NZ618025B2 - Antibody polypeptides that antagonize cd40 - Google Patents
Antibody polypeptides that antagonize cd40 Download PDFInfo
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- NZ618025B2 NZ618025B2 NZ618025A NZ61802512A NZ618025B2 NZ 618025 B2 NZ618025 B2 NZ 618025B2 NZ 618025 A NZ618025 A NZ 618025A NZ 61802512 A NZ61802512 A NZ 61802512A NZ 618025 B2 NZ618025 B2 NZ 618025B2
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- antibody polypeptide
- bms3h269
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Abstract
Disclosed is an antibody polypeptide comprising a first variable domain, wherein the antibody polypeptide specifically binds an epitope of human CD40, wherein the antibody polypeptide competes with the binding of domain antibody (dAb) BMS3h-56-269 (SEQ ID NO: 417) to CD40, wherein CD40 comprises the amino acid sequence of SEQ ID NO: 1, and wherein the epitope comprises at least one CD40 amino acid residue selected from the group consisting of Trp109, Leu121, His122, Ser124, Ser156, Ala157, Phe158, Glu159, and His162, wherein the antibody polypeptide is a domain antibody, and wherein the binding of the antibody polypeptide to CD40 antagonizes CD40 activity, wherein the sequence is as defined in the specification. amino acid sequence of SEQ ID NO: 1, and wherein the epitope comprises at least one CD40 amino acid residue selected from the group consisting of Trp109, Leu121, His122, Ser124, Ser156, Ala157, Phe158, Glu159, and His162, wherein the antibody polypeptide is a domain antibody, and wherein the binding of the antibody polypeptide to CD40 antagonizes CD40 activity, wherein the sequence is as defined in the specification.
Description
PATENT
Attorney Docket No. 20089600-W0
ANTIBODY POLYPEPTIDES THAT ANTAGONIZE CD40
TECHNICAL FIELD
Antibodies and fragments thereof that target CD40, and do not exhibit CD40 agonist
activity, compositions comprising the same, and methods of using the same for treatment of
diseases involving CD40 activity are provided.
CROSS-REFERENCE TO RELATED APPLICATIONS
The instant application claims the benefit of U.S. Provisional Application No.
61/477,904, filed April 21, 2011, the entire contents of which are herein incorporated by
reference.
SEQUENCE LISTING
The instant application contains a Sequence Listing in ASCII format and is hereby
incorporated by reference in its entirety. Said ASCII copy, created on April 20, 2012, is named
200896WO.txt and is 1,188,533 bytes in size.
BACKGROUND
CD40 is a co-stimulatory molecule belonging to the tumor necrosis factor (TNF)
receptor superfamily that is present on antigen presenting cells (APC), including dendritic
cells, B cells, and macrophages. APCs are activated when CD40 binds its ligand, CD154
(CD40L), on T cells. CD40-mediated APC activation is involved in a variety of immune
responses, including cytokine production, up-regulation of co-stimulatory molecules (such as
CD86), and enhanced antigen presentation and B cell proliferation. CD40 can also be
expressed by endothelial cells, smooth muscle cells, fibroblasts, and epithelial cells.
CD40 activation is also involved in a variety of undesired T cell responses related to
autoimmunity, transplant rejection, or allergic responses, for example. One strategy for
controlling undesirable T cell responses is to target CD40 with an antagonistic antibody. For
example, monoclonal antibody HCD122 (Lucatumumab), formerly known as Chiron 1212, is
currently in clinical trials for the treatment of certain CD40-mediated inflammatory diseases.
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
See “Study of HCD122 (Lucatumumab) and Bendamustine Combination Therapy in CD40
Rituximab-Refractory Follicular Lymphoma,” Clinical Trials Feeds, on the Internet at
hypertext transfer protocol: clinicaltrialsfeeds.org/clinical-trials/show/NCT01275209 (last
updated January 11, 2011). Monoclonal antibodies, however, can display agonist activity. For
example, the usefulness of the anti-CD40 antibody Chi220 is limited by its weak stimulatory
potential. See Adams, et al., “Development of a chimeric anti-CD40 monoclonal antibody that
synergizes with LEA29Y to prolong islet allograft survival,” J. Immunol. 174: 542-50 (2005).
SUMMARY
Anti-CD40 antibody antagonists that do not possess partial agonist activity are still
needed in a clinical setting. Novel antibody polypeptides that specifically bind a novel epitope
of human CD40 are provided. The CD40 epitope does not overlap the Chi220 epitope, as
shown by competition analysis and by the structure derived from co-crystallization of an
antibody polypeptide with CD40. The antibody polypeptides advantageously do not exhibit
CD40 agonist activity. The antibody polypeptides are useful in the treatment of diseases
involving CD40 activation, including autoimmune diseases, transplant rejection, and allergic
responses. The antibody polypeptides comprise a variable domain. In one embodiment, the
antibody polypeptides are in the form of a domain antibody (dAb) that contains a single
variable domain. In another embodiment, the dAbs are bi-specific reagents that comprise a
second variable domain that can bind human serum albumin (HSA), for example.
Provided is an antibody polypeptide comprising a first variable domain, where said
antibody polypeptide specifically binds an epitope of human CD40, where the antibody
polypeptide competes with the binding of domain antibody (dAb) BMS3h269 (SEQ ID
NO: 417) to CD40, wherein CD40 comprises the amino acid sequence of SEQ ID NO: 1, and
where the epitope comprises at least one CD40 amino acid residue selected from the group
consisting of Trp109, Leu121, His122, Ser124, Ser156, Ala157, Phe158, Glu159, and His162;
wherein the antibody polypeptide is a domain antibody, and wherein the binding of the
antibody polypeptide to CD40 antagonizes CD40 activity.
Further provided is an antibody polypeptide where the first variable domain comprises
the amino acid sequence of one of the antibody polypeptides selected from the lineage group
consisting of BMS3h-37, BMS3h-38, BMS3h-56, and BMS3h-198, and where the first
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variable domain has an apparent binding constant of 1 pM to 100 nM. Further provided is an
antibody polypeptide where the first variable domain has an apparent binding constant of 1 pM
to 10 nM.
Also provided is an antibody polypeptide where the amino acid sequence of the first
variable domain comprises (a) a CDR1 region which differs from the CDR1 region of BMS3h-
56-269 (SEQ ID NO: 417) by up to two amino acids, (b) a CDR2 region which differs from the
CDR2 region of BMS3h269 (SEQ ID NO: 417) by up to two amino acids, (c) a CDR3
region which differs from the CDR3 region of BMS3h269 (SEQ ID NO: 417) by up to two
amino acids, (d) a FR1 region which differs from the FR1 region of BMS3h269 (SEQ ID
NO: 417) by up to two amino acids, (e) a FR2 region which differs from the FR2 region of
BMS3h269 (SEQ ID NO: 417) by up to two amino acids, (f) a FR3 region which differs
from the FR3 region of BMS3h269 (SEQ ID NO: 417) by up to two amino acids, and (g) a
FR4 region which differs from the FR4 region of BMS3h269 (SEQ ID NO: 417) by up to
two amino acids.
Also provided is an antibody polypeptide where the amino acid sequence of the first
variable domain comprises (a) a CDR1 region which differs from the CDR1 region of BMS3h-
56-269 (SEQ ID NO: 417) by up to two amino acids, (b) a CDR2 region which differs from the
CDR2 region of BMS3h269 (SEQ ID NO: 417) by up to two amino acids, (c) a CDR3
region which differs from the CDR3 region of BMS3h269 (SEQ ID NO: 417) by up to two
amino acids.
Further provided is an antibody polypeptide comprising a first variable domain,
wherein said antibody polypeptide specifically binds human CD40, wherein CD40 comprises
the amino acid sequence of SEQ ID No: 1, wherein the first variable domain comprises the
amino acid sequence of BMS3h258 (SEQ ID NO: 10) or BMS3h269 (SEQ ID NO:
417), or differs from the the amino acid sequence of BMS3h258 (SEQ ID NO: 10) or
BMS3h269 (SEQ ID NO: 417) by up to 10 amino acids.
Further provided is an antibody polypeptide where the amino acid sequence of the first
variable domain differs from the amino acid sequence of BMS3h258 (SEQ ID NO: 10) or
BMS3h269 (SEQ ID NO: 417) by up to 10 amino acids.
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Further provided is an antibody polypeptide where the amino acid sequence of the first
variable domain differs from the amino acid sequence of BMS3h258 (SEQ ID NO: 10) or
BMS3h269 (SEQ ID NO: 417) by up to 5 amino acids.
Further provided is an antibody polypeptide where the amino acid sequence of the first
variable domain differs from the amino acid sequence of BMS3h258 (SEQ ID NO: 10) or
BMS3h269 (SEQ ID NO: 417) by two amino acids.
Further provided is an antibody polypeptide where the amino acid sequence of the first
variable domain differs from the amino acid sequence of BMS3h258 (SEQ ID NO: 10) or
BMS3h269 (SEQ ID NO: 417) by one amino acid.
Further provided is an antibody polypeptide where the antibody polypeptide is selected
from the lineage group of BMS3h-56, and where the amino acid sequence of the first variable
domain further comprises: (a) a CDR1 region having a sequence X -Tyr-Glu-Y -Trp (SEQ ID
NO: 1274), where X is Asp or Gly, and Y is Met or Leu; (b) a CDR2 region having a
sequence Ala-Ile-Asn-Pro-X -Gly-Y -Z -Thr-Tyr-Tyr-Ala-Asp-Ser-Val-A -Gly (SEQ ID NO:
2 2 2 2
1275), where X is Gln, Tyr, Pro, Trp, or Ala, Y is Thr, Ser, Asn, Gly, Met, or Gln, Z is Arg,
2 2 2
Leu, Tyr, His, or Phe, and A is Lys or Met; and (c) a CDR3 region having a sequence X -Pro-
Y -Z -Phe-A -B (SEQ ID NO: 1276), where X is Leu or Pro, Y is Phe, Gln, Thr, or Met, Z
3 3 3 3 3 3 3
is Tyr, Pro, Leu, Thr, Ile, Phe, or Met, A is Gln, His, Asp, Ser, Lys, Glu, or Gly, and B is
Glu, Asp, or Tyr.
Further provided is an antibody polypeptide where the amino acid sequence of the first
variable domain comprises: (a) a FR1 region having a sequence Glu-Val-Gln-Leu-Leu-Glu-
Ser-Gly-Gly-Gly--Leu-Val-Gln-Pro-Gly-Gly-Ser-X -Arg-Leu-Ser-Cys-Ala-Ala-Ser-Gly-Phe-
Thr-Phe-Y (SEQ ID NO: 1277), where X is Leu or Arg, and Y isArg or Ala; (b) a FR2
1 1 1
region having a sequence Trp-Val-Arg-X -Ala-Pro-Gly-Y -Z -Leu-Glu-Arg-Val-Ser (SEQ ID
2 2 2
NO: 1278), where X is Gln or Arg, Y is Lys or Arg, and Z is Gly or Val; (c) a FR3 region
2 2 2
having a sequence Arg-Phe-Thr-Ile-Ser-Arg-Asp-Asn-Ser-Lys-Asn-X -Lys-Tyr-Leu-Gln-Met-
Asn-Ser-Leu-Arg-Ala-Y -Asp-Thr-Z -Val-Tyr-A -Cys-B -Lys (SEQ ID NO: 1279), where X
3 3 3 3 3
is Thr or Met, Y is Glu or Asp, Z is Ala or Ser, A is Tyr or His, and B is Ala or Thr; and (d)
3 3 3 3
a FR4 region having a sequence X -Gly-Y -Gly-Thr-Leu-Val-Thr-Val-Ser-Z (SEQ ID NO:
4 4 4
1280), where X is Trp or Arg, Y is Gln or Pro, and Z is Ser or Asn.
4 4 4
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Further provided is an antibody polypeptide where the first variable domain comprises
the amino acid sequence of BMS3h258 (SEQ ID NO: 10) or BMS3h269 (SEQ ID
NO:417).
Further provided is an antibody polypeptide where the antibody polypeptide is selected
from the lineage group of BMS3h-37, where the first variable domain comprises the sequence
Glu-Val-Gln-Leu-Leu-Glu-Ser-Gly-Gly-Gly-Leu-Val-X -Pro-Gly-Gly-Ser-Leu-Arg-Leu-Ser-
Cys-Ala-Ala-Ser-Gly-Phe-Thr-Phe-Glu-Trp-Tyr-Glu-Met-Gln-Trp-Val-Arg-Arg-Ala-Pro-Gly-
Lys-Gly-Leu-Glu-Trp-Val-Ser-Ala-Ile-Ser-Gly-Asp-Gly-Tyr-Arg-Thr-Tyr-Tyr-Ala-Asp-Ser-
Val-Lys-Gly-Arg-Phe-Thr-Ile-Ser-Arg-Asp-Asn-Ser-Lys-Asn-Thr-Leu-Tyr-Leu-Gln-Met-
Asn-Ser-Leu-Arg-Ala-Glu-Asp-Thr-Ala-Val-Tyr-Tyr-Cys-Ala-Lys-Y -Leu-Z -A -Phe-Asp-
1 1 1
-Gly-Arg-Gly-Thr-Leu-Val-Thr-Val-Ser-Ser (SEQ ID NO: 1281); and where X is Gln
Tyr-B
or Arg; Y is Glu or Gly; Z is Ala, Leu, or Glu; A is Phe or Tyr; and B is Trp or Arg.
1 1 1 1
Also provided is an antibody polypeptide where the antibody polypeptide is selected
from the lineage group of BMS3h-38, where the first variable domain comprises the sequence
Glu-Val-Gln-Leu-Leu-Ala-Ser-Gly-Gly-Gly-Leu-Val-Gln-Pro-Gly-Gly-Ser-Leu-Arg-Leu-Ser-
Cys-Ala-Ala-Ser-Gly-Phe-X -Phe-Glu-Glu-Glu-Glu-Met-Ile-Trp-Val-Arg-Gln-Ala-Pro-Gly-
Lys-Gly-Leu-Glu-Trp-Val-Ser-Y -Ile-Ser-Z -A -Gly- B -C -Thr-Tyr-Tyr-Ala-Asp-Ser-Val-
1 1 1 1 1
Lys-Gly-Arg-Phe-Thr-Ile-Ser-Arg-Asp-Asn-Ser-Lys-Asn-Thr-Leu-Tyr-Leu-Gln-Met-Asn-Ser-
Leu-Arg-Ala-Glu-Asp-Thr-Ala-Val-Tyr-Tyr-Cys-Gly-Lys-Glu-Pro-Phe-D -Tyr-Asp-Tyr-Trp-
Gly-Gln-Gly-Thr-Leu-Val-Thr-Val-Ser-Ser (SEQ ID NO: 1282); and where X is Thr or Pro;
Y is Ala or Ser; Z is Arg or Gly; A is Arg, Ser, Asn, Gln, Gly, His, or Leu; B is Tyr, Phe,
1 1 1 1
Trp, or Gly; C is Ser or Gly; and D is Arg, Met, or Pro.
Also provided is an antibody polypeptide where the antibody polypeptide is selected
from the lineage group of BMS3h-198, where the first variable domain comprises the sequence
Glu-Val-Gln-Leu-Leu-Glu-Ser-Gly-Gly-Gly-Leu-Val-Gln-Pro-Gly-Gly-Ser-Leu-Arg-Leu-Ser-
Cys-Ala-Ala-Ser-Gly-Phe-Thr-Phe-Ala-Gly-Try-Glu-X -Trp-Trp-Y -Arg-Gln-Ala-Pro-Gly-
Lys-Gly-Leu-Glu-Arg-Val-Ser-Ala-Ile-Ser-Gly-Ser-Gly-Gly-Ser-Thr-Tyr-Tyr-Ala-Asp-Ser-
Val-Lys-Gly-Arg-Phe-Thr-Ile-Ser-Arg-Asp-Z -A -Lys-Asn-Thr-Leu-Tyr-Leu-Gln-Met-Asn-
Ser-Leu-Arg-Ala-Glu-Asp-Thr-Ala-Val-Tyr-B -Cys-Ala-C -D -Pro-Tyr-Ser-E -Asp-Tyr-F -
1 1 1 1 1
G -H -Gly-Thr-Leu-Val-Thr-Val-Ser-Ser (SEQ ID NO: 1283); and where X is Met or Leu; Y
1 1 1 1
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is Val or Phe; Z is Asp or Asn; A is Ser or Thr; B is Tyr or His; C is Lys or Arg; D is Asp
1 1 1 1 1
or Glu; E is Tyr or Phe; F is Trp or Arg; G is Gly or Arg; and H is Gln or His.
1 1 1 1
Further provided is an antibody polypeptide where the antibody polypeptide is a
domain antibody (dAb).
Further provided is an antibody polypeptide where the variable domain is fused to an
Fc domain.
Further provided is an antibody polypeptide where the antibody polypeptide further
comprises a second variable domain that specifically binds a second antigen, where the second
antigen is an antigen other than human CD40.
Also provided is an antibody polypeptide where the second antigen is a cluster of
differentiation (CD) molecule or a Major Histocompatibility Complex (MHC) Class II
molecule.
Also provided is an antibody polypeptide where the second antigen is serum albumin
(SA).
Provided is a nucleic acid encoding the antibody polypeptide disclosed herein.
Also provided is a vector comprising the nucleic acid disclosed herein.
Also provided is a host cell comprising the vector disclosed herein.
Provided is a pharmaceutical composition comprising a therapeutically-effective
amount of the antibody polypeptide disclosed herein and a pharmaceutically acceptable carrier.
Also provided is a pharmaceutical composition further comprising an
immunosuppressive/immunomodulatory and/or anti-inflammatory agent.
Described herein is a method of treating an immune disease in a patient in need of such
treatment, comprising administering to the patient a therapeutically effective amount of the
pharmaceutical composition disclosed herein. Also described is a method where the
pharmaceutical composition is administered in combination with an
immunosuppressive/immunomodulatory and/or anti-inflammatory agent.
Described herein is a method of treating an immune disease where the immune disease
is an autoimmune disease or a graft-related disease. Also described is a method of treating an
immune disease where the immune disease is selected from the group consisting of selected
from the group consisting of Addison’s disease, allergies, ankylosing spondylitis, asthma,
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atherosclerosis, autoimmune diseases of the ear, autoimmune diseases of the eye, autoimmune
hepatitis, autoimmune parotitis, colitis, coronary heart disease, Crohn’s disease, diabetes,
including Type 1 and/or Type 2 diabetes, epididymitis, glomerulonephritis, Graves’ disease,
Guillain-Barre syndrome, Hashimoto’s disease, hemolytic anemia, idiopathic
thrombocytopenic purpura, inflammatory bowel disease, immune response to recombinant
drug products, systemic lupus erythematosus, male infertility, multiple sclerosis, myasthenia
gravis, pemphigus, psoriasis, rheumatic fever, rheumatoid arthritis, sarcoidosis, scleroderma,
Sjogren’s syndrome, spondyloarthropathies, thyroiditis, transplant rejection, vasculitis, AIDS,
atopic allergy, bronchial asthma, eczema, leprosy, schizophrenia, inherited depression,
transplantation of tissues and organs, chronic fatigue syndrome, Alzheimer’s disease,
Parkinson’s disease, myocardial infarction, stroke, autism, epilepsy, Arthus’s phenomenon,
anaphylaxis, alcohol addiction, and drug addiction.
Also described is a method of targeting CD40 using a first variable domain that
specifically binds an epitope of human CD40 comprising the amino acid sequence of SEQ ID
NO: 1, where the antibody polypeptide competes with the binding of domain antibody (dAb)
BMS3h269 (SEQ ID NO:417).
Described herein is the use in medicine of an antibody polypeptide comprising a first
variable domain that specifically binds an epitope of human CD40 comprising the amino acid
sequence of SEQ ID NO: 1, wherein the antibody polypeptide competes with the binding of
domain antibody (dAb) BMS3h201 (SEQ ID NO: 9), or a pharmaceutically acceptable salt
thereof.
Also described is the use of an antibody polypeptide comprising a first variable domain
that specifically binds an epitope of human CD40 comprising the amino acid sequence of SEQ
ID NO: 1, wherein the antibody polypeptide competes with the binding of domain antibody
(dAb) BMS3h201 (SEQ ID NO: 9), or a pharmaceutically acceptable salt thereof, in the
preparation of a medicament for treatment of an immune disease. In some embodiments, the
pharmaceutical composition is administered in combination with an
immunosuppressive/immunomodulatory and/or anti-inflammatory agent. In further
embodiments, the immune disease is an autoimmune disease or a graft-related disease. In yet
further embodiments, the immune disease is selected from the group consisting of selected
from the group consisting of Addison’s disease, allergies, ankylosing spondylitis, asthma,
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atherosclerosis, autoimmune diseases of the ear, autoimmune diseases of the eye, autoimmune
hepatitis, autoimmune parotitis, colitis, coronary heart disease, Crohn’s disease, diabetes,
including Type 1 and/or Type 2 diabetes, epididymitis, glomerulonephritis, Graves’ disease,
Guillain-Barre syndrome, Hashimoto’s disease, hemolytic anemia, idiopathic
thrombocytopenic purpura, inflammatory bowel disease, immune response to recombinant
drug products, systemic lupus erythematosus, male infertility, multiple sclerosis, myasthenia
gravis, pemphigus, psoriasis, rheumatic fever, rheumatoid arthritis, sarcoidosis, scleroderma,
Sjogren’s syndrome, spondyloarthropathies, thyroiditis, transplant rejection, vasculitis, AIDS,
atopic allergy, bronchial asthma, eczema, leprosy, schizophrenia, inherited depression,
transplantation of tissues and organs, chronic fatigue syndrome, Alzheimer’s disease,
Parkinson’s disease, myocardial infarction, stroke, autism, epilepsy, Arthus’s phenomenon,
anaphylaxis, alcohol addiction, and drug addiction.
Also described is an antibody polypeptide comprising a first variable domain that
specifically binds an epitope of human CD40 comprising the amino acid sequence of SEQ ID
NO: 1, wherein the antibody polypeptide competes with the binding of domain antibody (dAb)
BMS3h201 (SEQ ID NO: 9), or a pharmaceutically acceptable salt thereof, for use in the
preparation of a medicament for treatment of an immune disease. The medicament can, for
example, be administered in combination with an immunosuppressive/immunomodulatory
and/or anti-inflammatory agent. The immune disease can be, for example, an autoimmune
disease or a graft-related disease. The immune disease can also be selected from the group
consisting of selected from the group consisting of Addison’s disease, allergies, ankylosing
spondylitis, asthma, atherosclerosis, autoimmune diseases of the ear, autoimmune diseases of
the eye, autoimmune hepatitis, autoimmune parotitis, colitis, coronary heart disease, Crohn’s
disease, diabetes, including Type 1 and/or Type 2 diabetes, epididymitis, glomerulonephritis,
Graves’ disease, Guillain-Barre syndrome, Hashimoto’s disease, hemolytic anemia, idiopathic
thrombocytopenic purpura, inflammatory bowel disease, immune response to recombinant
drug products, systemic lupus erythematosus, male infertility, multiple sclerosis, myasthenia
gravis, pemphigus, psoriasis, rheumatic fever, rheumatoid arthritis, sarcoidosis, scleroderma,
Sjogren’s syndrome, spondyloarthropathies, thyroiditis, transplant rejection, vasculitis, AIDS,
atopic allergy, bronchial asthma, eczema, leprosy, schizophrenia, inherited depression,
transplantation of tissues and organs, chronic fatigue syndrome, Alzheimer’s disease,
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Parkinson’s disease, myocardial infarction, stroke, autism, epilepsy, Arthus’s phenomenon,
anaphylaxis, alcohol addiction, and drug addiction.
BRIEF DESCRIPTION OF THE FIGURES
depicts the binding modes of two different co-crystal structures of human CD40
(SEQ ID NO: 1), one with the dAb BMS3h5 (SEQ ID NO: 321) and one with the Fab' of
Chi220 antibody. The BMS3h5 and Chi 220 Fab' molecules are shown as cartoons with β-
strands (represented as arrows in the dAb) and non-repetitive secondary structure (represented
as loops in th dAb). Complementarity-determing regions (CDRs) are also shown CD40 is also
shown as a cartoon with the BMS3h5 epitope residues of human CD40. The Chi220
epitope residues are also shown. Disulfide bonds are also shown The N-terminus (N) and C-
terminus (C) of CD40 are labeled.
depicts a space filling model of BMS3h5 (SEQ ID NO: 321) contacting
human CD40 (SEQ ID NO: 1), which is shown as a cartoon. Surface residues of the dAb
BMS3h5 that contact CD40 are shown. The BMS3h5 CDR3 region and FR-2 residues
Leu45, Arg47, Arg56 and Phe99 are labeled. Kabat numbering (Kabat et al., Sequences of
Immunological Interest, 5 ed., U.S. Dept. Health & Human Services, Washington, D.C.
(1991)) is used in this diagram and differs from sequential numbering in that insertion residues
are used to keep the residue numbering of the β-strands identical. Thus for BMS3h5,
sequential residue 53 becomes residue 52A, sequential residues 84, 85, and 86 become,
respectively, 82A, 82B, 82C and Kabat residue number 100 is missing (it would be between
sequential residues 103 and 104); CD40 is also represented as a cartoon with non-repetitive
secondary structure and the BMS3h5 epitope. CD40 residues that differ between human
and Macaca fascicularis (cynomolgus monkey), Ala115, Phe99, Ser126, His162, Leu121, and
Trp109, are shown in stick representation. CD40 residues that differ between human and
cynomolgus monkey that are part of the BMS3h5 epitope are Trp109, Leu121, and His162.
CD40 residues Trp109 and Leu121 lie in a cleft between the BMS3h5 CDR3 and FR-2.
Mutation of Trp109 either greatly reduces or ablates BMS3h5 activity.
depicts binding of a PEGylated anti-human CD40 dAb, BMS3h38-2C-P40Br,
on blood samples from human and primate species. shows BMS3h38-2C-P40Br
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binding to human and cynomolgus B cells; shows BMS3h38-2C-P40Br binding to
human, rhesus, and chimp B cells.
and show ClustalW2 alignments of representative
domain antibody polypeptides from lineages BMS3h-56, BMS3h-37, BMS3h-38, and BMS3h-
198, respectively.
DETAILED DESCRIPTION
Antibody polypeptides that specifically bind to human CD40 are provided. The
antibody polypeptides do not exhibit CD40 agonist activity, and the antibody polypeptides are
useful in the treatment of diseases involving CD40 activation, such as autoimmune diseases.
The antibody polypeptides may be selected using a primary screen that utilizes cell binding
assays, followed by one or more rounds of error-prone or degenerate oligonucleotide-directed
affinity maturation. As a result, a genus of antibody polypeptides that specifically bind a
single CD40 epitope are provided.
A “lineage” is a set of related antibody polypeptides that were prepared from a common
precursor by error-prone or degenerate oligonucleotide-directed affinity maturation, as
disclosed in the examples below, and that are expected to bind the same CD40 epitope. The
nomenclature of the antibody polypeptides is used to designate the various lineages. The
nomenclature “BMS3h-56,” for example, refers to antibody polypeptides of lineage 56, which
were raised against human CD40. “Lineage BMS3h-56” antibody polypeptides include
BMS3h1 through BMS3h33, and BMS3h202 through BMS3h288.
Accordingly, in one aspect, an antibody polypeptide comprises a variable domain that
specifically binds human CD40, where the antibody polypeptide competes with the binding of
any one of the domain antibodies (dAbs) listed in TABLE 3. For example, the dAb may
belong to a lineage selected from the group consisting of BMS3h-37, BMS3h-38, BMS3h-41,
BMS3h-43, BMS3h-56, BMS3h-131, BMS3h-198, and BMS3h-202, such as the dAb
BMS3h5, BMS3h201, or BMS3h258, for instance. In another aspect, an antibody
polypeptide specifically binds the same human CD40 epitope as any one of the dAbs listed in
TABLE 3. For example, the antibody polypeptide may comprise a variable domain that
specifically binds the same human CD40 epitope as the dAb BMS3h5, BMS3h201, or
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BMS3h258, for instance. As disclosed below, the human CD40 epitope may comprise
amino acid residue Trp109 of SEQ ID NO: 1, for example.
The antibody polypeptides may be domain antibodies containing a single variable
domain. The antibody polypeptides also may comprise additional domains, such as an Fc
domain. For instance, the antibody polypeptide may comprise a second variable domain that
specifically binds human serum albumin (HSA). Such dual specific antibody polypeptides
may have an increased half-life, for example.
In the Sequence Listing, SEQ ID NO: 1 is the amino acid sequence of human CD40;
SEQ ID NO: 2 is the amino acid sequence of Macaca fascicularis CD40. The amino acid
sequence of the domain antibody BMS3h5 is SEQ ID NO: 321.
As used herein, “specific binding” refers to the binding of an antigen by an antibody
polypeptide with a dissociation constant (K ) of about 1 μM or lower as measured, for
example, by surface plasmon resonance. Suitable assay systems include the BIAcore
surface plasmon resonance system and BIAcore kinetic evaluation software (e.g., version
2.1). The affinity or K for a specific binding interaction may be about 500 nM or lower or
about 300 nM or lower.
The term “about” will be understood by persons of ordinary skill in the art and will
vary to some extent on the context in which it is used. Generally, about encompasses a range
of values that are plus/minus 10% of a referenced value.
In accordance with this detailed description, the following abbreviations and definitions
apply. It must be noted that as used herein, the singular forms “a”, “an”, and “the” include
plural referents unless the context clearly dictates otherwise. Thus, for example, reference to
“an antibody” includes a plurality of such antibodies and reference to “the dosage” includes
reference to one or more dosages and equivalents thereof known to those skilled in the art, and
so forth.
1. CD40 and CD40 Activities
Antibody polypeptides are provided that bind human CD40. CD40 is also known as B-
cell surface antigen CD40, Bp50, CD40L receptor, CDw40, CDW40, MGC9013, p50,
TNFRSF5, and Tumor necrosis factor receptor superfamily member 5. Relevant structural
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information for human CD40 can be found, for example, at UniProt Accession Numbers
P25942, Q9BYU0, and Q53GN5. “Human CD40” refers to the CD40 comprising the
following amino acid sequence:
MVRLPLQCVL WGCLLTAVHP EPPTACREKQ YLINSQCCSL CQPGQKLVSD
CTEFTETECL PCGESEFLDT WNRETHCHQH KYCDPNLGLR VQQKGTSETD
TICTCEEGWH CTSEACESCV LHRSCSPGFG VKQIATGVSD TICEPCPVGF
FSNVSSAFEK CHPWTSCETK DLVVQQAGTN KTDVVCGPQD RLRALVVIPI
IFGILFAILL VLVFIKKVAK KPTNKAPHPK QEPQEINFPD DLPGSNTAAP
VQETLHGCQP VTQEDGKESR ISVQERQ (SEQ ID NO: 1).
CD40 also has been sequenced in Mus musculus, Sus scrofa, Bos taurus, Gallus gallus, Canis
familiaris, Macaca fascicularis (cynomolgus monkey), Ovis aries, Equus caballus, and Rattus
norvegicus.
Binding of the present antibody polypeptides to CD40 antagonizes CD40 activity.
“CD40 activities” include, but are not limited to, T cell activation (e.g., induction of T cell
proliferation or cytokine secretion), macrophage activation (e.g., the induction of reactive
oxygen species and nitric oxide in the macrophage), and B cell activation (e.g., B cell
proliferation, antibody isotype switching, or differentiation to plasma cells). CD40 activities
can be mediated by interaction with other molecules. “CD40 activities” include the functional
interaction between CD40 and the following molecules, which are identified by their Uniprot
Accession Number is parentheses:
CALR (P27797);
ERP44 (Q9BS26);
FBL (P22087);
POLR2H (P52434);
RFC5 (P40937);
SGK1 (O00141);
SLC30A7 (Q8NEW0);
SLC39A7 (Q92504);
TRAF2 (Q5T1L5);
TRAF3 (Q13114);
TRAF6 (Q9Y4K3);
TXN (Q5T937);
UGGT1 (Q9NYU2); and
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USP15 (Q9Y4E8).
For example, a CD40 “activity” includes an interaction with TRAF2. CD40/TRAF2
interaction activates NF-κB and JNK. See Davies et al., Mol. Cell Biol. 25: 9806-19 (2005).
This CD40 activity thus can be determined by CD40-dependent cellular NF-κB and JNK
activation, relative to a reference.
As used herein, the terms “activate,” “activates,” and “activated” refer to an increase in
a given measurable CD40 activity by at least 10% relative to a reference, for example, at least
%, 25%, 50%, 75%, or even 100%, or more. A CD40 activity is “antagonized” if the
activity is reduced by at least 10%, and in an exemplary embodiment, at least about 20%, 30%,
40%, 50%, 60%, 70%, 80%, 90%, 95%, 97%, or even 100% (i.e., no detectable activity),
relative to the absence of the antagonist. For example, an antibody polypeptide may
antagonize some or all CD40 activity, while not activating CD40. In one embodiment, the
antibody polypeptide does not activate B cell proliferation. In another embodiment, the
antibody polypeptide does not activate cytokine secretion by T cells, where the cytokine is at
least one cytokine selected from the group consisting of IL-2, IL-6, IL-10, IL-13, TNF-α,
IFN-γ.
2. The CD40 Epitope
X-ray crystallography of a complex between human CD40 (SEQ ID NO: 1) and the
dAb BMS3h5 (SEQ ID NO: 321) was used to reveal an epitope recognized by the antibody
polypeptides of the disclosure. Structural models of CD40 and BMS3h5 were fitted to
electron density data to yield seven models or versions of the CD40/BMS3h5 complex,
which come from three crystallographically independent complexes in one crystal form and
four crystallographically independent complexes in a second crystal form. The versions have
real space correlation coefficients of about 0.92 for main-chain atoms and 0.80 for side-chain
atoms. The CD40 molecule has a certain amount of flexibility in the seven versions, but the
overall nature of the CD40/BMS3h5 interaction is retained in all versions. The versions
differ in the interaction between the CD40 residue Trp109 and BMS3h5 Trp103 (Kabat
Numbering, see below). BMS3h5 Trp103 forms an edge-to-face interaction with CD40
Trp109 in one version, while forming a displaced stacking (i.e., face-to-face) interaction in
other versions.
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The shape complementarity statistic, Sc, for the seven versions ranges from 0.70 – 0.77,
which shows a higher degree of shape complementarity than for typical antibody/antigen
complexes. For example, these values compare to ranges of 0.71 – 0.76 for four
protease/protein inhibitor complexes, 0.70 – 0.74 for five oligomeric interfaces, and 0.64 –
0.68 for six antibody/antigen complexes. See Lawrence et al., “Shape Complementarity at
Protein/Protein Interfaces,” J. Mol. Biol. 234: 946-950 (1993).
A model of the human CD40/BMS3H5 complex is shown in One
BMS3h5 dAb binds to one CD40 molecule. The BMS3h5 epitope does not overlap
the Chi220 Fab' fragment epitope. All versions of the complex define a set of CD40 residues
that contact BMS3h5: Trp109, Leu121, His122, Ser124, Ser156, Ala157, Phe158, Glu159,
and His162 (with reference to SEQ ID NO: 1). CD40 residues that contact BMS3h5 in
some versions of the complex are Pro85, Asn86, Leu87, Gly88, Glu106, Glu107, Gly108,
His110, Thr112, Cys119, Val120, Gln133, Ile134, Ala135, Thr136, Ser155, and Lys160.
Val154 is a buried CD40 residue in all versions. Other CD40 residues buried in some versions
are Ser118, Arg123, Thr141, Phe151, Asp153, Cys161, and Pro163.
As used herein, the term “in contact” refers to an interatomic distance whose maximum
is determined by an atom type distance dependency as defined by Sheriff et al., J. Mol. Biol.
197: 273-296 (1987) and Sheriff, Immunomethods 3: 191-196 (1993).
As used herein, the term “buried” refers to a residue that has a least one atom with
surface area defined by the program MS (Connolly, J. Appl. Crystallogr. 16: 548-558 (1983)),
a probe sphere of 1.7Å, and atom type dependent Van der Waals radii as defined by Sheriff,
Immunomethods 3: 191-196 (1993).
shows the surface of BMS3h5 (SEQ ID NO: 321) including contacting
residues and buried residues. CD40 (SEQ ID NO: 1) is represented as a ribbon diagram with
orange representing non-repetitive secondary structure and magenta representing the epitope
residues. CD40 residues Trp109, Ala115, Leu121, Ser126, and His162, which are shown,
differ in various non-human primate sequences. CD40 residues Ala115 and Ser126 are on the
opposite side of the BMS3h5 binding site. Trp109 and Leu121 bind in a cleft that lies
between CDR3 and FR-2 (residues Leu45 and Arg47) of BMS3h5. His162 interacts with
residues in CDR2 of BMS3h5, especially Lys 56. In summary, the CD40 epitope
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comprises one or more residues listed in TABLE 1, with reference to the numbering used in
SEQ ID NO: 1.
TABLE 1
CD40 residues contacting BMS3h5:
Trp109, Leu121, His122, Ser124, Ser156,
Ala157, Phe158, Glu159, His162
BMS3h5, like the other dAbs listed in TABLE 3, was prepared by a screening and
affinity maturation method described in more detail below, using human CD40 as the antigen.
It is expected that dAbs created by affinity maturation from a common precursor dAb will bind
the same human CD40 epitope. Competition studies described below, for example, indicate
that dAbs generated from a common precursor dAb by affinity maturation compete for binding
with each other to human CD40. The same competition studies, however, show that the dAbs
do not compete with at least the Chi220 or G28-5 antibodies.
3. Antibody Polypeptides
The antibody polypeptides comprise a variable domain. In one embodiment, the
antibody polypeptides are in the form of a dAb that contains a single variable domain.
Antibody polypeptides may be full-length anti-CD40 immunoglobulin molecules comprising
two heavy (H) chains and two light (L) chains interconnected by disulfide bonds. In this
embodiment, the amino terminal portion of each chain includes a variable domain (V or V )
of about 100-110 amino acids primarily responsible for antigen recognition via the
complementarity determining regions (CDRs) contained therein. The carboxy-terminal "half"
of each heavy chain defines a constant region (Fc) primarily responsible for effector function.
Antibody polypeptides also may be “fragments” comprising a portion of the full-length
anti-CD40 immunoglobulin molecule that comprises a variable domain that specifically binds
CD40. Thus, the term “antibody polypeptides” includes an antigen-binding heavy chain, light
chain, heavy chain-light chain dimer, Fab fragment, F(ab') fragment, Fv fragment, single
chain Fv (scFv), and dAb, for example. The term “antibody polypeptides” thus includes
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polypeptides made by recombinant engineering and expression, as well as monoclonal
antibodies produced by natural recombination and secretion by hybridoma cell clones.
Light chains are classified as kappa (κ) or lambda (λ), and are characterized by a
particular constant region, C , as known in the art. Heavy chains are classified as γ, μ, α, δ, or
ε, and define the isotype of an antibody as IgG, IgM, IgA, IgD, or IgE, respectively. The
heavy chain constant region is comprised of three domains (CH1, CH2, and CH3) for IgG,
IgD, and IgA; and four domains (CH1, CH2, CH3, and CH4) for IgM and IgE. Anti-CD40
antibodies may have a heavy chain constant region selected from any of the immunoglobulin
classes (IgA, IgD, IgG, IgM, and IgE).
Each light chain variable domain (V ) and heavy chain variable domain (V ) is
composed of three CDRs and four framework regions (FRs), arranged from amino-terminus to
carboxy-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. The
three CDRs of the light chain are referred to as “LCDR1, LCDR2, and LCDR3” and the three
CDRs of the heavy chain are referred to as “HCDR1, HCDR2, and HCDR3.”
As used herein, the term “Fc domain” refers to the constant region antibody sequences
comprising CH2 and CH3 constant domains as delimited according to Kabat et al., Sequences
of Immunological Interest, 5 ed., U.S. Dept. Health & Human Services, Washington, D.C.
(1991). The Fc region may be derived from an IgG1 or an IgG4 Fc region, for example. A
variable domain may be fused to an Fc domain. In this case, the carboxyl terminus of the
variable domain (either a V or V domain, including dAbs) may be linked or fused to the
amino terminus of the Fc CH2 domain. Alternatively, the carboxyl terminus of the variable
domain may be linked or fused to the amino terminus of a CH1 domain, which itself is fused to
the Fc CH2 domain. The protein may comprise the hinge region between the CH1 and CH2
domains in whole or in part.
The CDRs contain most of the residues that form specific interactions with the antigen.
As shown in for example, CDR2 and CDR3, plus FR4 residue Trp103, form most of
the contacts between CD40 and the dAb BMS3h5. For example, the variable domain of an
antibody polypeptide comprises CDR1, CDR2, and CDR3 regions that have the same amino
acid sequence as the CDR1, CDR2, and CDR3 regions of one of the dAbs listed in TABLE 3
or that each differ from the CDR1, CDR2, and CDR3 regions by one or two amino acids. For
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example, the antibody polypeptide may comprise CDR1, CDR2, and CDR3 regions that have
the same amino acid sequence as the CDR1, CDR2, and CDR3 regions of BMS3h5,
BMS3h258, or BMS3h201, for example.
A “domain antibody” (dAb) comprises a single variable (V or V ) domain that is
capable of specifically and monovalently binding an antigen, such as CD40. For example, a
dAb may have a V structure, characteristic of a camelid dAb. A “V domain” as used herein
HH H
is meant to include a V structure. In another embodiment, the V domains of the present
HH H
invention (including all features and combination of features presented as embodiments herein)
are other than V domains. dAbs may form homo- or heterodimers in solution. Bivalent
anti-CD40 antibodies are believed to exhibit agonist activity because of the ability to cross-link
bound CD40 molecules on the cell surface. While not limited by any particular theory, it is
believed that monovalent dAbs do not activate CD40, because the dAbs do not cross-link
CD40.
As used herein, the term “variable domain” refers to immunoglobulin variable domains
defined by Kabat et al., Sequences of Immunological Interest, 5 ed., U.S. Dept. Health &
Human Services, Washington, D.C. (1991). The numbering and positioning of CDR amino
acid residues within the variable domains is in accordance with the well-known Kabat
numbering convention. For example, the Kabat numbering for BMS3h5 (SEQ ID NO:
321) is compared in TABLE 2 to the same sequence numbered sequentially. In the Kabat
numbering, BMS3h5 has insertion residues 52A, 82A, 82B, 82C, and is missing residue
100. In both numbering systems, the Ser and Thr at the N-terminus that are part of the
expression construct are given negative numbers.
