Thr Gly 1670 1675 1680 1670 1675 1680

Gly Cys Cys Thr Gly Gly Cys Gly Cys Gly Thr Gly Thr Ala Cys Gly Cys Cys Thr Gly Gly Cys Gly Cys Gly Thr Gly Thr Ala Cys 1685 1690 1695 1685 1690 1695

Gly Ala Cys Gly Ala Gly Cys Ala Gly Thr Thr Cys Cys Gly Gly Gly Ala Cys Gly Ala Gly Cys Ala Gly Thr Thr Cys Cys Gly Gly 1700 1705 1710 1700 1705 1710

Gly Gly Cys Thr Cys Gly Cys Ala Gly Cys Ala Gly Gly Gly Gly Gly Gly Cys Thr Cys Gly Cys Ala Gly Cys Ala Gly Gly Gly Gly 1715 1720 1725 1715 1720 1725

Ala Ala Gly Gly Thr Gly Thr Cys Cys Ala Thr Cys Gly Cys Cys Ala Ala Gly Gly Thr Gly Thr Cys Cys Ala Thr Cys Gly Cys Cys 1730 1735 1740 1730 1735 1740

Cys Thr Gly Cys Ala Gly Gly Cys Cys Gly Ala Cys Thr Gly Gly Cys Thr Gly Cys Ala Gly Gly Cys Cys Gly Ala Cys Thr Gly Gly 1745 1750 1755 1745 1750 1755

Gly Thr Gly Gly Ala Gly Cys Cys Cys Gly Cys Cys Thr Gly Cys Gly Thr Gly Gly Ala Gly Cys Cys Cys Gly Cys Cys Thr Gly Cys 1760 1765 1770 1760 1765 1770

Cys Cys Cys Thr Cys Cys Thr Cys Cys Cys Ala Gly Ala Ala Gly Cys Cys Cys Thr Cys Cys Thr Cys Cys Cys Ala Gly Ala Ala Gly 1775 1780 1785 1775 1780 1785

Gly Ala Cys Cys Gly Cys Gly Ala Ala Gly Thr Gly Gly Cys Cys Gly Ala Cys Cys Gly Cys Gly Ala Ala Gly Thr Gly Gly Cys Cys 1790 1795 1800 1790 1795 1800

Gly Ala Gly Ala Gly Gly Gly Thr Thr Cys Thr Gly Gly Ala Gly Gly Ala Gly Ala Gly Gly Gly Thr Thr Cys Thr Gly Gly Ala Gly 1805 1810 1815 1805 1810 1815

Page 404 Page 404

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Thr Thr Cys Gly Ala Cys Gly Thr Cys Gly Gly Cys Thr Gly Gly Thr Thr Cys Gly Ala Cys Gly Thr Cys Gly Gly Cys Thr Gly Gly 1820 1825 1830 1820 1825 1830

Cys Thr Gly Gly Cys Cys Gly Ala Gly Cys Cys Cys Ala Thr Cys Cys Thr Gly Gly Cys Cys Gly Ala Gly Cys Cys Cys Ala Thr Cys 1835 1840 1845 1835 1840 1845

Thr Thr Cys Gly Gly Cys Thr Cys Cys Gly Gly Gly Gly Ala Cys Thr Thr Cys Gly Gly Cys Thr Cys Cys Gly Gly Gly Gly Ala Cys 1850 1855 1860 1850 1855 1860

Thr Ala Cys Cys Cys Gly Cys Gly Gly Cys Thr Gly Ala Thr Gly Thr Ala Cys Cys Cys Gly Cys Gly Gly Cys Thr Gly Ala Thr Gly 1865 1870 1875 1865 1870 1875

Cys Gly Cys Gly Ala Cys Thr Gly Gly Cys Thr Cys Ala Cys Cys Cys Gly Cys Gly Ala Cys Thr Gly Gly Cys Thr Cys Ala Cys Cys 1880 1885 1890 1880 1885 1890

Cys Gly Gly Ala Gly Ala Gly Ala Cys Cys Ala Thr Thr Cys Cys Cys Gly Gly Ala Gly Ala Gly Ala Cys Cys Ala Thr Thr Cys Cys 1895 1900 1905 1895 1900 1905

Cys Thr Cys Cys Thr Gly Cys Cys Cys Thr Ala Thr Thr Thr Cys Cys Thr Cys Cys Thr Gly Cys Cys Cys Thr Ala Thr Thr Thr Cys 1910 1915 1920 1910 1915 1920

Ala Cys Thr Gly Ala Cys Gly Ala Ala Gly Ala Gly Ala Ala Gly Ala Cys Thr Gly Ala Cys Gly Ala Ala Gly Ala Gly Ala Ala Gly 1925 1930 1935 1925 1930 1935

Ala Gly Gly Cys Thr Ala Ala Thr Cys Cys Gly Gly Gly Gly Thr Ala Gly Gly Cys Thr Ala Ala Thr Cys Cys Gly Gly Gly Gly Thr 1940 1945 1950 1940 1945 1950

Thr Cys Cys Thr Thr Thr Gly Ala Cys Thr Thr Cys Cys Thr Gly Thr Cys Cys Thr Thr Thr Gly Ala Cys Thr Thr Cys Cys Thr Gly 1955 1960 1965 1955 1960 1965

Gly Cys Cys Thr Thr Gly Ala Gly Cys Cys Ala Thr Thr Ala Cys Gly Cys Cys Thr Thr Gly Ala Gly Cys Cys Ala Thr Thr Ala Cys 1970 1975 1980 1970 1975 1980

Ala Cys Cys Ala Cys Cys Ala Thr Cys Cys Thr Cys Gly Thr Gly Ala Cys Cys Ala Cys Cys Ala Thr Cys Cys Thr Cys Gly Thr Gly 1985 1990 1995 1985 1990 1995

Gly Ala Cys Thr Gly Gly Gly Ala Ala Ala Ala Gly Gly Ala Ala Gly Ala Cys Thr Gly Gly Gly Ala Ala Ala Ala Gly Gly Ala Ala 2000 2005 2010 2000 2005 2010

Page 405 Page 405

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Gly Ala Cys Cys Cys Ala Gly Thr Cys Ala Ala Ala Thr Ala Cys Gly Ala Cys Cys Cys Ala Gly Thr Cys Ala Ala Ala Thr Ala Cys 2015 2020 2025 2015 2020 2025

Ala Ala Thr Gly Ala Thr Thr Ala Cys Cys Thr Gly Gly Ala Ala Ala Ala Thr Gly Ala Thr Thr Ala Cys Cys Thr Gly Gly Ala Ala 2030 2035 2040 2030 2035 2040

Gly Thr Gly Cys Ala Gly Gly Ala Gly Ala Thr Gly Ala Cys Cys Gly Thr Gly Cys Ala Gly Gly Ala Gly Ala Thr Gly Ala Cys Cys 2045 2050 2055 2045 2050 2055

Gly Ala Cys Ala Thr Cys Ala Cys Cys Thr Gly Gly Cys Thr Cys Gly Ala Cys Ala Thr Cys Ala Cys Cys Thr Gly Gly Cys Thr Cys 2060 2065 2070 2060 2065 2070

Ala Ala Cys Thr Cys Cys Cys Cys Cys Ala Gly Thr Cys Ala Gly Ala Ala Cys Thr Cys Cys Cys Cys Cys Ala Gly Thr Cys Ala Gly 2075 2080 2085 2075 2080 2085

Gly Thr Gly Gly Cys Cys Gly Thr Ala Gly Thr Gly Cys Cys Cys Gly Thr Gly Gly Cys Cys Gly Thr Ala Gly Thr Gly Cys Cys Cys 2090 2095 2100 2090 2095 2100

Thr Gly Gly Gly Gly Cys Cys Thr Gly Cys Gly Cys Ala Ala Ala Thr Gly Gly Gly Gly Cys Cys Thr Gly Cys Gly Cys Ala Ala Ala 2105 2110 2115 2105 2110 2115

Gly Thr Gly Cys Thr Cys Ala Ala Cys Thr Gly Gly Cys Thr Cys Gly Thr Gly Cys Thr Cys Ala Ala Cys Thr Gly Gly Cys Thr Cys 2120 2125 2130 2120 2125 2130

Ala Ala Gly Thr Thr Cys Ala Ala Gly Thr Ala Cys Gly Gly Ala Ala Ala Gly Thr Thr Cys Ala Ala Gly Thr Ala Cys Gly Gly Ala 2135 2140 2145 2135 2140 2145

Gly Ala Cys Cys Thr Cys Cys Cys Cys Ala Thr Gly Thr Ala Thr Gly Ala Cys Cys Thr Cys Cys Cys Cys Ala Thr Gly Thr Ala Thr 2150 2155 2160 2150 2155 2160

Ala Thr Cys Gly Thr Ala Thr Cys Cys Ala Ala Cys Gly Gly Cys Ala Thr Cys Gly Thr Ala Thr Cys Cys Ala Ala Cys Gly Gly Cys 2165 2170 2175 2165 2170 2175

Ala Thr Ala Gly Ala Thr Gly Ala Cys Gly Ala Thr Cys Cys Gly Ala Thr Ala Gly Ala Thr Gly Ala Cys Gly Ala Thr Cys Cys Gly 2180 2185 2190 2180 2185 2190

Cys Gly Gly Gly Cys Ala Gly Cys Cys Cys Ala Gly Gly Ala Cys Cys Gly Gly Gly Cys Ala Gly Cys Cys Cys Ala Gly Gly Ala Cys 2195 2200 2205 2195 2200 2205

Page 406 Page 406

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Thr Cys Gly Thr Thr Gly Ala Gly Gly Gly Thr Gly Thr Ala Thr Thr Cys Gly Thr Thr Gly Ala Gly Gly Gly Thr Gly Thr Ala Thr 2210 2215 2220 2210 2215 2220

Thr Ala Cys Ala Thr Gly Cys Ala Gly Ala Ala Cys Thr Ala Thr Thr Ala Cys Ala Thr Gly Cys Ala Gly Ala Ala Cys Thr Ala Thr 2225 2230 2235 2225 2230 2235

Gly Thr Ala Ala Ala Thr Gly Ala Ala Gly Cys Thr Cys Thr Gly Gly Thr Ala Ala Ala Thr Gly Ala Ala Gly Cys Thr Cys Thr Gly 2240 2245 2250 2240 2245 2250

Ala Ala Ala Gly Cys Cys Thr Ala Cys Gly Thr Ala Thr Thr Gly Ala Ala Ala Gly Cys Cys Thr Ala Cys Gly Thr Ala Thr Thr Gly 2255 2260 2265 2255 2260 2265

Gly Ala Thr Gly Gly Thr Ala Thr Cys Ala Ala Thr Cys Thr Thr Gly Ala Thr Gly Gly Thr Ala Thr Cys Ala Ala Thr Cys Thr Thr 2270 2275 2280 2270 2275 2280

Thr Gly Thr Gly Gly Ala Thr Ala Cys Thr Thr Thr Gly Cys Cys Thr Gly Thr Gly Gly Ala Thr Ala Cys Thr Thr Thr Gly Cys Cys 2285 2290 2295 2285 2290 2295

Thr Ala Cys Thr Cys Ala Thr Thr Thr Ala Ala Thr Gly Ala Thr Thr Ala Cys Thr Cys Ala Thr Thr Thr Ala Ala Thr Gly Ala Thr 2300 2305 2310 2300 2305 2310

Cys Gly Cys Ala Cys Ala Gly Cys Thr Cys Cys Gly Ala Ala Gly Cys Gly Cys Ala Cys Ala Gly Cys Thr Cys Cys Gly Ala Ala Gly 2315 2320 2325 2315 2320 2325

Thr Thr Thr Gly Gly Cys Cys Thr Cys Thr Ala Thr Cys Ala Thr Thr Thr Thr Gly Gly Cys Cys Thr Cys Thr Ala Thr Cys Ala Thr 2330 2335 2340 2330 2335 2340

Thr Ala Thr Gly Cys Thr Gly Cys Ala Ala Ala Cys Cys Ala Gly Thr Ala Thr Gly Cys Thr Gly Cys Ala Ala Ala Cys Cys Ala Gly 2345 2350 2355 2345 2350 2355

Thr Thr Thr Gly Ala Gly Cys Cys Cys Ala Ala Ala Cys Cys Gly Thr Thr Thr Gly Ala Gly Cys Cys Cys Ala Ala Ala Cys Cys Gly 2360 2365 2370 2360 2365 2370

Thr Cys Gly Gly Thr Gly Ala Ala Gly Cys Ala Thr Thr Ala Cys Thr Cys Gly Gly Thr Gly Ala Ala Gly Cys Ala Thr Thr Ala Cys 2375 2380 2385 2375 2380 2385

Ala Gly Gly Ala Ala Ala Ala Thr Thr Ala Thr Thr Gly Ala Cys Ala Gly Gly Ala Ala Ala Ala Thr Thr Ala Thr Thr Gly Ala Cys 2390 2395 2400 2390 2395 2400

Page 407 Page 407

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Ala Ala Cys Ala Ala Thr Gly Gly Cys Thr Thr Cys Cys Cys Ala Ala Ala Cys Ala Ala Thr Gly Gly Cys Thr Thr Cys Cys Cys Ala 2405 2410 2415 2405 2410 2415

Gly Gly Cys Cys Cys Thr Gly Ala Ala Ala Cys Thr Thr Thr Gly Gly Gly Cys Cys Cys Thr Gly Ala Ala Ala Cys Thr Thr Thr Gly 2420 2425 2430 2420 2425 2430

Gly Gly Gly Cys Gly Gly Thr Thr Thr Thr Gly Thr Cys Cys Ala Gly Gly Gly Cys Gly Gly Thr Thr Thr Thr Gly Thr Cys Cys Ala 2435 2440 2445 2435 2440 2445

Gly Ala Gly Gly Ala Ala Thr Thr Cys Ala Cys Cys Cys Thr Gly Gly Ala Gly Gly Ala Ala Thr Thr Cys Ala Cys Cys Cys Thr Gly 2450 2455 2460 2450 2455 2460

Thr Gly Cys Ala Cys Cys Gly Ala Ala Thr Gly Cys Ala Gly Cys Thr Gly Cys Ala Cys Cys Gly Ala Ala Thr Gly Cys Ala Gly Cys 2465 2470 2475 2465 2470 2475

Thr Thr Thr Thr Thr Thr Cys Ala Cys Ala Cys Cys Cys Gly Ala Thr Thr Thr Thr Thr Thr Cys Ala Cys Ala Cys Cys Cys Gly Ala 2480 2485 2490 2480 2485 2490

Ala Ala Gly Thr Cys Thr Thr Thr Ala Cys Thr Gly Gly Cys Thr Ala Ala Gly Thr Cys Thr Thr Thr Ala Cys Thr Gly Gly Cys Thr 2495 2500 2505 2495 2500 2505

Thr Thr Cys Ala Thr Ala Gly Cys Thr Thr Thr Cys Cys Thr Ala Thr Thr Cys Ala Thr Ala Gly Cys Thr Thr Thr Cys Cys Thr Ala 2510 2515 2520 2510 2515 2520

Cys Thr Thr Thr Thr Thr Gly Cys Thr Thr Thr Thr Ala Thr Thr Cys Thr Thr Thr Thr Thr Gly Cys Thr Thr Thr Thr Ala Thr Thr 2525 2530 2535 2525 2530 2535

Ala Thr Thr Thr Cys Thr Cys Thr Thr Thr Cys Thr Cys Thr Gly Ala Thr Thr Thr Cys Thr Cys Thr Thr Thr Cys Thr Cys Thr Gly 2540 2545 2550 2540 2545 2550

Ala Thr Thr Thr Thr Cys Thr Ala Cys Thr Ala Cys Thr Cys Thr Ala Thr Thr Thr Thr Cys Thr Ala Cys Thr Ala Cys Thr Cys Thr 2555 2560 2565 2555 2560 2565

Ala Gly Gly Ala Ala Ala Gly Gly Cys Ala Gly Ala Ala Gly Ala Ala Gly Gly Ala Ala Ala Gly Gly Cys Ala Gly Ala Ala Gly Ala 2570 2575 2580 2570 2575 2580

Ala Gly Thr Thr Ala Thr Ala Ala Ala Thr Ala Gly Thr Cys Cys Ala Gly Thr Thr Ala Thr Ala Ala Ala Thr Ala Gly Thr Cys Cys 2585 2590 2595 2585 2590 2595

Page 408 Page 408

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Thr Gly Ala Ala Cys Ala Thr Thr Thr Thr Cys Cys Thr Ala Thr Thr Gly Ala Ala Cys Ala Thr Thr Thr Thr Cys Cys Thr Ala Thr 2600 2605 2610 2600 2605 2610

Thr Cys Ala Thr Cys Thr Ala Thr Thr Thr Thr Gly Ala Ala Ala Thr Cys Ala Thr Cys Thr Ala Thr Thr Thr Thr Gly Ala Ala Ala 2615 2620 2625 2615 2620 2625

Thr Ala Ala Thr Thr Ala Thr Gly Cys Ala Cys Ala Thr Ala Cys Thr Ala Ala Thr Thr Ala Thr Gly Cys Ala Cys Ala Thr Ala Cys 2630 2635 2640 2630 2635 2640

Ala Thr Cys Ala Gly Cys Thr Gly Thr Thr Ala Ala Cys Cys Ala Ala Thr Cys Ala Gly Cys Thr Gly Thr Thr Ala Ala Cys Cys Ala 2645 2650 2655 2645 2650 2655

Thr Thr Thr Gly Cys Ala Cys Thr Thr Cys Thr Cys Ala Gly Thr Thr Thr Thr Gly Cys Ala Cys Thr Thr Cys Thr Cys Ala Gly Thr 2660 2665 2670 2660 2665 2670

Gly Thr Thr Gly Thr Gly Ala Ala Ala Cys Thr Ala Thr Ala Gly Gly Thr Thr Gly Thr Gly Ala Ala Ala Cys Thr Ala Thr Ala Gly 2675 2680 2685 2675 2680 2685

Gly Thr Thr Thr Cys Gly Thr Thr Ala Thr Thr Cys Cys Gly Gly Gly Thr Thr Thr Cys Gly Thr Thr Ala Thr Thr Cys Cys Gly Gly 2690 2695 2700 2690 2695 2700

Cys Thr Thr Cys Thr Ala Gly Ala Ala Gly Ala Ala Ala Ala Ala Cys Thr Thr Cys Thr Ala Gly Ala Ala Gly Ala Ala Ala Ala Ala 2705 2710 2715 2705 2710 2715

Thr Thr Thr Thr Thr Gly Thr Gly Gly Cys Ala Thr Ala Thr Gly Thr Thr Thr Thr Thr Gly Thr Gly Gly Cys Ala Thr Ala Thr Gly 2720 2725 2730 2720 2725 2730

Ala Cys Ala Gly Ala Cys Gly Thr Thr Thr Gly Thr Ala Ala Ala Ala Cys Ala Gly Ala Cys Gly Thr Thr Thr Gly Thr Ala Ala Ala 2735 2740 2745 2735 2740 2745

Thr Gly Ala Gly Cys Ala Thr Ala Gly Cys Thr Gly Ala Thr Thr Thr Gly Ala Gly Cys Ala Thr Ala Gly Cys Thr Gly Ala Thr Thr 2750 2755 2760 2750 2755 2760

Gly Thr Ala Ala Ala Ala Thr Ala Thr Thr Gly Gly Ala Thr Ala Gly Thr Ala Ala Ala Ala Thr Ala Thr Thr Gly Gly Ala Thr Ala 2765 2770 2775 2765 2770 2775

Ala Thr Gly Thr Gly Ala Ala Thr Ala Gly Thr Gly Cys Cys Thr Ala Thr Gly Thr Gly Ala Ala Thr Ala Gly Thr Gly Cys Cys Thr 2780 2785 2790 2780 2785 2790

Page 409 Page 409

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Gly Gly Ala Thr Thr Thr Gly Thr Thr Cys Thr Thr Thr Thr Thr Gly Gly Ala Thr Thr Thr Gly Thr Thr Cys Thr Thr Thr Thr Thr 2795 2800 2805 2795 2800 2805

Thr Thr Gly Ala Ala Gly Gly Gly Thr Ala Ala Thr Cys Ala Ala Thr Thr Gly Ala Ala Gly Gly Gly Thr Ala Ala Thr Cys Ala Ala 2810 2815 2820 2810 2815 2820

Ala Gly Ala Cys Thr Gly Thr Cys Ala Gly Gly Gly Gly Cys Cys Ala Gly Ala Cys Thr Gly Thr Cys Ala Gly Gly Gly Gly Cys Cys 2825 2830 2835 2825 2830 2835

Ala Thr Cys Ala Thr Thr Cys Cys Thr Gly Thr Ala Ala Cys Ala Ala Thr Cys Ala Thr Thr Cys Cys Thr Gly Thr Ala Ala Cys Ala 2840 2845 2850 2840 2845 2850

Cys Ala Cys Ala Cys Thr Gly Thr Ala Ala Cys Ala Ala Ala Thr Cys Ala Cys Ala Cys Thr Gly Thr Ala Ala Cys Ala Ala Ala Thr 2855 2860 2865 2855 2860 2865

Gly Thr Ala Thr Gly Gly Gly Ala Ala Gly Thr Gly Gly Gly Gly Gly Thr Ala Thr Gly Gly Gly Ala Ala Gly Thr Gly Gly Gly Gly 2870 2875 2880 2870 2875 2880

Gly Thr Cys Ala Cys Thr Cys Thr Gly Cys Ala Ala Cys Ala Thr Gly Thr Cys Ala Cys Thr Cys Thr Gly Cys Ala Ala Cys Ala Thr 2885 2890 2895 2885 2890 2895

Thr Thr Thr Thr Ala Cys Ala Gly Ala Ala Ala Thr Thr Gly Ala Thr Thr Thr Thr Ala Cys Ala Gly Ala Ala Ala Thr Thr Gly Ala 2900 2905 2910 2900 2905 2910

Ala Thr Gly Gly Thr Gly Cys Cys Cys Ala Thr Thr Cys Ala Ala Ala Thr Gly Gly Thr Gly Cys Cys Cys Ala Thr Thr Cys Ala Ala 2915 2920 2925 2915 2920 2925

Thr Thr Ala Gly Thr Gly Cys Cys Cys Ala Thr Thr Cys Thr Thr Thr Thr Ala Gly Thr Gly Cys Cys Cys Ala Thr Thr Cys Thr Thr 2930 2935 2940 2930 2935 2940

Ala Ala Ala Thr Gly Thr Ala Ala Thr Gly Thr Thr Thr Ala Thr Ala Ala Ala Thr Gly Thr Ala Ala Thr Gly Thr Thr Thr Ala Thr 2945 2950 2955 2945 2950 2955

Cys Thr Cys Gly Ala Ala Gly Thr Ala Ala Thr Ala Ala Thr Thr Cys Thr Cys Gly Ala Ala Gly Thr Ala Ala Thr Ala Ala Thr Thr 2960 2965 2970 2960 2965 2970

Gly Cys Ala Gly Ala Thr Gly Thr Thr Gly Gly Ala Ala Thr Ala Gly Cys Ala Gly Ala Thr Gly Thr Thr Gly Gly Ala Ala Thr Ala 2975 2980 2985 2975 2980 2985

Page 410 Page 410

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Ala Ala Ala Ala Gly Thr Thr Ala Ala Ala Ala Gly Gly Thr Cys Ala Ala Ala Ala Gly Thr Thr Ala Ala Ala Ala Gly Gly Thr Cys 2990 2995 3000 2990 2995 3000

Cys Cys Ala Ala Gly Cys Ala Ala Cys Cys Ala Thr Cys Thr Cys Cys Cys Ala Ala Gly Cys Ala Ala Cys Cys Ala Thr Cys Thr Cys 3005 3010 3015 3005 3010 3015

Thr Ala Ala Ala Cys Cys Gly Cys Cys Ala Thr Gly Ala Thr Ala Thr Ala Ala Ala Cys Cys Gly Cys Cys Ala Thr Gly Ala Thr Ala 3020 3025 3030 3020 3025 3030

Thr Gly Cys Cys Thr Ala Ala Gly Gly Gly Thr Thr Cys Gly Cys Thr Gly Cys Cys Thr Ala Ala Gly Gly Gly Thr Thr Cys Gly Cys 3035 3040 3045 3035 3040 3045

Thr Gly Thr Thr Gly Ala Ala Cys Cys Ala Ala Gly Thr Thr Thr Thr Gly Thr Thr Gly Ala Ala Cys Cys Ala Ala Gly Thr Thr Thr 3050 3055 3060 3050 3055 3060

Cys Cys Cys Cys Thr Gly Ala Ala Ala Ala Ala Cys Ala Ala Ala Cys Cys Cys Cys Thr Gly Ala Ala Ala Ala Ala Cys Ala Ala Ala 3065 3070 3075 3065 3070 3075

Gly Gly Gly Gly Thr Ala Gly Ala Ala Thr Ala Thr Ala Gly Gly Gly Gly Gly Gly Thr Ala Gly Ala Ala Thr Ala Thr Ala Gly Gly 3080 3085 3090 3080 3085 3090

Ala Gly Ala Ala Gly Thr Gly Ala Cys Ala Ala Gly Gly Gly Gly Ala Gly Ala Ala Gly Thr Gly Ala Cys Ala Ala Gly Gly Gly Gly 3095 3100 3105 3095 3100 3105

Cys Cys Ala Ala Gly Gly Gly Gly Gly Gly Cys Ala Gly Cys Ala Cys Cys Ala Ala Gly Gly Gly Gly Gly Gly Cys Ala Gly Cys Ala 3110 3115 3120 3110 3115 3120

Ala Cys Gly Thr Thr Cys Cys Thr Thr Thr Thr Ala Ala Ala Ala Ala Cys Gly Thr Thr Cys Cys Thr Thr Thr Thr Ala Ala Ala Ala 3125 3130 3135 3125 3130 3135

Gly Cys Ala Gly Thr Gly Thr Thr Thr Cys Thr Ala Gly Cys Ala Gly Cys Ala Gly Thr Gly Thr Thr Thr Cys Thr Ala Gly Cys Ala 3140 3145 3150 3140 3145 3150

Ala Ala Thr Gly Cys Thr Gly Cys Thr Ala Ala Thr Ala Thr Thr Ala Ala Thr Gly Cys Thr Gly Cys Thr Ala Ala Thr Ala Thr Thr 3155 3160 3165 3155 3160 3165

Ala Gly Thr Thr Thr Cys Cys Gly Thr Gly Thr Cys Thr Gly Gly Ala Gly Thr Thr Thr Cys Cys Gly Thr Gly Thr Cys Thr Gly Gly 3170 3175 3180 3170 3175 3180

Page 411 Page 411

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Thr Thr Ala Ala Thr Gly Ala Thr Ala Thr Gly Thr Thr Thr Ala Thr Thr Ala Ala Thr Gly Ala Thr Ala Thr Gly Thr Thr Thr Ala 3185 3190 3195 3185 3190 3195

Gly Cys Ala Gly Ala Gly Cys Ala Gly Ala Thr Thr Ala Thr Ala Gly Cys Ala Gly Ala Gly Cys Ala Gly Ala Thr Thr Ala Thr Ala 3200 3205 3210 3200 3205 3210

Gly Ala Ala Cys Thr Thr Cys Ala Thr Cys Gly Thr Thr Thr Gly Gly Ala Ala Cys Thr Thr Cys Ala Thr Cys Gly Thr Thr Thr Gly 3215 3220 3225 3215 3220 3225

Thr Gly Ala Cys Thr Thr Thr Thr Gly Ala Gly Gly Thr Cys Thr Thr Gly Ala Cys Thr Thr Thr Thr Gly Ala Gly Gly Thr Cys Thr 3230 3235 3240 3230 3235 3240

Cys Cys Ala Gly Gly Cys Cys Cys Gly Gly Gly Gly Gly Thr Cys Cys Cys Ala Gly Gly Cys Cys Cys Gly Gly Gly Gly Gly Thr Cys 3245 3250 3255 3245 3250 3255

Cys Thr Thr Gly Ala Gly Gly Ala Cys Thr Thr Thr Gly Thr Gly Cys Thr Thr Gly Ala Gly Gly Ala Cys Thr Thr Thr Gly Thr Gly 3260 3265 3270 3260 3265 3270

Thr Thr Ala Cys Thr Gly Gly Gly Gly Cys Cys Thr Thr Ala Cys Thr Thr Ala Cys Thr Gly Gly Gly Gly Cys Cys Thr Thr Ala Cys 3275 3280 3285 3275 3280 3285

Cys Ala Ala Gly Gly Gly Cys Cys Thr Gly Cys Gly Cys Ala Ala Cys Ala Ala Gly Gly Gly Cys Cys Thr Gly Cys Gly Cys Ala Ala 3290 3295 3300 3290 3295 3300

Ala Ala Ala Gly Gly Ala Cys Thr Cys Thr Thr Ala Ala Thr Gly Ala Ala Ala Gly Gly Ala Cys Thr Cys Thr Thr Ala Ala Thr Gly 3305 3310 3315 3305 3310 3315

Thr Thr Thr Gly Thr Ala Gly Ala Ala Ala Ala Ala Thr Ala Ala Thr Thr Thr Gly Thr Ala Gly Ala Ala Ala Ala Ala Thr Ala Ala 3320 3325 3330 3320 3325 3330

Gly Thr Ala Thr Gly Ala Ala Thr Cys Gly Thr Gly Ala Gly Ala Gly Thr Ala Thr Gly Ala Ala Thr Cys Gly Thr Gly Ala Gly Ala 3335 3340 3345 3335 3340 3345

Thr Gly Thr Thr Gly Gly Cys Cys Thr Cys Thr Thr Cys Ala Gly Thr Gly Thr Thr Gly Gly Cys Cys Thr Cys Thr Thr Cys Ala Gly 3350 3355 3360 3350 3355 3360

Gly Ala Ala Gly Cys Ala Thr Gly Ala Ala Cys Thr Gly Ala Thr Gly Ala Ala Gly Cys Ala Thr Gly Ala Ala Cys Thr Gly Ala Thr 3365 3370 3375 3365 3370 3375

Page 412 Page 412

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Cys Thr Thr Gly Ala Ala Ala Thr Gly Cys Ala Thr Thr Gly Thr Cys Thr Thr Gly Ala Ala Ala Thr Gly Cys Ala Thr Thr Gly Thr 3380 3385 3390 3380 3385 3390

Ala Cys Thr Gly Cys Gly Thr Gly Gly Cys Thr Cys Thr Ala Gly Ala Cys Thr Gly Cys Gly Thr Gly Gly Cys Thr Cys Thr Ala Gly 3395 3400 3405 3395 3400 3405

Gly Gly Gly Gly Ala Gly Gly Ala Ala Ala Gly Gly Ala Gly Gly Gly Gly Gly Gly Ala Gly Gly Ala Ala Ala Gly Gly Ala Gly Gly 3410 3415 3420 3410 3415 3420

Ala Ala Ala Ala Ala Gly Thr Ala Cys Thr Thr Ala Thr Thr Ala Ala Ala Ala Ala Ala Gly Thr Ala Cys Thr Thr Ala Thr Thr Ala 3425 3430 3435 3425 3430 3435

Thr Gly Ala Gly Cys Ala Ala Cys Gly Gly Thr Ala Thr Gly Ala Thr Gly Ala Gly Cys Ala Ala Cys Gly Gly Thr Ala Thr Gly Ala 3440 3445 3450 3440 3445 3450

Thr Thr Ala Ala Thr Thr Thr Gly Ala Thr Thr Ala Thr Ala Ala Thr Thr Ala Ala Thr Thr Thr Gly Ala Thr Thr Ala Thr Ala Ala 3455 3460 3465 3455 3460 3465

Ala Cys Thr Cys Thr Thr Cys Gly Ala Thr Thr Thr Thr Ala Gly Ala Cys Thr Cys Thr Thr Cys Gly Ala Thr Thr Thr Thr Ala Gly 3470 3475 3480 3470 3475 3480

Ala Gly Cys Ala Cys Thr Cys Cys Ala Thr Gly Cys Ala Ala Thr Ala Gly Cys Ala Cys Thr Cys Cys Ala Thr Gly Cys Ala Ala Thr 3485 3490 3495 3485 3490 3495

Gly Ala Ala Thr Gly Ala Thr Gly Thr Gly Ala Cys Cys Thr Thr Gly Ala Ala Thr Gly Ala Thr Gly Thr Gly Ala Cys Cys Thr Thr 3500 3505 3510 3500 3505 3510

Thr Cys Cys Thr Gly Ala Gly Cys Ala Ala Gly Thr Gly Ala Gly Thr Cys Cys Thr Gly Ala Gly Cys Ala Ala Gly Thr Gly Ala Gly 3515 3520 3525 3515 3520 3525

Ala Ala Cys Gly Ala Ala Ala Thr Ala Ala Thr Ala Ala Cys Thr Ala Ala Cys Gly Ala Ala Ala Thr Ala Ala Thr Ala Ala Cys Thr 3530 3535 3540 3530 3535 3540

Cys Ala Thr Cys Cys Gly Cys Thr Gly Ala Cys Gly Ala Gly Thr Cys Ala Thr Cys Cys Gly Cys Thr Gly Ala Cys Gly Ala Gly Thr 3545 3550 3555 3545 3550 3555

Gly Ala Cys Thr Thr Cys Gly Cys Thr Thr Gly Cys Thr Gly Thr Gly Ala Cys Thr Thr Cys Gly Cys Thr Thr Gly Cys Thr Gly Thr 3560 3565 3570 3560 3565 3570

Page 413 Page 413

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Thr Cys Thr Thr Cys Ala Gly Ala Ala Thr Gly Thr Gly Thr Cys Thr Cys Thr Thr Cys Ala Gly Ala Ala Thr Gly Thr Gly Thr Cys 3575 3580 3585 3575 3580 3585

Ala Thr Gly Ala Thr Thr Thr Cys Thr Thr Thr Gly Ala Ala Thr Ala Thr Gly Ala Thr Thr Thr Cys Thr Thr Thr Gly Ala Ala Thr 3590 3595 3600 3590 3595 3600

Thr Gly Ala Gly Gly Thr Thr Thr Thr Thr Ala Ala Ala Ala Thr Thr Gly Ala Gly Gly Thr Thr Thr Thr Thr Ala Ala Ala Ala Thr 3605 3610 3615 3605 3610 3615

Thr Cys Thr Thr Ala Gly Thr Ala Gly Gly Cys Thr Cys Cys Ala Thr Cys Thr Thr Ala Gly Thr Ala Gly Gly Cys Thr Cys Cys Ala 3620 3625 3630 3620 3625 3630

Ala Ala Gly Cys Ala Thr Thr Thr Gly Gly Thr Cys Thr Gly Ala Ala Ala Gly Cys Ala Thr Thr Thr Gly Gly Thr Cys Thr Gly Ala 3635 3640 3645 3635 3640 3645

Thr Ala Ala Cys Ala Cys Thr Gly Gly Gly Ala Gly Ala Thr Thr Thr Ala Ala Cys Ala Cys Thr Gly Gly Gly Ala Gly Ala Thr Thr 3650 3655 3660 3650 3655 3660

Thr Gly Thr Thr Cys Cys Thr Ala Thr Gly Ala Thr Thr Gly Cys Thr Gly Thr Thr Cys Cys Thr Ala Thr Gly Ala Thr Thr Gly Cys 3665 3670 3675 3665 3670 3675

Thr Gly Ala Gly Gly Thr Thr Thr Ala Thr Thr Thr Thr Ala Cys Thr Gly Ala Gly Gly Thr Thr Thr Ala Thr Thr Thr Thr Ala Cys 3680 3685 3690 3680 3685 3690

Ala Thr Thr Gly Thr Thr Gly Cys Thr Gly Cys Ala Ala Cys Thr Ala Thr Thr Gly Thr Thr Gly Cys Thr Gly Cys Ala Ala Cys Thr 3695 3700 3705 3695 3700 3705

Thr Cys Thr Gly Thr Gly Gly Ala Ala Cys Thr Ala Gly Cys Thr Thr Cys Thr Gly Thr Gly Gly Ala Ala Cys Thr Ala Gly Cys Thr 3710 3715 3720 3710 3715 3720

Thr Thr Gly Ala Ala Cys Thr Ala Gly Thr Thr Thr Thr Gly Cys Thr Thr Gly Ala Ala Cys Thr Ala Gly Thr Thr Thr Thr Gly Cys 3725 3730 3735 3725 3730 3735

Thr Thr Thr Gly Ala Ala Cys Thr Thr Thr Cys Ala Cys Ala Gly Thr Thr Thr Gly Ala Ala Cys Thr Thr Thr Cys Ala Cys Ala Gly 3740 3745 3750 3740 3745 3750

Thr Gly Ala Ala Ala Cys Ala Gly Gly Cys Thr Ala Cys Thr Gly Thr Gly Ala Ala Ala Cys Ala Gly Gly Cys Thr Ala Cys Thr Gly 3755 3760 3765 3755 3760 3765

Page 414 Page 414

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Ala Thr Thr Thr Cys Thr Ala Gly Ala Ala Ala Gly Gly Gly Cys Ala Thr Thr Thr Cys Thr Ala Gly Ala Ala Ala Gly Gly Gly Cys 3770 3775 3780 3770 3775 3780

Thr Ala Ala Thr Gly Ala Gly Gly Thr Cys Thr Thr Ala Thr Cys Thr Ala Ala Thr Gly Ala Gly Gly Thr Cys Thr Thr Ala Thr Cys 3785 3790 3795 3785 3790 3795

Cys Thr Thr Gly Ala Ala Ala Gly Cys Cys Cys Cys Thr Thr Ala Cys Thr Thr Gly Ala Ala Ala Gly Cys Cys Cys Cys Thr Thr Ala 3800 3805 3810 3800 3805 3810

Ala Gly Thr Thr Thr Thr Gly Ala Thr Gly Ala Thr Thr Thr Thr Ala Gly Thr Thr Thr Thr Gly Ala Thr Gly Ala Thr Thr Thr Thr 3815 3820 3825 3815 3820 3825

Cys Ala Gly Ala Cys Ala Gly Gly Gly Gly Thr Cys Thr Thr Thr Cys Ala Gly Ala Cys Ala Gly Gly Gly Gly Thr Cys Thr Thr Thr 3830 3835 3840 3830 3835 3840

Cys Thr Gly Thr Thr Ala Cys Ala Cys Thr Gly Gly Ala Gly Thr Cys Thr Gly Thr Thr Ala Cys Ala Cys Thr Gly Gly Ala Gly Thr 3845 3850 3855 3845 3850 3855

Thr Gly Cys Gly Gly Ala Thr Gly Ala Thr Cys Ala Thr Gly Thr Thr Gly Cys Gly Gly Ala Thr Gly Ala Thr Cys Ala Thr Gly Thr 3860 3865 3870 3860 3865 3870

Thr Ala Thr Thr Thr Cys Thr Thr Thr Thr Cys Thr Ala Gly Ala Thr Ala Thr Thr Thr Cys Thr Thr Thr Thr Cys Thr Ala Gly Ala 3875 3880 3885 3875 3880 3885

Thr Ala Ala Gly Cys Cys Ala Ala Thr Ala Thr Cys Ala Thr Ala Thr Ala Ala Gly Cys Cys Ala Ala Thr Ala Thr Cys Ala Thr Ala 3890 3895 3900 3890 3895 3900

Thr Cys Ala Gly Gly Cys Ala Ala Gly Gly Thr Ala Ala Ala Cys Thr Cys Ala Gly Gly Cys Ala Ala Gly Gly Thr Ala Ala Ala Cys 3905 3910 3915 3905 3910 3915

Cys Ala Cys Thr Ala Thr Cys Ala Thr Ala Thr Cys Thr Ala Gly Cys Ala Cys Thr Ala Thr Cys Ala Thr Ala Thr Cys Thr Ala Gly 3920 3925 3930 3920 3925 3930

Cys Ala Thr Cys Gly Cys Thr Ala Ala Thr Cys Thr Thr Gly Cys Cys Ala Thr Cys Gly Cys Thr Ala Ala Thr Cys Thr Thr Gly Cys 3935 3940 3945 3935 3940 3945

Thr Gly Ala Cys Ala Cys Ala Gly Gly Gly Thr Gly Ala Thr Ala Thr Gly Ala Cys Ala Cys Ala Gly Gly Gly Thr Gly Ala Thr Ala 3950 3955 3960 3950 3955 3960

Page 415 Page 415

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Gly Thr Gly Thr Gly Cys Ala Ala Ala Ala Ala Ala Ala Thr Thr Gly Thr Gly Thr Gly Cys Ala Ala Ala Ala Ala Ala Ala Thr Thr 3965 3970 3975 3965 3970 3975

Gly Cys Thr Gly Thr Ala Cys Thr Gly Thr Ala Thr Thr Ala Thr Gly Cys Thr Gly Thr Ala Cys Thr Gly Thr Ala Thr Thr Ala Thr 3980 3985 3990 3980 3985 3990

Gly Thr Ala Thr Cys Ala Thr Cys Thr Thr Cys Ala Gly Ala Gly Gly Thr Ala Thr Cys Ala Thr Cys Thr Thr Cys Ala Gly Ala Gly 3995 4000 4005 3995 4000 4005

Gly Thr Gly Gly Thr Ala Gly Gly Ala Thr Thr Thr Thr Thr Thr Gly Thr Gly Gly Thr Ala Gly Gly Ala Thr Thr Thr Thr Thr Thr 4010 4015 4020 4010 4015 4020

Thr Thr Cys Cys Ala Thr Gly Ala Ala Ala Gly Ala Thr Gly Ala Thr Thr Cys Cys Ala Thr Gly Ala Ala Ala Gly Ala Thr Gly Ala 4025 4030 4035 4025 4030 4035

Gly Cys Thr Thr Thr Thr Gly Thr Thr Gly Gly Thr Ala Ala Thr Gly Cys Thr Thr Thr Thr Gly Thr Thr Gly Gly Thr Ala Ala Thr 4040 4045 4050 4040 4045 4050

Cys Thr Thr Thr Thr Ala Ala Ala Ala Ala Thr Thr Gly Gly Ala Cys Thr Thr Thr Thr Ala Ala Ala Ala Ala Thr Thr Gly Gly Ala 4055 4060 4065 4055 4060 4065

Cys Thr Thr Gly Gly Thr Ala Thr Thr Ala Ala Ala Ala Thr Thr Cys Thr Thr Gly Gly Thr Ala Thr Thr Ala Ala Ala Ala Thr Thr 4070 4075 4080 4070 4075 4080

Ala Gly Ala Ala Ala Cys Thr Ala Gly Ala Thr Ala Thr Ala Ala Ala Gly Ala Ala Ala Cys Thr Ala Gly Ala Thr Ala Thr Ala Ala 4085 4090 4095 4085 4090 4095

Thr Ala Gly Thr Thr Thr Cys Thr Thr Thr Thr Ala Thr Gly Thr Thr Ala Gly Thr Thr Thr Cys Thr Thr Thr Thr Ala Thr Gly Thr 4100 4105 4110 4100 4105 4110

Ala Thr Ala Thr Ala Thr Thr Thr Thr Thr Thr Cys Cys Gly Ala Ala Thr Ala Thr Ala Thr Thr Thr Thr Thr Thr Cys Cys Gly Ala 4115 4120 4125 4115 4120 4125

Thr Thr Cys Thr Thr Ala Gly Ala Gly Thr Ala Ala Thr Thr Thr Thr Thr Cys Thr Thr Ala Gly Ala Gly Thr Ala Ala Thr Thr Thr 4130 4135 4140 4130 4135 4140

Ala Thr Gly Thr Thr Cys Ala Thr Thr Gly Thr Ala Ala Ala Ala Ala Thr Gly Thr Thr Cys Ala Thr Thr Gly Thr Ala Ala Ala Ala 4145 4150 4155 4145 4150 4155

Page 416 Page 416

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Ala Ala Thr Thr Gly Ala Ala Ala Ala Ala Cys Ala Cys Ala Gly Ala Ala Thr Thr Gly Ala Ala Ala Ala Ala Cys Ala Cys Ala Gly 4160 4165 4170 4160 4165 4170

Ala Ala Ala Cys Thr Ala Thr Ala Thr Gly Thr Ala Ala Ala Gly Ala Ala Ala Cys Thr Ala Thr Ala Thr Gly Thr Ala Ala Ala Gly 4175 4180 4185 4175 4180 4185

Ala Gly Ala Ala Ala Ala Ala Thr Gly Ala Cys Cys Thr Ala Thr Ala Gly Ala Ala Ala Ala Ala Thr Gly Ala Cys Cys Thr Ala Thr 4190 4195 4200 4190 4195 4200

Ala Ala Gly Cys Thr Cys Ala Cys Thr Ala Cys Cys Ala Ala Ala Ala Ala Gly Cys Thr Cys Ala Cys Thr Ala Cys Cys Ala Ala Ala 4205 4210 4215 4205 4210 4215

Gly Thr Gly Gly Cys Cys Ala Cys Thr Ala Thr Thr Ala Ala Cys Gly Thr Gly Gly Cys Cys Ala Cys Thr Ala Thr Thr Ala Ala Cys 4220 4225 4230 4220 4225 4230

Ala Thr Ala Gly Cys Cys Gly Ala Thr Gly Thr Ala Thr Thr Thr Ala Thr Ala Gly Cys Cys Gly Ala Thr Gly Thr Ala Thr Thr Thr 4235 4240 4245 4235 4240 4245

Thr Ala Thr Thr Thr Thr Gly Cys Ala Thr Gly Gly Ala Gly Thr Thr Ala Thr Thr Thr Thr Gly Cys Ala Thr Gly Gly Ala Gly Thr 4250 4255 4260 4250 4255 4260

Cys Ala Gly Ala Thr Cys Ala Thr Ala Thr Thr Gly Cys Ala Ala Cys Ala Gly Ala Thr Cys Ala Thr Ala Thr Thr Gly Cys Ala Ala 4265 4270 4275 4265 4270 4275

Ala Thr Ala Ala Thr Thr Ala Thr Gly Thr Gly Thr Cys Thr Thr Ala Thr Ala Ala Thr Thr Ala Thr Gly Thr Gly Thr Cys Thr Thr 4280 4285 4290 4280 4285 4290

Thr Ala Thr Thr Ala Ala Thr Thr Thr Cys Thr Ala Thr Cys Gly Thr Ala Thr Thr Ala Ala Thr Thr Thr Cys Thr Ala Thr Cys Gly 4295 4300 4305 4295 4300 4305

Thr Gly Thr Gly Thr Gly Thr Thr Thr Cys Thr Thr Thr Thr Gly Thr Gly Thr Gly Thr Gly Thr Thr Thr Cys Thr Thr Thr Thr Gly 4310 4315 4320 4310 4315 4320

Thr Cys Ala Thr Thr Ala Gly Thr Cys Thr Thr Cys Ala Ala Ala Thr Cys Ala Thr Thr Ala Gly Thr Cys Thr Thr Cys Ala Ala Ala 4325 4330 4335 4325 4330 4335

Ala Gly Cys Ala Thr Gly Ala Thr Thr Thr Cys Thr Ala Ala Thr Ala Gly Cys Ala Thr Gly Ala Thr Thr Thr Cys Thr Ala Ala Thr 4340 4345 4350 4340 4345 4350

Page 417 Page 417

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Ala Gly Thr Thr Gly Thr Ala Gly Ala Gly Thr Gly Ala Thr Thr Ala Gly Thr Thr Gly Thr Ala Gly Ala Gly Thr Gly Ala Thr Thr 4355 4360 4365 4355 4360 4365