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TABLE 2
1
BMS3h5 ST
CDR1_ _
Kabat 10 20 30 40 50
- | - | - | - | - |
Sequential 10 20 30 40 50
- | - | - | - | - |
BMS3h5 EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSA
______CDR2______ __
Kabat 60 70 80 90
A - | - | - | ABC - | -
Sequential 60 70 80 90 100
- | - | - | - | - |
BMS3h5 INPQGTRTYYADSVMGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKLP
CDR3_
Kabat 101 110 116
| - | -|
Sequential 110 119
- | - |
BMS3h5 FTFDDWGQGTLVTVSSAAA (SEQ ID NO: 3)
The term “human,” when applied to antibody polypeptides, means that the antibody
polypeptide has a sequence, e.g., FR and/or CH domains, derived from a human
immunoglobulin. A sequence is “derived from” a human immunoglobulin coding sequence
when the sequence is either: (a) isolated from a human individual or from a cell or cell line
from a human individual; (b) isolated from a library of cloned human antibody gene sequences
or of human antibody variable domain sequences; or (c) diversified by mutation and selection
from one or more of the polypeptides above. An “isolated” compound as used herein means
that the compound is removed from at least one component with which the compound is
naturally associated with in nature.
Antibody polypeptides can be administered to human patients while largely avoiding
the anti-antibody immune response often provoked by the administration of antibodies from
other species, e.g., mouse. For example, murine antibodies can be “humanized” by grafting
murine CDRs onto a human variable domain FR, according to procedures well known in the
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art. Human antibodies as disclosed herein, however, can be produced without the need for
genetic manipulation of a murine antibody sequence.
Variable domains may comprise one or more framework regions (FR) with the same
amino acid sequence as a corresponding framework region encoded by a human germline
antibody gene segment. For example, a domain antibody may comprise the V germline gene
segments DP47, DP45, or DP38, the V germline gene segment DPK9, the J segment JH4b,
or the J segment J 1.
Changes may be made to antibody polypeptide sequences while retaining the ability to
bind CD40 specifically. Specifically, the antibody polypeptides (e.g., a dAb) may comprise a
variant variable domain that retains the function of specifically binding the same CD40 epitope
as the dAb BMS3h5. See TABLE 1. That is, the variant variable domain may bind a
human CD40 epitope comprising at least one of Trp109, Leu121, His122, Ser124, Ser156,
Ala157, Phe158, Glu159, and His162 of SEQ ID NO: 1. In one embodiment, the variant
variable domain epitope may comprise Trp109, Leu121, His122, Ser124, Ser156, Ala157,
Phe158, Glu159, and His162. Alternatively, the variant variable domain may specifically bind
a CD40 epitope comprising CD40 residue Trp109. In yet another embodiment, the variant
variable domain may compete with BMS3h5 for specific binding to CD40. Error-prone
affinity maturation, as disclosed in the examples below, provides one exemplary method for
making and identifying antibody polypeptides with variant sequences that specifically bind the
same CD40 epitope.
For example, a variant variable domain may differ from one of the variable domains
listed in TABLE 3 by up to 10 amino acids or any integral value between, where the variant
variable domain specifically binds CD40. Alternatively, the variant variable domain may have
at least 90% sequence identity (e.g., at least 92%, 95%, or 98% sequence identity) relative to a
sequence listed in the present Sequence Listing. Non-identical amino acid residues or amino
acids that differ between two sequences may represent amino acid substitutions, additions, or
deletions. Residues that differ between two sequences appear as non-identical positions, when
the two sequences are aligned by any appropriate amino acid sequence alignment algorithm,
such as BLAST.
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It is provided that amino acid substitutions may be made to individual FR regions, such
that one or more FR comprises up to two amino acid differences relative to the amino acid
sequence of the corresponding FR encoded by a human germline antibody gene segment. It is
further provided that the variant variable domain may contain one or two amino acid
substitutions in one or more CDR. Representative variable domains that specifically bind
CD40 are listed in TABLE 3.
ClustalW2 alignments between representative variable domains of antibody
polypeptides from lineages BMS3h-56, BMS3h-37, BMS3h-38, and BMS3h-198 are shown in
and respectively. As a general rule, the degree to which an
amino acid is conserved in an alignment of related protein sequences is proportional to the
relative importance of the amino acid position to the function of the protein. That is, amino
acids that are common in all related sequences likely play an important role and cannot be
easily substituted. On the other hand, positions that vary between the sequences likely can be
substituted with other amino acids or otherwise modified, while maintaining the activity of the
protein. The alignments shown in and and the structural
relationships ascertained from and for example, can guide the construction of
variant antibody polypeptides that specifically bind an epitope of human CD40 comprising the
amino acid sequence of SEQ ID NO: 1, wherein the antibody polypeptide competes with the
binding of dAb BMS3h201 (SEQ ID NO: 9). Such variant antibody polypeptides include,
but are not limited to, those with an amino acid modification corresponding to a substitution,
insertion, or deletion with reference to any of the variable domains listed in TABLE 3. Variant
antibody polypeptides also include those with an amino acid modification corresponding to an
amino acid modification conserved between the sequences listed in TABLE 3.
The information regarding the boundaries of the V or V domains of heavy and light
chain genes may be used to design PCR primers to amplify the variable domain from a cloned
heavy or light chain coding sequence encoding an antibody polypeptide known to bind CD40.
The amplified variable domain may be inserted into a suitable expression vector, e.g., pHEN-1
(Hoogenboom et al. (1991) Nucleic Acids Res. 19:4133-4137) and expressed, either alone or as
a fusion with another polypeptide sequence, using techniques well known in the art. Based on
the disclosed amino acid and polynucleotide sequences, the fusion protein can be produced and
purified using only ordinary skill in any suitable mammalian host cell line, such as CHO, 293,
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COS, NSO, and the like, followed by purification using one or a combination of methods,
including protein A affinity chromatography, ion exchange, reverse phase techniques, or the
like.
In one aspect, the antibody polypeptide is a “dual specific” antibody polypeptide
comprising a first variable domain that specifically binds human CD40 comprising the amino
acid sequence of SEQ ID NO: 1. Dual specific antibody polypeptides comprise a second
variable domain that specifically binds a second antigen that is other than human CD40.
In another embodiment, the second antigen may be a cell surface molecule of an
immune effector cell or a soluble molecule such as a cytokine, for example. Binding of the
dual specificity antibody polypeptide could be used to antagonize CD40 and antagonize a
biological activity of the second antigen. Cell surface molecules of immune effector cells
include the cluster of differentiation (CD) molecules. Representative CD markers are listed on
the Internet at hypertext transfer protocol en.wikipedia.org/wiki/List_of_human_ clusters_of
_differentiation (last modified on February 22, 2012). Cell surface molecules of immune
effector cells also include Major Histocompatibility Complex (MHC) Class II molecules.
Antibodies against these cell surface molecules are known in the art and can be used a source
of a variable domain to construct a dual specific antibody polypeptide.
In one embodiment, antibody polypeptides of a dual specific ligand may be linked by
an “amino acid linker” or “linker.” For example, a dAb may be fused to the N-terminus of an
amino acid linker, and another dAb may be fused to the C-terminus of the linker. Although
amino acid linkers can be any length and consist of any combination of amino acids, the linker
length may be relatively short (e.g., five or fewer amino acids) to reduce interactions between
the linked domains. The amino acid composition of the linker also may be adjusted to reduce
the number of amino acids with bulky side chains or amino acids likely to introduce secondary
structure. Suitable amino acid linkers include, but are not limited to, those up to 3, 4, 5, 6, 7,
, 15, 20, or 25 amino acids in length. Representative amino acid linker sequences include
(GGGGS) (SEQ ID NO: 4), where n may be any integer between 1 and 5. Other suitable
linker sequences may be selected from the group consisting of AST (SEQ ID NO: 5),
TVAAPS (SEQ ID NO: 6), TVA (SEQ ID NO: 7), and ASTSGPS (SEQ ID NO: 8).
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The binding of the second antigen can increase the in vivo half-life of the antibody
polypeptide. For example, the second variable domain of the dual specific antibody
polypeptide may specifically bind serum albumin (SA), e.g., human serum albumin (HSA).
The antibody polypeptide formatted to bind HSA can have an increased in vivo t-α (“alpha
half-life”) or t-β (“beta half-life”) half-life relative to the same unformatted antibody
polypeptide. The t-α and t-β half-lives measure how quickly a substance is distributed in and
eliminated from the body. The linkage to HSA may be accomplished by fusion of the antibody
polypeptide with a second variable domain capable of specifically binding HSA, for example.
Anti-human serum albumin antibodies are well-known in the art. See, e.g., Abcam®, Human
Serum Albumin antibodies ab10241, ab2406, and ab8940, available on the Internet at
hypertext transfer protocol www.abcam.com/index.html, or GenWay, ALB antibody, available
on the Internet at hypertext transfer protocol www.genwaybio.com. Variable domains that
specifically bind HSA can be obtained from any of these antibodies, and then fused to an
antibody polypeptide of the disclosure using recombinant techniques that are well known in the
art.
Alternatively, the linking of the antibody polypeptide to HSA can be accomplished by
directly fusing the antibody polypeptide sequence to an HSA coding sequence using techniques
well known to the skilled artisan. The HSA coding sequences can be obtained by PCR using
primers derived from the cDNA sequence available at GenBank Accession No. NM000477, for
example.
In one embodiment, the tα-half-life of the HSA-linked domain antibody composition is
increased by 10% or more. In another embodiment, the tα-half-life of the HSA-linked domain
antibody composition is in the range of 0.25 hours to 6 hours. In another embodiment, the tβ-
half-life of the HSA-linked domain antibody composition is increased by 10% or more. In
another embodiment, the tβ-half-life of the HSA-linked domain antibody composition is in the
range of 12 to 48 hours.
In another embodiment, an antibody polypeptide may be formatted to increase its in
vivo half-life by PEGylation. In one embodiment, the PEG is covalently linked. In another
embodiment, the PEG is linked to the antibody polypeptide at a cysteine or lysine residue. In
yet another embodiment, the PEG-linked antibody polypeptide has a hydrodynamic size of at
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least 24 kD. In yet another embodiment, the total PEG size is from 20 to 60 kD, inclusive. In
yet another embodiment, the PEG-linked domain antibody has a hydrodynamic size of at least
200 kD.
PEGylation can be achieved using several PEG attachment moieties including, but not
limited to N-hydroxylsuccinimide active ester, succinimidyl propionate, maleimide, vinyl
sulfone, or thiol. A PEG polymer can be linked to an antibody polypeptide at either a
predetermined position, or can be randomly linked to the domain antibody molecule.
PEGylation can also be mediated through a peptide linker attached to a domain antibody. That
is, the PEG moiety can be attached to a peptide linker fused to an antibody polypeptide, where
the linker provides the site (e.g., a free cysteine or lysine) for PEG attachment. Methods of
PEGylating antibodies are well known in the art, as disclosed in Chapman, et al., “PEGylated
antibodies and antibody fragments for improved therapy: a review,” Adv. Drug Deliv. Rev.
54(4):531-45 (2002), for example.
Antibody polypeptides also may be designed to form a dimer, trimer, tetramer, or other
multimer. Antibody polypeptides, e.g., dAbs, can be linked to form a multimer by several
methods known in the art, including, but not limited to, expression of monomers as a fusion
protein, linkage of two or more monomers via a peptide linker between monomers, or by
chemically joining monomers after translation, either to each other directly, or through a linker
by disulfide bonds, or by linkage to a di-, tri- or multivalent linking moiety (e.g., a multi-arm
PEG). In one embodiment, the multimer can bind a single molecule of CD40.
4. Pharmaceutical Compositions and Methods of Treatment
A pharmaceutical composition comprises a therapeutically-effective amount of one or
more antibody polypeptides and optionally a pharmaceutically acceptable carrier.
Pharmaceutically acceptable carriers include, for example, water, saline, phosphate buffered
saline, dextrose, glycerol, ethanol and the like, as well as combinations thereof.
Pharmaceutically acceptable carriers can further comprise minor amounts of auxiliary
substances, such as wetting or emulsifying agents, preservatives, or buffers that enhance the
shelf-life or effectiveness of the fusion protein. The compositions can be formulated to
provide quick, sustained, or delayed release of the active ingredient(s) after administration.
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Suitable pharmaceutical compositions and processes for preparing them are well known in the
art. See, e.g., Remington, THE SCIENCE AND PRACTICE OF PHARMACY, A. Gennaro, et al., eds.,
21st ed., Mack Publishing Co. (2005).
The pharmaceutical composition further may comprise an immuno-
suppressive/immunomodulatory and/or anti-inflammatory agent. A method of treating an
immune disease in a patient in need of such treatment may comprise administering to the
patient a therapeutically effective amount of the pharmaceutical composition. Antagonizing
CD40-mediated T cell activation could inhibit undesired T cell responses occurring during
autoimmunity, transplant rejection, or allergic responses, for example. Inhibiting CD40-
mediated T cell activation could moderate the progression and/or severity of these diseases.
As used herein, a “patient” means an animal, e.g. mammal, including humans. The
patient may be diagnosed with an immune disease. “Treatment” or “treat” or “treating” refers
to the process involving alleviating the progression or severity of a symptom, disorder,
condition, or disease. An “immune disease” refers to any disease associated with the
development of an immune reaction in an individual, including a cellular and/or a humoral
immune reaction. Examples of immune diseases include, but are not limited to, inflammation,
allergy, autoimmune disease, or graft-related disease. The autoimmune disease may be
selected from the group consisting of systemic lupus erythematosus, multiple sclerosis,
rheumatoid arthritis, diabetes, psoriasis, scleroderma, atherosclerosis, inflammatory bowel
disease, and ulcerative colitis.
Diseases that can be treated by administering the pharmaceutical composition may be
selected from the group consisting of Addison’s disease, allergies, ankylosing spondylitis,
asthma, atherosclerosis, autoimmune diseases of the ear, autoimmune diseases of the eye,
autoimmune hepatitis, autoimmune parotitis, colitis, coronary heart disease, Crohn’s disease,
diabetes, including Type 1 and/or Type 2 diabetes, epididymitis, glomerulonephritis, Graves’
disease, Guillain-Barre syndrome, Hashimoto’s disease, hemolytic anemia, idiopathic
thrombocytopenic purpura, inflammatory bowel disease, immune response to recombinant
drug products (e.g., Factor VII in hemophiliacs), systemic lupus erythematosus, male
infertility, multiple sclerosis, myasthenia gravis, pemphigus, psoriasis, rheumatic fever,
rheumatoid arthritis, sarcoidosis, scleroderma, Sjogren’s syndrome, spondyloarthropathies,
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thyroiditis, transplant rejection, and vasculitis. Autoimmune-mediated conditions include, but
are not limited to, conditions in which the tissue affected is the primary target, and in some
cases, the secondary target. Such conditions include, but are not limited to, AIDS, atopic
allergy, bronchial asthma, eczema, leprosy, schizophrenia, inherited depression, transplantation
of tissues and organs, chronic fatigue syndrome, Alzheimer’s disease, Parkinson’s disease,
myocardial infarction, stroke, autism, epilepsy, Arthus’ phenomenon, anaphylaxis, alcohol
addiction, and drug addiction.
The pharmaceutical composition may be administered alone or in combination therapy,
(i.e., simultaneously or sequentially) with an immunosuppressive/immunomodulatory and/or
anti-inflammatory agent. Different immune diseases can require use of specific auxiliary
compounds useful for treating immune diseases, which can be determined on a patient-to-
patient basis. For example, the pharmaceutical composition may be administered in
combination with one or more suitable adjuvants, e.g., cytokines (IL-10 and IL-13, for
example) or other immune stimulators, e.g., chemokines, tumor-associated antigens, and
peptides. Suitable adjuvants are known in the art.
Any suitable method or route can be used to administer the antibody polypeptide or the
pharmaceutical composition. Routes of administration include, for example, oral, intravenous,
intraperitoneal, subcutaneous, or intramuscular administration. A therapeutically effective
dose of administered antibody polypeptide(s) depends on numerous factors, including, for
example, the type and severity of the immune disease being treated, the use of combination
therapy, the route of administration of the antibody polypeptide(s) or pharmaceutical
composition, and the weight of the patient. A non-limiting range for a therapeutically effective
amount of a domain antibody is 0.1-20 mg/kg, and in an aspect, 1-10 mg/kg, relative to the
body weight of the patient. The dose of antibody polypeptide(s) can be further guided by the
amount of antibody polypeptide(s) required for CD40 antagonism in in vitro and/or in vivo
models of disease states. Representative models are described below and in the examples.
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. In Vitro and In Vivo Models
The ability of antibody polypeptides of the disclosure to antagonize CD40 can be tested
in one of several available in vitro or in vivo model systems. Appropriate animal and cell
model systems are described below. Further cell assay systems are described in the examples.
5.1. Inflammatory Bowel Disease (IBD) Models:
IBD is a multifactorial immune disorder of uncertain etiology. Several mouse models
of mucosal inflammation that resemble IBD have provided insight into the mechanisms
governing both normal and pathological mucosal immune function. IBD models include using
the mucosal immunity and inflammation system of De Winter et al., Am. J. Physiol. 276:
G1317-1321 (1999). In one aspect, the injection into immunodeficient mice of a subset of
CD4(+) T lymphocytes, the CD4(+)CD45RBhigh cells, leads to inflammation of the intestine.
Pathogenesis is due in part to the secretion of proinflammatory cytokines. The induction of
colitis can be prevented by co-transfer of another CD4(+) subpopulation, the
CD4(+)CD45RBlow T cells. This population behaves analogously to the CD4(+)CD45RBhigh
population in terms of the acquisition of activation markers and homing to the host intestine.
However, their lymphokine profile when activated is different, and anti-inflammatory
cytokines secreted and/or induced by CD4(+)CD45RBlow T cells prevent colitis. De Winter et
al. provide a description of the adoptive transfer model and the factors that promote and
prevent colitis pathogenesis.
5.2. Spontaneous Arthritis Models:
A model of organ-specific disease provoked by systemic autoimmunity is provided by
Kouskoff et al., Cell 87: 811-822 (1996). Rheumatoid arthritis (RA) is a chronic joint disease
characterized by leukocyte invasion and synoviocyte activation followed by cartilage and bone
destruction. Kouskoff et al. disclose a spontaneous mouse model of RA, generated by crossing
a T cell receptor (TCR) transgenic line with the NOD strain. All offspring develop a joint
disease highly reminiscent of RA in man. The trigger for the murine disorder is chance
recognition of a NOD-derived major histocompatibility complex (MHC) class II molecule by
the transgenic TCR; progression to arthritis involves CD4+ T, B, and probably myeloid cells.
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PATENT
Attorney Docket No. 20089600-W0
.3. Collagen Induced Arthritis (CIA) Model:
A mouse model of collagen-induced arthritis is provided by Brand et al., Methods Mol.
Med. 102: 295-312 (2004). Collagen-induced arthritis (CIA) is an autoimmune disease that
can be elicited in susceptible strains of rodents (rat and mouse) and non-human primates by
immunization with type II collagen (CII), the major constituent protein of articular cartilage.
After immunization, the animals develop an autoimmune polyarthritis that shares several
clinical and histological features with RA. Susceptibility to CIA in rodents is linked to the
class II molecules of the major histocompatibility complex (MHC), and the immune response
to CII is characterized by both the stimulation of collagen-specific T cells and the production
of high titers of antibody specific for both the immunogen (heterologous CII) and the
autoantigen (mouse CII). Histologically, murine CIA is characterized by an intense synovitis
that corresponds with the clinical onset of arthritis. This experimental data is useful evaluating
CIA because of the pathological similarities between CIA and RA.
.4. Antigen Induced T Cell Proliferation In Vivo Model:
The use of adoptive transfer of T cell receptor (TCR)-transgenic T cells provides an in
vivo model for antigen-induced T-cell proliferation. Pape et al., Immunol. Rev. 156: 67-78
(1997) discloses adoptive transfer of TCR-transgenic T cells uniformly expressing an
identifiable TCR of a known peptide/MHC specificity. The model can be used to monitor the
in vivo behavior of antigen-specific T cells. Naive T cells are initially activated within T-cell
zones of secondary lymphoid tissue to proliferate in a B7-dependent manner. If adjuvants or
inflammatory cytokines are present during this period, enhanced numbers of T cells
accumulate, migrate into B-cell-rich follicles, and acquire the capacity to produce IFN-γ and
help B cells produce IgG2a. If inflammation is effectively antagonized, most of the initially
activated antigen-specific T cells disappear without entering the follicles, and the survivors are
poor producers of IL-2 and IFN-γ.
EXAMPLES
TABLE 3 lists representative anti-human CD40 variable domain amino acid sequences
useful for the antibody polypeptides of the disclosure. TABLE 4 discloses representative
nucleic acids that encode the variable domain sequences listed in TABLE 3. As is well known
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Attorney Docket No. 20089600-W0
in the art, multiple codons can encode the same amino acid. Nucleic acids encoding a protein
sequence thus include nucleic acids having codon degeneracy. The antibody polypeptides
disclosed in TABLE 3 specifically bind CD40 and were made using the reiterative
initial/primary screening and affinity maturation methodologies described in the examples that
follow.
TABLE 3
Anti-Human CD40 Variable Domain Amino Acid Sequences
BMS3h201
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFYFQEWGQGTLVTVSS (SEQ ID NO: 9)
BMS3h258
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFYFHEWGQGTLVTVSS (SEQ ID NO: 10)
BMS3h-37
EVQLLESGGGLVQPGGSLRLSCAASGFTFEWYEMQWVRQAPGKGLEWVSAISGDGYRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKELGYFDYWGQGTLVTVSS (SEQ ID NO: 11)
BMS3h-38
EVQLLESGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKEPFRFDYWGQGTLVTVSS (SEQ ID NO: 12)
BMS3h-41
EVQLLESGGGLVQPGGSLRLSCAASGFTFTEYEMIWVRQAPGKGLEWVSSISGNGANTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKEPLRFDYWGQGTLVTVSS (SEQ ID NO: 13)
BMS3h-43
EVQLLESGGGLVQPGGSLRLSCTASGFTFNMYEMSWVRQAPGKGLEWVSGISRRGFTTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKEPITYAMRYARFDYWGQGTLVTVSS (SEQ ID NO: 14)
BMS3h-56
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFIFDYWGQGTLVTVSS (SEQ ID NO: 15)
BMS3h-106
EVQLLESGGGLVQPGGSLRLSCAASGFTFSTYHMQWVRQAPGKGLEWVSMIDADGLGTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKPGPQFGQFDYWGQGTLVTVSS (SEQ ID NO: 16)
40 BMS3h-107
EVQLLESGGGLVQPGGSLRLSCAASGFTFSGYDMQWVRQAPGKGLEWVSTISASGVFTYYADSVKGRFTTSRDNSKNTL
YLQMNSLRAEDTAVYYCAKYPNRFALNNFDYWGQGTLVTVSS (SEQ ID NO: 17)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h-131
DIQMTQSPSSLSASVGDRVTITCRANSSILWALAWYQQKPGKAPKLLIESSSGLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCVQNAGWPGTFGQGTKVEIKR (SEQ ID NO: 18)
BMS3h-193
DIQMTQSPSSLSASVGDRVTITCRASQTIERRLNWYQQKPGKAPKLLIYLASRLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCHQYASPPLTFGQGTKVEIKR (SEQ ID NO: 19)
BMS3h-198
EVQLLESGGGLVQPGGSLRLSCAASGFTFAGYEMWWVRQAPGKGLERVSAISGSGGSTYYADSVKGRFTISRDDSKNTL
YLQMNSLRAEDTAVYYCAKDPYSFDYWGQGTLVTVSS (SEQ ID NO: 20)
BMS3h-202
EVQLLESGGGLVQPGGSLRLSCAASGFTFPTAEMVWVRQAPGKGLEWVSSISASGGSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKEPVSYVATFDYWGQGTLVTVSS (SEQ ID NO: 21)
BMS3h-217
DIQMTQSPSSLSASVGDRVTITCRASHFIGTLLSWYQQKPGKAPKLLITYGSLLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPATFGQGTKVEIKR (SEQ ID NO: 22)
BMS3h-1
EVQLLESGGGLVQPGGSLRLSCAASGFTFPKNEMTWVRQAPGKGLEWVSAIESDGQATYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKNRIPDLVFDYWGQGTLVTVSS (SEQ ID NO: 23)
BMS3h-2
EVQLLESGGGLVQPGGSLRLSCAASGFTFDAGAMTWVRQAPGKGLEWVSSIDKEGLSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGRIPGLVFDYWGQGTLVTVSS (SEQ ID NO: 24)
BMS3h-3
EVQLLESGGGLVQPGGSLRLSCAASGFTFGDAAMTWVRQAPGKGLEWVSAIQPMGDGTYYADSVKGRFTVSRDNSKNTL
YLQMNSLRAEDTAVYYCAKGRIPTLQFDYWGQGTLVTVSS (SEQ ID NO: 25)
BMS3h-4
EVQLLESGGGLVQPGGSLRLSCAASGFTFEDSPMTWVRQAPGKGLEWVSAITSNGYETYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGRIPTLHFDYWGQGTLVTVSS (SEQ ID NO: 26)
BMS3h-5
EVQLLESGGGLVQPGGSLRLSCAASGFTFDEHDMSWVRQAPGKGLEWVSRIGPDGFHTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGRIPTLHFDYWGQGTLVTVSS (SEQ ID NO: 27)
BMS3h-6
EVQLLESGGGLVQPGGSLRLSCAASGFTFGEYHMSWVRQAPGKGLEWVSRITPLGTLTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGRIPSLTFDYWGQGTLVTVSS (SEQ ID NO: 28)
45 BMS3h-7
EVQLLESGGGLVQPGGSLRLSCAASGFTFGTNAMSWVRQAPGKGLEWVSRISPGGDYTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGRVPDLLFDYWGQGTLVTVSS (SEQ ID NO: 29)
BMS3h-8
50 EVQLLESGGGLVQPGGSLRLSCAASGFTFPSEEMSWVRQAPGKGLEWVSRISADGANTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDAAVYYCAKGRVPDLLFDYWGQGTLVTVSS (SEQ ID NO: 30)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h-9
EVQLLESGGGLVQPGGSLRLSCAASGFTFAEDDMTWVRQAPGKGLEWVSRIAVDGDRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGKVPSLHFDYWGQGTLVTVSS (SEQ ID NO: 31)
BMS3h-10
EVQLLESGGGLVQPGGSLRLSCAASGFTFRTMDMSWVRQAPGKGLEWVSRITGDGMNTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAGDTAVYYCAKGVTPDLTFDYWGQGTLVTVSS (SEQ ID NO: 32)
BMS3h-11
EVQLLESGGGLVQPGGSLRLSCAASGFTFERDDMTWVRQAPGKGLEWVSRINAGGVHTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGVTPDLTFDYWGQGTLVTVSS (SEQ ID NO: 33)
BMS3h-12
EVQLLESGGGLVQPGGSLRLSCAASGFTFDDDSMTWVRQAPGKGLEWVSRISSDGASTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGVTPDLTFDYWGQGTLVTVSS (SEQ ID NO: 34)
BMS3h-13
EVQLLESGGGLVQPGGSLRLSCAASGFTFTEEDMTWVRQAPGKGLEWVSRIDSVGEGTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGVTPDLTFDYWGQGTLVTVSS (SEQ ID NO: 35)
BMS3h-14
EVQLLESGGGLVQPGGSLRLSCAASGFTFSDSAMSWVRQAPGKGLEWVSRIDNPGQHTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGTVPTLEFDYWGQGTLVTVSS (SEQ ID NO: 36)
BMS3h-15
EVQLLESGGGLVQPGGSLRLSCAASGFTFGQHSMTWVRQAPGKGLEWVSRIDGGGYNTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGEVPRLHFDYWGQGTLVTVSS (SEQ ID NO: 37)
BMS3h-16
EVQLLESGGGLVQPGGSLRLSCAASGFTFGQEPMTWVRQAPGKGLEWVSRIAYNGGDTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGITPNLTFDYWGQGTLVTVSS (SEQ ID NO: 38)
BMS3h-17
EVQLLESGGGLVQPGGSLRLSCAASGFTFENYPMSWVRQAPGKGLEWVSRINATGSITYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGVIPHLMFDYWGQGTLVTVSS (SEQ ID NO: 39)
BMS3h-18
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYDMSWVRQAPGKGLEWVSRITGTGNSTYYADSVKGRFTISRDNSKNTL
40 YLQMNSLRAEDTAVYYCAQGVVPYLAFDYWGQGTLVTVSS (SEQ ID NO: 40)
BMS3h-19
EVQLLESGGGLVQPGGSLRLSCAASGFTFEADAMTWVRQAPGKGLEWVSRINVDGDRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGTVPTLEFDYWGQGTLVTVSS (SEQ ID NO: 41)
BMS3h-21
EVQLLESGGGLVQPGGSLRLSCAASGFTFDRADMTWVRQAPGKGLEWVSRISGEGKCTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGMVPNLVFDYWGQGTLVTVSS (SEQ ID NO: 42)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h-22
EVQLLESGGGLVQPGGSLRLSCAASGFTFHWEPMSWVRQAPGKGLEWVSRINSSGWDTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGMVPNLVFDYWGQGTLVTVSS (SEQ ID NO: 43)
BMS3h-24
EVQLLESGGGLVQPGGSLRLSCAASGFTFADEPMTWVRQAPGKGLEWVSRIPPEGAPTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGITPNLTFDYWGQGTLVTVSS (SEQ ID NO: 44)
BMS3h-26
EVQLLESGGGLVQPGGSLRLSCAASGFTFHNHDMSWVRQAPGKGLEWVSRISRGGLQTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGIVPDLHFDYWGQGTLVTVSS (SEQ ID NO: 45)
BMS3h-27
EVQLLESGGGLVQPGGSLRLSCAASGFTFNEYPMSWVRQAPGKGLEWVSRINGDGANTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGIIPAMQFDYWGQGTLVTVSS (SEQ ID NO: 46)
BMS3h-28
EVQLLESGGGLVQPGGSLRLSCAASGFTFGDVPMSWVRQAPGKGLEWVSRIDPYGSNTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGIMPSLTFDYWGQGTLVTVSS (SEQ ID NO: 47)
BMS3h-29
EVQLLESGGGLVQPGGSLRLSCAASGFTFADYDMSWVRQAPGKGLEWVSRISALGATTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGQLPALEFDYWGQGTLVTVSS (SEQ ID NO: 48)
BMS3h-30
EVQLLESGGGLVQPGGSLRLSCAASGFTFKRYYMTWVRQAPGKDLEWVSGIVPSGNRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGRIPDLHFDYWGQGTLVTVSS (SEQ ID NO: 49)
BMS3h-31
EVQLLESGGGLVQPGGSLRLSCAASGFTFADYDMTWVRQAPGKGLEWVSRISPTGGQTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGVIPYLSFSPFDYWGQGTLVTVSS (SEQ ID NO: 50)
BMS3h-32
EVQLLESGGGLVQPGGSLRLSCAASGFTFSKYWMGWARQAPGKGLEWVSSIDSHGAGTYYADSVKGRFTISRDNSKNTL
YLQMNSLRVEDTAVYYCAKGAPKFMTTYTFDYWGQGTLVTVSS (SEQ ID NO: 51)
BMS3h-33
EVQLLESGGGLVQPGGSLRLSCAASGFTFLSYPMHWVRQAPGKGLEWVSSIDSRGSVTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGHSWTFDYWGQGTLVTVSS (SEQ ID NO: 52)
BMS3h-34
EVQLLESGGGLVQPGGSLRLSCAASGFTFANSNMTWVRQAPGKGLEWVSRINPDGGSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAEGRIPTLHFDYWGQGTLVTVSS (SEQ ID NO: 53)
45 BMS3h-35
EVQLLESGGGLVQPGGSLRLSCAASGFTFGPRRMGWVRQAPGKGLEWVSSIDDIGRRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAEGAQGVLLFDYWGQGTLVTVSS (SEQ ID NO: 54)
BMS3h-36
50 EVQLLESGGGLVQPGGSLRLSCAASGFTFEDYRMVWVRQAPGKGLEWVSSISTSGELTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAETAGQFFDYWGQGTLVTVSS (SEQ ID NO: 55)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h-39
EVQLLESGGGLVQPGGSLRLSCAASGFTFPEYEMVWVRQAPGKGLEWVSAISREGRATYYADSVKGRFTISRDNSKNTL
YLQMNNLRAEDTAVYYCAKEPVRFDYWGQGTLVTVSS (SEQ ID NO: 56)
BMS3h-40
EVQLLESGGGLVQPGGSLRLSCAASGFTFSTYEMLWVRQAPGKGLEWVSSISSSGNYTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKEPLMFDYWGQGTLVTVSS (SEQ ID NO: 57)
BMS3h-42
EVQLLESGGGLVQPGGSLRLSCAASGFTFDTEEMSWVRQAPGKGLEWVSAISPNGAFTFYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKEPILFDYWGQGTLVTVSS (SEQ ID NO: 58)
BMS3h-44
EVQLLESGGGLVQPGGSLRLSCAASGFTFGHYDMVWVRQAPGRGLEWVSTINGAGLNTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAQSASRIFDYWGQGTLVTVSS (SEQ ID NO: 59)
BMS3h-45
EVQLLESGGGLVQPGGSLRLSCAASGFTFRSYEMAWVRQAPGKGLEWVSSISTLGTKTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAQSSTHIFDYWGQGTLVTVSS (SEQ ID NO: 60)
BMS3h-46
EVQLLESGGGLVQPGGSLRLSCAASGFTFIRYEMAWVRQAPGKGLEWVSSISSSGWTTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKSDAHIFDYWGQGTLVTVSS (SEQ ID NO: 61)
BMS3h-47
EVQLLESGGGLVQPGGSLRLSCAASGFTFYAYEMAWVRQAPGKGLEWVSSISDDGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKDLGQGFDYWGQGTLVTVSS (SEQ ID NO: 62)
BMS3h-48
EVQLLESGGGLVQPGGSLRLSCAASGFTFADHGMTWVRQAPGKGLEWVSGIGPSGEATYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKDRIPNLVFDYWGQGTLVTVSS (SEQ ID NO: 63)
BMS3h-49
EVQLLESGGGLVQPGGSLRLSCAASGFTFESQDMSWVRQAPGKGLEWVSGISPNGWDTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKDRSDFDYWGQGTLVTVSS (SEQ ID NO: 64)
BMS3h-50
EVQLLESGGGLVQPGGSLRLSCAASGFTFGDYDMWWVRQAPGKGLEWVSRIRHPGGVTYYADSVKGRFTISRDNSKNTL
40 YLQMNSLRAEDTAVYYCAKAVPKGFDYWGQGTLVTVSS (SEQ ID NO: 65)
BMS3h-51
EVQLLESGGGLVQPGGSLRLSCAASGFTFRVYWMTWVRQAPGKGLEWVSSIDPQGGMTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKARIPNLEFDYWGQGTLVTVSS (SEQ ID NO: 66)
BMS3h-52
EVQLLESGGGLVQPGESLRLSCAASGFTFSAYDMTWVRQAPGKGLEWVSRINPTGSYTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKAKIPNLVFDYWGQGTLVTVSS (SEQ ID NO: 67)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h-53
EVQLLESGGGLVQPGGSLRLSCAASGFTFADSEMMWVRQAPGKGLEWVSGIAHNGGHTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKAGHPQQTEAFDYWGQGTLVTVSS (SEQ ID NO: 68)
BMS3h-54
EMQLLESGGGLVQPGGSLRLSCAASGFTFATYDMYWVRQAPGKGLEWVSKISPNGWSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKYQTHFDYWGQGTLVTVSS (SEQ ID NO: 69)
BMS3h-55
EVQLLESGGGLVQPGGSLRLSCAASGFTFSVYDMRWVRQAPGKGLEWVSTISSSGTYTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKYPKNFDYWGQGTLVTVSS (SEQ ID NO: 70)
BMS3h-57
EVQLLESGGGLVQPGGSLRLSCAASGFTFSHEDMTWVRQAPGKGLEWVSSISPNGWDTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKRTRSKFDYWGQGTLVTVSS (SEQ ID NO: 71)
BMS3h-58
EVQLLESGGGLVQPGGSLRLSCAASGFTFEKYIMGWARQAPGKGLEWVSTIDYWGQHTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKRSHLIPLQFDYWGQGTLVTVSS (SEQ ID NO: 72)
BMS3h-59
EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYAMGWVRQAPGKGLEWVSTISYVGYYTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKKALRGEAFTERFDYWGQGTLVTVSS (SEQ ID NO: 73)
BMS3h-60
EVQLLESGGGLVQPGGSLRLSCAASGFTFGPYMMHWVRQAPGKGLEWVSTIEVNGNRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKWVGSKTSSDKSFDYWGQGTLVTVSS (SEQ ID NO: 74)
BMS3h-61
EVQLLESGGGLVQPGGSLRLSCAASGFTFGTTEMAWVRQAPGKGLEWVSSIGSAGAWTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKIGGHPQGQFDYWGQGTLVTVSS (SEQ ID NO: 75)
BMS3h-62
EVQLLESGGGLVQPGGSLRLSCAASGFTFPREWMAWVRQAPGKGLEWVSSIQPMGQTTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKYSRNKGFFDYWGQGTLVTVSS (SEQ ID NO: 76)
BMS3h-63
EVQLLESGGGLVQPGGSLRLSCAASGFTFTSEYMGWVRQAPGKGLEWVSSIQRYGSTTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKHESNWETFDYWGQGTLVTVSS (SEQ ID NO: 77)
BMS3h-70
EVQLLESGGGLVQPGGSLRLSCAASGFTFSVYSMQWVRQAPGKGLEWVSAITPNGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKTLGRGSYPGVDFDYWGQGTLVTVSS (SEQ ID NO: 78)
45 BMS3h-71
EVQLLESGGGLVQPGGSLRLSCAASGFTFPSYAMTWVRQAPGKGLEWVSRITADGTVTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGSIPMLTFDYWGQGTLVTVSS (SEQ ID NO: 79)
BMS3h-72
50 EVQLLESGGGLVQPGGSLRLSCAASGFTFSTYDMIWVRQAPGKGLEWVSAISPNGTGIYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKNQSVHHAVFDYWGQGTLVTVSS (SEQ ID NO: 80)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h-73
EVQLLESGGGLVQPGGSLRLSCAASGFTFENYEMTWVRQAPGKGLEWVSRIAPHGRLTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGQIPMLDFDYWGQGTLVTVSS (SEQ ID NO: 81)
BMS3h-74
EVQLLESGGGLVQPGGSLRLSCAASGFTFSHYMMMWVRQAPGKGLEWVSTISHFGDITYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKNDMVMKNGGFDYWGQGTLVTVSS (SEQ ID NO: 82)
BMS3h-75
EVQLLESGGGLVQPGGSLRLSCAASGFTFERYDMSWVRQAPGKGLEWVSRIDSRGWSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGLVPHLRFDYWGQGTLVTVSS (SEQ ID NO: 83)
BMS3h-76
EVQLLESGGGLVQPGGSLRLSCAASGFTFANAQMTWVRQAPGKGLEWVSRIDAMGDATYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGKVPSIDYWGQGTLVTVSS (SEQ ID NO: 84)
BMS3h-77
EVQLLESGGGLVQPGGSLRLSCAASGFTFANAQMTWVRQAPGKGLEWVSRIDAMGDATYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGVIPAFDYWGQGTLVTVSS (SEQ ID NO: 85)
BMS3h-78
EVQLLESGGGLVQPGGSLRLSCAASGFTFQNDRMHWVRQAPGKGLEWVSSISATGGDTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKQTGTNRFDYWGQGTLVTVSS (SEQ ID NO: 86)
BMS3h-79
EVQLLESGGGLVQPGGSLRLSCAASGFTFNQPYMSWVRQAPGKGLEWVSSIDASGGTTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDAAVYYCAKDRIPNLVFDYWGQGTLVTVSS (SEQ ID NO: 87)
BMS3h-80
EVQLLESGGGLVQPGGSLRLSCAASGFTFDNENMTWVRQAPGKGLEWVSRIDGGGYNTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGQVPELLFDYWGQGTLVTVSS (SEQ ID NO: 88)
BMS3h-81
EVQLLESGGGLVQPGGSLRLSCAASGFTFVSSNMTWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGRIPTLVFDYWGQGTLVTVSS (SEQ ID NO: 89)
BMS3h-82
EVQLLESGGGLVQPGGSLRLSCAASGFTFVSSNMTWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTL
40 YLQMNSLRAEDTAVYYCAKDRIPNLVFDYWGQGTLVTVSS (SEQ ID NO: 90)
BMS3h-83
EVQLLESGGGLVQPGGSLRLSCAASGFTFSDDSMSWVRQAPGKGLEWVSRINDAGSSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGTIPLLEFDYWGQGTLVTVSS (SEQ ID NO: 91)
BMS3h-84
EMQLLESGGGLVQPGGSLRLSCAASGFTFVSDTMSWVRQAPGKGLEWVSRIDGTGGDTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAGDTAVYYCAKGLIPDLQFDYWGQGTLVTVSS (SEQ ID NO: 92)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h-85
EVQLLESGGGLVQPGGSLRLSCAASGFTFDEEEMTWVRQAPGKGLEWVSRIIGGGHETYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGTIPLLEFDYWGQGTLVTVSS (SEQ ID NO: 93)
BMS3h-86
EVQLLESGGGLVQPGGSLRLSCAASGFTFDNENMTWVRQAPGKDLEWVSRITERGDVTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGTVPTLEFDYWGQGTLVTVSS (SEQ ID NO: 94)
BMS3h-87
EVQLLESGGGLVQPGGSLRLSCAASGFTFDEEEMTWVRQAPGKGLEWVSRIIGGGHETYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGTVPTLEFDYWGQGTLVTVSS (SEQ ID NO: 95)
BMS3h-88
EVQLLESGGGLVQPGGSLRLSCAASGFTFHETEMTWVRQAPGKGLEWVSAINRLGQDTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGRIPGLVFDYWGQGTLVTVSS (SEQ ID NO: 96)
BMS3h-89
EVQLLESGGGLVQPGGSLRLSCAASGFTFSDDSMSWVRQAPGKGLEWVSRINDAGSSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGTVPTLEFDYWGQGTLVTVSS (SEQ ID NO: 97)
BMS3h-90
EVQLLESGGGLVQPGGSLRLSCAASGFTFDNENMTWVRQAPGKDLEWVSRITERGDVTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGRIPTLVFDYWGQGTLVTVSS (SEQ ID NO: 98)
BMS3h-91
EVQLLESGGGLVQPGGSLRLSCAASGFTFSDDSMSWVRQAPGKGLEWVSRINDAGSSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGITPNLTFDYWGQGTLVTVSS (SEQ ID NO: 99)
BMS3h-92
EVQLLESGGGLVQPGGSLRLSCAASGFTFADEPMTWVRQAPGKGLEWVSRIPPEGAPTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGLIPDLQFDYWGQGTLVTVSS (SEQ ID NO: 100)
BMS3h-93
EVQLLESGGGLVQPGGSLRLSCAASGFTFQDSDMTWVRQAPGKGLEWVSAIAAPGGSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKDRIPNLRFDYWGQGTLVTVSS (SEQ ID NO: 101)
BMS3h-94
EVQLLESGGGLVQPGGSLRLSCAASGFTFVSDTMSWVRQAPGKGLEWVSRIDGTGGDTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGQVPELLFDYWGQGTLVTVSS (SEQ ID NO: 102)
BMS3h-95
EVQLLESGGGLVQPGGSLRLSCAASGFTFQDSDMTWVRQAPGKGLEWVSAIAAPGGSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKDRIPNLVFDYWGQGTLVTVSS (SEQ ID NO: 103)
45 BMS3h-96
EVQLLESGGGLVQPGGSLRLSCAAAGFTFDLAEMTWVRQAPGKGLEWVSRIDEDGASTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDAAVYYCAEGVIPSLTFDYWGQGTLVTVSS (SEQ ID NO: 104)
BMS3h-97
50 EVQLLESGGGLVQPGGSLRLSCAASGFTFTDKHMSWVRQAPGKGLEWVSRISPDGTYTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDAAVYYCAEGVIPSLTFDYWGQGTLVTVSS (SEQ ID NO: 105)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h-98
EVQLLESGGGLVQPGGSLRLSCAASGFTFAEDDMTWVRQAPGKGLEWVSRIAVDGDRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRTEDTAVYYCAKGKTPHLVFDYWGQGTLVTVSS (SEQ ID NO: 106)
BMS3h-99
EVQLLESGGGLVQPGGSLRLSCAAAGFTFDLAEMTWVRQAPGKGLEWVSRIDEDGASTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGQVPALVFDYWGQGTLVTVSS (SEQ ID NO: 107)
BMS3h-100
EVQLLESGGGLVQPGGSLRLSCAASGFTFEDSMMSWVRQAPGKGLEWVSRIDPGGAQTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGVTPDLTFDYWGQGTLVTVSS (SEQ ID NO: 108)
BMS3h-101
EVQLLESGGGLVQPGGSLRLSCAASGFTFEHADMSWVRQASGKGLEWVSRIDNSGQSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGVTPDLTFDYWGQGTLVTVSS (SEQ ID NO: 109)
BMS3h-102
EVQLLESGGGLVQPGGSLRLSCAASGFTFSEAEMNWVRQAPGKGLEWVSRITTDGDSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGRIPTLHFDYWGQGTLVTVSS (SEQ ID NO: 110)
BMS3h-103
EVQLLESGGGLVQPGGSLRLSCAASGFTFDDSDMTWVRQAPGKSLEWVSYIRGDDDETYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKNRIPDLVFDYWGQGTLVTVSS (SEQ ID NO: 111)
BMS3h-108
EVQLLESGGGLVQPGGSLRLSCAASGFTFNVADMQWVRQAPGKGLEWVSSISPNGWDTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKHASTEGPTAFDYWGQGTLVTVSS (SEQ ID NO: 112)
BMS3h-109
EVQLLESGGGLVQPGGSLRLSCAASGFTFGPYDMGWVRQAPGKGLEWVSWISAHGSFTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKWPYKFDYWGQGTLVTVSS (SEQ ID NO: 113)
BMS3h-110
EVQLLESGGGLVQPGGSLRLSCAASGFTFGSGSMSWVRQAPGKGLEWVSRIGSNGADTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGMVPNLVFDYWGQGTLVTVSS (SEQ ID NO: 114)
BMS3h-111
EVQLLESGGGLVQPGGSLRLSCAASGFTFNRFDMTWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTL
40 YLQMNSLRAEDTAVYYCAKDRIPNLVFDYWGQGTLVTVSS (SEQ ID NO: 115)
BMS3h-112
EVQLLESGGGLVQPGGSLRLSCAASGFTFGESDMKWVRQAPGKGLEWVSSISPNGWDTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKSPSSRLKFDYWGQGTLVTVSS (SEQ ID NO: 116)
BMS3h-139
EVQLLESGGGLVQPGGSLRLSCAASGFTFDSSEMSWVRQAPGKGLEWVSSIENQGGATYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKDRIPNLVFDYWGQGTLVTVSS (SEQ ID NO: 117)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h-140
EVQLLESGGGLVQPGGSLRLSCAASGFTLDAYPMYWVRQAPGKGLEWVSWIASGGGATYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKRTKNFDYWGQGTLVTVSS (SEQ ID NO: 118)
BMS3h-141
EVQLLESGGGLVQPGGSLRLSCAASGFTFMSYSMAWVRQAPGKGLEWVSGITSNGNRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKSTGANSRNFDYWGQGTLVTVSS (SEQ ID NO: 119)
BMS3h-142
EVQLLESGGGLVQPGGSLRLSCAASGFTFEGYLMSWVRQAPGKGLEWVSSIAANGMQTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKKPRGIWDGDFDYWGQGTLVTVSS (SEQ ID NO: 120)
BMS3h-143
EVQLLESGGGLVQPGGSLRLSCAASGFTFHESTMTWVRQAPGKGLEWVSTIRHPGEFTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAGDTAVYYCAKGLIPDLQFDYWGQGTLVTVSS (SEQ ID NO: 121)
BMS3h-144
EVQLLESGGGLVQPGGSLRLSCAASGFTFAMYSMSWVRQAPGKGLEWVSSIAPPGGRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKQSLTGYSRSFDYWGQGTLVTVSS (SEQ ID NO: 122)
BMS3h-145
EVQLLESGGGLVQPGGSLRLSCAASGFTFSQNPMSWVRHAPGKGLEWVSTIPANGRPTSYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKYSQQPGRRFDYWGQGTLVTVSS (SEQ ID NO: 123)
BMS3h-146
EVQLLESGGGLVQPGGSLRLSCAASGFTFANYHMTWVRQAPGKGLEWVSSIPDSGKQTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGRIPSLLFDYWGQGTLVTVSS (SEQ ID NO: 124)
BMS3h-147
EVQLLESGGGLVQPGGSLRLSCAASGFTFAQYHMRWVRQAPGKGLEWVSTINDIGSNTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKVGGRGSFSFDYWGQGTLVTVSS (SEQ ID NO: 125)
BMS3h-148
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYDMKWVRQAPGKGLEWVSTISASGVFTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKREHAGQPPFDYWGQGTLVTVSS (SEQ ID NO: 126)
BMS3h-149
EVQLLESGGGLVQPGGSLRLSCAASGFTFNGYAMSWVRQAPGKGLEWVSTINANGKYTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKKLTLASNYFDYWGQGTLVTVSS (SEQ ID NO: 127)
BMS3h-150
EVQLLESGGGLVQPGGSLRLSCAASGFTFMDYDMKWVRQAPGKGLEWVSSITALGKKTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKDSVKYPLNLFDYWGQGTLVTVSS (SEQ ID NO: 128)
45 BMS3h-151
EVQLLESGGGLVQPGGSLRLSCAASGFTFPHYTMAWVRQAPGKGLEWVSSIQSPGWRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKYGDGLPLTFDYWGQGTLVTVSS (SEQ ID NO: 129)
BMS3h-167
50 EVQLLESGGGLVQPGGSLRLSCAASGFTFSGTPMSWVRQAPGKGLEWVSRIGDEGQETYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGVTPDLTFDYWGQGTLVTVSS (SEQ ID NO: 130)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h-168
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSSSMSWVRQAPGKGLEWVSAIGSDGPSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGRIPTLHFDYWGQGTLVTVSS (SEQ ID NO: 131)
BMS3h-169
EVQLLESGGGLVQPGGSLRLSCAASGFTFNPGEMTWVRQAPGKGLEWVSSIDGSGSSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRADDTAVYYCAKGRIPTLHFDYWGQGTLVTVSS (SEQ ID NO: 132)
BMS3h-170
EVQLLESGGGLVQPGGSLRLSCAASGFTFPESMMGWVRQAPGKGLEWVSSIGYPGATTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGGSRDDNFDYWGQGTLVTVSS (SEQ ID NO: 133)
BMS3h-171
EVQLLESGGGLVQPGGSLRLSCAASGFTFGQHSMHWVRQAPGKGLEWVSSISVPGPKTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKSLRDLRPGDSKSFDYWGQGTLVTVSS (SEQ ID NO: 134)
BMS3h-197
EVQLLESGGGLVQPGGSLRLSCAASGFTFGSAAMDWVRQAPGKGLEWVSSINDMGSNTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKQGGRFDYWGQGTLVTVSS (SEQ ID NO: 135)
BMS3h-199
EVQLLESGGGLVQPGGSLRLSCAASGFTFGYDRMAWVRQAPGKGLEWVSSIDGPGGATYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAEGRRVPDFDYWGQGTLVTVSS (SEQ ID NO: 136)
BMS3h-200
EVQLLESGGGLVQPGGSLRLSCAASGFTFGEYEMTWVRQAPGKGLEWVSRIDPFGSETYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAEGVVPDLNFDYWGQGTLVTVSS (SEQ ID NO: 137)
BMS3h-201
EVQLLESGGGLVQPGGSLRLSCAASGFTFDKYVMGWVRQAPGKGLEWVSTIGSYGGATYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKRLTLSATKFDYWGQGTLVTVSS (SEQ ID NO: 138)
BMS3h-203
EVQLLESGGGLVQPGGSLRLSCAASGFTFEDYVMGWVRQAPGKGLEWVSTIAHRGDITYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKRRRLSDYRFDYWGQGTLVTVSS (SEQ ID NO: 139)
BMS3h-204
EVQLLESGGGLVQPGGSLRLSCAASGFTFGQFDMYWVRQAPGKGLEWVSAISPAGTGTYYADSVKGRFTISRDNSKNTL
40 YLQMNSLRAEDTAVYYCAKAGDRSSLFDYRGQGTLVTVSS (SEQ ID NO: 140)
BMS3h-205
EVQLLESGGGLVQPGGSLRLSCAASGFTFKDTGMTWVRQAPGKGLEWVSSISSYGRDTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDAAVYYCAKLNAALGFDYWGQGTLVTVSS (SEQ ID NO: 141)
BMS3h-206
EVQLLESGGGLVQPGGSLRLSCAASGFTFGPYPMSWVRQAPGKGLEWVSGINAPGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAQQMSSGVFDYWGQGTLVTVSS (SEQ ID NO: 142)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h-207
EVQLLESGGGLVQPGGSLRLSCAASGFTFSNQDMTWVRQAPGKGLEWVSSIDSSGQLTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKVKSLARFDYWGQGTLVTVSS (SEQ ID NO: 143)
BMS3h-208
EVQLLESGGGLVQPGGSLRLSCAASGFTFPESDMKWVRQAPGKGLEWVSSISPNGWDTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKPAQVLFDYWGQGTLVTVSS (SEQ ID NO: 144)
BMS3h-209
EVQLLESGGGLVQPGGSLRLSCAASGFTFEQYVMGWVRQAPGKGLEWVSTIGTSGKYTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAQRRSLTRVHFDYWGQGTLVTVSS (SEQ ID NO: 145)
BMS3h-210
EVQLLESGGGLVQPGGSLRLSCAASGFTFGVEHMSWVRQAPGKGLEWVSAITGDGDRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKTVSWNGRFDYWGQGTLVTVSS (SEQ ID NO: 146)
BMS3h-211
EVQLLESGGGLVQPGGSLRLSCAASGFTFAWYNMGWVRQAPGKGLEWVSRIAPSGIITYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGLRGKFDYWGQGTLVTVSS (SEQ ID NO: 147)
BMS3h-212
EVQLLESGGGLVQPGGSLRLSCAASGFTFSNYEMRWVRQAPGKGLEWVSSISSAGTDTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKQSLNFDYWGQGTLVTVSS (SEQ ID NO: 148)
BMS3h-213
EVQLLESGGGLVQPGGSLRLSCVASGFTFDEEPMTWVRQAPGKGLEWVSIIDPGGGATYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKSNSMFDYWGQGTLVTVSS (SEQ ID NO: 149)
BMS3h-214
EVQLLESGGGLVQPGGSLRLSCAASGFTFSAYPMHWVRQAPGKGLEWVSSIASSGITTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKFTRLHFPAQFDYWGQGTLVTVSS (SEQ ID NO: 150)
BMS3h-215
EVQLLESGGGLVQPGGSLRLSCAASGFTFADYAMGWVRQAPGKGLEWVSRISPEGSRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLRPYASKFDYWGQGTLVTVSS (SEQ ID NO: 151)
BMS3h-230
EVQLLESGGGLVQPGGSLRLSCAASGFTFRPYDMGWVRQAPGKGLEWVSTISHQGNRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKVSHHFDYWGQGTLVTVSS (SEQ ID NO: 152)
BMS3h-231
EVQLLESGGGLVQPGGSLRLSCAASGFTFSAYNMWWARQAPGKGLEWVSWINSTGSRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKNWHRGRFDYWGQGTLVTVSS (SEQ ID NO: 153)
45 BMS3h-232
EVQLLESGGGLVQPGGSLRLSCAASGFTFDRYRMGWVRQAPGKGLEWVSTINRLGQSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKVKKHKFDYWGQGTLVTVSS (SEQ ID NO: 154)
BMS3h-233
50 EVQLLESGGGLVQPGGSLRLSCAASGFTFAHYNMRWVRQAPGKGLEWVSTITKTGFRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKAGQFDFDYWGQGTLVTVSS (SEQ ID NO: 155)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h-234
EVQLLESGGGLVQPGGSLRLSCAASGFTFYPYSMHWVRQAPGKGLEWVSTIDGSGMFTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAEDSLKASFDYWGQGTLVTVSS (SEQ ID NO: 156)
BMS3h-235
EVQLLESGGGLVQPGGSLRLSCAASGFTFPLYGMWWVRQAPGKGLEWVSYIGPYGHTTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKKRKKKFDYWGQGTLVTVSS (SEQ ID NO: 157)
BMS3h-236
EVQLLESGGGLVQPGGSLRLSCAASGFTFPRYRMSWVRQAPGKGLEWVSSITPYGAHTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKYGKWYFDYWGQGTLVTVSS (SEQ ID NO: 158)
BMS3h-237
EVQLLESGGGLVQPGGSLRLSCAASGFTFNEYAMRWVRQAPGKGLEWVSTIDRLGLHTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKSGPFTFDYWGQGTLVTVSS (SEQ ID NO: 159)
BMS3h-238
EVQLLESGGGLVQPGGSLRLSCAASGFTFERYNMRWVRQAPGKGLEWVSTIDRLGLATYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKAGSWSFDYWGQGTLVTVSS (SEQ ID NO: 160)
BMS3h-239
EVQLLESGGGLVQPGGSLRLSCAASGFTFGIYDMKWVRQAPGKGLEWVSTISSSGTHTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKYPQPYPFDYWGQGTLVTVSS (SEQ ID NO: 161)
BMS3h-240
EVQLLESGGGLVQPGGSLRLSCAASGFTFWVYDMRWVRQAPGKGLEWVSTISATGVHTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKYPPAGRFDYWGQGTLVTVSS (SEQ ID NO: 162)
BMS3h-241
EVQLLESGGGLVQPGGSLRLSCAASGFTFSTYDMIWVRQAPGKGLEWVSAISPNGTGTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKPPQVNTEFDYRGQGTLVTVSS (SEQ ID NO: 163)
BMS3h-243
EVQLLESGGGLVQPGGSLRLSCAASGFTFEKEDMGWVRQAPGKGLEWVSHISPNGYATYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKSWSSFDYWGQGTLVTVSS (SEQ ID NO: 164)
BMS3h-244
EVQLLESGGGLVQPGGSLRLSCAASGFTFSATPMEWARQAPGKGLEWVSTISESGYSTYYADSVKGRFTISRDNSKNTL
40 YLQMNSLRAEDTAVYYCAKWNSTTGFDYWGQGTLVTVSS (SEQ ID NO: 165)
BMS3h-245
EVQLLESGGGLVQPGGSLRLSCAASGFTFNTVDMEWVRQAPGKGLEWVSSISPNGWDTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAEAPHRAFDYWGQGTLVTVSS (SEQ ID NO: 166)
BMS3h-246
EVQLLESGGGLVQPGGSLRLSCAASGFTFEDKEMSWVRQAPGKGLEWVSRIDALGDSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAEGMVPRLKFDYWGQGTLVTVSS (SEQ ID NO: 167)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h-247
EVQLLESGGGLVQPGGSLRLSCAASGFTFSDHSMMWVRQAPGKGLEWVSDIEPHGVHTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCANPTFDYWGQGTLVTVSS (SEQ ID NO: 168)
BMS3h-248
EVQLLESGGGLVQPGGSLRLSCAASGFTFSPHTMHWVRQAPGKGLEWVSGIGPDGTTTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKRSYSWDRGWTFDYWGQGTLVTVSS (SEQ ID NO: 169)
BMS3h-249
EVQLLESGGGLVQPGGSLRLSCAASGFTFYASDMKWVRQAPGKGLEWVSSISPNGWDTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKADYTYHSFDYWGQGTLVTVSS (SEQ ID NO: 170)
BMS3h-250
EVQLLESGGGLVQPGGSLRLSCAASGFTFAHYNMRWVRQAPGKGLEWVSTITKTGFRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKAGQFDFDYWGQGTLVTVSS (SEQ ID NO: 171)
BMS3h-251
EVQLLESGGGLVQPGGSLRLSCAASGFTFSHYHMGWARQAPGKGLEWVSVIGPRGISTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKSPSRHRFDYWGQGTLVTVSS (SEQ ID NO: 172)
BMS3h-252
EVQLLESGGGLVQPGGSLRLSCAASGFTFNEYAMRWVRQAPGKGLEWVSTIDRLGLHTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKSGPFTFDYWGQGTLVTVSS (SEQ ID NO: 173)
BMS3h-253
EVQLLESGGGLVQPGGSLRLSCAASGFTFGNYSMKWARQAPGKGLEWVSTITPDGWYTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKVGDAVWGWIGGFDYWGQGTLVTVSS (SEQ ID NO: 174)
BMS3h-254
EVQLLESGGGLVQPGGSLRLSCAASGFTFGDYGMKWVRQAPGKGLEWVSAITSNGDFTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKSLYKFDYWGQGTLVTVSS (SEQ ID NO: 175)
BMS3h-255
EVQLLESGGGLVQPGGSLRLSCAGSGFTFPTYKMGWVRQAPGKGLEWVSFIDYWGWRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKSPYSWTHDSPHFDYWGQGTLVTVSS (SEQ ID NO: 176)
BMS3h-256
EVQLLESGGGLVQPGGSLRLSCAASGFTFRPYTMCWARQAPGKGLEWVSCISDAGSFTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKRMSSFDYWGQGTLVTVSS (SEQ ID NO: 177)
BMS3h-257
EVQLLESGGGLVQPGGSLRLSCAASGFTFQNYQMAWVRQAPGKGLEWVSTISGTGKNTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKTPQNYFSVRRFDYWGQGTLVTVSS (SEQ ID NO: 178)
45 BMS3h-258
EVQLLESGGGLVQPGGSLRLSCAASGFTFGAYTMGWVRQAPGKGLEWVSKISTSGGQTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKPLNWWAFDYWGQGTLVTVSS (SEQ ID NO: 179)
BMS3h-272
50 EVQLLESGGGLVQPGGSLRLSCAASGFTFNAYPMTWVRQAPGKGLEWVSRIDGYGRHTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGIIPNFDYWGQGTLVTVSS (SEQ ID NO: 180)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h-273
EVQLLESGGGLVQPGGSLRLSCAASGFTFGAVDMTWVRQAPGKGLEWVSAISPSGSATYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGRVPDLGFDYWGQGTLVTVSS (SEQ ID NO: 181)
BMS3h-274
EVQLLESGGGLVQPGGSLRLSCAASGFTFDSYAMGWARQAPGKGLEWVSAIGAKGLSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKAARGKFDYWGQGTLVTVSS (SEQ ID NO: 182)
BMS3h-275
EVQLLESGGGLVQPGGSLRLSCAASGFTFTRYQMGWVRQAPGKGLEWVSVINVWGSSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKMSGKFAYWGQGTLVTVSS (SEQ ID NO: 183)
BMS3h-276
EVQLLESGGGLVQPGGSLRLSCAASGFTFGNYSMMWVRQAPGKGLEWVSTIIPAGTSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKPSIRLFDYWGQGTLVTVSS (SEQ ID NO: 184)
BMS3h-279
EVQLLESGGGLVQPGGSLRLSCAASGFTFGAYDMGWVRQAPGKGLEWVSWISPNGYDTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGGVKFDYWGQGTLVTVSS (SEQ ID NO: 185)
BMS3h-282
EVQLLESGGGLVQPGGSLRLSCAASGFTFVWYEMAWVRQAPGKGLEWVSTIQADGEQTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKASYALVYPPEEFDYWGQGTLVTVSS (SEQ ID NO: 186)
BMS3h-287
EVQLLESGGGLVQPGGSLRLSCAASGFTFTNYRMSWVRQAPGKGLEWVSAIDDLGVSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKWRLKNSQPTDFDYWGQGTLVTVSS (SEQ ID NO: 187)
BMS3h-292
EVQLLESGGGLVQPGGSLRLSCAASGFTFDQAHMWWVRQAPGKGLEWVSFINPSGYYTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKPSLSPSSFDYWGQGTLVTVSS (SEQ ID NO: 188)
BMS3h-293
EVQLLESGGGLVQPGGSLRLSCAASGFTFETGQMGWARQAPGKGLEWVSNIDGSGTYTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKSTQNYRFDYWGQGTLVTVSS (SEQ ID NO: 189)
BMS3h-296
EVQLLESGGGLVQPGGSLRLSCAASGFTFGAYPMYWVRQAPGKGLEWVSSIHKDGRITYYADSVKGRFTISRDNSKNTL
40 YLQMNSLRAEDTAVYYCAKQGTPVDGFDYWGQGTLVTVSS (SEQ ID NO: 190)
BMS3h-297
EVQLLESGGGLVQPGGSLRLSCAASGFTFPDEGMTWVRQAPGKGLEWVSTIETGGTVTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKMDGSGTWQTFDYWGQGTLVTVSS (SEQ ID NO: 191)
BMS3h-298
EVQLLESGGGLVQPGGSLRLSCAASGFTFDSLGMGWARQAPGKGLEWVSYIRAEGAYTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKYLADSDYWGQGTLVTVSS (SEQ ID NO: 192)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h-299
EVQLLESGGGLVQPGGSLRLSCAASGFTFSESYMEWVRQAPGKGLEWVSGIDHIGGGTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKDDGRGGSMFDYWGQGTLVTVSS (SEQ ID NO: 193)
BMS3h-300
EVQLLESGGGLVQPGGSLRLSCAASGFTFSGGYMWWVRQAPGKGLEWVSSIGASGAYTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKTGGRLDYWGQGTLVTVSS (SEQ ID NO: 194)
BMS3h-301
EVQLLESGGGLVQPGGSLRLSCAASGFTFDEGHMGWVRQAPGKDLEWVSYIGSLGLHTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKREFSNGGFDYWGQGTLVTVSS (SEQ ID NO: 195)
BMS3h-302
EVQLLESGGGLVQPGGSLRLSCAASGFTFKTSPMYWVRQAPGKGLEWVSSIDRTGGHTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKQALLTDAKRFDYWGQGTLVTVSS (SEQ ID NO: 196)
BMS3h-303
EVQLLESGGGLVQPGGSLRLSCAASGFTFDGRDMVWVRQAPGKGLEWVSAISPSGLDTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAERPQMLVTNFDYWGQGTLVTVSS (SEQ ID NO: 197)
BMS3h-304
EVQLLESGGGLVQPGGSLRLSCAASGFTFGNDPMSWVRQAPGKGLEWVSGIGREGDSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKDSMRHQPFDYWGQGTLVTVSS (SEQ ID NO: 198)
BMS3h-305
EVQLLESGGGLVQPGGSLRLSCAASGFTFDETYMKWVRQAPGKGLEWVSAIGASGADTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKFTHLNGRFDYWGQGTLVTVSS (SEQ ID NO: 199)
BMS3h-306
EVQLLESGGGLVQPGGSLRLSCAASGFTFGGWPMGWVRQAPGKGLEWVSGIDIDGAPTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKEEAGSWSFDYWGQGTLVTVSS (SEQ ID NO: 200)
BMS3h-307
EVQLLESGGGLVQPGGSLRLSCAASGFTFSDQAMWWARQAPGKGLEWVSFIQGDGGFTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKPSKPFDYWGQGTLVTVSS (SEQ ID NO: 201)
BMS3h-308
EVQLLESGGGLVQPGGSLRLSCAASGFTFETGQMGWARQAPGKGLEWVSNIDGSGTYTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKAVRNFAFDYWGQGTLVTVSS (SEQ ID NO: 202)
BMS3h-309
EVQLLESGGGLVQPGGSLRLSCAASGFTFSGHDMSWVRQAPGKGLEWVSAISPHGTHTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGIRGWIGHDTQPFDYWGQGTLVTVSS (SEQ ID NO: 203)
45 BMS3h-310
EVQLLESGGGLVQPGGSLRLSCAASGFTFESKDMLWVRQAPGKGLEWVSSISSDGTHTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAQELGGSWQFDYWGQGTLVTVSS (SEQ ID NO: 204)
BMS3h-311
50 EVQLLESGGGLVQPGGSLRLSCAASGFTFADRDMVWVRQAPGKGLEWVSGIGASGTSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDAAVYYCAKGGTGPTDLWDFDYWGQGTLVTVSS (SEQ ID NO: 205)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h-312
EVQLLESGGGLVQPGGSLRLSCAASGFTFDDEKMLWVRQAPGKGLEWVSSISVSGLHTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKEEAGSWSFDYWGQGTLVTVSS (SEQ ID NO: 206)
BMS3h-313
EVQLLESGGGLVQPGGSLRLSCAASGFTFGQERMIWVRQAPGKGLEWVSDISASGGTTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKEEAGSWSFDYWGQGTLVTVSS (SEQ ID NO: 207)
BMS3h1
EVQLLESGGGLVQPGGSLRLSCAASGFTFEWYEMQWVRQAPGKGLEWVSAISGDGYRTYYADSVKGRFTISRDNSMNTL
YLQMNSLRAEDTAVYYCAKELGYFDYRGRGTLVTVSS (SEQ ID NO: 208)
BMS3h2
EVQLLESGGGLVQPGGSLRLSCAASGFTFEWYEMQWVRRAPGKGLEWVSAISGDGYRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKELGYFDYWGRGTLVTVSS (SEQ ID NO: 209)
BMS3h3
EVQLLESGGGLVQPGGSLRLSCAASGFTFEWYEMQWVRRAPGKGLEWVSAISGDGYRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKELGYFDYRVQGTLVTVSS (SEQ ID NO: 210)
BMS3h4
EVQLLESGGGLVQPGGSLRLSCAASGFTFEWYEMQWVRKAPGKGLEWVSAISGDGYRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKELGYFDYWGRGTLVTVSS (SEQ ID NO: 211)
BMS3h5
EVQLLESGGGLVQPGGSLRLSCAASGFTFEWYEMQWVRQAPGKGLEWISAISGDGYRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKELGYFDYRVQGTLVTVSS (SEQ ID NO: 212)
BMS3h6
EVQLLESGGGLVQPGGSLRLSCAASGFTFEWYEMQWVRRAPGKGLEWVSAISGDGYRTYYADSVKGRFTISRDNSENTL
YLQMNSLRAEDTAVYYCAKELGYFDYWGRGTLVTVSS (SEQ ID NO: 213)
BMS3h7
EVQLLETGGGLVQPGGSLRLSCAASGFTFEWYEMQWVRRAPGKGLEWVSAISGDGYRTYYADSVKGRFTISRDNSKNTL
YLQMDSLRAEDTAVYYCAKELGYFDYWGRGTLVTVTS (SEQ ID NO: 214)
BMS3h8
EVQLLESGGGLVQPGGSLRLSCAASGFTFEWYEMQWVRQAPGKGLEWVSAISGDGYRTYYADSVKGRFTISRDNSKNTL
40 YLQMNSLRAEDTAVYYCAKELGYFHYWGRGTLVTVSS (SEQ ID NO: 215)
BMS3h9
EVQLLESGGGLVQPGGSLRLSCVASGFTFEWYEMQWVRQAPGNGLEWISAISGDGYRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKELGYFDYWGRGTLVTVSS (SEQ ID NO: 216)
BMS3h10
EVQLLESGGGLVQPGGSLRLSCAASGFTFEWYEMQWVRRAPGKGLEWVSAISGDGYRTYYADSVKGRFTISRDNSKNTL
YLLMNSLRAEDTAVYYCAKELGYFDYWGRGTLVTVSS (SEQ ID NO: 217)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h11
EVQLLESGGGLVQPGGSLRLSCAASGFTFEWYEMQWVRKAPGKGLEWVSAISGDGYRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKELGYFDYRGRGTLVTVSS (SEQ ID NO: 218)
BMS3h12
EVQLLESGGGLVQPGGSMRLSCAASGFTFEWYEMQWVRRAPGKGLEWVSAISGDGYRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKELGYFDYRGRGTLVTVSS (SEQ ID NO: 219)
BMS3h201
EVQLLESGGGLVQPGGSLRLSCAASGFTFEWYEMQWVRRAPGKGLEWVSMISGDGYRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKELGYFDYWGRGTLVTVSS (SEQ ID NO: 220)
BMS3h202
EVQLLESGGGLVQPGGSLRLSCAASGFTFEWYEMQWVRRAPGKGLEWVSAISGDGWRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKELGYFDYWGRGTLVTVSS (SEQ ID NO: 221)
BMS3h203
EVQLLESGGGLVQPGGSLRLSCAASGFTFGWYEMQWVRRAPGKGLEWVSAISGDGYRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKELLYFDYWGRGTLVTVSS (SEQ ID NO: 222)
BMS3h204
EVQLLESGGGLVQPGGSLRLSCAASGFTFEWYEMQWVRRAPGKGLEWVSAISGDGYRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKELGFFDYWGRGTLVTVSS (SEQ ID NO: 223)
BMS3h205
EVQLLESGGGLVQPGGSLRLSCAASGFTFEWYEMQWVRRAPGKGLEWVSAISGDGYRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKELEYFDYWGRGTLVTVSS (SEQ ID NO: 224)
BMS3h206
EVQLLESGGGLVQPGGSLRLSCAASGFTFEWYEMQWVRRAPGKGLEWVSAISGDGYRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKGLEYFDYWGRGTLVTVSS (SEQ ID NO: 225)
BMS3h207
EVQLLESGGGLVQPGGSLRLSCAASGFTFEWYEMQWVRRAPGKGLEWVSAISGDGYRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKELAFFDYWGRGTLVTVSS (SEQ ID NO: 226)
BMS3h208
EVQLLESGGGLVQPGGSLRLSCAASGFTFEWYEMQWVRRAPGKGLEWVSAISGDGYRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKELLYFDYWGRGTLVTVSS (SEQ ID NO: 227)
BMS3h209
EVQLLESGGGLVQPGGSLRLSCAASGFTFEWYEMQWVRRAPGKGLEWVSAISGDGYRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKELEFFDYWGRGTLVTVSS (SEQ ID NO: 228)
45 BMS3h210
EVQLLESGGGLVQPGGSLRLSCAASGFTFEWYEMQWVRRAPGKGLEWVSAISGDGYRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKELQFFDYWGRGTLVTVSS (SEQ ID NO: 229)
BMS3h211
50 EVQLLESGGGLVQPGGSLRLSCAASGFTFEWYEMQWVRRAPGKGLEWVSAISGDGYRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKELLFFDYWGRGTLVTVSS (SEQ ID NO: 230)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h212
EVQLLESGGGLVRPGGSLRLSCAASGFTFEWYEMQWVRRAPGKGLEWVSAISGDGYRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKELEFFDYWGRGTLVTVSS (SEQ ID NO: 231)
BMS3h213
EVQLLESGGGLVQPGGSLRLSCAASGFTFEWYEMQWVRRAPGKGLEWVSAISGDGYRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKELLFFDYRGRGTLVTVSS (SEQ ID NO: 232)
BMS3h214
EVQLLESGGGLVQPGGSLRLSCAASGFIFEWYEMQWVRRAPGKGLEWVSAISGDGYRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKNLEYFDYWGRGTLVTVSS (SEQ ID NO: 233)
BMS3h215
EVRLLESGGGLVQPGGSLRLSCAASGFTFEWYEMQWVRRAPGKGLEWVSAISGDGYRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKELQFFDYWGRGTLVTVSS (SEQ ID NO: 234)
BMS3h1
EVQLLGSGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCSKEPFRFDYWGQGTLVTVSS (SEQ ID NO: 235)
BMS3h2
EVQLLASGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSS (SEQ ID NO: 236)
BMS3h3
EVQLLASGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWISAISGSGGSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFRFDYWGQGTLVTVSS (SEQ ID NO: 237)
BMS3h4
EVQLLDPGGGLVQPGGSLRLSCAASGFTFGKEEMIWVRQAPGKGLEWVSSISGSGGSTYYADSVKGRFTISRDNSRNTL
YLQMNSLRAEDTAVYYCGKEPFRFDYWGQGTLVTVSS (SEQ ID NO: 238)
BMS3h5
EVQLLGSGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFRFDYWGQGTLVTVSS (SEQ ID NO: 239)
BMS3h6
EVQLLEPGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTL
40 YLLMNSLRAEDTAVYYCSKEPFRFDYWGQGALVTVSS (SEQ ID NO: 240)
BMS3h7
EVQLLDPGGGLVQPGGSLRLSCAASGFTFGKEEMIWVRQAPGKGLEWVSSISGSGGSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKEPLRFDYWGQGTLVTVSS (SEQ ID NO: 241)
BMS3h8
EVQLLESGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWISAISGSGGSTYYADSVKGRFTIHRDNSKNTL
YLQMNSLRAEDTAVYYCSKEPFRFDYRGLGTLVTVSS (SEQ ID NO: 242)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h9
EVQLLDPGGGLVQPGGSLRLSCAASGFTFGKEEMIWVRQAPGKGLEWVSSISGSGGSTYYADSVKGRFTISRDNSRNTL
YLQMNSLRAEDTAVYYCAKEPLRFDYWGQGTLVTVSS (SEQ ID NO: 243)
BMS3h10
EVQLLDSGGGFVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWISAISGSGGSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKEPFRFDYWGQGTLVTVSS (SEQ ID NO: 244)
BMS3h11
EVQLLDPGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWISAISGSGGSTYYADSVKGRFTISRDNSNNTL
YLQMNSLRAEDTAVYYCGREPFRFDYWGQGTLVTVSS (SEQ ID NO: 245)
BMS3h12
EVRLLESGEGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFRFDYWGQGTLVTVSS (SEQ ID NO: 246)
BMS3h13
EVQQLESGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFRFDYWGQGTLVTVSS (SEQ ID NO: 247)
BMS3h201
EVQLLASGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFYYDYWGQGTLVTVSS (SEQ ID NO: 248)
BMS3h202
EVQLLASGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFYFDYWGQGTLVTVSS (SEQ ID NO: 249)
BMS3h203
EVQLLASGGGLVQPGGSLRLSCAASGFTFEEKEMIWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFFYDYWGQGTLVTVSS (SEQ ID NO: 250)
BMS3h204
EVQLLASGGGLVQPGGSLRLSCAASGFTFPQEEMIWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSS (SEQ ID NO: 251)
BMS3h205
EVQLLASGGGLVQPGGSLRLSCAASGFTFFAAEMIWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSS (SEQ ID NO: 252)
BMS3h206
EVQLLASGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISRPGTSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSS (SEQ ID NO: 253)
45 BMS3h207
EVQLLASGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISRMGFSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSS (SEQ ID NO: 254)
BMS3h208
50 EVQLLASGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISRWGHSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSS (SEQ ID NO: 255)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h209
EVQLLASGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISRLGWSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSS (SEQ ID NO: 256)
BMS3h210
EVQLLASGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISRWGASTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSS (SEQ ID NO: 257)
BMS3h211
EVQLLASGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISRQGGSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSS (SEQ ID NO: 258)
BMS3h212
EVQLLASGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISVSGWSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSS (SEQ ID NO: 259)
BMS3h213
EVQLLASGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISRWGWSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSS (SEQ ID NO: 260)
BMS3h214
EVQLLASGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISRNGLSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSS (SEQ ID NO: 261)
BMS3h215
EVQLLASGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISGLGWSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSS (SEQ ID NO: 262)
BMS3h216
EVQLLASGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISALGWSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSS (SEQ ID NO: 263)
BMS3h217
EVQLLASGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISRRGYSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSS (SEQ ID NO: 264)
BMS3h218
EVQLLASGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISRHGWSTYYADSVKGRFTISRDNSKNTL
40 YLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSS (SEQ ID NO: 265)
BMS3h219
EVQLLASGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSSISRSGGSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSS (SEQ ID NO: 266)
BMS3h220
EVQLLASGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISRIGNSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSS (SEQ ID NO: 267)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h221
EVQLLASGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISGHGWSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSS (SEQ ID NO: 268)
BMS3h222
EVQLLASGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISRWGGSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSS (SEQ ID NO: 269)
BMS3h223
EVQLLASGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFMYDYWGQGTLVTVSS (SEQ ID NO: 270)
BMS3h224
EVQLLASGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFPYDYWGQGTLVTVSS (SEQ ID NO: 271)
BMS3h225
EVQLLASGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISGSGGGTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSS (SEQ ID NO: 272)
BMS3h226
EVQLLASGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPLYYDYWGQGTLVTVSS (SEQ ID NO: 273)
BMS3h227
EVQLLASGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPMYYDYWGQGTLVTVSS (SEQ ID NO: 274)
BMS3h228
EVQLLASGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISRNGFSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSS (SEQ ID NO: 275)
BMS3h229
EVQLLASGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISRTGGSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSS (SEQ ID NO: 276)
BMS3h230
EVQLLASGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISREGGSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSS (SEQ ID NO: 277)
BMS3h231
EVQLLASGGGLVQPGGSLRLSCAASGFPFEEEEMIWVRQAPGKGLEWVSAISRQGWSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSS (SEQ ID NO: 278)
45 BMS3h232
EVQLLASGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISRGGGSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSS (SEQ ID NO: 279)
BMS3h233
50 EVQLLASGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISRTGYSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSS (SEQ ID NO: 280)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h234
EVQLLASGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISRNGRSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSS (SEQ ID NO: 281)
BMS3h235
EVQLLASGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISRNGYSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSS (SEQ ID NO: 282)
BMS3h236
EVQLLASGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISRKGSSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSS (SEQ ID NO: 283)
BMS3h237
EVQLLASGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISRGGWSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSS (SEQ ID NO: 284)
BMS3h238
EVQLLASGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISRSGYSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSS (SEQ ID NO: 285)
BMS3h239
EVQLLASGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISRNGMSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSS (SEQ ID NO: 286)
BMS3h240
EVQLLESGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISRNGYSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSS (SEQ ID NO: 287)
BMS3h1
EVQLLESGEGLVQPGGSLRLSCAASGFTFTEHEMIWVRQAPGKGLEWVSSISGNGANTYYADSVKGRFTISRDNSKNTL
YLQMNSLRPEDTAVYYCAKEPLRFDYWGQGTLVTVSS (SEQ ID NO: 288)
BMS3h2
EVQLLESGGGLVQPGGSLRLSCAASGSTFTEYEMIWVRQAPGKGLEWISSISGNGANTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYFCAKEPLRFDYRGQGTLVTVSS (SEQ ID NO: 289)
BMS3h3
EVQLLEPGGGLVQPGGSLRLSCAASGFTFTEYEMIWVRKAPGKGMEWVSSISGNGANTYYADSVKGRFTISRDNSKNML
40 YLQMNSLRAEDTAVYYCAKEPLRFGYWGQGTLVTVSS (SEQ ID NO: 290)
BMS3h4
EVQLLDSGGGLVQPGGSLRLSCAASGFTFTEYEMIWVRQAPGKGLEWVSSISGNGANTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKEPLRFDYWGRGTLVTVSS (SEQ ID NO: 291)
BMS3h5
EVQLLGSGGGLVQPGGSLRLSCAASGFTFTEYEMIWVRQAPGKSLEWVSSISGNGANTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKEPLRYDDWGQGTLVTVSS (SEQ ID NO: 292)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h6
EVQPLESGGGLVQPGGSLRLSCSASGFTFNEYEMIWVRQAPGKGLEWVSSISGNGANTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKEPLRFDYWGQGTLVTVSS (SEQ ID NO: 293)
BMS3h7
EVQLLESGEGLVQPGGSLRLSCAASGFTFAEYEMIWVRQAPGKGLEWVSSISGNGANTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKEPLRFDYWGQGTLVTVSS (SEQ ID NO: 294)
BMS3h8
EVQLLDPGGGLVQPGGSLRLSCAASGFTFTESEMIWVRQAPGKGLEWVSSISGNGANTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKEPLRFDYWGQGTLVTVSS (SEQ ID NO: 295)
BMS3h9
EVQLLEPGGGLVQPGGSLRLSCAASGFTFTEYEMIWVRKAPGKGMEWVSSISGNGANTYYADSVKGRFTISRDNSKNTL
YLQMNSLRPEDTAVYYCAKEPLRFDDWGQGTLVTVSS (SEQ ID NO: 296)
BMS3h10
EVQLLESGVGLVQPGGSLRLSCAASGFTFTEYEMIWVRKAPGKGLEWVSSISGNGANTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKEPLRFDNWGQGTLVTVSS (SEQ ID NO: 297)
BMS3h11
EVQLLESRGGLVQPGGSLRLSCAASGFTFTEHEMIWVRQAPGKGLEWVSSISGNGANTYYADSVKGRFSVSRDNSKNTL
YLQMNSLRAEDTAVYYCAKEPLRFDYWGQGTLVTVSS (SEQ ID NO: 298)
BMS3h12
EVQPLESGGGLVQPGGSLRLSCAASGFTFTEYEMIWVRQAPGKGLEWVSSISGNGANTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKEPLRFDYWGQGTLVTVSS (SEQ ID NO: 299)
BMS3h13
EVQLLESAGGLVQPGGSLRLSCAASGFTFAEYEMIWVRQAPGKGLEWVSSISGNGANTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKEPLRFDYWGQGALVTVSS (SEQ ID NO: 300)
BMS3h14
EVQLLEPGGGLVQPGGSLRLSCAASGFTFTEYEMIWVRQAPGKGLEWVSSISGNGANTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKEPLRFDNWGQGTLVTVSS (SEQ ID NO: 301)
BMS3h1
EVQLLESGGGLVQPGGSLRLSCTASGFTFNMYEMSWVRQAPGKGLEWVSGISRRGFTTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKEPITYDLRYARFDYSGQGTLVTVSS (SEQ ID NO: 302)
BMS3h2
EEQLLESGGGLVQPGGSLRLSCTASGFTFNMYEMSWVRQAPGKGLEWVSGISRRGFTTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKEPITYATRYARFDYWGQGTLVTVSS (SEQ ID NO: 303)
45 BMS3h3
EVQLLESGGGLVQPGGSLRLSCTASGFTFNMYEMSWVRQAPGKGLEWVSGISRRGFTTYYADSVKGRFTISRDNFKNTL
YLQMNSLRAEDTAVYYCAKEPITYDMRYARFDYGGQGTLVTVSS (SEQ ID NO: 304)
BMS3h4
50 EVQLLESGGGLVQPGGSLRLSCTASGFTFNMYEMSWVRQAPGKGLEWVSGISRRGFTTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKEPITYDMRYARFDNWGQGTLVTVSN (SEQ ID NO: 305)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h5
EVQLLESGGGLVQPGGSLRLSCTASGFTFNTYEMSWVRQAPGKGLEWVSGIGRRGFTTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKEPITYDLRYARFDYSGQGTLVTVSS (SEQ ID NO: 306)
BMS3h6
EVQLMESGGGLVQPGGSLRLSCTASGFSFNMYEMSWVRQAPGKGLEWVSGISRRGYTTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKEPITYDMRYARFDYWGRGTLVTVSS (SEQ ID NO: 307)
BMS3h7
EVQLLESGGGLVQPGGSLRLSCTASGFAFNMYEMSWVRQAPGKGLEWVSGISRHGFTTYYADSVKGRFTVSRDNSKNTL
YLQMNSLRAEDTAVYYCAKEPITYDMRYARSDYWGQGTLVTVSS (SEQ ID NO: 308)
BMS3h8
EVQLLESGGGLVQPGGSLRLSCTASGFTFNMYEMSWVRQAPGKGLEWVSGISRRGFTTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYFCAKEPITYDMRYARSDYWGQGTLVTVSS (SEQ ID NO: 309)
BMS3h9
EVQLLESGGGLVQPGGSLRLSCTASGFTFNMYEMSWVRQAPGKGLEWVSGISRRGFTTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKEPITYSMRYARFDYSGLGTMVTVSS (SEQ ID NO: 310)
BMS3h10
EVQLLESGGGLVQPGGSLRLSCTASGFTFNMYEMSWVRQAPGKGLEWVSGISRRGFTTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKEPITYDMRYARFDYSGQGTLVTVSS (SEQ ID NO: 311)
BMS3h11
EVQLLESGGGLVQPGGSLRLSCTASGFTFNMYEMSWVRKAPGKGLEWVSGISRHGFTTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKEPITYDMRYARFDYWGQGTLVTVSS (SEQ ID NO: 312)
BMS3h12
EVQLFESGGGLVQPGGSLRLSCTASGFTFNMYEMSWVRQAPGKGLEWVSGISRRGFTTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKEPITYDMRYARFDYWGRGTLVTVSS (SEQ ID NO: 313)
BMS3h13
EVQLLESGGGLVQPGGSLRLSCTASGFTFNMYEMSWVRQAPGKGLEWVSGISRRGFTTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKEPITYDMRYARFDYWGRGTLVTVSS (SEQ ID NO: 314)
BMS3h14
EVQLLESGGGSVQPGGSLRLSCTASGFSFNMYEMSWVRQAPGKGLEWVSGISRRGFTTYYADSVKGRFTISRDNSKNTL
40 YLQMNSLRAEDTAVYYCAKEPITYDMRYARFDYWGQGTLVTVSG (SEQ ID NO: 315)
BMS3h15
EVQLLESGGGLVQPGGSLRLSCTASGFTFNMYEMSWVRKAPGKGLEWVSGISRRGFTTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKEPITYDMRYARFDYWGQGTLVTVSS (SEQ ID NO: 316)
BMS3h1
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFEDWGQGTLVTVSS (SEQ ID NO: 317)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h2
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFDDWGQGTLVTVSS (SEQ ID NO: 318)
BMS3h3
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCTKLPFIFEYWGQGTLVTVSS (SEQ ID NO: 319)
BMS3h4
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFMFDDRGQGTLVTVSS (SEQ ID NO: 320)
BMS3h5
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVMGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFDDWGQGTLVTVSS (SEQ ID NO: 321)
BMS3h6
EVQLLESGGGLVQPGGSLRLSCAASGFSFRDYEMWWYRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFIFDNRGQGTLVTVSS (SEQ ID NO: 322)
BMS3h7
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTSVYHCAKPPFIFGDWGPGTLVTVSS (SEQ ID NO: 323)
BMS3h8
EVQLLESGGGLVQPGGSRRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFEDWGQGTLVTVSS (SEQ ID NO: 324)
BMS3h9
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVMGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFMFDDRGQGTLVTVSS (SEQ ID NO: 325)
BMS3h10
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKVLERVSAINPQGTRTYYADSVKGRFTISRDNSKNML
YLQMNSLRAEDTAVYYCAKLPFMFDDRGQGTLVTVSS (SEQ ID NO: 326)
BMS3h11
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFMFDDRGQGTLVTVSS (SEQ ID NO: 327)
BMS3h12
EVQLLESGGGLIQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCLKLPFIFDYWGQGTLVTVSS (SEQ ID NO: 328)
45 BMS3h13
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRADDTAVYHCTKLPFIFDYWGQGTLVTVSS (SEQ ID NO: 329)
BMS3h14
50 EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGMVLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFFFDSRGQGTLVTVSS (SEQ ID NO: 330)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h15
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRRAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFEDWGQGTLVTVSS (SEQ ID NO: 331)
BMS3h16
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVMGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFEDWGQGTLVTVSS (SEQ ID NO: 332)
BMS3h17
EVQLLESGGGLVQPGGSLRLSCAASGFSFRDYEMWWYRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFEDWGQGTLVTVSS (SEQ ID NO: 333)
BMS3h18
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKVLERVSAINPQGTRTYYADSVKGRFTISRDNSKNML
YLQMNSLRAEDTAVYYCAKLPFTFEDWGQGTLVTVSS (SEQ ID NO: 334)
BMS3h19
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYHCAKLPFTFEDWGQGTLVTVSS (SEQ ID NO: 335)
BMS3h20
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCTKLPFTFEDWGQGTLVTVSS (SEQ ID NO: 336)
BMS3h21
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCLKLPFTFEDWGQGTLVTVSS (SEQ ID NO: 337)
BMS3h22
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRADDTAVYHCTKLPFIFEYWGQGTLVTVSS (SEQ ID NO: 338)
BMS3h23
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVMGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKEPYSFDSWGQGTLVTVSS (SEQ ID NO: 339)
BMS3h24
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVMGRFTISRDNSKNTL
40 YLQMNSLRAEDTAVYHCAKEPYSYDYWGQGTLVTVSS (SEQ ID NO: 340)
BMS3h25
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRRAPGKGLERVSAINPQGTRTYYADSVMGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFDDWGQGTLVTVSS (SEQ ID NO: 341)
BMS3h26
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRRAPGKGLERVSAINPQGTRTYYADSVMGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFMFDDRGQGTLVTVSS (SEQ ID NO: 342)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h27
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVMGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFMFDDWGQGTLVTVSS (SEQ ID NO: 343)
BMS3h28
EVQLLESGGGLVQPGGSLRLSCAASGFTFAGYELWWVRQAPGKGLERVSAINPQGTRTYYADSVMGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFDDWGQGTLVTVSS (SEQ ID NO: 344)
BMS3h29
EVQLLESGGGLVQPGGSLRLSCAASGFTFAGYELWWVRQAPGKGLERVSAINPQGTRTYYADSVMGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFMFDDRGQGTLVTVSS (SEQ ID NO: 345)
BMS3h30
EVQLLESGGGLVQPGGSLRLSCAASGFTFAGYEMWWFRQAPGKGLERVSAINPQGTRTYYADSVMGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFDDWGQGTLVTVSS (SEQ ID NO: 346)
BMS3h31
EVQLLESGGGLVQPGGSLRLSCAASGFTFAGYEMWWFRQAPGKGLERVSAINPQGTRTYYADSVMGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFMFDDRGQGTLVTVSS (SEQ ID NO: 347)
BMS3h32
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLEWVSAINPQGTRTYYADSVMGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFDDWGQGTLVTVSS (SEQ ID NO: 348)
BMS3h33
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLEWVSAINPQGTRTYYADSVMGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFMFDDRGQGTLVTVSS (SEQ ID NO: 349)
BMS3h202
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPTYFSDRGQGTLVTVSS (SEQ ID NO: 350)
BMS3h203
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFFFEEWGQGTLVTVSS (SEQ ID NO: 351)
BMS3h204
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPTYFKDWGQGTLVTVSS (SEQ ID NO: 352)
BMS3h205
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFYFSEWGQGTLVTVSS (SEQ ID NO: 353)
45 BMS3h206
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYHCAKLPMFFEDWGQGTLVTVSN (SEQ ID NO: 354)
BMS3h207
50 EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFPFSEWGQGTLVTVSS (SEQ ID NO: 355)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h208
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMDSLRAEDTAVYYCAKLPFYFSEWGQGTLVTVSS (SEQ ID NO: 356)
BMS3h209
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPYGNLTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFEDWGQGTLVTVSS (SEQ ID NO: 357)
BMS3h210
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPPGTLTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFEDRGQGTLVTVSS (SEQ ID NO: 358)
BMS3h211
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPWGGLTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFEDWGQGTLVTVSS (SEQ ID NO: 359)
BMS3h212
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPMGGFTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFEDWGQGTLVTVSS (SEQ ID NO: 360)
BMS3h213
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPWGSHTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFEDWGQGTLVTVSS (SEQ ID NO: 361)
BMS3h214
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPSGGLTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFDDRGQGTLVTVSS (SEQ ID NO: 362)
BMS3h215
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPHGSLTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFDDWGQGTLVTVSS (SEQ ID NO: 363)
BMS3h216
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPAGRLTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFEDWGQGTLVTVSS (SEQ ID NO: 364)
BMS3h217
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPWGSLTYYADSVKGRFTISRDNSKNTL
40 YLQMNSLRAEDTAVYYCAKLPFTFEDWGQGTLVTVSS (SEQ ID NO: 365)
BMS3h218
EVQLLESGGGLVQPGGSLRLSCAASGFTFPDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYHCAKLPFTFDDWGQGTLVTVSS (SEQ ID NO: 366)
BMS3h219
EVQLLESGGGLVQPGGSLRLSCADSGFTFPPVEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFEDWGQGTLVTVSS (SEQ ID NO: 367)
50 BMS3h220
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPYGGLTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFDDWGQGTLVTVSS (SEQ ID NO: 368)
BMS3h221
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPWGNHTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFEDWGQGTLVTVSS (SEQ ID NO: 369)
BMS3h222
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPHGGYTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFEDWGQGTLVTVSS (SEQ ID NO: 370)
BMS3h223
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGRGLERVSAINPPGMLTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFDDWGQGTLVTVSS (SEQ ID NO: 371)
BMS3h224
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPWGQLTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFEDWGQGTLVTVSS (SEQ ID NO: 372)
BMS3h225
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPWGGYTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFDDWGQGTLVTVSS (SEQ ID NO: 373)
BMS3h226
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPSGGLTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFEDWGQGTLVTVSS (SEQ ID NO: 374)
BMS3h227
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPSGGLTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFDDWGQGTLVTVSS (SEQ ID NO: 375)
BMS3h228
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPSGTLTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFEDWGQGTLVTVSS (SEQ ID NO: 376)
BMS3h229
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPYGSLTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFDDWGQGTLVTVSS (SEQ ID NO: 377)
40 BMS3h230
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPWGGYTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFEDWGQGTLVTVSS (SEQ ID NO: 378)
BMS3h231
45 EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGGLTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFEDWGQGTLVTVSS (SEQ ID NO: 379)
BMS3h232
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPWGSHTYYADSVKGRFTISRDNSKNTL
50 YLQMNSLRAEDTAVYYCAKLPFTFDDWGQGTLVTVSS (SEQ ID NO: 380)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h233
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPWGTLTYYADSVKGRFTISRDNSRNTL
YLQMNSLRAEDTAVYYCAKLPFTFDDWGQGTLVTVSS (SEQ ID NO: 381)
BMS3h234
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPNGRLTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFADWGQGTLVTVSS (SEQ ID NO: 382)
BMS3h235
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPWGQLTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFDDWGQGTLVTVSS (SEQ ID NO: 383)
BMS3h236
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPHGGLTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFDDWGQGTLVTVSS (SEQ ID NO: 384)
BMS3h237
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPAGMLTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFDDWGQGTLVTVSS (SEQ ID NO: 385)
BMS3h238
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPHGTLTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFEDWGQGTLVTVSS (SEQ ID NO: 386)
BMS3h239
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPWGSLTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFDDWGQGTLVTVSS (SEQ ID NO: 387)
BMS3h240
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPYGGLTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFEDWGQGTLVTVSS (SEQ ID NO: 388)
BMS3h241
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPAGFLTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFEDWGQGTLVTVSS (SEQ ID NO: 389)
BMS3h242
EVQLLESGGGLVRPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPYGGLTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFEDWGQGTLVTVSS (SEQ ID NO: 390)
BMS3h243
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPWGGFTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFEDWGQGTLVTVSS (SEQ ID NO: 391)
45 BMS3h244
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPWGGLTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFDDWGQGTLVTVSS (SEQ ID NO: 392)
BMS3h245
50 EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPYGGLTYYADSVKGRFTISRDNSKNTL
YLQMDSLRAEDTAVYYCAKLPFTFEDWGQGTLVTVSS (SEQ ID NO: 393)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h246
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPWGTLTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFEDWGQGTLVTVSS (SEQ ID NO: 394)
BMS3h247
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPWGGYTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFEDWGRGTLVTVSS (SEQ ID NO: 395)
BMS3h248
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPYGNLTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFDDWGQGTLVTVSS (SEQ ID NO: 396)
BMS3h249
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPHGGFTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFEDWGQGTLVTVSS (SEQ ID NO: 397)
BMS3h250
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPAGFYTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFDDWGQGTLVTVSS (SEQ ID NO: 398)
BMS3h251
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPAGGLTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFDDWGQGTLVTVSS (SEQ ID NO: 399)
BMS3h252
EVQLLESGGGLVQPGGSLRLSCAASGFAFRDYEMWWVRQAPGKGLERVSAINPHGSLTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFTFEDWGQGTLVTVSS (SEQ ID NO: 400)
BMS3h253
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPAGGYTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYHCAKLPFTFEDWGQGTLVTVSS (SEQ ID NO: 401)
BMS3h254
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFWFTEWGQGTLVTVSS (SEQ ID NO: 402)
BMS3h255
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
40 YLQMNSLRAEDTAVYYCAKLPFMFSDRGQGTLVTVSS (SEQ ID NO: 403)
BMS3h256
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFLFQEWGQGTLVTVSS (SEQ ID NO: 404)
BMS3h257
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPTRFEDWGQGTLVTVSS (SEQ ID NO: 405)
50 BMS3h258
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFYFHEWGQGTLVTVSS (SEQ ID NO: 406)
BMS3h259
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSS (SEQ ID NO: 407)
BMS3h260
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPTFFKDWGQGTLVTVSS (SEQ ID NO: 408)
BMS3h261
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFFFQEWGQGTLVTVSS (SEQ ID NO: 409)
BMS3h262
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPQLFHDRGQGTLVTVSS (SEQ ID NO: 410)
BMS3h263
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPQLFEDWGQGTLVTVSS (SEQ ID NO: 411)
BMS3h264
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYHCAKLPFGFSEWGQGTLVTVSS (SEQ ID NO: 412)
BMS3h265
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPQLFQDWGQGTLVTVSS (SEQ ID NO: 413)
BMS3h266
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFFFHEWGQGTLVTVSS (SEQ ID NO: 414)
BMS3h267
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPHYFKDWGQGTLVTVSS (SEQ ID NO: 415)
40 BMS3h268
EVQLLESGGGLVQSGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFYFEEWGQGTLVTVSS (SEQ ID NO: 416)
BMS3h269
45 EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFRFSDRGQGTLVTVSS (SEQ ID NO: 417)
BMS3h270
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
50 YLQMNSLRAEDTAVYYCAKLPTLFQDWGQGTLVTVSS (SEQ ID NO: 418)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h271
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFYFSEWGQGTLVTVSN (SEQ ID NO: 419)
BMS3h272
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFWFQEWGQGTLVTVSS (SEQ ID NO: 420)
BMS3h273
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPWGSLTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFYFQEWGQGTLVTVSS (SEQ ID NO: 421)
BMS3h274
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPWGSLTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYHCAKLPMFFEDWGQGTLVTVSN (SEQ ID NO: 422)
BMS3h275
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPWGSLTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFYFHEWGQGTLVTVSS (SEQ ID NO: 423)
BMS3h276
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPWGSLTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFFFQEWGQGTLVTVSS (SEQ ID NO: 424)
BMS3h277
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPWGSLTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFFFHEWGQGTLVTVSS (SEQ ID NO: 425)
BMS3h278
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPWGGFTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFYFQEWGQGTLVTVSS (SEQ ID NO: 426)
BMS3h279
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPWGGFTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYHCAKLPMFFEDWGQGTLVTVSN (SEQ ID NO: 427)
BMS3h280
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPWGGFTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFYFHEWGQGTLVTVSS (SEQ ID NO: 428)
BMS3h281
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPWGGFTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFFFQEWGQGTLVTVSS (SEQ ID NO: 429)
45 BMS3h282
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPWGGFTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFFFHEWGQGTLVTVSS (SEQ ID NO: 430)
BMS3h283
50 EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPWGGLTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFYFQEWGQGTLVTVSS (SEQ ID NO: 431)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h284
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPWGGLTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYHCAKLPMFFEDWGQGTLVTVSN (SEQ ID NO: 432)
BMS3h285
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPWGGLTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFYFHEWGQGTLVTVSS (SEQ ID NO: 433)
BMS3h286