Cys Thr Gly Cys Thr Thr Thr Ala Thr Gly Ala Ala Thr Thr Thr Cys Thr Gly Cys Thr Thr Thr Ala Thr Gly Ala Ala Thr Thr Thr 4370 4375 4380 4370 4375 4380

Ala Thr Cys Ala Cys Ala Ala Cys Thr Cys Ala Thr Gly Thr Ala Ala Thr Cys Ala Cys Ala Ala Cys Thr Cys Ala Thr Gly Thr Ala 4385 4390 4395 4385 4390 4395

Ala Cys Cys Ala Thr Thr Cys Cys Thr Ala Thr Thr Gly Gly Thr Ala Cys Cys Ala Thr Thr Cys Cys Thr Ala Thr Thr Gly Gly Thr 4400 4405 4410 4400 4405 4410

Thr Gly Gly Ala Cys Cys Ala Gly Thr Thr Thr Ala Thr Thr Gly Thr Gly Gly Ala Cys Cys Ala Gly Thr Thr Thr Ala Thr Thr Gly 4415 4420 4425 4415 4420 4425

Thr Thr Ala Ala Thr Thr Ala Cys Thr Gly Thr Thr Ala Ala Ala Thr Thr Ala Ala Thr Thr Ala Cys Thr Gly Thr Thr Ala Ala Ala 4430 4435 4440 4430 4435 4440

Thr Ala Ala Thr Gly Thr Thr Thr Ala Ala Ala Ala Ala Thr Ala Thr Ala Ala Thr Gly Thr Thr Thr Ala Ala Ala Ala Ala Thr Ala 4445 4450 4455 4445 4450 4455

Thr Thr Cys Thr Thr Gly Cys Thr Ala Cys Ala Ala Cys Ala Thr Thr Thr Cys Thr Thr Gly Cys Thr Ala Cys Ala Ala Cys Ala Thr 4460 4465 4470 4460 4465 4470

Thr Ala Ala Thr Thr Thr Thr Cys Ala Thr Thr Thr Cys Cys Thr Thr Ala Ala Thr Thr Thr Thr Cys Ala Thr Thr Thr Cys Cys Thr 4475 4480 4485 4475 4480 4485

Thr Gly Ala Gly Thr Gly Thr Ala Gly Ala Cys Ala Gly Ala Ala Thr Gly Ala Gly Thr Gly Thr Ala Gly Ala Cys Ala Gly Ala Ala 4490 4495 4500 4490 4495 4500

Gly Thr Ala Ala Thr Thr Cys Thr Gly Thr Cys Cys Cys Thr Thr Gly Thr Ala Ala Thr Thr Cys Thr Gly Thr Cys Cys Cys Thr Thr 4505 4510 4515 4505 4510 4515

Gly Ala Thr Gly Ala Ala Gly Thr Ala Thr Thr Gly Thr Ala Ala Gly Ala Thr Gly Ala Ala Gly Thr Ala Thr Thr Gly Thr Ala Ala 4520 4525 4530 4520 4525 4530

Thr Ala Ala Ala Thr Cys Thr Gly Cys Cys Thr Gly Ala Gly Gly Thr Ala Ala Ala Thr Cys Thr Gly Cys Cys Thr Gly Ala Gly Gly 4535 4540 4545 4535 4540 4545

Page 418 Page 418

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Cys Thr Thr Thr Gly Cys Thr Thr Cys Thr Thr Thr Cys Cys Thr Cys Thr Thr Thr Gly Cys Thr Thr Cys Thr Thr Thr Cys Cys Thr 4550 4555 4560 4550 4555 4560

Ala Ala Thr Thr Ala Thr Ala Ala Ala Thr Thr Ala Thr Ala 4565 4570 4565 4570

<210> 122 <210> 122 <211> 2805 <211> 2805 <212> PRT <212> PRT <213> Felis catus <213> Felis catus

<400> 122 <400> 122

Cys Ala Thr Gly Gly Thr Gly Ala Thr Thr Ala Gly Thr Gly Gly Ala Cys Ala Thr Gly Gly Thr Gly Ala Thr Thr Ala Gly Thr Gly Gly Ala 1 5 10 15 1 5 10 15

Cys Thr Ala Gly Gly Cys Thr Cys Ala Thr Gly Cys Cys Ala Ala Ala Cys Thr Ala Gly Gly Cys Thr Cys Ala Thr Gly Cys Cys Ala Ala Ala 20 25 30 20 25 30

Ala Thr Cys Thr Gly Gly Cys Ala Thr Cys Thr Cys Thr Ala Cys Ala Ala Thr Cys Thr Gly Gly Cys Ala Thr Cys Thr Cys Thr Ala Cys Ala 35 40 45 35 40 45

Ala Thr Ala Cys Thr Thr Cys Thr Thr Thr Cys Cys Gly Thr Cys Cys Ala Thr Ala Cys Thr Thr Cys Thr Thr Thr Cys Cys Gly Thr Cys Cys 50 55 60 50 55 60

Ala Ala Cys Thr Cys Ala Gly Gly Gly Ala Gly Gly Cys Cys Ala Gly Ala Ala Cys Thr Cys Ala Gly Gly Gly Ala Gly Gly Cys Cys Ala Gly 65 70 75 80 70 75 80

Gly Thr Cys Thr Cys Cys Ala Thr Cys Gly Cys Cys Cys Thr Ala Ala Gly Thr Cys Thr Cys Cys Ala Thr Cys Gly Cys Cys Cys Thr Ala Ala 85 90 95 85 90 95

Gly Cys Thr Cys Cys Cys Ala Cys Thr Gly Gly Ala Thr Cys Ala Ala Gly Cys Thr Cys Cys Cys Ala Cys Thr Gly Gly Ala Thr Cys Ala Ala 100 105 110 100 105 110

Thr Cys Cys Thr Cys Gly Ala Ala Gly Ala Ala Thr Gly Ala Cys Cys Thr Cys Cys Thr Cys Gly Ala Ala Gly Ala Ala Thr Gly Ala Cys Cys 115 120 125 115 120 125

Gly Ala Cys Cys Ala Cys Ala Gly Cys Ala Thr Cys Ala Ala Ala Gly Gly Ala Cys Cys Ala Cys Ala Gly Cys Ala Thr Cys Ala Ala Ala Gly 130 135 140 130 135 140

Page 419 Page 419

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Ala Ala Thr Gly Thr Cys Ala Ala Ala Ala Gly Thr Cys Thr Cys Thr Ala Ala Thr Gly Thr Cys Ala Ala Ala Ala Gly Thr Cys Thr Cys Thr 145 150 155 160 145 150 155 160

Thr Gly Ala Cys Thr Thr Thr Gly Thr Ala Cys Thr Ala Gly Gly Cys Thr Gly Ala Cys Thr Thr Thr Gly Thr Ala Cys Thr Ala Gly Gly Cys 165 170 175 165 170 175

Thr Gly Gly Thr Thr Thr Gly Cys Cys Ala Ala Ala Cys Cys Cys Ala Thr Gly Gly Thr Thr Thr Gly Cys Cys Ala Ala Ala Cys Cys Cys Ala 180 185 190 180 185 190

Thr Ala Thr Thr Thr Ala Thr Thr Gly Ala Thr Gly Gly Thr Gly Ala Thr Ala Thr Thr Thr Ala Thr Thr Gly Ala Thr Gly Gly Thr Gly Ala 195 200 205 195 200 205

Cys Thr Ala Thr Cys Cys Thr Gly Ala Gly Ala Gly Cys Ala Thr Gly Cys Thr Ala Thr Cys Cys Thr Gly Ala Gly Ala Gly Cys Ala Thr Gly 210 215 220 210 215 220

Ala Ala Gly Ala Ala Thr Ala Ala Thr Cys Thr Thr Thr Cys Ala Cys Ala Ala Gly Ala Ala Thr Ala Ala Thr Cys Thr Thr Thr Cys Ala Cys 225 230 235 240 225 230 235 240

Ala Thr Cys Thr Thr Cys Thr Gly Cys Cys Thr Gly Ala Thr Thr Thr Ala Thr Cys Thr Thr Cys Thr Gly Cys Cys Thr Gly Ala Thr Thr Thr 245 250 255 245 250 255

Thr Ala Cys Thr Gly Ala Ala Gly Cys Thr Gly Ala Gly Ala Ala Ala Thr Ala Cys Thr Gly Ala Ala Gly Cys Thr Gly Ala Gly Ala Ala Ala 260 265 270 260 265 270

Ala Ala Gly Thr Thr Cys Ala Thr Thr Ala Ala Gly Gly Gly Ala Ala Ala Ala Gly Thr Thr Cys Ala Thr Thr Ala Ala Gly Gly Gly Ala Ala 275 280 285 275 280 285

Cys Ala Gly Cys Thr Gly Ala Cys Thr Thr Thr Thr Thr Thr Gly Cys Cys Ala Gly Cys Thr Gly Ala Cys Thr Thr Thr Thr Thr Thr Gly Cys 290 295 300 290 295 300

Thr Cys Thr Thr Thr Cys Thr Thr Thr Thr Gly Gly Ala Cys Cys Ala Thr Cys Thr Thr Thr Cys Thr Thr Thr Thr Gly Gly Ala Cys Cys Ala 305 310 315 320 305 310 315 320

Ala Cys Cys Thr Thr Gly Ala Gly Thr Thr Thr Thr Cys Ala Ala Cys Ala Cys Cys Thr Thr Gly Ala Gly Thr Thr Thr Thr Cys Ala Ala Cys 325 330 335 325 330 335

Thr Ala Thr Thr Gly Gly Ala Cys Cys Cys Cys Cys Ala Cys Ala Thr Thr Ala Thr Thr Gly Gly Ala Cys Cys Cys Cys Cys Ala Cys Ala Thr 340 345 350 340 345 350

Page 420 Page 420

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Gly Ala Ala Gly Thr Thr Cys Cys Gly Cys Cys Ala Gly Thr Thr Ala Gly Ala Ala Gly Thr Thr Cys Cys Gly Cys Cys Ala Gly Thr Thr Ala 355 360 365 355 360 365

Gly Ala Ala Thr Cys Thr Cys Cys Cys Ala Gly Cys Cys Thr Gly Ala Gly Ala Ala Thr Cys Thr Cys Cys Cys Ala Gly Cys Cys Thr Gly Ala 370 375 380 370 375 380

Gly Gly Cys Ala Ala Cys Thr Cys Cys Thr Thr Thr Cys Thr Thr Gly Gly Gly Cys Ala Ala Cys Thr Cys Cys Thr Thr Thr Cys Thr Thr Gly 385 390 395 400 385 390 395 400

Gly Ala Thr Thr Gly Ala Cys Cys Thr Thr Gly Ala Ala Thr Ala Thr Gly Ala Thr Thr Gly Ala Cys Cys Thr Thr Gly Ala Ala Thr Ala Thr 405 410 415 405 410 415

Ala Ala Cys Cys Ala Cys Cys Cys Thr Cys Ala Ala Ala Thr Ala Thr Ala Ala Cys Cys Ala Cys Cys Cys Thr Cys Ala Ala Ala Thr Ala Thr 420 425 430 420 425 430

Thr Thr Ala Thr Thr Gly Thr Gly Gly Ala Ala Ala Ala Thr Gly Gly Thr Thr Ala Thr Thr Gly Thr Gly Gly Ala Ala Ala Ala Thr Gly Gly 435 440 445 435 440 445

Cys Thr Gly Gly Thr Thr Thr Gly Thr Cys Thr Cys Ala Gly Gly Gly Cys Thr Gly Gly Thr Thr Thr Gly Thr Cys Thr Cys Ala Gly Gly Gly 450 455 460 450 455 460

Ala Cys Cys Ala Cys Cys Ala Ala Gly Ala Gly Ala Gly Ala Cys Gly Ala Cys Cys Ala Cys Cys Ala Ala Gly Ala Gly Ala Gly Ala Cys Gly 465 470 475 480 465 470 475 480

Ala Cys Gly Cys Cys Ala Ala Ala Thr Ala Thr Ala Thr Gly Thr Ala Ala Cys Gly Cys Cys Ala Ala Ala Thr Ala Thr Ala Thr Gly Thr Ala 485 490 495 485 490 495

Thr Thr Ala Cys Cys Thr Cys Ala Ala Ala Ala Ala Ala Thr Thr Cys Thr Thr Ala Cys Cys Thr Cys Ala Ala Ala Ala Ala Ala Thr Thr Cys 500 505 510 500 505 510

Gly Thr Ala Ala Thr Gly Gly Ala Ala Ala Cys Cys Thr Thr Ala Ala Gly Thr Ala Ala Thr Gly Gly Ala Ala Ala Cys Cys Thr Thr Ala Ala 515 520 525 515 520 525

Ala Ala Gly Cys Cys Ala Thr Thr Ala Gly Gly Cys Thr Gly Gly Ala Ala Ala Gly Cys Cys Ala Thr Thr Ala Gly Gly Cys Thr Gly Gly Ala 530 535 540 530 535 540

Thr Gly Gly Gly Gly Thr Gly Gly Ala Cys Gly Thr Cys Ala Thr Thr Thr Gly Gly Gly Gly Thr Gly Gly Ala Cys Gly Thr Cys Ala Thr Thr 545 550 555 560 545 550 555 560

Page 421 Page 421

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Gly Gly Gly Thr Ala Cys Ala Cys Gly Gly Cys Cys Thr Gly Gly Thr Gly Gly Gly Thr Ala Cys Ala Cys Gly Gly Cys Cys Thr Gly Gly Thr 565 570 575 565 570 575

Cys Cys Cys Thr Thr Ala Thr Gly Gly Ala Thr Gly Gly Cys Thr Thr Cys Cys Cys Thr Thr Ala Thr Gly Gly Ala Thr Gly Gly Cys Thr Thr 580 585 590 580 585 590

Cys Gly Ala Ala Thr Gly Gly Cys Ala Cys Ala Gly Ala Gly Gly Thr Cys Gly Ala Ala Thr Gly Gly Cys Ala Cys Ala Gly Ala Gly Gly Thr 595 600 605 595 600 605

Thr Ala Cys Ala Gly Cys Ala Thr Cys Ala Gly Gly Cys Gly Thr Gly Thr Ala Cys Ala Gly Cys Ala Thr Cys Ala Gly Gly Cys Gly Thr Gly 610 615 620 610 615 620

Gly Ala Cys Thr Cys Thr Thr Cys Thr Ala Thr Gly Thr Thr Gly Ala Gly Ala Cys Thr Cys Thr Thr Cys Thr Ala Thr Gly Thr Thr Gly Ala 625 630 635 640 625 630 635 640

Cys Thr Thr Thr Cys Thr Ala Ala Gly Cys Cys Ala Gly Gly Ala Thr Cys Thr Thr Thr Cys Thr Ala Ala Gly Cys Cys Ala Gly Gly Ala Thr 645 650 655 645 650 655

Ala Ala Gly Ala Ala Ala Cys Thr Gly Thr Thr Gly Cys Cys Gly Ala Ala Ala Gly Ala Ala Ala Cys Thr Gly Thr Thr Gly Cys Cys Gly Ala 660 665 670 660 665 670

Ala Ala Thr Cys Thr Thr Cys Ala Gly Cys Cys Thr Thr Gly Thr Thr Ala Ala Thr Cys Thr Thr Cys Ala Gly Cys Cys Thr Thr Gly Thr Thr 675 680 685 675 680 685

Cys Thr Ala Cys Cys Ala Ala Ala Ala Gly Cys Thr Gly Ala Thr Ala Cys Thr Ala Cys Cys Ala Ala Ala Ala Gly Cys Thr Gly Ala Thr Ala 690 695 700 690 695 700

Gly Ala Gly Ala Ala Ala Ala Ala Thr Gly Gly Cys Thr Thr Cys Cys Gly Ala Gly Ala Ala Ala Ala Ala Thr Gly Gly Cys Thr Thr Cys Cys 705 710 715 720 705 710 715 720

Cys Thr Cys Cys Thr Thr Thr Ala Cys Cys Thr Gly Ala Ala Ala Ala Cys Thr Cys Cys Thr Thr Thr Ala Cys Cys Thr Gly Ala Ala Ala Ala 725 730 735 725 730 735

Thr Cys Ala Ala Cys Cys Thr Cys Thr Ala Gly Ala Ala Gly Gly Gly Thr Cys Ala Ala Cys Cys Thr Cys Thr Ala Gly Ala Ala Gly Gly Gly 740 745 750 740 745 750

Ala Cys Ala Thr Thr Thr Cys Cys Cys Thr Gly Thr Gly Ala Cys Thr Ala Cys Ala Thr Thr Thr Cys Cys Cys Thr Gly Thr Gly Ala Cys Thr 755 760 765 755 760 765

Page 422 Page 422

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Thr Thr Gly Cys Thr Thr Gly Gly Gly Gly Ala Ala Thr Thr Gly Thr Thr Thr Gly Cys Thr Thr Gly Gly Gly Gly Ala Ala Thr Thr Gly Thr 770 775 780 770 775 780

Thr Gly Ala Cys Ala Ala Cys Thr Ala Cys Ala Thr Thr Cys Ala Ala Thr Gly Ala Cys Ala Ala Cys Thr Ala Cys Ala Thr Thr Cys Ala Ala 785 790 795 800 785 790 795 800

Gly Thr Gly Gly Ala Cys Ala Cys Cys Ala Cys Thr Cys Thr Gly Thr Gly Thr Gly Gly Ala Cys Ala Cys Cys Ala Cys Thr Cys Thr Gly Thr 805 810 815 805 810 815

Cys Thr Cys Ala Gly Thr Thr Thr Ala Cys Cys Gly Ala Cys Cys Cys Cys Thr Cys Ala Gly Thr Thr Thr Ala Cys Cys Gly Ala Cys Cys Cys 820 825 830 820 825 830

Gly Ala Ala Cys Gly Thr Thr Thr Ala Cys Cys Thr Gly Thr Gly Gly Gly Ala Ala Cys Gly Thr Thr Thr Ala Cys Cys Thr Gly Thr Gly Gly 835 840 845 835 840 845

Gly Ala Cys Gly Thr Cys Cys Ala Cys Cys Ala Cys Ala Gly Thr Ala Gly Ala Cys Gly Thr Cys Cys Ala Cys Cys Ala Cys Ala Gly Thr Ala 850 855 860 850 855 860

Ala Gly Ala Gly Gly Cys Thr Ala Ala Thr Thr Ala Ala Gly Gly Thr Ala Gly Ala Gly Gly Cys Thr Ala Ala Thr Thr Ala Ala Gly Gly Thr 865 870 875 880 865 870 875 880

Gly Gly Ala Cys Gly Gly Gly Gly Thr Thr Gly Thr Gly Ala Cys Cys Gly Gly Ala Cys Gly Gly Gly Gly Thr Thr Gly Thr Gly Ala Cys Cys 885 890 895 885 890 895

Ala Ala Gly Ala Ala Gly Cys Gly Gly Ala Ala Gly Thr Cys Cys Thr Ala Ala Gly Ala Ala Gly Cys Gly Gly Ala Ala Gly Thr Cys Cys Thr 900 905 910 900 905 910

Ala Cys Thr Gly Cys Gly Thr Gly Gly Ala Cys Thr Thr Cys Gly Cys Ala Cys Thr Gly Cys Gly Thr Gly Gly Ala Cys Thr Thr Cys Gly Cys 915 920 925 915 920 925

Thr Gly Cys Cys Ala Thr Cys Cys Gly Gly Cys Cys Cys Cys Ala Gly Thr Gly Cys Cys Ala Thr Cys Cys Gly Gly Cys Cys Cys Cys Ala Gly 930 935 940 930 935 940

Ala Thr Ala Gly Cys Cys Thr Thr Ala Cys Thr Cys Cys Ala Gly Gly Ala Thr Ala Gly Cys Cys Thr Thr Ala Cys Thr Cys Cys Ala Gly Gly 945 950 955 960 945 950 955 960

Ala Gly Ala Thr Gly Cys Ala Cys Gly Thr Thr Thr Cys Cys Cys Ala Ala Gly Ala Thr Gly Cys Ala Cys Gly Thr Thr Thr Cys Cys Cys Ala 965 970 975 965 970 975

Page 423 Page 423

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Thr Thr Thr Cys Cys Ala Cys Thr Thr Cys Thr Cys Cys Cys Thr Gly Thr Thr Thr Cys Cys Ala Cys Thr Thr Cys Thr Cys Cys Cys Thr Gly 980 985 990 980 985 990

Gly Ala Cys Thr Gly Gly Gly Cys Cys Cys Thr Gly Ala Thr Cys Cys Gly Ala Cys Thr Gly Gly Gly Cys Cys Cys Thr Gly Ala Thr Cys Cys 995 1000 1005 995 1000 1005

Thr Gly Cys Cys Gly Cys Thr Gly Gly Gly Cys Ala Ala Cys Cys Thr Gly Cys Cys Gly Cys Thr Gly Gly Gly Cys Ala Ala Cys Cys 1010 1015 1020 1010 1015 1020

Ala Gly Thr Cys Cys Cys Ala Gly Gly Thr Gly Ala Ala Cys Cys Ala Gly Thr Cys Cys Cys Ala Gly Gly Thr Gly Ala Ala Cys Cys 1025 1030 1035 1025 1030 1035

Ala Cys Ala Cys Gly Gly Thr Cys Cys Thr Cys Gly Ala Cys Thr Ala Cys Ala Cys Gly Gly Thr Cys Cys Thr Cys Gly Ala Cys Thr 1040 1045 1050 1040 1045 1050

Ala Cys Thr Ala Cys Cys Gly Cys Thr Gly Cys Gly Thr Gly Gly Ala Cys Thr Ala Cys Cys Gly Cys Thr Gly Cys Gly Thr Gly Gly 1055 1060 1065 1055 1060 1065

Thr Cys Ala Gly Cys Gly Ala Gly Cys Thr Cys Gly Thr Gly Cys Thr Cys Ala Gly Cys Gly Ala Gly Cys Thr Cys Gly Thr Gly Cys 1070 1075 1080 1070 1075 1080

Gly Cys Gly Cys Cys Ala Ala Cys Ala Thr Cys Ala Cys Cys Cys Gly Cys Gly Cys Cys Ala Ala Cys Ala Thr Cys Ala Cys Cys Cys 1085 1090 1095 1085 1090 1095

Cys Gly Gly Thr Gly Gly Thr Gly Gly Cys Gly Cys Thr Cys Thr Cys Gly Gly Thr Gly Gly Thr Gly Gly Cys Gly Cys Thr Cys Thr 1100 1105 1110 1100 1105 1110

Gly Gly Cys Gly Ala Cys Cys Cys Gly Cys Gly Gly Cys Cys Cys Gly Gly Cys Gly Ala Cys Cys Cys Gly Cys Gly Gly Cys Cys Cys 1115 1120 1125 1115 1120 1125

Cys Gly Cys Ala Cys Cys Ala Ala Gly Gly Gly Cys Thr Gly Cys Cys Gly Cys Ala Cys Cys Ala Ala Gly Gly Gly Cys Thr Gly Cys 1130 1135 1140 1130 1135 1140

Cys Gly Cys Gly Gly Cys Cys Cys Cys Thr Gly Gly Cys Cys Ala Cys Gly Cys Gly Gly Cys Cys Cys Cys Thr Gly Gly Cys Cys Ala 1145 1150 1155 1145 1150 1155

Ala Gly Cys Ala Cys Gly Gly Ala Gly Cys Cys Thr Gly Gly Gly Ala Gly Cys Ala Cys Gly Gly Ala Gly Cys Cys Thr Gly Gly Gly 1160 1165 1170 1160 1165 1170

Page 424 Page 424

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Ala Gly Ala Ala Cys Cys Cys Ala Cys Ala Cys Ala Cys Cys Gly Ala Gly Ala Ala Cys Cys Cys Ala Cys Ala Cys Ala Cys Cys Gly 1175 1180 1185 1175 1180 1185

Cys Cys Thr Cys Gly Gly Cys Thr Thr Thr Thr Gly Cys Ala Gly Cys Cys Thr Cys Gly Gly Cys Thr Thr Thr Thr Gly Cys Ala Gly 1190 1195 1200 1190 1195 1200

Ala Gly Thr Ala Cys Gly Cys Cys Cys Gly Gly Cys Thr Gly Thr Ala Gly Thr Ala Cys Gly Cys Cys Cys Gly Gly Cys Thr Gly Thr 1205 1210 1215 1205 1210 1215

Gly Cys Thr Thr Cys Ala Ala Gly Gly Ala Thr Cys Thr Cys Gly Gly Cys Thr Thr Cys Ala Ala Gly Gly Ala Thr Cys Thr Cys Gly 1220 1225 1230 1220 1225 1230

Gly Cys Cys Ala Cys Cys Ala Cys Gly Thr Cys Ala Ala Gly Thr Gly Cys Cys Ala Cys Cys Ala Cys Gly Thr Cys Ala Ala Gly Thr 1235 1240 1245 1235 1240 1245

Thr Cys Thr Gly Gly Ala Thr Cys Ala Cys Gly Ala Thr Gly Gly Thr Cys Thr Gly Gly Ala Thr Cys Ala Cys Gly Ala Thr Gly Gly 1250 1255 1260 1250 1255 1260

Gly Cys Gly Ala Gly Cys Cys Gly Thr Ala Cys Ala Cys Ala Cys Gly Cys Gly Ala Gly Cys Cys Gly Thr Ala Cys Ala Cys Ala Cys 1265 1270 1275 1265 1270 1275

Gly Gly Ala Ala Cys Ala Thr Gly Ala Cys Cys Thr Ala Cys Ala Gly Gly Ala Ala Cys Ala Thr Gly Ala Cys Cys Thr Ala Cys Ala 1280 1285 1290 1280 1285 1290

Gly Cys Gly Cys Gly Gly Gly Gly Cys Ala Cys Ala Ala Thr Cys Gly Cys Gly Cys Gly Gly Gly Gly Cys Ala Cys Ala Ala Thr Cys 1295 1300 1305 1295 1300 1305

Thr Thr Cys Thr Gly Ala Ala Gly Gly Cys Thr Cys Ala Cys Gly Thr Thr Cys Thr Gly Ala Ala Gly Gly Cys Thr Cys Ala Cys Gly 1310 1315 1320 1310 1315 1320

Cys Gly Thr Thr Gly Gly Cys Cys Thr Gly Gly Cys Gly Cys Gly Cys Gly Thr Thr Gly Gly Cys Cys Thr Gly Gly Cys Gly Cys Gly 1325 1330 1335 1325 1330 1335

Thr Gly Thr Ala Cys Gly Ala Thr Gly Ala Ala Ala Ala Cys Thr Thr Gly Thr Ala Cys Gly Ala Thr Gly Ala Ala Ala Ala Cys Thr 1340 1345 1350 1340 1345 1350

Thr Thr Cys Gly Gly Gly Gly Cys Thr Cys Thr Cys Ala Gly Ala Thr Thr Cys Gly Gly Gly Gly Cys Thr Cys Thr Cys Ala Gly Ala 1355 1360 1365 1355 1360 1365

Page 425 Page 425

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Ala Gly Gly Gly Gly Ala Ala Ala Ala Thr Ala Thr Cys Cys Ala Ala Gly Gly Gly Gly Ala Ala Ala Ala Thr Ala Thr Cys Cys Ala 1370 1375 1380 1370 1375 1380

Thr Ala Gly Cys Cys Cys Thr Gly Cys Ala Gly Gly Cys Cys Gly Thr Ala Gly Cys Cys Cys Thr Gly Cys Ala Gly Gly Cys Cys Gly 1385 1390 1395 1385 1390 1395

Ala Cys Thr Gly Gly Ala Thr Ala Gly Ala Gly Cys Cys Gly Gly Ala Cys Thr Gly Gly Ala Thr Ala Gly Ala Gly Cys Cys Gly Gly 1400 1405 1410 1400 1405 1410

Cys Cys Thr Gly Cys Cys Cys Thr Thr Thr Cys Thr Cys Cys Cys Cys Cys Thr Gly Cys Cys Cys Thr Thr Thr Cys Thr Cys Cys Cys 1415 1420 1425 1415 1420 1425

Ala Ala Ala Ala Gly Gly Ala Cys Ala Ala Ala Gly Ala Ala Gly Ala Ala Ala Ala Gly Gly Ala Cys Ala Ala Ala Gly Ala Ala Gly 1430 1435 1440 1430 1435 1440

Thr Gly Gly Cys Ala Gly Ala Gly Ala Gly Ala Gly Thr Thr Thr Thr Gly Gly Cys Ala Gly Ala Gly Ala Gly Ala Gly Thr Thr Thr 1445 1450 1455 1445 1450 1455

Thr Gly Gly Ala Ala Thr Thr Thr Gly Ala Cys Ala Thr Thr Gly Thr Gly Gly Ala Ala Thr Thr Thr Gly Ala Cys Ala Thr Thr Gly 1460 1465 1470 1460 1465 1470

Gly Cys Thr Gly Gly Cys Thr Gly Gly Cys Cys Gly Ala Gly Cys Gly Cys Thr Gly Gly Cys Thr Gly Gly Cys Cys Gly Ala Gly Cys 1475 1480 1485 1475 1480 1485

Cys Cys Ala Thr Thr Thr Thr Cys Gly Gly Cys Thr Cys Thr Gly Cys Cys Ala Thr Thr Thr Thr Cys Gly Gly Cys Thr Cys Thr Gly 1490 1495 1500 1490 1495 1500

Gly Gly Gly Ala Thr Thr Ala Thr Cys Cys Gly Cys Gly Thr Gly Gly Gly Gly Ala Thr Thr Ala Thr Cys Cys Gly Cys Gly Thr Gly 1505 1510 1515 1505 1510 1515

Thr Gly Ala Thr Gly Ala Gly Gly Gly Ala Cys Thr Gly Gly Cys Thr Gly Ala Thr Gly Ala Gly Gly Gly Ala Cys Thr Gly Gly Cys 1520 1525 1530 1520 1525 1530

Thr Cys Ala Cys Gly Cys Ala Gly Ala Gly Ala Ala Ala Cys Ala Thr Cys Ala Cys Gly Cys Ala Gly Ala Gly Ala Ala Ala Cys Ala 1535 1540 1545 1535 1540 1545

Ala Thr Thr Thr Cys Cys Thr Thr Cys Thr Ala Cys Cys Thr Thr Ala Thr Thr Thr Cys Cys Thr Thr Cys Thr Ala Cys Cys Thr Thr 1550 1555 1560 1550 1555 1560

Page 426 Page 426

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Ala Thr Thr Thr Cys Ala Cys Thr Gly Ala Ala Gly Ala Thr Gly Ala Thr Thr Thr Cys Ala Cys Thr Gly Ala Ala Gly Ala Thr Gly 1565 1570 1575 1565 1570 1575

Ala Ala Ala Ala Ala Ala Ala Gly Cys Thr Ala Ala Thr Cys Cys Ala Ala Ala Ala Ala Ala Ala Gly Cys Thr Ala Ala Thr Cys Cys 1580 1585 1590 1580 1585 1590

Gly Gly Gly Gly Thr Thr Cys Cys Thr Thr Cys Gly Ala Cys Thr Gly Gly Gly Gly Thr Thr Cys Cys Thr Thr Cys Gly Ala Cys Thr 1595 1600 1605 1595 1600 1605

Thr Thr Cys Thr Gly Gly Cys Cys Gly Thr Ala Ala Gly Cys Cys Thr Thr Cys Thr Gly Gly Cys Cys Gly Thr Ala Ala Gly Cys Cys 1610 1615 1620 1610 1615 1620

Ala Thr Thr Ala Cys Ala Cys Cys Ala Cys Cys Ala Thr Cys Cys Ala Thr Thr Ala Cys Ala Cys Cys Ala Cys Cys Ala Thr Cys Cys 1625 1630 1635 1625 1630 1635

Thr Cys Gly Thr Cys Gly Ala Cys Thr Gly Gly Gly Ala Ala Ala Thr Cys Gly Thr Cys Gly Ala Cys Thr Gly Gly Gly Ala Ala Ala 1640 1645 1650 1640 1645 1650

Ala Ala Gly Ala Ala Gly Ala Thr Cys Cys Ala Ala Thr Gly Ala Ala Ala Gly Ala Ala Gly Ala Thr Cys Cys Ala Ala Thr Gly Ala 1655 1660 1665 1655 1660 1665

Ala Ala Thr Ala Cys Ala Ala Cys Gly Ala Thr Thr Ala Cys Cys Ala Ala Thr Ala Cys Ala Ala Cys Gly Ala Thr Thr Ala Cys Cys 1670 1675 1680 1670 1675 1680

Thr Gly Gly Ala Gly Gly Thr Gly Cys Ala Gly Gly Ala Ala Ala Thr Gly Gly Ala Gly Gly Thr Gly Cys Ala Gly Gly Ala Ala Ala 1685 1690 1695 1685 1690 1695

Thr Gly Ala Cys Cys Gly Ala Cys Ala Thr Cys Ala Cys Gly Thr Thr Gly Ala Cys Cys Gly Ala Cys Ala Thr Cys Ala Cys Gly Thr 1700 1705 1710 1700 1705 1710

Gly Gly Cys Thr Cys Ala Ala Cys Thr Cys Cys Cys Cys Cys Ala Gly Gly Cys Thr Cys Ala Ala Cys Thr Cys Cys Cys Cys Cys Ala 1715 1720 1725 1715 1720 1725

Gly Thr Cys Ala Gly Gly Thr Gly Gly Cys Ala Gly Thr Ala Gly Gly Thr Cys Ala Gly Gly Thr Gly Gly Cys Ala Gly Thr Ala Gly 1730 1735 1740 1730 1735 1740

Thr Gly Cys Cys Cys Thr Gly Gly Gly Gly Cys Thr Thr Ala Cys Thr Gly Cys Cys Cys Thr Gly Gly Gly Gly Cys Thr Thr Ala Cys 1745 1750 1755 1745 1750 1755

Page 427 Page 427

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Gly Cys Ala Ala Ala Ala Thr Thr Cys Thr Cys Ala Ala Cys Thr Gly Cys Ala Ala Ala Ala Thr Thr Cys Thr Cys Ala Ala Cys Thr 1760 1765 1770 1760 1765 1770

Gly Gly Cys Thr Gly Ala Ala Gly Cys Thr Gly Ala Ala Gly Thr Gly Gly Cys Thr Gly Ala Ala Gly Cys Thr Gly Ala Ala Gly Thr 1775 1780 1785 1775 1780 1785

Ala Cys Gly Gly Ala Gly Ala Cys Cys Thr Cys Cys Cys Cys Ala Ala Cys Gly Gly Ala Gly Ala Cys Cys Thr Cys Cys Cys Cys Ala 1790 1795 1800 1790 1795 1800

Thr Gly Thr Ala Thr Ala Thr Ala Ala Thr Ala Thr Cys Cys Ala Thr Gly Thr Ala Thr Ala Thr Ala Ala Thr Ala Thr Cys Cys Ala 1805 1810 1815 1805 1810 1815

Ala Cys Gly Gly Cys Ala Thr Ala Gly Ala Cys Gly Ala Cys Gly Ala Cys Gly Gly Cys Ala Thr Ala Gly Ala Cys Gly Ala Cys Gly 1820 1825 1830 1820 1825 1830

Ala Thr Cys Cys Gly Cys Ala Gly Gly Cys Ala Gly Cys Gly Cys Ala Thr Cys Cys Gly Cys Ala Gly Gly Cys Ala Gly Cys Gly Cys 1835 1840 1845 1835 1840 1845

Ala Ala Gly Ala Cys Ala Ala Gly Cys Thr Gly Ala Gly Gly Gly Ala Ala Gly Ala Cys Ala Ala Gly Cys Thr Gly Ala Gly Gly Gly 1850 1855 1860 1850 1855 1860

Thr Gly Thr Ala Thr Thr Ala Cys Ala Thr Gly Cys Ala Ala Ala Thr Gly Thr Ala Thr Thr Ala Cys Ala Thr Gly Cys Ala Ala Ala 1865 1870 1875 1865 1870 1875

Ala Thr Thr Ala Thr Gly Thr Ala Ala Ala Thr Gly Ala Ala Gly Ala Thr Thr Ala Thr Gly Thr Ala Ala Ala Thr Gly Ala Ala Gly 1880 1885 1890 1880 1885 1890

Cys Thr Cys Thr Gly Ala Ala Ala Gly Cys Cys Thr Ala Cys Gly Cys Thr Cys Thr Gly Ala Ala Ala Gly Cys Cys Thr Ala Cys Gly 1895 1900 1905 1895 1900 1905

Thr Ala Thr Thr Gly Gly Ala Thr Gly Gly Thr Gly Thr Cys Ala Thr Ala Thr Thr Gly Gly Ala Thr Gly Gly Thr Gly Thr Cys Ala 1910 1915 1920 1910 1915 1920

Ala Thr Cys Thr Thr Thr Gly Thr Gly Gly Ala Thr Ala Cys Thr Ala Thr Cys Thr Thr Thr Gly Thr Gly Gly Ala Thr Ala Cys Thr 1925 1930 1935 1925 1930 1935

Thr Thr Gly Cys Thr Thr Ala Thr Thr Cys Ala Thr Thr Cys Ala Thr Thr Gly Cys Thr Thr Ala Thr Thr Cys Ala Thr Thr Cys Ala 1940 1945 1950 1940 1945 1950

Page 428 Page 428

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Ala Thr Gly Ala Thr Cys Gly Cys Ala Cys Ala Gly Cys Thr Cys Ala Thr Gly Ala Thr Cys Gly Cys Ala Cys Ala Gly Cys Thr Cys 1955 1960 1965 1955 1960 1965

Cys Ala Ala Ala Gly Thr Thr Thr Gly Gly Cys Thr Thr Cys Thr Cys Ala Ala Ala Gly Thr Thr Thr Gly Gly Cys Thr Thr Cys Thr 1970 1975 1980 1970 1975 1980

Ala Thr Cys Ala Thr Thr Ala Cys Gly Cys Thr Gly Cys Ala Ala Ala Thr Cys Ala Thr Thr Ala Cys Gly Cys Thr Gly Cys Ala Ala 1985 1990 1995 1985 1990 1995

Ala Thr Cys Ala Gly Thr Thr Thr Gly Ala Gly Cys Cys Cys Ala Ala Thr Cys Ala Gly Thr Thr Thr Gly Ala Gly Cys Cys Cys Ala 2000 2005 2010 2000 2005 2010

Ala Ala Cys Cys Gly Thr Cys Cys Ala Thr Gly Ala Ala Ala Cys Ala Ala Cys Cys Gly Thr Cys Cys Ala Thr Gly Ala Ala Ala Cys 2015 2020 2025 2015 2020 2025

Ala Thr Thr Ala Thr Cys Gly Gly Ala Ala Ala Ala Thr Gly Ala Ala Thr Thr Ala Thr Cys Gly Gly Ala Ala Ala Ala Thr Gly Ala 2030 2035 2040 2030 2035 2040

Thr Thr Gly Ala Cys Ala Gly Cys Ala Ala Thr Gly Gly Cys Thr Thr Thr Gly Ala Cys Ala Gly Cys Ala Ala Thr Gly Gly Cys Thr 2045 2050 2055 2045 2050 2055

Thr Cys Thr Cys Cys Gly Gly Thr Cys Cys Thr Gly Ala Cys Ala Thr Cys Thr Cys Cys Gly Gly Thr Cys Cys Thr Gly Ala Cys Ala 2060 2065 2070 2060 2065 2070

Cys Thr Cys Thr Gly Gly Gly Gly Ala Gly Ala Thr Thr Thr Thr Cys Thr Cys Thr Gly Gly Gly Gly Ala Gly Ala Thr Thr Thr Thr 2075 2080 2085 2075 2080 2085

Gly Thr Cys Cys Ala Gly Ala Ala Gly Ala Ala Thr Thr Cys Ala Gly Thr Cys Cys Ala Gly Ala Ala Gly Ala Ala Thr Thr Cys Ala 2090 2095 2100 2090 2095 2100

Cys Cys Cys Thr Gly Thr Gly Cys Ala Cys Cys Gly Ala Ala Thr Cys Cys Cys Thr Gly Thr Gly Cys Ala Cys Cys Gly Ala Ala Thr 2105 2110 2115 2105 2110 2115

Gly Cys Gly Gly Cys Thr Thr Thr Thr Thr Thr Cys Ala Cys Ala Gly Cys Gly Gly Cys Thr Thr Thr Thr Thr Thr Cys Ala Cys Ala 2120 2125 2130 2120 2125 2130

Cys Cys Cys Gly Cys Ala Ala Ala Thr Cys Thr Thr Thr Ala Cys Cys Cys Cys Gly Cys Ala Ala Ala Thr Cys Thr Thr Thr Ala Cys 2135 2140 2145 2135 2140 2145

Page 429 Page 429

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing.1 TXT Thr Gly Gly Cys Thr Thr Thr Cys Ala Thr Ala Gly Cys Thr Thr Thr Gly Gly Cys Thr Thr Thr Cys Ala Thr Ala Gly Cys Thr Thr 2150 2155 2160 2150 2155 2160

Thr Cys Cys Thr Ala Cys Thr Thr Thr Thr Thr Gly Cys Thr Thr Thr Cys Cys Thr Ala Cys Thr Thr Thr Thr Thr Gly Cys Thr Thr 2165 2170 2175 2165 2170 2175

Thr Thr Ala Thr Thr Ala Thr Thr Thr Cys Thr Cys Thr Thr Thr Thr Thr Ala Thr Thr Ala Thr Thr Thr Cys Thr Cys Thr Thr Thr 2180 2185 2190 2180 2185 2190

Cys Thr Cys Thr Gly Ala Thr Thr Thr Thr Thr Thr Ala Cys Thr Cys Thr Cys Thr Gly Ala Thr Thr Thr Thr Thr Thr Ala Cys Thr 2195 2200 2205 2195 2200 2205

Ala Cys Thr Cys Thr Ala Ala Gly Ala Ala Ala Gly Gly Cys Ala Ala Cys Thr Cys Thr Ala Ala Gly Ala Ala Ala Gly Gly Cys Ala 2210 2215 2220 2210 2215 2220

Ala Ala Ala Gly Ala Ala Gly Thr Thr Ala Cys Ala Ala Gly Thr Ala Ala Ala Gly Ala Ala Gly Thr Thr Ala Cys Ala Ala Gly Thr 2225 2230 2235 2225 2230 2235

Ala Gly Thr Cys Cys Thr Gly Ala Cys Cys Thr Thr Thr Thr Thr Ala Gly Thr Cys Cys Thr Gly Ala Cys Cys Thr Thr Thr Thr Thr 2240 2245 2250 2240 2245 2250

Cys Cys Thr Ala Thr Thr Cys Ala Thr Thr Thr Ala Cys Thr Thr Cys Cys Thr Ala Thr Thr Cys Ala Thr Thr Thr Ala Cys Thr Thr 2255 2260 2265 2255 2260 2265

Thr Gly Ala Ala Ala Thr Gly Ala Thr Thr Ala Thr Gly Cys Ala Thr Gly Ala Ala Ala Thr Gly Ala Thr Thr Ala Thr Gly Cys Ala 2270 2275 2280 2270 2275 2280

Cys Ala Cys Ala Cys Ala Thr Cys Ala Gly Cys Thr Gly Thr Thr Cys Ala Cys Ala Cys Ala Thr Cys Ala Gly Cys Thr Gly Thr Thr 2285 2290 2295 2285 2290 2295

Cys Ala Cys Cys Ala Thr Thr Thr Gly Cys Ala Cys Thr Thr Cys Cys Ala Cys Cys Ala Thr Thr Thr Gly Cys Ala Cys Thr Thr Cys 2300 2305 2310 2300 2305 2310

Thr Cys Ala Gly Thr Gly Thr Cys Gly Thr Ala Ala Gly Ala Cys Thr Cys Ala Gly Thr Gly Thr Cys Gly Thr Ala Ala Gly Ala Cys 2315 2320 2325 2315 2320 2325

Thr Gly Gly Ala Thr Thr Thr Cys Ala Cys Thr Thr Ala Thr Cys Thr Gly Gly Ala Thr Thr Thr Cys Ala Cys Thr Thr Ala Thr Cys 2330 2335 2340 2330 2335 2340

Page 430 Page 430

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Thr Gly Ala Cys Thr Thr Cys Thr Ala Gly Ala Ala Ala Ala Ala Thr Gly Ala Cys Thr Thr Cys Thr Ala Gly Ala Ala Ala Ala Ala 2345 2350 2355 2345 2350 2355

Ala Ala Ala Thr Gly Thr Gly Thr Gly Gly Cys Gly Thr Ala Thr Ala Ala Ala Thr Gly Thr Gly Thr Gly Gly Cys Gly Thr Ala Thr 2360 2365 2370 2360 2365 2370

Gly Ala Cys Ala Gly Ala Gly Gly Thr Ala Thr Gly Gly Ala Ala Gly Ala Cys Ala Gly Ala Gly Gly Thr Ala Thr Gly Gly Ala Ala 2375 2380 2385 2375 2380 2385

Gly Thr Gly Ala Gly Cys Ala Thr Ala Gly Gly Thr Gly Ala Thr Gly Thr Gly Ala Gly Cys Ala Thr Ala Gly Gly Thr Gly Ala Thr 2390 2395 2400 2390 2395 2400

Thr Gly Thr Ala Ala Ala Ala Thr Ala Cys Thr Gly Ala Ala Thr Thr Gly Thr Ala Ala Ala Ala Thr Ala Cys Thr Gly Ala Ala Thr 2405 2410 2415 2405 2410 2415

Ala Ala Thr Gly Thr Gly Ala Ala Thr Ala Gly Thr Gly Cys Cys Ala Ala Thr Gly Thr Gly Ala Ala Thr Ala Gly Thr Gly Cys Cys 2420 2425 2430 2420 2425 2430

Thr Gly Gly Ala Thr Thr Thr Gly Thr Thr Cys Thr Thr Thr Cys Thr Gly Gly Ala Thr Thr Thr Gly Thr Thr Cys Thr Thr Thr Cys 2435 2440 2445 2435 2440 2445

Thr Thr Gly Gly Ala Gly Gly Ala Thr Gly Ala Thr Cys Ala Ala Thr Thr Gly Gly Ala Gly Gly Ala Thr Gly Ala Thr Cys Ala Ala 2450 2455 2460 2450 2455 2460

Ala Gly Ala Cys Gly Gly Thr Thr Ala Gly Gly Gly Gly Cys Cys Ala Gly Ala Cys Gly Gly Thr Thr Ala Gly Gly Gly Gly Cys Cys 2465 2470 2475 2465 2470 2475

Ala Thr Cys Ala Thr Cys Thr Cys Thr Gly Cys Ala Ala Cys Ala Ala Thr Cys Ala Thr Cys Thr Cys Thr Gly Cys Ala Ala Cys Ala 2480 2485 2490 2480 2485 2490

Cys Ala Thr Thr Cys Thr Gly Thr Ala Ala Cys Ala Ala Ala Thr Cys Ala Thr Thr Cys Thr Gly Thr Ala Ala Cys Ala Ala Ala Thr 2495 2500 2505 2495 2500 2505

Gly Thr Ala Thr Gly Gly Gly Ala Ala Gly Thr Gly Gly Gly Ala Gly Thr Ala Thr Gly Gly Gly Ala Ala Gly Thr Gly Gly Gly Ala 2510 2515 2520 2510 2515 2520

Cys Cys Cys Ala Thr Thr Cys Thr Gly Gly Ala Ala Cys Ala Thr Cys Cys Cys Ala Thr Thr Cys Thr Gly Gly Ala Ala Cys Ala Thr 2525 2530 2535 2525 2530 2535