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPWGGLTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFFFQEWGQGTLVTVSS (SEQ ID NO: 434)
BMS3h287
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPWGGLTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKLPFFFHEWGQGTLVTVSS (SEQ ID NO: 435)
BMS3h288
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYHCAKLPMFFEDWGQGTLVTVSS (SEQ ID NO: 436)
BMS3h1
EVQLLETGGGLVQPGGSLRLSCAASGFTFSTYHMQWVRRAPGKGLEWVSMIDADGLGTYYADPVKGRFTISRDNSKNTL
YLQMNSLRAKDTAVYYCARPGPQFGQFDYLGQGTLVTVSS (SEQ ID NO: 437)
BMS3h2
EVQLFESGGGLVQTGGSLRLSCAASGFTFSTYHMQWVRQAPGKGLEWVSMIDADGLGKYYADPVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCVKPGPQFGQYDYWGQGTLVTVSS (SEQ ID NO: 438)
BMS3h1
EVQLLESGGGLVQPGGSLRLSCSASGFTFSGYDMQWVRQAPGKGLEWVSTISASGVYTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKYPNRFALNSFDYRGRGTLVTVSS (SEQ ID NO: 439)
BMS3h2
EVQLLESGGGLVQPGGSLRLSCAASGFTFSGYDMQWVRQAPGRGLEWVSTISASGVYTYYTDSVKGRFTTSRDNSKNTL
YLQMNSLRAEDTAVYYCTKYPNRFARNNFDYWGQGTLVTVSS (SEQ ID NO: 440)
BMS3h1
DILMTQSPSSLSASVGDRVTITCRANSSILWALAWYQQKPGEAPKLLIESSSGLQSGVPSRFSGSGSGTDFTLTISSLQ
40 PEDFATYYCVQNAVWPGTFSQGTKVEIKR (SEQ ID NO: 441)
BMS3h2
DIQMTQSPSSLSASVGDRVTITCRADSSILWALAWYQQKPGKAPKLLIESSSGLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCVQNAVWPGTFGQGTKVEIKR (SEQ ID NO: 442)
BMS3h3
DIQMTVSPSSLSASVGDRVTITCRADSSILWALAWYQQKPGKAPKLLIESSSGLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCVQNAVWPGTFGQGTKVEIKR (SEQ ID NO: 443)
50 BMS3h4
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
DIQMTQSPSSLSASVGDRVTITCRANSSILWALAWYQQKPGKAPKLLIESSSGLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCVQNAVWPGTFDQGTKVEIKR (SEQ ID NO: 444)
BMS3h5
DIQMTQSPSSLSASVGDRVTITCRANSSILWALAWYQQKPGKAPKLLIESSTGLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCVQNAVWPGTFGQGTKVEIKR (SEQ ID NO: 445)
BMS3h6
DIQMTVSPSSLSASVGDRVTITCRANSSILWALAWYQQKPGKAPKLLIESSSGLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCVQNAVWPGTFGQGTKVEIKR (SEQ ID NO: 446)
BMS3h7
DIQMTQSPSSLSASVGDRVTITCRADSSILWALAWYQQKPGKAPKLLIESSSGLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCVQNAVWPGTFDQGTKVEIKR (SEQ ID NO: 447)
BMS3h8
DIQMTQSPSSLSASVGDRVTITCRANSSILWALAWYQQKPGKAPELLIESSSGLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCVQNAVWPGTFGQGTKVEIKR (SEQ ID NO: 448)
BMS3h9
DIQMTQSPSSLSASVGDRVTITCRANSSILWALAWYQQKPGKAPKLLIESSSGLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCVQNAVWPGTFGQGTKVENKR (SEQ ID NO: 449)
BMS3h10
DIQMTQSPSSLSASVGDRVTITCRANSSILWALAWYQQKPGKAPKLLIESSSGLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCVQNAVWPGTFGQGTKVEIKR (SEQ ID NO: 450)
BMS3h11
DIQMTQSPSSLSASVGDRVTITCRANSSILWALAWYQQKPGKAPKLLIESSSGLQSGIPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCVQNAVWPGTFGQGTKVEIKR (SEQ ID NO: 451)
BMS3h12
DIQMTQSPSSLSASVGDRVTITCRANSSILWALAWYQQKPGKAPKLLIESSSGLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCVQNAVWPGTFGQGTKVEIKR (SEQ ID NO: 452)
BMS3h13
DILLTQSPSSLSASVGDRVTITCRANSSILWALAWYQQKPGKAPKLLIESSSGLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCVQNAVWPGTFGQGTKVEIKR (SEQ ID NO: 453)
40 BMS3h14
DIQMTQSPSSLSASVGDRVTITCRANSSILWALAWYQQKPGKAPKLLIESSSGLQSGVPSRFSGSGTGTDFTLTISGLQ
PEDFATYYCVQNAVWPGTFDQGTKVEIKR (SEQ ID NO: 454)
BMS3h15
45 DIQMTQSPSSLSASVGDRVTIPCRANSSILWALAWYQQKPGKAPKLLIESSSGLQSGVPSRFSGSASGTDFTLTISSLQ
PEDFATYYCVQNAVWPGTFGQGTKVEIKR (SEQ ID NO: 455)
BMS3h1
DIQMAQSPSSLSASVGDRVTITCRASQTIERRLNWYQQKPGKAPKLLIYLASRLQSGVPSRFSGSGSGTDFTLTISSLQ
50 PEDFATYYCHQYASPPLTLGQGTKVEIKR (SEQ ID NO: 456)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h2
DIQMTQSPSSLSASVGDSVTITCRASQTIERRLNWYQQKPGEAPKLLIYLASRLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCHQYASPPLTFGQGTNVEIKR (SEQ ID NO: 457)
BMS3h3
DIQMTQSPSSLSASVGDRVTITCRASQTIERRLNWYQQKPGKAPKLLIYLASRLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFAAYYCHQYESPPLTFGQGTKVEIKR (SEQ ID NO: 458)
BMS3h4
DIQMTQSPSSLSASVGDRVTITCRASRTIERRLNWYQQKPGKAPKLLIYLASRLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCHQYESPPLTFGQGTKVEIKR (SEQ ID NO: 459)
BMS3h5
DIQMTQSPSSLSASVGERVTITCRASQTIERRLNWYQQKPGKAPKLLIYLASRLQSGVPSRFSGSGSGTDFTLTISNLQ
PEDSATYYCHQYASPPLTLGQGTKVEIKR (SEQ ID NO: 460)
BMS3h6
DIQMTQSPSSLSASVGDRVTITCRASQTIERRLNWYQQKPGKAPKLLIYLASRLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCHQYASPPLTLGQGTKVEIKR (SEQ ID NO: 461)
BMS3h7
DIQITQSPSSLSASVGDRVTITCRASQTIERRLNWYQQKPGKDPKLLIYLASRLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCHQYESPPLTFGQGTKVEIKR (SEQ ID NO: 462)
BMS3h8
DIQMTQSPSSLSASVGDRVTITCRASQTIERRLNWYQQKPGEAPKLLIYLASRLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCHQYESPPLTFGQGTKVEIKW (SEQ ID NO: 463)
BMS3h9
DIQLTQSPSSLSASVGDRVTITCRASQTIERRLNWYQQKPGKAPKLLIYLASRLQSGVPSRFSGSGSGTEFTLTISSLQ
PEDFATYYCHQYESPPLTFGQGTKVEIKR (SEQ ID NO: 464)
BMS3h10
DIQMSQSPSTLSASVGDRVTITCRASQTIERRLNWYQQKPGKAPKLLIYLASRLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCHQYESPPLMFGQGTKVEIKR (SEQ ID NO: 465)
BMS3h11
DIQMTQSPSSLSASVGDRVTITCRASQTIERRLNWYQQKPGKDPKLLIYLASRLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCHQYESPPLTFGQGTKVEIKR (SEQ ID NO: 466)
BMS3h12
DIQMTQSPSSLSASVGDRVTITCRASQTIERRLNWYQQKPGKAPKLLIYLASRLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCHQYESPPLTFGQGTKVEIKR (SEQ ID NO: 467)
45 BMS3h13
DIQMTQSPSSLFASVGDRVTITCRASQTIERRLNWYQQKPGKAPKLLIYLASRLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCHQYESPPLTFGQGTKVEIKR (SEQ ID NO: 468)
BMS3h14
50 DIQMTQYPSSLSASVGDRVTITCRASQSIERRLNWYQQKPGEAPKLLIYLASRLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCHQYESPPLTFGQGTKVEIKR (SEQ ID NO: 469)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h15
DIQMTQSPSSLSASVGDRVTITCRASRTIERRLNWYQQKPGKAPKLLIYLASRLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCHPYESPPLTFGQGTKVEIKR (SEQ ID NO: 470)
BMS3h16
DIQMTQSPSSLSASVGDRVTITCRASQAIERRLNWYQQKPGKAPKLLIYLASRLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCHQYASPPLTLGQGTKVEIKR (SEQ ID NO: 471)
BMS3h17
NIQMTQSPSSLSASVGDRVTITCRASQAIERRLNWYQQKPGKAPKLLIYLASRLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCHQYESPPLTFGQGTKVEIKR (SEQ ID NO: 472)
BMS3h18
DIQMTQSPSSLSASVGDRVTITCRASQTIGRRLNWYQQKPGKAPKLLIYLASRLQSGVPSRFSGSGSGSDFTLTISSLQ
PEDFATYYCHQYESPPLTFGQGTKVEIKR (SEQ ID NO: 473)
BMS3h19
DIQMTQSPSSLSASVGDRVTITCRASQTIERRLNWYQQKPGKAPKLLIYLASRLQSGVPSRFSGSGSGTEFTLTISSLQ
PEDFATYYCHQYESPPLTFGQGTKVEIKR (SEQ ID NO: 474)
BMS3h20
DIQMTQTPSSLSASVGDRVTITCRASQTIERRLNWYQQKPGEAPKLLIYLASRLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCHQYESPPLTFGQGTKVKIKR (SEQ ID NO: 475)
BMS3h21
DIQMTQSPSSLSASVGDSVTITCRASQTIERRLNWYQQKPGKAPKLLIYLASRLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCHQYESPPLTFGQGTKVEIKR (SEQ ID NO: 476)
BMS3h22
HIQMTQSPSSLSASVGDRVTITCRASQTIERRLNWYQQKPGKAPKLLIYLASRLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCHQYESPPLTFGQGTKVEIKR (SEQ ID NO: 477)
BMS3h23
DVQMTQSPSSLSASVGDRVTITCRASQTIERRLNWYQQKPGEAPKLLIYLTSRLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCHQYASPPLTFGQGTKVEIKR (SEQ ID NO: 478)
BMS3h24
DIQMTQSPSSLSASVGDRVTITCRASQTIERRLNWYQQKPGKAPKLLIYLASRLQSGVPSRFSGSGSGTDFTLTISSLQ
40 PEDFATYYCHQYESPPLTFGQGTKVVIKR (SEQ ID NO: 479)
BMS3h25
DIQMTQSPSSLSASVGDRVTITCRASQTIERRLNWYQQKPGKAPRLLIYLATRLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCHQYESPPLTFGQGTKVEIKR (SEQ ID NO: 480)
BMS3h26
DIQMTQSPSSLSASVGDRVTITCRASQPIERRLNWYQQKPGKAPKLLIYLASRLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCHQYESPPLTFGQGTKVEIKR (SEQ ID NO: 481)
50 BMS3h27
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
DIQMTQSPSSLSASVGDRVTITCRASQTIGRRLNWYQQKPGKAPKLLIYLASRLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCHQYESPPLTFGQGTKVEIKR (SEQ ID NO: 482)
BMS3h28
DIQMTQSPSSLSASVGDRVTITCRASQSIERRLNWYQQKPGKAPKLLIYLASRLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCHQYESPPLTFGQGTKVEIIR (SEQ ID NO: 483)
BMS3h29
DIQMTQSPSSLSASVGDRVTITCRASQTIERRLNWYQQKPGKAPKLLIYLATRLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCHQYESPPLTFGQGTKVEIKR (SEQ ID NO: 484)
BMS3h30
DIQMTQSPSSLSASVGDRVTITCRASQSIERRLNWYQQKPGKAPKLLIYLASRLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCHQYESPPLTFGQGTKVEIKR (SEQ ID NO: 485)
BMS3h2501
DIQMTQSPSSLSASVGDRVTITCRASQTIERRLNWYQQKPGKAPRLLIYLATRLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCHQFEHPPLTFGQGTKVEIKR (SEQ ID NO: 486)
BMS3h2502
DIQMTQSPSSLSASVGDRVTITCRASFPIDRRLNWYQQKPGKAPRLLIYLATRLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCHQYESPPLTFGQGTKVEIKR (SEQ ID NO: 487)
BMS3h2503
DIQMTQSPSSLSASVGDRVTITCRASSTIGRRLNWYQQKPGKAPRLLIYLATRLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCHQYESPPLTFGQGTKVEIKR (SEQ ID NO: 488)
BMS3h2504
DIQMTQSPSSLSASVGDRVTITCRASSQIGRRLNWYQQKPGKAPRLLIYLATRLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCHQYESPPLTFGQGTKVEIKR (SEQ ID NO: 489)
BMS3h2505
DIQMTQSPSSLSASVGDRVTITCRASERIGRRLNWYQQKPGKAPRLLIYLATRLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCHQYESPPLTFGQGTKVEIKR (SEQ ID NO: 490)
BMS3h2506
DIQMTQSPSSLSASVGDRVTITCRASQQIGRRLNWYQQKPGKAPRLLIYLATRLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCHQYESPPLTFGQGTKVEIKR (SEQ ID NO: 491)
40 BMS3h2507
DIQMTQSPSSLSASVGDRVTITCRASQPIARRLNWYQQKPGKAPRLLIYLATRLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCHQYESPPLTFGQGTKVEIKR (SEQ ID NO: 492)
BMS3h2508
45 DIQMTQSPSSLSASVGDRVTITCRASGNIGRRLNWYQQKPGKAPRLLIYLATRLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCHQYESPPLTFGQGTKVEIKR (SEQ ID NO: 493)
BMS3h2509
DIQMTQSPSSLSASVGDRVTITCRASRNIDRRLNWYQQKPGKAPRLLIYLATRLQSGVPSRFSGSGSGTDFTLTISSLQ
50 PEDFATYYCHQYESPPLTFGQGTKVEIKR (SEQ ID NO: 494)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h2510
DIQMTQSPSSLSASVGDRVTITCRASQSIGRRLNWYQQKPGKAPRLLIYLATRLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCHQYESPPLTFGQGTKVEIKR (SEQ ID NO: 495)
BMS3h2511
DIQMTQSPSSLSASVGDRVTITCRASQNIGTRLNWYQQKPGKAPRLLIYLATRLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCHQYESPPLTFGQGTKVEIKR (SEQ ID NO: 496)
BMS3h2512
DIQMTQSPSSLSASVGDRVTITCRASEVIGRRLNWYQQKPGKAPRLLIYLATRLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCHQYESPPLTFGQGTKVEIKR (SEQ ID NO: 497)
BMS3h2513
DIQMTQSPSSLSASVGDRVTITCRASEAIGRRLNWYQQKPGKAPRLLIYLATRLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCHQYESPPLTFGQGTKVEIKR (SEQ ID NO: 498)
BMS3h2514
DIQMTQSPSSLSASVGDRVTITCRASTSIARRLNWYQQKPGKAPRLLIYLATRLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCHQYESPPLTFGQGTKVEIKR (SEQ ID NO: 499)
BMS3h2515
DIQMTQSPSSLSASVGDRVTITCRASLNIGRRLNWYQQKPGKAPRLLIYLATRLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCHQYESPPLTFGQGTKVEIKR (SEQ ID NO: 500)
BMS3h2516
DIQMTQSPSSLSASVGDRVTITCRASQTIERRLNWYQQKPGKAPRLLIYLSSKLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCHQYESPPLTFGQGTKVEIKR (SEQ ID NO: 501)
BMS3h1
EVQLLESGGGLVQPGGSLRLSCAASGSTIAGYEMWWVRQAPGKGLERVSAISGSGGSTYYADSVKGRFTISRDDSKNTL
YLQMNSLRAEDTAVYYCARDPYSFDYWGQGTLVTVSS (SEQ ID NO: 502)
BMS3h2
EVQPLESGGGLVQPGGSLRLSCAASGFTFAGYEMWWVRQAPGKGLERISAISGSGGSTYYADSVKGRFTISRDDSKNTL
YLQMNSLRAEDTAVYYCARDPYSFDYWGQGTLVTVSS (SEQ ID NO: 503)
BMS3h3
EVQLLESGGGSVQPGGSLRLSCAATGSTFAGYEMWWVRQAPGKGLERVSAISGSGGSTYYADSVKGRFTISRDDSKNTL
YLQMNSLRAEDTAVYYCARDPYSYDYWGQGTLVSVSS (SEQ ID NO: 504)
BMS3h4
EVQLLESGGGLVQPGGSLRLSCAASGLTFAGYEMWWVRQAPGKGLERVSAISGSGGSTYYADSVKGRFTISRDDSKNTL
YLQMNSLRAEDTAVYHCARDPYSFDYWGQGTLVTVSS (SEQ ID NO: 505)
45 BMS3h5
EVQLLESGGGLVQPGGSLRLSCAASGFTFAGYEMWWVRQAPGKGLERVSAISGSGGSTYYADSVKGRFTISRDDSKNTL
YLQMNSLRAEDTAVYHCAKEPYSYDYWGQGTLVTVSS (SEQ ID NO: 506)
BMS3h6
50 EVQLLESGGGLVQPGGSLRLSCAASGSTFAGYEMWWVRQAPGKGLERVSAISGSGGSTYYADSVKGRFTISRDDSKNTL
YLQMNSLRPEDTAVYYCVKDPYSFDYWGQGTLVTVSS (SEQ ID NO: 507)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h7
EVQLLESGGGLVQPGGSLRLSCAASGSTIAGYEMWWVRQAPGKGLERVSAISGSGGSTYYADSVKGRFTISRDDSKNTL
YLQMNSLRAEDTAVYYCARDPYSFDYWGQGTPVTVSS (SEQ ID NO: 508)
BMS3h8
EVQLMESGGGLVQPGGSLRLSCAASGSTFAGYEMWWYRQAPGKGLERVSAISGSGRSTYYADSVKGRFTISRDDSKNTL
YLQMNSLRAEDTAVYYCAKDPYSFDYWGQGTLVTVSS (SEQ ID NO: 509)
BMS3h9
EVQLLESGGGLVQPGGSLRLSCAASGFTFAGYEMWWVRQAPGKGLERVSAISGSGGSTYYADSVKGRFTISRDDSKNTL
YLQMNSLRAEDTAVYYCAKEPYSFDYWGQGTLVTVSS (SEQ ID NO: 510)
BMS3h10
EVQLLESGGGLVQPGGSLRLSCAASGSTIAGYEMWWVRQAPGKGLERVSAISGSGGSTYYADSVKGRFTISRDDSKNTL
YLQMNSLRAEDTAVYYCAKDPYSFDYWGQGTLVTVSS (SEQ ID NO: 511)
BMS3h11
EVQLLESGGGLVQPGGSLRLSCAASGFTFAGYEMWWVRQAPGKGLERVSAISGSGGSTYYADSVKGRFTISRDDSKNTL
YLQMNSLRAEDTAVYYCARDPYSFDYWGQGTLVSVSS (SEQ ID NO: 512)
BMS3h12
EVQLLESGGGLVQPGGSLRLSCAASGFTIAGYEMWWVRQAPGKGLERVSAISGSGGSTYYADSVKGRFTISRDDSKNTL
YLQMNSLRAEDTAVYYCAKDPYSFDYWGQGTLVTVSS (SEQ ID NO: 513)
BMS3h13
EVQLLESGGGLVQPGGSLRLSCAASGFTFAGYEMWWVRQAPGKGLERVSAISGSGGSTYYADSVKGRFTITRDDSKNTL
YLQMNSLRAEDTAVYYCAKEPYSFDYWGQGTLVTVSS (SEQ ID NO: 514)
BMS3h14
EVQLLESGGGLVQPGGSLRLSCAASGFTFAGYEMWWFRQAPGKGLERVSAISGSGGSTYYADSVKGRFTISRDDTKNTL
YLQMNSLRAEDTAVYYCAKDPYSFDYWRQGTLVTVSS (SEQ ID NO: 515)
BMS3h15
EVQLLESGGGLVQPGGSLRLSCAASGSTFAGYEVWWVRQAPGKGLERVSAISGSGGSTYYADSVKGRFTISRDDSKNTL
YLQMNSLRAEDTAVYYCARDPYSFDYWGQGTLVTVSS (SEQ ID NO: 516)
BMS3h16
EVQLLESGGGLVQPGGSLRLSCAASGSTFAGYEMWWVRQAPGKGLERISAISGSGGSTYYADSVKGRFTISRDDSKNTL
40 YLKMNSLRAEDTAVYYCAKDPYSFDYWGQGTLVTVSS (SEQ ID NO: 517)
BMS3h17
EVQLLESGGGLVQPGGSLRLSCAASGFTFAGYEMWWVRQAPGKGLERVSAISGSGGSTYYADSVKGRFTISRDDSKNTL
YLQMNSLRAEDTAVYYCARDPYSFDYWGQGTLVTVSS (SEQ ID NO: 518)
BMS3h18
EVQLLESGGGLVQPGGSLRLSCAASGLTFAGYEMWWVRRAPGKGLERVAAISGSGGSTYYADSVKGRFTISRDDSKNTL
YLQMNSLRAEDTAVYYCARDPYSFDYWGQGTLVTVSS (SEQ ID NO: 519)
50 BMS3h19
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
EVQLLESGGGLVQPGGSLRLSCAASGFTFAGYELWWVRQAPGKGLERVSAISGSGGSTYYADSVKGRFTISRDDSKNTL
YLQMNSLRAEDTAVYYCARDPYSFDYRGQGTLVTVSS (SEQ ID NO: 520)
BMS3h20
EVQLLESGGGLVQPGGSLRLSCAAPGFTLAGYEMWWVRQAPGKGLERVSAISGSGGSTYYADSVKGRFTISRDDSKNTL
YLQMNSLRAEDTAVYYCAKEPYSFDYWGQGTLVTVSS (SEQ ID NO: 521)
BMS3h21
EVQLLESGGGLVQPGGSLRLSCAASGLTFAGYEMWWVRRAPGKGLERVSAISGSGGSTYYADSVKGRFTTSRDDSKNTL
YLQMNSLRAEDTAVYYCARDPYSFDYWGRGTLVTVSS (SEQ ID NO: 522)
BMS3h22
EVQLLESGGGLVQPGGSLRLSCAASGFTFAGYEMWWVRQAPGKGLERVSAISGSGGSTYYADSVKGRFTISRDDSKNTL
YLQMNSLRAEDTAVYYCAKEPYSYDYWGHGTLVTVSS (SEQ ID NO: 523)
BMS3h23
EVQPLESGGGLVQPGGSLRLSCAASGFTFAGYEMWWVRQAPGKGLERVSAISGSGGNTYYADSVKGRFTISRDDSKNTL
YLQMNSLRAEDTGVYYCARDPYSFDYWGQGTLVTVSS (SEQ ID NO: 524)
BMS3h24
EVQLLESGGGLVQPGGSLRLSCAASGFTFAGYEMWWVRQAPGKGLERVSAISGSGGSTYYADSVKGRFTISRDDSKNTL
YLQMNSLRAEDTAVYYCAKEPYSFDSWGQGTLVTVSS (SEQ ID NO: 525)
BMS3h25
EAQLLESGGGLVQPGGSLRLSCAASGLTFAGYEMWWVRQAPGKGLERVSAISGSGGSTYYADSVKGRFTISRDDSKNTL
YLQMNSLRAEDTAVYYCARDPYSFDYWGQGTLVTVSS (SEQ ID NO: 526)
BMS3h26
EVQLLESGGGLVQPGGSLRLSCAASGSTFAGYEMWWVRQAPGKGLERVSAISGSGGSTYYADSVKGRFSISRDDSKNTL
YLQMNSLRAEDTAVYYCAKEPYSFDHWGQGTLVTVSS (SEQ ID NO: 527)
BMS3h27
EVQLLESGGGLVQPGGSLRLSCAASGSTFAGYEMWWVRRAPGKGLERVSAISGSGGSTYYADSVKGRFTISRDDSKNTL
YLQMNSLRAEDTAVYYCARDPYSFDYWGQGTLVTVSS (SEQ ID NO: 528)
BMS3h28
EVQLLESGGGLVQPGGSLRLSCAASGFTFAGYEMWWFRQAPGKGLERVSAISGSGGSTYYADSVKGRFTISRDDSKNTL
YLQMNSLRAEDTAVYYCAKDPYSFDNWGQGTLVTVSS (SEQ ID NO: 529)
40 BMS3h29
EVQLLESGGGLVEPGGSLRLSCAASGFTFAGYEMWWVRQAPGKGLERVSAISGSGGSTYYADSVKGRFTISRDDSKNTL
YLQMNSLRAEDTAVYYCAKEPYSFDHRGQGTLVTVSS (SEQ ID NO: 530)
BMS3h30
45 EVQLLESGGGLVQPGGSLRLSCAASGYTFAGYEMWWVRQAPGKGLERVSAISGSGGSTYYADSVKGRFTISRDDSKNTL
YLQMNSLRAEDTAVYYCAKEPYSFDHRGQGTLVTVSS (SEQ ID NO: 531)
BMS3h31
EVQLLESGGGLVQPGGSLRLSCAASGFTFAGYEMWWVRQAPGKGLERVSAISGSGGSTYYADSVKGRFTISRDNSKNTL
50 YLQMNSLRAEDTAVYHCAKEPYSYDYWGQGTLVTVSS (SEQ ID NO: 532)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h32
EVQLLESGGGLVQPGGSLRLSCAASGFTFAGYEMWWFRQAPGKGLERVSAISGSGGSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKDPYSFDNWGQGTLVTVSS (SEQ ID NO: 533)
BMS3h33
EVQLLESGGGLVQPGGSLRLSCAASGFTFAGYEMWWVRQAPGKGLERVSAISGSGGSTYYADSVKGRFTISRDDSKNTL
YLQMNSLRAEDTAVYYCAKEPYSYDYWGQGTLVTVSS (SEQ ID NO: 534)
BMS3h34
EVQLLESGGGLVQPGGSLRLSCAASGFTFAGYEMWWVRQAPGKGLERVSAISGSGGSTYYADSVKGRFTISRDDSKNTL
YLQMNSLRAEDTAVYYCAKDPYSFDNWGQGTLVTVSS (SEQ ID NO: 535)
BMS3h35
EVQLLESGGGLVQPGGSLRLSCAASGFTFAGYEMWWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDDSKNTL
YLQMNSLRAEDTAVYHCAKEPYSYDYWGQGTLVTVSS (SEQ ID NO: 536)
BMS3h36
EVQLLESGGGLVQPGGSLRLSCAASGFTFAGYEMWWFRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDDSKNTL
YLQMNSLRAEDTAVYYCAKDPYSFDNWGQGTLVTVSS (SEQ ID NO: 537)
BMS3h37
EVQLLESGGGLVQPGGSLRLSCAASGFTFAGYELWWVRQAPGKGLERVSAISGSGGSTYYADSVKGRFTISRDDSKNTL
YLQMNSLRAEDTAVYYCAKDPYSFDYRGQGTLVTVSS (SEQ ID NO: 538)
BMS3h38
EVQLLESGGGLVQPGGSLRLSCAASGFTFAGYELWWVRQAPGKGLERVSAISGSGGSTYYADSVKGRFTISRDDSKNTL
YLQMNSLRAEDTAVYYCARDPYSFDYWGQGTLVTVSS (SEQ ID NO: 539)
BMS3h1
EVQLLESGGGLVQPGGSLRLSCAASGFTFPTAEMLWVRKAPGKGLEWVSSISASGGSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKEPVSYVATFDYWGQGTLVTVSS (SEQ ID NO: 540)
BMS3h2
EVQLLVSGGGLVQPGGSLRLSCAASGFTFPTAEMLWVRQAPGKGPEWVSSISASGGSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKEPVSYVATFDYWGQGTLVTVSS (SEQ ID NO: 541)
BMS3h3
EVQLLESGGGLVQPGGSLRLSCAASGFTFPTAEMVWVRKAPGMGLEWVSSISASGGYTYYADSVKGRFTISRDNSKNML
YLQMNSLRAEDTAVYYCAKEPVSYVATFDYWGQGALVTVTS (SEQ ID NO: 542)
BMS3h4
EVQLLVSGGGLVQPGGSLRLSCAASGFTFPTAEMVWVRQAPGKGLEWVSSISASGGSTYYADSVKGRFSISRDDSKNTL
YLQMNSLRAEDTAVYYCAKEPVSYVATFDYWGHGALVTVSS (SEQ ID NO: 543)
45 BMS3h5
EVQLLESGGGLVQPGGSLRLSCAASGFTFPTAEMLWVRQAPGKGLEWVSSISASGGSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKEPVSYVATFDYWGQGTLVTVSS (SEQ ID NO: 544)
BMS3h6
50 EAQLLESGGGLVQPGGSLRLSCAASGFTFPTAEMVWVRQAPGKGLEWISSISASGGSTYYADSVKGRFTISRDNSKNTL
YLQLNSLRAEDTAVYYCAKEPVSYVATFDYWGRGTLVTVSS (SEQ ID NO: 545)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h7
EVQLLESGGGLVQPGGSLRLSCAASGFTFPTAEMLWVRQAPGKGLEWVSSISASGGSTYYADSVKGRFTISRDNSKSTL
YLQMNSLRAEDTAVYYCAKEPVSYVATFDYWGPGALVTVSS (SEQ ID NO: 546)
BMS3h8
EVQLLESGGGLVQPGGSLRLSCAASGFTFPTAEMLWVRKAPGKGLEWVSSISASGGSTYYADSVKGRFTISRDNSKNTL
FLQMNSLRAEDTAVYYCAKEPVSYVATFDYWGQGTLVTVSS (SEQ ID NO: 547)
BMS3h9
EVQLLESGGGLVQPGGSLRLSCAASGFTFPTAEMLWVRQAPGKGLEWVSSISASGGSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKEPVSYVATFDYWGPGALVTVSS (SEQ ID NO: 548)
BMS3h10
EVQLLESGGGLVQPGGSLRLSCAASGFTFPTAEMLWVRQAPGKGLEWVSSISASGGSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCAKEPVYYVATFDYWGQGTLVTVSS (SEQ ID NO: 549)
BMS3h11
EVQLLESGGGLVQPGGSLRLSCAASGFTFPTAEMLWVRKAPGKGLEWVSSISASGGSTYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDAAVYYCAKEPVSYVATFDYWGQGTLVTVSS (SEQ ID NO: 550)
BMS3h1
NIQMTQSPSSLSASVGDRVTITCRASHFIGTLLTWYQHKPGKAPKLLITYGSLLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPATFGQGTKVEIKR (SEQ ID NO: 551)
BMS3h2
DIQMTQSPSSLSASVGDRVTITCRASHFIGTLLSWYQQKPRKAPKLLITYGSLLQSGVPSRFSGSGSGTDFTLTISSLH
PEDFATYYCGQGVLWPPTFGQGTKVEIKR (SEQ ID NO: 552)
BMS3h3
DIQMTQSPSSLTASVGDRVTITCRASHFIGTLLSWYQQKPGKAPKLLVTYGSLLQSGVPSRFSGSGSGTDFTLTISNLQ
PEDFATYYCGQGVLWPPTFGQGTKVENIR (SEQ ID NO: 553)
BMS3h4
DIQMTQSPSSLSASVGDRVTITCRASHFIATLLSWYQQKPGKAPKLLITYGSLLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPPTFGQGTKVEIKR (SEQ ID NO: 554)
BMS3h5
DIQMTQSPSFLSASVGDRVTITCRASHFIATLLSWYQQKPGKAPKLLITYGSLLQSGVPSRFSGSGSGTDFTLTISSLQ
40 PEDFATYYCGQGVLWPPTFGQGTKVEIKR (SEQ ID NO: 555)
BMS3h6
DIQMTQSPSSLSASVGDRVTITCRASHFIGTLLSWYQQKPGKATKLLITYGSLLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPPTFGQGTKVEIKR (SEQ ID NO: 556)
BMS3h7
DIQMTQSPSSLSASVGDRVTITCRASHFIGSLLSWYQHKPGKAPKLLITYGSLLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPATFGQGTKVEIKR (SEQ ID NO: 557)
50 BMS3h8
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
DIQMTQSPSSLSASVGDRVTITCRASHFIGTLLSWYQHKPGKAPKLLITYGSLLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPATFGQGTKVEIKR (SEQ ID NO: 558)
BMS3h9
DIQMTQSPSSLSASVGDRVTITCRASHFIGTLLSWYQHKPGKAPKLLITYGSMLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPATFGQGTKVEIKR (SEQ ID NO: 559)
BMS3h10
DIQMTQSPSSLSASVGDRVTITCRASHFIGTLLSWYQHKPGKAPKLLITYGSLLQSGVPSRFSGSGSGTEFTLTISSLQ
PEDFATYYCGQGVLWPATFGQGTKVEIKR (SEQ ID NO: 560)
BMS3h11
DIQMTQSPSSLTASVGDRVTITCRASHFIGTLLSWYQHKPGKAPKLLITYGSLLQSGVPSRFSGSGSGTEFTLTISSLQ
PEDFATYYCGQGVLWPATFGQGTKVEIKR (SEQ ID NO: 561)
BMS3h12
NIQMTQSPSSLSASVGDRVTITCRASHFIGTLLSWYQHKPGKAPKLLITYGSLLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPATFGQGTKVEIKR (SEQ ID NO: 562)
BMS3h13
DIQMTQSPSSLSASVGDRVTINCRASHFIGTLLSWYQHKPGKAPKLLITYGSLLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPATFGQGTKVEIKR (SEQ ID NO: 563)
BMS3h14
DIQLTQSPSSLSASVGDRVTITCRASHFIGTLLSWYQQKPGKATKLLITYGSLLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPPTFGQGTKVEIKR (SEQ ID NO: 564)
BMS3h15
DIQMTQSPSSLYASVGDRVTITCRVSHFIGTLLSWYQQKPGKAPKLLITYGSLLQSGVPSRFSGSGSGTDFTLSISSLQ
PEDFATYYCGQGVLWPPTFGQGTKVEIKQ (SEQ ID NO: 565)
BMS3h16
DIQMTQSPSSLSASVGDRVTITCRASHFIGTLLSWYQQKPRKAPKLLITYGSLLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPPTFGQGTKVEIKR (SEQ ID NO: 566)
BMS3h17
DIQIIQSPSSLSASVGDRVTITCRASHFIGTLLSWYQQKPGKAPKLLITYGSLLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPPTFGQGTKVEIKR (SEQ ID NO: 567)
40 BMS3h18
DIQMTQSPSSLSASVGDRVTITCRASHFIGTLLSWYQLKPGKAPKLLITYGSLLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPATFGQGTKVEIKR (SEQ ID NO: 568)
BMS3h19
45 DIQMTQSPSSLSASVGDRVTITCRASHFIGTLLSWYQLKPGKAPKLLITYGSWLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPATFGQGTKVENKR (SEQ ID NO: 569)
BMS3h20
DIQMTQSPSSLSASVGDRVTITCRASHFIGTLLSWYQLKPGKAPKLLITYGSLLQRGVPSRFSGSGSGTDFTLTISSLQ
50 PEDFATYYCGQGVLWPATFGQGTKVEIKR (SEQ ID NO: 570)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h21
DIQMTQAPSSLSASVGDRVTITCRASHFIGTLLSWYQLKPGKAPKLLITYGSLLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPATFGQGTKVENKR (SEQ ID NO: 571)
BMS3h22
DIQMTQSPSSLSASVGDRVTITCRASHFIGSLLSWYQQKPGKAPKLLITYGSLLQSGVPSRFSGSGSGTDFALTISSLQ
PEDFATYYCGQGVLWPATFGQGTKVEIKR (SEQ ID NO: 572)
BMS3h23
DIQMTQSPSSLSASVGDRVTITCRASHFIGSLLSWYQVKPGKAPKLLITYGSLLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPATFGQGTTVEIKR (SEQ ID NO: 573)
BMS3h24
DILMTQSPSSLSASVGDRVTITCRASHFIGSLLSWYQQKPGKAPKLLITYGSLLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPATFGQGTKVEIKR (SEQ ID NO: 574)
BMS3h25
DIQMTQSPSSLSASVGDRVTITCRASHFIGTLVSWYQQKPGKAPKLLITYGSLLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPATYGQGTKVEIKR (SEQ ID NO: 575)
BMS3h26
DIQMTQSPSSLSASVGDRVTITCRASHFIGTLVSWYQQKPGKAPKLLITYGSLLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPATFGQGTKVENKR (SEQ ID NO: 576)
BMS3h27
DIKMTQSPSSLSASVGDRVTITCRASHFIGTLVSWYQQKPGKAPKLLITYGSMLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPATFGQGTKVEIKR (SEQ ID NO: 577)
BMS3h28
DIQMTQSPSSLSASVGDRVTITCQASHFIGTLVSWYQQKPGKAPKLLITYGSLLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPATFGQGTKVEIKR (SEQ ID NO: 578)
BMS3h29
DIQMTQSPSSLSASVGDRVTITCRASHFIGTLLSWYQQKPGKAPKLLITYGSWLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPATFGQGTKVEIKR (SEQ ID NO: 579)
BMS3h30
DIQMTQSPSSLSASVGDRVTITCRASHFIGTLLSWYQLKPGKAPKLLITYGSWLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPATFGQGTKVEIKR (SEQ ID NO: 580)
BMS3h31
DIQMTQSPSSLSASVGDRVTITCRASHFIGTLLSWYQQKPGKAPKLLITYGSLLQSGVPSRFSGSGFGTDFTLTISSLQ
PEDFATYYCGQEVLWPATFGQGTKVEIKR (SEQ ID NO: 581)
45 BMS3h32
DIQMTQSPSSLSASVGDRVSITCRASHFIGTLLSWYQQKPGKAPKLLITYGSLLQSGVPSRFSGSGFGTDFTLTISSLQ
PEDLATYYCGQEVLWPATFGQGTKVEIKR (SEQ ID NO: 582)
BMS3h33
50 DIQMTQSPSSLSASVGDRVTITCQASHFIGTLLSWYQQKPGKAPKLLITYGSLLQSGVPSRFSGSGFGTDFTLTISSLQ
PEDFATYYCGQEVLWPATFGQGTKVEIKR (SEQ ID NO: 583)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h34
DIQMTQSPSSLSASVGDRVTITCRASHFIGTLLSWYQQKPGKAPKLLITYGSLLQSGVPSRFSGSGFGTEFTLTIGSLQ
PEDFATYYCGQGVLWPATFGQGTKVEIKR (SEQ ID NO: 584)
BMS3h35
DIQMTQSPSSLSASVGDRVTITCRASHFIGTLLSWYQQKPGKATKLLITYGSLLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPPTFGQGTKVEIKR (SEQ ID NO: 585)
BMS3h2301
DIQMTQSPSSLSASVGDRVTITCRASHFIASLLSWYQVKPGKAPKLLITYGSLLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPATFGQGTTVEIKR (SEQ ID NO: 586)
BMS3h2302
DIQMTQSPSSLSASVGDRVTITCRASHFIAQLLSWYQVKPGKAPKLLITYGSLLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPATFGQGTTVEIKR (SEQ ID NO: 587)
BMS3h2303
DIQMTQSPSSLSASVGDRVTITCRASHFIAQLLSWYQVKPGKAPKLLITYGSLLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPATFGQGTTVEIRR (SEQ ID NO: 588)
BMS3h2304
DIQMTQSPSSLSASVGDRVTITCRASHYIASLLSWYQVKPGKAPKLLITYGSLLQSGAPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPATFGQGTTVEIKR (SEQ ID NO: 589)
BMS3h2305
DIQMTQSPSSLSASVGDRVTITCRASHFIGSLLSWYQVKPGKAPKLLITWASYLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPATFGQGTTVEIKR (SEQ ID NO: 590)
BMS3h2306
DIQMTQSPSSLSASVGDRVTITCRASHFIGSLLSWYQVKPGKAPKLLITWTSYLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPATFGQGTTVEIKR (SEQ ID NO: 591)
BMS3h2307
DIQMTQSPSSLSASVGDRVTITCRASHFIGSLLSWYQVKPGKAPKLLITWSSYLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPATFGQGTTVEIKR (SEQ ID NO: 592)
BMS3h2308
DIQMTQSPSSLSASVGDRVTITCRASHFIGSLLSWYQVKPGKAPKLLITWGSWLQSGVPSRFSGSGSGTDFTLTISSLQ
40 PEDFATYYCGQGVLWPATFGQGTTVEIKR (SEQ ID NO: 593)
BMS3h2309
DIQMTQSPSSLSASVGDRVTITCRASHFIGSLLSWYQVKPGKAPKLLITWASWLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPATFGQGTTVEIKR (SEQ ID NO: 594)
BMS3h2310
DIQMTQSPSSLSASVGDRVTITCRASHFIGSLLSWYQVKPGKAPKLLITWSSWLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPATFGQGTTVEIKR (SEQ ID NO: 595)
50 BMS3h2311
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
DIQMTQSPSSLSASVGDRVTITCRASHWIAQLLSWYQVKPGKAPKLLITYGSLLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPATFGQGTTVEIKR (SEQ ID NO: 596)
BMS3h2312
DIQMTQSPSSLSASVGDRVTITCRASHFIGSLLRWYQVKPGKAPKLLITYGSLLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPATFGQGTTVEIKR (SEQ ID NO: 597)
BMS3h2313
DIQMTQSPSSLSASVGDRVTITCRASHRIAQLLSWYQVKPGKAPKLLITYGSLLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPATFGQGTTVEIKR (SEQ ID NO: 598)
BMS3h2314
DIQMTQSPSSLSASVGDRVTITCRASHYIASLLSWYQVKPGKAPKLLITYGSLLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPATFGQGTTVEIKR (SEQ ID NO: 599)
BMS3h2315
DIQMTQSPSSLSASVGDRVTITCRASHFIGSLLSWYQVKPGKAPKLLIRFGSLLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPATFGQGTTVEIKR (SEQ ID NO: 600)
BMS3h2316
DIQMTQSPSSLSASVGDRVTITCRASHFIGSLLSWYQVKPGKAPKLLITYKSYLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPATFGQGTTVEIKR (SEQ ID NO: 601)
BMS3h2317
DIQMTQSPSSLSASVGDRVTITCRASHFIGSLLSWYQVKPGKAPKLLITWGSYLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPATFGQGTTVEIKR (SEQ ID NO: 602)
BMS3h2318
DIQMTQSPSSLSASVGDRVTITCRASHFIWGPLSWYQVKPGKAPKLLITYGSLLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDSATYYCGQGVLWPATFGQGTTVEIKR (SEQ ID NO: 603)
BMS3h2319
DIQMTQSPSSLSASVGDRVTITCRASHWIATLLSWYQVKPGKAPKLLITYGSLLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPATFGQGTTVEIKR (SEQ ID NO: 604)
BMS3h2320
DIQMTQSPSSLSASVGDRVTITCRASHFIWGPLSWYQVKPGKAPKLLITYGSLLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPATFGQGTTVEIKR (SEQ ID NO: 605)
40 BMS3h2321
DIQMTQSPSSLSASVGDRVTITCRASHFIGSLLNWYQVKPGKAPKLLITYGSLLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPATFGQGTTVEIKR (SEQ ID NO: 606)
BMS3h2322
45 GIQMTQSPSSLSASVGDRVTITCRASHFIGSLLSWYQVKPGKAPKLLITYGSWLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCGQGVLWPATFGQGTTVEIKR (SEQ ID NO: 607)
TABLE 4
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
Human Anti-CD40 Variable Domain Encoding Nucleotide Sequences
BMS3h201
GAGGTGCAGCTGTTGGAGTCCGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCGTTTTACTTTCAGGAGT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 608)
BMS3h258
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCGTTTTACTTTCACGAGT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 609)
BMS3h-37
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGTGGTATGAGATGCAGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCGATTTCTGG
TGATGGTTATCGTACATACTACGCAGACTCCGTGAAAGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCTTGGGTATTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 610)
BMS3h-38
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGAGCCGTTTCGTTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 611)
BMS3h-41
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTACTGAGTATGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTGGAGTGGGTCTCATCTATTTCGGG
TAATGGTGCTAATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCCGCTTAGGTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 612)
BMS3h-43
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTACAGCCTCCGGAT
40 TCACCTTTAATATGTATGAGATGTCGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGGTATTAGTAG
GCGTGGTTTTACTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGAGCCGATTACGTATGCTATGA
GGTATGCGCGTTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 613)
45 BMS3h-56
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTATTTTTGACTACT
50 GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 614)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h-106
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTTCGACTTATCATATGCAGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTGGAGTGGGTCTCAATGATTGATGC
GGATGGTCTTGGGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACCGGGTCCGCAGTTTGGTCAGT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 615)
BMS3h-107
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCTTCCGGAT
TCACCTTTTCGGGGTATGATATGCAGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAACGATTAGTGC
GTCGGGTGTTTTTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCACCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAATATCCTAATCGTTTTGCGCTTA
ATAATTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 616)
BMS3h-131
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAATA
GTTCTATTTTGTGGGCGTTAGCTTGGTACCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCGAGAGTTCTTCCGG
TTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGTTCAGAATGCGGGTTGGCCTGGTACGTTCGGCCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 617)
BMS3h-193
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
AGACGATTGAGCGTCGTTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATCTTGCTTCCCG
TTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTCATCAGTATGCGAGTCCACCTTTGACGTTCGGCCAAGGGACCAAAGTGGAAA
TCAAACGG (SEQ ID NO: 618)
BMS3h-198
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCTGGGTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACGATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGATCCTTATAGTTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 619)
BMS3h-202
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCCGACTGCTGAGATGGTGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATCTATTTCGGC
TAGTGGTGGTTCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCCGGTGAGTTATGTGGCGA
CGTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 620)
BMS3h-217
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
45 ATTTTATTGGTACTCTGTTATCTTGGTACCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTATGGTTCCTT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 621)
50 BMS3h-1
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCCGAAGAATGAGATGACGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCGATTGAGTC
GGATGGTCAGGCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCTGAGGACACCGCGGTATATTACTGTGCGAAAAATCGGATTCCTGATCTTGTGT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 622)
BMS3h-2
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGATGCTGGGGCTATGACGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATCTATTGATAA
GGAGGGTCTGTCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGGTAGGATTCCTGGGCTGGTTT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 623)
BMS3h-3
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGGTGATGCGGCGATGACTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCGATTCAGCC
TATGGGTGATGGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCGTCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGGCGTATTCCTACTCTTCAGT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 624)
BMS3h-4
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGGATTCGCCTATGACTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTACTTC
GAATGGTTATGAGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGGCGTATTCCTACTCTTCATT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 625)
BMS3h-5
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGATGAGCATGATATGAGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACGTATTGGTCC
GGATGGTTTTCATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGGCGTATTCCTACTCTTCATT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 626)
BMS3h-6
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGGTGAGTATCATATGTCTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAAGGATTACTCC
TCTTGGTACGCTTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGGCGTATTCCTTCGCTTACGT
40 TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 627)
BMS3h-7
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGGTACGAATGCGATGAGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTGGAGTGGGTCTCAAGGATTTCGCC
45 GGGTGGTGATTATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTGTATTACTGTGCGAAAGGGCGTGTTCCGGATCTGCTTT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 628)
BMS3h-8
50 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCCGTCTGAGGAGATGTCTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAAGGATTTCGGC
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
TGATGGTGCTAATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACGCCGCGGTATATTACTGTGCGAAAGGGCGTGTTCCGGATCTGCTTT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 629)
BMS3h-9
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCTGAGGATGATATGACTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACGTATTGCGGT
TGATGGTGATCGGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGTAAGGTTCCGTCTCTTCATT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 630)
BMS3h-10
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGATCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTAGGACGATGGATATGTCTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACGTATTACGGG
TGATGGTATGAATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGGGGACACCGCGGTATATTACTGTGCGAAAGGGGTGACTCCGGATTTGACTT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 631)
BMS3h-11
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGCGTGATGATATGACGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACGTATTAATGC
TGGGGGTGTGCATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGGGGTGACTCCGGATTTGACTT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 632)
BMS3h-12
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGATGATGATTCTATGACGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACGGATTTCGAG
TGATGGTGCGAGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGGGTGACTCCGGATTTGACTT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 633)
BMS3h-13
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTACTGAGGAGGATATGACGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACGTATTGATAG
TGTTGGTGAGGGGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGGGTGACTCCGGATTTGACTT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 634)
40 BMS3h-14
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTTCTGATTCGGCGATGAGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACGGATTGATAA
TCCTGGTCAGCATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGGTACTGTTCCTACGCTGGAGT
45 TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 635)
BMS3h-15
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGGGCAGCATAGTATGACTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACGTATTGATGG
50 TGGGGGTTATAATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGGGAGGTTCCTCGTCTTCATT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 636)
BMS3h-16
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGGTCAGGAGCCTATGACTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACGGATTGCGTA
TAATGGTGGTGATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGGATTACTCCTAATTTGACTT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 637)
BMS3h-17
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGAATTATCCGATGTCTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACGTATTAATGC
TACGGGTTCTATTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGGGTTATTCCTCATTTGATGT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 638)
BMS3h-18
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGTGATTATGATATGAGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACGTATTACTGG
TACTGGTAATAGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGCAAGGGGTGGTGCCGTATCTTGCTT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 639)
BMS3h-19
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGGCTGATGCGATGACGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAAGGATTAATGT
GGATGGTGATCGGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGTACTGTTCCTACGCTGGAGT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 640)
BMS3h-21
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGATCGGGCGGATATGACGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAAGGATTTCGGG
GGAGGGTAAGTGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGGATGGTTCCTAATTTGGTTT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 641)
BMS3h-22
40 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCATTGGGAGCCGATGTCTTGGGTCCGCCAGGCTCCGGGGAAGGGTCTAGAGTGGGTCTCACGTATTAATTC
TTCTGGTTGGGATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGGATGGTTCCTAATTTGGTTT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 642)
BMS3h-24
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCTGATGAGCCGATGACTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACGTATTCCTCC
TGAGGGTGCTCCGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
50 TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGGATTACTCCTAATTTGACTT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 643)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h-26
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCATAATCATGATATGTCTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACGTATTAGTCG
GGGTGGTCTTCAGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGGATTGTGCCGGATCTGCATT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 644)
BMS3h-27
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTAATGAGTATCCTATGTCGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACGTATTAATGG
GGATGGTGCTAATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGGATTATTCCGGCTATGCAGT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 645)
BMS3h-28
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGGGGATGTGCCTATGTCGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAAGGATTGATCC
TTATGGTTCTAATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGTATTATGCCTAGTCTTACTT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 646)
BMS3h-29
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCGGATTATGATATGTCTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACGTATTTCGGC
GCTTGGTGCTACTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGTCAGCTTCCGGCGTTGGAGT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 647)
BMS3h-30
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTAAGCGTTATTATATGACTTGGGTCCGCCAGGCTCCAGGGAAGGATCTAGAGTGGGTCTCAGGTATTGTTCC
TTCTGGTAATAGGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGTAGGATTCCGGATCTGCATT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 648)
BMS3h-31
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCTGATTATGATATGACTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAAGGATTTCTCC
40 GACGGGTGGGCAGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGTGTTATTCCGTATTTGTCTT
TTTCTCCGTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 649)
BMS3h-32
45 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTTCTAAGTATTGGATGGGTTGGGCCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATCGATTGATTC
GCATGGTGCTGGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGTCGAGGACACCGCGGTATATTACTGTGCGAAAGGTGCTCCTAAGTTTATGACTA
CGTATACGTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 650)
BMS3h-33
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTTTGTCTTATCCGATGCATTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATCGATTGATTC
GAGGGGTTCGGTTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGTCATAGTTGGACGTTTGACT
ACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 651)
BMS3h-34
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCGAATAGTAATATGACTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACGTATTAATCC
GGATGGTGGGTCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGGAAGGGCGTATTCCTACTCTTCATT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 652)
BMS3h-35
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGGGCCGAGGAGGATGGGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATCGATTGATGA
TATTGGTCGTAGGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGGAAGGGGCGCAGGGTGTGTTGTTGT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 653)
BMS3h-36
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGGATTATAGGATGGTTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATCGATTTCTAC
TTCTGGTGAGCTGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGGAAACGGCGGGTCAGTTTTTTGACT
ACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 654)
BMS3h-39
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCCGGAGTATGAGATGGTTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTGGAGTGGGTCTCAGCGATTTCGCG
TGAGGGTCGGGCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAACCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGAGCCTGTTCGTTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 655)
BMS3h-40
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTTCGACTTATGAGATGCTTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATCTATTTCTTC
TTCTGGTAATTATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCCGCTGATGTTTGACTACT
40 GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 656)
BMS3h-42
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGATACTGAGGAGATGAGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCGATTAGTCC
45 TAATGGTGCTTTTACATTCTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCCTATTCTGTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 657)
BMS3h-44
50 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGGTCATTATGATATGGTTTGGGTCCGCCAGGCTCCAGGGAGGGGTCTAGAGTGGGTCTCAACTATTAATGG
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
TGCTGGTCTGAATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGCAAAGTGCTAGTCGTATTTTTGACT
ACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 658)
BMS3h-45
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTAGGAGTTATGAGATGGCGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATCTATTAGTAC
TCTGGGTACGAAGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGCAATCTTCTACTCATATTTTTGACT
ACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 659)
BMS3h-46
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTATTAGGTATGAGATGGCTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAAGTATTTCGTC
GTCTGGTTGGACGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAAGTGATGCTCATATTTTTGACT
ACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 660)
BMS3h-47
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTTATGCTTATGAGATGGCTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATCTATTTCGGA
TGATGGTACGCGGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGATCTGGGGCAGGGGTTTGACT
ACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 661)
BMS3h-48
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCTGATCATGGGATGACGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGGGATTGGTCC
GTCTGGTGAGGCGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGATCGTATTCCTAATCTTGTGT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 662)
BMS3h-49
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGTCTCAGGATATGTCTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGGTATTAGTCC
GAATGGTTGGGATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGATAGGTCTGATTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 663)
40 BMS3h-50
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGGGGATTATGATATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAAGGATTCGTCA
TCCGGGTGGTGTTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGCTGTTCCTAAGGGTTTTGACT
45 ACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 664)
BMS3h-51
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGTTTATTGGATGACTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATCTATTGATCC
50 GCAGGGTGGGATGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCTCGCGACAATTCCAAGAACACGCTG
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGCGCGTATTCCTAATTTGGAGT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 665)
BMS3h-52
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGAGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTAGTGCTTATGATATGACGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTTGAGTGGGTCTCACGTATTAATCC
GACGGGTTCTTATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGCTAAGATTCCGAATTTGGTTT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 666)
BMS3h-53
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCGGATAGTGAGATGATGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGGTATTGCGCA
TAATGGTGGGCATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGCTGGTCATCCTCAGCAGACTG
AGGCTTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 667)
BMS3h-54
GAGATGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCTACTTATGATATGTATTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAAAGATTTCTCC
GAATGGTTGGAGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAATATCAGACGCATTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 668)
BMS3h-55
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTAGTGTTTATGATATGAGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAACGATTTCTTC
TTCGGGTACGTATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAATATCCTAAGAATTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 669)
BMS3h-57
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTTCTCATGAGGATATGACTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAAGTATTAGTCC
GAATGGTTGGGATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACGTACTAGGAGTAAGTTTGACT
ACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 670)
BMS3h-58
40 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGAAGTATATTATGGGTTGGGCCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAACGATTGATTA
TTGGGGTCAGCATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACTATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACGTAGTCATCTTATTCCTCTGC
AGTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 671)
BMS3h-59
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTTCTGATTATGCGATGGGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTGGAGTGGGTCTCAACGATTTCGTA
TGTGGGTTATTATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
50 TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAAAGGCTCTGCGGGGGGAGGCGT
TTACGGAGCGTTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 672)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h-60
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGGTCCGTATATGATGCATTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAACGATTGAGGT
TAATGGTAATAGGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAATGGGTTGGTTCGAAGACGTCGT
CGGATAAGAGTTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 673)
BMS3h-61
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGGTACGACGGAGATGGCTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAAGTATTGGTAG
TGCTGGTGCTTGGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAATTGGTGGGCATCCTCAGGGTC
AGTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 674)
BMS3h-62
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGCCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCCTAGGGAGTGGATGGCTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAAGTATTCAGCC
TATGGGTCAGACTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAATATTCTCGGAATAAGGGGTTTT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 675)
BMS3h-63
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTACGAGTGAGTATATGGGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATCTATTCAGAG
GTATGGTAGTACGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACATGAGTCTAATTGGGAGACTT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 676)
BMS3h-70
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTTCGGTGTATAGTATGCAGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCGATTACTCC
TAATGGTACTCGGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAACTCTTGGTCGGGGTTCTTATC
CTGGTGTTGATTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 677)
BMS3h-71
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCCGAGTTATGCTATGACGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTGGAGTGGGTCTCACGTATTACGGC
40 GGATGGTACTGTTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGTTCTATTCCGATGCTTACGT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 678)
BMS3h-72
45 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTTCGACTTATGATATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTTCTCC
TAATGGTACTGGTATATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAAATCAGAGTGTTCATCATGCTG
TTTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 679)
BMS3h-73
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGAATTATGAGATGACGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACGTATTGCGCC
GCATGGTCGGCTTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGGTCAGATTCCGATGCTTGATT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 680)
BMS3h-74
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTTCGCATTATATGATGATGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAACGATTTCTCA
TTTTGGTGATATTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAAATGATATGGTGATGAAGAATG
GGGGGTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 681)
BMS3h-75
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGAGGTATGATATGAGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACGTATTGATTC
GCGGGGTTGGTCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGGTTGGTGCCGCATCTGAGGT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 682)
BMS3h-76
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCGAATGCGCAGATGACTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAAGGATTGATGC
TATGGGTGATGCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGTAAGGTTCCGAGTATTGACT
ACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 683)
BMS3h-77
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCGAATGCGCAGATGACTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAAGGATTGATGC
TATGGGTGATGCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGGTGTTATTCCGGCGTTTGACT
ACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 684)
BMS3h-78
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCAGAATGATCGGATGCATTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATCGATTTCTGC
TACTGGTGGTGATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACAGACGGGTACGAATCGTTTTG
40 ACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 685)
BMS3h-79
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTAATCAGCCTTATATGTCGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTGGAGTGGGTCTCATCTATTGATGC
45 TTCGGGTGGTACTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACGCCGCGGTATATTACTGTGCGAAAGATCGTATTCCTAATCTTGTGT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 686)
BMS3h-80
50 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGATAATGAGAATATGACTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACGTATTGATGG
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
TGGGGGTTATAATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGGCAGGTTCCTGAGCTGCTGT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 687)
BMS3h-81
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGTTTCGTCGAATATGACTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTATGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGTCGGATTCCTACGTTGGTGT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 688)
BMS3h-82
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGTTTCGTCGAATATGACTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTATGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGATCGTATTCCTAATCTTGTGT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 689)
BMS3h-83
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTTCTGATGATTCGATGAGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACGTATTAATGA
TGCTGGTAGTTCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGTACTATTCCTCTTCTGGAGT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 690)
BMS3h-84
GAGATGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGTTTCGGATACTATGAGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACGTATTGATGG
GACTGGTGGTGATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGGGGACACCGCGGTATATTACTGTGCGAAAGGGCTTATTCCTGATCTTCAGT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 691)
BMS3h-85
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGATGAGGAGGAGATGACGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACGTATTATTGG
TGGTGGTCATGAGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGTACTATTCCTCTTCTGGAGT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 692)
40 BMS3h-86
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGATAATGAGAATATGACTTGGGTCCGCCAGGCTCCAGGGAAGGATCTAGAGTGGGTCTCACGGATTACTGA
GAGGGGTGATGTGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGTACTGTTCCTACGCTGGAGT
45 TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 693)
BMS3h-87
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGATGAGGAGGAGATGACGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACGTATTATTGG
50 TGGTGGTCATGAGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGTACTGTTCCTACGCTGGAGT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 694)
BMS3h-88
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCATGAGACGGAGATGACGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAATCG
GCTGGGTCAGGATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGTAGGATTCCTGGGCTGGTTT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 695)
BMS3h-89
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTTCTGATGATTCGATGAGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACGTATTAATGA
TGCTGGTAGTTCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGTACTGTTCCTACGCTGGAGT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 696)
BMS3h-90
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGATAATGAGAATATGACTTGGGTCCGCCAGGCTCCAGGGAAGGATCTAGAGTGGGTCTCACGGATTACTGA
GAGGGGTGATGTGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGTCGGATTCCTACGTTGGTGT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 697)
BMS3h-91
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTTCTGATGATTCGATGAGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACGTATTAATGA
TGCTGGTAGTTCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGGATTACTCCTAATTTGACTT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 698)
BMS3h-92
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCTGATGAGCCGATGACTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACGTATTCCTCC
TGAGGGTGCTCCGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGGCTTATTCCTGATCTTCAGT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 699)
BMS3h-93
40 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCAGGATAGTGATATGACGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTGCTGC
GCCTGGTGGTAGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGATCGTATTCCTAATCTTAGGT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 700)
BMS3h-94
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGTTTCGGATACTATGAGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACGTATTGATGG
GACTGGTGGTGATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
50 TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGGCAGGTTCCTGAGCTGCTGT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 701)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h-95
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCAGGATAGTGATATGACGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTGCTGC
GCCTGGTGGTAGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGATCGTATTCCTAATCTTGTGT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 702)
BMS3h-96
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCGCCGGAT
TCACCTTTGATCTGGCGGAGATGACTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACGTATTGATGA
GGATGGTGCTTCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACGCCGCGGTATATTACTGTGCGGAAGGTGTTATTCCGTCTCTGACTT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 703)
BMS3h-97
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTACTGATAAGCATATGAGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACGGATTTCGCC
TGATGGTACGTATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACGCCGCGGTATATTACTGTGCGGAAGGTGTTATTCCGTCTCTGACTT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 704)
BMS3h-98
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCTGAGGATGATATGACTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACGTATTGCGGT
TGATGGTGATCGGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTACCGAGGACACCGCGGTATATTACTGTGCGAAAGGGAAGACGCCGCATCTTGTGT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 705)
BMS3h-99
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCGCCGGAT
TCACCTTTGATCTGGCGGAGATGACTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACGTATTGATGA
GGATGGTGCTTCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGTCAGGTTCCTGCTTTGGTTT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 706)
BMS3h-100
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGGATTCGATGATGTCGTGGGTCCGCCAGGCGCCAGGGAAGGGTCTAGAGTGGGTCTCACGGATTGATCC
40 TGGGGGTGCTCAGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGGGTGACTCCGGATTTGACTT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 707)
BMS3h-101
45 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGCATGCGGATATGAGTTGGGTCCGCCAGGCTTCAGGGAAGGGTCTAGAGTGGGTCTCACGTATTGATAA
TAGTGGTCAGTCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGGGTGACTCCGGATTTGACGT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 708)
BMS3h-102
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTAGTGAGGCGGAGATGAATTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACGTATTACGAC
GGATGGTGATTCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGGCGTATTCCTACTCTTCATT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 709)
BMS3h-103
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCAGGAT
TCACCTTTGATGATAGTGATATGACTTGGGTCCGCCAGGCTCCAGGGAAGAGTCTAGAGTGGGTCTCATATATTCGGGG
TGATGATGATGAGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAAATCGGATTCCTGATCTTGTGT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 710)
BMS3h-108
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTAATGTGGCGGATATGCAGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAAGTATTAGTCC
GAATGGTTGGGATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACATGCTTCTACGGAGGGGCCGA
CTGCTTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 711)
BMS3h-109
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGGGCCGTATGATATGGGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTGGAGTGGGTCTCATGGATTTCTGC
TCATGGTTCGTTTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAATGGCCTTATAAGTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 712)
BMS3h-110
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGGGAGTGGGTCTATGAGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACGGATTGGTAG
TAATGGTGCGGATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGGATGGTTCCTAATTTGGTTT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 713)
BMS3h-111
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTAATCGTTTTGATATGACGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGATCGTATTCCTAATCTTGTGT
40 TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 714)
BMS3h-112
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGGGGAGAGTGATATGAAGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAAGTATTAGTCC
45 GAATGGTTGGGATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAATCTCCTTCTTCTCGTCTTAAGT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 715)
BMS3h-139
50 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGATAGTAGTGAGATGAGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATCGATTGAGAA
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
TCAGGGTGGTGCGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGATCGTATTCCTAATCTTGTGT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 716)
BMS3h-140
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCCTTGATGCGTATCCTATGTATTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATGGATTGCTTC
GGGTGGTGGTGCGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACGTACGAAGAATTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 717)
BMS3h-141
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTATGAGTTATTCTATGGCTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGGGATTACTTC
TAATGGTAATCGGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAATCGACTGGGGCTAATAGTAGGA
ATTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 718)
BMS3h-142
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGGGGTATCTGATGTCGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAAGTATTGCGGC
TAATGGTATGCAGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAAAGCCGAGGGGTATTTGGGATG
GGGATTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 719)
BMS3h-143
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCATGAGTCTACGATGACGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAACTATTCGGCA
TCCGGGTGAGTTTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGGGGACACCGCGGTATATTACTGTGCGAAAGGGCTTATTCCTGATCTTCAGT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 720)
BMS3h-144
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCGATGTATAGTATGAGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATCGATTGCGCC
GCCGGGTGGTAGGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACAGTCGCTGACGGGGTATAGTA
GGTCTTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 721)
40 BMS3h-145
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTTCGCAGAATCCGATGTCGTGGGTCCGCCACGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAACGATTCCTGC
GAATGGTCGTCCTACATCCTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAATATAGTCAGCAGCCGGGTCGTC
45 GGTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 722)
BMS3h-146
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCTAATTATCATATGACGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATCGATTCCTGA
50 TAGTGGTAAGCAGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
TATCTACAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGTAGGATTCCGTCTCTTCTTT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 723)
BMS3h-147
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCGCAGTATCATATGCGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAACGATTAATGA
TATTGGTAGTAATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGTTGGGGGGCGGGGGAGTTTTT
CTTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 724)
BMS3h-148
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTTCTTCGTATGATATGAAGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAACGATTAGTGC
GTCTGGTGTGTTTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACGGGAGCATGCGGGTCAGCCGC
CTTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 725)
BMS3h-149
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTAATGGTTATGCTATGAGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAACTATTAATGC
TAATGGTAAGTATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAAAGTTGACTCTTGCTTCTAATT
ATTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 726)
BMS3h-150
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTATGGATTATGATATGAAGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAAGTATTACTGC
GCTTGGTAAGAAGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGATAGTGTTAAGTATCCTCTTA
ATCTTTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 727)
BMS3h-151
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCCGCATTATACGATGGCGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTGGAGTGGGTCTCATCTATTCAGTC
GCCTGGTTGGCGGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAATATGGGGATGGTCTTCCTTTGA
CTTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 728)
BMS3h-167
40 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTAGTGGTACGCCGATGTCTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACGTATTGGGGA
TGAGGGTCAGGAGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGGGTGACTCCGGATTTGACTT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 729)
BMS3h-168
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTAGTAGTAGTTCGATGTCTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCGATTGGGTC
TGATGGTCCGAGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
50 TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGGCGTATTCCTACTCTTCATT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 730)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h-169
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTAATCCTGGTGAGATGACGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAAGTATTGATGG
GTCTGGTTCTTCGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGATGACACCGCGGTATATTACTGTGCGAAAGGGCGTATTCCTACTCTTCATT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 731)
BMS3h-170
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCCTGAGTCTATGATGGGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATCGATTGGGTA
TCCTGGTGCTACTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGGTGGTAGTCGGGATGATAATT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 732)
BMS3h-171
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGCCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGGTCAGCATAGTATGCATTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAAGTATTAGTGT
TCCGGGTCCGAAGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAAGTCTTAGGGATTTGCGTCCGG
GTGATAGTAAGAGTTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 733)
BMS3h-197
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGGTTCTGCTGCTATGGATTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATCTATTAATGA
TATGGGTTCTAATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACAGGGTGGTCGTTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 734)
BMS3h-199
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGGTTATGATAGGATGGCTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATCGATTGATGG
TCCTGGTGGGGCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGGAAGGGAGGAGGGTTCCTGATTTTG
ACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 735)
BMS3h-200
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGGTGAGTATGAGATGACTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAAGGATTGATCC
40 GTTTGGTTCTGAGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGGAAGGTGTGGTTCCTGATTTGAATT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 736)
BMS3h-201
45 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGATAAGTATGTTATGGGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAACTATTGGTAG
TTATGGTGGGGCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAAGGCTTACTCTTAGTGCGACTA
AGTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 737)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h-203
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGGATTATGTGATGGGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAACTATTGCGCA
TCGGGGTGATATTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACGTAGGCGTCTTAGTGATTATC
GGTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 738)
BMS3h-204
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGGGCAGTTTGATATGTATTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCGATTAGTCC
GGCTGGTACTGGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGCGGGGGATCGGTCTAGTCTTT
TTGACTACAGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 739)
BMS3h-205
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTAAGGATACGGGTATGACGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAAGTATTTCTAG
TTATGGTCGTGATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACGCCGCGGTATATTACTGTGCGAAATTGAATGCGGCGCTGGGTTTTG
ACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 740)
BMS3h-206
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGGTCCGTATCCGATGAGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGGTATTAATGC
GCCGGGTACGAGGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGCAACAGATGTCTAGTGGGGTTTTTG
ACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 741)
BMS3h-207
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTTCGAATCAGGATATGACTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAAGTATTGATAG
TTCTGGTCAGCTTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGTTAAGTCTCTTGCGCGGTTTG
ACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 742)
BMS3h-208
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGAT
TCACCTTTCCTGAGTCTGATATGAAGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAAGTATTAGTCC
GAATGGTTGGGATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACCGGCTCAGGTTCTGTTTGACT
ACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 743)
BMS3h-209
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
45 TCACCTTTGAGCAGTATGTGATGGGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAACGATTGGTAC
GTCGGGTAAGTATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGCAACGTAGGTCTCTGACTCGGGTTC
ATTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 744)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h-210
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGGTGTGGAGCATATGAGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCGATTACGGG
TGATGGTGATCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAACGGTTTCGTGGAATGGTCGTT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 745)
BMS3h-211
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCGTGGTATAATATGGGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTGGAGTGGGTCTCAAGGATTGCTCC
GTCTGGTATTATTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGGTTGCGTGGTAAGTTTGACT
ACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 746)
BMS3h-212
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTTCGAATTATGAGATGAGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATCTATTTCTTC
GGCTGGTACTGATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACAGTCGCTTAATTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 747)
BMS3h-213
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGTAGCCTCCGGAT
TCACCTTTGATGAGGAGCCGATGACTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAATTATTGATCC
GGGTGGTGGGGCGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAATCTAATAGTATGTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 748)
BMS3h-214
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTTCTGCGTATCCTATGCATTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATCTATTGCTTC
TTCGGGTATTACGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAATTTACTCGGCTGCATTTTCCTG
CGCAGTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 749)
BMS3h-215
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCTGATTATGCGATGGGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAAGGATTTCTCC
TGAGGGTTCTAGGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAATTGCGGCCGTATGCGTCGAAGT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 750)
BMS3h-230
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
45 TCACCTTTAGGCCGTATGATATGGGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAACGATTTCTCA
TCAGGGTAATCGGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGTGTCTCATCATTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 751)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h-231
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTTCTGCGTATAATATGTGGTGGGCCCGCCAGGCTCCAGGGAAGGGTTTAGAGTGGGTCTCATGGATTAATTC
GACTGGTTCTCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAAATTGGCATCGGGGGAGGTTTG
ACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 752)
BMS3h-232
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGATAGGTATCGGATGGGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAACGATTAATCG
GCTGGGTCAGAGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGTGAAGAAGCATAAGTTTGACT
ACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 753)
BMS3h-233
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCGCATTATAATATGCGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAACGATTACGAA
GACTGGTTTTCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGTGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGCGGGGCAGTTTGATTTTGACT
ACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 754)
BMS3h-234
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTAGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTTATCCTTATAGTATGCATTGGGTCCGCCAGGCTCCAGGGAAGGGTCTGGAGTGGGTCTCAACTATTGATGG
TAGTGGTATGTTTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGGAAGATTCTCTGAAGGCTTCTTTTG
ACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 755)
BMS3h-235
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCCGCTTTATGGGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATATATTGGGCC
TTATGGTCATACTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAAAGCGGAAGAAGAAGTTTGACT
ACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 756)
BMS3h-236
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCCTAGGTATCGGATGAGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAAGTATTACTCC
GTATGGTGCTCATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAATATGGTAAGTGGTATTTTGACT
ACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 757)
BMS3h-237
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
45 TCACCTTTAATGAGTATGCGATGAGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAACGATTGATCG
TCTGGGTCTTCATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAAGTGGGCCTTTTACGTTTGACT
ACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 758)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h-238
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGCGGTATAATATGCGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAACGATTGATCG
GCTGGGTCTTGCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGCGGGTTCGTGGTCTTTTGACT
ACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 759)
BMS3h-239
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGGTATTTATGATATGAAGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAACGATTTCGTC
GTCGGGTACTCATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAATATCCTCAGCCTTATCCTTTTG
ACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 760)
BMS3h-240
GAGGTGCAGCTATTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTTGGGTGTATGATATGCGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAACGATTTCTGC
GACTGGTGTGCATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAATATCCGCCTGCTGGTCGGTTTG
ACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 761)
BMS3h-241
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTTCGACTTATGATATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTTCTCC
TAATGGTACTGGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACCTCCGCAGGTGAATACTGAGT
TTGACTACCGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 762)
BMS3h-243
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGAAGGAGGATATGGGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACATATTTCGCC
GAATGGTTATGCGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAAGTTGGTCTAGTTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 763)
BMS3h-244
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTAGTGCTACTCCGATGGAGTGGGCCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAACTATTTCTGA
GAGTGGTTATAGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAATGGAATTCGACTACTGGTTTTG
ACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 764)
BMS3h-245
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
45 TCACCTTTAATACGGTGGATATGGAGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAAGTATTAGTCC
GAATGGTTGGGATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGGAAGCTCCGCATCGGGCGTTTGACT
ACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 765)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h-246
GAGGTGCAGCTGTTGGAGTCTGGGGGGGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGGATAAGGAGATGAGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACGGATTGATGC
TTTGGGTGATTCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGGAAGGGATGGTTCCTCGTCTGAAGT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 766)
BMS3h-247
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTAGTGATCATTCGATGATGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGATATTGAGCC
GCATGGTGTTCATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAATCCTACTTTTGACTACTGGGGTC
AGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 767)
BMS3h-248
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTTCGCCGCATACTATGCATTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGGTATTGGTCC
GGATGGTACTACTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACGTTCGTATAGTTGGGATCGTG
GGTGGACGTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 768)
BMS3h-249
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTTATGCTTCGGATATGAAGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAAGTATTAGTCC
GAATGGTTGGGATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGCTGATTATACTTATCATTCTT
TTGACTACTGGGGTCAGGGGACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 769)
BMS3h-250
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCGCATTATAATATGCGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAACGATTACGAA
GACTGGTTTTCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGTGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGCGGGGCAGTTTGATTTTGACT
ACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 770)
BMS3h-251
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTTCGCATTATCATATGGGTTGGGCCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGTTATTGGGCC
GAGGGGTATTTCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAATCGCCTTCGCGTCATAGGTTTG
ACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 771)
BMS3h-252
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
45 TCACCTTTAATGAGTATGCGATGAGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAACGATTGATCG
TCTGGGTCTTCATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAAGTGGGCCTTTTACGTTTGACT
ACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 772)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h-253
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGGTAATTATAGTATGAAGTGGGCCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAACTATTACTCC
TGATGGTTGGTATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGTGGGGGATGCTGTTTGGGGGT
GGATTGGTGGGTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 773)
BMS3h-254
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGGGGATTATGGTATGAAGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTACGTC
TAATGGTGATTTTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAATCTTTGTATAAGTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 774)
BMS3h-255
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGGCTCCGGAT
TCACCTTTCCTACTTATAAGATGGGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATTTATTGATTA
TTGGGGTTGGCGGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAAGTCCGTATTCTTGGACTCATG
ATAGTCCTCATTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 775)
BMS3h-256
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTAGGCCTTATACGATGTGTTGGGCCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATGTATTAGTGA
TGCTGGTTCTTTTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAAGGATGTCTTCTTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 776)
BMS3h-257
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCAGAATTATCAGATGGCTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAACTATTAGTGG
GACTGGTAAGAATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAACTCCTCAGAATTATTTTAGTG
TGCGTCGGTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 777)
BMS3h-258
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGGGGCGTATACTATGGGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAAAGATTTCGAC
GTCTGGTGGGCAGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACCTTTGAATTGGTGGGCGTTTG
ACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 778)
BMS3h-272
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
45 TCACCTTTAATGCGTATCCTATGACTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACGGATTGATGG
TTATGGTCGGCATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGGATTATTCCTAATTTTGACT
ACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 779)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h-273
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGGGGCGGTTGATATGACGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCGATTTCGCC
TAGTGGTTCTGCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGGCGTGTGCCGGATCTTGGTT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 780)
BMS3h-274
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGATAGTTATGCGATGGGGTGGGCCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTGGGGC
TAAGGGTTTGTCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGCGGCTAGGGGTAAGTTTGACT
ACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 781)
BMS3h-275
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTACTCGGTATCAGATGGGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGTTATTAATGT
TTGGGGTTCGAGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAATGTCTGGGAAGTTTGCCTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 782)
BMS3h-276
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTTTCCTGTGCAGCCTCCGGAT
TCACCTTTGGGAATTATAGTATGATGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAACGATTATTCC
TGCTGGTACGTCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACCGTCGATTAGGTTGTTTGACT
ACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 783)
BMS3h-279
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGGTGCGTATGATATGGGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATGGATTTCTCC
GAATGGTTATGATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGGGGTGTGAAGTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 784)
BMS3h-282
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGTTTGGTATGAGATGGCTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAACGATTCAGGC
TGATGGTGAGCAGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGCTTCGTATGCTCTTGTGTATC
CTCCTGAGGAGTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 785)
BMS3h-287
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
45 TCACCTTTACGAATTATAGGATGTCTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTGATGA
TCTGGGTGTGTCGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAATGGAGGCTTAAGAATAGTCAGC
CGACGGATTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 786)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h-292
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGATCAGGCTCATATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATTTATTAATCC
TTCGGGTTATTATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACCTTCGCTTAGTCCGTCTTCTT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 787)
BMS3h-293
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGACTGGTCAGATGGGTTGGGCCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAAATATTGATGG
GTCTGGTACGTATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAAGTACGCAGAATTATCGGTTTG
ACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 788)
BMS3h-296
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGGTGCTTATCCGATGTATTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATCTATTCATAA
GGATGGTAGGATTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACAGGGTACGCCGGTTGATGGGT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 789)
BMS3h-297
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCCTGATGAGGGTATGACGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAACGATTGAGAC
TGGTGGTACGGTGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAATGGATGGGTCTGGTACATGGC
AGACGTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 790)
BMS3h-298
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGATAGTCTGGGTATGGGTTGGGCCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATATATTCGGGC
TGAGGGTGCTTATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAATATCTTGCGGATTCTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 791)
BMS3h-299
GAGGTGCAGCTGTTGGAATCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTAGTGAGTCGTATATGGAGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGGTATTGATCA
TATTGGTGGTGGGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGATGATGGTCGTGGTGGGTCTA
TGTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 792)
BMS3h-300
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
45 TCACCTTTTCTGGTGGGTATATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAAGTATTGGGGC
TAGTGGTGCGTATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAACGGGGGGTAGGTTAGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 793)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h-301
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGATGAGGGGCATATGGGGTGGGTCCGCCAGGCTCCAGGGAAGGATCTAGAGTGGGTCTCATATATTGGGAG
TCTGGGTTTGCATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACGGGAGTTTAGTAATGGGGGGT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 794)
BMS3h-302
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTAAGACTAGTCCTATGTATTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATCGATTGATCG
GACTGGTGGGCATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACAGGCTCTGCTTACTGATGCGA
AGCGTTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 795)
BMS3h-303
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGATGGTCGGGATATGGTTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTCC
GAGTGGTCTGGATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGGAACGTCCTCAGATGCTGGTTACTA
ATTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 796)
BMS3h-304
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGGTAATGATCCGATGAGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGGGATTGGTCG
GGAGGGTGATTCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGATTCTATGCGGCATCAGCCGT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 797)
BMS3h-305
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGATGAGACTTATATGAAGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCGATTGGGGC
GTCGGGTGCTGATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAATTTACGCATCTGAATGGTCGGT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 798)
BMS3h-306
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGGGGGGTGGCCTATGGGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGGTATTGATAT
TGATGGTGCTCCGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGGAGGCGGGTTCTTGGTCTT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 799)
BMS3h-307
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
45 TCACCTTTAGTGATCAGGCGATGTGGTGGGCCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATTTATTCAGGG
TGATGGTGGTTTTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACCTAGTAAGCCGTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 800)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h-308
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGACTGGTCAGATGGGTTGGGCCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAAATATTGATGG
GTCTGGTACGTATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGCGGTGCGGAATTTTGCTTTTG
ACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 801)
BMS3h-309
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTAGTGGGCATGATATGTCTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTCC
TCATGGTACGCATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGGGATTAGGGGTTGGATTGGTC
ATGATACGCAGCCTTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 802)
BMS3h-310
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGAGTAAGGATATGCTTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATCTATTTCGTC
GGATGGTACTCATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGCAAGAGCTGGGTGGGTCTTGGCAGT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 803)
BMS3h-311
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCGGATCGTGATATGGTTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGGTATTGGGGC
GTCGGGTACGTCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACGCCGCGGTATATTACTGTGCGAAAGGTGGGACGGGTCCTACTGATT
TGTGGGATTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 804)
BMS3h-312
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGATGATGAGAAGATGCTTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAAGTATTAGTGT
GAGTGGTCTGCATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGGAGGCGGGTTCTTGGTCTT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 805)
BMS3h-313
GAGGTGCAGCTGTTGGAGTCCGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGGGCAGGAGAGGATGATTTGGGTCCGCCAGGCTCCTGGGAAGGGTCTAGAGTGGGTCTCAGATATTTCGGC
TTCGGGTGGGACTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGGAGGCGGGTTCTTGGTCTT
TTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 806)
BMS3h1
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCTCTGCGTCTCTCCTGTGCAGCCTCCGGAT
45 TCACCTTTGAGTGGTATGAGATGCAGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCGATTTCTGG
TGATGGTTATCGTACATACTACGCAGACTCCGTGAAAGGCCGGTTCACCATCTCCCGCGACAATTCCATGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCTTGGGTATTTTGACTACA
GGGGTCGGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 807)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h2
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGTGGTATGAGATGCAGTGGGTCCGCCGGGCTCCAGGGAAGGGACTAGAGTGGGTCTCAGCGATTTCTGG
TGATGGTTATCGTACATACTACGCAGACTCCGTGAAAGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCTTGGGTATTTTGACTACT
GGGGTCGGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 808)
BMS3h3
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGTGGTATGAGATGCAGTGGGTCCGCCGGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCGATTTCTGG
TGATGGTTATCGTACATACTACGCAGACTCCGTGAAAGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCTTGGGTATTTTGACTACC
GGGTTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 809)
BMS3h4
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGTGGTATGAGATGCAGTGGGTCCGCAAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCGATTTCTGG
TGATGGTTATCGTACATACTACGCAGACTCCGTGAAAGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCTTGGGTATTTTGACTACT
GGGGTCGGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 810)
BMS3h5
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGTGGTATGAGATGCAGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGATCTCAGCGATTTCTGG
TGATGGTTATCGTACATACTACGCAGACTCCGTGAAAGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCTTGGGTATTTTGACTACA
GGGTTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 811)
BMS3h6
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGTGGTATGAGATGCAGTGGGTCCGCCGGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCGATTTCTGG
TGATGGTTATCGTACATACTACGCAGACTCCGTGAAAGGCCGGTTCACCATCTCCCGCGACAATTCCGAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCTTGGGTATTTTGACTACT
GGGGTCGGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 812)
BMS3h7
GAGGTGCAGCTGTTGGAGACTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGTGGTATGAGATGCAGTGGGTCCGCCGGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCGATTTCTGG
TGATGGTTATCGTACATACTACGCAGACTCCGTGAAAGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTGCAAATGGACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCTTGGGTATTTTGACTACT
GGGGTCGGGGAACCCTGGTCACCGTCACGAGC (SEQ ID NO: 813)
BMS3h8
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
45 TCACCTTTGAGTGGTATGAGATGCAGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCGATTTCTGG
TGATGGTTATCGTACATACTACGCAGACTCCGTGAAAGGCCGGTTCACCATCTCACGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCTTGGGTATTTTCACTACT
GGGGTCGGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 814)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h9
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGTAGCCTCCGGAT
TCACCTTTGAGTGGTATGAGATGCAGTGGGTCCGCCAGGCTCCAGGGAATGGTCTAGAGTGGATCTCAGCGATTTCTGG
TGATGGTTATCGTACATACTACGCAGACTCCGTGAAAGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCTTGGGTATTTTGACTACT
GGGGTCGGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 815)
BMS3h10
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCTGGAT
TCACCTTTGAGTGGTATGAGATGCAGTGGGTCCGCCGGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCGATATCTGG
TGATGGTTATCGTACATACTACGCAGACTCCGTGAAAGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCTAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCTTGGGTATTTCGACTACT
GGGGTCGGGGAACCCTCGTCACCGTCTCGAGC (SEQ ID NO: 816)
BMS3h11
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGTGGTATGAGATGCAGTGGGTCCGCAAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCGATTTCTGG
TGATGGTTATCGTACATACTACGCAGACTCCGTGAAAGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCTTGGGTATTTTGACTACA
GGGGTCGGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 817)
BMS3h12
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCATGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGTGGTATGAGATGCAGTGGGTCCGCCGGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCGATTTCTGG
TGATGGTTATCGTACATACTACGCAGACTCCGTGAAAGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCTTGGGTATTTTGACTACA
GGGGTCGGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 818)
BMS3h201
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGTGGTATGAGATGCAGTGGGTCCGCCGGGCTCCAGGGAAGGGATTAGAGTGGGTCTCAATGATTTCCGG
GGATGGTTATCGTACATACTACGCAGACTCCGTGAAAGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCTTGGGTATTTTGACTACT
GGGGTCGGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 819)
BMS3h202
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGTGGTATGAGATGCAGTGGGTCCGCCGGGCTCCAGGGAAGGGACTAGAGTGGGTCTCAGCGATTTCTGG
TGACGGTTGGCGCACATACTACGCAGACTCCGTGAAAGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCTTGGGTATTTTGACTACT
GGGGTCGGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 820)
BMS3h203
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
45 TCACCTTTGGGTGGTATGAGATGCAGTGGGTCCGCCGGGCTCCAGGGAAGGGACTAGAGTGGGTCTCAGCGATTTCTGG
TGATGGTTATCGTACATACTACGCAGACTCCGTGAAAGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCTGCTCTACTTTGACTACT
GGGGTCGGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 821)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h204
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGTGGTATGAGATGCAGTGGGTCCGCCGGGCTCCAGGGAAGGGACTAGAGTGGGTCTCAGCGATTTCTGG
TGATGGTTATCGTACATACTACGCAGACTCCGTGAAAGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCTGGGGTTCTTTGACTACT
GGGGTCGGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 822)
BMS3h205
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGTGGTATGAGATGCAGTGGGTCCGCCGGGCTCCAGGGAAGGGACTAGAGTGGGTCTCAGCGATTTCTGG
TGATGGTTATCGTACATACTACGCAGACTCCGTGAAAGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGTTGGAGTATTTTGACTACT
GGGGTCGGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 823)
BMS3h206
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGTGGTATGAGATGCAGTGGGTCCGCCGGGCTCCAGGGAAGGGACTAGAGTGGGTCTCAGCGATTTCTGG
TGATGGTTATCGTACATACTACGCAGACTCCGTGAAAGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGGGTTGGAGTATTTTGACTACT
GGGGTCGGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 824)
BMS3h207
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGTGGTATGAGATGCAGTGGGTCCGCCGGGCTCCAGGGAAGGGACTAGAGTGGGTCTCAGCGATTTCTGG
TGATGGTTATCGTACATACTACGCAGACTCCGTGAAAGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCTGGCCTTCTTTGACTACT
GGGGTCGGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 825)
BMS3h208
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGTGGTATGAGATGCAGTGGGTCCGCCGGGCTCCAGGGAAGGGACTAGAGTGGGTCTCAGCGATTTCTGG
TGATGGTTATCGTACATACTACGCAGACTCCGTGAAAGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCTCTTGTACTTTGACTACT
GGGGTCGGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 826)
BMS3h209
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGTGGTATGAGATGCAGTGGGTCCGCCGGGCTCCAGGGAAGGGACTAGAGTGGGTCTCAGCGATTTCTGG
TGATGGTTATCGTACATACTACGCAGACTCCGTGAAAGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGTTGGAGTTCTTTGACTACT
GGGGTCGGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 827)
BMS3h210
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
45 TCACCTTTGAGTGGTATGAGATGCAGTGGGTCCGCCGGGCTCCAGGGAAGGGACTAGAGTGGGTCTCAGCGATTTCTGG
TGATGGTTATCGTACATACTACGCAGACTCCGTGAAAGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCTGCAGTTCTTTGACTACT
GGGGTCGGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 828)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h211
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGTGGTATGAGATGCAGTGGGTCCGCCGGGCTCCAGGGAAGGGACTAGAGTGGGTCTCAGCGATTTCTGG
TGATGGTTATCGTACATACTACGCAGACTCCGTGAAAGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGAGCTGCTCTTCTTTGACTACT
GGGGTCGGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 829)
BMS3h212
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACGGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGTGGTATGAGATGCAGTGGGTCCGCCGGGCTCCAGGGAAGGGACTAGAGTGGGTCTCAGCGATTTCTGG
TGATGGTTATCGTACATACTACGCAGACTCCGTGAAAGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGAGTTGGAGTTCTTTGACTACT
GGGGTCGGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 830)
BMS3h213
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGTGGTATGAGATGCAGTGGGTCCGCCGGGCTCCAGGGAAGGGACTAGAGTGGGTCTCAGCGATTTCTGG
TGATGGTTATCGTACATACTACGCAGACTCCGTGAAAGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGTTGCTCTTCTTTGACTACC
GGGGTCGGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 831)
BMS3h214
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCATCTTTGAGTGGTATGAGATGCAGTGGGTCCGCCGGGCTCCAGGGAAGGGACTAGAGTGGGTCTCAGCGATTTCTGG
TGATGGTTATCGTACATACTACGCAGACTCCGTGAAAGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAAACTTGGAGTATTTTGACTACT
GGGGTCGGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 832)
BMS3h215
GAGGTGCGGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGTGGTATGAGATGCAGTGGGTCCGCCGGGCTCCAGGGAAGGGACTAGAGTGGGTCTCAGCGATTTCTGG
TGATGGTTATCGTACATACTACGCAGACTCCGTGAAAGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGTTGCAGTTCTTTGACTACT
GGGGTCGGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 833)
BMS3h1
GAGGTGCAGCTGTTGGGGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTTCGAAAGAGCCGTTTCGTTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 834)
BMS3h2
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGAT
45 TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGTCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 835)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h3
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGATCTCAGCTATTAGTGG
AAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTTACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 836)
BMS3h4
GAGGTGCAGCTGTTGGATCCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGGGAAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAGGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 837)
BMS3h5
GAGGTGCAGCTGTTGGGGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 838)
BMS3h6
GAGGTGCAGCTGTTGGAGCCTGGGGGAGGCTTGGTACAGCCTGGGGGCTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCTAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTTCGAAAGAGCCGTTTCGTTTTGACTACT
GGGGTCAGGGAGCCCTGGTCACCGTCTCGAGC (SEQ ID NO: 839)
BMS3h7
GAGGTGCAGCTGTTGGATCCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGGGAAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTTAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGAGCCGTTACGTTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 840)
BMS3h8
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGGAGGAGGAGATGATCTGGGTCCGCCAGGCTCCTGGGAAGGGTCTAGAGTGGATCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCCACCGCGACAATTCTAAGAACACTCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTTCGAAAGAGCCGTTTCGTTTTGACTACA
GGGGTCTGGGAACCTTGGTCACCGTCTCGAGC (SEQ ID NO: 841)
BMS3h9
GAGGTGCAGCTGTTGGATCCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
45 TCACCTTTGGGAAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAGGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGAGCCGTTACGTTTTGACTACT
GGGGTCAGGGGACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 842)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h10
GAGGTGCAGCTGTTGGATTCTGGGGGAGGCTTTGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGATCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTGTATTACTGTGCGAAAGAGCCGTTTCGTTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 843)
BMS3h11
GAGGTGCAGCTGTTGGATCCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGATCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAATAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAGAGAGCCGTTTCGTTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 844)
BMS3h12
GAGGTGCGGCTGTTGGAGTCTGGGGAAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCACGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 845)
BMS3h13
GAGGTGCAGCAGTTGGAGTCTGGGGGAGGCCTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 846)
BMS3h201
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGAT
TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGTCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTCTACTACGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 847)
BMS3h202
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGAT
TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGTCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTCTACTTCGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 848)
BMS3h203
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGAT
45 TCACCTTTGAGGAGAAGGAGATGATTTGGGTCCGTCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTCTTCTACGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 849)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h204
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGAT
TCACCTTTCCCCAGGAGGAGATGATTTGGGTCCGTCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 850)
BMS3h205
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGAT
TCACCTTTTTCGCCGCCGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 851)
BMS3h206
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGAT
TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTAG
GCCCGGTACGAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 852)
BMS3h207
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGAT
TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTCG
GATGGGTTTCAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 853)
BMS3h208
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGAT
TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTCG
GTGGGGTCACAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 854)
BMS3h209
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGAT
TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTCG
CCTCGGTTGGAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 855)
BMS3h210
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGAT
45 TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGTCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTCG
CTGGGGTGCCAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 856)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h211
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGAT
TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGTCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTAG
GCAGGGTGGGAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGTGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 857)
BMS3h212
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGAT
TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTGT
GTCCGGTTGGAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 858)
BMS3h213
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGAT
TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTCG
GTGGGGTTGGAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 859)
BMS3h214
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGAT
TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTCG
GAACGGTCTGAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 860)
BMS3h215
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGAT
TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTGG
GCTGGGTTGGAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 861)
BMS3h216
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGAT
TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTGC
GTTGGGTTGGAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 862)
BMS3h217
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGAT
45 TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTCG
CAGGGGTTACAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 863)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h218
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGAT
TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGTCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTAG
GCACGGTTGGAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 864)
BMS3h219
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGAT
TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAAGCATTAGCAG
GAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 865)
BMS3h220
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGAT
TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTCG
GATCGGTAACAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 866)
BMS3h221
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGAT
TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTGG
GCACGGTTGGAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 867)
BMS3h222
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGAT
TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTTCGAG
GTGGGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 868)
BMS3h223
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGAT
TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGTCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTCATGTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 869)
BMS3h224
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGAT
45 TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGTCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTCCCGTACGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 870)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h225
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTGCAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGAT
TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGTCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTGG
TAGTGGTGGTGGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 871)
BMS3h226
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGAT
TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGTCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTGTACTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 872)
BMS3h227
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGAT
TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGTCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCCATGTACTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 873)
BMS3h228
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGAT
TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTAG
GAACGGTTTCAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 874)
BMS3h229
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGAT
TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTCG
CACGGGTGGGAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 875)
BMS3h230
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGAT
TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTCG
GGAGGGTGGGAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 876)
BMS3h231
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGGT
45 TCCCCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTCG
GCAGGGTTGGAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 877)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h232
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGAT
TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTAG
GGGCGGTGGGAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 878)
BMS3h233
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGAT
TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTCG
CACGGGTTACAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 879)
BMS3h234
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGAT
TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTAG
GAACGGTAGGAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 880)
BMS3h235
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGAT
TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTAG
GAACGGTTACAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 881)
BMS3h236
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGAT
TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTAG
GAAGGGTAGCAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 882)
BMS3h237
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGAT
TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTCG
GGGCGGTTGGAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 883)
BMS3h238
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGAT
45 TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTCG
CTCGGGTTACAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 884)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h239
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGAT
TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTAG
GAACGGTATGAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 885)
BMS3h240
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGAT
TCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTAG
GAACGGTTACAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 886)
BMS3h1
GAGGTGCAGCTGTTGGAGTCTGGGGAAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTACTGAGCATGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTGGAGTGGGTCTCATCTATTTCGGG
TAATGGTGCTAATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTCCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCCGCTTAGGTTTGACTACT
GGGGCCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 887)
BMS3h2
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
CCACCTTTACTGAGTATGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTGGAGTGGATCTCATCTATTTCGGG
TAATGGTGCTAATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTTCTGTGCGAAAGAGCCGCTTAGGTTTGACTACA
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 888)
BMS3h3
GAGGTGCAGCTGTTGGAGCCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTACTGAGTATGAGATGATTTGGGTCCGCAAGGCTCCAGGGAAGGGTATGGAGTGGGTCTCATCTATTTCGGG
TAATGGTGCTAATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACATGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCCGCTTAGGTTTGGCTACT
GGGGTCAGGGTACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 889)
BMS3h4
GAGGTGCAGCTGTTGGATTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCACTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTACTGAGTATGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTGGAGTGGGTCTCATCTATTTCGGG
TAATGGTGCTAATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTACAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCCGCTTAGGTTTGACTACT
GGGGTCGGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 890)
BMS3h5
GAGGTGCAGCTGTTGGGGTCAGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
45 TCACCTTTACTGAGTATGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGAGTCTGGAGTGGGTCTCATCTATTTCGGG
TAATGGTGCTAATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCCGCTTAGGTATGACGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 891)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h6
GAGGTGCAGCCGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTTCAGCCTCCGGAT
TCACCTTTAATGAGTATGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTGGAGTGGGTCTCATCTATTTCGGG
TAATGGTGCTAATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCCGCTTAGGTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 892)
BMS3h7
GAGGTGCAGCTGTTGGAGTCTGGGGAAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCTGAGTATGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAAGGTCTGGAGTGGGTCTCATCTATTTCGGG
TAATGGTGCTAATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCCGCTTAGGTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 893)
BMS3h8
GAGGTGCAGCTGTTGGACCCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTACTGAGTCTGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTGGAGTGGGTCTCATCTATTTCGGG
AAATGGTGCTAATACATACTACGCGGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCCGCTTAGGTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 894)
BMS3h9
GAGGTGCAGCTGTTGGAGCCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTACTGAGTATGAGATGATTTGGGTCCGCAAGGCTCCAGGGAAGGGTATGGAGTGGGTCTCATCTATTTCGGG
TAATGGTGCTAATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTCCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCCGCTTAGGTTTGACGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 895)
BMS3h10
GAGGTGCAGCTGTTGGAGTCTGGGGTAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTACTGAGTATGAGATGATTTGGGTCCGCAAGGCCCCAGGGAAGGGTCTGGAGTGGGTCTCATCTATTTCGGG
TAATGGTGCTAATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAACCGCTTAGGTTTGACAACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 896)
BMS3h11
GAGGTGCAGTTGTTGGAGTCTCGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTACTGAGCATGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTGGAGTGGGTCTCATCTATTTCGGG
TAATGGTGCTAATACATACTACGCAGACTCCGTGAAGGGCCGGTTCTCCGTCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCCGCTTAGGTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 897)
BMS3h12
GAGGTGCAGCCGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCTGCCTCCGGAT
45 TCACCTTTACTGAGTATGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTGGAGTGGGTCTCATCTATTTCGGG
TAATGGTGCTAATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCCGCTTAGGTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 898)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h13
GAGGTGCAGCTGTTGGAGTCTGCGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCTGAGTATGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTGGAGTGGGTCTCATCAATTTCGGG
TAATGGTGCTAATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCCGCTTAGGTTTGACTACT
GGGGTCAGGGAGCCCTGGTCACCGTCTCGAGC (SEQ ID NO: 899)
BMS3h14
GAGGtGCAGCtGTTGGAGCCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCGCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTACTGAGTATGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTGGAGTGGGTCTCATCTATTTCGGG
TAATGGTGCTAATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCCGCTTAGGTTTGACAACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 900)
BMS3h1
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCTCTGCGTCTCTCCTGTACAGCCTCCGGAT
TCACCTTTAATATGTATGAGATGTCGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGGTATTAGTAG
ACGTGGTTTTACTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGAGCCGATTACGTATGATTTGA
GGTATGCGCGTTTTGACTACTCGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 901)
BMS3h2
GAGGAGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTACAGCCTCCGGAT
TCACCTTTAATATGTATGAGATGTCGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGGTATTAGTAG
ACGTGGTTTTACTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGAGCCGATTACGTATGCTACGA
GGTATGCGCGTTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 902)
BMS3h3
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTACAGCCTCCGGAT
TCACCTTTAATATGTATGAGATGTCGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGGTATTAGTAG
GCGTGGTTTTACTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTTCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGAGCCGATTACGTATGATATGA
GGTATGCGCGTTTTGACTACGGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 903)
BMS3h4
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTACAGCCTCCGGAT
TCACCTTTAATATGTATGAGATGTCGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGGTATTAGTAG
GCGTGGTTTTACTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGAGCCGATTACGTATGATATGA
GGTATGCGCGTTTTGACAACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAAC (SEQ ID NO: 904)
BMS3h5
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTACAGCCTCCGGAT
45 TCACCTTTAATACGTATGAGATGTCGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGGTATTGGTAG
GCGTGGTTTTACTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGAGCCGATTACGTATGATTTGA
GGTATGCGCGTTTTGACTACTCGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 905)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h6
GAGGTGCAGCTGATGGAGTCAGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTACAGCCTCCGGAT
TCTCCTTTAATATGTATGAGATGTCGTGGGTCCGCCAGGCTCCAGGGAAAGGTCTAGAGTGGGTCTCAGGTATTAGTAG
GCGTGGTTATACTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGAGCCGATTACGTATGATATGA
GGTATGCGCGTTTTGACTACTGGGGTCGGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 906)
BMS3h7
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTGCAGCCTGGGGGGTCCCTGCGTCTCTCCTGTACAGCCTCCGGAT
TCGCCTTTAATATGTATGAGATGTCGTGGGTCCGCCAGGCTCCAGGGAAGGGACTAGAGTGGGTCTCAGGTATTAGTAG
GCATGGTTTTACTACGTACTACGCAGACTCCGTGAAGGGCCGGTTCACCGTCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGAGCCGATTACGTATGATATGC
GGTATGCGCGTTCTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 907)
BMS3h8
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTACAGCCTCCGGAT
TCACCTTTAATATGTATGAGATGTCGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGGTATTAGTAG
GCGTGGTTTTACTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTTCTGTGCGAAAGAGCCGATTACGTATGATATGA
GGTATGCGCGTTCTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 908)
BMS3h9
GAGGTGCAGCTGTTGGAGTCTGGGGGGGGCTTGGTTCAGCCTGGGGGGTCCCTGCGTCTCTCCTGTACAGCCTCCGGGT
TCACCTTTAATATGTATGAGATGTCGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGGTATTAGTAG
GCGTGGTTTTACTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGAGCCGATTACGTATTCTATGA
GGTATGCGCGTTTTGACTACTCGGGTCTGGGAACCATGGTCACCGTCTCGAGC (SEQ ID NO: 909)
BMS3h10
GAGGTGCAGCTGCTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTTCGTCTCTCCTGTACAGCCTCCGGAT
TCACCTTTAATATGTATGAGATGTCGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGGTATTAGTAG
GCGTGGTTTTACTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGAGCCGATTACGTATGATATGA
GGTATGCGCGTTTTGACTACAGTGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 910)
BMS3h11
GAGGTGCAGCTGTTGGAGTCTGGAGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTACAGCCTCCGGAT
TCACCTTTAATATGTATGAGATGTCGTGGGTCCGCAAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGGTATTAGTAG
GCATGGTTTTACTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGAGCCGATTACGTATGATATGA
GGTATGCGCGTTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 911)
BMS3h12
GAGGTGCAGCTGTTCGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTACAGCCTCCGGAT
45 TCACCTTTAATATGTATGAGATGTCGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGGTATTAGTAG
GCGTGGTTTTACTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAGGAGCCGATTACGTATGATATGA
GGTATGCGCGTTTTGACTACTGGGGTCGGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 912)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h13
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGATCCCTGCGTCTCTCCTGTACAGCCTCCGGTT
TCACCTTTAATATGTATGAGATGTCGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGGTATTAGTAG
GCGTGGTTTTACTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGAGCCGATTACGTATGATATGA
GGTATGCGCGTTTTGACTACTGGGGTCGGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 913)
BMS3h14
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTCGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTACAGCCTCCGGAT
TCTCCTTTAATATGTATGAGATGTCGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGGTATTAGTAG
GCGTGGTTTTACTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGAGCCGATTACGTATGATATGA
GGTATGCGCGTTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGGGC (SEQ ID NO: 914)
BMS3h15
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAACCTGGGGGGTCCCTGCGTCTCTCCTGTACAGCCTCCGGAT
TCACCTTTAATATGTATGAGATGTCGTGGGTCCGCAAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGGTATTAGTAG
GCGTGGTTTTACTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGTGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGAGCCGATTACGTATGATATGA
GGTATGCGCGTTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 915)
BMS3h1
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 916)
BMS3h2
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGACGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 917)
BMS3h3
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCAGAGGATACCGCGGTATATTACTGTACGAAACTTCCGTTTATTTTTGAATACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 918)
BMS3h4
GAGGTGCAGCTGTTGGAGTCCGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
45 TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTATGTTTGACGACC
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 919)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h5
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGATGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGACGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 920)
BMS3h6
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCTCCTTTCGGGATTATGAGATGTGGTGGTACCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATATTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTATTTTTGACAACC
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 921)
BMS3h7
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCTCGGTATATCACTGTGCGAAACCTCCGTTTATTTTTGGCGACT
GGGGTCCGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 922)
BMS3h8
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCGGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCGGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACGATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 923)
BMS3h9
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTATCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGATGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACTGCGGTATATTACTGTGCGAAACTTCCGTTTATGTTTGACGACC
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 924)
BMS3h10
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGTTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACATGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACTGCGGTATATTACTGTGCGAAACTTCCGTTTATGTTTGACGACC
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 925)
BMS3h11
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
45 TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGAGCCGAGGATACTGCGGTATATTACTGTGCGAAACTTCCGTTTATGTTTGACGACC
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 926)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h12
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGATACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTTTGAAACTTCCGTTTATTTTCGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 927)
BMS3h13
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTATCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAACCC
GCAGGGTACGCGTACATACTATGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGATGATACCGCGGTATATCACTGTACGAAACTTCCGTTTATTTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 928)
BMS3h14
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGATGGTTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTA
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTTTTTTTGACTCCA
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 929)
BMS3h15
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCGGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCTGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 930)
BMS3h16
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGATGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 931)
BMS3h17
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCTCCTTTCGGGATTATGAGATGTGGTGGTACCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATATTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 932)
BMS3h18
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
45 TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGTTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACATGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 933)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h19
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATCACTGTGCGAAACTTCCGTTTACTTTTGAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 934)
BMS3h20
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTACGAAACTTCCGTTTACTTTTGAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 935)
BMS3h21
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTTTGAAACTTCCGTTTACTTTTGAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 936)
BMS3h22
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTATCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAACCC
GCAGGGTACGCGTACATACTATGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGATGATACCGCGGTATATCACTGTACGAAACTTCCGTTTATTTTTGAATACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 937)
BMS3h23
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGATGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAACCTTATAGTTTTGACTCCT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 938)
BMS3h24
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGATGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATCACTGTGCGAAAGAACCTTATAGTTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 939)
BMS3h25
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
45 TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCGGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGATGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGACGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 940)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h26
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTATCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCGGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGATGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACTGCGGTATATTACTGTGCGAAACTTCCGTTTATGTTTGACGACC
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 941)
BMS3h27
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTATCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGATGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACTGCGGTATATTACTGTGCGAAACTTCCGTTTATGTTTGACGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 942)
BMS3h28
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCTGGGTATGAGTTGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGATGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGACGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 943)
BMS3h29
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCTGGGTATGAGTTGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGATGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACTGCGGTATATTACTGTGCGAAACTTCCGTTTATGTTTGACGACC
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 944)
BMS3h30
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCTGGGTATGAGATGTGGTGGTTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGATGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGACGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 945)
BMS3h31
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCTGGGTATGAGATGTGGTGGTTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGATGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACTGCGGTATATTACTGTGCGAAACTTCCGTTTATGTTTGACGACC
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 946)
BMS3h32
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
45 TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGATGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGACGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 947)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h33
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTATCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGATGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACTGCGGTATATTACTGTGCGAAACTTCCGTTTATGTTTGACGACC
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 948)
BMS3h202
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCGACCTACTTTTCCGACC
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 949)
BMS3h203
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCGTTTTTCTTTGAGGAGT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 950)
BMS3h204
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCGACGTACTTTAAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 951)
BMS3h205
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCGTTTTACTTTTCCGAGT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 952)
BMS3h206
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATCACTGTGCGAAACTTCCGATGTTCTTTGAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAAC (SEQ ID NO: 953)
BMS3h207
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
45 TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCGTTTCCGTTTTCGGAGT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 954)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h208
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGGACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCGTTTTACTTTTCCGAGT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 955)
BMS3h209
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GTACGGTAACCTCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 956)
BMS3h210
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCCCGGTACCTTGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGAGGACC
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 957)
BMS3h211
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GTGGGGTGGCTTGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 958)
BMS3h212
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GATGGGTGGGTTCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 959)
BMS3h213
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GTGGGGTTCGCACACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 960)
BMS3h214
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
45 TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GTCCGGTGGGCTGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGACGACC
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 961)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h215
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCACGGTTCGTTGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGACGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 962)
BMS3h216
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GGCCGGTCGGTTGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 963)
BMS3h217
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GTGGGGTAGCTTGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 964)
BMS3h218
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCCCGACTACGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATCACTGTGCGAAACTTCCGTTTACTTTTGACGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 965)
BMS3h219
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGACTCCGGAT
TCACCTTTCCGCCCGTGGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 966)
BMS3h220
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GTACGGTGGGCTGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGACGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 967)
BMS3h221
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
45 TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GTGGGGTAACCACACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 968)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h222
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCACGGTGGCTACACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 969)
BMS3h223
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAGGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCCCGGTATGCTCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGACGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 970)
BMS3h224
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GTGGGGTCAGTTGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 971)
BMS3h225
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GTGGGGTGGCTACACATACTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGACGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 972)
BMS3h226
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GTCGGGTGGGCTGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 973)
BMS3h227
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GTCGGGTGGGTTGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGACGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 974)
BMS3h228
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
45 TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GTCGGGTACGCTCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 975)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h229
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GTACGGTTCGTTGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGACGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 976)
BMS3h230
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GTGGGGTGGCTACACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 977)
BMS3h231
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTGGGCTGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 978)
BMS3h232
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GTGGGGTTCCCACACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGACGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 979)
BMS3h233
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GTGGGGTACCTTGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAGGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGACGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 980)
BMS3h234
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GAACGGTCGGCTGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGCGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 981)
BMS3h235
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
45 TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GTGGGGTCAGCTGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGACGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 982)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h236
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCACGGTGGCCTCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGACGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 983)
BMS3h237
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTGGAGCGGGTCTCAGCTATTAATCC
GGCGGGTATGTTGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGACGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 984)
BMS3h238
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCACGGTACCTTGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 985)
BMS3h239
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GTGGGGTTCGTTGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGACGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 986)
BMS3h240
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GTACGGTGGCCTGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 987)
BMS3h241
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTACGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GGCCGGTTTCTTGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 988)
BMS3h242
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACGGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
45 TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTGGAGCGGGTCTCAGCTATTAATCC
GTACGGTGGCCTGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 989)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h243
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GTGGGGTGGGTTCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 990)
BMS3h244
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GTGGGGTGGGTTGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGACGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 991)
BMS3h245
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GTACGGTGGGCTGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGGACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 992)
BMS3h246
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GTGGGGTACGTTGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 993)
BMS3h247
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GTGGGGTGGCTACACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGAGGACT
GGGGTCGGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 994)
BMS3h248