Page 431 Page 431

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Thr Thr Thr Thr Ala Thr Ala Gly Ala Ala Ala Thr Thr Gly Ala Thr Thr Thr Thr Ala Thr Ala Gly Ala Ala Ala Thr Thr Gly Ala 2540 2545 2550 2540 2545 2550

Ala Thr Ala Gly Cys Ala Ala Gly Ala Thr Cys Ala Gly Thr Gly Ala Thr Ala Gly Cys Ala Ala Gly Ala Thr Cys Ala Gly Thr Gly 2555 2560 2565 2555 2560 2565

Cys Cys Cys Gly Thr Thr Cys Cys Thr Ala Ala Ala Thr Thr Ala Cys Cys Cys Gly Thr Thr Cys Cys Thr Ala Ala Ala Thr Thr Ala 2570 2575 2580 2570 2575 2580

Thr Cys Thr Thr Gly Ala Ala Gly Thr Ala Ala Ala Ala Cys Ala Thr Cys Thr Thr Gly Ala Ala Gly Thr Ala Ala Ala Ala Cys Ala 2585 2590 2595 2585 2590 2595

Ala Ala Thr Gly Thr Gly Gly Ala Ala Ala Thr Ala Ala Ala Ala Ala Ala Thr Gly Thr Gly Gly Ala Ala Ala Thr Ala Ala Ala Ala 2600 2605 2610 2600 2605 2610

Ala Gly Thr Thr Ala Ala Gly Thr Cys Cys Cys Ala Ala Ala Thr Ala Gly Thr Thr Ala Ala Gly Thr Cys Cys Cys Ala Ala Ala Thr 2615 2620 2625 2615 2620 2625

Ala Ala Cys Cys Ala Thr Cys Thr Cys Thr Ala Ala Ala Cys Thr Ala Ala Cys Cys Ala Thr Cys Thr Cys Thr Ala Ala Ala Cys Thr 2630 2635 2640 2630 2635 2640

Thr Cys Cys Ala Thr Gly Ala Thr Ala Thr Gly Cys Cys Thr Ala Thr Cys Cys Ala Thr Gly Ala Thr Ala Thr Gly Cys Cys Thr Ala 2645 2650 2655 2645 2650 2655

Ala Thr Gly Gly Thr Cys Thr Cys Thr Gly Thr Thr Gly Gly Ala Ala Thr Gly Gly Thr Cys Thr Cys Thr Gly Thr Thr Gly Gly Ala 2660 2665 2670 2660 2665 2670

Cys Cys Cys Ala Gly Thr Thr Thr Cys Cys Cys Thr Thr Gly Ala Cys Cys Cys Ala Gly Thr Thr Thr Cys Cys Cys Thr Thr Gly Ala 2675 2680 2685 2675 2680 2685

Ala Ala Ala Ala Gly Ala Ala Ala Thr Gly Gly Thr Ala Gly Ala Ala Ala Ala Ala Gly Ala Ala Ala Thr Gly Gly Thr Ala Gly Ala 2690 2695 2700 2690 2695 2700

Ala Thr Ala Thr Thr Ala Gly Ala Gly Ala Cys Ala Thr Gly Ala Ala Thr Ala Thr Thr Ala Gly Ala Gly Ala Cys Ala Thr Gly Ala 2705 2710 2715 2705 2710 2715

Cys Ala Gly Ala Gly Gly Gly Cys Cys Cys Thr Ala Cys Gly Cys Cys Ala Gly Ala Gly Gly Gly Cys Cys Cys Thr Ala Cys Gly Cys 2720 2725 2730 2720 2725 2730

Page 432 Page 432

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Thr Ala Gly Ala Ala Cys Gly Thr Thr Cys Cys Thr Thr Thr Thr Thr Ala Gly Ala Ala Cys Gly Thr Thr Cys Cys Thr Thr Thr Thr 2735 2740 2745 2735 2740 2745

Ala Thr Thr Thr Thr Thr Thr Thr Thr Thr Thr Thr Ala Ala Ala Ala Thr Thr Thr Thr Thr Thr Thr Thr Thr Thr Thr Ala Ala Ala 2750 2755 2760 2750 2755 2760

Thr Thr Thr Thr Thr Thr Thr Thr Cys Ala Ala Thr Gly Thr Thr Thr Thr Thr Thr Thr Thr Thr Thr Cys Ala Ala Thr Gly Thr Thr 2765 2770 2775 2765 2770 2775

Thr Thr Thr Ala Thr Thr Thr Ala Thr Thr Thr Thr Thr Gly Gly Thr Thr Thr Ala Thr Thr Thr Ala Thr Thr Thr Thr Thr Gly Gly 2780 2785 2790 2780 2785 2790

Gly Ala Cys Ala Gly Ala Gly Ala Gly Ala Gly Ala Gly Ala Cys Ala Gly Ala Gly Ala Gly Ala Gly Ala 2795 2800 2805 2795 2800 2805

<210> 123 <210> 123 <211> 3178 <211> 3178 <212> PRT <212> PRT <213> Felis catus <213> Felis catus

<400> 123 <400> 123

Gly Gly Gly Gly Thr Cys Ala Cys Cys Cys Ala Cys Thr Ala Cys Cys Gly Gly Gly Gly Thr Cys Ala Cys Cys Cys Ala Cys Thr Ala Cys Cys 1 5 10 15 1 5 10 15

Gly Cys Thr Thr Cys Thr Cys Cys Ala Thr Cys Thr Cys Gly Thr Gly Gly Cys Thr Thr Cys Thr Cys Cys Ala Thr Cys Thr Cys Gly Thr Gly 20 25 30 20 25 30

Gly Gly Cys Gly Cys Gly Gly Gly Thr Gly Cys Thr Cys Cys Cys Cys Gly Gly Cys Gly Cys Gly Gly Gly Thr Gly Cys Thr Cys Cys Cys Cys 35 40 45 35 40 45

Ala Ala Thr Gly Gly Cys Ala Gly Cys Gly Cys Gly Gly Gly Cys Gly Ala Ala Thr Gly Gly Cys Ala Gly Cys Gly Cys Gly Gly Gly Cys Gly 50 55 60 50 55 60

Cys Cys Cys Cys Cys Ala Ala Cys Cys Gly Cys Gly Ala Gly Gly Gly Cys Cys Cys Cys Cys Ala Ala Cys Cys Gly Cys Gly Ala Gly Gly Gly 65 70 75 80 70 75 80

Gly Cys Thr Gly Cys Gly Cys Thr Ala Cys Thr Ala Cys Cys Gly Gly Gly Cys Thr Gly Cys Gly Cys Thr Ala Cys Thr Ala Cys Cys Gly Gly 85 90 95 85 90 95

Cys Gly Cys Cys Thr Gly Cys Thr Gly Gly Ala Gly Cys Gly Gly Cys Cys Gly Cys Cys Thr Gly Cys Thr Gly Gly Ala Gly Cys Gly Gly Cys Page 433 Page 433

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing TXT 100 105 110 100 105 110

Thr Gly Cys Gly Gly Gly Ala Gly Cys Thr Gly Gly Gly Cys Gly Thr Thr Gly Cys Gly Gly Gly Ala Gly Cys Thr Gly Gly Gly Cys Gly Thr 115 120 125 115 120 125

Gly Cys Ala Gly Cys Cys Cys Gly Thr Gly Gly Thr Cys Ala Cys Cys Gly Cys Ala Gly Cys Cys Cys Gly Thr Gly Gly Thr Cys Ala Cys Cys 130 135 140 130 135 140

Cys Thr Gly Thr Ala Cys Cys Ala Cys Thr Ala Gly Gly Ala Cys Cys Cys Thr Gly Thr Ala Cys Cys Ala Cys Thr Ala Gly Gly Ala Cys Cys 145 150 155 160 145 150 155 160

Thr Gly Cys Cys Cys Cys Ala Gly Cys Gly Cys Cys Thr Gly Cys Ala Thr Gly Cys Cys Cys Cys Ala Gly Cys Gly Cys Cys Thr Gly Cys Ala 165 170 175 165 170 175

Gly Gly Ala Cys Gly Cys Cys Thr Ala Cys Gly Gly Cys Gly Gly Cys Gly Gly Ala Cys Gly Cys Cys Thr Ala Cys Gly Gly Cys Gly Gly Cys 180 185 190 180 185 190

Thr Gly Gly Gly Cys Cys Ala Ala Cys Cys Gly Cys Gly Cys Cys Cys Thr Gly Gly Gly Cys Cys Ala Ala Cys Cys Gly Cys Gly Cys Cys Cys 195 200 205 195 200 205

Thr Gly Gly Cys Cys Gly Ala Cys Cys Ala Cys Thr Thr Cys Ala Gly Thr Gly Gly Cys Cys Gly Ala Cys Cys Ala Cys Thr Thr Cys Ala Gly 210 215 220 210 215 220

Gly Gly Ala Thr Thr Ala Cys Gly Cys Cys Gly Ala Gly Cys Thr Cys Gly Gly Ala Thr Thr Ala Cys Gly Cys Cys Gly Ala Gly Cys Thr Cys 225 230 235 240 225 230 235 240

Thr Gly Cys Thr Thr Cys Cys Gly Cys Cys Ala Cys Thr Thr Cys Gly Thr Gly Cys Thr Thr Cys Cys Gly Cys Cys Ala Cys Thr Thr Cys Gly 245 250 255 245 250 255

Gly Cys Gly Gly Cys Cys Ala Gly Gly Thr Cys Ala Ala Gly Thr Ala Gly Cys Gly Gly Cys Cys Ala Gly Gly Thr Cys Ala Ala Gly Thr Ala 260 265 270 260 265 270

Cys Thr Gly Gly Ala Thr Cys Ala Cys Cys Ala Thr Cys Gly Ala Cys Cys Thr Gly Gly Ala Thr Cys Ala Cys Cys Ala Thr Cys Gly Ala Cys 275 280 285 275 280 285

Ala Ala Cys Cys Cys Cys Thr Ala Cys Gly Thr Gly Gly Thr Gly Gly Ala Ala Cys Cys Cys Cys Thr Ala Cys Gly Thr Gly Gly Thr Gly Gly 290 295 300 290 295 300

Cys Cys Thr Gly Gly Cys Ala Cys Gly Gly Cys Thr Ala Cys Gly Cys Cys Cys Thr Gly Gly Cys Ala Cys Gly Gly Cys Thr Ala Cys Gly Cys Page 434 Page 434

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 305 310 315 320 305 310 315 320

Cys Ala Cys Cys Gly Gly Gly Cys Gly Cys Cys Thr Gly Gly Cys Cys Cys Ala Cys Cys Gly Gly Gly Cys Gly Cys Cys Thr Gly Gly Cys Cys 325 330 335 325 330 335

Cys Cys Thr Gly Gly Cys Gly Thr Cys Cys Gly Gly Gly Gly Cys Ala Cys Cys Thr Gly Gly Cys Gly Thr Cys Cys Gly Gly Gly Gly Cys Ala 340 345 350 340 345 350

Gly Cys Gly Cys Gly Cys Gly Gly Cys Thr Cys Gly Gly Gly Thr Ala Gly Cys Gly Cys Gly Cys Gly Gly Cys Thr Cys Gly Gly Gly Thr Ala 355 360 365 355 360 365

Cys Cys Thr Gly Gly Thr Gly Gly Cys Gly Cys Ala Cys Ala Ala Cys Cys Cys Thr Gly Gly Thr Gly Gly Cys Gly Cys Ala Cys Ala Ala Cys 370 375 380 370 375 380

Cys Thr Cys Cys Thr Cys Cys Thr Gly Gly Cys Thr Cys Ala Thr Gly Cys Thr Cys Cys Thr Cys Cys Thr Gly Gly Cys Thr Cys Ala Thr Gly 385 390 395 400 385 390 395 400

Cys Cys Ala Ala Ala Ala Thr Cys Thr Gly Gly Cys Ala Thr Cys Thr Cys Cys Ala Ala Ala Ala Thr Cys Thr Gly Gly Cys Ala Thr Cys Thr 405 410 415 405 410 415

Cys Thr Ala Cys Ala Ala Thr Ala Cys Thr Thr Cys Thr Thr Thr Cys Cys Thr Ala Cys Ala Ala Thr Ala Cys Thr Thr Cys Thr Thr Thr Cys 420 425 430 420 425 430

Cys Gly Thr Cys Cys Ala Ala Cys Thr Cys Ala Gly Gly Gly Ala Gly Cys Gly Thr Cys Cys Ala Ala Cys Thr Cys Ala Gly Gly Gly Ala Gly 435 440 445 435 440 445

Gly Cys Cys Ala Gly Gly Thr Cys Thr Cys Cys Ala Thr Cys Gly Cys Gly Cys Cys Ala Gly Gly Thr Cys Thr Cys Cys Ala Thr Cys Gly Cys 450 455 460 450 455 460

Cys Cys Thr Ala Ala Gly Cys Thr Cys Cys Cys Ala Cys Thr Gly Gly Cys Cys Thr Ala Ala Gly Cys Thr Cys Cys Cys Ala Cys Thr Gly Gly 465 470 475 480 465 470 475 480

Ala Thr Cys Ala Ala Thr Cys Cys Thr Cys Gly Ala Ala Gly Ala Ala Ala Thr Cys Ala Ala Thr Cys Cys Thr Cys Gly Ala Ala Gly Ala Ala 485 490 495 485 490 495

Thr Gly Ala Cys Cys Gly Ala Cys Cys Ala Cys Ala Gly Cys Ala Thr Thr Gly Ala Cys Cys Gly Ala Cys Cys Ala Cys Ala Gly Cys Ala Thr 500 505 510 500 505 510

Cys Ala Ala Ala Gly Ala Ala Thr Gly Thr Cys Ala Ala Ala Ala Gly Cys Ala Ala Ala Gly Ala Ala Thr Gly Thr Cys Ala Ala Ala Ala Gly Page 435 Page 435

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 515 520 525 515 520 525

Thr Cys Thr Cys Thr Thr Gly Ala Cys Thr Thr Thr Gly Thr Ala Cys Thr Cys Thr Cys Thr Thr Gly Ala Cys Thr Thr Thr Gly Thr Ala Cys 530 535 540 530 535 540

Thr Ala Gly Gly Cys Thr Gly Gly Thr Thr Thr Gly Cys Cys Ala Ala Thr Ala Gly Gly Cys Thr Gly Gly Thr Thr Thr Gly Cys Cys Ala Ala 545 550 555 560 545 550 555 560

Ala Cys Cys Cys Ala Thr Ala Thr Thr Thr Ala Thr Thr Gly Ala Thr Ala Cys Cys Cys Ala Thr Ala Thr Thr Thr Ala Thr Thr Gly Ala Thr 565 570 575 565 570 575

Gly Gly Thr Gly Ala Cys Thr Ala Thr Cys Cys Thr Gly Ala Gly Ala Gly Gly Thr Gly Ala Cys Thr Ala Thr Cys Cys Thr Gly Ala Gly Ala 580 585 590 580 585 590

Gly Cys Ala Thr Gly Ala Ala Gly Ala Ala Thr Ala Ala Thr Cys Thr Gly Cys Ala Thr Gly Ala Ala Gly Ala Ala Thr Ala Ala Thr Cys Thr 595 600 605 595 600 605

Thr Thr Cys Ala Cys Ala Thr Cys Thr Thr Cys Thr Gly Cys Cys Thr Thr Thr Cys Ala Cys Ala Thr Cys Thr Thr Cys Thr Gly Cys Cys Thr 610 615 620 610 615 620

Gly Ala Thr Thr Thr Thr Ala Cys Thr Gly Ala Ala Gly Cys Thr Gly Gly Ala Thr Thr Thr Thr Ala Cys Thr Gly Ala Ala Gly Cys Thr Gly 625 630 635 640 625 630 635 640

Ala Gly Ala Ala Ala Ala Ala Gly Thr Thr Cys Ala Thr Thr Ala Ala Ala Gly Ala Ala Ala Ala Ala Gly Thr Thr Cys Ala Thr Thr Ala Ala 645 650 655 645 650 655

Gly Gly Gly Ala Ala Cys Ala Gly Cys Thr Gly Ala Cys Thr Thr Thr Gly Gly Gly Ala Ala Cys Ala Gly Cys Thr Gly Ala Cys Thr Thr Thr 660 665 670 660 665 670

Thr Thr Thr Gly Cys Thr Cys Thr Thr Thr Cys Thr Thr Thr Thr Gly Thr Thr Thr Gly Cys Thr Cys Thr Thr Thr Cys Thr Thr Thr Thr Gly 675 680 685 675 680 685

Gly Ala Cys Cys Ala Ala Cys Cys Thr Thr Gly Ala Gly Thr Thr Thr Gly Ala Cys Cys Ala Ala Cys Cys Thr Thr Gly Ala Gly Thr Thr Thr 690 695 700 690 695 700

Thr Cys Ala Ala Cys Thr Ala Thr Thr Gly Gly Ala Cys Cys Cys Cys Thr Cys Ala Ala Cys Thr Ala Thr Thr Gly Gly Ala Cys Cys Cys Cys 705 710 715 720 705 710 715 720

Cys Ala Cys Ala Thr Gly Ala Ala Gly Thr Thr Cys Cys Gly Cys Cys Cys Ala Cys Ala Thr Gly Ala Ala Gly Thr Thr Cys Cys Gly Cys Cys Page 436 Page 436

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 725 730 735 725 730 735

Ala Gly Thr Thr Ala Gly Ala Ala Thr Cys Thr Cys Cys Cys Ala Gly Ala Gly Thr Thr Ala Gly Ala Ala Thr Cys Thr Cys Cys Cys Ala Gly 740 745 750 740 745 750

Cys Cys Thr Gly Ala Gly Gly Cys Ala Ala Cys Thr Cys Cys Thr Thr Cys Cys Thr Gly Ala Gly Gly Cys Ala Ala Cys Thr Cys Cys Thr Thr 755 760 765 755 760 765

Thr Cys Thr Thr Gly Gly Ala Thr Thr Gly Ala Cys Cys Thr Thr Gly Thr Cys Thr Thr Gly Gly Ala Thr Thr Gly Ala Cys Cys Thr Thr Gly 770 775 780 770 775 780

Ala Ala Thr Ala Thr Ala Ala Cys Cys Ala Cys Cys Cys Thr Cys Ala Ala Ala Thr Ala Thr Ala Ala Cys Cys Ala Cys Cys Cys Thr Cys Ala 785 790 795 800 785 790 795 800

Ala Ala Thr Ala Thr Thr Thr Ala Thr Thr Gly Thr Gly Gly Ala Ala Ala Ala Thr Ala Thr Thr Thr Ala Thr Thr Gly Thr Gly Gly Ala Ala 805 810 815 805 810 815

Ala Ala Thr Gly Gly Cys Thr Gly Gly Thr Thr Thr Gly Thr Cys Thr Ala Ala Thr Gly Gly Cys Thr Gly Gly Thr Thr Thr Gly Thr Cys Thr 820 825 830 820 825 830

Cys Ala Gly Gly Gly Ala Cys Cys Ala Cys Cys Ala Ala Gly Ala Gly Cys Ala Gly Gly Gly Ala Cys Cys Ala Cys Cys Ala Ala Gly Ala Gly 835 840 845 835 840 845

Ala Gly Ala Cys Gly Ala Cys Gly Cys Cys Ala Ala Ala Thr Ala Thr Ala Gly Ala Cys Gly Ala Cys Gly Cys Cys Ala Ala Ala Thr Ala Thr 850 855 860 850 855 860

Ala Thr Gly Thr Ala Thr Thr Ala Cys Cys Thr Cys Ala Ala Ala Ala Ala Thr Gly Thr Ala Thr Thr Ala Cys Cys Thr Cys Ala Ala Ala Ala 865 870 875 880 865 870 875 880

Ala Ala Thr Thr Cys Gly Thr Ala Ala Thr Gly Gly Ala Ala Ala Cys Ala Ala Thr Thr Cys Gly Thr Ala Ala Thr Gly Gly Ala Ala Ala Cys 885 890 895 885 890 895

Cys Thr Thr Ala Ala Ala Ala Gly Cys Cys Ala Thr Thr Ala Gly Gly Cys Thr Thr Ala Ala Ala Ala Gly Cys Cys Ala Thr Thr Ala Gly Gly 900 905 910 900 905 910

Cys Thr Gly Gly Ala Thr Gly Gly Gly Gly Thr Gly Gly Ala Cys Gly Cys Thr Gly Gly Ala Thr Gly Gly Gly Gly Thr Gly Gly Ala Cys Gly 915 920 925 915 920 925

Thr Cys Ala Thr Thr Gly Gly Gly Thr Ala Cys Ala Cys Gly Gly Cys Thr Cys Ala Thr Thr Gly Gly Gly Thr Ala Cys Ala Cys Gly Gly Cys Page 437 Page 437

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 930 935 940 930 935 940

Cys Thr Gly Gly Thr Cys Cys Cys Thr Thr Ala Thr Gly Gly Ala Thr Cys Thr Gly Gly Thr Cys Cys Cys Thr Thr Ala Thr Gly Gly Ala Thr 945 950 955 960 945 950 955 960

Gly Gly Cys Thr Thr Cys Gly Ala Ala Thr Gly Gly Cys Ala Cys Ala Gly Gly Cys Thr Thr Cys Gly Ala Ala Thr Gly Gly Cys Ala Cys Ala 965 970 975 965 970 975

Gly Ala Gly Gly Thr Thr Ala Cys Ala Gly Cys Ala Thr Cys Ala Gly Gly Ala Gly Gly Thr Thr Ala Cys Ala Gly Cys Ala Thr Cys Ala Gly 980 985 990 980 985 990

Gly Cys Gly Thr Gly Gly Ala Cys Thr Cys Thr Thr Cys Thr Ala Thr Gly Cys Gly Thr Gly Gly Ala Cys Thr Cys Thr Thr Cys Thr Ala Thr 995 1000 1005 995 1000 1005

Gly Thr Thr Gly Ala Cys Thr Thr Thr Cys Thr Ala Ala Gly Cys Gly Thr Thr Gly Ala Cys Thr Thr Thr Cys Thr Ala Ala Gly Cys 1010 1015 1020 1010 1015 1020

Cys Ala Gly Gly Ala Thr Ala Ala Gly Ala Ala Ala Cys Thr Gly Cys Ala Gly Gly Ala Thr Ala Ala Gly Ala Ala Ala Cys Thr Gly 1025 1030 1035 1025 1030 1035

Thr Thr Gly Cys Cys Gly Ala Ala Ala Thr Cys Thr Thr Cys Ala Thr Thr Gly Cys Cys Gly Ala Ala Ala Thr Cys Thr Thr Cys Ala 1040 1045 1050 1040 1045 1050

Gly Cys Cys Thr Thr Gly Thr Thr Cys Thr Ala Cys Cys Ala Ala Gly Cys Cys Thr Thr Gly Thr Thr Cys Thr Ala Cys Cys Ala Ala 1055 1060 1065 1055 1060 1065

Ala Ala Gly Cys Thr Gly Ala Thr Ala Gly Ala Gly Ala Ala Ala Ala Ala Gly Cys Thr Gly Ala Thr Ala Gly Ala Gly Ala Ala Ala 1070 1075 1080 1070 1075 1080

Ala Ala Thr Gly Gly Cys Thr Thr Cys Cys Cys Thr Cys Cys Thr Ala Ala Thr Gly Gly Cys Thr Thr Cys Cys Cys Thr Cys Cys Thr 1085 1090 1095 1085 1090 1095

Thr Thr Ala Cys Cys Thr Gly Ala Ala Ala Ala Thr Cys Ala Ala Thr Thr Ala Cys Cys Thr Gly Ala Ala Ala Ala Thr Cys Ala Ala 1100 1105 1110 1100 1105 1110

Cys Cys Thr Cys Thr Ala Gly Ala Ala Gly Gly Gly Ala Cys Ala Cys Cys Thr Cys Thr Ala Gly Ala Ala Gly Gly Gly Ala Cys Ala 1115 1120 1125 1115 1120 1125

Thr Thr Thr Cys Cys Cys Thr Gly Thr Gly Ala Cys Thr Thr Thr Thr Thr Thr Cys Cys Cys Thr Gly Thr Gly Ala Cys Thr Thr Thr Page 438 Page 438

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 1130 1135 1140 1130 1135 1140

Gly Cys Thr Thr Gly Gly Gly Gly Ala Ala Thr Thr Gly Thr Thr Gly Cys Thr Thr Gly Gly Gly Gly Ala Ala Thr Thr Gly Thr Thr 1145 1150 1155 1145 1150 1155

Gly Ala Cys Ala Ala Cys Thr Ala Cys Ala Thr Thr Cys Ala Ala Gly Ala Cys Ala Ala Cys Thr Ala Cys Ala Thr Thr Cys Ala Ala 1160 1165 1170 1160 1165 1170

Gly Thr Gly Gly Ala Cys Ala Cys Cys Ala Cys Thr Cys Thr Gly Gly Thr Gly Gly Ala Cys Ala Cys Cys Ala Cys Thr Cys Thr Gly 1175 1180 1185 1175 1180 1185

Thr Cys Thr Cys Ala Gly Thr Thr Thr Ala Cys Cys Gly Ala Cys Thr Cys Thr Cys Ala Gly Thr Thr Thr Ala Cys Cys Gly Ala Cys 1190 1195 1200 1190 1195 1200

Cys Cys Gly Ala Ala Cys Gly Thr Thr Thr Ala Cys Cys Thr Gly Cys Cys Gly Ala Ala Cys Gly Thr Thr Thr Ala Cys Cys Thr Gly 1205 1210 1215 1205 1210 1215

Thr Gly Gly Gly Ala Cys Gly Thr Cys Cys Ala Cys Cys Ala Cys Thr Gly Gly Gly Ala Cys Gly Thr Cys Cys Ala Cys Cys Ala Cys 1220 1225 1230 1220 1225 1230

Ala Gly Thr Ala Ala Gly Ala Gly Gly Cys Thr Ala Ala Thr Thr Ala Gly Thr Ala Ala Gly Ala Gly Gly Cys Thr Ala Ala Thr Thr 1235 1240 1245 1235 1240 1245

Ala Ala Gly Gly Thr Gly Gly Ala Cys Gly Gly Gly Gly Thr Thr Ala Ala Gly Gly Thr Gly Gly Ala Cys Gly Gly Gly Gly Thr Thr 1250 1255 1260 1250 1255 1260

Gly Thr Gly Ala Cys Cys Ala Ala Gly Ala Ala Gly Cys Gly Gly Gly Thr Gly Ala Cys Cys Ala Ala Gly Ala Ala Gly Cys Gly Gly 1265 1270 1275 1265 1270 1275

Ala Ala Gly Thr Cys Cys Thr Ala Cys Thr Gly Cys Gly Thr Gly Ala Ala Gly Thr Cys Cys Thr Ala Cys Thr Gly Cys Gly Thr Gly 1280 1285 1290 1280 1285 1290

Gly Ala Cys Thr Thr Cys Gly Cys Thr Gly Cys Cys Ala Thr Cys Gly Ala Cys Thr Thr Cys Gly Cys Thr Gly Cys Cys Ala Thr Cys 1295 1300 1305 1295 1300 1305

Cys Gly Gly Cys Cys Cys Cys Ala Gly Ala Thr Ala Gly Cys Cys Cys Gly Gly Cys Cys Cys Cys Ala Gly Ala Thr Ala Gly Cys Cys 1310 1315 1320 1310 1315 1320

Thr Thr Ala Cys Thr Cys Cys Ala Gly Gly Ala Gly Ala Thr Gly Thr Thr Ala Cys Thr Cys Cys Ala Gly Gly Ala Gly Ala Thr Gly Page 439 Page 439

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 1325 1330 1335 1325 1330 1335

Cys Ala Cys Gly Thr Thr Thr Cys Cys Cys Ala Thr Thr Thr Cys Cys Ala Cys Gly Thr Thr Thr Cys Cys Cys Ala Thr Thr Thr Cys 1340 1345 1350 1340 1345 1350

Cys Ala Cys Thr Thr Cys Thr Cys Cys Cys Thr Gly Gly Ala Cys Cys Ala Cys Thr Thr Cys Thr Cys Cys Cys Thr Gly Gly Ala Cys 1355 1360 1365 1355 1360 1365

Thr Gly Gly Gly Cys Cys Cys Thr Gly Ala Thr Cys Cys Thr Gly Thr Gly Gly Gly Cys Cys Cys Thr Gly Ala Thr Cys Cys Thr Gly 1370 1375 1380 1370 1375 1380

Cys Cys Gly Cys Thr Gly Gly Gly Cys Ala Ala Cys Cys Ala Gly Cys Cys Gly Cys Thr Gly Gly Gly Cys Ala Ala Cys Cys Ala Gly 1385 1390 1395 1385 1390 1395

Thr Cys Cys Cys Ala Gly Gly Thr Gly Ala Ala Cys Cys Ala Cys Thr Cys Cys Cys Ala Gly Gly Thr Gly Ala Ala Cys Cys Ala Cys 1400 1405 1410 1400 1405 1410

Ala Cys Gly Gly Thr Cys Cys Thr Cys Gly Ala Cys Thr Ala Cys Ala Cys Gly Gly Thr Cys Cys Thr Cys Gly Ala Cys Thr Ala Cys 1415 1420 1425 1415 1420 1425

Thr Ala Cys Cys Gly Cys Thr Gly Cys Gly Thr Gly Gly Thr Cys Thr Ala Cys Cys Gly Cys Thr Gly Cys Gly Thr Gly Gly Thr Cys 1430 1435 1440 1430 1435 1440

Ala Gly Cys Gly Ala Gly Cys Thr Cys Gly Thr Gly Cys Gly Cys Ala Gly Cys Gly Ala Gly Cys Thr Cys Gly Thr Gly Cys Gly Cys 1445 1450 1455 1445 1450 1455

Gly Cys Cys Ala Ala Cys Ala Thr Cys Ala Cys Cys Cys Cys Gly Gly Cys Cys Ala Ala Cys Ala Thr Cys Ala Cys Cys Cys Cys Gly 1460 1465 1470 1460 1465 1470

Gly Thr Gly Gly Thr Gly Gly Cys Gly Cys Thr Cys Thr Gly Gly Gly Thr Gly Gly Thr Gly Gly Cys Gly Cys Thr Cys Thr Gly Gly 1475 1480 1485 1475 1480 1485

Cys Gly Ala Cys Cys Cys Gly Cys Gly Gly Cys Cys Cys Cys Gly Cys Gly Ala Cys Cys Cys Gly Cys Gly Gly Cys Cys Cys Cys Gly 1490 1495 1500 1490 1495 1500

Cys Ala Cys Cys Ala Ala Gly Gly Gly Cys Thr Gly Cys Cys Gly Cys Ala Cys Cys Ala Ala Gly Gly Gly Cys Thr Gly Cys Cys Gly 1505 1510 1515 1505 1510 1515

Cys Gly Gly Cys Cys Cys Cys Thr Gly Gly Cys Cys Ala Ala Gly Cys Gly Gly Cys Cys Cys Cys Thr Gly Gly Cys Cys Ala Ala Gly Page 440 Page 440

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 1520 1525 1530 1520 1525 1530

Cys Ala Cys Gly Gly Ala Gly Cys Cys Thr Gly Gly Gly Ala Gly Cys Ala Cys Gly Gly Ala Gly Cys Cys Thr Gly Gly Gly Ala Gly 1535 1540 1545 1535 1540 1545

Ala Ala Cys Cys Cys Ala Cys Ala Cys Ala Cys Cys Gly Cys Cys Ala Ala Cys Cys Cys Ala Cys Ala Cys Ala Cys Cys Gly Cys Cys 1550 1555 1560 1550 1555 1560

Thr Cys Gly Gly Cys Thr Thr Thr Thr Gly Cys Ala Gly Ala Gly Thr Cys Gly Gly Cys Thr Thr Thr Thr Gly Cys Ala Gly Ala Gly 1565 1570 1575 1565 1570 1575

Thr Ala Cys Gly Cys Cys Cys Gly Gly Cys Thr Gly Thr Gly Cys Thr Ala Cys Gly Cys Cys Cys Gly Gly Cys Thr Gly Thr Gly Cys 1580 1585 1590 1580 1585 1590

Thr Thr Cys Ala Ala Gly Gly Ala Thr Cys Thr Cys Gly Gly Cys Thr Thr Cys Ala Ala Gly Gly Ala Thr Cys Thr Cys Gly Gly Cys 1595 1600 1605 1595 1600 1605

Cys Ala Cys Cys Ala Cys Gly Thr Cys Ala Ala Gly Thr Thr Cys Cys Ala Cys Cys Ala Cys Gly Thr Cys Ala Ala Gly Thr Thr Cys 1610 1615 1620 1610 1615 1620

Thr Gly Gly Ala Thr Cys Ala Cys Gly Ala Thr Gly Gly Gly Cys Thr Gly Gly Ala Thr Cys Ala Cys Gly Ala Thr Gly Gly Gly Cys 1625 1630 1635 1625 1630 1635

Gly Ala Gly Cys Cys Gly Thr Ala Cys Ala Cys Ala Cys Gly Gly Gly Ala Gly Cys Cys Gly Thr Ala Cys Ala Cys Ala Cys Gly Gly 1640 1645 1650 1640 1645 1650

Ala Ala Cys Ala Thr Gly Ala Cys Cys Thr Ala Cys Ala Gly Cys Ala Ala Cys Ala Thr Gly Ala Cys Cys Thr Ala Cys Ala Gly Cys 1655 1660 1665 1655 1660 1665

Gly Cys Gly Gly Gly Gly Cys Ala Cys Ala Ala Thr Cys Thr Thr Gly Cys Gly Gly Gly Gly Cys Ala Cys Ala Ala Thr Cys Thr Thr 1670 1675 1680 1670 1675 1680

Cys Thr Gly Ala Ala Gly Gly Cys Thr Cys Ala Cys Gly Cys Gly Cys Thr Gly Ala Ala Gly Gly Cys Thr Cys Ala Cys Gly Cys Gly 1685 1690 1695 1685 1690 1695

Thr Thr Gly Gly Cys Cys Thr Gly Gly Cys Gly Cys Gly Thr Gly Thr Thr Gly Gly Cys Cys Thr Gly Gly Cys Gly Cys Gly Thr Gly 1700 1705 1710 1700 1705 1710

Thr Ala Cys Gly Ala Thr Gly Ala Ala Ala Ala Cys Thr Thr Thr Thr Ala Cys Gly Ala Thr Gly Ala Ala Ala Ala Cys Thr Thr Thr Page 441 Page 441

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 1715 1720 1725 1715 1720 1725

Cys Gly Gly Gly Gly Cys Thr Cys Thr Cys Ala Gly Ala Ala Gly Cys Gly Gly Gly Gly Cys Thr Cys Thr Cys Ala Gly Ala Ala Gly 1730 1735 1740 1730 1735 1740

Gly Gly Gly Ala Ala Ala Ala Thr Ala Thr Cys Cys Ala Thr Ala Gly Gly Gly Ala Ala Ala Ala Thr Ala Thr Cys Cys Ala Thr Ala 1745 1750 1755 1745 1750 1755

Gly Cys Cys Cys Thr Gly Cys Ala Gly Gly Cys Cys Gly Ala Cys Gly Cys Cys Cys Thr Gly Cys Ala Gly Gly Cys Cys Gly Ala Cys 1760 1765 1770 1760 1765 1770

Thr Gly Gly Ala Thr Ala Gly Ala Gly Cys Cys Gly Gly Cys Cys Thr Gly Gly Ala Thr Ala Gly Ala Gly Cys Cys Gly Gly Cys Cys 1775 1780 1785 1775 1780 1785

Thr Gly Cys Cys Cys Thr Thr Thr Cys Thr Cys Cys Cys Ala Ala Thr Gly Cys Cys Cys Thr Thr Thr Cys Thr Cys Cys Cys Ala Ala 1790 1795 1800 1790 1795 1800

Ala Ala Gly Gly Ala Cys Ala Ala Ala Gly Ala Ala Gly Thr Gly Ala Ala Gly Gly Ala Cys Ala Ala Ala Gly Ala Ala Gly Thr Gly 1805 1810 1815 1805 1810 1815

Gly Cys Ala Gly Ala Gly Ala Gly Ala Gly Thr Thr Thr Thr Gly Gly Cys Ala Gly Ala Gly Ala Gly Ala Gly Thr Thr Thr Thr Gly 1820 1825 1830 1820 1825 1830

Gly Ala Ala Thr Thr Thr Gly Ala Cys Ala Thr Thr Gly Gly Cys Gly Ala Ala Thr Thr Thr Gly Ala Cys Ala Thr Thr Gly Gly Cys 1835 1840 1845 1835 1840 1845

Thr Gly Gly Cys Thr Gly Gly Cys Cys Gly Ala Gly Cys Cys Cys Thr Gly Gly Cys Thr Gly Gly Cys Cys Gly Ala Gly Cys Cys Cys 1850 1855 1860 1850 1855 1860

Ala Thr Thr Thr Thr Cys Gly Gly Cys Thr Cys Thr Gly Gly Gly Ala Thr Thr Thr Thr Cys Gly Gly Cys Thr Cys Thr Gly Gly Gly 1865 1870 1875 1865 1870 1875

Gly Ala Thr Thr Ala Thr Cys Cys Gly Cys Gly Thr Gly Thr Gly Gly Ala Thr Thr Ala Thr Cys Cys Gly Cys Gly Thr Gly Thr Gly 1880 1885 1890 1880 1885 1890

Ala Thr Gly Ala Gly Gly Gly Ala Cys Thr Gly Gly Cys Thr Cys Ala Thr Gly Ala Gly Gly Gly Ala Cys Thr Gly Gly Cys Thr Cys 1895 1900 1905 1895 1900 1905

Ala Cys Gly Cys Ala Gly Ala Gly Ala Ala Ala Cys Ala Ala Thr Ala Cys Gly Cys Ala Gly Ala Gly Ala Ala Ala Cys Ala Ala Thr Page 442 Page 442

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 1910 1915 1920 1910 1915 1920

Thr Thr Cys Cys Thr Thr Cys Thr Ala Cys Cys Thr Thr Ala Thr Thr Thr Cys Cys Thr Thr Cys Thr Ala Cys Cys Thr Thr Ala Thr 1925 1930 1935 1925 1930 1935

Thr Thr Cys Ala Cys Thr Gly Ala Ala Gly Ala Thr Gly Ala Ala Thr Thr Cys Ala Cys Thr Gly Ala Ala Gly Ala Thr Gly Ala Ala 1940 1945 1950 1940 1945 1950

Ala Ala Ala Ala Ala Gly Cys Thr Ala Ala Thr Cys Cys Gly Gly Ala Ala Ala Ala Ala Gly Cys Thr Ala Ala Thr Cys Cys Gly Gly 1955 1960 1965 1955 1960 1965

Gly Gly Thr Thr Cys Cys Thr Thr Cys Gly Ala Cys Thr Thr Thr Gly Gly Thr Thr Cys Cys Thr Thr Cys Gly Ala Cys Thr Thr Thr 1970 1975 1980 1970 1975 1980

Cys Thr Gly Gly Cys Cys Gly Thr Ala Ala Gly Cys Cys Ala Thr Cys Thr Gly Gly Cys Cys Gly Thr Ala Ala Gly Cys Cys Ala Thr 1985 1990 1995 1985 1990 1995

Thr Ala Cys Ala Cys Cys Ala Cys Cys Ala Thr Cys Cys Thr Cys Thr Ala Cys Ala Cys Cys Ala Cys Cys Ala Thr Cys Cys Thr Cys 2000 2005 2010 2000 2005 2010

Gly Thr Cys Gly Ala Cys Thr Gly Gly Gly Ala Ala Ala Ala Ala Gly Thr Cys Gly Ala Cys Thr Gly Gly Gly Ala Ala Ala Ala Ala 2015 2020 2025 2015 2020 2025

Gly Ala Ala Gly Ala Thr Cys Cys Ala Ala Thr Gly Ala Ala Ala Gly Ala Ala Gly Ala Thr Cys Cys Ala Ala Thr Gly Ala Ala Ala 2030 2035 2040 2030 2035 2040

Thr Ala Cys Ala Ala Cys Gly Ala Thr Thr Ala Cys Cys Thr Gly Thr Ala Cys Ala Ala Cys Gly Ala Thr Thr Ala Cys Cys Thr Gly 2045 2050 2055 2045 2050 2055

Gly Ala Gly Gly Thr Gly Cys Ala Gly Gly Ala Ala Ala Thr Gly Gly Ala Gly Gly Thr Gly Cys Ala Gly Gly Ala Ala Ala Thr Gly 2060 2065 2070 2060 2065 2070

Ala Cys Cys Gly Ala Cys Ala Thr Cys Ala Cys Gly Thr Gly Gly Ala Cys Cys Gly Ala Cys Ala Thr Cys Ala Cys Gly Thr Gly Gly 2075 2080 2085 2075 2080 2085

Cys Thr Cys Ala Ala Cys Thr Cys Cys Cys Cys Cys Ala Gly Thr Cys Thr Cys Ala Ala Cys Thr Cys Cys Cys Cys Cys Ala Gly Thr 2090 2095 2100 2090 2095 2100

Cys Ala Gly Gly Thr Gly Gly Cys Ala Gly Thr Ala Gly Thr Gly Cys Ala Gly Gly Thr Gly Gly Cys Ala Gly Thr Ala Gly Thr Gly Page 443 Page 443

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 2105 2110 2115 2105 2110 2115

Cys Cys Cys Thr Gly Gly Gly Gly Cys Thr Thr Ala Cys Gly Cys Cys Cys Cys Thr Gly Gly Gly Gly Cys Thr Thr Ala Cys Gly Cys 2120 2125 2130 2120 2125 2130

Ala Ala Ala Ala Thr Thr Cys Thr Cys Ala Ala Cys Thr Gly Gly Ala Ala Ala Ala Thr Thr Cys Thr Cys Ala Ala Cys Thr Gly Gly 2135 2140 2145 2135 2140 2145

Cys Thr Gly Ala Ala Gly Cys Thr Gly Ala Ala Gly Thr Ala Cys Cys Thr Gly Ala Ala Gly Cys Thr Gly Ala Ala Gly Thr Ala Cys 2150 2155 2160 2150 2155 2160

Gly Gly Ala Gly Ala Cys Cys Thr Cys Cys Cys Cys Ala Thr Gly Gly Gly Ala Gly Ala Cys Cys Thr Cys Cys Cys Cys Ala Thr Gly 2165 2170 2175 2165 2170 2175

Thr Ala Thr Ala Thr Ala Ala Thr Ala Thr Cys Cys Ala Ala Cys Thr Ala Thr Ala Thr Ala Ala Thr Ala Thr Cys Cys Ala Ala Cys 2180 2185 2190 2180 2185 2190

Gly Gly Cys Ala Thr Ala Gly Ala Cys Gly Ala Cys Gly Ala Thr Gly Gly Cys Ala Thr Ala Gly Ala Cys Gly Ala Cys Gly Ala Thr 2195 2200 2205 2195 2200 2205

Cys Cys Gly Cys Ala Gly Gly Cys Ala Gly Cys Gly Cys Ala Ala Cys Cys Gly Cys Ala Gly Gly Cys Ala Gly Cys Gly Cys Ala Ala 2210 2215 2220 2210 2215 2220

Gly Ala Cys Ala Ala Gly Cys Thr Gly Ala Gly Gly Gly Thr Gly Gly Ala Cys Ala Ala Gly Cys Thr Gly Ala Gly Gly Gly Thr Gly 2225 2230 2235 2225 2230 2235

Thr Ala Thr Thr Ala Cys Ala Thr Gly Cys Ala Ala Ala Ala Thr Thr Ala Thr Thr Ala Cys Ala Thr Gly Cys Ala Ala Ala Ala Thr 2240 2245 2250 2240 2245 2250

Thr Ala Thr Gly Thr Ala Ala Ala Thr Gly Ala Ala Gly Cys Thr Thr Ala Thr Gly Thr Ala Ala Ala Thr Gly Ala Ala Gly Cys Thr 2255 2260 2265 2255 2260 2265

Cys Thr Gly Ala Ala Ala Gly Cys Cys Thr Ala Cys Gly Thr Ala Cys Thr Gly Ala Ala Ala Gly Cys Cys Thr Ala Cys Gly Thr Ala 2270 2275 2280 2270 2275 2280

Thr Thr Gly Gly Ala Thr Gly Gly Thr Gly Thr Cys Ala Ala Thr Thr Thr Gly Gly Ala Thr Gly Gly Thr Gly Thr Cys Ala Ala Thr 2285 2290 2295 2285 2290 2295

Cys Thr Thr Thr Gly Thr Gly Gly Ala Thr Ala Cys Thr Thr Thr Cys Thr Thr Thr Gly Thr Gly Gly Ala Thr Ala Cys Thr Thr Thr Page 444 Page 444

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 2300 2305 2310 2300 2305 2310

Gly Cys Thr Thr Ala Thr Thr Cys Ala Thr Thr Cys Ala Ala Thr Gly Cys Thr Thr Ala Thr Thr Cys Ala Thr Thr Cys Ala Ala Thr 2315 2320 2325 2315 2320 2325

Gly Ala Thr Cys Gly Cys Ala Cys Ala Gly Cys Thr Cys Cys Ala Gly Ala Thr Cys Gly Cys Ala Cys Ala Gly Cys Thr Cys Cys Ala 2330 2335 2340 2330 2335 2340

Ala Ala Gly Thr Thr Thr Gly Gly Cys Thr Thr Cys Thr Ala Thr Ala Ala Gly Thr Thr Thr Gly Gly Cys Thr Thr Cys Thr Ala Thr 2345 2350 2355 2345 2350 2355

Cys Ala Thr Thr Ala Cys Gly Cys Thr Gly Cys Ala Ala Ala Thr Cys Ala Thr Thr Ala Cys Gly Cys Thr Gly Cys Ala Ala Ala Thr 2360 2365 2370 2360 2365 2370

Cys Ala Gly Thr Thr Thr Gly Ala Gly Cys Cys Cys Ala Ala Ala Cys Ala Gly Thr Thr Thr Gly Ala Gly Cys Cys Cys Ala Ala Ala 2375 2380 2385 2375 2380 2385

Cys Cys Gly Thr Cys Cys Ala Thr Gly Ala Ala Ala Cys Ala Thr Cys Cys Gly Thr Cys Cys Ala Thr Gly Ala Ala Ala Cys Ala Thr 2390 2395 2400 2390 2395 2400

Thr Ala Thr Cys Gly Gly Ala Ala Ala Ala Thr Gly Ala Thr Thr Thr Ala Thr Cys Gly Gly Ala Ala Ala Ala Thr Gly Ala Thr Thr 2405 2410 2415 2405 2410 2415

Gly Ala Cys Ala Gly Cys Ala Ala Thr Gly Gly Cys Thr Thr Cys Gly Ala Cys Ala Gly Cys Ala Ala Thr Gly Gly Cys Thr Thr Cys 2420 2425 2430 2420 2425 2430

Thr Cys Cys Gly Gly Thr Cys Cys Thr Gly Ala Cys Ala Cys Thr Thr Cys Cys Gly Gly Thr Cys Cys Thr Gly Ala Cys Ala Cys Thr 2435 2440 2445 2435 2440 2445

Cys Thr Gly Gly Gly Gly Ala Gly Ala Thr Thr Thr Thr Gly Thr Cys Thr Gly Gly Gly Gly Ala Gly Ala Thr Thr Thr Thr Gly Thr 2450 2455 2460 2450 2455 2460

Cys Cys Ala Gly Ala Ala Gly Ala Ala Thr Thr Cys Ala Cys Cys Cys Cys Ala Gly Ala Ala Gly Ala Ala Thr Thr Cys Ala Cys Cys 2465 2470 2475 2465 2470 2475

Cys Thr Gly Thr Gly Cys Ala Cys Cys Gly Ala Ala Thr Gly Cys Cys Thr Gly Thr Gly Cys Ala Cys Cys Gly Ala Ala Thr Gly Cys 2480 2485 2490 2480 2485 2490

Gly Gly Cys Thr Thr Thr Thr Thr Thr Cys Ala Cys Ala Cys Cys Gly Gly Cys Thr Thr Thr Thr Thr Thr Cys Ala Cys Ala Cys Cys Page 445 Page 445

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 2495 2500 2505 2495 2500 2505

Cys Gly Cys Ala Ala Ala Thr Cys Thr Thr Thr Ala Cys Thr Gly Cys Gly Cys Ala Ala Ala Thr Cys Thr Thr Thr Ala Cys Thr Gly 2510 2515 2520 2510 2515 2520

Gly Cys Thr Thr Thr Cys Ala Thr Ala Gly Cys Thr Thr Thr Cys Gly Cys Thr Thr Thr Cys Ala Thr Ala Gly Cys Thr Thr Thr Cys 2525 2530 2535 2525 2530 2535

Cys Thr Ala Cys Thr Thr Thr Thr Thr Gly Cys Thr Thr Thr Thr Cys Thr Ala Cys Thr Thr Thr Thr Thr Gly Cys Thr Thr Thr Thr 2540 2545 2550 2540 2545 2550

Ala Thr Thr Ala Thr Thr Thr Cys Thr Cys Thr Thr Thr Cys Thr Ala Thr Thr Ala Thr Thr Thr Cys Thr Cys Thr Thr Thr Cys Thr 2555 2560 2565 2555 2560 2565

Cys Thr Gly Ala Thr Thr Thr Thr Thr Thr Ala Cys Thr Ala Cys Cys Thr Gly Ala Thr Thr Thr Thr Thr Thr Ala Cys Thr Ala Cys 2570 2575 2580 2570 2575 2580

Thr Cys Thr Ala Ala Gly Ala Ala Ala Gly Gly Cys Ala Ala Ala Thr Cys Thr Ala Ala Gly Ala Ala Ala Gly Gly Cys Ala Ala Ala 2585 2590 2595 2585 2590 2595

Ala Gly Ala Ala Gly Thr Thr Ala Cys Ala Ala Gly Thr Ala Gly Ala Gly Ala Ala Gly Thr Thr Ala Cys Ala Ala Gly Thr Ala Gly 2600 2605 2610 2600 2605 2610

Thr Cys Cys Thr Gly Ala Cys Cys Thr Thr Thr Thr Thr Cys Cys Thr Cys Cys Thr Gly Ala Cys Cys Thr Thr Thr Thr Thr Cys Cys 2615 2620 2625 2615 2620 2625

Thr Ala Thr Thr Cys Ala Thr Thr Thr Ala Cys Thr Thr Thr Gly Thr Ala Thr Thr Cys Ala Thr Thr Thr Ala Cys Thr Thr Thr Gly 2630 2635 2640 2630 2635 2640

Ala Ala Ala Thr Gly Ala Thr Thr Ala Thr Gly Cys Ala Cys Ala Ala Ala Ala Thr Gly Ala Thr Thr Ala Thr Gly Cys Ala Cys Ala 2645 2650 2655 2645 2650 2655

Cys Ala Cys Ala Thr Cys Ala Gly Cys Thr Gly Thr Thr Cys Ala Cys Ala Cys Ala Thr Cys Ala Gly Cys Thr Gly Thr Thr Cys Ala 2660 2665 2670 2660 2665 2670

Cys Cys Ala Thr Thr Thr Gly Cys Ala Cys Thr Thr Cys Thr Cys Cys Cys Ala Thr Thr Thr Gly Cys Ala Cys Thr Thr Cys Thr Cys 2675 2680 2685 2675 2680 2685

Ala Gly Thr Gly Thr Cys Gly Thr Ala Ala Gly Ala Cys Thr Gly Ala Gly Thr Gly Thr Cys Gly Thr Ala Ala Gly Ala Cys Thr Gly Page 446 Page 446

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 2690 2695 2700 2690 2695 2700

Gly Ala Thr Thr Thr Cys Ala Cys Thr Thr Ala Thr Cys Thr Gly Gly Ala Thr Thr Thr Cys Ala Cys Thr Thr Ala Thr Cys Thr Gly 2705 2710 2715 2705 2710 2715

Ala Cys Thr Thr Cys Thr Ala Gly Ala Ala Ala Ala Ala Ala Ala Ala Cys Thr Thr Cys Thr Ala Gly Ala Ala Ala Ala Ala Ala Ala 2720 2725 2730 2720 2725 2730

Ala Thr Gly Thr Gly Thr Gly Gly Cys Gly Thr Ala Thr Gly Ala Ala Thr Gly Thr Gly Thr Gly Gly Cys Gly Thr Ala Thr Gly Ala 2735 2740 2745 2735 2740 2745

Cys Ala Gly Ala Gly Gly Thr Ala Thr Gly Gly Ala Ala Gly Thr Cys Ala Gly Ala Gly Gly Thr Ala Thr Gly Gly Ala Ala Gly Thr 2750 2755 2760 2750 2755 2760

Gly Ala Gly Cys Ala Thr Ala Gly Gly Thr Gly Ala Thr Thr Gly Gly Ala Gly Cys Ala Thr Ala Gly Gly Thr Gly Ala Thr Thr Gly 2765 2770 2775 2765 2770 2775

Thr Ala Ala Ala Ala Thr Ala Cys Thr Gly Ala Ala Thr Ala Ala Thr Ala Ala Ala Ala Thr Ala Cys Thr Gly Ala Ala Thr Ala Ala 2780 2785 2790 2780 2785 2790

Thr Gly Thr Gly Ala Ala Thr Ala Gly Thr Gly Cys Cys Thr Gly Thr Gly Thr Gly Ala Ala Thr Ala Gly Thr Gly Cys Cys Thr Gly 2795 2800 2805 2795 2800 2805

Gly Ala Thr Thr Thr Gly Thr Thr Cys Thr Thr Thr Cys Thr Thr Gly Ala Thr Thr Thr Gly Thr Thr Cys Thr Thr Thr Cys Thr Thr 2810 2815 2820 2810 2815 2820

Gly Gly Ala Gly Gly Ala Thr Gly Ala Thr Cys Ala Ala Ala Gly Gly Gly Ala Gly Gly Ala Thr Gly Ala Thr Cys Ala Ala Ala Gly 2825 2830 2835 2825 2830 2835

Ala Cys Gly Gly Thr Thr Ala Gly Gly Gly Gly Cys Cys Ala Thr Ala Cys Gly Gly Thr Thr Ala Gly Gly Gly Gly Cys Cys Ala Thr 2840 2845 2850 2840 2845 2850

Cys Ala Thr Cys Thr Cys Thr Gly Cys Ala Ala Cys Ala Cys Ala Cys Ala Thr Cys Thr Cys Thr Gly Cys Ala Ala Cys Ala Cys Ala 2855 2860 2865 2855 2860 2865

Thr Thr Cys Thr Gly Thr Ala Ala Cys Ala Ala Ala Thr Gly Thr Thr Thr Cys Thr Gly Thr Ala Ala Cys Ala Ala Ala Thr Gly Thr 2870 2875 2880 2870 2875 2880

Ala Thr Gly Gly Gly Ala Ala Gly Thr Gly Gly Gly Ala Cys Cys Ala Thr Gly Gly Gly Ala Ala Gly Thr Gly Gly Gly Ala Cys Cys Page 447 Page 447

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 2885 2890 2895 2885 2890 2895

Cys Ala Thr Thr Cys Thr Gly Gly Ala Ala Cys Ala Thr Thr Thr Cys Ala Thr Thr Cys Thr Gly Gly Ala Ala Cys Ala Thr Thr Thr 2900 2905 2910 2900 2905 2910

Thr Thr Ala Thr Ala Gly Ala Ala Ala Thr Thr Gly Ala Ala Thr Thr Thr Ala Thr Ala Gly Ala Ala Ala Thr Thr Gly Ala Ala Thr 2915 2920 2925 2915 2920 2925

Ala Gly Cys Ala Ala Gly Ala Thr Cys Ala Gly Thr Gly Cys Cys Ala Gly Cys Ala Ala Gly Ala Thr Cys Ala Gly Thr Gly Cys Cys 2930 2935 2940 2930 2935 2940

Cys Gly Thr Thr Cys Cys Thr Ala Ala Ala Thr Thr Ala Thr Cys Cys Gly Thr Thr Cys Cys Thr Ala Ala Ala Thr Thr Ala Thr Cys 2945 2950 2955 2945 2950 2955

Thr Thr Gly Ala Ala Gly Thr Ala Ala Ala Ala Cys Ala Ala Ala Thr Thr Gly Ala Ala Gly Thr Ala Ala Ala Ala Cys Ala Ala Ala 2960 2965 2970 2960 2965 2970

Thr Gly Thr Gly Gly Ala Ala Ala Thr Ala Ala Ala Ala Ala Gly Thr Gly Thr Gly Gly Ala Ala Ala Thr Ala Ala Ala Ala Ala Gly 2975 2980 2985 2975 2980 2985

Thr Thr Ala Ala Gly Thr Cys Cys Cys Ala Ala Ala Thr Ala Ala Thr Thr Ala Ala Gly Thr Cys Cys Cys Ala Ala Ala Thr Ala Ala 2990 2995 3000 2990 2995 3000

Cys Cys Ala Thr Cys Thr Cys Thr Ala Ala Ala Cys Thr Thr Cys Cys Cys Ala Thr Cys Thr Cys Thr Ala Ala Ala Cys Thr Thr Cys 3005 3010 3015 3005 3010 3015

Cys Ala Thr Gly Ala Thr Ala Thr Gly Cys Cys Thr Ala Ala Thr Cys Ala Thr Gly Ala Thr Ala Thr Gly Cys Cys Thr Ala Ala Thr 3020 3025 3030 3020 3025 3030

Gly Gly Thr Cys Thr Cys Thr Gly Thr Thr Gly Gly Ala Cys Cys Gly Gly Thr Cys Thr Cys Thr Gly Thr Thr Gly Gly Ala Cys Cys 3035 3040 3045 3035 3040 3045

Cys Ala Gly Thr Thr Thr Cys Cys Cys Thr Thr Gly Ala Ala Ala Cys Ala Gly Thr Thr Thr Cys Cys Cys Thr Thr Gly Ala Ala Ala 3050 3055 3060 3050 3055 3060

Ala Ala Gly Ala Ala Ala Thr Gly Gly Thr Ala Gly Ala Ala Thr Ala Ala Gly Ala Ala Ala Thr Gly Gly Thr Ala Gly Ala Ala Thr 3065 3070 3075 3065 3070 3075

Ala Thr Thr Ala Gly Ala Gly Ala Cys Ala Thr Gly Ala Cys Ala Ala Thr Thr Ala Gly Ala Gly Ala Cys Ala Thr Gly Ala Cys Ala Page 448 Page 448

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 3080 3085 3090 3080 3085 3090

Gly Ala Gly Gly Gly Cys Cys Cys Thr Ala Cys Gly Cys Thr Ala Gly Ala Gly Gly Gly Cys Cys Cys Thr Ala Cys Gly Cys Thr Ala 3095 3100 3105 3095 3100 3105

Gly Ala Ala Cys Gly Thr Thr Cys Cys Thr Thr Thr Thr Ala Thr Gly Ala Ala Cys Gly Thr Thr Cys Cys Thr Thr Thr Thr Ala Thr 3110 3115 3120 3110 3115 3120

Thr Thr Thr Thr Thr Thr Thr Thr Thr Thr Ala Ala Ala Thr Thr Thr Thr Thr Thr Thr Thr Thr Thr Thr Thr Ala Ala Ala Thr Thr 3125 3130 3135 3125 3130 3135

Thr Thr Thr Thr Thr Thr Cys Ala Ala Thr Gly Thr Thr Thr Thr Thr Thr Thr Thr Thr Thr Cys Ala Ala Thr Gly Thr Thr Thr Thr 3140 3145 3150 3140 3145 3150

Thr Ala Thr Thr Thr Ala Thr Thr Thr Thr Thr Gly Gly Gly Ala Thr Ala Thr Thr Thr Ala Thr Thr Thr Thr Thr Gly Gly Gly Ala 3155 3160 3165 3155 3160 3165

Cys Ala Gly Ala Gly Ala Gly Ala Gly Ala Cys Ala Gly Ala Gly Ala Gly Ala Gly Ala 3170 3175 3170 3175

<210> 124 <210> 124 <211> 2968 <211> 2968 <212> PRT <212> PRT <213> Felis catus <213> Felis catus

<400> 124 <400> 124

Thr Cys Thr Thr Thr Cys Thr Gly Gly Ala Thr Thr Gly Cys Thr Cys Thr Cys Thr Thr Thr Cys Thr Gly Gly Ala Thr Thr Gly Cys Thr Cys 1 5 10 15 1 5 10 15

Cys Gly Thr Cys Ala Thr Gly Ala Gly Ala Ala Cys Cys Gly Gly Thr Cys Gly Thr Cys Ala Thr Gly Ala Gly Ala Ala Cys Cys Gly Gly Thr 20 25 30 20 25 30

Gly Thr Cys Ala Gly Cys Ala Cys Gly Thr Gly Gly Gly Cys Thr Gly Gly Thr Cys Ala Gly Cys Ala Cys Gly Thr Gly Gly Gly Cys Thr Gly 35 40 45 35 40 45

Gly Thr Thr Thr Ala Cys Thr Gly Ala Ala Ala Gly Gly Thr Gly Ala Gly Thr Thr Thr Ala Cys Thr Gly Ala Ala Ala Gly Gly Thr Gly Ala 50 55 60 50 55 60

Ala Gly Ala Cys Ala Gly Ala Cys Thr Thr Thr Gly Gly Ala Ala Gly Ala Gly Ala Cys Ala Gly Ala Cys Thr Thr Thr Gly Gly Ala Ala Gly 65 70 75 80 70 75 80

Page 449 Page 449

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Ala Thr Cys Ala Ala Ala Gly Ala Thr Cys Ala Cys Cys Cys Thr Gly Ala Thr Cys Ala Ala Ala Gly Ala Thr Cys Ala Cys Cys Cys Thr Gly 85 90 95 85 90 95

Gly Ala Thr Gly Thr Thr Cys Thr Cys Gly Cys Cys Ala Cys Cys Gly Gly Ala Thr Gly Thr Thr Cys Thr Cys Gly Cys Cys Ala Cys Cys Gly 100 105 110 100 105 110

Gly Thr Gly Ala Gly Ala Thr Cys Cys Cys Ala Gly Cys Thr Gly Ala Gly Thr Gly Ala Gly Ala Thr Cys Cys Cys Ala Gly Cys Thr Gly Ala 115 120 125 115 120 125

Gly Thr Gly Cys Ala Gly Cys Thr Ala Thr Ala Thr Gly Cys Gly Thr Gly Thr Gly Cys Ala Gly Cys Thr Ala Thr Ala Thr Gly Cys Gly Thr 130 135 140 130 135 140

Gly Ala Cys Cys Thr Cys Thr Gly Cys Thr Ala Cys Ala Thr Cys Ala Gly Ala Cys Cys Thr Cys Thr Gly Cys Thr Ala Cys Ala Thr Cys Ala 145 150 155 160 145 150 155 160

Cys Ala Thr Gly Gly Ala Gly Cys Ala Gly Ala Gly Gly Ala Ala Cys Cys Ala Thr Gly Gly Ala Gly Cys Ala Gly Ala Gly Gly Ala Ala Cys 165 170 175 165 170 175

Thr Gly Thr Cys Cys Ala Gly Gly Cys Thr Cys Ala Thr Gly Cys Cys Thr Gly Thr Cys Cys Ala Gly Gly Cys Thr Cys Ala Thr Gly Cys Cys 180 185 190 180 185 190

Ala Ala Ala Ala Thr Cys Thr Gly Gly Cys Ala Thr Cys Thr Cys Thr Ala Ala Ala Ala Thr Cys Thr Gly Gly Cys Ala Thr Cys Thr Cys Thr 195 200 205 195 200 205

Ala Cys Ala Ala Thr Ala Cys Thr Thr Cys Thr Thr Thr Cys Cys Gly Ala Cys Ala Ala Thr Ala Cys Thr Thr Cys Thr Thr Thr Cys Cys Gly 210 215 220 210 215 220

Thr Cys Cys Ala Ala Cys Thr Cys Ala Gly Gly Gly Ala Gly Gly Cys Thr Cys Cys Ala Ala Cys Thr Cys Ala Gly Gly Gly Ala Gly Gly Cys 225 230 235 240 225 230 235 240

Cys Ala Gly Gly Thr Cys Thr Cys Cys Ala Thr Cys Gly Cys Cys Cys Cys Ala Gly Gly Thr Cys Thr Cys Cys Ala Thr Cys Gly Cys Cys Cys 245 250 255 245 250 255

Thr Ala Ala Gly Cys Thr Cys Cys Cys Ala Cys Thr Gly Gly Ala Thr Thr Ala Ala Gly Cys Thr Cys Cys Cys Ala Cys Thr Gly Gly Ala Thr 260 265 270 260 265 270

Cys Ala Ala Thr Cys Cys Thr Cys Gly Ala Ala Gly Ala Ala Thr Gly Cys Ala Ala Thr Cys Cys Thr Cys Gly Ala Ala Gly Ala Ala Thr Gly 275 280 285 275 280 285 Page 450 Page 450

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Ala Cys Cys Gly Ala Cys Cys Ala Cys Ala Gly Cys Ala Thr Cys Ala Ala Cys Cys Gly Ala Cys Cys Ala Cys Ala Gly Cys Ala Thr Cys Ala 290 295 300 290 295 300

Ala Ala Gly Ala Ala Thr Gly Thr Cys Ala Ala Ala Ala Gly Thr Cys Ala Ala Gly Ala Ala Thr Gly Thr Cys Ala Ala Ala Ala Gly Thr Cys 305 310 315 320 305 310 315 320

Thr Cys Thr Thr Gly Ala Cys Thr Thr Thr Gly Thr Ala Cys Thr Ala Thr Cys Thr Thr Gly Ala Cys Thr Thr Thr Gly Thr Ala Cys Thr Ala 325 330 335 325 330 335

Gly Gly Cys Thr Gly Gly Thr Thr Thr Gly Cys Cys Ala Ala Ala Cys Gly Gly Cys Thr Gly Gly Thr Thr Thr Gly Cys Cys Ala Ala Ala Cys 340 345 350 340 345 350

Cys Cys Ala Thr Ala Thr Thr Thr Ala Thr Thr Gly Ala Thr Gly Gly Cys Cys Ala Thr Ala Thr Thr Thr Ala Thr Thr Gly Ala Thr Gly Gly 355 360 365 355 360 365

Thr Gly Ala Cys Thr Ala Thr Cys Cys Thr Gly Ala Gly Ala Gly Cys Thr Gly Ala Cys Thr Ala Thr Cys Cys Thr Gly Ala Gly Ala Gly Cys 370 375 380 370 375 380

Ala Thr Gly Ala Ala Gly Ala Ala Thr Ala Ala Thr Cys Thr Thr Thr Ala Thr Gly Ala Ala Gly Ala Ala Thr Ala Ala Thr Cys Thr Thr Thr 385 390 395 400 385 390 395 400

Cys Ala Cys Ala Thr Cys Thr Thr Cys Thr Gly Cys Cys Thr Gly Ala Cys Ala Cys Ala Thr Cys Thr Thr Cys Thr Gly Cys Cys Thr Gly Ala 405 410 415 405 410 415

Thr Thr Thr Thr Ala Cys Thr Gly Ala Ala Gly Cys Thr Gly Ala Gly Thr Thr Thr Thr Ala Cys Thr Gly Ala Ala Gly Cys Thr Gly Ala Gly 420 425 430 420 425 430

Ala Ala Ala Ala Ala Gly Thr Thr Cys Ala Thr Thr Ala Ala Gly Gly Ala Ala Ala Ala Ala Gly Thr Thr Cys Ala Thr Thr Ala Ala Gly Gly 435 440 445 435 440 445

Gly Ala Ala Cys Ala Gly Cys Thr Gly Ala Cys Thr Thr Thr Thr Thr Gly Ala Ala Cys Ala Gly Cys Thr Gly Ala Cys Thr Thr Thr Thr Thr 450 455 460 450 455 460

Thr Gly Cys Thr Cys Thr Thr Thr Cys Thr Thr Thr Thr Gly Gly Ala Thr Gly Cys Thr Cys Thr Thr Thr Cys Thr Thr Thr Thr Gly Gly Ala 465 470 475 480 465 470 475 480

Cys Cys Ala Ala Cys Cys Thr Thr Gly Ala Gly Thr Thr Thr Thr Cys Cys Cys Ala Ala Cys Cys Thr Thr Gly Ala Gly Thr Thr Thr Thr Cys 485 490 495 485 490 495 Page 451 Page 451

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Ala Ala Cys Thr Ala Thr Thr Gly Gly Ala Cys Cys Cys Cys Cys Ala Ala Ala Cys Thr Ala Thr Thr Gly Gly Ala Cys Cys Cys Cys Cys Ala 500 505 510 500 505 510

Cys Ala Thr Gly Ala Ala Gly Thr Thr Cys Cys Gly Cys Cys Ala Gly Cys Ala Thr Gly Ala Ala Gly Thr Thr Cys Cys Gly Cys Cys Ala Gly 515 520 525 515 520 525

Thr Thr Ala Gly Ala Ala Thr Cys Thr Cys Cys Cys Ala Gly Cys Cys Thr Thr Ala Gly Ala Ala Thr Cys Thr Cys Cys Cys Ala Gly Cys Cys 530 535 540 530 535 540

Thr Gly Ala Gly Gly Cys Ala Ala Cys Thr Cys Cys Thr Thr Thr Cys Thr Gly Ala Gly Gly Cys Ala Ala Cys Thr Cys Cys Thr Thr Thr Cys 545 550 555 560 545 550 555 560

Thr Thr Gly Gly Ala Thr Thr Gly Ala Cys Cys Thr Thr Gly Ala Ala Thr Thr Gly Gly Ala Thr Thr Gly Ala Cys Cys Thr Thr Gly Ala Ala 565 570 575 565 570 575

Thr Ala Thr Ala Ala Cys Cys Ala Cys Cys Cys Thr Cys Ala Ala Ala Thr Ala Thr Ala Ala Cys Cys Ala Cys Cys Cys Thr Cys Ala Ala Ala 580 585 590 580 585 590

Thr Ala Thr Thr Thr Ala Thr Thr Gly Thr Gly Gly Ala Ala Ala Ala Thr Ala Thr Thr Thr Ala Thr Thr Gly Thr Gly Gly Ala Ala Ala Ala 595 600 605 595 600 605

Thr Gly Gly Cys Thr Gly Gly Thr Thr Thr Gly Thr Cys Thr Cys Ala Thr Gly Gly Cys Thr Gly Gly Thr Thr Thr Gly Thr Cys Thr Cys Ala 610 615 620 610 615 620

Gly Gly Gly Ala Cys Cys Ala Cys Cys Ala Ala Gly Ala Gly Ala Gly Gly Gly Gly Ala Cys Cys Ala Cys Cys Ala Ala Gly Ala Gly Ala Gly 625 630 635 640 625 630 635 640

Ala Cys Gly Ala Cys Gly Cys Cys Ala Ala Ala Thr Ala Thr Ala Thr Ala Cys Gly Ala Cys Gly Cys Cys Ala Ala Ala Thr Ala Thr Ala Thr 645 650 655 645 650 655

Gly Thr Ala Thr Thr Ala Cys Cys Thr Cys Ala Ala Ala Ala Ala Ala Gly Thr Ala Thr Thr Ala Cys Cys Thr Cys Ala Ala Ala Ala Ala Ala 660 665 670 660 665 670

Thr Thr Cys Gly Thr Ala Ala Thr Gly Gly Ala Ala Ala Cys Cys Thr Thr Thr Cys Gly Thr Ala Ala Thr Gly Gly Ala Ala Ala Cys Cys Thr 675 680 685 675 680 685

Thr Ala Ala Ala Ala Gly Cys Cys Ala Thr Thr Ala Gly Gly Cys Thr Thr Ala Ala Ala Ala Gly Cys Cys Ala Thr Thr Ala Gly Gly Cys Thr 690 695 700 690 695 700 Page 452 Page 452

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Gly Gly Ala Thr Gly Gly Gly Gly Thr Gly Gly Ala Cys Gly Thr Cys Gly Gly Ala Thr Gly Gly Gly Gly Thr Gly Gly Ala Cys Gly Thr Cys 705 710 715 720 705 710 715 720

Ala Thr Thr Gly Gly Gly Thr Ala Cys Ala Cys Gly Gly Cys Cys Thr Ala Thr Thr Gly Gly Gly Thr Ala Cys Ala Cys Gly Gly Cys Cys Thr 725 730 735 725 730 735

Gly Gly Thr Cys Cys Cys Thr Thr Ala Thr Gly Gly Ala Thr Gly Gly Gly Gly Thr Cys Cys Cys Thr Thr Ala Thr Gly Gly Ala Thr Gly Gly 740 745 750 740 745 750

Cys Thr Thr Cys Gly Ala Ala Thr Gly Gly Cys Ala Cys Ala Gly Ala Cys Thr Thr Cys Gly Ala Ala Thr Gly Gly Cys Ala Cys Ala Gly Ala 755 760 765 755 760 765

Gly Gly Thr Thr Ala Cys Ala Gly Cys Ala Thr Cys Ala Gly Gly Cys Gly Gly Thr Thr Ala Cys Ala Gly Cys Ala Thr Cys Ala Gly Gly Cys 770 775 780 770 775 780

Gly Thr Gly Gly Ala Cys Thr Cys Thr Thr Cys Thr Ala Thr Gly Thr Gly Thr Gly Gly Ala Cys Thr Cys Thr Thr Cys Thr Ala Thr Gly Thr 785 790 795 800 785 790 795 800

Thr Gly Ala Cys Thr Thr Thr Cys Thr Ala Ala Gly Cys Cys Ala Gly Thr Gly Ala Cys Thr Thr Thr Cys Thr Ala Ala Gly Cys Cys Ala Gly 805 810 815 805 810 815

Gly Ala Thr Ala Ala Gly Ala Ala Ala Cys Thr Gly Thr Thr Gly Cys Gly Ala Thr Ala Ala Gly Ala Ala Ala Cys Thr Gly Thr Thr Gly Cys 820 825 830 820 825 830

Cys Gly Ala Ala Ala Thr Cys Thr Thr Cys Ala Gly Cys Cys Thr Thr Cys Gly Ala Ala Ala Thr Cys Thr Thr Cys Ala Gly Cys Cys Thr Thr 835 840 845 835 840 845

Gly Thr Thr Cys Thr Ala Cys Cys Ala Ala Ala Ala Gly Cys Thr Gly Gly Thr Thr Cys Thr Ala Cys Cys Ala Ala Ala Ala Gly Cys Thr Gly 850 855 860 850 855 860

Ala Thr Ala Gly Ala Gly Ala Ala Ala Ala Ala Thr Gly Gly Cys Thr Ala Thr Ala Gly Ala Gly Ala Ala Ala Ala Ala Thr Gly Gly Cys Thr 865 870 875 880 865 870 875 880

Thr Cys Cys Cys Thr Cys Cys Thr Thr Thr Ala Cys Cys Thr Gly Ala Thr Cys Cys Cys Thr Cys Cys Thr Thr Thr Ala Cys Cys Thr Gly Ala 885 890 895 885 890 895

Ala Ala Ala Thr Cys Ala Ala Cys Cys Thr Cys Thr Ala Gly Ala Ala Ala Ala Ala Thr Cys Ala Ala Cys Cys Thr Cys Thr Ala Gly Ala Ala 900 905 910 900 905 910

Page 453 Page 453

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Gly Gly Gly Ala Cys Ala Thr Thr Thr Cys Cys Cys Thr Gly Thr Gly Gly Gly Gly Ala Cys Ala Thr Thr Thr Cys Cys Cys Thr Gly Thr Gly 915 920 925 915 920 925

Ala Cys Thr Thr Thr Gly Cys Thr Thr Gly Gly Gly Gly Ala Ala Thr Ala Cys Thr Thr Thr Gly Cys Thr Thr Gly Gly Gly Gly Ala Ala Thr 930 935 940 930 935 940

Thr Gly Thr Thr Gly Ala Cys Ala Ala Cys Thr Ala Cys Ala Thr Thr Thr Gly Thr Thr Gly Ala Cys Ala Ala Cys Thr Ala Cys Ala Thr Thr 945 950 955 960 945 950 955 960

Cys Ala Ala Gly Thr Gly Gly Ala Cys Ala Cys Cys Ala Cys Thr Cys Cys Ala Ala Gly Thr Gly Gly Ala Cys Ala Cys Cys Ala Cys Thr Cys 965 970 975 965 970 975

Thr Gly Thr Cys Thr Cys Ala Gly Thr Thr Thr Ala Cys Cys Gly Ala Thr Gly Thr Cys Thr Cys Ala Gly Thr Thr Thr Ala Cys Cys Gly Ala 980 985 990 980 985 990

Cys Cys Cys Gly Ala Ala Cys Gly Thr Thr Thr Ala Cys Cys Thr Gly Cys Cys Cys Gly Ala Ala Cys Gly Thr Thr Thr Ala Cys Cys Thr Gly 995 1000 1005 995 1000 1005

Thr Gly Gly Gly Ala Cys Gly Thr Cys Cys Ala Cys Cys Ala Cys Thr Gly Gly Gly Ala Cys Gly Thr Cys Cys Ala Cys Cys Ala Cys 1010 1015 1020 1010 1015 1020

Ala Gly Thr Ala Ala Gly Ala Gly Gly Cys Thr Ala Ala Thr Thr Ala Gly Thr Ala Ala Gly Ala Gly Gly Cys Thr Ala Ala Thr Thr 1025 1030 1035 1025 1030 1035

Ala Ala Gly Gly Thr Gly Gly Ala Cys Gly Gly Gly Gly Thr Thr Ala Ala Gly Gly Thr Gly Gly Ala Cys Gly Gly Gly Gly Thr Thr 1040 1045 1050 1040 1045 1050

Gly Thr Gly Ala Cys Cys Ala Ala Gly Ala Ala Gly Cys Gly Gly Gly Thr Gly Ala Cys Cys Ala Ala Gly Ala Ala Gly Cys Gly Gly 1055 1060 1065 1055 1060 1065

Ala Ala Gly Thr Cys Cys Thr Ala Cys Thr Gly Cys Gly Thr Gly Ala Ala Gly Thr Cys Cys Thr Ala Cys Thr Gly Cys Gly Thr Gly 1070 1075 1080 1070 1075 1080

Gly Ala Cys Thr Thr Cys Gly Cys Thr Gly Cys Cys Ala Thr Cys Gly Ala Cys Thr Thr Cys Gly Cys Thr Gly Cys Cys Ala Thr Cys 1085 1090 1095 1085 1090 1095

Cys Gly Gly Cys Cys Cys Cys Ala Gly Ala Thr Ala Gly Cys Cys Cys Gly Gly Cys Cys Cys Cys Ala Gly Ala Thr Ala Gly Cys Cys 1100 1105 1110 1100 1105 1110 Page 454 Page 454

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Thr Thr Ala Cys Thr Cys Cys Ala Gly Gly Ala Gly Ala Thr Gly Thr Thr Ala Cys Thr Cys Cys Ala Gly Gly Ala Gly Ala Thr Gly 1115 1120 1125 1115 1120 1125

Cys Ala Cys Gly Thr Thr Thr Cys Cys Cys Ala Thr Thr Thr Cys Cys Ala Cys Gly Thr Thr Thr Cys Cys Cys Ala Thr Thr Thr Cys 1130 1135 1140 1130 1135 1140

Cys Ala Cys Thr Thr Cys Thr Cys Cys Cys Thr Gly Gly Ala Cys Cys Ala Cys Thr Thr Cys Thr Cys Cys Cys Thr Gly Gly Ala Cys 1145 1150 1155 1145 1150 1155

Thr Gly Gly Gly Cys Cys Cys Thr Gly Ala Thr Cys Cys Thr Gly Thr Gly Gly Gly Cys Cys Cys Thr Gly Ala Thr Cys Cys Thr Gly 1160 1165 1170 1160 1165 1170

Cys Cys Gly Cys Thr Gly Gly Gly Cys Ala Ala Cys Cys Ala Gly Cys Cys Gly Cys Thr Gly Gly Gly Cys Ala Ala Cys Cys Ala Gly 1175 1180 1185 1175 1180 1185

Thr Cys Cys Cys Ala Gly Gly Thr Gly Ala Ala Cys Cys Ala Cys Thr Cys Cys Cys Ala Gly Gly Thr Gly Ala Ala Cys Cys Ala Cys 1190 1195 1200 1190 1195 1200

Ala Cys Gly Gly Thr Cys Cys Thr Cys Gly Ala Cys Thr Ala Cys Ala Cys Gly Gly Thr Cys Cys Thr Cys Gly Ala Cys Thr Ala Cys 1205 1210 1215 1205 1210 1215

Thr Ala Cys Cys Gly Cys Thr Gly Cys Gly Thr Gly Gly Thr Cys Thr Ala Cys Cys Gly Cys Thr Gly Cys Gly Thr Gly Gly Thr Cys 1220 1225 1230 1220 1225 1230

Ala Gly Cys Gly Ala Gly Cys Thr Cys Gly Thr Gly Cys Gly Cys Ala Gly Cys Gly Ala Gly Cys Thr Cys Gly Thr Gly Cys Gly Cys 1235 1240 1245 1235 1240 1245

Gly Cys Cys Ala Ala Cys Ala Thr Cys Ala Cys Cys Cys Cys Gly Gly Cys Cys Ala Ala Cys Ala Thr Cys Ala Cys Cys Cys Cys Gly 1250 1255 1260 1250 1255 1260

Gly Thr Gly Gly Thr Gly Gly Cys Gly Cys Thr Cys Thr Gly Gly Gly Thr Gly Gly Thr Gly Gly Cys Gly Cys Thr Cys Thr Gly Gly 1265 1270 1275 1265 1270 1275

Cys Gly Ala Cys Cys Cys Gly Cys Gly Gly Cys Cys Cys Cys Gly Cys Gly Ala Cys Cys Cys Gly Cys Gly Gly Cys Cys Cys Cys Gly 1280 1285 1290 1280 1285 1290

Cys Ala Cys Cys Ala Ala Gly Gly Gly Cys Thr Gly Cys Cys Gly Cys Ala Cys Cys Ala Ala Gly Gly Gly Cys Thr Gly Cys Cys Gly 1295 1300 1305 1295 1300 1305

Page 455 Page 455

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Cys Gly Gly Cys Cys Cys Cys Thr Gly Gly Cys Cys Ala Ala Gly Cys Gly Gly Cys Cys Cys Cys Thr Gly Gly Cys Cys Ala Ala Gly 1310 1315 1320 1310 1315 1320

Cys Ala Cys Gly Gly Ala Gly Cys Cys Thr Gly Gly Gly Ala Gly Cys Ala Cys Gly Gly Ala Gly Cys Cys Thr Gly Gly Gly Ala Gly 1325 1330 1335 1325 1330 1335

Ala Ala Cys Cys Cys Ala Cys Ala Cys Ala Cys Cys Gly Cys Cys Ala Ala Cys Cys Cys Ala Cys Ala Cys Ala Cys Cys Gly Cys Cys 1340 1345 1350 1340 1345 1350

Thr Cys Gly Gly Cys Thr Thr Thr Thr Gly Cys Ala Gly Ala Gly Thr Cys Gly Gly Cys Thr Thr Thr Thr Gly Cys Ala Gly Ala Gly 1355 1360 1365 1355 1360 1365

Thr Ala Cys Gly Cys Cys Cys Gly Gly Cys Thr Gly Thr Gly Cys Thr Ala Cys Gly Cys Cys Cys Gly Gly Cys Thr Gly Thr Gly Cys 1370 1375 1380 1370 1375 1380

Thr Thr Cys Ala Ala Gly Gly Ala Thr Cys Thr Cys Gly Gly Cys Thr Thr Cys Ala Ala Gly Gly Ala Thr Cys Thr Cys Gly Gly Cys 1385 1390 1395 1385 1390 1395

Cys Ala Cys Cys Ala Cys Gly Thr Cys Ala Ala Gly Thr Thr Cys Cys Ala Cys Cys Ala Cys Gly Thr Cys Ala Ala Gly Thr Thr Cys 1400 1405 1410 1400 1405 1410

Thr Gly Gly Ala Thr Cys Ala Cys Gly Ala Thr Gly Gly Gly Cys Thr Gly Gly Ala Thr Cys Ala Cys Gly Ala Thr Gly Gly Gly Cys 1415 1420 1425 1415 1420 1425

Gly Ala Gly Cys Cys Gly Thr Ala Cys Ala Cys Ala Cys Gly Gly Gly Ala Gly Cys Cys Gly Thr Ala Cys Ala Cys Ala Cys Gly Gly 1430 1435 1440 1430 1435 1440

Ala Ala Cys Ala Thr Gly Ala Cys Cys Thr Ala Cys Ala Gly Cys Ala Ala Cys Ala Thr Gly Ala Cys Cys Thr Ala Cys Ala Gly Cys 1445 1450 1455 1445 1450 1455

Gly Cys Gly Gly Gly Gly Cys Ala Cys Ala Ala Thr Cys Thr Thr Gly Cys Gly Gly Gly Gly Cys Ala Cys Ala Ala Thr Cys Thr Thr 1460 1465 1470 1460 1465 1470

Cys Thr Gly Ala Ala Gly Gly Cys Thr Cys Ala Cys Gly Cys Gly Cys Thr Gly Ala Ala Gly Gly Cys Thr Cys Ala Cys Gly Cys Gly 1475 1480 1485 1475 1480 1485

Thr Thr Gly Gly Cys Cys Thr Gly Gly Cys Gly Cys Gly Thr Gly Thr Thr Gly Gly Cys Cys Thr Gly Gly Cys Gly Cys Gly Thr Gly 1490 1495 1500 1490 1495 1500 Page 456 Page 456

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Thr Ala Cys Gly Ala Thr Gly Ala Ala Ala Ala Cys Thr Thr Thr Thr Ala Cys Gly Ala Thr Gly Ala Ala Ala Ala Cys Thr Thr Thr 1505 1510 1515 1505 1510 1515

Cys Gly Gly Gly Gly Cys Thr Cys Thr Cys Ala Gly Ala Ala Gly Cys Gly Gly Gly Gly Cys Thr Cys Thr Cys Ala Gly Ala Ala Gly 1520 1525 1530 1520 1525 1530

Gly Gly Gly Ala Ala Ala Ala Thr Ala Thr Cys Cys Ala Thr Ala Gly Gly Gly Ala Ala Ala Ala Thr Ala Thr Cys Cys Ala Thr Ala 1535 1540 1545 1535 1540 1545

Gly Cys Cys Cys Thr Gly Cys Ala Gly Gly Cys Cys Gly Ala Cys Gly Cys Cys Cys Thr Gly Cys Ala Gly Gly Cys Cys Gly Ala Cys 1550 1555 1560 1550 1555 1560

Thr Gly Gly Ala Thr Ala Gly Ala Gly Cys Cys Gly Gly Cys Cys Thr Gly Gly Ala Thr Ala Gly Ala Gly Cys Cys Gly Gly Cys Cys 1565 1570 1575 1565 1570 1575

Thr Gly Cys Cys Cys Thr Thr Thr Cys Thr Cys Cys Cys Ala Ala Thr Gly Cys Cys Cys Thr Thr Thr Cys Thr Cys Cys Cys Ala Ala 1580 1585 1590 1580 1585 1590

Ala Ala Gly Gly Ala Cys Ala Ala Ala Gly Ala Ala Gly Thr Gly Ala Ala Gly Gly Ala Cys Ala Ala Ala Gly Ala Ala Gly Thr Gly 1595 1600 1605 1595 1600 1605

Gly Cys Ala Gly Ala Gly Ala Gly Ala Gly Thr Thr Thr Thr Gly Gly Cys Ala Gly Ala Gly Ala Gly Ala Gly Thr Thr Thr Thr Gly 1610 1615 1620 1610 1615 1620

Gly Ala Ala Thr Thr Thr Gly Ala Cys Ala Thr Thr Gly Gly Cys Gly Ala Ala Thr Thr Thr Gly Ala Cys Ala Thr Thr Gly Gly Cys 1625 1630 1635 1625 1630 1635

Thr Gly Gly Cys Thr Gly Gly Cys Cys Gly Ala Gly Cys Cys Cys Thr Gly Gly Cys Thr Gly Gly Cys Cys Gly Ala Gly Cys Cys Cys 1640 1645 1650 1640 1645 1650

Ala Thr Thr Thr Thr Cys Gly Gly Cys Thr Cys Thr Gly Gly Gly Ala Thr Thr Thr Thr Cys Gly Gly Cys Thr Cys Thr Gly Gly Gly 1655 1660 1665 1655 1660 1665

Gly Ala Thr Thr Ala Thr Cys Cys Gly Cys Gly Thr Gly Thr Gly Gly Ala Thr Thr Ala Thr Cys Cys Gly Cys Gly Thr Gly Thr Gly 1670 1675 1680 1670 1675 1680

Ala Thr Gly Ala Gly Gly Gly Ala Cys Thr Gly Gly Cys Thr Cys Ala Thr Gly Ala Gly Gly Gly Ala Cys Thr Gly Gly Cys Thr Cys 1685 1690 1695 1685 1690 1695 Page 457 Page 457

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Ala Cys Gly Cys Ala Gly Ala Gly Ala Ala Ala Cys Ala Ala Thr Ala Cys Gly Cys Ala Gly Ala Gly Ala Ala Ala Cys Ala Ala Thr 1700 1705 1710 1700 1705 1710

Thr Thr Cys Cys Thr Thr Cys Thr Ala Cys Cys Thr Thr Ala Thr Thr Thr Cys Cys Thr Thr Cys Thr Ala Cys Cys Thr Thr Ala Thr 1715 1720 1725 1715 1720 1725

Thr Thr Cys Ala Cys Thr Gly Ala Ala Gly Ala Thr Gly Ala Ala Thr Thr Cys Ala Cys Thr Gly Ala Ala Gly Ala Thr Gly Ala Ala 1730 1735 1740 1730 1735 1740

Ala Ala Ala Ala Ala Gly Cys Thr Ala Ala Thr Cys Cys Gly Gly Ala Ala Ala Ala Ala Gly Cys Thr Ala Ala Thr Cys Cys Gly Gly 1745 1750 1755 1745 1750 1755

Gly Gly Thr Thr Cys Cys Thr Thr Cys Gly Ala Cys Thr Thr Thr Gly Gly Thr Thr Cys Cys Thr Thr Cys Gly Ala Cys Thr Thr Thr 1760 1765 1770 1760 1765 1770

Cys Thr Gly Gly Cys Cys Gly Thr Ala Ala Gly Cys Cys Ala Thr Cys Thr Gly Gly Cys Cys Gly Thr Ala Ala Gly Cys Cys Ala Thr 1775 1780 1785 1775 1780 1785

Thr Ala Cys Ala Cys Cys Ala Cys Cys Ala Thr Cys Cys Thr Cys Thr Ala Cys Ala Cys Cys Ala Cys Cys Ala Thr Cys Cys Thr Cys 1790 1795 1800 1790 1795 1800

Gly Thr Cys Gly Ala Cys Thr Gly Gly Gly Ala Ala Ala Ala Ala Gly Thr Cys Gly Ala Cys Thr Gly Gly Gly Ala Ala Ala Ala Ala 1805 1810 1815 1805 1810 1815

Gly Ala Ala Gly Ala Thr Cys Cys Ala Ala Thr Gly Ala Ala Ala Gly Ala Ala Gly Ala Thr Cys Cys Ala Ala Thr Gly Ala Ala Ala 1820 1825 1830 1820 1825 1830

Thr Ala Cys Ala Ala Cys Gly Ala Thr Thr Ala Cys Cys Thr Gly Thr Ala Cys Ala Ala Cys Gly Ala Thr Thr Ala Cys Cys Thr Gly 1835 1840 1845 1835 1840 1845

Gly Ala Gly Gly Thr Gly Cys Ala Gly Gly Ala Ala Ala Thr Gly Gly Ala Gly Gly Thr Gly Cys Ala Gly Gly Ala Ala Ala Thr Gly 1850 1855 1860 1850 1855 1860

Ala Cys Cys Gly Ala Cys Ala Thr Cys Ala Cys Gly Thr Gly Gly Ala Cys Cys Gly Ala Cys Ala Thr Cys Ala Cys Gly Thr Gly Gly 1865 1870 1875 1865 1870 1875

Cys Thr Cys Ala Ala Cys Thr Cys Cys Cys Cys Cys Ala Gly Thr Cys Thr Cys Ala Ala Cys Thr Cys Cys Cys Cys Cys Ala Gly Thr 1880 1885 1890 1880 1885 1890 Page 458 Page 458

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Cys Ala Gly Gly Thr Gly Gly Cys Ala Gly Thr Ala Gly Thr Gly Cys Ala Gly Gly Thr Gly Gly Cys Ala Gly Thr Ala Gly Thr Gly 1895 1900 1905 1895 1900 1905

Cys Cys Cys Thr Gly Gly Gly Gly Cys Thr Thr Ala Cys Gly Cys Cys Cys Cys Thr Gly Gly Gly Gly Cys Thr Thr Ala Cys Gly Cys 1910 1915 1920 1910 1915 1920

Ala Ala Ala Ala Thr Thr Cys Thr Cys Ala Ala Cys Thr Gly Gly Ala Ala Ala Ala Thr Thr Cys Thr Cys Ala Ala Cys Thr Gly Gly 1925 1930 1935 1925 1930 1935

Cys Thr Gly Ala Ala Gly Cys Thr Gly Ala Ala Gly Thr Ala Cys Cys Thr Gly Ala Ala Gly Cys Thr Gly Ala Ala Gly Thr Ala Cys 1940 1945 1950 1940 1945 1950

Gly Gly Ala Gly Ala Cys Cys Thr Cys Cys Cys Cys Ala Thr Gly Gly Gly Ala Gly Ala Cys Cys Thr Cys Cys Cys Cys Ala Thr Gly 1955 1960 1965 1955 1960 1965

Thr Ala Thr Ala Thr Ala Ala Thr Ala Thr Cys Cys Ala Ala Cys Thr Ala Thr Ala Thr Ala Ala Thr Ala Thr Cys Cys Ala Ala Cys 1970 1975 1980 1970 1975 1980

Gly Gly Cys Ala Thr Ala Gly Ala Cys Gly Ala Cys Gly Ala Thr Gly Gly Cys Ala Thr Ala Gly Ala Cys Gly Ala Cys Gly Ala Thr 1985 1990 1995 1985 1990 1995

Cys Cys Gly Cys Ala Gly Gly Cys Ala Gly Cys Gly Cys Ala Ala Cys Cys Gly Cys Ala Gly Gly Cys Ala Gly Cys Gly Cys Ala Ala 2000 2005 2010 2000 2005 2010

Gly Ala Cys Ala Ala Gly Cys Thr Gly Ala Gly Gly Gly Thr Gly Gly Ala Cys Ala Ala Gly Cys Thr Gly Ala Gly Gly Gly Thr Gly 2015 2020 2025 2015 2020 2025

Thr Ala Thr Thr Ala Cys Ala Thr Gly Cys Ala Ala Ala Ala Thr Thr Ala Thr Thr Ala Cys Ala Thr Gly Cys Ala Ala Ala Ala Thr 2030 2035 2040 2030 2035 2040

Thr Ala Thr Gly Thr Ala Ala Ala Thr Gly Ala Ala Gly Cys Thr Thr Ala Thr Gly Thr Ala Ala Ala Thr Gly Ala Ala Gly Cys Thr 2045 2050 2055 2045 2050 2055

Cys Thr Gly Ala Ala Ala Gly Cys Cys Thr Ala Cys Gly Thr Ala Cys Thr Gly Ala Ala Ala Gly Cys Cys Thr Ala Cys Gly Thr Ala 2060 2065 2070 2060 2065 2070

Thr Thr Gly Gly Ala Thr Gly Gly Thr Gly Thr Cys Ala Ala Thr Thr Thr Gly Gly Ala Thr Gly Gly Thr Gly Thr Cys Ala Ala Thr 2075 2080 2085 2075 2080 2085 Page 459 Page 459

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Cys Thr Thr Thr Gly Thr Gly Gly Ala Thr Ala Cys Thr Thr Thr Cys Thr Thr Thr Gly Thr Gly Gly Ala Thr Ala Cys Thr Thr Thr 2090 2095 2100 2090 2095 2100

Gly Cys Thr Thr Ala Thr Thr Cys Ala Thr Thr Cys Ala Ala Thr Gly Cys Thr Thr Ala Thr Thr Cys Ala Thr Thr Cys Ala Ala Thr 2105 2110 2115 2105 2110 2115

Gly Ala Thr Cys Gly Cys Ala Cys Ala Gly Cys Thr Cys Cys Ala Gly Ala Thr Cys Gly Cys Ala Cys Ala Gly Cys Thr Cys Cys Ala 2120 2125 2130 2120 2125 2130

Ala Ala Gly Thr Thr Thr Gly Gly Cys Thr Thr Cys Thr Ala Thr Ala Ala Gly Thr Thr Thr Gly Gly Cys Thr Thr Cys Thr Ala Thr 2135 2140 2145 2135 2140 2145

Cys Ala Thr Thr Ala Cys Gly Cys Thr Gly Cys Ala Ala Ala Thr Cys Ala Thr Thr Ala Cys Gly Cys Thr Gly Cys Ala Ala Ala Thr 2150 2155 2160 2150 2155 2160

Cys Ala Gly Thr Thr Thr Gly Ala Gly Cys Cys Cys Ala Ala Ala Cys Ala Gly Thr Thr Thr Gly Ala Gly Cys Cys Cys Ala Ala Ala 2165 2170 2175 2165 2170 2175

Cys Cys Gly Thr Cys Cys Ala Thr Gly Ala Ala Ala Cys Ala Thr Cys Cys Gly Thr Cys Cys Ala Thr Gly Ala Ala Ala Cys Ala Thr 2180 2185 2190 2180 2185 2190

Thr Ala Thr Cys Gly Gly Ala Ala Ala Ala Thr Gly Ala Thr Thr Thr Ala Thr Cys Gly Gly Ala Ala Ala Ala Thr Gly Ala Thr Thr 2195 2200 2205 2195 2200 2205

Gly Ala Cys Ala Gly Cys Ala Ala Thr Gly Gly Cys Thr Thr Cys Gly Ala Cys Ala Gly Cys Ala Ala Thr Gly Gly Cys Thr Thr Cys 2210 2215 2220 2210 2215 2220

Thr Cys Cys Gly Gly Thr Cys Cys Thr Gly Ala Cys Ala Cys Thr Thr Cys Cys Gly Gly Thr Cys Cys Thr Gly Ala Cys Ala Cys Thr 2225 2230 2235 2225 2230 2235

Cys Thr Gly Gly Gly Gly Ala Gly Ala Thr Thr Thr Thr Gly Thr Cys Thr Gly Gly Gly Gly Ala Gly Ala Thr Thr Thr Thr Gly Thr 2240 2245 2250 2240 2245 2250

Cys Cys Ala Gly Ala Ala Gly Ala Ala Thr Thr Cys Ala Cys Cys Cys Cys Ala Gly Ala Ala Gly Ala Ala Thr Thr Cys Ala Cys Cys 2255 2260 2265 2255 2260 2265

Cys Thr Gly Thr Gly Cys Ala Cys Cys Gly Ala Ala Thr Gly Cys Cys Thr Gly Thr Gly Cys Ala Cys Cys Gly Ala Ala Thr Gly Cys 2270 2275 2280 2270 2275 2280 Page 460 Page 460

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Gly Gly Cys Thr Thr Thr Thr Thr Thr Cys Ala Cys Ala Cys Cys Gly Gly Cys Thr Thr Thr Thr Thr Thr Cys Ala Cys Ala Cys Cys 2285 2290 2295 2285 2290 2295

Cys Gly Cys Ala Ala Ala Thr Cys Thr Thr Thr Ala Cys Thr Gly Cys Gly Cys Ala Ala Ala Thr Cys Thr Thr Thr Ala Cys Thr Gly 2300 2305 2310 2300 2305 2310

Gly Cys Thr Thr Thr Cys Ala Thr Ala Gly Cys Thr Thr Thr Cys Gly Cys Thr Thr Thr Cys Ala Thr Ala Gly Cys Thr Thr Thr Cys 2315 2320 2325 2315 2320 2325

Cys Thr Ala Cys Thr Thr Thr Thr Thr Gly Cys Thr Thr Thr Thr Cys Thr Ala Cys Thr Thr Thr Thr Thr Gly Cys Thr Thr Thr Thr 2330 2335 2340 2330 2335 2340

Ala Thr Thr Ala Thr Thr Thr Cys Thr Cys Thr Thr Thr Cys Thr Ala Thr Thr Ala Thr Thr Thr Cys Thr Cys Thr Thr Thr Cys Thr 2345 2350 2355 2345 2350 2355

Cys Thr Gly Ala Thr Thr Thr Thr Thr Thr Ala Cys Thr Ala Cys Cys Thr Gly Ala Thr Thr Thr Thr Thr Thr Ala Cys Thr Ala Cys 2360 2365 2370 2360 2365 2370

Thr Cys Thr Ala Ala Gly Ala Ala Ala Gly Gly Cys Ala Ala Ala Thr Cys Thr Ala Ala Gly Ala Ala Ala Gly Gly Cys Ala Ala Ala 2375 2380 2385 2375 2380 2385

Ala Gly Ala Ala Gly Thr Thr Ala Cys Ala Ala Gly Thr Ala Gly Ala Gly Ala Ala Gly Thr Thr Ala Cys Ala Ala Gly Thr Ala Gly 2390 2395 2400 2390 2395 2400

Thr Cys Cys Thr Gly Ala Cys Cys Thr Thr Thr Thr Thr Cys Cys Thr Cys Cys Thr Gly Ala Cys Cys Thr Thr Thr Thr Thr Cys Cys 2405 2410 2415 2405 2410 2415

Thr Ala Thr Thr Cys Ala Thr Thr Thr Ala Cys Thr Thr Thr Gly Thr Ala Thr Thr Cys Ala Thr Thr Thr Ala Cys Thr Thr Thr Gly 2420 2425 2430 2420 2425 2430

Ala Ala Ala Thr Gly Ala Thr Thr Ala Thr Gly Cys Ala Cys Ala Ala Ala Ala Thr Gly Ala Thr Thr Ala Thr Gly Cys Ala Cys Ala 2435 2440 2445 2435 2440 2445

Cys Ala Cys Ala Thr Cys Ala Gly Cys Thr Gly Thr Thr Cys Ala Cys Ala Cys Ala Thr Cys Ala Gly Cys Thr Gly Thr Thr Cys Ala 2450 2455 2460 2450 2455 2460

Cys Cys Ala Thr Thr Thr Gly Cys Ala Cys Thr Thr Cys Thr Cys Cys Cys Ala Thr Thr Thr Gly Cys Ala Cys Thr Thr Cys Thr Cys 2465 2470 2475 2465 2470 2475 Page 461 Page 461

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Ala Gly Thr Gly Thr Cys Gly Thr Ala Ala Gly Ala Cys Thr Gly Ala Gly Thr Gly Thr Cys Gly Thr Ala Ala Gly Ala Cys Thr Gly 2480 2485 2490 2480 2485 2490

Gly Ala Thr Thr Thr Cys Ala Cys Thr Thr Ala Thr Cys Thr Gly Gly Ala Thr Thr Thr Cys Ala Cys Thr Thr Ala Thr Cys Thr Gly 2495 2500 2505 2495 2500 2505

Ala Cys Thr Thr Cys Thr Ala Gly Ala Ala Ala Ala Ala Ala Ala Ala Cys Thr Thr Cys Thr Ala Gly Ala Ala Ala Ala Ala Ala Ala 2510 2515 2520 2510 2515 2520

Ala Thr Gly Thr Gly Thr Gly Gly Cys Gly Thr Ala Thr Gly Ala Ala Thr Gly Thr Gly Thr Gly Gly Cys Gly Thr Ala Thr Gly Ala 2525 2530 2535 2525 2530 2535

Cys Ala Gly Ala Gly Gly Thr Ala Thr Gly Gly Ala Ala Gly Thr Cys Ala Gly Ala Gly Gly Thr Ala Thr Gly Gly Ala Ala Gly Thr 2540 2545 2550 2540 2545 2550

Gly Ala Gly Cys Ala Thr Ala Gly Gly Thr Gly Ala Thr Thr Gly Gly Ala Gly Cys Ala Thr Ala Gly Gly Thr Gly Ala Thr Thr Gly 2555 2560 2565 2555 2560 2565

Thr Ala Ala Ala Ala Thr Ala Cys Thr Gly Ala Ala Thr Ala Ala Thr Ala Ala Ala Ala Thr Ala Cys Thr Gly Ala Ala Thr Ala Ala 2570 2575 2580 2570 2575 2580

Thr Gly Thr Gly Ala Ala Thr Ala Gly Thr Gly Cys Cys Thr Gly Thr Gly Thr Gly Ala Ala Thr Ala Gly Thr Gly Cys Cys Thr Gly 2585 2590 2595 2585 2590 2595

Gly Ala Thr Thr Thr Gly Thr Thr Cys Thr Thr Thr Cys Thr Thr Gly Ala Thr Thr Thr Gly Thr Thr Cys Thr Thr Thr Cys Thr Thr 2600 2605 2610 2600 2605 2610

Gly Gly Ala Gly Gly Ala Thr Gly Ala Thr Cys Ala Ala Ala Gly Gly Gly Ala Gly Gly Ala Thr Gly Ala Thr Cys Ala Ala Ala Gly 2615 2620 2625 2615 2620 2625

Ala Cys Gly Gly Thr Thr Ala Gly Gly Gly Gly Cys Cys Ala Thr Ala Cys Gly Gly Thr Thr Ala Gly Gly Gly Gly Cys Cys Ala Thr 2630 2635 2640 2630 2635 2640

Cys Ala Thr Cys Thr Cys Thr Gly Cys Ala Ala Cys Ala Cys Ala Cys Ala Thr Cys Thr Cys Thr Gly Cys Ala Ala Cys Ala Cys Ala 2645 2650 2655 2645 2650 2655

Thr Thr Cys Thr Gly Thr Ala Ala Cys Ala Ala Ala Thr Gly Thr Thr Thr Cys Thr Gly Thr Ala Ala Cys Ala Ala Ala Thr Gly Thr 2660 2665 2670 2660 2665 2670 Page 462 Page 462

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Ala Thr Gly Gly Gly Ala Ala Gly Thr Gly Gly Gly Ala Cys Cys Ala Thr Gly Gly Gly Ala Ala Gly Thr Gly Gly Gly Ala Cys Cys 2675 2680 2685 2675 2680 2685

Cys Ala Thr Thr Cys Thr Gly Gly Ala Ala Cys Ala Thr Thr Thr Cys Ala Thr Thr Cys Thr Gly Gly Ala Ala Cys Ala Thr Thr Thr 2690 2695 2700 2690 2695 2700

Thr Thr Ala Thr Ala Gly Ala Ala Ala Thr Thr Gly Ala Ala Thr Thr Thr Ala Thr Ala Gly Ala Ala Ala Thr Thr Gly Ala Ala Thr 2705 2710 2715 2705 2710 2715

Ala Gly Cys Ala Ala Gly Ala Thr Cys Ala Gly Thr Gly Cys Cys Ala Gly Cys Ala Ala Gly Ala Thr Cys Ala Gly Thr Gly Cys Cys 2720 2725 2730 2720 2725 2730

Cys Gly Thr Thr Cys Cys Thr Ala Ala Ala Thr Thr Ala Thr Cys Cys Gly Thr Thr Cys Cys Thr Ala Ala Ala Thr Thr Ala Thr Cys 2735 2740 2745 2735 2740 2745

Thr Thr Gly Ala Ala Gly Thr Ala Ala Ala Ala Cys Ala Ala Ala Thr Thr Gly Ala Ala Gly Thr Ala Ala Ala Ala Cys Ala Ala Ala 2750 2755 2760 2750 2755 2760

Thr Gly Thr Gly Gly Ala Ala Ala Thr Ala Ala Ala Ala Ala Gly Thr Gly Thr Gly Gly Ala Ala Ala Thr Ala Ala Ala Ala Ala Gly 2765 2770 2775 2765 2770 2775

Thr Thr Ala Ala Gly Thr Cys Cys Cys Ala Ala Ala Thr Ala Ala Thr Thr Ala Ala Gly Thr Cys Cys Cys Ala Ala Ala Thr Ala Ala 2780 2785 2790 2780 2785 2790

Cys Cys Ala Thr Cys Thr Cys Thr Ala Ala Ala Cys Thr Thr Cys Cys Cys Ala Thr Cys Thr Cys Thr Ala Ala Ala Cys Thr Thr Cys 2795 2800 2805 2795 2800 2805

Cys Ala Thr Gly Ala Thr Ala Thr Gly Cys Cys Thr Ala Ala Thr Cys Ala Thr Gly Ala Thr Ala Thr Gly Cys Cys Thr Ala Ala Thr 2810 2815 2820 2810 2815 2820

Gly Gly Thr Cys Thr Cys Thr Gly Thr Thr Gly Gly Ala Cys Cys Gly Gly Thr Cys Thr Cys Thr Gly Thr Thr Gly Gly Ala Cys Cys 2825 2830 2835 2825 2830 2835

Cys Ala Gly Thr Thr Thr Cys Cys Cys Thr Thr Gly Ala Ala Ala Cys Ala Gly Thr Thr Thr Cys Cys Cys Thr Thr Gly Ala Ala Ala 2840 2845 2850 2840 2845 2850

Ala Ala Gly Ala Ala Ala Thr Gly Gly Thr Ala Gly Ala Ala Thr Ala Ala Gly Ala Ala Ala Thr Gly Gly Thr Ala Gly Ala Ala Thr 2855 2860 2865 2855 2860 2865

Page 463 Page 463

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Ala Thr Thr Ala Gly Ala Gly Ala Cys Ala Thr Gly Ala Cys Ala Ala Thr Thr Ala Gly Ala Gly Ala Cys Ala Thr Gly Ala Cys Ala 2870 2875 2880 2870 2875 2880

Gly Ala Gly Gly Gly Cys Cys Cys Thr Ala Cys Gly Cys Thr Ala Gly Ala Gly Gly Gly Cys Cys Cys Thr Ala Cys Gly Cys Thr Ala 2885 2890 2895 2885 2890 2895

Gly Ala Ala Cys Gly Thr Thr Cys Cys Thr Thr Thr Thr Ala Thr Gly Ala Ala Cys Gly Thr Thr Cys Cys Thr Thr Thr Thr Ala Thr 2900 2905 2910 2900 2905 2910

Thr Thr Thr Thr Thr Thr Thr Thr Thr Thr Ala Ala Ala Thr Thr Thr Thr Thr Thr Thr Thr Thr Thr Thr Thr Ala Ala Ala Thr Thr 2915 2920 2925 2915 2920 2925

Thr Thr Thr Thr Thr Thr Cys Ala Ala Thr Gly Thr Thr Thr Thr Thr Thr Thr Thr Thr Thr Cys Ala Ala Thr Gly Thr Thr Thr Thr 2930 2935 2940 2930 2935 2940

Thr Ala Thr Thr Thr Ala Thr Thr Thr Thr Thr Gly Gly Gly Ala Thr Ala Thr Thr Thr Ala Thr Thr Thr Thr Thr Gly Gly Gly Ala 2945 2950 2955 2945 2950 2955

Cys Ala Gly Ala Gly Ala Gly Ala Gly Ala Cys Ala Gly Ala Gly Ala Gly Ala Gly Ala 2960 2965 2960 2965

<210> 125 <210> 125 <211> 1204 <211> 1204 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> Signal_ECD_34_981_2xGS_Fc <223> Signal_ECD_34_981_2xGS_Fc

<400> 125 <400> 125

Met Ala Arg Leu Thr Val Leu Ala Leu Leu Ala Gly Leu Leu Ala Ser Met Ala Arg Leu Thr Val Leu Ala Leu Leu Ala Gly Leu Leu Ala Ser 1 5 10 15 1 5 10 15

Ser Arg Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser Ser Arg Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Val Ser 20 25 30 20 25 30

Arg Pro Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Arg Pro Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro 35 40 45 35 40 45

Page 464 Page 464

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Asp Gly Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Asp Gly Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly 50 55 60 50 55 60

Gly Trp Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr Gly Trp Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr 65 70 75 80 70 75 80

His His Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro His His Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro 85 90 95 85 90 95

Leu Gly Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Leu Gly Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser 100 105 110 100 105 110

Asp Ser Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Asp Ser Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu 115 120 125 115 120 125

Gly Val Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Gly Val Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro 130 135 140 130 135 140

Asn Gly Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Asn Gly Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg 145 150 155 160 145 150 155 160

Arg Leu Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Arg Leu Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr 165 170 175 165 170 175

Leu Tyr His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Leu Tyr His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly 180 185 190 180 185 190

Trp Ala Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Trp Ala Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu 195 200 205 195 200 205

Cys Phe Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Cys Phe Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp 210 215 220 210 215 220

Asn Pro Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Asn Pro Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala 225 230 235 240 225 230 235 240

Pro Gly Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Pro Gly Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn 245 250 255 245 250 255

Page 465 Page 465

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Leu Leu Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Leu Leu Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe 260 265 270 260 265 270

Arg Pro Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Arg Pro Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp 275 280 285 275 280 285

Ile Asn Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ile Asn Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys 290 295 300 290 295 300

Ser Leu Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Ser Leu Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp 305 310 315 320 305 310 315 320

Gly Asp Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Gly Asp Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro 325 330 335 325 330 335

Asp Phe Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Asp Phe Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe 340 345 350 340 345 350

Phe Ala Leu Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro Phe Ala Leu Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro 355 360 365 355 360 365

His Met Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu His Met Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu 370 375 380 370 375 380

Ser Trp Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Ser Trp Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu 385 390 395 400 385 390 395 400

Asn Gly Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Asn Gly Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr 405 410 415 405 410 415

Met Tyr Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Met Tyr Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys 420 425 430 420 425 430

Leu Asp Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Leu Asp Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp 435 440 445 435 440 445

Gly Phe Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Gly Phe Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr 450 455 460 450 455 460

Page 466 Page 466

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Val Asp Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Val Asp Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala 465 470 475 480 465 470 475 480

Leu Phe Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Leu Phe Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro 485 490 495 485 490 495

Glu Asn Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Glu Asn Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly 500 505 510 500 505 510

Val Val Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Val Val Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr 515 520 525 515 520 525

Asp Leu Asn Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Asp Leu Asn Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile 530 535 540 530 535 540

Lys Val Asp Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Lys Val Asp Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp 545 550 555 560 545 550 555 560

Phe Ala Ala Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Phe Ala Ala Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val 565 570 575 565 570 575

Thr His Phe Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Thr His Phe Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly 580 585 590 580 585 590

Asn Gln Ser Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Asn Gln Ser Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met 595 600 605 595 600 605

Ala Ser Glu Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Ala Ser Glu Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp 610 615 620 610 615 620

Gln Pro Met Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gln Pro Met Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln 625 630 635 640 625 630 635 640

Gly Ala Trp Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Gly Ala Trp Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala 645 650 655 645 650 655

Arg Leu Cys Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Arg Leu Cys Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr 660 665 670 660 665 670

Page 467 Page 467

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Met Asn Glu Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Met Asn Glu Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn 675 680 685 675 680 685

Leu Leu Lys Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Leu Leu Lys Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe 690 695 700 690 695 700

Arg His Ala Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Arg His Ala Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp 705 710 715 720 705 710 715 720

Ile Glu Pro Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Ile Glu Pro Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu 725 730 735 725 730 735

Arg Val Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Arg Val Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly 740 745 750 740 745 750

Ser Gly Asp Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Ser Gly Asp Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn 755 760 765 755 760 765

Asn Phe Leu Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Asn Phe Leu Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln 770 775 780 770 775 780

Gly Thr Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Gly Thr Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val 785 790 795 800 785 790 795 800

Asp Ser Glu Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Asp Ser Glu Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val 805 810 815 805 810 815

Gln Glu Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Gln Glu Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala 820 825 830 820 825 830

Val Val Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Val Val Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys 835 840 845 835 840 845

Tyr Gly Asp Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Tyr Gly Asp Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly 850 855 860 850 855 860

Leu His Ala Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Leu His Ala Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr 865 870 875 880 865 870 875 880

Page 468 Page 468

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Ile Asn Glu Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Ile Asn Glu Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys 885 890 895 885 890 895

Gly Tyr Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Gly Tyr Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly 900 905 910 900 905 910

Leu Tyr Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys Leu Tyr Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys 915 920 925 915 920 925

His Tyr Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr His Tyr Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr 930 935 940 930 935 940

Leu Glu Arg Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Leu Glu Arg Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser 945 950 955 960 945 950 955 960

Phe Phe His Thr Arg Lys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Phe Phe His Thr Arg Lys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 965 970 975 965 970 975

Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 980 985 990 980 985 990

Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 995 1000 1005 995 1000 1005

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 1010 1015 1020 1010 1015 1020

Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 1025 1030 1035 1025 1030 1035

Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 1040 1045 1050 1040 1045 1050

Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 1055 1060 1065 1055 1060 1065

Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 1070 1075 1080 1070 1075 1080

Page 469 Page 469

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 1085 1090 1095 1085 1090 1095

Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp 1100 1105 1110 1100 1105 1110

Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 1115 1120 1125 1115 1120 1125

Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln 1130 1135 1140 1130 1135 1140

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp 1145 1150 1155 1145 1150 1155

Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 1160 1165 1170 1160 1165 1170

Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 1175 1180 1185 1175 1180 1185

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 1190 1195 1200 1190 1195 1200

Lys Lys

<210> 126 <210> 126 <211> 1223 <211> 1223 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> 1_981_V45F_3xGS__IgG1_noCH1_Fc_Fusion <223> 1_981_V45F_3xGS__IgG1_noCH1_Fc_Fusion

<400> 126 <400> 126

Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser 1 5 10 15 1 5 10 15

Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg 20 25 30 20 25 30

Page 470 Page 470

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. - TXT

Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro 35 40 45 35 40 45

Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly 50 55 60 50 55 60

Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp 65 70 75 80 70 75 80

Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His 85 90 95 85 90 95

Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly 100 105 110 100 105 110

Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser 115 120 125 115 120 125

Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val 130 135 140 130 135 140

Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly 145 150 155 160 145 150 155 160

Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu 165 170 175 165 170 175

Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr 180 185 190 180 185 190

His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala 195 200 205 195 200 205

Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe 210 215 220 210 215 220

Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro 225 230 235 240 225 230 235 240

Page 471 Page 471

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly 245 250 255 245 250 255

Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu 260 265 270 260 265 270

Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro 275 280 285 275 280 285

Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn 290 295 300 290 295 300

Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu 305 310 315 320 305 310 315 320

Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp 325 330 335 325 330 335

Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe 340 345 350 340 345 350

Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala 355 360 365 355 360 365

Leu Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Leu Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met 370 375 380 370 375 380

Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp 385 390 395 400 385 390 395 400

Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly 405 410 415 405 410 415

Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr 420 425 430 420 425 430

Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp 435 440 445 435 440 445

Page 472 Page 472

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe 450 455 460 450 455 460

Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp 465 470 475 480 465 470 475 480

Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe 485 490 495 485 490 495

Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn 500 505 510 500 505 510

Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val 515 520 525 515 520 525

Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu 530 535 540 530 535 540

Asn Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asn Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val 545 550 555 560 545 550 555 560

Asp Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Asp Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala 565 570 575 565 570 575

Ala Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Ala Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His 580 585 590 580 585 590

Phe Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Phe Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln 595 600 605 595 600 605

Ser Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Ser Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser 610 615 620 610 615 620

Glu Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Glu Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro 625 630 635 640 625 630 635 640

Met Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Met Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala 645 650 655 645 650 655

Page 473 Page 473

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Trp Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Trp Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu 660 665 670 660 665 670

Cys Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Cys Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn 675 680 685 675 680 685

Glu Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Glu Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu 690 695 700 690 695 700

Lys Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Lys Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His 705 710 715 720 705 710 715 720

Ala Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Ala Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu 725 730 735 725 730 735

Pro Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Pro Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val 740 745 750 740 745 750

Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly 755 760 765 755 760 765

Asp Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Asp Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe 770 775 780 770 775 780

Leu Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Leu Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr 785 790 795 800 785 790 795 800

Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser 805 810 815 805 810 815

Glu Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Glu Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu 820 825 830 820 825 830

Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val 835 840 845 835 840 845

Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly 850 855 860 850 855 860

Page 474 Page 474

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Asp Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Asp Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His 865 870 875 880 865 870 875 880

Ala Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Ala Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn 885 890 895 885 890 895

Glu Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Glu Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr 900 905 910 900 905 910

Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr 915 920 925 915 920 925

Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr 930 935 940 930 935 940

Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu 945 950 955 960 945 950 955 960

Arg Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe Arg Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe 965 970 975 965 970 975

His Thr Arg Lys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly His Thr Arg Lys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 980 985 990 980 985 990

Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 995 1000 1005 995 1000 1005

Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 1010 1015 1020 1010 1015 1020

Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 1025 1030 1035 1025 1030 1035

Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 1040 1045 1050 1040 1045 1050

Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg 1055 1060 1065 1055 1060 1065

Page 475 Page 475

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 1070 1075 1080 1070 1075 1080

Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys 1085 1090 1095 1085 1090 1095

Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser 1100 1105 1110 1100 1105 1110

Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 1115 1120 1125 1115 1120 1125

Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys 1130 1135 1140 1130 1135 1140

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 1145 1150 1155 1145 1150 1155

Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 1160 1165 1170 1160 1165 1170

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 1175 1180 1185 1175 1180 1185

Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 1190 1195 1200 1190 1195 1200

Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 1205 1210 1215 1205 1210 1215

Leu Ser Pro Gly Lys Leu Ser Pro Gly Lys 1220 1220

<210> 127 <210> 127 <211> 1572 <211> 1572 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> HSA_Signal_HSA_Seq_GS_ECD_34_981 <223> HSA_Signal_HSA_Seq_GS_ECD_34_981 Page 476 Page 476

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

<400> 127 <400> 127

Met Lys Trp Val Thr Phe Ile Ser Leu Leu Phe Leu Phe Ser Ser Ala Met Lys Trp Val Thr Phe Ile Ser Leu Leu Phe Leu Phe Ser Ser Ala 1 5 10 15 1 5 10 15

Tyr Ser Arg Gly Val Phe Arg Arg Asp Ala His Lys Ser Glu Val Ala Tyr Ser Arg Gly Val Phe Arg Arg Asp Ala His Lys Ser Glu Val Ala 20 25 30 20 25 30

His Arg Phe Lys Asp Leu Gly Glu Glu Asn Phe Lys Ala Leu Val Leu His Arg Phe Lys Asp Leu Gly Glu Glu Asn Phe Lys Ala Leu Val Leu 35 40 45 35 40 45

Ile Ala Phe Ala Gln Tyr Leu Gln Gln Cys Pro Phe Glu Asp His Val Ile Ala Phe Ala Gln Tyr Leu Gln Gln Cys Pro Phe Glu Asp His Val 50 55 60 50 55 60

Lys Leu Val Asn Glu Val Thr Glu Phe Ala Lys Thr Cys Val Ala Asp Lys Leu Val Asn Glu Val Thr Glu Phe Ala Lys Thr Cys Val Ala Asp 65 70 75 80 70 75 80

Glu Ser Ala Glu Asn Cys Asp Lys Ser Leu His Thr Leu Phe Gly Asp Glu Ser Ala Glu Asn Cys Asp Lys Ser Leu His Thr Leu Phe Gly Asp 85 90 95 85 90 95

Lys Leu Cys Thr Val Ala Thr Leu Arg Glu Thr Tyr Gly Glu Met Ala Lys Leu Cys Thr Val Ala Thr Leu Arg Glu Thr Tyr Gly Glu Met Ala 100 105 110 100 105 110

Asp Cys Cys Ala Lys Gln Glu Pro Glu Arg Asn Glu Cys Phe Leu Gln Asp Cys Cys Ala Lys Gln Glu Pro Glu Arg Asn Glu Cys Phe Leu Gln 115 120 125 115 120 125

His Lys Asp Asp Asn Pro Asn Leu Pro Arg Leu Val Arg Pro Glu Val His Lys Asp Asp Asn Pro Asn Leu Pro Arg Leu Val Arg Pro Glu Val 130 135 140 130 135 140

Asp Val Met Cys Thr Ala Phe His Asp Asn Glu Glu Thr Phe Leu Lys Asp Val Met Cys Thr Ala Phe His Asp Asn Glu Glu Thr Phe Leu Lys 145 150 155 160 145 150 155 160

Lys Tyr Leu Tyr Glu Ile Ala Arg Arg His Pro Tyr Phe Tyr Ala Pro Lys Tyr Leu Tyr Glu Ile Ala Arg Arg His Pro Tyr Phe Tyr Ala Pro 165 170 175 165 170 175

Glu Leu Leu Phe Phe Ala Lys Arg Tyr Lys Ala Ala Phe Thr Glu Cys Glu Leu Leu Phe Phe Ala Lys Arg Tyr Lys Ala Ala Phe Thr Glu Cys 180 185 190 180 185 190

Cys Gln Ala Ala Asp Lys Ala Ala Cys Leu Leu Pro Lys Leu Asp Glu Cys Gln Ala Ala Asp Lys Ala Ala Cys Leu Leu Pro Lys Leu Asp Glu Page 477 Page 477

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 195 200 205 195 200 205

Leu Arg Asp Glu Gly Lys Ala Ser Ser Ala Lys Gln Arg Leu Lys Cys Leu Arg Asp Glu Gly Lys Ala Ser Ser Ala Lys Gln Arg Leu Lys Cys 210 215 220 210 215 220

Ala Ser Leu Gln Lys Phe Gly Glu Arg Ala Phe Lys Ala Trp Ala Val Ala Ser Leu Gln Lys Phe Gly Glu Arg Ala Phe Lys Ala Trp Ala Val 225 230 235 240 225 230 235 240

Ala Arg Leu Ser Gln Arg Phe Pro Lys Ala Glu Phe Ala Glu Val Ser Ala Arg Leu Ser Gln Arg Phe Pro Lys Ala Glu Phe Ala Glu Val Ser 245 250 255 245 250 255

Lys Leu Val Thr Asp Leu Thr Lys Val His Thr Glu Cys Cys His Gly Lys Leu Val Thr Asp Leu Thr Lys Val His Thr Glu Cys Cys His Gly 260 265 270 260 265 270

Asp Leu Leu Glu Cys Ala Asp Asp Arg Ala Asp Leu Ala Lys Tyr Ile Asp Leu Leu Glu Cys Ala Asp Asp Arg Ala Asp Leu Ala Lys Tyr Ile 275 280 285 275 280 285

Cys Glu Asn Gln Asp Ser Ile Ser Ser Lys Leu Lys Glu Cys Cys Glu Cys Glu Asn Gln Asp Ser Ile Ser Ser Lys Leu Lys Glu Cys Cys Glu 290 295 300 290 295 300

Lys Pro Leu Leu Glu Lys Ser His Cys Ile Ala Glu Val Glu Asn Asp Lys Pro Leu Leu Glu Lys Ser His Cys Ile Ala Glu Val Glu Asn Asp 305 310 315 320 305 310 315 320

Glu Met Pro Ala Asp Leu Pro Ser Leu Ala Ala Asp Phe Val Glu Ser Glu Met Pro Ala Asp Leu Pro Ser Leu Ala Ala Asp Phe Val Glu Ser 325 330 335 325 330 335

Lys Asp Val Cys Lys Asn Tyr Ala Glu Ala Lys Asp Val Phe Leu Gly Lys Asp Val Cys Lys Asn Tyr Ala Glu Ala Lys Asp Val Phe Leu Gly 340 345 350 340 345 350

Met Phe Leu Tyr Glu Tyr Ala Arg Arg His Pro Asp Tyr Ser Val Val Met Phe Leu Tyr Glu Tyr Ala Arg Arg His Pro Asp Tyr Ser Val Val 355 360 365 355 360 365

Leu Leu Leu Arg Leu Ala Lys Thr Tyr Glu Thr Thr Leu Glu Lys Cys Leu Leu Leu Arg Leu Ala Lys Thr Tyr Glu Thr Thr Leu Glu Lys Cys 370 375 380 370 375 380

Cys Ala Ala Ala Asp Pro His Glu Cys Tyr Ala Lys Val Phe Asp Glu Cys Ala Ala Ala Asp Pro His Glu Cys Tyr Ala Lys Val Phe Asp Glu 385 390 395 400 385 390 395 400

Phe Lys Pro Leu Val Glu Glu Pro Gln Asn Leu Ile Lys Gln Asn Cys Phe Lys Pro Leu Val Glu Glu Pro Gln Asn Leu Ile Lys Gln Asn Cys Page 478 Page 478

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 405 410 415 405 410 415

Glu Leu Phe Glu Gln Leu Gly Glu Tyr Lys Phe Gln Asn Ala Leu Leu Glu Leu Phe Glu Gln Leu Gly Glu Tyr Lys Phe Gln Asn Ala Leu Leu 420 425 430 420 425 430

Val Arg Tyr Thr Lys Lys Val Pro Gln Val Ser Thr Pro Thr Leu Val Val Arg Tyr Thr Lys Lys Val Pro Gln Val Ser Thr Pro Thr Leu Val 435 440 445 435 440 445

Glu Val Ser Arg Asn Leu Gly Lys Val Gly Ser Lys Cys Cys Lys His Glu Val Ser Arg Asn Leu Gly Lys Val Gly Ser Lys Cys Cys Lys His 450 455 460 450 455 460

Pro Glu Ala Lys Arg Met Pro Cys Ala Glu Asp Tyr Leu Ser Val Val Pro Glu Ala Lys Arg Met Pro Cys Ala Glu Asp Tyr Leu Ser Val Val 465 470 475 480 465 470 475 480

Leu Asn Gln Leu Cys Val Leu His Glu Lys Thr Pro Val Ser Asp Arg Leu Asn Gln Leu Cys Val Leu His Glu Lys Thr Pro Val Ser Asp Arg 485 490 495 485 490 495

Val Thr Lys Cys Cys Thr Glu Ser Leu Val Asn Arg Arg Pro Cys Phe Val Thr Lys Cys Cys Thr Glu Ser Leu Val Asn Arg Arg Pro Cys Phe 500 505 510 500 505 510

Ser Ala Leu Glu Val Asp Glu Thr Tyr Val Pro Lys Glu Phe Asn Ala Ser Ala Leu Glu Val Asp Glu Thr Tyr Val Pro Lys Glu Phe Asn Ala 515 520 525 515 520 525

Glu Thr Phe Thr Phe His Ala Asp Ile Cys Thr Leu Ser Glu Lys Glu Glu Thr Phe Thr Phe His Ala Asp Ile Cys Thr Leu Ser Glu Lys Glu 530 535 540 530 535 540

Arg Gln Ile Lys Lys Gln Thr Ala Leu Val Glu Leu Val Lys His Lys Arg Gln Ile Lys Lys Gln Thr Ala Leu Val Glu Leu Val Lys His Lys 545 550 555 560 545 550 555 560

Pro Lys Ala Thr Lys Glu Gln Leu Lys Ala Val Met Asp Asp Phe Ala Pro Lys Ala Thr Lys Glu Gln Leu Lys Ala Val Met Asp Asp Phe Ala 565 570 575 565 570 575

Ala Phe Val Glu Lys Cys Cys Lys Ala Asp Asp Lys Glu Thr Cys Phe Ala Phe Val Glu Lys Cys Cys Lys Ala Asp Asp Lys Glu Thr Cys Phe 580 585 590 580 585 590

Ala Glu Glu Gly Lys Lys Leu Val Ala Ala Ser Gln Ala Ala Leu Gly Ala Glu Glu Gly Lys Lys Leu Val Ala Ala Ser Gln Ala Ala Leu Gly 595 600 605 595 600 605

Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Page 479 Page 479

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 610 615 620 610 615 620

Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro 625 630 635 640 625 630 635 640

Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe 645 650 655 645 650 655

Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln 660 665 670 660 665 670

Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro 675 680 685 675 680 685

Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala 690 695 700 690 695 700

Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr 705 710 715 720 705 710 715 720

Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr 725 730 735 725 730 735

His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser 740 745 750 740 745 750

Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu 755 760 765 755 760 765

Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His 770 775 780 770 775 780

Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn 785 790 795 800 785 790 795 800

Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg 805 810 815 805 810 815

His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Page 480 Page 480

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing TXT 820 825 830 820 825 830

Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile 835 840 845 835 840 845

Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu 850 855 860 850 855 860

Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr 865 870 875 880 865 870 875 880

Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro 885 890 895 885 890 895

Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp 900 905 910 900 905 910

Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr 915 920 925 915 920 925

Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr 930 935 940 930 935 940

Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu 945 950 955 960 945 950 955 960

Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys 965 970 975 965 970 975

Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile 980 985 990 980 985 990

Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp 995 1000 1005 995 1000 1005

Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr 1010 1015 1020 1010 1015 1020

Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Page 481 Page 481

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 1025 1030 1035 1025 1030 1035

Asp Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Asp Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp 1040 1045 1050 1040 1045 1050

Gly Phe Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Gly Phe Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe 1055 1060 1065 1055 1060 1065

Tyr Val Asp Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Tyr Val Asp Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser 1070 1075 1080 1070 1075 1080

Ser Ala Leu Phe Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Ser Ala Leu Phe Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro 1085 1090 1095 1085 1090 1095

Pro Leu Pro Glu Asn Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Pro Leu Pro Glu Asn Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp 1100 1105 1110 1100 1105 1110

Phe Ala Trp Gly Val Val Asp Asn Tyr Ile Gln Val Asp Thr Thr Phe Ala Trp Gly Val Val Asp Asn Tyr Ile Gln Val Asp Thr Thr 1115 1120 1125 1115 1120 1125

Leu Ser Gln Phe Thr Asp Leu Asn Val Tyr Leu Trp Asp Val His Leu Ser Gln Phe Thr Asp Leu Asn Val Tyr Leu Trp Asp Val His 1130 1135 1140 1130 1135 1140

His Ser Lys Arg Leu Ile Lys Val Asp Gly Val Val Thr Lys Lys His Ser Lys Arg Leu Ile Lys Val Asp Gly Val Val Thr Lys Lys 1145 1150 1155 1145 1150 1155

Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Ile Gln Pro Gln Ile Arg Lys Ser Tyr Cys Val Asp Phe Ala Ala Ile Gln Pro Gln Ile 1160 1165 1170 1160 1165 1170

Ala Leu Leu Gln Glu Met His Val Thr His Phe Arg Phe Ser Leu Ala Leu Leu Gln Glu Met His Val Thr His Phe Arg Phe Ser Leu 1175 1180 1185 1175 1180 1185

Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Gln Val Asn Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Ser Gln Val Asn 1190 1195 1200 1190 1195 1200

His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu Leu Val His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Glu Leu Val 1205 1210 1215 1205 1210 1215

Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met Ala Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Met Ala Page 482 Page 482

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 1220 1225 1230 1220 1225 1230

Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Trp 1235 1240 1245 1235 1240 1245

Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu 1250 1255 1260 1250 1255 1260

Cys Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Cys Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met 1265 1270 1275 1265 1270 1275

Asn Glu Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Asn Glu Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn 1280 1285 1290 1280 1285 1290

Leu Leu Lys Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Leu Leu Lys Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys 1295 1300 1305 1295 1300 1305

Phe Arg His Ala Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Phe Arg His Ala Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala 1310 1315 1320 1310 1315 1320

Asp Trp Ile Glu Pro Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Asp Trp Ile Glu Pro Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu 1325 1330 1335 1325 1330 1335

Val Ala Glu Arg Val Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Val Ala Glu Arg Val Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu 1340 1345 1350 1340 1345 1350

Pro Ile Phe Gly Ser Gly Asp Tyr Pro Trp Val Met Arg Asp Trp Pro Ile Phe Gly Ser Gly Asp Tyr Pro Trp Val Met Arg Asp Trp 1355 1360 1365 1355 1360 1365

Leu Asn Gln Arg Asn Asn Phe Leu Leu Pro Tyr Phe Thr Glu Asp Leu Asn Gln Arg Asn Asn Phe Leu Leu Pro Tyr Phe Thr Glu Asp 1370 1375 1380 1370 1375 1380

Glu Lys Lys Leu Ile Gln Gly Thr Phe Asp Phe Leu Ala Leu Ser Glu Lys Lys Leu Ile Gln Gly Thr Phe Asp Phe Leu Ala Leu Ser 1385 1390 1395 1385 1390 1395

His Tyr Thr Thr Ile Leu Val Asp Ser Glu Lys Glu Asp Pro Ile His Tyr Thr Thr Ile Leu Val Asp Ser Glu Lys Glu Asp Pro Ile 1400 1405 1410 1400 1405 1410

Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Thr Asp Ile Thr Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Met Thr Asp Ile Thr Page 483 Page 483

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 1415 1420 1425 1415 1420 1425

Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Trp Gly Leu Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Pro Trp Gly Leu 1430 1435 1440 1430 1435 1440

Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp Leu Pro Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Asp Leu Pro 1445 1450 1455 1445 1450 1455

Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala Glu Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Ala Glu 1460 1465 1470 1460 1465 1470

Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Glu 1475 1480 1485 1475 1480 1485

Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr 1490 1495 1500 1490 1495 1500

Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu 1505 1510 1515 1505 1510 1515

Tyr Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys Tyr Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys 1520 1525 1530 1520 1525 1530

His Tyr Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu His Tyr Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu 1535 1540 1545 1535 1540 1545

Thr Leu Glu Arg Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Thr Leu Glu Arg Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu 1550 1555 1560 1550 1555 1560

Cys Ser Phe Phe His Thr Arg Lys Ser Cys Ser Phe Phe His Thr Arg Lys Ser 1565 1570 1565 1570

<210> 128 <210> 128 <211> 1581 <211> 1581 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> Native_1_981_GS_HSA_Seq <223> Native_1_981_GS_HSA_Seq

<400> 128 <400> 128

Page 484 Page 484

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser 1 5 10 15 1 5 10 15

Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg 20 25 30 20 25 30

Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro 35 40 45 35 40 45

Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly 50 55 60 50 55 60

Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp 65 70 75 80 70 75 80

Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His 85 90 95 85 90 95

Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly 100 105 110 100 105 110

Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser 115 120 125 115 120 125

Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val 130 135 140 130 135 140

Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly 145 150 155 160 145 150 155 160

Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu 165 170 175 165 170 175

Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr 180 185 190 180 185 190

His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala 195 200 205 195 200 205

Page 485 Page 485

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe 210 215 220 210 215 220

Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro 225 230 235 240 225 230 235 240

Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly 245 250 255 245 250 255

Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu 260 265 270 260 265 270

Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro 275 280 285 275 280 285

Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn 290 295 300 290 295 300

Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu 305 310 315 320 305 310 315 320

Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp 325 330 335 325 330 335

Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe 340 345 350 340 345 350

Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala 355 360 365 355 360 365

Leu Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Leu Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met 370 375 380 370 375 380

Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp 385 390 395 400 385 390 395 400

Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly 405 410 415 405 410 415

Page 486 Page 486

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr 420 425 430 420 425 430

Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp 435 440 445 435 440 445

Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe 450 455 460 450 455 460

Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp 465 470 475 480 465 470 475 480

Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe 485 490 495 485 490 495

Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn 500 505 510 500 505 510

Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val 515 520 525 515 520 525

Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu 530 535 540 530 535 540

Asn Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asn Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val 545 550 555 560 545 550 555 560

Asp Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Asp Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala 565 570 575 565 570 575

Ala Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Ala Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His 580 585 590 580 585 590

Phe Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Phe Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln 595 600 605 595 600 605

Ser Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Ser Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser 610 615 620 610 615 620

Page 487 Page 487

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Glu Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Glu Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro 625 630 635 640 625 630 635 640

Met Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Met Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala 645 650 655 645 650 655

Trp Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Trp Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu 660 665 670 660 665 670

Cys Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Cys Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn 675 680 685 675 680 685

Glu Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Glu Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu 690 695 700 690 695 700

Lys Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Lys Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His 705 710 715 720 705 710 715 720

Ala Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Ala Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu 725 730 735 725 730 735

Pro Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Pro Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val 740 745 750 740 745 750

Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly 755 760 765 755 760 765

Asp Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Asp Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe 770 775 780 770 775 780

Leu Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Leu Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr 785 790 795 800 785 790 795 800

Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser 805 810 815 805 810 815

Glu Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Glu Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu 820 825 830 820 825 830

Page 488 Page 488

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val 835 840 845 835 840 845

Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly 850 855 860 850 855 860

Asp Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Asp Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His 865 870 875 880 865 870 875 880

Ala Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Ala Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn 885 890 895 885 890 895

Glu Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Glu Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr 900 905 910 900 905 910

Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr 915 920 925 915 920 925

Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr 930 935 940 930 935 940

Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu 945 950 955 960 945 950 955 960

Arg Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe Arg Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe 965 970 975 965 970 975

His Thr Arg Lys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly His Thr Arg Lys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 980 985 990 980 985 990

Gly Gly Gly Ser Asp Ala His Lys Ser Glu Val Ala His Arg Phe Lys Gly Gly Gly Ser Asp Ala His Lys Ser Glu Val Ala His Arg Phe Lys 995 1000 1005 995 1000 1005

Asp Leu Gly Glu Glu Asn Phe Lys Ala Leu Val Leu Ile Ala Phe Asp Leu Gly Glu Glu Asn Phe Lys Ala Leu Val Leu Ile Ala Phe 1010 1015 1020 1010 1015 1020

Ala Gln Tyr Leu Gln Gln Cys Pro Phe Glu Asp His Val Lys Leu Ala Gln Tyr Leu Gln Gln Cys Pro Phe Glu Asp His Val Lys Leu 1025 1030 1035 1025 1030 1035

Page 489 Page 489

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Val Asn Glu Val Thr Glu Phe Ala Lys Thr Cys Val Ala Asp Glu Val Asn Glu Val Thr Glu Phe Ala Lys Thr Cys Val Ala Asp Glu 1040 1045 1050 1040 1045 1050

Ser Ala Glu Asn Cys Asp Lys Ser Leu His Thr Leu Phe Gly Asp Ser Ala Glu Asn Cys Asp Lys Ser Leu His Thr Leu Phe Gly Asp 1055 1060 1065 1055 1060 1065

Lys Leu Cys Thr Val Ala Thr Leu Arg Glu Thr Tyr Gly Glu Met Lys Leu Cys Thr Val Ala Thr Leu Arg Glu Thr Tyr Gly Glu Met 1070 1075 1080 1070 1075 1080

Ala Asp Cys Cys Ala Lys Gln Glu Pro Glu Arg Asn Glu Cys Phe Ala Asp Cys Cys Ala Lys Gln Glu Pro Glu Arg Asn Glu Cys Phe 1085 1090 1095 1085 1090 1095

Leu Gln His Lys Asp Asp Asn Pro Asn Leu Pro Arg Leu Val Arg Leu Gln His Lys Asp Asp Asn Pro Asn Leu Pro Arg Leu Val Arg 1100 1105 1110 1100 1105 1110

Pro Glu Val Asp Val Met Cys Thr Ala Phe His Asp Asn Glu Glu Pro Glu Val Asp Val Met Cys Thr Ala Phe His Asp Asn Glu Glu 1115 1120 1125 1115 1120 1125

Thr Phe Leu Lys Lys Tyr Leu Tyr Glu Ile Ala Arg Arg His Pro Thr Phe Leu Lys Lys Tyr Leu Tyr Glu Ile Ala Arg Arg His Pro 1130 1135 1140 1130 1135 1140

Tyr Phe Tyr Ala Pro Glu Leu Leu Phe Phe Ala Lys Arg Tyr Lys Tyr Phe Tyr Ala Pro Glu Leu Leu Phe Phe Ala Lys Arg Tyr Lys 1145 1150 1155 1145 1150 1155

Ala Ala Phe Thr Glu Cys Cys Gln Ala Ala Asp Lys Ala Ala Cys Ala Ala Phe Thr Glu Cys Cys Gln Ala Ala Asp Lys Ala Ala Cys 1160 1165 1170 1160 1165 1170

Leu Leu Pro Lys Leu Asp Glu Leu Arg Asp Glu Gly Lys Ala Ser Leu Leu Pro Lys Leu Asp Glu Leu Arg Asp Glu Gly Lys Ala Ser 1175 1180 1185 1175 1180 1185

Ser Ala Lys Gln Arg Leu Lys Cys Ala Ser Leu Gln Lys Phe Gly Ser Ala Lys Gln Arg Leu Lys Cys Ala Ser Leu Gln Lys Phe Gly 1190 1195 1200 1190 1195 1200

Glu Arg Ala Phe Lys Ala Trp Ala Val Ala Arg Leu Ser Gln Arg Glu Arg Ala Phe Lys Ala Trp Ala Val Ala Arg Leu Ser Gln Arg 1205 1210 1215 1205 1210 1215

Phe Pro Lys Ala Glu Phe Ala Glu Val Ser Lys Leu Val Thr Asp Phe Pro Lys Ala Glu Phe Ala Glu Val Ser Lys Leu Val Thr Asp 1220 1225 1230 1220 1225 1230

Page 490 Page 490

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Leu Thr Lys Val His Thr Glu Cys Cys His Gly Asp Leu Leu Glu Leu Thr Lys Val His Thr Glu Cys Cys His Gly Asp Leu Leu Glu 1235 1240 1245 1235 1240 1245

Cys Ala Asp Asp Arg Ala Asp Leu Ala Lys Tyr Ile Cys Glu Asn Cys Ala Asp Asp Arg Ala Asp Leu Ala Lys Tyr Ile Cys Glu Asn 1250 1255 1260 1250 1255 1260

Gln Asp Ser Ile Ser Ser Lys Leu Lys Glu Cys Cys Glu Lys Pro Gln Asp Ser Ile Ser Ser Lys Leu Lys Glu Cys Cys Glu Lys Pro 1265 1270 1275 1265 1270 1275

Leu Leu Glu Lys Ser His Cys Ile Ala Glu Val Glu Asn Asp Glu Leu Leu Glu Lys Ser His Cys Ile Ala Glu Val Glu Asn Asp Glu 1280 1285 1290 1280 1285 1290

Met Pro Ala Asp Leu Pro Ser Leu Ala Ala Asp Phe Val Glu Ser Met Pro Ala Asp Leu Pro Ser Leu Ala Ala Asp Phe Val Glu Ser 1295 1300 1305 1295 1300 1305

Lys Asp Val Cys Lys Asn Tyr Ala Glu Ala Lys Asp Val Phe Leu Lys Asp Val Cys Lys Asn Tyr Ala Glu Ala Lys Asp Val Phe Leu 1310 1315 1320 1310 1315 1320

Gly Met Phe Leu Tyr Glu Tyr Ala Arg Arg His Pro Asp Tyr Ser Gly Met Phe Leu Tyr Glu Tyr Ala Arg Arg His Pro Asp Tyr Ser 1325 1330 1335 1325 1330 1335

Val Val Leu Leu Leu Arg Leu Ala Lys Thr Tyr Glu Thr Thr Leu Val Val Leu Leu Leu Arg Leu Ala Lys Thr Tyr Glu Thr Thr Leu 1340 1345 1350 1340 1345 1350

Glu Lys Cys Cys Ala Ala Ala Asp Pro His Glu Cys Tyr Ala Lys Glu Lys Cys Cys Ala Ala Ala Asp Pro His Glu Cys Tyr Ala Lys 1355 1360 1365 1355 1360 1365

Val Phe Asp Glu Phe Lys Pro Leu Val Glu Glu Pro Gln Asn Leu Val Phe Asp Glu Phe Lys Pro Leu Val Glu Glu Pro Gln Asn Leu 1370 1375 1380 1370 1375 1380

Ile Lys Gln Asn Cys Glu Leu Phe Glu Gln Leu Gly Glu Tyr Lys Ile Lys Gln Asn Cys Glu Leu Phe Glu Gln Leu Gly Glu Tyr Lys 1385 1390 1395 1385 1390 1395

Phe Gln Asn Ala Leu Leu Val Arg Tyr Thr Lys Lys Val Pro Gln Phe Gln Asn Ala Leu Leu Val Arg Tyr Thr Lys Lys Val Pro Gln 1400 1405 1410 1400 1405 1410

Val Ser Thr Pro Thr Leu Val Glu Val Ser Arg Asn Leu Gly Lys Val Ser Thr Pro Thr Leu Val Glu Val Ser Arg Asn Leu Gly Lys 1415 1420 1425 1415 1420 1425

Page 491 Page 491

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Val Gly Ser Lys Cys Cys Lys His Pro Glu Ala Lys Arg Met Pro Val Gly Ser Lys Cys Cys Lys His Pro Glu Ala Lys Arg Met Pro 1430 1435 1440 1430 1435 1440

Cys Ala Glu Asp Tyr Leu Ser Val Val Leu Asn Gln Leu Cys Val Cys Ala Glu Asp Tyr Leu Ser Val Val Leu Asn Gln Leu Cys Val 1445 1450 1455 1445 1450 1455

Leu His Glu Lys Thr Pro Val Ser Asp Arg Val Thr Lys Cys Cys Leu His Glu Lys Thr Pro Val Ser Asp Arg Val Thr Lys Cys Cys 1460 1465 1470 1460 1465 1470

Thr Glu Ser Leu Val Asn Arg Arg Pro Cys Phe Ser Ala Leu Glu Thr Glu Ser Leu Val Asn Arg Arg Pro Cys Phe Ser Ala Leu Glu 1475 1480 1485 1475 1480 1485

Val Asp Glu Thr Tyr Val Pro Lys Glu Phe Asn Ala Glu Thr Phe Val Asp Glu Thr Tyr Val Pro Lys Glu Phe Asn Ala Glu Thr Phe 1490 1495 1500 1490 1495 1500

Thr Phe His Ala Asp Ile Cys Thr Leu Ser Glu Lys Glu Arg Gln Thr Phe His Ala Asp Ile Cys Thr Leu Ser Glu Lys Glu Arg Gln 1505 1510 1515 1505 1510 1515

Ile Lys Lys Gln Thr Ala Leu Val Glu Leu Val Lys His Lys Pro Ile Lys Lys Gln Thr Ala Leu Val Glu Leu Val Lys His Lys Pro 1520 1525 1530 1520 1525 1530

Lys Ala Thr Lys Glu Gln Leu Lys Ala Val Met Asp Asp Phe Ala Lys Ala Thr Lys Glu Gln Leu Lys Ala Val Met Asp Asp Phe Ala 1535 1540 1545 1535 1540 1545

Ala Phe Val Glu Lys Cys Cys Lys Ala Asp Asp Lys Glu Thr Cys Ala Phe Val Glu Lys Cys Cys Lys Ala Asp Asp Lys Glu Thr Cys 1550 1555 1560 1550 1555 1560

Phe Ala Glu Glu Gly Lys Lys Leu Val Ala Ala Ser Gln Ala Ala Phe Ala Glu Glu Gly Lys Lys Leu Val Ala Ala Ser Gln Ala Ala 1565 1570 1575 1565 1570 1575

Leu Gly Leu Leu Gly Leu 1580 1580

<210> 129 <210> 129 <211> 15 <211> 15 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> GS_linker_3x <223> GS_linker_3x Page 492 Page 492

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. - TXT

<400> 129 <400> 129

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 1 5 10 15 1 5 10 15

<210> 130 <210> 130 <211> 24 <211> 24 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> HSA_Signal <223> HSA_Signal

<400> 130 <400> 130

Met Lys Trp Val Thr Phe Ile Ser Leu Leu Phe Leu Phe Ser Ser Ala Met Lys Trp Val Thr Phe Ile Ser Leu Leu Phe Leu Phe Ser Ser Ala 1 5 10 15 1 5 10 15

Tyr Ser Arg Gly Val Phe Arg Arg Tyr Ser Arg Gly Val Phe Arg Arg 20 20

<210> 131 <210> 131 <211> 585 <211> 585 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> HSA_Seq <223> HSA_Seq

<400> 131 <400> 131

Asp Ala His Lys Ser Glu Val Ala His Arg Phe Lys Asp Leu Gly Glu Asp Ala His Lys Ser Glu Val Ala His Arg Phe Lys Asp Leu Gly Glu 1 5 10 15 1 5 10 15

Glu Asn Phe Lys Ala Leu Val Leu Ile Ala Phe Ala Gln Tyr Leu Gln Glu Asn Phe Lys Ala Leu Val Leu Ile Ala Phe Ala Gln Tyr Leu Gln 20 25 30 20 25 30

Gln Cys Pro Phe Glu Asp His Val Lys Leu Val Asn Glu Val Thr Glu Gln Cys Pro Phe Glu Asp His Val Lys Leu Val Asn Glu Val Thr Glu 35 40 45 35 40 45

Phe Ala Lys Thr Cys Val Ala Asp Glu Ser Ala Glu Asn Cys Asp Lys Phe Ala Lys Thr Cys Val Ala Asp Glu Ser Ala Glu Asn Cys Asp Lys 50 55 60 50 55 60

Ser Leu His Thr Leu Phe Gly Asp Lys Leu Cys Thr Val Ala Thr Leu Ser Leu His Thr Leu Phe Gly Asp Lys Leu Cys Thr Val Ala Thr Leu Page 493 Page 493

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 65 70 75 80 70 75 80

Arg Glu Thr Tyr Gly Glu Met Ala Asp Cys Cys Ala Lys Gln Glu Pro Arg Glu Thr Tyr Gly Glu Met Ala Asp Cys Cys Ala Lys Gln Glu Pro 85 90 95 85 90 95

Glu Arg Asn Glu Cys Phe Leu Gln His Lys Asp Asp Asn Pro Asn Leu Glu Arg Asn Glu Cys Phe Leu Gln His Lys Asp Asp Asn Pro Asn Leu 100 105 110 100 105 110

Pro Arg Leu Val Arg Pro Glu Val Asp Val Met Cys Thr Ala Phe His Pro Arg Leu Val Arg Pro Glu Val Asp Val Met Cys Thr Ala Phe His 115 120 125 115 120 125

Asp Asn Glu Glu Thr Phe Leu Lys Lys Tyr Leu Tyr Glu Ile Ala Arg Asp Asn Glu Glu Thr Phe Leu Lys Lys Tyr Leu Tyr Glu Ile Ala Arg 130 135 140 130 135 140

Arg His Pro Tyr Phe Tyr Ala Pro Glu Leu Leu Phe Phe Ala Lys Arg Arg His Pro Tyr Phe Tyr Ala Pro Glu Leu Leu Phe Phe Ala Lys Arg 145 150 155 160 145 150 155 160

Tyr Lys Ala Ala Phe Thr Glu Cys Cys Gln Ala Ala Asp Lys Ala Ala Tyr Lys Ala Ala Phe Thr Glu Cys Cys Gln Ala Ala Asp Lys Ala Ala 165 170 175 165 170 175

Cys Leu Leu Pro Lys Leu Asp Glu Leu Arg Asp Glu Gly Lys Ala Ser Cys Leu Leu Pro Lys Leu Asp Glu Leu Arg Asp Glu Gly Lys Ala Ser 180 185 190 180 185 190

Ser Ala Lys Gln Arg Leu Lys Cys Ala Ser Leu Gln Lys Phe Gly Glu Ser Ala Lys Gln Arg Leu Lys Cys Ala Ser Leu Gln Lys Phe Gly Glu 195 200 205 195 200 205

Arg Ala Phe Lys Ala Trp Ala Val Ala Arg Leu Ser Gln Arg Phe Pro Arg Ala Phe Lys Ala Trp Ala Val Ala Arg Leu Ser Gln Arg Phe Pro 210 215 220 210 215 220

Lys Ala Glu Phe Ala Glu Val Ser Lys Leu Val Thr Asp Leu Thr Lys Lys Ala Glu Phe Ala Glu Val Ser Lys Leu Val Thr Asp Leu Thr Lys 225 230 235 240 225 230 235 240

Val His Thr Glu Cys Cys His Gly Asp Leu Leu Glu Cys Ala Asp Asp Val His Thr Glu Cys Cys His Gly Asp Leu Leu Glu Cys Ala Asp Asp 245 250 255 245 250 255

Arg Ala Asp Leu Ala Lys Tyr Ile Cys Glu Asn Gln Asp Ser Ile Ser Arg Ala Asp Leu Ala Lys Tyr Ile Cys Glu Asn Gln Asp Ser Ile Ser 260 265 270 260 265 270

Ser Lys Leu Lys Glu Cys Cys Glu Lys Pro Leu Leu Glu Lys Ser His Ser Lys Leu Lys Glu Cys Cys Glu Lys Pro Leu Leu Glu Lys Ser His Page 494 Page 494

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 275 280 285 275 280 285

Cys Ile Ala Glu Val Glu Asn Asp Glu Met Pro Ala Asp Leu Pro Ser Cys Ile Ala Glu Val Glu Asn Asp Glu Met Pro Ala Asp Leu Pro Ser 290 295 300 290 295 300

Leu Ala Ala Asp Phe Val Glu Ser Lys Asp Val Cys Lys Asn Tyr Ala Leu Ala Ala Asp Phe Val Glu Ser Lys Asp Val Cys Lys Asn Tyr Ala 305 310 315 320 305 310 315 320

Glu Ala Lys Asp Val Phe Leu Gly Met Phe Leu Tyr Glu Tyr Ala Arg Glu Ala Lys Asp Val Phe Leu Gly Met Phe Leu Tyr Glu Tyr Ala Arg 325 330 335 325 330 335

Arg His Pro Asp Tyr Ser Val Val Leu Leu Leu Arg Leu Ala Lys Thr Arg His Pro Asp Tyr Ser Val Val Leu Leu Leu Arg Leu Ala Lys Thr 340 345 350 340 345 350

Tyr Glu Thr Thr Leu Glu Lys Cys Cys Ala Ala Ala Asp Pro His Glu Tyr Glu Thr Thr Leu Glu Lys Cys Cys Ala Ala Ala Asp Pro His Glu 355 360 365 355 360 365

Cys Tyr Ala Lys Val Phe Asp Glu Phe Lys Pro Leu Val Glu Glu Pro Cys Tyr Ala Lys Val Phe Asp Glu Phe Lys Pro Leu Val Glu Glu Pro 370 375 380 370 375 380

Gln Asn Leu Ile Lys Gln Asn Cys Glu Leu Phe Glu Gln Leu Gly Glu Gln Asn Leu Ile Lys Gln Asn Cys Glu Leu Phe Glu Gln Leu Gly Glu 385 390 395 400 385 390 395 400

Tyr Lys Phe Gln Asn Ala Leu Leu Val Arg Tyr Thr Lys Lys Val Pro Tyr Lys Phe Gln Asn Ala Leu Leu Val Arg Tyr Thr Lys Lys Val Pro 405 410 415 405 410 415

Gln Val Ser Thr Pro Thr Leu Val Glu Val Ser Arg Asn Leu Gly Lys Gln Val Ser Thr Pro Thr Leu Val Glu Val Ser Arg Asn Leu Gly Lys 420 425 430 420 425 430

Val Gly Ser Lys Cys Cys Lys His Pro Glu Ala Lys Arg Met Pro Cys Val Gly Ser Lys Cys Cys Lys His Pro Glu Ala Lys Arg Met Pro Cys 435 440 445 435 440 445

Ala Glu Asp Tyr Leu Ser Val Val Leu Asn Gln Leu Cys Val Leu His Ala Glu Asp Tyr Leu Ser Val Val Leu Asn Gln Leu Cys Val Leu His 450 455 460 450 455 460

Glu Lys Thr Pro Val Ser Asp Arg Val Thr Lys Cys Cys Thr Glu Ser Glu Lys Thr Pro Val Ser Asp Arg Val Thr Lys Cys Cys Thr Glu Ser 465 470 475 480 465 470 475 480

Leu Val Asn Arg Arg Pro Cys Phe Ser Ala Leu Glu Val Asp Glu Thr Leu Val Asn Arg Arg Pro Cys Phe Ser Ala Leu Glu Val Asp Glu Thr Page 495 Page 495

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 485 490 495 485 490 495

Tyr Val Pro Lys Glu Phe Asn Ala Glu Thr Phe Thr Phe His Ala Asp Tyr Val Pro Lys Glu Phe Asn Ala Glu Thr Phe Thr Phe His Ala Asp 500 505 510 500 505 510

Ile Cys Thr Leu Ser Glu Lys Glu Arg Gln Ile Lys Lys Gln Thr Ala Ile Cys Thr Leu Ser Glu Lys Glu Arg Gln Ile Lys Lys Gln Thr Ala 515 520 525 515 520 525

Leu Val Glu Leu Val Lys His Lys Pro Lys Ala Thr Lys Glu Gln Leu Leu Val Glu Leu Val Lys His Lys Pro Lys Ala Thr Lys Glu Gln Leu 530 535 540 530 535 540

Lys Ala Val Met Asp Asp Phe Ala Ala Phe Val Glu Lys Cys Cys Lys Lys Ala Val Met Asp Asp Phe Ala Ala Phe Val Glu Lys Cys Cys Lys 545 550 555 560 545 550 555 560

Ala Asp Asp Lys Glu Thr Cys Phe Ala Glu Glu Gly Lys Lys Leu Val Ala Asp Asp Lys Glu Thr Cys Phe Ala Glu Glu Gly Lys Lys Leu Val 565 570 575 565 570 575

Ala Ala Ser Gln Ala Ala Leu Gly Leu Ala Ala Ser Gln Ala Ala Leu Gly Leu 580 585 580 585

<210> 132 <210> 132 <211> 609 <211> 609 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> HSA_Full_Signal_Seq <223> HSA_Full_Signal_Seq

<400> 132 <400> 132

Met Lys Trp Val Thr Phe Ile Ser Leu Leu Phe Leu Phe Ser Ser Ala Met Lys Trp Val Thr Phe Ile Ser Leu Leu Phe Leu Phe Ser Ser Ala 1 5 10 15 1 5 10 15

Tyr Ser Arg Gly Val Phe Arg Arg Asp Ala His Lys Ser Glu Val Ala Tyr Ser Arg Gly Val Phe Arg Arg Asp Ala His Lys Ser Glu Val Ala 20 25 30 20 25 30

His Arg Phe Lys Asp Leu Gly Glu Glu Asn Phe Lys Ala Leu Val Leu His Arg Phe Lys Asp Leu Gly Glu Glu Asn Phe Lys Ala Leu Val Leu 35 40 45 35 40 45

Ile Ala Phe Ala Gln Tyr Leu Gln Gln Cys Pro Phe Glu Asp His Val Ile Ala Phe Ala Gln Tyr Leu Gln Gln Cys Pro Phe Glu Asp His Val 50 55 60 50 55 60

Page 496 Page 496

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Lys Leu Val Asn Glu Val Thr Glu Phe Ala Lys Thr Cys Val Ala Asp Lys Leu Val Asn Glu Val Thr Glu Phe Ala Lys Thr Cys Val Ala Asp 65 70 75 80 70 75 80

Glu Ser Ala Glu Asn Cys Asp Lys Ser Leu His Thr Leu Phe Gly Asp Glu Ser Ala Glu Asn Cys Asp Lys Ser Leu His Thr Leu Phe Gly Asp 85 90 95 85 90 95

Lys Leu Cys Thr Val Ala Thr Leu Arg Glu Thr Tyr Gly Glu Met Ala Lys Leu Cys Thr Val Ala Thr Leu Arg Glu Thr Tyr Gly Glu Met Ala 100 105 110 100 105 110

Asp Cys Cys Ala Lys Gln Glu Pro Glu Arg Asn Glu Cys Phe Leu Gln Asp Cys Cys Ala Lys Gln Glu Pro Glu Arg Asn Glu Cys Phe Leu Gln 115 120 125 115 120 125

His Lys Asp Asp Asn Pro Asn Leu Pro Arg Leu Val Arg Pro Glu Val His Lys Asp Asp Asn Pro Asn Leu Pro Arg Leu Val Arg Pro Glu Val 130 135 140 130 135 140

Asp Val Met Cys Thr Ala Phe His Asp Asn Glu Glu Thr Phe Leu Lys Asp Val Met Cys Thr Ala Phe His Asp Asn Glu Glu Thr Phe Leu Lys 145 150 155 160 145 150 155 160

Lys Tyr Leu Tyr Glu Ile Ala Arg Arg His Pro Tyr Phe Tyr Ala Pro Lys Tyr Leu Tyr Glu Ile Ala Arg Arg His Pro Tyr Phe Tyr Ala Pro 165 170 175 165 170 175

Glu Leu Leu Phe Phe Ala Lys Arg Tyr Lys Ala Ala Phe Thr Glu Cys Glu Leu Leu Phe Phe Ala Lys Arg Tyr Lys Ala Ala Phe Thr Glu Cys 180 185 190 180 185 190

Cys Gln Ala Ala Asp Lys Ala Ala Cys Leu Leu Pro Lys Leu Asp Glu Cys Gln Ala Ala Asp Lys Ala Ala Cys Leu Leu Pro Lys Leu Asp Glu 195 200 205 195 200 205

Leu Arg Asp Glu Gly Lys Ala Ser Ser Ala Lys Gln Arg Leu Lys Cys Leu Arg Asp Glu Gly Lys Ala Ser Ser Ala Lys Gln Arg Leu Lys Cys 210 215 220 210 215 220

Ala Ser Leu Gln Lys Phe Gly Glu Arg Ala Phe Lys Ala Trp Ala Val Ala Ser Leu Gln Lys Phe Gly Glu Arg Ala Phe Lys Ala Trp Ala Val 225 230 235 240 225 230 235 240

Ala Arg Leu Ser Gln Arg Phe Pro Lys Ala Glu Phe Ala Glu Val Ser Ala Arg Leu Ser Gln Arg Phe Pro Lys Ala Glu Phe Ala Glu Val Ser 245 250 255 245 250 255

Lys Leu Val Thr Asp Leu Thr Lys Val His Thr Glu Cys Cys His Gly Lys Leu Val Thr Asp Leu Thr Lys Val His Thr Glu Cys Cys His Gly 260 265 270 260 265 270

Page 497 Page 497

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Asp Leu Leu Glu Cys Ala Asp Asp Arg Ala Asp Leu Ala Lys Tyr Ile Asp Leu Leu Glu Cys Ala Asp Asp Arg Ala Asp Leu Ala Lys Tyr Ile 275 280 285 275 280 285

Cys Glu Asn Gln Asp Ser Ile Ser Ser Lys Leu Lys Glu Cys Cys Glu Cys Glu Asn Gln Asp Ser Ile Ser Ser Lys Leu Lys Glu Cys Cys Glu 290 295 300 290 295 300

Lys Pro Leu Leu Glu Lys Ser His Cys Ile Ala Glu Val Glu Asn Asp Lys Pro Leu Leu Glu Lys Ser His Cys Ile Ala Glu Val Glu Asn Asp 305 310 315 320 305 310 315 320

Glu Met Pro Ala Asp Leu Pro Ser Leu Ala Ala Asp Phe Val Glu Ser Glu Met Pro Ala Asp Leu Pro Ser Leu Ala Ala Asp Phe Val Glu Ser 325 330 335 325 330 335

Lys Asp Val Cys Lys Asn Tyr Ala Glu Ala Lys Asp Val Phe Leu Gly Lys Asp Val Cys Lys Asn Tyr Ala Glu Ala Lys Asp Val Phe Leu Gly 340 345 350 340 345 350

Met Phe Leu Tyr Glu Tyr Ala Arg Arg His Pro Asp Tyr Ser Val Val Met Phe Leu Tyr Glu Tyr Ala Arg Arg His Pro Asp Tyr Ser Val Val 355 360 365 355 360 365

Leu Leu Leu Arg Leu Ala Lys Thr Tyr Glu Thr Thr Leu Glu Lys Cys Leu Leu Leu Arg Leu Ala Lys Thr Tyr Glu Thr Thr Leu Glu Lys Cys 370 375 380 370 375 380

Cys Ala Ala Ala Asp Pro His Glu Cys Tyr Ala Lys Val Phe Asp Glu Cys Ala Ala Ala Asp Pro His Glu Cys Tyr Ala Lys Val Phe Asp Glu 385 390 395 400 385 390 395 400

Phe Lys Pro Leu Val Glu Glu Pro Gln Asn Leu Ile Lys Gln Asn Cys Phe Lys Pro Leu Val Glu Glu Pro Gln Asn Leu Ile Lys Gln Asn Cys 405 410 415 405 410 415

Glu Leu Phe Glu Gln Leu Gly Glu Tyr Lys Phe Gln Asn Ala Leu Leu Glu Leu Phe Glu Gln Leu Gly Glu Tyr Lys Phe Gln Asn Ala Leu Leu 420 425 430 420 425 430

Val Arg Tyr Thr Lys Lys Val Pro Gln Val Ser Thr Pro Thr Leu Val Val Arg Tyr Thr Lys Lys Val Pro Gln Val Ser Thr Pro Thr Leu Val 435 440 445 435 440 445

Glu Val Ser Arg Asn Leu Gly Lys Val Gly Ser Lys Cys Cys Lys His Glu Val Ser Arg Asn Leu Gly Lys Val Gly Ser Lys Cys Cys Lys His 450 455 460 450 455 460

Pro Glu Ala Lys Arg Met Pro Cys Ala Glu Asp Tyr Leu Ser Val Val Pro Glu Ala Lys Arg Met Pro Cys Ala Glu Asp Tyr Leu Ser Val Val 465 470 475 480 465 470 475 480

Page 498 Page 498

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Leu Asn Gln Leu Cys Val Leu His Glu Lys Thr Pro Val Ser Asp Arg Leu Asn Gln Leu Cys Val Leu His Glu Lys Thr Pro Val Ser Asp Arg 485 490 495 485 490 495

Val Thr Lys Cys Cys Thr Glu Ser Leu Val Asn Arg Arg Pro Cys Phe Val Thr Lys Cys Cys Thr Glu Ser Leu Val Asn Arg Arg Pro Cys Phe 500 505 510 500 505 510

Ser Ala Leu Glu Val Asp Glu Thr Tyr Val Pro Lys Glu Phe Asn Ala Ser Ala Leu Glu Val Asp Glu Thr Tyr Val Pro Lys Glu Phe Asn Ala 515 520 525 515 520 525

Glu Thr Phe Thr Phe His Ala Asp Ile Cys Thr Leu Ser Glu Lys Glu Glu Thr Phe Thr Phe His Ala Asp Ile Cys Thr Leu Ser Glu Lys Glu 530 535 540 530 535 540

Arg Gln Ile Lys Lys Gln Thr Ala Leu Val Glu Leu Val Lys His Lys Arg Gln Ile Lys Lys Gln Thr Ala Leu Val Glu Leu Val Lys His Lys 545 550 555 560 545 550 555 560

Pro Lys Ala Thr Lys Glu Gln Leu Lys Ala Val Met Asp Asp Phe Ala Pro Lys Ala Thr Lys Glu Gln Leu Lys Ala Val Met Asp Asp Phe Ala 565 570 575 565 570 575

Ala Phe Val Glu Lys Cys Cys Lys Ala Asp Asp Lys Glu Thr Cys Phe Ala Phe Val Glu Lys Cys Cys Lys Ala Asp Asp Lys Glu Thr Cys Phe 580 585 590 580 585 590

Ala Glu Glu Gly Lys Lys Leu Val Ala Ala Ser Gln Ala Ala Leu Gly Ala Glu Glu Gly Lys Lys Leu Val Ala Ala Ser Gln Ala Ala Leu Gly 595 600 605 595 600 605

Leu Leu

<210> 133 <210> 133 <211> 989 <211> 989 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> Native_1_981_GG_6xHis <223> Native_1_981_GG_6xHis

<400> 133 <400> 133

Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser 1 5 10 15 1 5 10 15

Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg Page 499 Page 499

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing TXT 20 25 30 20 25 30

Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro 35 40 45 35 40 45

Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly 50 55 60 50 55 60

Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp 65 70 75 80 70 75 80

Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His 85 90 95 85 90 95

Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly 100 105 110 100 105 110

Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser 115 120 125 115 120 125

Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val 130 135 140 130 135 140

Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly 145 150 155 160 145 150 155 160

Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu 165 170 175 165 170 175

Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr 180 185 190 180 185 190

His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala 195 200 205 195 200 205

Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe 210 215 220 210 215 220

Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Page 500 Page 500

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 225 230 235 240 225 230 235 240

Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly 245 250 255 245 250 255

Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu 260 265 270 260 265 270

Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro 275 280 285 275 280 285

Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn 290 295 300 290 295 300

Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu 305 310 315 320 305 310 315 320

Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp 325 330 335 325 330 335

Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe 340 345 350 340 345 350

Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala 355 360 365 355 360 365

Leu Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Leu Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met 370 375 380 370 375 380

Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp 385 390 395 400 385 390 395 400

Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly 405 410 415 405 410 415

Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr 420 425 430 420 425 430

Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Page 501 Page 501

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 435 440 445 435 440 445

Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe 450 455 460 450 455 460

Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp 465 470 475 480 465 470 475 480

Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Phe Leu Ser Gln Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe 485 490 495 485 490 495

Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Tyr Gln Lys Leu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn 500 505 510 500 505 510

Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Gln Pro Leu Glu Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val 515 520 525 515 520 525

Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu Asp Asn Tyr Ile Gln Val Asp Thr Thr Leu Ser Gln Phe Thr Asp Leu 530 535 540 530 535 540

Asn Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val Asn Val Tyr Leu Trp Asp Val His His Ser Lys Arg Leu Ile Lys Val 545 550 555 560 545 550 555 560

Asp Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala Asp Gly Val Val Thr Lys Lys Arg Lys Ser Tyr Cys Val Asp Phe Ala 565 570 575 565 570 575

Ala Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His Ala Ile Gln Pro Gln Ile Ala Leu Leu Gln Glu Met His Val Thr His 580 585 590 580 585 590

Phe Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln Phe Arg Phe Ser Leu Asp Trp Ala Leu Ile Leu Pro Leu Gly Asn Gln 595 600 605 595 600 605

Ser Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser Ser Gln Val Asn His Thr Ile Leu Gln Tyr Tyr Arg Cys Met Ala Ser 610 615 620 610 615 620

Glu Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro Glu Leu Val Arg Val Asn Ile Thr Pro Val Val Ala Leu Trp Gln Pro 625 630 635 640 625 630 635 640

Met Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Met Ala Pro Asn Gln Gly Leu Pro Arg Leu Leu Ala Arg Gln Gly Ala Page 502 Page 502

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 645 650 655 645 650 655

Trp Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu Trp Glu Asn Pro Tyr Thr Ala Leu Ala Phe Ala Glu Tyr Ala Arg Leu 660 665 670 660 665 670

Cys Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn Cys Phe Gln Glu Leu Gly His His Val Lys Leu Trp Ile Thr Met Asn 675 680 685 675 680 685

Glu Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu Glu Pro Tyr Thr Arg Asn Met Thr Tyr Ser Ala Gly His Asn Leu Leu 690 695 700 690 695 700

Lys Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His Lys Ala His Ala Leu Ala Trp His Val Tyr Asn Glu Lys Phe Arg His 705 710 715 720 705 710 715 720

Ala Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu Ala Gln Asn Gly Lys Ile Ser Ile Ala Leu Gln Ala Asp Trp Ile Glu 725 730 735 725 730 735

Pro Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val Pro Ala Cys Pro Phe Ser Gln Lys Asp Lys Glu Val Ala Glu Arg Val 740 745 750 740 745 750

Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly Leu Glu Phe Asp Ile Gly Trp Leu Ala Glu Pro Ile Phe Gly Ser Gly 755 760 765 755 760 765

Asp Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe Asp Tyr Pro Trp Val Met Arg Asp Trp Leu Asn Gln Arg Asn Asn Phe 770 775 780 770 775 780

Leu Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr Leu Leu Pro Tyr Phe Thr Glu Asp Glu Lys Lys Leu Ile Gln Gly Thr 785 790 795 800 785 790 795 800

Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser Phe Asp Phe Leu Ala Leu Ser His Tyr Thr Thr Ile Leu Val Asp Ser 805 810 815 805 810 815

Glu Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu Glu Lys Glu Asp Pro Ile Lys Tyr Asn Asp Tyr Leu Glu Val Gln Glu 820 825 830 820 825 830

Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val Met Thr Asp Ile Thr Trp Leu Asn Ser Pro Ser Gln Val Ala Val Val 835 840 845 835 840 845

Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Pro Trp Gly Leu Arg Lys Val Leu Asn Trp Leu Lys Phe Lys Tyr Gly Page 503 Page 503

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT 850 855 860 850 855 860

Asp Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His Asp Leu Pro Met Tyr Ile Ile Ser Asn Gly Ile Asp Asp Gly Leu His 865 870 875 880 865 870 875 880

Ala Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn Ala Glu Asp Asp Gln Leu Arg Val Tyr Tyr Met Gln Asn Tyr Ile Asn 885 890 895 885 890 895

Glu Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr Glu Ala Leu Lys Ala His Ile Leu Asp Gly Ile Asn Leu Cys Gly Tyr 900 905 910 900 905 910

Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr Phe Ala Tyr Ser Phe Asn Asp Arg Thr Ala Pro Arg Phe Gly Leu Tyr 915 920 925 915 920 925

Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr Arg Tyr Ala Ala Asp Gln Phe Glu Pro Lys Ala Ser Met Lys His Tyr 930 935 940 930 935 940

Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu Arg Lys Ile Ile Asp Ser Asn Gly Phe Pro Gly Pro Glu Thr Leu Glu 945 950 955 960 945 950 955 960

Arg Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe Arg Phe Cys Pro Glu Glu Phe Thr Val Cys Thr Glu Cys Ser Phe Phe 965 970 975 965 970 975

His Thr Arg Lys Ser Gly Gly His His His His His His His Thr Arg Lys Ser Gly Gly His His His His His His 980 985 980 985

<210> 134 < :210> 134 <211> 8 <211> 8 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> GG_6xHis <223> GG_6xHis

<400> 134 <400> 134

Gly Gly His His His His His His Gly Gly His His His His His His 1 5 1 5

<210> 135 < 210> 135 <211> 6 <211> 6 <212> PRT <212> PRT Page 504 Page 504

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> 6xHis <223> 6xHis

<400> 135 <400> 135

His His His His His His His His His His His His 1 5 1 5

<210> 136 <210> 136 <211> 2 <211> 2 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> GG_linker <223> GG_linker

<400> 136 <400> 136

Gly Gly Gly Gly 1 1

<210> 137 <210> 137 <211> 3654 <211> 3654 <212> DNA <212> DNA <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> 1_981_2xGS_linker_ IgG1‐noCH1‐Fc <223> 1_981_2xGS_linker_ IgG1-noCH1-Fc -

<400> 137 <400> 137 atgcccgcca gcgccccgcc gcgccgcccg cggccgccgc cgccgtcgct gtcgctgctg 60 atgcccgcca gcgccccgcc gcgccgcccg cggccgccgc cgccgtcgct gtcgctgctg 60

ctggtgctgc tgggcctggg cggccgccgc ctgcgtgcgg agccgggcga cggcgcgcag 120 ctggtgctgc tgggcctggg cggccgccgc ctgcgtgcgg agccgggcga cggcgcgcag 120

acctgggccc gtttctcgcg gcctcctgcc cccgaggccg cgggcctctt ccagggcacc 180 acctgggccc gtttctcgcg gcctcctgcc cccgaggccg cgggcctctt ccagggcaco 180

ttccccgacg gcttcctctg ggccgtgggc agcgccgcct accagaccga gggcggctgg 240 ttccccgacg gcttcctctg ggccgtgggc agcgccgcct accagaccga gggcggctgg 240

cagcagcacg gcaagggtgc gtccatctgg gatacgttca cccaccaccc cctggcaccc 300 cagcagcacg gcaagggtgc gtccatctgg gatacgttca cccaccaccc cctggcaccc 300

ccgggagact cccggaacgc cagtctgccg ttgggcgccc cgtcgccgct gcagcccgcc 360 ccgggagact cccggaacgc cagtctgccg ttgggcgccc cgtcgccgct gcagcccgcc 360

accggggacg tagccagcga cagctacaac aacgtcttcc gcgacacgga ggcgctgcgc 420 accggggacg tagccagcga cagctacaac aacgtcttcc gcgacacgga ggcgctgcgc 420

gagctcgggg tcactcacta ccgcttctcc atctcgtggg cgcgagtgct ccccaatggc 480 gagctcgggg tcactcacta ccgcttctcc atctcgtggg cgcgagtgct ccccaatggc 480

agcgcgggcg tccccaaccg cgaggggctg cgctactacc ggcgcctgct ggagcggctg 540 agcgcgggcg tccccaaccg cgaggggctg cgctactacc ggcgcctgct ggagcggctg 540

Page 505 Page 505

20780‐15A_SequenceListing.TXT cgggagctgg gcgtgcagcc cgtggtcacc ctgtaccact gggacctgcc ccagcgcctg 600 009

caggacgcct acggcggctg ggccaaccgc gccctggccg accacttcag ggattacgcg 660 099

gagctctgct tccgccactt cggcggtcag gtcaagtact ggatcaccat cgacaacccc 720 OZL

tacgtggtgg cctggcacgg ctacgccacc gggcgcctgg cccccggcat ccggggcagc 780 08L

ccgcggctcg ggtacctggt ggcgcacaac ctcctcctgg ctcatgccaa agtctggcat 840

ctctacaata cttctttccg tcccactcag ggaggtcagg tgtccattgc cctaagctct 900 006

cactggatca atcctcgaag aatgaccgac cacagcatca aagaatgtca aaaatctctg 960 096

the gactttgtac taggttggtt tgccaaaccc gtatttattg atggtgacta tcccgagagc 1020 0201

atgaagaata acctttcatc tattctgcct gattttactg aatctgagaa aaagttcatc 1080 080I

the aaaggaactg ctgacttttt tgctctttgc tttggaccca ccttgagttt tcaacttttg 1140

gaccctcaca tgaagttccg ccaattggaa tctcccaacc tgaggcaact gctttcctgg 1200

attgaccttg aatttaacca tcctcaaata tttattgtgg aaaatggctg gtttgtctca 1260 092T

gggaccacca agagagatga tgccaaatat atgtattacc tcaaaaagtt catcatggaa 1320 OZET

e accttaaaag ccatcaagct ggatggggtg gatgtcatcg ggtataccgc atggtccctc 1380 08ET

atggatggtt tcgagtggca cagaggttac agcatcaggc gtggactctt ctatgttgac 1440

tttctaagcc aggacaagat gttgttgcca aagtcttcag ccttgttcta ccaaaagctg 1500 00ST

atagagaaaa atggcttccc tcctttacct gaaaatcagc ccctagaagg gacatttccc 1560 09ST

tgtgactttg cttggggagt tgttgacaac tacattcaag tagataccac tctgtctcag 1620 029T

tttaccgacc tgaatgttta cctgtgggat gtccaccaca gtaaaaggct tattaaagtg 1680 089T

gatggggttg tgaccaagaa gaggaaatcc tactgtgttg actttgctgc catccagccc 1740 DATE

cagatcgctt tactccagga aatgcacgtt acacattttc gcttctccct ggactgggcc 1800 008T

ctgattctcc ctctgggtaa ccagtcccag gtgaaccaca ccatcctgca gtactatcgc 1860 098T

tgcatggcca gcgagcttgt ccgtgtcaac atcaccccag tggtggccct gtggcagcct 1920 026T

atggccccga accaaggact gccgcgcctc ctggccaggc agggcgcctg ggagaacccc 1980 086T

tacactgccc tggcctttgc agagtatgcc cgactgtgct ttcaagagct cggccatcac 2040

gtcaagcttt ggataacgat gaatgagccg tatacaagga atatgacata cagtgctggc 2100 0012

Page 506 90S

e

20780‐15A_SequenceListing.TXT

11848/97 cacaaccttc tgaaggccca tgccctggct tggcatgtgt acaatgaaaa gtttaggcat 2160 0912

gctcagaatg ggaaaatatc catagccttg caggctgatt ggatagaacc tgcctgccct 2220 0222

ttctcccaaa aggacaaaga ggtggccgag agagttttgg aatttgacat tggctggctg 2280 0822

gctgagccca ttttcggctc tggagattat ccatgggtga tgagggactg gctgaaccaa 2340 OTEC

e agaaacaatt ttcttcttcc ttatttcact gaagatgaaa aaaagctaat ccagggtacc 2400

tttgactttt tggctttaag ccattatacc accatccttg tagactcaga aaaagaagat 2460

ccaataaaat acaatgatta cctagaagtg caagaaatga ccgacatcac gtggctcaac 2520 0252

tcccccagtc aggtggcggt agtgccctgg gggttgcgca aagtgctgaa ctggctgaag 2580 0852

ttcaagtacg gagacctccc catgtacata atatccaacg gaatcgatga cgggctgcat 2640 797 gctgaggacg accagctgag ggtgtattat atgcagaatt acataaacga agctctcaaa 2700 00LZ

gcccacatac tggatggtat caatctttgc ggatactttg cttattcgtt taacgaccgc 2760 09/2

acagctccga ggtttggcct ctatcgttat gctgcagatc agtttgagcc caaggcatcc 2820 0782

atgaaacatt acaggaaaat tattgacagc aatggtttcc cgggcccaga aactctggaa 2880 0887

agattttgtc cagaagaatt cacagtatgt accgaatgct cattcttcca cactcgcaaa 2940

e tctggcggcg gcgggtctgg tggggggggc agtgataaga cccatacgtg tccaccatgt 3000

e the 9999999997 9970788858 0008

ccagcgccag aactgttggg aggcccaagt gtcttccttt tcccacctaa gcctaaggac 3060 090E

accttgatga tttcacggac acccgaggtc acgtgtgtgg tggtcgatgt ttcccatgag 3120 OZIE

gacccagaag ttaaatttaa ttggtatgtg gatggagtcg aggtccacaa cgcgaagact 3180 Seeded 08IE

aagcccagag aggagcagta caatagcacg tatagagtcg tctccgtctt gacggtactt 3240

catcaggatt ggttgaatgg aaaagaatac aaatgtaagg tctcaaataa agcattgcct 3300 00EE

gcaccgatcg aaaagacaat cagcaaagcg aagggacagc cccgagaacc acaggtttat 3360 09EE

accctgcccc cgtccagaga tgaattgaca aaaaatcagg tctccttgac ctgtctcgtg 3420

aaaggattct atccgagcga tatcgctgta gagtgggaga gcaacggaca acctgaaaac 3480

aattacaaaa caaccccacc cgttcttgac tcagatggtt ccttctttct gtatagcaag 3540

eee ctcactgttg ataagtcacg atggcagcaa ggtaatgtgt tctcttgctc agttatgcac 3600 009E

the gaagcgctgc acaaccacta cactcagaag tccctctccc tcagtcccgg aaaa 3654 eeee 954

Page 507 LOS aged

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

<210> 138 <210> 138 <211> 30 <211> 30 <212> DNA <212> DNA <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> 2xGS_linker <223> 2xGS_linker

<400> 138 <400> 138 ggcggcggcg ggtctggtgg ggggggcagt 30 ggcggcggcg ggtctggtgg ggggggcagt 30

<210> 139 <210> 139 <211> 681 <211> 681 <212> DNA <212> DNA <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> IgG1‐noCH1‐Fc <223> IgG1-noCH1-Fo

<400> 139 <400> 139 gataagaccc atacgtgtcc accatgtcca gcgccagaac tgttgggagg cccaagtgtc 60 gataagaccc atacgtgtcc accatgtcca gcgccagaac tgttgggagg cccaagtgtc 60

ttccttttcc cacctaagcc taaggacacc ttgatgattt cacggacacc cgaggtcacg 120 ttccttttcc cacctaagcc taaggacacc ttgatgattt cacggacacc cgaggtcacg 120

tgtgtggtgg tcgatgtttc ccatgaggac ccagaagtta aatttaattg gtatgtggat 180 tgtgtggtgg tcgatgtttc ccatgaggad ccagaagtta aatttaattg gtatgtggat 180

ggagtcgagg tccacaacgc gaagactaag cccagagagg agcagtacaa tagcacgtat 240 ggagtcgagg tccacaacgc gaagactaag cccagagagg agcagtacaa tagcacgtat 240

agagtcgtct ccgtcttgac ggtacttcat caggattggt tgaatggaaa agaatacaaa 300 agagtcgtct ccgtcttgac ggtacttcat caggattggt tgaatggaaa agaatacaaa 300

tgtaaggtct caaataaagc attgcctgca ccgatcgaaa agacaatcag caaagcgaag 360 tgtaaggtct caaataaagc attgcctgca ccgatcgaaa agacaatcag caaagcgaag 360

ggacagcccc gagaaccaca ggtttatacc ctgcccccgt ccagagatga attgacaaaa 420 ggacagcccc gagaaccaca ggtttatacc ctgcccccgt ccagagatga attgacaaaa 420

aatcaggtct ccttgacctg tctcgtgaaa ggattctatc cgagcgatat cgctgtagag 480 aatcaggtct ccttgacctg tctcgtgaaa ggattctatc cgagcgatat cgctgtagag 480

tgggagagca acggacaacc tgaaaacaat tacaaaacaa ccccacccgt tcttgactca 540 tgggagagca acggacaacc tgaaaacaat tacaaaacaa ccccacccgt tcttgactca 540

gatggttcct tctttctgta tagcaagctc actgttgata agtcacgatg gcagcaaggt 600 gatggttcct tctttctgta tagcaagctc actgttgata agtcacgatg gcagcaaggt 600

aatgtgttct cttgctcagt tatgcacgaa gcgctgcaca accactacac tcagaagtcc 660 aatgtgttct cttgctcagt tatgcacgaa gcgctgcaca accactacao tcagaagtcc 660

ctctccctca gtcccggaaa a 681 ctctccctca gtcccggaaa a 681

<210> 140 <210> 140 <211> 1676 <211> 1676 <212> DNA <212> DNA <213> Artificial Sequence <213> Artificial Sequence

Page 508 Page 508

20780‐15A_SequenceListing.TXT <220> <022> <223> wtSP_Seq6_Sc <EZZ> X1bes80 <00 DST <400> 140 aagcttaccg ccaccatgcc ggcgtccgcc cccccccgcc gcccgaggcc ccccccgccc 60 09

tccctgtccc tgctcctcgt cctgctcggc ctggggggcc gccggctgcg cgccgagccg 120

ggcgacgggg cccagacctg ggcccgcttc agcaggcccc cggcccccga ggcggcgggt 180 08T

ctgttccagg ggaccttccc ggacggtttc ctgtgggccg tcggctccgc cgcgtaccag 240

acggagggcg ggtggcaaca acacgggaag ggcgcgtcga tctgggacac tttcacccac 300 00E

Seed caccccctgg cccccccggg ggactcgcgg aacgcgagcc tcccgctggg cgcccccagc 360 09E 8881080007 9990000000 cccctccagc cggccaccgg cgacgtggcg agcgacagct acaacaatgt cttcagggac 420

accgaggccc tccgggaact cggcgtcacg cactaccgct tcagcatcag ctgggcgcgg 480 08/

gtcctgccga acggctccgc cggcgtgccg aaccgagagg gcctgaggta ctacaggcgc 540

ctcctggaga ggctccggga gctgggcgta cagcccgtcg tcaccctcta ccactgggac 600 009

ctcccgcagc gcctgcagga cgcgtacggg gggtgggcca accgcgccct ggccgaccac 660 099

e ttccgggact acgccgagct ctgcttccgc cacttcgggg gccaggtcaa gtactggatc 720

8870088780 02L

accatcgaca acccctacgt cgtggcctgg cacggctacg ccaccggtcg cctggccccg 780 08L

ggcatccggg gctccccgcg gctgggctac ctcgtcgcgc ataacctgct gctcgcgcac 840

gcgaaggtct ggcacctcta caacaccagc ttccggccga cccagggcgg ccaggtgagc 900 006

atcgcgctgt cgagccactg gatcaacccc cgccgtatga ctgaccactc gatcaaggaa 960 096

tgccagaaga gcctggactt cgtcctgggg tggttcgcca agccggtgtt catcgacggt 1020 020T

the e gactacccgg aatcgatgaa gaacaacctg tcctcgatcc tgcccgactt caccgagtcc 1080 080T

gagaagaagt tcattaaggg caccgccgac ttcttcgcgc tgtgcttcgg gcccaccctg 1140

tccttccagc tgctggaccc ccacatgaag ttccgccagc tagagtctcc gaacctgcgc 1200 0020

cagctcctgt cgtggatcga cctggagttc aaccacccgc agatcttcat cgtcgagaac 1260 092T

ggctggttcg tctcggggac caccaaacgg gacgacgcca agtatatgta ctacctcaag 1320 OZET

aagttcatca tggagaccct gaaggcgatc aagctggacg gggtcgacgt catcgggtac 1380 08ET

accgcctggt ccctgatgga cggcttcgag tggcaccgcg gctactcgat cagacgcggc 1440 7887008000

Page 509 60S aged

20780‐15A_SequenceListing.TXT ctgttctacg tcgacttcct gtcgcaggac aagatgctcc tgccgaagtc cagcgcgctc 1500 00ST

ttctaccaga agctgatcga gaagaacggc ttcccaccgc tgcccgagaa ccagccactc 1560 09ST been gaaggcacct tcccgtgcga cttcgcctgg ggcgtcgtgg acaactacat ccaggtgtcg 1620 The cagctcacga agccgatctc ctcgctcacc aagccgtacc actgataatc tagagt 1676

<210> 141 <0IZ> <211> 3641 <IIZ> <212> DNA <ZIZ> ANC <213> Artificial Sequence <ETZ>

<220> <022> and 25-Ebas-dsant <223> LubSP_Seq3_Sc <EZZ>

<400> 141 <00 aagcttaccg ccaccatggc ctggaagact ctccccatct acctcctgct gctcctgtcg 60 09

gtcttcgtca tccagcaggt gtcctccgag ccgggcgacg gcgcgcagac ctgggcgcgc 120 OZI

ttcagccggc cgccggcccc ggaggcagcc ggcctgttcc aggggacctt cccggacggc 180 08I

ttcctctggg ccgtcggctc ggccgcctac cagaccgagg gtggctggca gcagcacggc 240

aagggcgcct ccatctggga caccttcacc caccacccgc tggccccgcc gggcgactcc 300 00E

cgcaacgcct ccctgccgct gggcgccccc tcgcccctgc agccggccac cggcgacgtg 360 09E

gcgtcggaca gctacaacaa cgtgttccgc gacaccgaag ccctgcggga gctgggcgtc 420

acccactacc gcttctccat cagctgggct agggtcctgc ccaacggcag cgcgggcgtg 480 08/7

cccaaccgcg agggcctgcg ttactaccgg cgcctgctgg agcgcctgcg cgaactcggg 540

gtccagccgg tcgtcaccct ctaccactgg gatctgcccc agcgccttca ggacgcctac 600 009

ggcggctggg ccaaccgggc cctggccgac cacttccgcg actacgccga gctctgcttc 660 099

cgccactttg gcggccaggt caagtactgg atcaccatcg acaacccgta cgtcgtcgcc 720 OZL

tggcacggct acgcaaccgg ccggctggcc ccgggcatcc gcggctcccc ccgcctgggc 780 08/

tacctcgtgg cgcacaacct cctgctggcc cacgccaagg tgtggcacct gtacaacacc 840

tccttccgcc cgacccaagg cggccaggtg tccatcgccc tgtccagcca ctggatcaac 900 006

ccccggcgca tgacggacca ctcgatcaag gagtgccaga agagcctcga cttcgtgctg 960 096

ggctggttcg cgaagccggt gttcatcgac ggtgactacc cggagtccat gaagaacaac 1020

Page 510 0TS aged

20780‐15A_SequenceListing.TXT ctgtcctcga tcctgcccga cttcaccgag agtgagaaga agttcatcaa gggcaccgcc 1080 080T

gacttcttcg cgctctgctt cggccccacc ctctcgttcc agctgctgga cccccacatg 1140

e aagttccggc agctggagag cccgaacctg cgccagctcc tgagctggat cgacctcgag 1200

7887788500 002T

ttcaatcacc cccagatctt catcgtggag aacggttggt tcgtgagcgg caccaccaag 1260 092T

cgcgacgacg ccaaatacat gtactacctg aagaagttta tcatggagac cctgaaggcg 1320 OZET

atcaagctgg acggcgtcga cgtgatcggc tacaccgcct ggtccctgat ggacggcttc 1380 08ET

gagtggcacc gggggtacag catccggcgg ggcctgttct acgtggactt cctgtcgcag 1440

gacaagatgt tgctgcccaa gtcgtcggcc ctcttctacc agaagctgat cgagaagaac 1500 00ST

the ggcttcccgc cgctgcccga gaaccagccc ctggagggca ccttcccgtg cgacttcgcc 1560 09ST

tggggcgtcg tggacaacta catccaggtc gacaccaccc tgagccagtt cacagacctc 1620 029T

aacgtgtacc tctgggacgt gcaccacagc aaacgcctca tcaaggtcga cggcgtagtc 1680 089T

accaagaagc ggaagagcta ttgcgtggac ttcgccgcga ttcaacccca aatcgcgctc 1740

ctccaggaga tgcacgtcac ccacttcagg ttcagcctcg actgggcgct gatcctgccg 1800 008T

ctcgggaacc agtcgcaggt gaaccacacg atcctgcaat actacaggtg catggcgtcg 1860 098T

gagctcgtcc gggtcaacat cacccccgtg gtcgccctct ggcagcccat ggcgcccaac 1920 026T

cagggcctgc cccgcctcct ggcccgccag ggcgcctggg agaacccgta caccgcgctg 1980 9897008588 086T

gccttcgcgg agtacgcgcg cctctgcttc caggagctgg ggcaccacgt gaagctgtgg 2040

atcaccatga acgaacccta cacgcgcaac atgacataca gcgcggggca caacctgctg 2100 00TZ

aaggcacacg ccctcgcgtg gcacgtctac aacgaaaagt tccggcacgc ccagaacggc 2160 0912

The aagatctcca tcgccctcca ggccgactgg atcgagcctg cctgcccgtt ctcgcagaag 2220 7780008700 0222

gacaaagagg tggccgagcg ggtgctggag ttcgacatcg gttggctggc ggagccgatc 2280 0877

ttcggctccg gcgactaccc ctgggtcatg cgggactggc tgaaccagcg caacaacttc 2340

ttgcttccct acttcaccga agacgaaaag aagctgatcc agggaacctt cgacttcctc 2400 SeeeeGoege

gccctcagcc actacaccac catcttggtc gactcggaga aggaggaccc catcaagtac 2460

aacgattacc tcgaggtcca ggagatgacg gacatcacgt ggctcaactc gccgtcccag 2520 0252

gtcgcggtgg tcccctgggg cctgcggaag gtgctcaact ggctgaagtt caagtacggc 2580 0852

Page 511 ITS and

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT gacctcccca tgtacatcat cagcaacgga atcgacgacg gcctgcacgc cgaggacgac 2640 gacctcccca tgtacatcat cagcaacgga atcgacgacg gcctgcacgc cgaggacgac 2640

cagctccgtg tctactacat gcagaactac atcaacgagg ccctgaaggc ccacatcctg 2700 cagctccgtg tctactacat gcagaactac atcaacgagg ccctgaaggc ccacatcctg 2700

gacggcatca acctgtgtgg ttacttcgcc tactcattca acgaccgcac cgccccccgg 2760 gacggcatca acctgtgtgg ttacttcgcc tactcattca acgaccgcac cgccccccgg 2760

ttcggcctct acaggtacgc ggcggaccag ttcgagccca aggcgtcgat gaagcactac 2820 ttcggcctct acaggtacgc ggcggaccag ttcgagccca aggcgtcgat gaagcactac 2820

cgcaagatca tcgacagcaa cggcttcccc ggcccggaga ccctcgaacg cttctgcccc 2880 cgcaagatca tcgacagcaa cggcttcccc ggcccggaga ccctcgaacg cttctgcccc 2880

gaggagttca cggtgtgcac cgagtgcagc ttcttccaca cccgcaagtc gggcgggggc 2940 gaggagttca cggtgtgcac cgagtgcagc ttcttccaca cccgcaagto gggcgggggc 2940

ggcagcggcg gcggcggctc ggacaagacc cacacctgtc ccccctgccc cgcccccgag 3000 ggcagcggcg gcggcggctc ggacaagacc cacacctgtc ccccctgccc cgcccccgag 3000

ctgctgggtg gcccgtccgt cttcctgttc cccccgaagc cgaaggacac tctcatgatc 3060 ctgctgggtg gcccgtccgt cttcctgttc cccccgaagc cgaaggacac tctcatgatc 3060

tcccggaccc ccgaggtcac ctgcgtggtc gtagacgtgt cccacgagga cccggaggtg 3120 tcccggaccc ccgaggtcac ctgcgtggtc gtagacgtgt cccacgagga cccggaggtg 3120

aagttcaact ggtacgtgga cggcgtggaa gtccacaacg ccaagaccaa gccgcgcgaa 3180 aagttcaact ggtacgtgga cggcgtggaa gtccacaacg ccaagaccaa gccgcgcgaa 3180

gagcagtaca actcgaccta ccgggtcgtc agcgtcctca cggtcctgca ccaggactgg 3240 gagcagtaca actcgaccta ccgggtcgtc agcgtcctca cggtcctgca ccaggactgg 3240

ctcaatggga aggaatacaa gtgcaaggtg tccaacaagg cgctgcccgc ccccatcgag 3300 ctcaatggga aggaatacaa gtgcaaggtg tccaacaagg cgctgcccgc ccccatcgag 3300

aagaccatca gcaaggccaa ggggcagccg cgggaaccgc aggtctacac gctcccgccc 3360 aagaccatca gcaaggccaa ggggcagccg cgggaaccgc aggtctacac gctcccgccc 3360

agccgggacg agctcaccaa gaatcaggtc agtctgacct gcctggtgaa gggcttctac 3420 agccgggacg agctcaccaa gaatcaggtc agtctgacct gcctggtgaa gggcttctac 3420

ccgagtgaca tcgccgtgga gtgggagtcg aatggccagc ccgagaacaa ctacaagaca 3480 ccgagtgaca tcgccgtgga gtgggagtcg aatggccagc ccgagaacaa ctacaagaca 3480

acgccccccg tcctggactc cgacggctcc ttcttcctgt actcgaagct cacggtcgac 3540 acgccccccg tcctggactc cgacggctcc ttcttcctgt actcgaagct cacggtcgac 3540

aagagccggt ggcagcaggg caacgtgttc agctgcagcg tcatgcacga ggccctgcac 3600 aagagccggt ggcagcaggg caacgtgttc agctgcagcg tcatgcacga ggccctgcac 3600

aaccactaca cgcagaagag cctgtcgctg tccccgggaa a 3641 aaccactaca cgcagaagag cctgtcgctg tccccgggaa a 3641

<210> 142 <210> 142 <211> 2972 <211> 2972 <212> DNA <212> DNA <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> wtSP_Seq2_Sc <223> wtSP_Seq2_Sc

<400> 142 <400> 142 aagcttaccg ccaccatgcc cgcctccgcg cccccccgcc gcccgcgtcc tcccccgccg 60 aagcttaccg ccaccatgcc cgcctccgcg cccccccgcc gcccgcgtcc tcccccgccg 60

agcctctccc tgctgctggt gctcctgggc ctgggcggac gccggctccg cgccgagccg 120 agcctctccc tgctgctggt gctcctgggc ctgggcggac gccggctccg cgccgagccg 120

ggcgacggcg cgcagacctg ggcgcgcgtg agccggccgc cggccccgga ggcagccggc 180 ggcgacggcg cgcagacctg ggcgcgcgtg agccggccgc cggccccgga ggcagccggc 180

Page 512 Page 512

20780‐15A_SequenceListing.TXT ctgttccagg ggaccttccc ggacggcttc ctctgggccg tcggctcggc cgcctaccag 240

184080 DATE

accgagggtg gctggcagca gcacggcaag ggcgcctcca tctgggacac cttcacccac 300 00E

cacccgctgg ccccgccggg cgactcccgc aacgcctccc tgccgctggg cgccccctcg 360 09E

cccctgcagc cggccaccgg cgacgtggcg tcggacagct acaacaacgt gttccgcgac 420

7 accgaagccc tgcgggagct gggcgtcacc cactaccgct tctccatcag ctgggctagg 480 08/

gtcctgccca acggcagcgc gggcgtgccc aaccgcgagg gcctgcgtta ctaccggcgc 540

ctgctggagc gcctgcgcga actcggggtc cagccggtcg tcaccctcta ccactgggat 600 009

ctgccccagc gccttcagga cgcctacggc ggctgggcca accgggccct ggccgaccac 660 099

ttccgcgact acgccgagct ctgcttccgc cactttggcg gccaggtcaa gtactggatc 720 OZL

accatcgaca acccgtacgt cgtcgcctgg cacggctacg caaccggccg gctggccccg 780 08L

ggcatccgcg gctccccccg cctgggctac ctcgtggcgc acaacctcct gctggcccac 840

gccaaggtgt ggcacctgta caacacctcc ttccgcccga cccaaggcgg ccaggtgtcc 900 006

atcgccctgt ccagccactg gatcaacccc cggcgcatga cggaccactc gatcaaggag 960 096

tgccagaaga gcctcgactt cgtgctgggc tggttcgcga agccggtgtt catcgacggt 1020 020T

gactacccgg agtccatgaa gaacaacctg tcctcgatcc tgcccgactt caccgagagt 1080 080T

gagaagaagt tcatcaaggg caccgccgac ttcttcgcgc tctgcttcgg ccccaccctc 1140

tcgttccagc tgctggaccc ccacatgaag ttccggcagc tggagagccc gaacctgcgc 1200

cagctcctga gctggatcga cctcgagttc aatcaccccc agatcttcat cgtggagaac 1260 092T

ggttggttcg tgagcggcac caccaagcgc gacgacgcca aatacatgta ctacctgaag 1320 9577881188 OZET

aagtttatca tggagaccct gaaggcgatc aagctggacg gcgtcgacgt gatcggctac 1380 08ET

the accgcctggt ccctgatgga cggcttcgag tggcaccggg ggtacagcat ccggcggggc 1440

ctgttctacg tggacttcct gtcgcaggac aagatgttgc tgcccaagtc gtcggccctc 1500 00ST

ttctaccaga agctgatcga gaagaacggc ttcccgccgc tgcccgagaa ccagcccctg 1560 09ST been gagggcacct tcccgtgcga cttcgcctgg ggcgtcgtgg acaactacat ccaggtcgac 1620 997857898 029T

accaccctga gccagttcac agacctcaac gtgtacctct gggacgtgca ccacagcaaa 1680 089T

cgcctcatca aggtcgacgg cgtagtcacc aagaagcgga agagctattg cgtggacttc 1740 DATE

Page 513 ETS aged

e

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT gccgcgattc aaccccaaat cgcgctcctc caggagatgc acgtcaccca cttcaggttc 1800 gccgcgattc aaccccaaat cgcgctcctc caggagatgo acgtcaccca cttcaggttc 1800

agcctcgact gggcgctgat cctgccgctc gggaaccagt cgcaggtgaa ccacacgatc 1860 agcctcgact gggcgctgat cctgccgctc gggaaccagt cgcaggtgaa ccacacgato 1860

ctgcaatact acaggtgcat ggcgtcggag ctcgtccggg tcaacatcac ccccgtggtc 1920 ctgcaatact acaggtgcat ggcgtcggag ctcgtccggg tcaacatcad ccccgtggtc 1920

gccctctggc agcccatggc gcccaaccag ggcctgcccc gcctcctggc ccgccagggc 1980 gccctctggc agcccatggc gcccaaccag ggcctgcccc gcctcctggc ccgccagggc 1980

gcctgggaga acccgtacac cgcgctggcc ttcgcggagt acgcgcgcct ctgcttccag 2040 gcctgggaga acccgtacac cgcgctggcc ttcgcggagt acgcgcgcct ctgcttccag 2040

gagctggggc accacgtgaa gctgtggatc accatgaacg aaccctacac gcgcaacatg 2100 gagctggggc accacgtgaa gctgtggatc accatgaacg aaccctacac gcgcaacatg 2100

acatacagcg cggggcacaa cctgctgaag gcacacgccc tcgcgtggca cgtctacaac 2160 acatacagcg cggggcacaa cctgctgaag gcacacgccc tcgcgtggca cgtctacaac 2160

gaaaagttcc ggcacgccca gaacggcaag atctccatcg ccctccaggc cgactggatc 2220 gaaaagttcc ggcacgccca gaacggcaag atctccatcg ccctccaggc cgactggatc 2220

gagcctgcct gcccgttctc gcagaaggac aaagaggtgg ccgagcgggt gctggagttc 2280 gagcctgcct gcccgttctc gcagaaggad aaagaggtgg ccgagcgggt gctggagttc 2280

gacatcggtt ggctggcgga gccgatcttc ggctccggcg actacccctg ggtcatgcgg 2340 gacatcggtt ggctggcgga gccgatcttc ggctccggcg actacccctg ggtcatgcgg 2340

gactggctga accagcgcaa caacttcttg cttccctact tcaccgaaga cgaaaagaag 2400 gactggctga accagcgcaa caacttcttg cttccctact tcaccgaaga cgaaaagaag 2400

ctgatccagg gaaccttcga cttcctcgcc ctcagccact acaccaccat cttggtcgac 2460 ctgatccagg gaaccttcga cttcctcgcc ctcagccact acaccaccat cttggtcgac 2460

tcggagaagg aggaccccat caagtacaac gattacctcg aggtccagga gatgacggac 2520 tcggagaagg aggaccccat caagtacaac gattacctcg aggtccagga gatgacggad 2520

atcacgtggc tcaactcgcc gtcccaggtc gcggtggtcc cctggggcct gcggaaggtg 2580 atcacgtggc tcaactcgcc gtcccaggtc gcggtggtcc cctggggcct gcggaaggtg 2580

ctcaactggc tgaagttcaa gtacggcgac ctccccatgt acatcatcag caacggaatc 2640 ctcaactggc tgaagttcaa gtacggcgac ctccccatgt acatcatcag caacggaato 2640

gacgacggcc tgcacgccga ggacgaccag ctccgtgtct actacatgca gaactacatc 2700 gacgacggcc tgcacgccga ggacgaccag ctccgtgtct actacatgca gaactacato 2700

aacgaggccc tgaaggccca catcctggac ggcatcaacc tgtgtggtta cttcgcctac 2760 aacgaggccc tgaaggccca catcctggad ggcatcaacc tgtgtggtta cttcgcctac 2760

tcattcaacg accgcaccgc cccccggttc ggcctctaca ggtacgcggc ggaccagttc 2820 tcattcaacg accgcaccgc cccccggttc ggcctctaca ggtacgcggc ggaccagttc 2820

gagcccaagg cgtcgatgaa gcactaccgc aagatcatcg acagcaacgg cttccccggc 2880 gagcccaagg cgtcgatgaa gcactaccgc aagatcatcg acagcaacgg cttccccggo 2880

ccggagaccc tcgaacgctt ctgccccgag gagttcacgg tgtgcaccga gtgcagcttc 2940 ccggagaccc tcgaacgctt ctgccccgag gagttcacgg tgtgcaccga gtgcagcttc 2940

ttccacaccc gcaagtcgtg ataatctaga gt 2972 ttccacaccc gcaagtcgtg ataatctaga gt 2972

<210> 143 <210> 143 <211> 2945 <211> 2945 <212> DNA <212> DNA <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> LubSP_Seq2_Sc <223> LubSP_Seq2_Sc

<400> 143 <400> 143

Page 514 Page 514

20780‐15A_SequenceListing.TXT aagcttaccg ccaccatggc ctggaagact ctccccatct acctcctgct gctcctgtcg 60 09

us80 gtcttcgtca tccagcaggt gtcctccgag ccgggcgacg gcgcgcagac ctgggcgcgc 120

gtgagccggc cgccggcccc ggaggcagcc ggcctgttcc aggggacctt cccggacggc 180 08T

ttcctctggg ccgtcggctc ggccgcctac cagaccgagg gtggctggca gcagcacggc 240 DATE

aagggcgcct ccatctggga caccttcacc caccacccgc tggccccgcc gggcgactcc 300 00E

cgcaacgcct ccctgccgct gggcgccccc tcgcccctgc agccggccac cggcgacgtg 360 09E

gcgtcggaca gctacaacaa cgtgttccgc gacaccgaag ccctgcggga gctgggcgtc 420

7 e acccactacc gcttctccat cagctgggct agggtcctgc ccaacggcag cgcgggcgtg 480 08/

cccaaccgcg agggcctgcg ttactaccgg cgcctgctgg agcgcctgcg cgaactcggg 540

gtccagccgg tcgtcaccct ctaccactgg gatctgcccc agcgccttca ggacgcctac 600 009

ggcggctggg ccaaccgggc cctggccgac cacttccgcg actacgccga gctctgcttc 660 099

cgccactttg gcggccaggt caagtactgg atcaccatcg acaacccgta cgtcgtcgcc 720 07L

tggcacggct acgcaaccgg ccggctggcc ccgggcatcc gcggctcccc ccgcctgggc 780 08L

tacctcgtgg cgcacaacct cctgctggcc cacgccaagg tgtggcacct gtacaacacc 840

tccttccgcc cgacccaagg cggccaggtg tccatcgccc tgtccagcca ctggatcaac 900 006

ccccggcgca tgacggacca ctcgatcaag gagtgccaga agagcctcga cttcgtgctg 960 096

ggctggttcg cgaagccggt gttcatcgac ggtgactacc cggagtccat gaagaacaac 1020 0201 been ctgtcctcga tcctgcccga cttcaccgag agtgagaaga agttcatcaa gggcaccgcc 1080 080T

gacttcttcg cgctctgctt cggccccacc ctctcgttcc agctgctgga cccccacatg 1140

e aagttccggc agctggagag cccgaacctg cgccagctcc tgagctggat cgacctcgag 1200

ttcaatcacc cccagatctt catcgtggag aacggttggt tcgtgagcgg caccaccaag 1260 092I

cgcgacgacg ccaaatacat gtactacctg aagaagttta tcatggagac cctgaaggcg 1320 OZET

atcaagctgg acggcgtcga cgtgatcggc tacaccgcct ggtccctgat ggacggcttc 1380 08ET

gagtggcacc gggggtacag catccggcgg ggcctgttct acgtggactt cctgtcgcag 1440

gacaagatgt tgctgcccaa gtcgtcggcc ctcttctacc agaagctgat cgagaagaac 1500 00ST

ggcttcccgc cgctgcccga gaaccagccc ctggagggca ccttcccgtg cgacttcgcc 1560 09ST

Page 515 STS aged

20780‐15A_SequenceListing.TXT tggggcgtcg tggacaacta catccaggtc gacaccaccc tgagccagtt cacagacctc 1620 029T

aacgtgtacc tctgggacgt gcaccacagc aaacgcctca tcaaggtcga cggcgtagtc 1680 089T

accaagaagc ggaagagcta ttgcgtggac ttcgccgcga ttcaacccca aatcgcgctc 1740

the ctccaggaga tgcacgtcac ccacttcagg ttcagcctcg actgggcgct gatcctgccg 1800 008T

ctcgggaacc agtcgcaggt gaaccacacg atcctgcaat actacaggtg catggcgtcg 1860 098T

gagctcgtcc gggtcaacat cacccccgtg gtcgccctct ggcagcccat ggcgcccaac 1920 0261

cagggcctgc cccgcctcct ggcccgccag ggcgcctggg agaacccgta caccgcgctg 1980 086T

gccttcgcgg agtacgcgcg cctctgcttc caggagctgg ggcaccacgt gaagctgtgg 2040

atcaccatga acgaacccta cacgcgcaac atgacataca gcgcggggca caacctgctg 2100 00T2

aaggcacacg ccctcgcgtg gcacgtctac aacgaaaagt tccggcacgc ccagaacggc 2160 09T2

The aagatctcca tcgccctcca ggccgactgg atcgagcctg cctgcccgtt ctcgcagaag 2220 7780008700 0222

gacaaagagg tggccgagcg ggtgctggag ttcgacatcg gttggctggc ggagccgatc 2280 0881088118 0822

ttcggctccg gcgactaccc ctgggtcatg cgggactggc tgaaccagcg caacaacttc 2340

ttgcttccct acttcaccga agacgaaaag aagctgatcc agggaacctt cgacttcctc 2400

gccctcagcc actacaccac catcttggtc gactcggaga aggaggaccc catcaagtac 2460

aacgattacc tcgaggtcca ggagatgacg gacatcacgt ggctcaactc gccgtcccag 2520

gtcgcggtgg tcccctgggg cctgcggaag gtgctcaact ggctgaagtt caagtacggc 2580 0857

gacctcccca tgtacatcat cagcaacgga atcgacgacg gcctgcacgc cgaggacgac 2640

cagctccgtg tctactacat gcagaactac atcaacgagg ccctgaaggc ccacatcctg 2700 00LZ

e gacggcatca acctgtgtgg ttacttcgcc tactcattca acgaccgcac cgccccccgg 2760 09/2

ttcggcctct acaggtacgc ggcggaccag ttcgagccca aggcgtcgat gaagcactac 2820 0787

cgcaagatca tcgacagcaa cggcttcccc ggcccggaga ccctcgaacg cttctgcccc 2880 0887

gaggagttca cggtgtgcac cgagtgcagc ttcttccaca cccgcaagtc gtgataatct 2940 9767

agagt 2945 78ege

<210> 144 <0TZ> <211> 3656 <IIZ> 9998 <212> DNA <ZIZ> ANC Page 516 9TS aged

20780‐15A_SequenceListing.TXT <213> Artificial Sequence <ETZ>

<220> <022> <223> LubSP_Seq1_Sc <EZZ>

<400> 144 <00 aagcttaccg ccaccatggc ctggaagact ctccccatct acctcctgct gctcctgtcg 60 09

gtcttcgtca tccagcaggt gtcctccgag ccgggcgacg gcgcgcagac ctgggcgcgc 120

gtgagccggc cgccggcccc ggaggcagcc ggcctgttcc aggggacctt cccggacggc 180 08T

ttcctctggg ccgtcggctc ggccgcctac cagaccgagg gtggctggca gcagcacggc 240 DATE

aagggcgcct ccatctggga caccttcacc caccacccgc tggccccgcc gggcgactcc 300 00E

cgcaacgcct ccctgccgct gggcgccccc tcgcccctgc agccggccac cggcgacgtg 360 09E

gcgtcggaca gctacaacaa cgtgttccgc gacaccgaag ccctgcggga gctgggcgtc 420

e acccactacc gcttctccat cagctgggct agggtcctgc ccaacggcag cgcgggcgtg 480 08/

cccaaccgcg agggcctgcg ttactaccgg cgcctgctgg agcgcctgcg cgaactcggg 540

gtccagccgg tcgtcaccct ctaccactgg gatctgcccc agcgccttca ggacgcctac 600 009

ggcggctggg ccaaccgggc cctggccgac cacttccgcg actacgccga gctctgcttc 660 099

cgccactttg gcggccaggt caagtactgg atcaccatcg acaacccgta cgtcgtcgcc 720 07L

tggcacggct acgcaaccgg ccggctggcc ccgggcatcc gcggctcccc ccgcctgggc 780 08L

tacctcgtgg cgcacaacct cctgctggcc cacgccaagg tgtggcacct gtacaacacc 840

tccttccgcc cgacccaagg cggccaggtg tccatcgccc tgtccagcca ctggatcaac 900 006

ccccggcgca tgacggacca ctcgatcaag gagtgccaga agagcctcga cttcgtgctg 960 096

ggctggttcg cgaagccggt gttcatcgac ggtgactacc cggagtccat gaagaacaac 1020 020I been ctgtcctcga tcctgcccga cttcaccgag agtgagaaga agttcatcaa gggcaccgcc 1080 080T

gacttcttcg cgctctgctt cggccccacc ctctcgttcc agctgctgga cccccacatg 1140

e aagttccggc agctggagag cccgaacctg cgccagctcc tgagctggat cgacctcgag 1200

ttcaatcacc cccagatctt catcgtggag aacggttggt tcgtgagcgg caccaccaag 1260 092T

cgcgacgacg ccaaatacat gtactacctg aagaagttta tcatggagac cctgaaggcg 1320 OZET

atcaagctgg acggcgtcga cgtgatcggc tacaccgcct ggtccctgat ggacggcttc 1380 08ET

Page 517 LTS aged

20780‐15A_SequenceListing.TXT gagtggcacc gggggtacag catccggcgg ggcctgttct acgtggactt cctgtcgcag 1440

gacaagatgt tgctgcccaa gtcgtcggcc ctcttctacc agaagctgat cgagaagaac 1500 00ST

ggcttcccgc cgctgcccga gaaccagccc ctggagggca ccttcccgtg cgacttcgcc 1560 09ST

tggggcgtcg tggacaacta catccaggtc gacaccaccc tgagccagtt cacagacctc 1620 9578598997 079T

aacgtgtacc tctgggacgt gcaccacagc aaacgcctca tcaaggtcga cggcgtagtc 1680 089T

accaagaagc ggaagagcta ttgcgtggac ttcgccgcga ttcaacccca aatcgcgctc 1740

ctccaggaga tgcacgtcac ccacttcagg ttcagcctcg actgggcgct gatcctgccg 1800 008T

ctcgggaacc agtcgcaggt gaaccacacg atcctgcaat actacaggtg catggcgtcg 1860 098T

gagctcgtcc gggtcaacat cacccccgtg gtcgccctct ggcagcccat ggcgcccaac 1920 026T

cagggcctgc cccgcctcct ggcccgccag ggcgcctggg agaacccgta caccgcgctg 1980 8897008588 8000800088 086T

gccttcgcgg agtacgcgcg cctctgcttc caggagctgg ggcaccacgt gaagctgtgg 2040 9707

atcaccatga acgaacccta cacgcgcaac atgacataca gcgcggggca caacctgctg 2100 0012

aaggcacacg ccctcgcgtg gcacgtctac aacgaaaagt tccggcacgc ccagaacggc 2160 09TZ

aagatctcca tcgccctcca ggccgactgg atcgagcctg cctgcccgtt ctcgcagaag 2220 0222

gacaaagagg tggccgagcg ggtgctggag ttcgacatcg gttggctggc ggagccgatc 2280 0822

ttcggctccg gcgactaccc ctgggtcatg cgggactggc tgaaccagcg caacaacttc 2340

ttgcttccct acttcaccga agacgaaaag aagctgatcc agggaacctt cgacttcctc 2400

gccctcagcc actacaccac catcttggtc gactcggaga aggaggaccc catcaagtac 2460

aacgattacc tcgaggtcca ggagatgacg gacatcacgt ggctcaactc gccgtcccag 2520 0252

gtcgcggtgg tcccctgggg cctgcggaag gtgctcaact ggctgaagtt caagtacggc 2580 0857

gacctcccca tgtacatcat cagcaacgga atcgacgacg gcctgcacgc cgaggacgac 2640 997 cagctccgtg tctactacat gcagaactac atcaacgagg ccctgaaggc ccacatcctg 2700 00/2

e gacggcatca acctgtgtgg ttacttcgcc tactcattca acgaccgcac cgccccccgg 2760 09/2

ttcggcctct acaggtacgc ggcggaccag ttcgagccca aggcgtcgat gaagcactac 2820 0787

cgcaagatca tcgacagcaa cggcttcccc ggcccggaga ccctcgaacg cttctgcccc 2880 0887

gaggagttca cggtgtgcac cgagtgcagc ttcttccaca cccgcaagtc gggcgggggc 2940 588889.888 9767

Page 518 8TS aded

20780‐15A_SequenceListing.TXT ggcagcggcg gcggcggctc ggacaagacc cacacctgtc ccccctgccc cgcccccgag 3000

(18080 000E

ctgctgggtg gcccgtccgt cttcctgttc cccccgaagc cgaaggacac tctcatgatc 3060 090E

tcccggaccc ccgaggtcac ctgcgtggtc gtagacgtgt cccacgagga cccggaggtg 3120 OTTE

eee aagttcaact ggtacgtgga cggcgtggaa gtccacaacg ccaagaccaa gccgcgcgaa 3180 08IE

gagcagtaca actcgaccta ccgggtcgtc agcgtcctca cggtcctgca ccaggactgg 3240

ctcaatggga aggaatacaa gtgcaaggtg tccaacaagg cgctgcccgc ccccatcgag 3300 00EE

aagaccatca gcaaggccaa ggggcagccg cgggaaccgc aggtctacac gctcccgccc 3360 09EE

e agccgggacg agctcaccaa gaatcaggtc agtctgacct gcctggtgaa gggcttctac 3420

ccgagtgaca tcgccgtgga gtgggagtcg aatggccagc ccgagaacaa ctacaagaca 3480

acgccccccg tcctggactc cgacggctcc ttcttcctgt actcgaagct cacggtcgac 3540

aagagccggt ggcagcaggg caacgtgttc agctgcagcg tcatgcacga ggccctgcac 3600 009E

aaccactaca cgcagaagag cctgtcgctg tccccgggaa agtgataatc tagagt 3656 9598

<210> 145 <0TZ> States

<211> 2387 <IIZ> <212> DNA <<<<> ANC <213> Artificial Sequence and <ETZ> <220> <022> <223> wtSP_Seq5_Sc <EZZ>

<400> 145 <00 aagcttaccg ccaccatgcc ggcgtccgcc cccccccgcc gcccgaggcc ccccccgccc 60 09

tccctgtccc tgctcctcgt cctgctcggc ctggggggcc gccggctgcg cgccgagccg 120

ggcgacgggg cccagacctg ggcccgcttc agcaggcccc cggcccccga ggcggcgggt 180 08T

ctgttccagg ggaccttccc ggacggtttc ctgtgggccg tcggctccgc cgcgtaccag 240 DATE

acggagggcg ggtggcaaca acacgggaag ggcgcgtcga tctgggacac tttcacccac 300 00E

caccccctgg cccccccggg ggactcgcgg aacgcgagcc tcccgctggg cgcccccagc 360 09E

cccctccagc cggccaccgg cgacgtggcg agcgacagct acaacaatgt cttcagggac 420

7 accgaggccc tccgggaact cggcgtcacg cactaccgct tcagcatcag ctgggcgcgg 480 08/7

gtcctgccga acggctccgc cggcgtgccg aaccgagagg gcctgaggta ctacaggcgc 540

Page 519 6TS aged

20780‐15A_SequenceListing.TXT ctcctggaga ggctccggga gctgggcgta cagcccgtcg tcaccctcta ccactgggac 600 009

1ues80 ctcccgcagc gcctgcagga cgcgtacggg gggtgggcca accgcgccct ggccgaccac 660 099

ttccgggact acgccgagct ctgcttccgc cacttcgggg gccaggtcaa gtactggatc 720 OZL

accatcgaca acccctacgt cgtggcctgg cacggctacg ccaccggtcg cctggccccg 780 9970088780 08L

ggcatccggg gctccccgcg gctgggctac ctcgtcgcgc ataacctgct gctcgcgcac 840

gcgaaggtct ggcacctcta caacaccagc ttccggccga cccagggcgg ccaggtgagc 900 006

atcgcgctgt cgagccactg gatcaacccc cgccgtatga ctgaccactc gatcaaggaa 960 096

tgccagaaga gcctggactt cgtcctgggg tggttcgcca agccggtgtt catcgacggt 1020

gactacccgg aatcgatgaa gaacaacctg tcctcgatcc tgcccgactt caccgagtcc 1080 080T

the gagaagaagt tcattaaggg caccgccgac ttcttcgcgc tgtgcttcgg gcccaccctg 1140

tccttccagc tgctggaccc ccacatgaag ttccgccagc tagagtctcc gaacctgcgc 1200 0021

cagctcctgt cgtggatcga cctggagttc aaccacccgc agatcttcat cgtcgagaac 1260 092T

ggctggttcg tctcggggac caccaaacgg gacgacgcca agtatatgta ctacctcaag 1320 OZET

aagttcatca tggagaccct gaaggcgatc aagctggacg gggtcgacgt catcgggtac 1380 08ET

accgcctggt ccctgatgga cggcttcgag tggcaccgcg gctactcgat cagacgcggc 1440

ctgttctacg tcgacttcct gtcgcaggac aagatgctcc tgccgaagtc cagcgcgctc 1500 00ST

ttctaccaga agctgatcga gaagaacggc ttcccaccgc tgcccgagaa ccagccactc 1560 09ST

gaaggcacct tcccgtgcga cttcgcctgg ggcgtcgtgg acaactacat ccaggtgtcg 1620 029T

cagctcacga agccgatctc ctcgctcacc aagccgtacc acgggggcgg cggtagcggc 1680 089T

ggcggcggct ccgacaagac ccacacctgc ccgccgtgcc ccgcgcccga gctgctcggc 1740 cheese ggcccctccg tcttcctgtt ccctcccaag cccaaggaca cgctgatgat ctcccggacc 1800 008T

cccgaggtca cctgcgtcgt ggtcgacgtg tcgcacgagg acccggaggt gaagttcaac 1860 098T

tggtacgtgg acggtgtgga ggtgcataac gccaagacca agccgcggga agagcagtac 1920 026T

aactccacgt acagggtcgt ctcggtgctg acggtcctgc accaagactg gctgaacggc 1980 086T

Page 520 025 aged e aaggagtaca agtgcaaggt gagcaacaag gccctcccgg cgcccatcga gaagaccatc 2040

agcaaggcga agggccagcc gcgggagccg caggtctaca ccctcccgcc gagccgtgac 2100 0012

e

20780‐15A_SequenceListing.TXT 120780-15A_SequenceListing. TXT gaactgacca agaaccaggt ctcgctcacg tgcctggtca aggggttcta cccgagcgac 2160 gaactgacca agaaccaggt ctcgctcacg tgcctggtca aggggttcta cccgagcgad 2160

atcgccgtgg agtgggaatc gaacggccag ccggagaaca actacaagac caccccgccc 2220 atcgccgtgg agtgggaatc gaacggccag ccggagaaca actacaagac caccccgccc 2220

gtgctggaca gcgacggctc cttcttcctc tactccaagc tgaccgtcga caagtcgcgc 2280 gtgctggaca gcgacggctc cttcttcctc tactccaagc tgaccgtcga caagtcgcgc 2280

tggcagcaag ggaacgtgtt ctcctgctcg gtcatgcacg aggccctgca caaccactat 2340 tggcagcaag ggaacgtgtt ctcctgctcg gtcatgcacg aggccctgca caaccactat 2340

acccaaaaga gtctgtcgct gtccccgggg aagtgataat ctagagt 2387 acccaaaaga gtctgtcgct gtccccgggg aagtgataat ctagagt 2387

<210> 146 <210> 146 <211> 3683 <211> 3683 <212> DNA <212> DNA <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> wtSP_Seq3_Sc <223> wtSP_Seq3_Sc

<400> 146 <400> 146 aagcttaccg ccaccatgcc cgcctccgcg cccccccgcc gcccgcgtcc tcccccgccg 60 aagcttaccg ccaccatgcc cgcctccgcg cccccccgcc gcccgcgtcc tcccccgccg 60

agcctctccc tgctgctggt gctcctgggc ctgggcggac gccggctccg cgccgagccg 120 agcctctccc tgctgctggt gctcctgggc ctgggcggac gccggctccg cgccgagccg 120

ggcgacggcg cgcagacctg ggcgcgcttc agccggccgc cggccccgga ggcagccggc 180 ggcgacggcg cgcagacctg ggcgcgcttc agccggccgc cggccccgga ggcagccggc 180

ctgttccagg ggaccttccc ggacggcttc ctctgggccg tcggctcggc cgcctaccag 240 ctgttccagg ggaccttccc ggacggcttc ctctgggccg tcggctcggc cgcctaccag 240

accgagggtg gctggcagca gcacggcaag ggcgcctcca tctgggacac cttcacccac 300 accgagggtg gctggcagca gcacggcaag ggcgcctcca tctgggacac cttcacccac 300

cacccgctgg ccccgccggg cgactcccgc aacgcctccc tgccgctggg cgccccctcg 360 cacccgctgg ccccgccggg cgactcccgc aacgcctccc tgccgctggg cgccccctcg 360

cccctgcagc cggccaccgg cgacgtggcg tcggacagct acaacaacgt gttccgcgac 420 cccctgcagc cggccaccgg cgacgtggcg tcggacagct acaacaacgt gttccgcgac 420

accgaagccc tgcgggagct gggcgtcacc cactaccgct tctccatcag ctgggctagg 480 accgaagccc tgcgggagct gggcgtcacc cactaccgct tctccatcag ctgggctagg 480

gtcctgccca acggcagcgc gggcgtgccc aaccgcgagg gcctgcgtta ctaccggcgc 540 gtcctgccca acggcagcgc gggcgtgccc aaccgcgagg gcctgcgtta ctaccggcgc 540

ctgctggagc gcctgcgcga actcggggtc cagccggtcg tcaccctcta ccactgggat 600 ctgctggagc gcctgcgcga actcggggtc cagccggtcg tcaccctcta ccactgggat 600

ctgccccagc gccttcagga cgcctacggc ggctgggcca accgggccct ggccgaccac 660 ctgccccagc gccttcagga cgcctacggc ggctgggcca accgggccct ggccgaccac 660

ttccgcgact acgccgagct ctgcttccgc cactttggcg gccaggtcaa gtactggatc 720 ttccgcgact acgccgagct ctgcttccgc cactttggcg gccaggtcaa gtactggatc 720

accatcgaca acccgtacgt cgtcgcctgg cacggctacg caaccggccg gctggccccg 780 accatcgaca acccgtacgt cgtcgcctgg cacggctacg caaccggccg gctggccccg 780

ggcatccgcg gctccccccg cctgggctac ctcgtggcgc acaacctcct gctggcccac 840 ggcatccgcg gctccccccg cctgggctac ctcgtggcgc acaacctcct gctggcccac 840

gccaaggtgt ggcacctgta caacacctcc ttccgcccga cccaaggcgg ccaggtgtcc 900 gccaaggtgt ggcacctgta caacacctcc ttccgcccga cccaaggcgg ccaggtgtcc 900

atcgccctgt ccagccactg gatcaacccc cggcgcatga cggaccactc gatcaaggag 960 atcgccctgt ccagccactg gatcaacccc cggcgcatga cggaccactc gatcaaggag 960

Page 521 Page 521

20780‐15A_SequenceListing.TXT tgccagaaga gcctcgactt cgtgctgggc tggttcgcga agccggtgtt catcgacggt 1020 0201

1x1480 gactacccgg agtccatgaa gaacaacctg tcctcgatcc tgcccgactt caccgagagt 1080 080T

e gagaagaagt tcatcaaggg caccgccgac ttcttcgcgc tctgcttcgg ccccaccctc 1140

tcgttccagc tgctggaccc ccacatgaag ttccggcagc tggagagccc gaacctgcgc 1200

cagctcctga gctggatcga cctcgagttc aatcaccccc agatcttcat cgtggagaac 1260

9077881188 092T

ggttggttcg tgagcggcac caccaagcgc gacgacgcca aatacatgta ctacctgaag 1320 OZET

aagtttatca tggagaccct gaaggcgatc aagctggacg gcgtcgacgt gatcggctac 1380 08ET

the accgcctggt ccctgatgga cggcttcgag tggcaccggg ggtacagcat ccggcggggc 1440

ctgttctacg tggacttcct gtcgcaggac aagatgttgc tgcccaagtc gtcggccctc 1500 00ST

ttctaccaga agctgatcga gaagaacggc ttcccgccgc tgcccgagaa ccagcccctg 1560 09ST

gagggcacct tcccgtgcga cttcgcctgg ggcgtcgtgg acaactacat ccaggtcgac 1620 0291

accaccctga gccagttcac agacctcaac gtgtacctct gggacgtgca ccacagcaaa 1680 089T

cgcctcatca aggtcgacgg cgtagtcacc aagaagcgga agagctattg cgtggacttc 1740

e. gccgcgattc aaccccaaat cgcgctcctc caggagatgc acgtcaccca cttcaggttc 1800 008T

agcctcgact gggcgctgat cctgccgctc gggaaccagt cgcaggtgaa ccacacgatc 1860 098T

ctgcaatact acaggtgcat ggcgtcggag ctcgtccggg tcaacatcac ccccgtggtc 1920 026T

gccctctggc agcccatggc gcccaaccag ggcctgcccc gcctcctggc ccgccagggc 1980 086T

gcctgggaga acccgtacac cgcgctggcc ttcgcggagt acgcgcgcct ctgcttccag 2040

gagctggggc accacgtgaa gctgtggatc accatgaacg aaccctacac gcgcaacatg 2100 0012

acatacagcg cggggcacaa cctgctgaag gcacacgccc tcgcgtggca cgtctacaac 2160 0912

gaaaagttcc ggcacgccca gaacggcaag atctccatcg ccctccaggc cgactggatc 2220 0222

gagcctgcct gcccgttctc gcagaaggac aaagaggtgg ccgagcgggt gctggagttc 2280 0822

gacatcggtt ggctggcgga gccgatcttc ggctccggcg actacccctg ggtcatgcgg 2340

gactggctga accagcgcaa caacttcttg cttccctact tcaccgaaga cgaaaagaag 2400

ctgatccagg gaaccttcga cttcctcgcc ctcagccact acaccaccat cttggtcgac 2460

tcggagaagg aggaccccat caagtacaac gattacctcg aggtccagga gatgacggac 2520 0252

Page 522 zzs aged

780-15A_SequenceListing. TXT 20780‐15A_SequenceListing.TXT atcacgtggc tcaactcgcc gtcccaggtc gcggtggtcc cctggggcct gcggaaggtg atcacgtggc tcaactcgcc gtcccaggtc gcggtggtcc cctggggcct gcggaaggtg 2580 2580 ctcaactggc tgaagttcaa gtacggcgac ctccccatgt acatcatcag caacggaatc ctcaactggc tgaagttcaa gtacggcgac ctccccatgt acatcatcag caacggaatc 2640 2640 gacgacggcc tgcacgccga ggacgaccag ctccgtgtct actacatgca gaactacatc gacgacggcc tgcacgccga ggacgaccag ctccgtgtct actacatgca gaactacatc 2700 2700 aacgaggccc tgaaggccca catcctggac ggcatcaacc tgtgtggtta cttcgcctac aacgaggccc tgaaggccca catcctggac ggcatcaacc tgtgtggtta cttcgcctac 2760 2760 tcattcaacg accgcaccgc cccccggttc ggcctctaca ggtacgcggc ggaccagttc tcattcaacg accgcaccgc cccccggttc ggcctctaca ggtacgcggc ggaccagttc 2820 2820 gagcccaagg cgtcgatgaa gcactaccgc aagatcatcg acagcaacgg cttccccggc gagcccaagg cgtcgatgaa gcactaccgc aagatcatcg acagcaacgg cttccccggc 2880 2880 ccggagaccc tcgaacgctt ctgccccgag gagttcacgg tgtgcaccga gtgcagcttc ccggagaccc tcgaacgctt ctgccccgag gagttcacgg tgtgcaccga gtgcagcttc 2940 2940 ttccacaccc gcaagtcggg cgggggcggc agcggcggcg gcggctcgga caagacccac ttccacaccc gcaagtcggg cgggggcggc agcggcggcg gcggctcgga caagacccac 3000 3000 acctgtcccc cctgccccgc ccccgagctg ctgggtggcc cgtccgtctt cctgttcccc acctgtcccc cctgccccgc ccccgagctg ctgggtggcc cgtccgtctt cctgttcccc 3060 3060 ccgaagccga aggacactct catgatctcc cggacccccg aggtcacctg cgtggtcgta ccgaagccga aggacactct catgatctcc cggacccccg aggtcacctg cgtggtcgta 3120 3120 gacgtgtccc acgaggaccc ggaggtgaag ttcaactggt acgtggaagg cgtggaagtc gacgtgtccc acgaggaccc ggaggtgaag ttcaactggt acgtggacgg cgtggaagtc 3180 3180 cacaacccca agaccaagcc gcgcgaagag cagtacaact cgacctaccg ggtcgtcagc cacaacgcca agaccaagcc gcgcgaagag cagtacaact cgacctaccg ggtcgtcagc 3240 3240 gtcctcacgg tcctgcacca ggactggctc aatgggaagg aatacaagtg caaggtgtcc gtcctcacgg tcctgcacca ggactggctc aatgggaagg aatacaagtg caaggtgtcc 3300 3300 aacaaggcgc tgcccgcccc catcgagaag accatcagca aggccaaggg gcagccgcgg aacaaggcgc tgcccgcccc catcgagaag accatcagca aggccaaggg gcagccgcgg 3360 3360 gaaccgcagg tctacacgct cccgcccagc cgggacgagc tcaccaagaa tcaggtcagt gaaccgcagg tctacacgct cccgcccagc cgggacgagc tcaccaagaa tcaggtcagt 3420 3420 ctgacctgcc tggtgaaggg cttctacccg agtgacatcg ccgtggagtg ggagtcgaat ctgacctgcc tggtgaaggg cttctacccg agtgacatcg ccgtggagtg ggagtcgaat 3480 3480 ggccagcccg agaacaacta caagacaacg ccccccgtcc tggactccga cggctccttc ggccagcccg agaacaacta caagacaacg ccccccgtcc tggactccga cggctccttc 3540 3540 ttcctgtact cgaagctcac ggtcgacaag agccggtggc agcagggcaa cgtgttcagc ttcctgtact cgaagctcac ggtcgacaag agccggtggc agcagggcaa cgtgttcagc 3600 3600 tgcagcgtca tgcacgaggc cctgcacaac cactacacgc agaagagcct gtcgctgtcc tgcagcgtca tgcacgaggc cctgcacaac cactacacgc agaagagcct gtcgctgtcc 3660 3660

ccgggaaagt gataatctag agt 3683 ccgggaaagt gataatctag agt 3683

<210> 147 <210> 147 <211> 2945 <211> 2945 <212> DNA <212> DNA <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> LubSP_Seq4_Sc <223> LubSP_Seq4_Sc

<400> 147 aagcttaccg <400> 147 ccaccatggc ctggaagact ctccccatct acctcctgct gctcctgtcg aagcttaccg ccaccatggc ctggaagact ctccccatct acctcctgct gctcctgtcg 60 60

Page 523 Page 523

20780‐15A_SequenceListing.TXT gtcttcgtca tccagcaggt gtcctccgag ccgggcgacg gcgcgcagac ctgggcgcgc 120

1x1480 ttcagccggc cgccggcccc ggaggcagcc ggcctgttcc aggggacctt cccggacggc 180 08T

ttcctctggg ccgtcggctc ggccgcctac cagaccgagg gtggctggca gcagcacggc 240 DATE

aagggcgcct ccatctggga caccttcacc caccacccgc tggccccgcc gggcgactcc 300 00E

eee cgcaacgcct ccctgccgct gggcgccccc tcgcccctgc agccggccac cggcgacgtg 360 09E

gcgtcggaca gctacaacaa cgtgttccgc gacaccgaag ccctgcggga gctgggcgtc 420 0800778780

e acccactacc gcttctccat cagctgggct agggtcctgc ccaacggcag cgcgggcgtg 480 08/

cccaaccgcg agggcctgcg ttactaccgg cgcctgctgg agcgcctgcg cgaactcggg 540

gtccagccgg tcgtcaccct ctaccactgg gatctgcccc agcgccttca ggacgcctac 600 009

ggcggctggg ccaaccgggc cctggccgac cacttccgcg actacgccga gctctgcttc 660 099

cgccactttg gcggccaggt caagtactgg atcaccatcg acaacccgta cgtcgtcgcc 720 02L

tggcacggct acgcaaccgg ccggctggcc ccgggcatcc gcggctcccc ccgcctgggc 780 08L

tacctcgtgg cgcacaacct cctgctggcc cacgccaagg tgtggcacct gtacaacacc 840

tccttccgcc cgacccaagg cggccaggtg tccatcgccc tgtccagcca ctggatcaac 900 006

ccccggcgca tgacggacca ctcgatcaag gagtgccaga agagcctcga cttcgtgctg 960 096

ggctggttcg cgaagccggt gttcatcgac ggtgactacc cggagtccat gaagaacaac 1020 0201

been ctgtcctcga tcctgcccga cttcaccgag agtgagaaga agttcatcaa gggcaccgcc 1080 080T

gacttcttcg cgctctgctt cggccccacc ctctcgttcc agctgctgga cccccacatg 1140

e aagttccggc agctggagag cccgaacctg cgccagctcc tgagctggat cgacctcgag 1200

ttcaatcacc cccagatctt catcgtggag aacggttggt tcgtgagcgg caccaccaag 1260 092T

cgcgacgacg ccaaatacat gtactacctg aagaagttta tcatggagac cctgaaggcg 1320 OZET

atcaagctgg acggcgtcga cgtgatcggc tacaccgcct ggtccctgat ggacggcttc 1380 08ET

gagtggcacc gggggtacag catccggcgg ggcctgttct acgtggactt cctgtcgcag 1440

gacaagatgt tgctgcccaa gtcgtcggcc ctcttctacc agaagctgat cgagaagaac 1500 00ST

ggcttcccgc cgctgcccga gaaccagccc ctggagggca ccttcccgtg cgacttcgcc 1560 09ST

tggggcgtcg tggacaacta catccaggtc gacaccaccc tgagccagtt cacagacctc 1620 9078599997 029T

Page 524

20780‐15A_SequenceListing.TXT aacgtgtacc tctgggacgt gcaccacagc aaacgcctca tcaaggtcga cggcgtagtc 1680 089T

1x180 accaagaagc ggaagagcta ttgcgtggac ttcgccgcga ttcaacccca aatcgcgctc 1740

ctccaggaga tgcacgtcac ccacttcagg ttcagcctcg actgggcgct gatcctgccg 1800 008T

ctcgggaacc agtcgcaggt gaaccacacg atcctgcaat actacaggtg catggcgtcg 1860 098T

gagctcgtcc gggtcaacat cacccccgtg gtcgccctct ggcagcccat ggcgcccaac 1920 026T

cagggcctgc cccgcctcct ggcccgccag ggcgcctggg agaacccgta caccgcgctg 1980 9897008588 086T

gccttcgcgg agtacgcgcg cctctgcttc caggagctgg ggcaccacgt gaagctgtgg 2040

atcaccatga acgaacccta cacgcgcaac atgacataca gcgcggggca caacctgctg 2100 00I2

aaggcacacg ccctcgcgtg gcacgtctac aacgaaaagt tccggcacgc ccagaacggc 2160 09T2

aagatctcca tcgccctcca ggccgactgg atcgagcctg cctgcccgtt ctcgcagaag 2220 0222

gacaaagagg tggccgagcg ggtgctggag ttcgacatcg gttggctggc ggagccgatc 2280 0822

ttcggctccg gcgactaccc ctgggtcatg cgggactggc tgaaccagcg caacaacttc 2340

ttgcttccct acttcaccga agacgaaaag aagctgatcc agggaacctt cgacttcctc 2400

gccctcagcc actacaccac catcttggtc gactcggaga aggaggaccc catcaagtac 2460

aacgattacc tcgaggtcca ggagatgacg gacatcacgt ggctcaactc gccgtcccag 2520 0252

gtcgcggtgg tcccctgggg cctgcggaag gtgctcaact ggctgaagtt caagtacggc 2580 0857

gacctcccca tgtacatcat cagcaacgga atcgacgacg gcctgcacgc cgaggacgac 2640

cagctccgtg tctactacat gcagaactac atcaacgagg ccctgaaggc ccacatcctg 2700 00/2

e gacggcatca acctgtgtgg ttacttcgcc tactcattca acgaccgcac cgccccccgg 2760 000000080 09/2

ttcggcctct acaggtacgc ggcggaccag ttcgagccca aggcgtcgat gaagcactac 2820 0787

cgcaagatca tcgacagcaa cggcttcccc ggcccggaga ccctcgaacg cttctgcccc 2880 0887

gaggagttca cggtgtgcac cgagtgcagc ttcttccaca cccgcaagtc gtgataatct 2940 9767

agagt 2945

<210> 148 <0TZ> <211> 2360 <IIZ> 0982 <212> DNA <ZIZ> ANC <213> Artificial Sequence <ETZ>

and Page 525 sas aged

20780‐15A_SequenceListing.TXT <220> <022> <223> LubSP_Seq5_Sc <EZZ>

<400> 148 <00

118 aagcttaccg ccaccatggc ctggaagact ctccccatct acctcctgct gctcctgtcg 60 09

gtcttcgtca tccagcaggt gtcctccgag ccgggcgacg gggcccagac ctgggcccgc 120

ttcagcaggc ccccggcccc cgaggcggcg ggtctgttcc aggggacctt cccggacggt 180 08T

ttcctgtggg ccgtcggctc cgccgcgtac cagacggagg gcgggtggca acaacacggg 240

aagggcgcgt cgatctggga cactttcacc caccaccccc tggccccccc gggggactcg 300 00E

cggaacgcga gcctcccgct gggcgccccc agccccctcc agccggccac cggcgacgtg 360 09E

gcgagcgaca gctacaacaa tgtcttcagg gacaccgagg ccctccggga actcggcgtc 420

acgcactacc gcttcagcat cagctgggcg cgggtcctgc cgaacggctc cgccggcgtg 480 08/7

ccgaaccgag agggcctgag gtactacagg cgcctcctgg agaggctccg ggagctgggc 540

gtacagcccg tcgtcaccct ctaccactgg gacctcccgc agcgcctgca ggacgcgtac 600 009

ggggggtggg ccaaccgcgc cctggccgac cacttccggg actacgccga gctctgcttc 660 9997899999 099

cgccacttcg ggggccaggt caagtactgg atcaccatcg acaaccccta cgtcgtggcc 720 022

tggcacggct acgccaccgg tcgcctggcc ccgggcatcc ggggctcccc gcggctgggc 780 08L

tacctcgtcg cgcataacct gctgctcgcg cacgcgaagg tctggcacct ctacaacacc 840

agcttccggc cgacccaggg cggccaggtg agcatcgcgc tgtcgagcca ctggatcaac 900 006

ccccgccgta tgactgacca ctcgatcaag gaatgccaga agagcctgga cttcgtcctg 960 096

gggtggttcg ccaagccggt gttcatcgac ggtgactacc cggaatcgat gaagaacaac 1020

ctgtcctcga tcctgcccga cttcaccgag tccgagaaga agttcattaa gggcaccgcc 1080 080T

gacttcttcg cgctgtgctt cgggcccacc ctgtccttcc agctgctgga cccccacatg 1140

aagttccgcc agctagagtc tccgaacctg cgccagctcc tgtcgtggat cgacctggag 1200

ttcaaccacc cgcagatctt catcgtcgag aacggctggt tcgtctcggg gaccaccaaa 1260 097T

cgggacgacg ccaagtatat gtactacctc aagaagttca tcatggagac cctgaaggcg 1320 OZET

atcaagctgg acggggtcga cgtcatcggg tacaccgcct ggtccctgat ggacggcttc 1380 08ET

gagtggcacc gcggctactc gatcagacgc ggcctgttct acgtcgactt cctgtcgcag 1440

Page 526 ested

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing TXT gacaagatgc tcctgccgaa gtccagcgcg ctcttctacc agaagctgat cgagaagaac 1500 gacaagatgc tcctgccgaa gtccagcgcg ctcttctacc agaagctgat cgagaagaao 1500

ggcttcccac cgctgcccga gaaccagcca ctcgaaggca ccttcccgtg cgacttcgcc 1560 ggcttcccac cgctgcccga gaaccagcca ctcgaaggca ccttcccgtg cgacttcgcc 1560

tggggcgtcg tggacaacta catccaggtg tcgcagctca cgaagccgat ctcctcgctc 1620 tggggcgtcg tggacaacta catccaggtg tcgcagctca cgaagccgat ctcctcgctc 1620

accaagccgt accacggggg cggcggtagc ggcggcggcg gctccgacaa gacccacacc 1680 accaagccgt accacggggg cggcggtago ggcggcggcg gctccgacaa gacccacacc 1680

tgcccgccgt gccccgcgcc cgagctgctc ggcggcccct ccgtcttcct gttccctccc tgcccgccgt gccccgcgcc cgagctgctc ggcggcccct ccgtcttcct gttccctccc 1740 1740

aagcccaagg acacgctgat gatctcccgg acccccgagg tcacctgcgt cgtggtcgac 1800 aagcccaagg acacgctgat gatctcccgg acccccgagg tcacctgcgt cgtggtcgad 1800

gtgtcgcacg aggacccgga ggtgaagttc aactggtacg tggacggtgt ggaggtgcat 1860 gtgtcgcacg aggacccgga ggtgaagttc aactggtacg tggacggtgt ggaggtgcat 1860

aacgccaaga ccaagccgcg ggaagagcag tacaactcca cgtacagggt cgtctcggtg 1920 aacgccaaga ccaagccgcg ggaagagcag tacaactcca cgtacagggt cgtctcggtg 1920

ctgacggtcc tgcaccaaga ctggctgaac ggcaaggagt acaagtgcaa ggtgagcaac 1980 ctgacggtcc tgcaccaaga ctggctgaac ggcaaggagt acaagtgcaa ggtgagcaad 1980

aaggccctcc cggcgcccat cgagaagacc atcagcaagg cgaagggcca gccgcgggag 2040 aaggccctcc cggcgcccat cgagaagacc atcagcaagg cgaagggcca gccgcgggag 2040

ccgcaggtct acaccctccc gccgagccgt gacgaactga ccaagaacca ggtctcgctc 2100 ccgcaggtct acaccctccc gccgagccgt gacgaactga ccaagaacca ggtctcgctc 2100

acgtgcctgg tcaaggggtt ctacccgagc gacatcgccg tggagtggga atcgaacggc 2160 acgtgcctgg tcaaggggtt ctacccgago gacatcgccg tggagtggga atcgaacggo 2160

cagccggaga acaactacaa gaccaccccg cccgtgctgg acagcgacgg ctccttcttc 2220 cagccggaga acaactacaa gaccaccccg cccgtgctgg acagcgacgg ctccttctto 2220

ctctactcca agctgaccgt cgacaagtcg cgctggcago aagggaacgt gttctcctgc ctctactcca agctgaccgt cgacaagtcg cgctggcagc aagggaacgt gttctcctgc 2280 2280

tcggtcatgc acgaggccct gcacaaccao tatacccaaa agagtctgtc gctgtccccg tcggtcatgc acgaggccct gcacaaccac tatacccaaa agagtctgtc gctgtccccg 2340 2340

gggaagtgat aatctagagt 2360 gggaagtgat aatctagagt 2360

<210> 149 <210> 149 <211> 3683 <211> 3683 <212> DNA <212> DNA <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> wtSP_Seq1_Sc <223> wtSP_Seq1_Sc

<400> 149 <400> 149 aagcttaccg ccaccatgcc cgcctccgcg cccccccgcc gcccgcgtcc tcccccgccg aagcttaccg ccaccatgcc cgcctccgcg cccccccgcc gcccgcgtcc tcccccgccg 60 60

agcctctccc tgctgctggt gctcctgggc ctgggcggad gccggctccg cgccgagccg agcctctccc tgctgctggt gctcctgggc ctgggcggac gccggctccg cgccgagccg 120 120

ggcgacggcg cgcagacctg ggcgcgcgtg agccggccgc cggccccgga ggcagccggc 180 ggcgacggcg cgcagacctg ggcgcgcgtg agccggccgc cggccccgga ggcagccggo 180

ctgttccagg ggaccttccc ggacggcttc ctctgggccg tcggctcggc cgcctaccag ctgttccagg ggaccttccc ggacggcttc ctctgggccg tcggctcggc cgcctaccag 240 240

accgagggtg gctggcagca gcacggcaag ggcgcctcca tctgggacac cttcacccad accgagggtg gctggcagca gcacggcaag ggcgcctcca tctgggacac cttcacccac 300 300

Page 527 Page 527

20780‐15A_SequenceListing.TXT cacccgctgg ccccgccggg cgactcccgc aacgcctccc tgccgctggg cgccccctcg 360 1ubesA802 09E

cccctgcagc cggccaccgg cgacgtggcg tcggacagct acaacaacgt gttccgcgac 420

accgaagccc tgcgggagct gggcgtcacc cactaccgct tctccatcag ctgggctagg 480 08/

gtcctgccca acggcagcgc gggcgtgccc aaccgcgagg gcctgcgtta ctaccggcgc 540 STS

ctgctggagc gcctgcgcga actcggggtc cagccggtcg tcaccctcta ccactgggat 600 009

ctgccccagc gccttcagga cgcctacggc ggctgggcca accgggccct ggccgaccac 660 099

ttccgcgact acgccgagct ctgcttccgc cactttggcg gccaggtcaa gtactggatc 720 OZL

accatcgaca acccgtacgt cgtcgcctgg cacggctacg caaccggccg gctggccccg 780 9870080780 08L

ggcatccgcg gctccccccg cctgggctac ctcgtggcgc acaacctcct gctggcccac 840

gccaaggtgt ggcacctgta caacacctcc ttccgcccga cccaaggcgg ccaggtgtcc 900 006

atcgccctgt ccagccactg gatcaacccc cggcgcatga cggaccactc gatcaaggag 960 096

tgccagaaga gcctcgactt cgtgctgggc tggttcgcga agccggtgtt catcgacggt 1020 0201

gactacccgg agtccatgaa gaacaacctg tcctcgatcc tgcccgactt caccgagagt 1080 080T

gagaagaagt tcatcaaggg caccgccgac ttcttcgcgc tctgcttcgg ccccaccctc 1140

tcgttccagc tgctggaccc ccacatgaag ttccggcagc tggagagccc gaacctgcgc 1200 002I

cagctcctga gctggatcga cctcgagttc aatcaccccc agatcttcat cgtggagaac 1260 092T

ggttggttcg tgagcggcac caccaagcgc gacgacgcca aatacatgta ctacctgaag 1320 8577881789 OZET

aagtttatca tggagaccct gaaggcgatc aagctggacg gcgtcgacgt gatcggctac 1380 08EI

accgcctggt ccctgatgga cggcttcgag tggcaccggg ggtacagcat ccggcggggc 1440

ctgttctacg tggacttcct gtcgcaggac aagatgttgc tgcccaagtc gtcggccctc 1500 00ST

ttctaccaga agctgatcga gaagaacggc ttcccgccgc tgcccgagaa ccagcccctg 1560 09ST

gagggcacct tcccgtgcga cttcgcctgg ggcgtcgtgg acaactacat ccaggtcgac 1620 029T

accaccctga gccagttcac agacctcaac gtgtacctct gggacgtgca ccacagcaaa 1680 089T

cgcctcatca aggtcgacgg cgtagtcacc aagaagcgga agagctattg cgtggacttc 1740

gccgcgattc aaccccaaat cgcgctcctc caggagatgc acgtcaccca cttcaggttc 1800 008T

agcctcgact gggcgctgat cctgccgctc gggaaccagt cgcaggtgaa ccacacgatc 1860 098T

Page 528 SUS aged

20780‐15A_SequenceListing.TXT ctgcaatact acaggtgcat ggcgtcggag ctcgtccggg tcaacatcac ccccgtggtc 1920 026T

gccctctggc agcccatggc gcccaaccag ggcctgcccc gcctcctggc ccgccagggc 1980 086T

gcctgggaga acccgtacac cgcgctggcc ttcgcggagt acgcgcgcct ctgcttccag 2040 9702

gagctggggc accacgtgaa gctgtggatc accatgaacg aaccctacac gcgcaacatg 2100 0012

acatacagcg cggggcacaa cctgctgaag gcacacgccc tcgcgtggca cgtctacaac 2160 09TZ

9999 gaaaagttcc ggcacgccca gaacggcaag atctccatcg ccctccaggc cgactggatc 2220 0222

gagcctgcct gcccgttctc gcagaaggac aaagaggtgg ccgagcgggt gctggagttc 2280 0822

be gacatcggtt ggctggcgga gccgatcttc ggctccggcg actacccctg ggtcatgcgg 2340

gactggctga accagcgcaa caacttcttg cttccctact tcaccgaaga cgaaaagaag 2400 SeeGeeeed,

ctgatccagg gaaccttcga cttcctcgcc ctcagccact acaccaccat cttggtcgac 2460

tcggagaagg aggaccccat caagtacaac gattacctcg aggtccagga gatgacggac 2520 0252

atcacgtggc tcaactcgcc gtcccaggtc gcggtggtcc cctggggcct gcggaaggtg 2580 0857

ctcaactggc tgaagttcaa gtacggcgac ctccccatgt acatcatcag caacggaatc 2640

gacgacggcc tgcacgccga ggacgaccag ctccgtgtct actacatgca gaactacatc 2700 00LZ

aacgaggccc tgaaggccca catcctggac ggcatcaacc tgtgtggtta cttcgcctac 2760 09/2

tcattcaacg accgcaccgc cccccggttc ggcctctaca ggtacgcggc ggaccagttc 2820 0787

gagcccaagg cgtcgatgaa gcactaccgc aagatcatcg acagcaacgg cttccccggc 2880 0887

ccggagaccc tcgaacgctt ctgccccgag gagttcacgg tgtgcaccga gtgcagcttc 2940 9767

ttccacaccc gcaagtcggg cgggggcggc agcggcggcg gcggctcgga caagacccac 3000 088999995 000E

acctgtcccc cctgccccgc ccccgagctg ctgggtggcc cgtccgtctt cctgttcccc 3060 090E

ccgaagccga aggacactct catgatctcc cggacccccg aggtcacctg cgtggtcgta 3120 OZIE

gacgtgtccc acgaggaccc ggaggtgaag ttcaactggt acgtggacgg cgtggaagtc 3180 08IE

I cacaacgcca agaccaagcc gcgcgaagag cagtacaact cgacctaccg ggtcgtcagc 3240

gtcctcacgg tcctgcacca ggactggctc aatgggaagg aatacaagtg caaggtgtcc 3300 89ee9997ee 00EE

aacaaggcgc tgcccgcccc catcgagaag accatcagca aggccaaggg gcagccgcgg 3360 0988

gaaccgcagg tctacacgct cccgcccagc cgggacgagc tcaccaagaa tcaggtcagt 3420

Page 529 625 aded

20780‐15A_SequenceListing.TXT ctgacctgcc tggtgaaggg cttctacccg agtgacatcg ccgtggagtg ggagtcgaat 3480

ggccagcccg agaacaacta caagacaacg ccccccgtcc tggactccga cggctccttc 3540

ttcctgtact cgaagctcac ggtcgacaag agccggtggc agcagggcaa cgtgttcagc 3600 009E

tgcagcgtca tgcacgaggc cctgcacaac cactacacgc agaagagcct gtcgctgtcc 3660 099E

ccgggaaagt gataatctag agt 3683 780 E89E

<210> 150 <0TZ> OST <211> 1649 <III> <212> DNA <ZIZ> ANC <213> Artificial Sequence <ETZ>

<220> <022> <223> LubSP_Seq6_Sc <EZZ>

<400> 150 <00 OST aagcttaccg ccaccatggc ctggaagact ctccccatct acctcctgct gctcctgtcg 60 09

gtcttcgtca tccagcaggt gtcctccgag ccgggcgacg gggcccagac ctgggcccgc 120 0800088970

ttcagcaggc ccccggcccc cgaggcggcg ggtctgttcc aggggacctt cccggacggt 180 08T

ttcctgtggg ccgtcggctc cgccgcgtac cagacggagg gcgggtggca acaacacggg 240

aagggcgcgt cgatctggga cactttcacc caccaccccc tggccccccc gggggactcg 300 00E

cggaacgcga gcctcccgct gggcgccccc agccccctcc agccggccac cggcgacgtg 360 0000080888 09E

gcgagcgaca gctacaacaa tgtcttcagg gacaccgagg ccctccggga actcggcgtc 420

acgcactacc gcttcagcat cagctgggcg cgggtcctgc cgaacggctc cgccggcgtg 480 08/

e ccgaaccgag agggcctgag gtactacagg cgcctcctgg agaggctccg ggagctgggc 540

gtacagcccg tcgtcaccct ctaccactgg gacctcccgc agcgcctgca ggacgcgtac 600 009

ggggggtggg ccaaccgcgc cctggccgac cacttccggg actacgccga gctctgcttc 660 099

cgccacttcg ggggccaggt caagtactgg atcaccatcg acaaccccta cgtcgtggcc 720 022

tggcacggct acgccaccgg tcgcctggcc ccgggcatcc ggggctcccc gcggctgggc 780 08L

tacctcgtcg cgcataacct gctgctcgcg cacgcgaagg tctggcacct ctacaacacc 840 798

agcttccggc cgacccaggg cggccaggtg agcatcgcgc tgtcgagcca ctggatcaac 900 006

ccccgccgta tgactgacca ctcgatcaag gaatgccaga agagcctgga cttcgtcctg 960 096

Page 530 OES aged

20780‐15A_SequenceListing.TXT gggtggttcg ccaagccggt gttcatcgac ggtgactacc cggaatcgat gaagaacaac 1020 0201 been ctgtcctcga tcctgcccga cttcaccgag tccgagaaga agttcattaa gggcaccgcc 1080 080T

gacttcttcg cgctgtgctt cgggcccacc ctgtccttcc agctgctgga cccccacatg 1140

aagttccgcc agctagagtc tccgaacctg cgccagctcc tgtcgtggat cgacctggag 1200

ttcaaccacc cgcagatctt catcgtcgag aacggctggt tcgtctcggg gaccaccaaa 1260 092T

cgggacgacg ccaagtatat gtactacctc aagaagttca tcatggagac cctgaaggcg 1320 OZET

e the atcaagctgg acggggtcga cgtcatcggg tacaccgcct ggtccctgat ggacggcttc 1380 08ET

gagtggcacc gcggctactc gatcagacgc ggcctgttct acgtcgactt cctgtcgcag 1440

gacaagatgc tcctgccgaa gtccagcgcg ctcttctacc agaagctgat cgagaagaac 1500 00ST

ggcttcccac cgctgcccga gaaccagcca ctcgaaggca ccttcccgtg cgacttcgcc 1560 09ST

tggggcgtcg tggacaacta catccaggtg tcgcagctca cgaagccgat ctcctcgctc 1620 9078098987 029T

accaagccgt accactgata atctagagt 1649

<210> 151 <0TZ> IST <211> 2972 <IIZ> 2267 <212> DNA <ZIZ> ANC <213> Artificial Sequence <ETZ>

<220> <022> and <223> wtSP_Seq4_Sc <EZZ>

<400> 151 <00 IST aagcttaccg ccaccatgcc cgcctccgcg cccccccgcc gcccgcgtcc tcccccgccg 60 09

agcctctccc tgctgctggt gctcctgggc ctgggcggac gccggctccg cgccgagccg 120

ggcgacggcg cgcagacctg ggcgcgcttc agccggccgc cggccccgga ggcagccggc 180 08T eee 0800880080 ctgttccagg ggaccttccc ggacggcttc ctctgggccg tcggctcggc cgcctaccag 240 DATE

accgagggtg gctggcagca gcacggcaag ggcgcctcca tctgggacac cttcacccac 300 00E

cacccgctgg ccccgccggg cgactcccgc aacgcctccc tgccgctggg cgccccctcg 360 09E

cccctgcagc cggccaccgg cgacgtggcg tcggacagct acaacaacgt gttccgcgac 420

7 accgaagccc tgcgggagct gggcgtcacc cactaccgct tctccatcag ctgggctagg 480 08/7

gtcctgccca acggcagcgc gggcgtgccc aaccgcgagg gcctgcgtta ctaccggcgc 540

Page 531 IES and

20780‐15A_SequenceListing.TXT ctgctggagc gcctgcgcga actcggggtc cagccggtcg tcaccctcta ccactgggat 600 1x14s80 009

ctgccccagc gccttcagga cgcctacggc ggctgggcca accgggccct ggccgaccac 660 099

ttccgcgact acgccgagct ctgcttccgc cactttggcg gccaggtcaa gtactggatc 720 OZL

e accatcgaca acccgtacgt cgtcgcctgg cacggctacg caaccggccg gctggccccg 780 9970080780 08L

ggcatccgcg gctccccccg cctgggctac ctcgtggcgc acaacctcct gctggcccac 840

gccaaggtgt ggcacctgta caacacctcc ttccgcccga cccaaggcgg ccaggtgtcc 900 000000000 006

atcgccctgt ccagccactg gatcaacccc cggcgcatga cggaccactc gatcaaggag 960 096

tgccagaaga gcctcgactt cgtgctgggc tggttcgcga agccggtgtt catcgacggt 1020 0201

gactacccgg agtccatgaa gaacaacctg tcctcgatcc tgcccgactt caccgagagt 1080 080T

gagaagaagt tcatcaaggg caccgccgac ttcttcgcgc tctgcttcgg ccccaccctc 1140

tcgttccagc tgctggaccc ccacatgaag ttccggcagc tggagagccc gaacctgcgc 1200 002T

cagctcctga gctggatcga cctcgagttc aatcaccccc agatcttcat cgtggagaac 1260 092T

ggttggttcg tgagcggcac caccaagcgc gacgacgcca aatacatgta ctacctgaag 1320 9577881188 OZET

aagtttatca tggagaccct gaaggcgatc aagctggacg gcgtcgacgt gatcggctac 1380 08ET

accgcctggt ccctgatgga cggcttcgag tggcaccggg ggtacagcat ccggcggggc 1440

ctgttctacg tggacttcct gtcgcaggac aagatgttgc tgcccaagtc gtcggccctc 1500 00ST

ttctaccaga agctgatcga gaagaacggc ttcccgccgc tgcccgagaa ccagcccctg 1560 09ST

gagggcacct tcccgtgcga cttcgcctgg ggcgtcgtgg acaactacat ccaggtcgac 1620 029T

accaccctga gccagttcac agacctcaac gtgtacctct gggacgtgca ccacagcaaa 1680 089T

cgcctcatca aggtcgacgg cgtagtcacc aagaagcgga agagctattg cgtggacttc 1740

gccgcgattc aaccccaaat cgcgctcctc caggagatgc acgtcaccca cttcaggttc 1800 008T

agcctcgact gggcgctgat cctgccgctc gggaaccagt cgcaggtgaa ccacacgatc 1860 098T

ctgcaatact acaggtgcat ggcgtcggag ctcgtccggg tcaacatcac ccccgtggtc 1920 026T

gccctctggc agcccatggc gcccaaccag ggcctgcccc gcctcctggc ccgccagggc 1980 086T

gcctgggaga acccgtacac cgcgctggcc ttcgcggagt acgcgcgcct ctgcttccag 2040

gagctggggc accacgtgaa gctgtggatc accatgaacg aaccctacac gcgcaacatg 2100 0012

Page 532 ZES aged

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT acatacagcg cggggcacaa cctgctgaag gcacacgccc tcgcgtggca cgtctacaac 2160 acatacagcg cggggcacaa cctgctgaag gcacacgccc tcgcgtggca cgtctacaac 2160

gaaaagttcc ggcacgccca gaacggcaag atctccatcg ccctccaggc cgactggatc 2220 gaaaagttcc ggcacgccca gaacggcaag atctccatcg ccctccaggo cgactggato 2220

gagcctgcct gcccgttctc gcagaaggac aaagaggtgg ccgagcgggt gctggagttc 2280 gagcctgcct gcccgttctc gcagaaggad aaagaggtgg ccgagcgggt gctggagttc 2280

gacatcggtt ggctggcgga gccgatcttc ggctccggcg actacccctg ggtcatgcgg 2340 gacatcggtt ggctggcgga gccgatcttc ggctccggcg actacccctg ggtcatgcgg 2340

gactggctga accagcgcaa caacttcttg cttccctact tcaccgaaga cgaaaagaag 2400 gactggctga accagcgcaa caacttcttg cttccctact tcaccgaaga cgaaaagaag 2400

ctgatccagg gaaccttcga cttcctcgcc ctcagccact acaccaccat cttggtcgac 2460 ctgatccagg gaaccttcga cttcctcgcc ctcagccact acaccaccat cttggtcgac 2460

tcggagaagg aggaccccat caagtacaac gattacctcg aggtccagga gatgacggac 2520 tcggagaagg aggaccccat caagtacaac gattacctcg aggtccagga gatgacggac 2520

atcacgtggc tcaactcgcc gtcccaggtc gcggtggtcc cctggggcct gcggaaggtg 2580 atcacgtggc tcaactcgcc gtcccaggto gcggtggtcc cctggggcct gcggaaggtg 2580

ctcaactggc tgaagttcaa gtacggcgac ctccccatgt acatcatcag caacggaatc 2640 ctcaactggc tgaagttcaa gtacggcgad ctccccatgt acatcatcag caacggaatc 2640

gacgacggcc tgcacgccga ggacgaccag ctccgtgtct actacatgca gaactacatc 2700 gacgacggcc tgcacgccga ggacgaccag ctccgtgtct actacatgca gaactacato 2700

aacgaggccc tgaaggccca catcctggac ggcatcaacc tgtgtggtta cttcgcctac 2760 aacgaggccc tgaaggccca catcctggac ggcatcaacc tgtgtggtta cttcgcctac 2760

tcattcaacg accgcaccgc cccccggttc ggcctctaca ggtacgcggc ggaccagttc 2820 tcattcaacg accgcaccgc cccccggttc ggcctctaca ggtacgcggo ggaccagtto 2820

gagcccaagg cgtcgatgaa gcactaccgc aagatcatcg acagcaacgg cttccccggc 2880 gagcccaagg cgtcgatgaa gcactaccgc aagatcatcg acagcaacgg cttccccggo 2880

ccggagaccc tcgaacgctt ctgccccgag gagttcacgg tgtgcaccga gtgcagcttc 2940 ccggagaccc tcgaacgctt ctgccccgag gagttcacgg tgtgcaccga gtgcagcttc 2940

ttccacaccc gcaagtcgtg ataatctaga gt 2972 ttccacaccc gcaagtcgtg ataatctaga gt 2972

<210> 152 <210> 152 <211> 1098 <211> 1098 <212> PRT <212> PRT <213> Artificial Sequence <213> Artificial Sequence

<220> <220> <223> Protein_1_549_Variant <223> Protein_1_549_Variant

<400> 152 <400> 152

Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser Met Pro Ala Ser Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser 1 5 10 15 1 5 10 15

Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg Leu Ser Leu Leu Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg 20 25 30 20 25 30

Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Ala Glu Pro Gly Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro 35 40 45 35 40 45

Page 533 Page 533

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Pro Ala Pro Glu Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly 50 55 60 50 55 60

Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Phe Leu Trp Ala Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp 65 70 75 80 70 75 80

Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Gln Gln His Gly Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His 85 90 95 85 90 95

Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Pro Leu Ala Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly 100 105 110 100 105 110

Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Ala Pro Ser Pro Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser 115 120 125 115 120 125

Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Tyr Asn Asn Val Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val 130 135 140 130 135 140

Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Thr His Tyr Arg Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly 145 150 155 160 145 150 155 160

Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Ser Ala Gly Val Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu 165 170 175 165 170 175

Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr Leu Glu Arg Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr 180 185 190 180 185 190

His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala His Trp Asp Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala 195 200 205 195 200 205

Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Asn Arg Ala Leu Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe 210 215 220 210 215 220

Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Arg His Phe Gly Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro 225 230 235 240 225 230 235 240

Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Tyr Val Val Ala Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly 245 250 255 245 250 255

Page 534 Page 534

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Ile Arg Gly Ser Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu 260 265 270 260 265 270

Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Leu Ala His Ala Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro 275 280 285 275 280 285

Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Thr Gln Gly Gly Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn 290 295 300 290 295 300

Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Pro Arg Arg Met Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu 305 310 315 320 305 310 315 320

Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Asp Phe Val Leu Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp 325 330 335 325 330 335

Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Tyr Pro Glu Ser Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe 340 345 350 340 345 350

Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Thr Glu Ser Glu Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala 355 360 365 355 360 365

Leu Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Leu Cys Phe Gly Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met 370 375 380 370 375 380

Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Lys Phe Arg Gln Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp 385 390 395 400 385 390 395 400

Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Ile Asp Leu Glu Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly 405 410 415 405 410 415

Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Trp Phe Val Ser Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr 420 425 430 420 425 430

Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Met Pro Ala Ser Tyr Leu Lys Lys Phe Ile Met Glu Thr Leu Lys Ala Met Pro Ala Ser 435 440 445 435 440 445

Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser Leu Ser Leu Leu Ala Pro Pro Arg Arg Pro Arg Pro Pro Pro Pro Ser Leu Ser Leu Leu 450 455 460 450 455 460

Page 535 Page 535

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg Ala Glu Pro Gly Leu Val Leu Leu Gly Leu Gly Gly Arg Arg Leu Arg Ala Glu Pro Gly 465 470 475 480 465 470 475 480

Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro Ala Pro Glu Asp Gly Ala Gln Thr Trp Ala Arg Phe Ser Arg Pro Pro Ala Pro Glu 485 490 495 485 490 495

Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Leu Trp Ala Ala Ala Gly Leu Phe Gln Gly Thr Phe Pro Asp Gly Phe Leu Trp Ala 500 505 510 500 505 510

Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Gln His Gly Val Gly Ser Ala Ala Tyr Gln Thr Glu Gly Gly Trp Gln Gln His Gly 515 520 525 515 520 525

Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Leu Ala Pro Lys Gly Ala Ser Ile Trp Asp Thr Phe Thr His His Pro Leu Ala Pro 530 535 540 530 535 540

Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Pro Ser Pro Pro Gly Asp Ser Arg Asn Ala Ser Leu Pro Leu Gly Ala Pro Ser Pro 545 550 555 560 545 550 555 560

Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Asn Asn Val Leu Gln Pro Ala Thr Gly Asp Val Ala Ser Asp Ser Tyr Asn Asn Val 565 570 575 565 570 575

Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr His Tyr Arg Phe Arg Asp Thr Glu Ala Leu Arg Glu Leu Gly Val Thr His Tyr Arg 580 585 590 580 585 590

Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala Gly Val Phe Ser Ile Ser Trp Ala Arg Val Leu Pro Asn Gly Ser Ala Gly Val 595 600 605 595 600 605

Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu Arg Leu Pro Asn Arg Glu Gly Leu Arg Tyr Tyr Arg Arg Leu Leu Glu Arg Leu 610 615 620 610 615 620

Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Trp Asp Leu Arg Glu Leu Gly Val Gln Pro Val Val Thr Leu Tyr His Trp Asp Leu 625 630 635 640 625 630 635 640

Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Arg Ala Leu Pro Gln Arg Leu Gln Asp Ala Tyr Gly Gly Trp Ala Asn Arg Ala Leu 645 650 655 645 650 655

Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His Phe Gly Ala Asp His Phe Arg Asp Tyr Ala Glu Leu Cys Phe Arg His Phe Gly 660 665 670 660 665 670

Page 536 Page 536

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val Val Ala Gly Gln Val Lys Tyr Trp Ile Thr Ile Asp Asn Pro Tyr Val Val Ala 675 680 685 675 680 685

Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg Gly Ser Trp His Gly Tyr Ala Thr Gly Arg Leu Ala Pro Gly Ile Arg Gly Ser 690 695 700 690 695 700

Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala His Ala Pro Arg Leu Gly Tyr Leu Val Ala His Asn Leu Leu Leu Ala His Ala 705 710 715 720 705 710 715 720

Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln Gly Gly Lys Val Trp His Leu Tyr Asn Thr Ser Phe Arg Pro Thr Gln Gly Gly 725 730 735 725 730 735

Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg Arg Met Gln Val Ser Ile Ala Leu Ser Ser His Trp Ile Asn Pro Arg Arg Met 740 745 750 740 745 750

Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Val Leu Thr Asp His Ser Ile Lys Glu Cys Gln Lys Ser Leu Asp Phe Val Leu 755 760 765 755 760 765

Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Pro Glu Ser Gly Trp Phe Ala Lys Pro Val Phe Ile Asp Gly Asp Tyr Pro Glu Ser 770 775 780 770 775 780

Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Glu Ser Glu Met Lys Asn Asn Leu Ser Ser Ile Leu Pro Asp Phe Thr Glu Ser Glu 785 790 795 800 785 790 795 800

Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Cys Phe Gly Lys Lys Phe Ile Lys Gly Thr Ala Asp Phe Phe Ala Leu Cys Phe Gly 805 810 815 805 810 815

Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Arg Gln Pro Thr Leu Ser Phe Gln Leu Leu Asp Pro His Met Lys Phe Arg Gln 820 825 830 820 825 830

Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Asp Leu Glu Leu Glu Ser Pro Asn Leu Arg Gln Leu Leu Ser Trp Ile Asp Leu Glu 835 840 845 835 840 845

Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Val Ser Phe Asn His Pro Gln Ile Phe Ile Val Glu Asn Gly Trp Phe Val Ser 850 855 860 850 855 860

Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Lys Lys Gly Thr Thr Lys Arg Asp Asp Ala Lys Tyr Met Tyr Tyr Leu Lys Lys 865 870 875 880 865 870 875 880

Page 537 Page 537

20780‐15A_SequenceListing.TXT 20780-15A_SequenceListing. TXT

Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Val Asp Val Phe Ile Met Glu Thr Leu Lys Ala Ile Lys Leu Asp Gly Val Asp Val 885 890 895 885 890 895

Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp His Arg Ile Gly Tyr Thr Ala Trp Ser Leu Met Asp Gly Phe Glu Trp His Arg 900 905 910 900 905 910

Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu Ser Gln Gly Tyr Ser Ile Arg Arg Gly Leu Phe Tyr Val Asp Phe Leu Ser Gln 915 920 925 915 920 925

Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys Leu Asp Lys Met Leu Leu Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys Leu 930 935 940 930 935 940

Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu Glu Ile Glu Lys Asn Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu Glu 945 950 955 960 945 950 955 960

Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Tyr Ile Gly Thr Phe Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Tyr Ile 965 970 975 965 970 975

Gln Val Ser Gln Leu Thr Lys Pro Ile Ser Ser Leu Thr Lys Pro Tyr Gln Val Ser Gln Leu Thr Lys Pro Ile Ser Ser Leu Thr Lys Pro Tyr 980 985 990 980 985 990

His Ile Lys Leu Asp Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser His Ile Lys Leu Asp Gly Val Asp Val Ile Gly Tyr Thr Ala Trp Ser 995 1000 1005 995 1000 1005

Leu Met Asp Gly Phe Glu Trp His Arg Gly Tyr Ser Ile Arg Arg Leu Met Asp Gly Phe Glu Trp His Arg Gly Tyr Ser Ile Arg Arg 1010 1015 1020 1010 1015 1020

Gly Leu Phe Tyr Val Asp Phe Leu Ser Gln Asp Lys Met Leu Leu Gly Leu Phe Tyr Val Asp Phe Leu Ser Gln Asp Lys Met Leu Leu 1025 1030 1035 1025 1030 1035

Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys Leu Ile Glu Lys Asn Pro Lys Ser Ser Ala Leu Phe Tyr Gln Lys Leu Ile Glu Lys Asn 1040 1045 1050 1040 1045 1050

Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu Glu Gly Thr Phe Gly Phe Pro Pro Leu Pro Glu Asn Gln Pro Leu Glu Gly Thr Phe 1055 1060 1065 1055 1060 1065

Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Tyr Ile Gln Val Pro Cys Asp Phe Ala Trp Gly Val Val Asp Asn Tyr Ile Gln Val 1070 1075 1080 1070 1075 1080

Page 538 Page 538

20780‐15A_SequenceListing.TXT 0780-15A_SequenceListing. TXT

Ser Gln Leu Thr Lys Pro Ile Ser Ser Leu Thr Lys Pro Tyr His Ser Gln Leu Thr Lys Pro Ile Ser Ser Leu Thr Lys Pro Tyr His 1085 1090 1095 1085 1090 1095

Page 539 Page 539

Claims (5)

THE CLAIMS DEFINING THE INVENTION ARE AS FOLLOWS:

1. A method of stabilizing Klotho protein in a mammalian blood sample, the method comprising: storing 20-800 pl of capillary blood from a mammalian subject in a container for at least 3 days at room temperature or without freezing, the capillary blood containing an amount of soluble Klotho protein, the container having a preservative or anti-coagulant disposed therein, the preservative or anti-coagulant being mixed with the capillary blood in the to container, the preservative or anti-coagulant stabilizing the soluble Klotho protein for at least 3 days at room temperature or without freezing, the preservative or anti-coagulant comprising heparin or EDTA; and after the storing step, performing an assay to quantify the amount of soluble ts Klotho protein in the capillary blood based on the amount of stabilized soluble Klotho protein in the container.

2. The method of claim 1, further comprising storing the capillary blood mixed with the preservative or anti-coagulant for at least 7 days at room temperature or without freezing, !o the preservative or anti-coagulant stabilizing the soluble Klotho protein for at least 7 days at room temperature or without freezing.

3. The method of claim 1 or claim 2, wherein the step of quantifying the amount of soluble Klotho protein comprises detecting the soluble Klotho protein using mass spectrometry, Multi-Analyte Profiling (xMAP), and/or a first antibody that binds to a portion of the soluble Klotho protein.

4. The method of claim 3, wherein the step of quantifying the amount of soluble Klotho protein further comprises detecting the soluble Klotho protein using a detection antibody that binds to a portion of the first antibody or performing an enzyme-linked immunosorbent assay (ELISA) to detect and quantify the soluble Klotho protein.

5. The method of any one of claims 1 to 4, wherein the storing step comprises storing 50-200ul of the capillary blood.