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GTACGGTAACCTGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGACGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 995)
BMS3h249
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
45 TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCACGGTGGGTTCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 996)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h250
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GGCCGGTTTCTACACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGACGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 997)
BMS3h251
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GGCGGGTGGCCTCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGACGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 998)
BMS3h252
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCGCCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCACGGTTCCCTCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTACTTTTGAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 999)
BMS3h253
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGTGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GGCCGGTGGGTACACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATCACTGTGCGAAACTTCCGTTTACTTTTGAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1000)
BMS3h254
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCGTTTTGGTTTACGGAGT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1001)
BMS3h255
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTCATGTTTTCCGACC
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1002)
BMS3h256
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
45 TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCGTTTTTGTTTCAGGAGT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1003)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h257
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCGACGCGGTTTGAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1004)
BMS3h258
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCGTTTTACTTTCACGAGT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1005)
BMS3h259
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1006)
BMS3h260
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCGACGTTCTTTAAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1007)
BMS3h261
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACACGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTTTCTTTCAGGAGT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1008)
BMS3h262
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCGCAGTTGTTTCACGACC
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1009)
BMS3h263
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
45 TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCGCAGCTCTTTGAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1010)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h264
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATCACTGTGCGAAACTTCCGTTTGGGTTTTCCGAGT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1011)
BMS3h265
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCGCAGTTGTTTCAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1012)
BMS3h266
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCGTTTTTCTTTCACGAGT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1013)
BMS3h267
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCGCACTACTTTAAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1014)
BMS3h268
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGTCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTTACTTTGAGGAGT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1015)
BMS3h269
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTAGGTTTTCCGACC
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1016)
BMS3h270
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
45 TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCGACGCTGTTTCAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1017)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h271
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCGTTTTACTTTTCCGAGT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAAC (SEQ ID NO: 1018)
BMS3h272
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCGTTTTGGTTTCAGGAGT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1019)
BMS3h273
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GTGGGGTTCGTTGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCGTTTTACTTTCAGGAGT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1020)
BMS3h274
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GTGGGGTTCGTTGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATCACTGTGCGAAACTTCCGATGTTCTTTGAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAAC (SEQ ID NO: 1021)
BMS3h275
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GTGGGGTTCGTTGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCGTTTTACTTTCACGAGT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1022)
BMS3h276
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GTGGGGTTCGTTGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCGTTTTTCTTTCAGGAGT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1023)
BMS3h277
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
45 TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GTGGGGTTCGTTGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCGTTTTTCTTTCACGAGT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1024)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h278
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GTGGGGTGGGTTCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTTACTTTCAGGAGT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1025)
BMS3h279
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GTGGGGTGGGTTCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATCACTGTGCGAAACTTCCGATGTTCTTTGAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAAC (SEQ ID NO: 1026)
BMS3h280
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GTGGGGTGGGTTCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCGTTTTACTTTCACGAGT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1027)
BMS3h281
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GTGGGGTGGGTTCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCGTTTTTCTTTCAGGAGT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1028)
BMS3h282
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GTGGGGTGGGTTCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTTTCTTTCACGAGT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1029)
BMS3h283
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GTGGGGTGGGTTGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTTACTTTCAGGAGT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1030)
BMS3h284
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
45 TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GTGGGGTGGGTTGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATCACTGTGCGAAACTTCCGATGTTCTTTGAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAAC (SEQ ID NO: 1031)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h285
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GTGGGGTGGGTTGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCGTTTTACTTTCACGAGT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1032)
BMS3h286
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GTGGGGTGGGTTGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTTTCTTTCAGGAGT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1033)
BMS3h287
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GTGGGGTGGGTTGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAACTTCCGTTTTTCTTTCACGAGT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1034)
BMS3h288
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCC
GCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATCACTGTGCGAAACTTCCGATGTTCTTTGAGGACT
GGGGTCAGGGAACCCTGGTCACCGTCTCCAGC (SEQ ID NO: 1035)
BMS3h1
GAGGTGCAGCTGTTGGAGACTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTTCGACTTATCATATGCAGTGGGTCCGCCGGGCTCCAGGGAAGGGCCTGGAGTGGGTCTCAATGATTGATGC
GGATGGTCTTGGGACATACTACGCAGACCCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCAAGGACACCGCGGTATATTACTGTGCGAGACCGGGTCCGCAGTTTGGTCAGT
TTGACTACTTGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1036)
BMS3h2
GAGGTGCAGCTGTTTGAGTCTGGGGGAGGCTTGGTACAGACTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTTCGACTTATCATATGCAGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTGGAGTGGGTCTCAATGATTGATGC
GGATGGTCTTGGGAAATACTACGCAGACCCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGTGAAACCGGGTCCGCAGTTTGGTCAGT
ATGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1037)
BMS3h1
GAGGTGCAGCTGTTGGAGTCAGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGGCTCTCCTGTTCAGCTTCCGGAT
45 TCACCTTTTCGGGGTATGATATGCAGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAACGATTAGTGC
GTCGGGTGTTTATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAATATCCTAATCGTTTTGCGCTTA
ATAGTTTTGACTACAGGGGTCGGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1038)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h2
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCTTCCGGAT
TCACCTTTTCGGGGTATGATATGCAGTGGGTCCGCCAGGCTCCAGGGAGGGGTCTAGAGTGGGTCTCAACGATTAGTGC
GTCGGGTGTTTATACATACTACACAGACTCCGTGAAGGGCCGGTTCACCACCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTACGAAATATCCAAATCGTTTTGCGCGTA
ATAATTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1039)
BMS3h1
GACATCCTGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAATA
GTTCTATTTTGTGGGCGTTAGCTTGGTACCAGCAGAAACCAGGGGAAGCCCCTAAGCTCCTGATCGAGAGTTCTTCCGG
TTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGTTCAGAATGCGGTTTGGCCTGGTACGTTCAGCCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 1040)
BMS3h2
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAGACA
GTTCTATTTTGTGGGCGTTAGCTTGGTACCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCGAGAGTTCATCCGG
TTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGTTCAGAATGCGGTTTGGCCTGGTACGTTCGGCCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 1041)
BMS3h3
GACATCCAGATGACCGTGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAGATA
GTTCTATTTTGTGGGCGTTAGCTTGGTACCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCGAGAGTTCTTCCGG
ATTGCAAAGCGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGTTCAGAATGCGGTTTGGCCTGGTACGTTCGGCCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 1042)
BMS3h4
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAATA
GTTCTATTTTGTGGGCGTTAGCTTGGTACCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCGAGAGTTCTTCCGG
TTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGTTCAGAATGCGGTTTGGCCTGGTACGTTCGACCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 1043)
BMS3h5
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAATA
GTTCTATTTTGTGGGCGTTAGCTTGGTACCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCGAGAGTTCTACCGG
TTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
40 CCTGAAGATTTTGCTACGTACTACTGTGTTCAGAATGCGGTTTGGCCTGGTACGTTCGGCCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 1044)
BMS3h6
GACATCCAGATGACCGTGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAATA
45 GTTCTATTTTGTGGGCGTTAGCTTGGTACCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCGAGAGTTCTTCCGG
ATTGCAAAGCGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGTTCAGAATGCGGTTTGGCCTGGTACGTTCGGCCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 1045)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h7
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAGATA
GTTCTATTTTGTGGGCGTTAGCTTGGTACCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCGAGAGTTCTTCCGG
TTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGTTCAGAATGCGGTTTGGCCTGGTACGTTCGACCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 1046)
BMS3h8
GACATCCAGATGACCCAGTCTCCATCCTCACTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAATA
GTTCTATTTTGTGGGCGTTAGCTTGGTACCAGCAGAAACCAGGGAAAGCCCCTGAGCTCCTGATCGAGAGTTCTTCCGG
TCTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGTTCAGAATGCGGTTTGGCCTGGTACGTTCGGCCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 1047)
BMS3h9
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCGAATA
GTTCTATATTGTGGGCGTTGGCTTGGTACCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCGAGAGTTCTTCCGG
TTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGTTCAGAATGCGGTTTGGCCTGGTACGTTCGGCCAAGGGACCAAGGTGGAAA
ACAAACGG (SEQ ID NO: 1048)
BMS3h10
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAATA
GTTCTATTCTGTGGGCGTTAGCTTGGTACCAGCAGAAACCTGGGAAAGCCCCTAAGCTCCTGATCGAGAGTTCTTCCGG
TTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCCGAAGATTTTGCTACGTACTACTGTGTTCAGAATGCGGTTTGGCCTGGTACGTTCGGCCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 1049)
BMS3h11
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCTTCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAATA
GTTCTATTTTGTGGGCGTTAGCTTGGTACCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCGAGAGTTCTTCCGG
TTTGCAAAGTGGGATCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGTTCAGAATGCGGTTTGGCCTGGTACGTTCGGCCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 1050)
BMS3h12
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTTGGAGACCGTGTCACCATCACTTGCCGGGCAAATA
GTTCTATTTTGTGGGCGTTAGCTTGGTACCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCGAGAGTTCTTCCGG
ATTGCAAAGCGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
40 CCTGAAGATTTTGCTACGTACTACTGTGTTCAGAATGCGGTTTGGCCTGGTACGTTCGGCCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 1051)
BMS3h13
GACATCCTGTTGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAATA
45 GTTCTATTTTGTGGGCGTTAGCTTGGTACCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCGAGAGTTCTTCCGG
TTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGTTCAGAATGCGGTTTGGCCTGGTACGTTCGGCCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 1052)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h14
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAATA
GTTCTATTTTGTGGGCGTTAGCTTGGTACCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCGAGAGTTCTTCCGG
TTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGAAGTGGAACTGGGACAGATTTCACTCTCACCATCAGCGGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGTTCAGAATGCGGTTTGGCCTGGTACGTTCGACCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 1053)
BMS3h15
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCCCTTGCCGGGCAAATA
GTTCTATTTTGTGGGCGTTAGCTTGGTACCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCGAGAGTTCTTCCGG
TTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGCATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGTTCAGAATGCGGTTTGGCCTGGTACGTTCGGCCAAGGGACCAAGGTGGAGA
TCAAACGG (SEQ ID NO: 1054)
BMS3h1
GACATCCAGATGGCCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
AGACGATTGAGCGTCGTTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATCTTGCTTCCCG
TTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTCATCAGTATGCGAGTCCACCTTTGACGTTAGGCCAAGGGACCAAAGTGGAAA
TCAAACGG (SEQ ID NO: 1055)
BMS3h2
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGTGTCACCATCACTTGCCGGGCAAGTC
AGACGATTGAGCGTCGTTTAAATTGGTATCAGCAGAAACCAGGGGAAGCCCCTAAGCTCCTGATCTATCTTGCTTCCCG
TTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGCCATCAGTATGCGAGTCCACCTTTGACGTTCGGCCAAGGGACCAATGTGGAAA
TCAAACGG (SEQ ID NO: 1056)
BMS3h3
GACATCCAGATGACCCAGTCTCCATCCTCCCTATCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
AGACGATTGAGCGTCGTTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATCTTGCTTCCCG
TTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTGCGTACTACTGTCATCAGTACGAGAGTCCACCTTTGACGTTTGGCCAAGGGACCAAAGTGGAAA
TCAAACGG (SEQ ID NO: 1057)
BMS3h4
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
GGACGATTGAGCGTCGTTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATCTTGCTTCGCG
TTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
40 CCTGAAGATTTTGCTACGTACTACTGTCATCAGTATGAGAGTCCACCTTTGACGTTCGGCCAAGGGACCAAAGTGGAAA
TCAAACGG (SEQ ID NO: 1058)
BMS3h5
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGAACGTGTCACCATCACTTGCCGGGCAAGTC
45 AGACGATTGAGCGTCGTTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATCTTGCTTCCCG
TTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAATCTGCAA
CCTGAAGATTCTGCTACGTACTACTGTCATCAGTATGCGAGTCCACCTTTGACGTTAGGCCAAGGGACCAAAGTGGAAA
TCAAACGG (SEQ ID NO: 1059)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h6
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGCC
AGACGATTGAGCGTCGTTTAAATTGGTATCAGCAGAAACCAGGGAAGGCCCCTAAGCTCCTGATCTATCTTGCTTCCCG
TTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTCATCAGTATGCGAGTCCACCTTTGACGTTAGGCCAAGGGACCAAAGTGGAAA
TCAAACGG (SEQ ID NO: 1060)
BMS3h7
GACATCCAGATAACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
AGACGATTGAGCGTCGTTTAAATTGGTATCAGCAGAAACCAGGGAAAGACCCTAAGCTCCTGATCTATCTTGCTTCCCG
TTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTCATCAGTATGAGAGTCCTCCTTTGACGTTCGGCCAAGGGACCAAAGTGGAAA
TCAAACGG (SEQ ID NO: 1061)
BMS3h8
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
AGACGATTGAGCGTCGTTTAAATTGGTATCAGCAGAAACCAGGGGAAGCCCCTAAGCTCCTGATCTATCTTGCTTCCCG
TTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTCATCAGTATGAGAGTCCACCTTTGACGTTCGGCCAAGGGACCAAAGTGGAAA
TCAAATGG (SEQ ID NO: 1062)
BMS3h9
GACATCCAGTTGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGAGTCACCATCACTTGCCGGGCAAGTC
AGACGATTGAGCGTCGTTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATCTTGCTTCCCG
TTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGAATTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTCATCAGTATGAGAGTCCACCTTTGACGTTCGGCCAAGGGACCAAAGTGGAAA
TCAAACGG (SEQ ID NO: 1063)
BMS3h10
GACATCCAGATGTCCCAGTCTCCATCCACCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
AGACGATTGAGCGTCGTTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATCTTGCTTCCCG
CTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTCATCAGTATGAGAGTCCACCTTTGATGTTCGGCCAAGGGACCAAAGTGGAAA
TCAAACGG (SEQ ID NO: 1064)
BMS3h11
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATTACTTGCCGGGCAAGTC
AGACGATTGAGCGTCGTTTAAATTGGTATCAGCAGAAACCAGGGAAAGACCCTAAGCTCCTGATCTATCTTGCTTCCCG
TTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
40 CCAGAAGATTTTGCTACGTACTACTGTCATCAGTATGAGAGTCCACCTTTGACGTTCGGCCAAGGGACCAAAGTGGAAA
TCAAACGG (SEQ ID NO: 1065)
BMS3h12
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCCGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
45 AGACGATTGAGCGTCGTTTAAACTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATCTTGCTTCCCG
TTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTCATCAGTATGAGAGTCCACCTTTGACGTTCGGCCAAGGGACCAAAGTGGAAA
TCAAACGG (SEQ ID NO: 1066)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h13
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTTTGCATCTGTAGGGGACCGTGTCACCATCACTTGCCGGGCAAGTC
AGACGATTGAGCGTCGTTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATCTTGCTTCCCG
TTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTCATCAGTATGAGAGTCCACCTTTGACGTTCGGCCAAGGGACCAAAGTGGAAA
TCAAACGG (SEQ ID NO: 1067)
BMS3h14
GACATCCAGATGACCCAGTATCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
AGTCGATTGAGCGTCGTTTAAATTGGTATCAGCAGAAACCAGGGGAAGCCCCTAAGCTCCTGATCTATCTTGCTTCCCG
TTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTCATCAGTATGAGAGTCCACCTTTGACGTTCGGCCAAGGGACTAAAGTGGAAA
TCAAACGG (SEQ ID NO: 1068)
BMS3h15
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
GGACGATTGAGCGTCGTTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATCTTGCTTCGCG
TTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTCATCCGTATGAGAGTCCACCTTTGACGTTCGGCCAAGGGACCAAAGTGGAAA
TCAAACGG (SEQ ID NO: 1069)
BMS3h16
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
AGGCGATTGAGCGTCGTTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATCTTGCTTCCCG
TTTGCAAAGTGGGGTCCCATCTCGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAG
CCAGAAGATTTTGCTACGTACTACTGTCATCAGTATGCGAGTCCACCTTTGACGCTCGGCCAAGGGACCAAAGTGGAAA
TCAAACGG (SEQ ID NO: 1070)
BMS3h17
AACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
AGGCGATTGAGCGTCGTTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATCTTGCTTCTCG
TTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTCATCAGTATGAGAGTCCACCTTTGACGTTCGGCCAAGGGACCAAAGTGGAAA
TCAAACGG (SEQ ID NO: 1071)
BMS3h18
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
AGACGATTGGGCGTCGTTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATCTTGCTTCCCG
TTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGTCAGATTTCACTCTCACCATCAGCAGTCTGCAA
40 CCTGAAGATTTTGCTACGTACTACTGTCATCAGTATGAGAGTCCACCTTTGACGTTCGGCCAAGGGACCAAAGTGGAAA
TCAAACGG (SEQ ID NO: 1072)
BMS3h19
GACATCCAGATGACCCAGTCTCCATCCTCCCTTTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGAGCAAGTC
45 AGACGATTGAGCGTCGTTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATCTTGCTTCCCG
TTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGAATTTACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTCATCAGTATGAGAGTCCACCTTTGACGTTCGGCCAAGGGACCAAAGTGGAAA
TCAAACGG (SEQ ID NO: 1073)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h20
GACATCCAGATGACCCAGACTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
AGACGATTGAGCGTCGTTTAAATTGGTATCAGCAGAAACCAGGGGAAGCCCCTAAGCTCCTGATCTATCTTGCTTCCCG
TTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCCACGTACTACTGTCATCAGTATGAGAGTCCACCTTTGACGTTCGGCCAAGGGACCAAAGTGAAAA
TCAAACGG (SEQ ID NO: 1074)
BMS3h21
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGTGTCACCATCACTTGCCGGGCAAGTC
AGACGATTGAGCGTCGTTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATCTTGCTTCCCG
TTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCCGAAGATTTTGCTACGTACTACTGTCATCAGTATGAGAGTCCACCTTTGACGTTCGGCCAAGGGACCAAAGTGGAAA
TCAAACGG (SEQ ID NO: 1075)
BMS3h22
CACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
AGACGATTGAGCGTCGTTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATCTTGCTTCCCG
TTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGCCATCAGTATGAGAGTCCACCTTTGACGTTCGGCCAAGGGACCAAAGTGGAAA
TCAAACGG (SEQ ID NO: 1076)
BMS3h23
GACGTCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
AGACGATTGAGCGTCGTTTAAATTGGTATCAGCAGAAACCAGGGGAAGCCCCTAAGCTCCTGATCTATCTTACTTCCCG
TTTGCAAAGCGGGGTCCCATCACGTTTCAGTGGTAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGCCATCAGTATGCGAGTCCACCTTTGACGTTCGGCCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 1077)
BMS3h24
GACATCCAGATGACCCAGTCGCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
AGACGATTGAGCGTCGTTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATCTTGCTTCCCG
TTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTCACCAGTATGAGAGTCCACCTTTGACGTTCGGCCAAGGGACCAAAGTGGTAA
TCAAACGG (SEQ ID NO: 1078)
BMS3h25
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGAGTCACCATCACTTGCCGGGCAAGTC
AGACGATTGAGCGTCGTTTAAATTGGTATCAGCAGAAACCTGGGAAAGCCCCTAGGCTCCTGATCTATCTTGCTACCCG
TTTGCAAAGTGGGGTCCCATCACGCTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
40 CCTGAAGATTTTGCTACGTACTACTGTCATCAGTATGAGAGTCCACCTTTGACGTTCGGCCAAGGGACCAAAGTGGAAA
TCAAACGG (SEQ ID NO: 1079)
BMS3h26
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
45 AGCCGATTGAGCGTCGTTTAAATTGGTATCAGCAGAAGCCAGGGAAAGCCCCTAAGCTCCTGATCTATCTTGCTTCCCG
TTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACATACTACTGTCATCAGTATGAGAGTCCACCTTTGACGTTCGGCCAAGGGACCAAAGTGGAAA
TCAAACGG (SEQ ID NO: 1080)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h27
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
AGACGATTGGGCGTCGTTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATCTTGCTTCCCG
TTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTCATCAGTATGAGAGTCCACCTTTGACGTTCGGCCAAGGGACCAAAGTGGAAA
TCAAACGG (SEQ ID NO: 1081)
BMS3h28
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
AGTCGATTGAGCGCCGTTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATCTTGCTTCCCG
TTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTCATCAGTATGAGAGTCCTCCTTTGACGTTCGGCCAAGGGACCAAAGTGGAAA
TCATACGG (SEQ ID NO: 1082)
BMS3h29
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGAGTCACCATCACTTGCCGGGCAAGTC
AGACGATTGAGCGTCGTTTAAATTGGTATCAGCAGAAACCTGGGAAAGCCCCTAAGCTCCTGATCTATCTTGCTACCCG
TTTGCAAAGTGGGGTCCCATCACGCTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTCATCAGTATGAGAGTCCACCTTTGACGTTCGGCCAAGGGACCAAAGTGGAAA
TCAAACGG (SEQ ID NO: 1083)
BMS3h30
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
AGTCGATTGAGCGCCGTTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATCTTGCTTCCCG
TTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTCATCAGTATGAGAGTCCTCCTTTGACGTTCGGCCAAGGGACCAAAGTGGAAA
TCAAACGG (SEQ ID NO: 1084)
BMS3h2501
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGAGTCACCATCACTTGCCGGGCAAGTC
AGACGATTGAGCGTCGTTTAAATTGGTATCAGCAGAAACCTGGGAAAGCCCCTAGGCTCCTGATCTATCTTGCTACCCG
TTTGCAAAGTGGGGTCCCATCACGCTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTCATCAGTTCGAGCACCCACCTTTGACGTTCGGCCAAGGGACCAAAGTGGAAA
TCAAACGG (SEQ ID NO: 1085)
BMS3h2502
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGAGTCACCATCACTTGCCGGGCAAGTT
TCCCCATTGACCGTCGTTTAAATTGGTATCAGCAGAAACCTGGGAAAGCCCCTAGGCTCCTGATCTATCTTGCTACCCG
TTTGCAAAGTGGGGTCCCATCACGCTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
40 CCTGAAGATTTTGCTACGTACTACTGTCATCAGTATGAGAGTCCACCTTTGACGTTCGGCCAAGGGACCAAAGTGGAAA
TCAAACGG (SEQ ID NO: 1086)
BMS3h2503
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGAGTCACCATCACTTGCCGGGCAAGTT
45 CCACCATTGGCCGTCGTTTAAATTGGTATCAGCAGAAACCTGGGAAAGCCCCTAGGCTCCTGATCTATCTTGCTACCCG
TTTGCAAAGTGGGGTCCCATCACGCTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTCATCAGTATGAGAGTCCACCTTTGACGTTCGGCCAAGGGACCAAAGTGGAAA
TCAAACGG (SEQ ID NO: 1087)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h2504
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGAGTTACCATCACTTGCCGGGCAAGTT
CCCAGATTGGGCGTCGTTTAAATTGGTACCAGCAGAAACCAGGGAAAGCCCCTAGGCTCCTGATCTATCTTGCTACCCG
TTTGCAAAGTGGGGTCCCATCACGCTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTCATCAGTATGAGAGTCCACCTTTGACGTTCGGCCAAGGGACCAAAGTGGAAA
TCAAACGG (SEQ ID NO: 1088)
BMS3h2505
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGAGTCACCATCACTTGCCGGGCAAGTG
AGCGGATTGGGCGTCGTTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAGGCTCCTGATCTATCTTGCTACCCG
TTTGCAAAGTGGGGTCCCATCACGCTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTCATCAGTATGAGAGTCCACCTTTGACGTTCGGCCAAGGGACCAAAGTGGAAA
TCAAACGG (SEQ ID NO: 1089)
BMS3h2506
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGAGTCACCATCACTTGCCGGGCAAGTC
AGCAGATTGGCCGCCGTTTAAATTGGTATCAGCAGAAACCTGGGAAAGCCCCTAGGCTCCTGATCTATCTTGCTACCCG
TTTGCAAAGTGGGGTCCCATCACGCTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTCATCAGTATGAGAGTCCACCTTTGACGTTCGGCCAAGGGACCAAAGTGGAAA
TCAAACGG (SEQ ID NO: 1090)
BMS3h2507
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGAGTCACCATCACTTGCCGGGCAAGTC
AGCCGATTGCCCGGCGTTTAAATTGGTACCAGCAGAAACCAGGGAAAGCCCCTAGGCTCCTGATCTATCTTGCTACCCG
TTTGCAAAGTGGGGTCCCATCACGCTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTCATCAGTATGAGAGTCCACCTTTGACGTTCGGCCAAGGGACCAAAGTGGAAA
TCAAACGG (SEQ ID NO: 1091)
BMS3h2508
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGAGTCACCATCACTTGCCGGGCAAGTG
GGAACATTGGCCGTCGTTTAAATTGGTACCAGCAGAAACCAGGGAAAGCCCCTAGGCTCCTGATCTATCTTGCTACCCG
TTTGCAAAGTGGGGTCCCATCACGCTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTCATCAGTATGAGAGTCCACCTTTGACGTTCGGCCAAGGGACCAAAGTGGAAA
TCAAGCGG (SEQ ID NO: 1092)
BMS3h2509
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGAGTCACCATCACTTGCCGGGCAAGTC
GGAACATTGACCGTCGTTTAAATTGGTACCAGCAGAAACCAGGGAAAGCCCCTAGGCTCCTGATCTATCTTGCTACCCG
TTTGCAAAGTGGGGTCCCATCACGCTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
40 CCTGAAGATTTTGCTACGTACTACTGTCATCAGTATGAGAGTCCACCTTTGACGTTCGGCCAAGGGACCAAAGTGGAAA
TCAAACGG (SEQ ID NO: 1093)
BMS3h2510
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGAGTCACCATCACTTGCCGGGCAAGTC
45 AGAGCATTGGGCGTCGTTTAAATTGGTACCAGCAGAAACCTGGGAAAGCCCCTAGGCTCCTGATCTATCTTGCTACCCG
TTTGCAAAGTGGGGTCCCATCACGCTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTCATCAGTATGAGAGTCCACCTTTGACGTTCGGCCAAGGGACCAAAGTGGAAA
TCAAACGG (SEQ ID NO: 1094)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h2511
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGAGTCACCATCACTTGCCGGGCAAGTC
AGAACATTGGGACGCGTTTAAATTGGTACCAGCAGAAACCAGGGAAAGCCCCTAGGCTCCTGATCTATCTTGCTACCCG
TTTGCAAAGTGGGGTCCCATCACGCTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTCATCAGTATGAGAGTCCACCTTTGACGTTCGGCCAAGGGACCAAAGTGGAAA
TCAAACGG (SEQ ID NO: 1095)
BMS3h2512
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGAGTCACCATCACTTGCCGGGCAAGTG
AGGTCATTGGGCGTCGTTTAAATTGGTACCAGCAGAAACCAGGGAAAGCCCCTAGGCTCCTGATCTATCTTGCTACCCG
TTTGCAAAGTGGGGTCCCATCACGCTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTCATCAGTATGAGAGTCCACCTTTGACGTTCGGCCAAGGGACCAAAGTGGAAA
TCAAACGG (SEQ ID NO: 1096)
BMS3h2513
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGAGTCACCATCACTTGCCGGGCAAGTG
AGGCGATTGGCCGTCGTTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAGGCTCCTGATCTATCTTGCTACCCG
TTTGCAAAGTGGGGTCCCATCACGCTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTCATCAGTATGAGAGTCCACCTTTGACGTTCGGCCAAGGGACCAAAGTGGAAA
TCAAACGG (SEQ ID NO: 1097)
BMS3h2514
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGAGTCACCATCACTTGCCGGGCAAGTA
CCAGCATTGCGCGTCGTTTAAATTGGTATCAGCAGAAACCTGGGAAAGCCCCTAGGCTCCTGATCTATCTTGCTACCCG
TTTGCAAAGTGGGGTCCCATCACGCTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTCATCAGTATGAGAGTCCACCTTTGACGTTCGGCCAAGGGACCAAAGTGGAAA
TCAAACGG (SEQ ID NO: 1098)
BMS3h2515
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGAGTCACCATCACTTGCCGGGCAAGTT
TGAACATTGGGCGTCGTTTAAATTGGTACCAGCAGAAACCAGGGAAAGCCCCTAGGCTCCTGATCTATCTTGCTACCCG
TTTGCAAAGTGGGGTCCCATCACGCTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTCATCAGTATGAGAGTCCACCTTTGACGTTCGGCCAAGGGACCAAAGTGGAAA
TCAAACGG (SEQ ID NO: 1099)
BMS3h2516
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGAGTCACCATCACTTGCCGGGCAAGTC
AGACGATTGAGCGTCGTTTAAATTGGTACCAGCAGAAACCAGGGAAAGCCCCTAGGCTCCTGATCTATCTTTCGTCGAA
GTTGCAAAGTGGGGTCCCATCACGCTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
40 CCTGAAGATTTTGCTACGTACTACTGTCATCAGTATGAGAGTCCACCTTTGACGTTCGGCCAAGGGACCAAAGTGGAAA
TCAAACGG (SEQ ID NO: 1100)
BMS3h1
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTTCAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
45 CCACCATTGCTGGGTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGTGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGAGACGATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAGAGATCCTTATAGTTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1101)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h2
GAGGTGCAGCCGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCTGGGTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGATCTCAGCTATTAGCGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACGATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAGAGATCCTTATAGTTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1102)
BMS3h3
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTCGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCACCGGAT
CCACCTTTGCTGGGTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACGATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAGAGATCCTTACAGTTATGACTACT
GGGGTCAGGGAACCCTGGTCTCCGTCTCGAGC (SEQ ID NO: 1103)
BMS3h4
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAC
TCACCTTTGCTGGGTATGAGATGTGGTGGGTCCGCCAGGCACCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACGATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCAGTATATCACTGTGCGAGAGATCCTTATAGTTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1104)
BMS3h5
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCTGGGTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCTGTGAAGGGCCGGTTCACCATCTCCCGCGACGATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATCACTGTGCGAAAGAACCTTATAGTTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1105)
BMS3h6
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
CCACCTTTGCTGGGTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACGATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTCCCGAGGATACCGCGGTATATTACTGTGTGAAAGATCCTTATAGTTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1106)
BMS3h7
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
CCACCATTGCCGGGTATGAGATGTGGTGGGTCCGCCAGGCTCCGGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACGATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAGAGATCCTTATAGTTTTGACTACT
GGGGTCAGGGAACCCCGGTCACCGTCTCGAGC (SEQ ID NO: 1107)
BMS3h8
GAGGTGCAGCTGATGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
45 CCACCTTTGCTGGGTATGAGATGTGGTGGTACCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAGTGG
AAGTGGTAGAAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACGATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGATCCTTATAGTTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1108)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h9
GAGGTGCAGCTGCTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCTGGGTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACGTACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACGATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCAGTATATTACTGTGCGAAAGAACCTTATAGTTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1109)
BMS3h10
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
CCACCATTGCTGGGTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACGATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGATCCATATAGTTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1110)
BMS3h11
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCTGGGTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACGATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAGAGACCCTTATAGTTTTGACTACT
GGGGTCAGGGAACCCTGGTCTCCGTCTCGAGC (SEQ ID NO: 1111)
BMS3h12
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCATTGCTGGGTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCCGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCGGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACGATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGATCCTTATAGTTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTTTCGAGC (SEQ ID NO: 1112)
BMS3h13
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCTGGGTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGTGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCACCCGCGACGATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGAGCCTTATAGTTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1113)
BMS3h14
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCTGGGTATGAGATGTGGTGGTTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACGATACCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGATCCTTATAGTTTTGACTACT
GGCGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1114)
BMS3h15
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
45 CCACCTTTGCTGGGTATGAGGTGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTGGAGCGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACGATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAGAGATCCTTATAGTTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1115)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h16
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
CCACCTTTGCTGGGTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGATCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACGATTCCAAGAACACGCTG
TATCTGAAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGATCCTTATAGTTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1116)
BMS3h17
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCTGGGTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACGATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAGAGATCCTTATAGTTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1117)
BMS3h18
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAC
TCACCTTTGCTGGGTATGAGATGTGGTGGGTCCGCCGGGCTCCAGGGAAGGGTCTAGAGCGGGTCGCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACGATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAGAGATCCTTATAGTTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1118)
BMS3h19
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCTGGGTATGAGTTGTGGTGGGTCCGCCAGGCCCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAGTGG
AAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACGATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAGAGATCCTTATAGTTTTGACTACC
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1119)
BMS3h20
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCCCCGGAT
TCACCTTAGCTGGGTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACGATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGAACCTTATAGTTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1120)
BMS3h21
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAC
TCACCTTTGCTGGGTATGAGATGTGGTGGGTCCGTCGGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCACCTCCCGCGACGATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAGAGATCCTTATAGTTTTGACTACT
GGGGTCGGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1121)
BMS3h22
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCCGGGGGGTCCCTGCGTCTCTCCTGTGCCGCCTCCGGAT
45 TCACCTTTGCTGGGTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAGTGG
TAGCGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACGATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGAACCTTATAGTTATGACTACT
GGGGTCATGGAACCCTGGTTACTGTCTCGAGC (SEQ ID NO: 1122)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h23
GAGGTGCAGCCGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCTGGGTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAACACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACGATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGGGGTATATTACTGTGCGAGAGATCCTTATAGTTTTGACTACT
GGGGTCAGGGTACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1123)
BMS3h24
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCTGGGTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACGATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGAACCTTATAGTTTTGACTCCT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1124)
BMS3h25
GAGGCGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TAACCTTCGCTGGGTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGCGTCTCAGCTATTAGTGG
TAGTGGCGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACGATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAGAGATCCTTATAGTTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1125)
BMS3h26
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
CCACCTTTGCTGGGTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCTCCATCTCCCGCGACGATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGAACCTTATAGTTTTGACCACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1126)
BMS3h27
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCGGGAT
CCACCTTTGCTGGGTATGAGATGTGGTGGGTCCGCAGGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACGATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAGAGATCCTTATAGTTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1127)
BMS3h28
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCTGGGTATGAGATGTGGTGGTTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACGATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGATCCTTATAGTTTTGACAACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1128)
BMS3h29
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTAGAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
45 TCACCTTTGCTGGGTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACGATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGAACCTTATAGTTTTGACCACC
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1129)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h30
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
ACACCTTTGCTGGGTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACGATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGAACCTTATAGTTTTGACCACC
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1130)
BMS3h31
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCTGGGTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCTGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATCACTGTGCGAAAGAACCTTATAGTTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1131)
BMS3h32
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCTGGGTATGAGATGTGGTGGTTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGATCCTTATAGTTTTGACAACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1132)
BMS3h33
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCTGGGTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCTGTGAAGGGCCGGTTCACCATCTCCCGCGACGATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGAACCTTATAGTTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1133)
BMS3h34
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCTGGGTATGAGATGTGGTGGGTCCGCCAGGCTCCCGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACGATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGATCCTTATAGTTTTGACAACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1134)
BMS3h35
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCTGGGTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCTGTGAAGGGCCGGTTCACCATCTCCCGCGACGATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATCACTGTGCGAAAGAACCTTATAGTTATGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1135)
BMS3h36
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
45 TCACCTTTGCTGGGTATGAGATGTGGTGGTTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTGG
TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACGATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGATCCTTATAGTTTTGACAACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1136)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h37
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCTGGGTATGAGTTGTGGTGGGTCCGCCAGGCCCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAGTGG
AAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACGATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAAAGATCCTTATAGTTTTGACTACC
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1137)
BMS3h38
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTGCTGGGTATGAGTTGTGGTGGGTCCGCCAGGCCCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAGTGG
AAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACGATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGCGAGAGATCCTTATAGTTTTGACTACT
GGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1138)
BMS3h1
GAGGTGCAGCTGTTGGAGTCTGGGGGGGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCCGACTGCTGAGATGCTGTGGGTCCGCAAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATCTATTTCGGC
TAGTGGTGGTTCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCCGGTGAGTTATGTGGCGA
CGTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1139)
BMS3h2
GAGGTGCAGCTGTTGGTGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCCGACTGCTGAGATGTTGTGGGTCCGCCAGGCTCCAGGGAAGGGTCCAGAGTGGGTCTCATCAATTTCGGC
TAGTGGTGGTTCTACATACTATGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCCGGTGAGTTATGTGGCGA
CGTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1140)
BMS3h3
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCGTGTGCAGCCTCCGGAT
TCACCTTTCCGACTGCCGAGATGGTGTGGGTCCGCAAGGCTCCAGGGATGGGTCTAGAGTGGGTCTCATCTATTTCGGC
TAGTGGTGGTTATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACATGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCCGGTGAGTTATGTGGCGA
CGTTTGACTACTGGGGTCAGGGAGCCCTGGTCACCGTCACGAGC (SEQ ID NO: 1141)
BMS3h4
GAGGTGCAGCTGTTGGTGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCCGACTGCTGAGATGGTGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATCTATTTCGGC
TAGTGGTGGTTCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCTCCATCTCCCGCGACGATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCCGGTGAGTTATGTGGCGA
CGTTTGACTACTGGGGTCATGGAGCCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1142)
BMS3h5
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
45 TCACATTTCCGACTGCTGAGATGTTGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATCTATTTCGGC
TAGTGGTGGTTCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGAGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCCGGTGAGTTATGTGGCAA
CGTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1143)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h6
GAGGCGCAGCTGTTGGAGTCTGGGGGTGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCCGACTGCTGAGATGGTGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGATCTCATCTATTTCGGC
TAGTGGTGGTTCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAATTGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCCGGTGAGTTATGTGGCGA
CGTTTGACTACTGGGGTCGGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1144)
BMS3h7
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACATTTCCGACTGCTGAGATGTTGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATCTATTTCGGC
TAGTGGTGGTTCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAGCACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCCGGTGAGTTATGTGGCGA
CGTTTGACTACTGGGGTCCAGGAGCCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1145)
BMS3h8
GAGGTGCAGCTGTTGGAGTCCGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCCGACTGCTGAGATGCTGTGGGTCCGCAAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATCTATTTCGGC
TAGTGGTGGTTCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TTTCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCCAAAGAGCCGGTGAGTTATGTGGCGA
CGTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1146)
BMS3h9
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACATTTCCGACTGCTGAGATGTTGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATCTATTTCGGC
TAGTGGTGGTTCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCCGGTGAGTTATGTGGCGA
CGTTTGACTACTGGGGTCCAGGAGCCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1147)
BMS3h10
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCCGACTGCTGAGATGCTGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATCTATTTCGGC
TAGTGGTGGTTCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
TATTTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAAGAGCCGGTGTATTATGTGGCGA
CGTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1148)
BMS3h11
GAGGTGCAGCTGTTGGAGTCCGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGAT
TCACCTTTCCGACTGCTGAGATGCTGTGGGTCCGCAAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATCTATTTCGGC
TAGTGGTGGTTCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTG
40 TATCTGCAAATGAACAGCCTGCGTGCCGAGGACGCCGCGGTATATTACTGTGCGAAAGAGCCGGTGAGTTATGTGGCGA
CGTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC (SEQ ID NO: 1149)
BMS3h1
AACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
45 ATTTTATTGGTACTCTGTTAACTTGGTACCAGCATAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTATGGTTCCTT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 1150)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h2
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
ATTTTATTGGTACTCTGTTATCTTGGTACCAGCAGAAACCACGGAAAGCCCCTAAACTCCTGATCACTTATGGTTCCTT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAT
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTCCGACGTTCGGTCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 1151)
BMS3h3
GACATCCAGATGACCCAGTCTCCGTCCTCCCTGACTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
ATTTTATTGGTACTCTGTTATCTTGGTACCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGGTCACTTATGGTTCCTT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAATCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTCCTACGTTCGGCCAAGGGACCAAGGTGGAAA
ACATACGG (SEQ ID NO: 1152)
BMS3h4
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
ATTTTATTGCTACTCTGTTATCTTGGTACCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTATGGTTCCTT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTCCGACGTTCGGCCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 1153)
BMS3h5
GACATCCAGATGACCCAGTCTCCATCCTTCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
ATTTTATTGCTACTCTGTTATCTTGGTACCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTATGGTTCCTT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTCCGACGTTCGGCCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 1154)
BMS3h6
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
ATTTTATTGGTACTCTGTTATCTTGGTACCAGCAGAAACCAGGGAAAGCCACTAAGCTCCTGATCACTTATGGTTCCTT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGACTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCCCCGACGTTCGGCCAGGGGACCAAGGTGGAAA
TCAAACGT (SEQ ID NO: 1155)
BMS3h7
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
ATTTTATTGGTTCTCTGTTATCTTGGTACCAGCATAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTATGGTTCCTT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
40 CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 1156)
BMS3h8
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
45 ATTTTATTGGTACTCTGTTATCTTGGTACCAGCATAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTATGGTTCCTT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 1157)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h9
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
ATTTTATTGGTACTCTGTTATCTTGGTACCAGCATAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTATGGTTCCAT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCAACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 1158)
BMS3h10
GACATCCAGATGACTCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGAGTCACCATCACTTGCCGGGCAAGTC
ATTTTATTGGTACTCTGTTATCCTGGTACCAGCATAAACCAGGGAAAGCCCCTAAGCTCCTGATCACCTATGGTTCCTT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGAATTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGAGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 1159)
BMS3h11
GACATCCAGATGACCCAGTCTCCATCCTCCCTGACTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
ATTTTATTGGTACTCTGTTATCTTGGTACCAGCATAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTATGGTTCCTT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGAATTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 1160)
BMS3h12
AACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
ATTTTATTGGTACTCTGTTATCTTGGTACCAGCATAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTATGGTTCCTT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 1161)
BMS3h13
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCAATTGCCGGGCAAGTC
ATTTTATTGGTACTCTGTTATCTTGGTACCAGCATAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTATGGTTCCTT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 1162)
BMS3h14
GACATCCAGTTGACCCAGTCACCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
ATTTTATTGGTACTCTGTTATCTTGGTACCAGCAGAAACCAGGGAAAGCCACTAAGCTCCTGATCACTTATGGTTCCTT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
40 CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTCCGACGTTCGGCCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 1163)
BMS3h15
GACATCCAGATGACACAGTCTCCATCCTCCCTGTATGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGTAAGTC
45 ATTTTATTGGTACTCTGTTATCTTGGTACCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTATGGTTCCTT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCAGCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCCCCGACGTTCGGACAAGGGACCAAGGTGGAAA
TCAAACAG (SEQ ID NO: 1164)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h16
GACATTCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
ATTTTATTGGTACTCTGTTATCTTGGTACCAGCAGAAACCAAGGAAAGCCCCTAAGCTCCTGATCACTTATGGTTCCTT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTCCGACGTTCGGCCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 1165)
BMS3h17
GACATCCAGATTATCCAGTCTCCATCCTCCCTTTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
ATTTTATTGGTACTCTGTTATCTTGGTACCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTATGGTTCCTT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTCCGACGTTCGGCCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 1166)
BMS3h18
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
ATTTTATTGGTACTCTGTTATCTTGGTACCAGCTGAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTATGGTTCCTT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 1167)
BMS3h19
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
ATTTTATTGGTACTCTGTTATCTTGGTACCAGCTGAAACCAGGGAAAGCCCCAAAGCTCCTGATCACTTATGGTTCCTG
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACCAAGGTAGAAA
ACAAACGG (SEQ ID NO: 1168)
BMS3h20
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
ATTTTATTGGTACTCTGTTATCTTGGTACCAGCTTAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTATGGTTCCTT
GTTGCAACGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 1169)
BMS3h21
GACATCCAGATGACCCAGGCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
ATTTTATTGGTACTCTGTTATCTTGGTACCAGCTGAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTATGGTTCCTT
GTTGCAGAGTGGGGTCCCATCACGTTTCAGTGGTAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
40 CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACCAAGGTTGAAA
ACAAACGG (SEQ ID NO: 1170)
BMS3h22
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
45 ATTTTATTGGTTCTCTGTTATCTTGGTACCAGCAGAAACCAGGGAAAGCCCCAAAGCTCCTGATCACTTATGGTTCCTT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCGCTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 1171)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h23
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
ATTTTATTGGTAGTCTGTTATCTTGGTACCAGGTGAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTATGGTTCCTT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACAACGGTGGAAA
TCAAACGG (SEQ ID NO: 1172)
BMS3h24
GACATCCTGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
ATTTTATTGGTAGTCTGTTATCTTGGTACCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTATGGTTCCTT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 1173)
BMS3h25
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
ATTTTATTGGTACTCTGGTATCTTGGTACCAGCAGAAACCGGGGAAAGCCCCTAAGCTCCTGATCACTTATGGTTCCTT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACGTACGGCCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 1174)
BMS3h26
GACATCCAGATGACCCAGTCTCCATCCTCTCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
ATTTTATTGGTACTCTGGTATCTTGGTACCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTATGGTTCCTT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACTTTCGGCCAAGGGACCAAGGTGGAAA
ACAAACGG (SEQ ID NO: 1175)
BMS3h27
GACATCAAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCGAGTC
ATTTTATTGGTACTCTGGTATCTTGGTACCAGCAGAAACCAGGGAAAGCCCCAAAGCTCCTGATCACTTATGGTTCCAT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 1176)
BMS3h28
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCAGGCAAGTC
ATTTTATTGGTACTCTGGTATCCTGGTACCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTATGGTTCCTT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
40 CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCCGCGACGTTCGGCCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 1177)
BMS3h29
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
45 ATTTTATTGGTACTCTGTTATCTTGGTACCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTATGGTTCCTG
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 1178)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h30
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTTGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
ATTTTATTGGTACTCTGTTATCTTGGTACCAGCTGAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTATGGTTCCTG
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 1179)
BMS3h31
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
ATTTTATTGGTACTCTGTTATCTTGGTACCAGCAGAAACCGGGGAAAGCCCCTAAGCTCCTGATCACTTATGGTTCCTT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATTTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGAGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACTAAGGTGGAAA
TCAAACGG (SEQ ID NO: 1180)
BMS3h32
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCTCCATCACTTGCCGAGCAAGTC
ATTTTATTGGTACTCTGTTATCTTGGTACCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTATGGTTCCTT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATTTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATCTTGCTACGTACTACTGTGGTCAGGAGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 1181)
BMS3h33
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCAGGCAAGTC
ATTTTATTGGTACTCTGTTATCTTGGTACCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTATGGTTCCTT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATTTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCCGAAGATTTTGCTACGTACTACTGTGGTCAGGAGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 1182)
BMS3h34
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCAGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
ATTTTATTGGTACTCTGTTATCTTGGTACCAGCAGAAACCTGGGAAAGCCCCTAAGCTCCTGATCACTTATGGTTCCTT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATTTGGGACAGAATTCACTCTCACCATCGGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 1183)
BMS3h35
GACATCCAGATGACCCAGTCACCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
ATTTTATTGGTACTCTGTTATCTTGGTACCAGCAGAAACCAGGGAAAGCCACTAAGCTCCTGATCACTTATGGTTCCTT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
40 CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTCCGACGTTCGGCCAAGGGACCAAGGTGGAAA
TCAAACGG (SEQ ID NO: 1184)
BMS3h2301
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
45 ACTTCATTGCCAGTCTGTTATCTTGGTACCAGGTGAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTATGGTTCCTT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACAACGGTGGAAA
TCAAACGG (SEQ ID NO: 1185)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h2302
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
ATTTCATTGCCCAGCTGTTATCTTGGTACCAGGTGAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTATGGTTCCTT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACAACGGTGGAAA
TCAAACGG (SEQ ID NO: 1186)
BMS3h2303
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
ATTTCATTGCCCAGCTGTTATCTTGGTACCAGGTGAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTATGGTTCCTT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACAACGGTGGAAA
TCAGACGG (SEQ ID NO: 1187)
BMS3h2304
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
ATTACATTGCCTCCCTGTTATCTTGGTACCAGGTGAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTATGGTTCCTT
GTTGCAGAGTGGGGCCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACAACGGTGGAAA
TCAAACGG (SEQ ID NO: 1188)
BMS3h2305
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
ATTTTATTGGTAGTCTGTTATCTTGGTACCAGGTGAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTGGGCCTCCTA
CTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACAACGGTGGAAA
TCAAACGG (SEQ ID NO: 1189)
BMS3h2306
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
ATTTTATTGGTAGTCTGTTATCTTGGTACCAGGTGAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTGGACGTCCTA
CTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACAACGGTGGAAA
TCAAACGG (SEQ ID NO: 1190)
BMS3h2307
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
ATTTTATTGGTAGTCTGTTATCTTGGTACCAGGTGAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTGGTCGTCCTA
CTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
40 CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACAACGGTGGAAA
TCAAACGG (SEQ ID NO: 1191)
BMS3h2308
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
45 ATTTTATTGGTAGTCTGTTATCTTGGTACCAGGTGAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTGGGGGTCCTG
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACAACGGTGGAAA
TCAAACGG (SEQ ID NO: 1192)
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BMS3h2309
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
ATTTTATTGGTAGTCTGTTATCTTGGTACCAGGTGAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTGGGCGTCCTG
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACAACGGTGGAAA
TCAAACGG (SEQ ID NO: 1193)
BMS3h2310
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
ATTTTATTGGTAGTCTGTTATCTTGGTACCAGGTGAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTGGAGCTCCTG
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACAACGGTGGAAA
TCAAACGG (SEQ ID NO: 1194)
BMS3h2311
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
ATTGGATTGCCCAGCTGTTATCTTGGTACCAGGTGAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTATGGTTCCTT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACAACGGTGGAAA
TCAAACGG (SEQ ID NO: 1195)
BMS3h2312
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
ATTTTATTGGTTCGCTCTTACGCTGGTACCAGGTGAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTATGGTTCCTT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACAACGGTGGAAA
TCAAACGG (SEQ ID NO: 1196)
BMS3h2313
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
ATCGGATTGCCCAGCTGTTATCTTGGTACCAGGTGAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTATGGTTCCTT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACAACGGTGGAAA
TCAAACGG (SEQ ID NO: 1197)
BMS3h2314
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
ATTACATTGCCTCCCTGTTATCTTGGTACCAGGTGAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTATGGTTCCTT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
40 CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACAACGGTGGAAA
TCAAACGG (SEQ ID NO: 1198)
BMS3h2315
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
45 ATTTTATTGGTAGTCTGTTATCTTGGTACCAGGTGAAACCAGGGAAAGCCCCTAAGCTCCTGATCCGGTTCGGCTCCTT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACAACGGTGGAAA
TCAAACGG (SEQ ID NO: 1199)
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BMS3h2316
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
ATTTTATTGGTAGTCTGTTATCTTGGTACCAGGTGAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTACAAGTCCTA
CTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACAACGGTGGAAA
TCAAACGG (SEQ ID NO: 1200)
BMS3h2317
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
ATTTTATTGGTAGTCTGTTATCTTGGTACCAGGTGAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTGGGGCTCCTA
CTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACAACGGTGGAAA
TCAAACGG (SEQ ID NO: 1201)
BMS3h2318
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
ATTTTATTTGGGGGCCCTTATCTTGGTACCAGGTGAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTATGGTTCCTT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTCTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACAACGGTGGAAA
TCAAACGG (SEQ ID NO: 1202)
BMS3h2319
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
ATTGGATTGCCACCCTGTTATCTTGGTACCAGGTGAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTATGGTTCCTT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACAACGGTGGAAA
TCAAACGG (SEQ ID NO: 1203)
BMS3h2320
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
ATTTTATTTGGGGGCCCTTATCTTGGTACCAGGTGAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTATGGTTCCTT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACAACGGTGGAAA
TCAAACGG (SEQ ID NO: 1204)
BMS3h2321
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
ATTTTATTGGTAGCCTCTTAAACTGGTACCAGGTGAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTATGGTTCCTT
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
40 CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACAACGGTGGAAA
TCAAACGG (SEQ ID NO: 1205)
BMS3h2322
GGCATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTC
45 ATTTTATTGGTAGTCTGTTATCTTGGTACCAGGTGAAACCAGGGAAAGCCCCTAAGCTCCTGATCACTTACGGGTCCTG
GTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGTGGTCAGGGGGTGCTGTGGCCTGCGACGTTCGGCCAAGGGACAACGGTGGAAA
TCAAACGG (SEQ ID NO: 1206)
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Example 1
Generation of Human Anti-CD40 Variable Domains
BMS3h-1 through BMS3h-225
The following example describes the generation of a series of anti-human CD40
variable domains, designated BMS3h-1 through BMS3h-225. Following recombinant
expression of a repertoire of single immunoglobulin variable domains on the surface of phage,
selection is performed by contacting the phage repertoire with immobilized target antigen,
washing to remove unbound phage, and propagating the bound phage. This process frequently
referred to as “panning.” It is applicable to the screening of single immunoglobulin variable
domains, as well as other antibody fragments that can be expressed on a display library, e.g.,
scFv, Fab, and Fab'. Alternatively, phage may be pre-selected for the expression of properly
folded member variants by panning against an immobilized generic ligand (e.g., protein A or
protein L) that is only bound by folded members. This has the advantage of reducing the
proportion of non-functional members, thereby increasing the proportion of members likely to
bind a target antigen. Pre-selection with generic ligands is taught in WO 99/20749, for
example. The screening of phage antibody libraries is generally described, for example, by
Harrison et al., Meth. Enzymol. 267: 83-109 (1996).
Screening is commonly performed using purified antigen immobilized on a solid
support, for example, plastic tubes or wells, or on a chromatography matrix, for example
Sepharose (Pharmacia). Screening or selection can also be performed on complex antigens,
such as the surface of cells (Marks et al., BioTechnology 11: 1145 (1993); de Kruif et al., Proc.
Natl. Acad. Sci. USA 92: 3938 (1995)). Another alternative involves selection by binding
biotinylated antigen in solution, followed by capture on streptavidin-coated beads.
Clones BMS3h-1 to BMS3h-69:
Three rounds of selections using decreasing concentrations of antigen (100 nM at round
1; 10 nM at round 2; 1 nM at round 3) were performed in parallel against both biotinylated
human CD40 monomer (supplied by BMS, 1.5 moles biotin / mole CD40) and biotinylated
human CD40-Ig (supplied by BMS, 3.3 moles biotin / mole CD40-Ig). Phage from the naïve
4G and 6G Domantis dAb libraries were combined as follows before initiating selections:
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1) 4G + 6G VH CDR3 lengths between 7 – 9 amino acids.
2) 4G + 6G VH CDR3 lengths between 10 – 12 amino acids.
3) 4G + 6G VH CDR3 lengths between 13 – 15 amino acids.
4) 4G VK
5) 6G VK
Each round of selection involved adding the desired concentration of antigen to a
mixture of 750 µl of phage from one of the naïve library pools or subsequent selection output
phage and 750 µl of PBS+2% Marvel (Phosphate Buffered Saline containing 2% (w/v) Marvel
[Premier Foods, UK]) and incubating at room temperature for 1 hour by mixing end-over-end.
The biotinylated antigen phage complex was then captured by adding 100 µl of resuspended
Dynabeads® M-280 Streptavidin [Invitrogen, UK] and incubated for 5 minutes with mixing
end-over-end at room temperature. The Dynabeads® were then recovered using a KingFisher
magnetic separator [Thermo Fisher Scientific, UK] and washed 7 x 1 ml PBS + 0.1% Tween
(PBS containing 0.1% (v/v) polyoxyethylenesorbitan monolaurate [Sigma-Aldrich, UK],
PBST) followed by 1 x 1 ml PBS. Bound phage retained on the washed Dynabeads® were
eluted by incubation with 500 µl of trypsin-PBS (50 µl of 10 mg/ml trypsin [Sigma-Aldrich,
UK] dissolved in 50 mM Tris-HCl pH 7.4, 1 mM CaCl added to 450 µl PBS). The phage-
containing solution was recovered and 250 µl used to infect 1.75 ml of logarithmic growth
phase E. coli TG1 (at an OD of 0.4) for 30 minutes at 37ºC. The E. coli TG1 phage infected
culture was centrifuged at 11,600 g in a micro centrifuge for 1 minute. The resulting cell pellet
was resuspended in 1 ml 2xTY (16 g Tryptone, 10 g Yeast Extract and 5 g NaCl in 1 litre,
autoclaved for 15 minutes at 121°C) and plated onto a 9 cm Petri dish containing TY
supplemented with 15 µg/ml tetracycline. The plates were incubated overnight at 37°C. Then
2 ml of 2xTY supplemented with 15% glycerol was added to each plate, and the cells were
loosened with a glass spreader and mixed thoroughly. Fifty microlitres of the scraped bacteria
were used to inoculate 50 ml of 2xTY supplemented with 15 µg/ml tetracycline and grown
overnight at 37°C with shaking at 250 rpm. The overnight culture was centrifuged at 3,300 g
for 15 min to pellet the bacteria. To precipitate phage, 10 ml PEG/NaCl (20% Polyethylene
glycol 8000, 2.5 M NaCl) was added to 40 ml supernatant. The phage/PEG solution was
mixed and left on ice for 1 h, then spun at 3,300 g for 30 min at 4ºC, and the supernatant
discarded. The pellet was resuspended in 2 ml PBS and spun at 11,600 g for 10 min in a micro
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centrifuge to remove the remaining bacterial debris. The resultant supernatant containing
phage was then used for the next round of selection against the appropriate biotinylated CD40
antigen.
Monoclonal phage ELISAs were carried out following selection rounds 2 and 3. All
washes were performed using 3 washes of 250 µl PBST followed by 3 washes of 250 µl PBS.
The plates were coated overnight at 4ºC with 50 µl/well of 1 µg/ml NeutrAvidin (Thermo
Scientific, UK) in 0.2 M carbonate-bicarbonate buffer, pH 9.4. The plates were washed and
then blocked with 2% MPBS (2% w/v Marvel skimmed milk powder [Premier Foods] in PBS)
for 1 hour at room temperature. The plates were then washed and incubated with 50 µl/well of
0.7 µg/ml biotinylated human CD40 in 2% MPBS. The plates were washed, and phage
supernatants were added to an equal volume of 2% MPBS. The plates were then incubated for
1 hour at room temperature. The plates were washed and bound phage detected with anti-
M13-HRP conjugate (GE Healthcare, UK) diluted 1:5000 in 2% MPBS and incubated for 1
hour at room temperature. The plates were washed, and the ELISA was developed using
SureBlue 1-Component TMB MicroWell Peroxidase solution (KPL Inc, USA). Specific phage
were identified by comparison to plates coated with NeutrAvidin but without biotinylated
CD40. A MidiPrep was used to isolate dAb V-genes from pDOM4 (Domantis) round 2 and
round 3 outputs and cloned into pDOM5 (Domantis). pDOM4, disclosed in ,
is a derivative of the Fd phage vector in which the gene III signal peptide sequence is replaced
with the yeast glycolipid anchored surface protein (GAS) signal peptide ().
pDOM4 also contains a c-myc tag between the leader sequence and gene III, which puts the
gene III back in frame.
Binding dAbs were identified as follows. Ninety-six individual colonies (in pDOM5)
were picked from each output into 200 µL Terrific Broth containing OnEx Autoinduction
media (Novagen, UK) overnight at 37º C with shaking at 250 rpm in Costar 96 Well Cell
Culture Clusters (Corning Incorporated, USA). The cultures were centrifuged to pellet the
cells, and the supernatants were assayed by antigen binding ELISA for CD40 binding dAbs.
MaxiSorp 96 well immunoplates (Nunc, USA) were coated overnight at 4ºC with 50 µl/well of
1 µg/ml NeutrAvidin in 0.2 M carbonate-bicarbonate buffer, pH 9.4. All washes were as
described for the phage ELISA. The plates were blocked for 1 hour at room temperature with
200 µl of PBS containing 1% Tween 20. The plate was then washed and incubated with 50
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µl/well of 0.7 µg/ml biotinylated human CD40 in 0.1% PBST. The clarified dAb-containing
culture supernatant was added to the ELISA plate with an equal volume of 0.1% PBST. The
plates were incubated for 1 hour at room temperature and then washed. Bound dAb was
detected using a two step process: firstly 9E10 (anti-myc IgG, Sigma-Aldrich, UK) diluted
1:2000 in 0.1 % PBST was added for 1 hour at room temperature then washed, followed by
anti-mouse Fc-HRP (Sigma-Aldrich, UK) diluted 1:2000 in 0.1% PBST for 1 hour at room
temperature. The plates were washed, and the ELISA was developed using SureBlue 1-
Component TMB MicroWell Peroxidase solution (KPL Inc, USA). The color was allowed to
develop, and the colorimetric reaction was stopped by the addition of an equal volume of 1 M
HCl. The ELISA plate was read at 450 nm. Specific phage were identified by comparison to
plates coated with NeutrAvidin but without biotinylated CD40.
Clones specific for CD40 were tested in either the bead- or ELISA-based receptor-
binding assay (RBA) to assess for inhibition of CD40 ligand binding. Domain antibodies that
showed inhibition in the RBA were tested in the B-cell proliferation assay and then in a variety
of other in vitro cell assays. These assays are described in greater detail below.
BMS3h-106 to -225:
BMS3h-106 to -225 were isolated from selections against biotinylated CD40 or
biotinylated CD40-Fc as described for BMS3h-1 to BMS3h-69, but with the following
modifications. Phage from the naïve 4G and 6G libraries were combined as follows before
initiating selections:
6) 4G VH CDR3 lengths between 7 – 9 amino acids.
7) 4G VH CDR3 lengths between 10 – 12 amino acids.
8) 4G VH CDR3 lengths between 13 – 15 amino acids.
9) 6G VH CDR3 lengths between 7 – 9 amino acids.
10) 6G VH CDR3 lengths between 10 – 12 amino acids.
11) 6G VH CDR3 lengths between 13 – 15 amino acids.
12) 4G VK
13) 6G VK
Round one was performed at an antigen concentration of 160 nM for CD40-Fc and 100 nM for
CD40. Output titres were in the range 2.0×10 to 9.0×10 TU/ml (functional viral titre).
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For round two, enriched phage from round one were combined in pairs before using in
selections:
1) 4G + 6G VH CDR3 lengths between 7 – 9 amino acids (pools 1 + 4 from round 1).
2) 4G + 6G VH CDR3 lengths between 10 – 12 amino acids (pools 2 + 5 from round 1).
3) 4G + 6G VH CDR3 lengths between 13 – 15 amino acids (pools 3+6 from round 1).
4) 4G + 6G VK (pools 7+8 from round 1)
Selections were performed at an antigen concentration of 100 nM, and the antigen-phage
complexes were captured using M-280 tosyl-activated Dynabeads® (Invitrogen) that had been
coupled with NeutrAvidin (Thermo Fisher Scientific, UK). Output titres were in the range
6.5×10 to 7.5×10 TU/ml.
Round three was performed at an antigen concentration of 20 nM and, in the case of the
CD40-Fc selections, in the presence of 6.7 µM free human Fc tail (BMS). Output titres were
in the range 4.3×10 to 1.6×10 TU/ml.
Round four was performed as described for round two but at an antigen concentration
of 2 nM and in the presence and absence of 500-fold excess unlabelled CD40-Fc. The addition
of this competitor was made after the initial one hour incubation of the phage with the
biotinylated antigen, and the mixture was then incubated overnight, as before. This
competition step was included with the aim of enhancing selection of dAbs with a slower off-
7 7 6
rate. Output titres were in the range 1.8×10 to 4.4×10 without competition and 1.8×10 to
2.3×10 TU/ml with competition.
To monitor the progress of the selections, monoclonal phage ELISAs were carried out
following rounds 2 and 3. These were performed as described for BMS3h-1 to BMS3h-69.
Binding dAbs were identified as described for BMS3h-1 to BMS3h-69 except that, in the case
of the VK library screening, protein L was included at a final concentration of 0.8 µg/ml.
Addition of protein L increased the signal strength by cross-linking the dAbs.
BMS3h-70 to -105:
BMS3h-70 to -105 were isolated from selections against antigen that had been
passively adsorbed to immunotubes. Phage from the naïve 4G and 6G Domantis dAb libraries
were combined as follows before initiating selections:
1) 4G VH CDR3 lengths between 7 – 9 amino acids.
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2) 4G VH CDR3 lengths between 10 – 12 amino acids.
3) 4G VH CDR3 lengths between 13 – 15 amino acids.
4) 6G VH CDR3 lengths between 7 – 9 amino acids.
) 6G VH CDR3 lengths between 10 – 12 amino acids.
6) 6G VH CDR3 lengths between 13 – 15 amino acids.
7) 4G VK
8) 6G VK
For the first round of selection, 1 ml of 10 µg/ml human CD40-Fc fusion (BMS) in
0.2 M carbonate-bicarbonate buffer, pH 9.4, was added to a Nunc MaxiSorp immunotube and
then incubated overnight at 4°C with rolling. The tube was then emptied and washed three
times with phosphate buffered saline (PBS). The tube was then blocked by filling to the brim
with MPBS and incubating for 1 h at room temperature. The tube was then emptied and
washed three times with PBS. Library phage in 4 ml MPBS were added to the tube and
incubated for 1 hour with rotation end-over-end at room temperature.
The tube was emptied and washed 10 times with PBST (PBS with 0.1% (v/v) Tween
). Bound phage retained on the washed tube were eluted by incubation with 500 µl of
trypsin-PBS (50 µl of 10 mg/ml trypsin [Sigma-Aldrich, UK] dissolved in 50 mM Tris-HCl pH
7.4, 1 mM CaCl added to 450 µl PBS) with rotation end-over-end for 10 min at room
temperature. The phage-containing solution was recovered, and 250 µl were used to infect
1.75 ml of logarithmic growth phase E. coli TG1 (at an OD of 0.4) for 30 minutes at 37°C.
The E. coli TG1 phage infected culture was centrifuged at 11,600 g in a microcentrifuge for
1 min, and the resulting cell pellet was re-suspended in 1 ml 2xTY (16 g Tryptone, 10 g Yeast
Extract, and 5 g NaCl in 1 litre. The suspension was autoclaved for 15 minutes at 121°C) and
plated onto a 9 cm Petri dish containing LB agar supplemented with 15 µg/ml tetracycline.
The plates were incubated overnight at 37°C. Two millilitres of 2xTY supplemented with 15%
glycerol was then added to each plate, and the cells were loosened with a glass spreader and
mixed thoroughly.
Fifty microlitres of the scraped bacteria were used to inoculate 50 ml of 2xTY
supplemented with 15 µg/ml tetracycline and grown overnight at 37°C with shaking at
250 rpm. The overnight culture was centrifuged at 3,300 g for 15 min to pellet the bacteria.
To precipitate phage, 10 ml PEG/NaCl (20% Polyethylene glycol 8000, 2.5 M NaCl) was
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added to 40 ml supernatant. The phage/PEG solution was mixed and left on ice for 1 h. The
solution was then spun at 3,300 g for 30 min at 4°C, and the supernatant was discarded. The
pellet was re-suspended in 2 ml PBS and spun at 11,600 g for 10 min in a micro centrifuge to
remove the remaining bacterial debris. The resultant supernatant containing phage was then
used for the next round of selection against CD40-Fc antigen. Output titres from round one
were in the range 7.5×10 to 1.5×10 TU/ml (transforming units per ml).
A second round of selection was performed using enriched phage recovered from the
first round of selection. This was performed exactly as described above and the output titres
were in the range 2.5×10 to 1.2×10 TU/ml.
A third round of selection was performed using enriched phage recovered from the
second round of selection. These were performed as described above but with an antigen
concentration of 1 µg/ml. Output titres were in the range 5.1×10 to 7.5×10 TU/ml.
To monitor the progress of the selections, monoclonal phage ELISAs were carried out
following rounds 2 and 3. A sample of individual colonies were picked into 200 µL 2xTY
supplemented with 15 µg/ml tetracycline and incubated overnight at 37°C with shaking at
250 rpm in Costar 96 Well Cell Culture Clusters (Corning Incorporated, USA). The cultures
were centrifuged to pellet the cells, and the supernatants were assayed by antigen binding
ELISA for CD40-binding phage dAbs. All washes were performed using 3 washes of 250 µl
PBST followed by 3 washes of 250 µl PBS. MaxiSorp 96 well immunoplates (Nunc, USA)
were coated overnight at 4°C with 50 µl/well of 0.5 µg/ml CD40-Fc (BMS) in 0.2 M
carbonate-bicarbonate buffer, pH 9.4. The plates were washed and then blocked with 250 µl of
2% MPBS for 1 hour at room temperature. The plates were washed, and phage supernatants
were added to an equal volume of 2% MPBS and incubated for 1 hour at room temperature.
The plates were washed, and bound phage were detected with anti-M13-HRP conjugate (GE
Healthcare, UK) diluted 1:5000 in 2% MPBS and incubated for 1 hour at room temperature.
The plates were washed, and the ELISA was developed using SureBlue 1-Component TMB
MicroWell Peroxidase solution (KPL Inc, USA). Specific phage dAbs were identified by
comparison to plates coated with free Fc.
The dAb genes from each of the above rounds two and three selection outputs were
sub-cloned, as a pool, into soluble expression vector pDOM5 in E. coli strain HB2151. This
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vector allowed expression of free dAb with a c-myc tag (Roche Diagnostics GmbH) in E. coli
and secretion to the supernatant.
CD40-binding dAbs from passive selections were identified as follows. Ninety-six
individual colonies (in pDOM5) were picked from each output into 200 µL Terrific Broth
containing OnEx Autoinduction media (Novagen, UK) overnight at 37°C with shaking at
250 rpm in Costar 96 Well Cell Culture Clusters (Corning Incorporated, USA). The cultures
were centrifuged to pellet the cells, and the supernatants were assayed by antigen binding
ELISA for CD40 binding dAbs. MaxiSorp 96 well immunoplates (Nunc, USA) were coated
overnight at 4°C with 50 µl/well of 0.5 µg/ml CD40-Fc (BMS) in 0.2 M carbonate-bicarbonate
buffer, pH 9.4. All washes were as described for the phage ELISA. The plates were blocked
for 1 hour at room temperature with 250 µl of PBS containing 1% Tween 20 (PBST). The
clarified dAb-containing culture supernatant was added to the ELISA plate with an equal
volume of 0.1% PBST. The plates were incubated for 1 hour at room temperature and then
washed. Bound dAb was detected using a two step process: firstly biotinylated 9E10 (anti-myc
IgG, Sigma-Aldrich, UK) diluted 1:2000 in 0.1% PBST was added for 1 hour at room
temperature then washed, followed by streptavidin-HRP (Bender MedSystems, Austria)
diluted 1:5000 in 0.1% PBST for 1 hour at room temperature. The plates were washed and the
ELISA developed using SureBlue 1-Component TMB. Specific dAbs were identified by
comparison to plates coated with free Fc.
Clones specific for CD40 were tested in either the bead- or ELISA-based receptor-
binding assay (RBA) to assess for inhibition of CD40 ligand binding. The potency
measurements obtained from the RBA are given in Table 5 (Primary Screening effort).
Domain antibodies that showed inhibition in the RBA were tested in the B-cell proliferation
assay and then in a variety of other in vitro cell assays.
BMS3h-210 to -225
BMS3h-210 to -225 were isolated from selections against whole cells. Phage from the
naïve 4G and 6G Domantis dAb libraries were combined as follows before initiating
selections:
1) 4G + 6G VH CDR3 lengths between 7 – 9 amino acids.
2) 4G + 6G VH CDR3 lengths between 10 – 12 amino acids.
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3) 4G + 6G VH CDR3 lengths between 13 – 15 amino acids.
4) 4G and 6G VK
For round one a DG44 CHO cell line stably transfected with cell-surface expressed
human CD40 (supplied by BMS) was used as antigen. Prior to selection against these cells, the
library pools outlined above were incubated with non-transfected CHO cells to deplete them of
phage displaying dAbs specific for cell surface antigens other than CD40. Both types of cells
were harvested by incubation with Versene (Invitrogen) before assessing for viability. Six
million viable non-transfected CHO cells were re-suspended in 4 ml PBS with 2% (w/v) BSA
(PBS/BSA) and rotated end-over-end at 4°C for 1 hour to block. All subsequent steps were
performed at 4°C unless otherwise noted. The cells were centrifuged at 185 g for 5 min and
the supernatant, containing the depleted library phage, transferred to a fresh tube. To this were
added 6×10 viable CHO-CD40 cells in 1 ml PBS/BSA and the mixture was rotated for 1 hour.
The cells were then washed five times by centrifuging at 185 g for 5 min and re-suspending in
ml PBS/BSA. After the final wash, the cells were pelleted as previously and were then re-
suspended in 0.5 ml of 1 mg/ml trypsin type XIII from bovine pancreas (Sigma Aldrich, UK)
in PBS supplemented with 5 mM Tris-HCl pH 7.4, 0.1 mM CaCl and transferred to a
microcentrifuge tube. The cells were rotated at room temperature for 10 min before
centrifuging at 16000 g for 5 min. Eluted phage in the supernatant were used to infect E. coli
and the output phage titres were determined to be between 5.1×10 and 2.7×10 TU/ml
(transforming units per ml).
A second round of selection was performed using enriched phage recovered from the
first round of selection. These were performed as above but without the initial depletion (de-
selection) step and using RAMOS human B cells (ATCC) instead of CHO-CD40. Output
titres were in the range 2.3×10 to 7.5×10 TU/ml.
A third round of selection was performed as for the second round. Output titres were in
the range 1.9×10 to 3.5×10 TU/ml.
The dAb genes from each of the above rounds two and three selection outputs were
sub-cloned, as a pool, into soluble expression vector pDOM5 in E. coli strain HB2151. This
vector allowed expression of free dAb with a c-myc tag in E. coli and secretion to the
supernatant.
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Clones specific for CD40 were tested in either the CHO cell receptor-binding assay
(RBA) to assess for inhibition of CD40 ligand binding. Domain antibodies that showed
inhibition in the RBA were tested in the B-cell proliferation assay and then in a variety of other
in vitro cell assays.
Affinity Maturation by error-prone PCR
Error-prone phage libraries were constructed for 13 BMS3h dAbs that showed
neutralization activity in the B-cell proliferation assay described below in Example 6 (See
TABLE 17). This was performed by using Mutazyme II polymerase (part of the GeneMorph II
kit from Agilent Technologies) to randomly introduce errors into the dAb gene during
amplification by polymerase chain reaction (PCR). The mutated dAb genes were cloned as a
genetic fusion with the fd phage gene III protein under the control of the GAS1 leader
sequence in pDOM4 vector, which contained all the fd genes necessary to generate infective
phage particles. These libraries were approximately 1×10 CFU (colony forming units) in size,
with an error-rate of 2-5 amino acids per dAb gene.
Phage generated from these libraries were subjected to three rounds of selection against
soluble biotinylated human CD40. The first round of phage selection was performed by
premixing the phage library with 2% MPBS (phosphate buffered saline supplemented with 2%
(w/v) Marvel dried skimmed milk powder) and adding biotinylated human CD40 (BMS) to a
final concentration of 20 nM in a final volume of 1 ml. The mixture was incubated for at least
one hour at room temperature with mixing end-over-end. The antigen-phage complexes were
then captured using 50 µl of M-280 streptavidin Dynabeads® (Invitrogen) and washed 7 times
with 1 ml PBST followed by a single wash in 1 ml PBS. The washed phage were eluted from
the antigen/bead complex by incubating with 0.5 ml of 1 mg/ml trypsin type XIII from bovine
pancreas (Sigma Aldrich, UK) in PBS supplemented with 5 mM Tris-HCl pH 7.4, 0.1 mM
CaCl . Eluted phage were used to infect E. coli and the output phage titres were determined to
be between 2×10 and 9×10 TU/ml (transforming units per ml).
A second round of selection was performed using enriched phage recovered from the
first round of selection, with a final concentration of 2 nM biotinylated CD40 followed by
capture using streptavidin beads as described above. Output titres were in the range 3×10 to
5×10 TU/ml.
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A third round of selection using 2 nM biotinylated CD40 followed by capture using
streptavidin beads was performed. The eluted phage titres were in the range 8×10 to 4×10
TU/ml.
BIAcore screening
The dAb genes from each of the above round three selection outputs were sub-cloned,
as a pool, into soluble expression vector pDOM13 (Domantis) in E. coli HB2151. The
pDOM13 vector is also known as pDOM33 and is disclosed in WO/2008/149143. This vector
allowed expression of free dAb in E. coli and secretion to the supernatant. Forty-seven
individual colonies were picked from each of the outputs and expressed in 200 µl Terrific
Broth (TB) containing Novagen Overnight Express Autoinduction media (Merck Chemicals,
UK) overnight at 37°C with shaking at 250 rpm in Costar 96 Well Cell Culture Clusters
(Corning Incorporated, USA). In the same plate, a single well was inoculated with E. coli
expressing the appropriate parental (wild-type) dAb. The cultures were centrifuged to pellet
the cells and the supernatants screened on a BIAcore 3000 instrument (GE Healthcare) for
improvements in “off-rate” (i.e. dissociation rate constant, k ) compared to parental dAb.
Approximately 1600 response units (RU) of biotinylated human CD40 (BMS) were
immobilized on one flow-cell of a streptavidin (SA) BIAcore chip. A second flow cell
without any ligand immobilized served as a reference flow-cell for inline referencing. Each
dAb supernatant to be analyzed was diluted 1:3 in HBS-EP buffer (0.01 M HEPES pH 7.4 with
0.15 M NaCl, 3 mM EDTA and 0.005% v/v Surfactant P20, GE Healthcare). Ten microlitres
of each dAb supernatant were injected, using the instrument’s KINJECT function, across the
CD40-immobilized and reference flow-cells in series, with inline subtraction of the signal from
the reference cell. The experiment was performed at 25°C and with a flow rate of 10 µl/min of
HBS-EP. After each injection had been completed, the dAb was allowed to dissociate from the
ligand in buffer for 120 s before regeneration with a 5 µl injection of 10 mM glycine pH 2.0.
BIAevaluation 4.1 software (GE Healthcare) was used to subtract the reference flow-cell trace
from each analyte trace. The same software was used to perform an approximate fit of a 1:1
(Langmuir) kinetic model to the dissociation phase of the analyte traces. This model yielded
approximate dissociation rate constants (“off-rate” or k ) for each clone and allowed relative
comparisons to be made with the wild type dAb.
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Clones with improved off-rates were identified for all lineages except BMS3h-129 and
-197. Clones with improved off-rates were tested in either the bead- or ELISA-based receptor-
binding assay (RBA) to assess for improved potency as described above. The potency
measurements obtained from the RBA are given in the Tables labeled “Error-Prone-Matured
Clones.” Clones that were more potent in the RBA were subsequently tested in a B-cell
proliferation assay to assess for enhanced biological potency and these measurements obtained
are given in TABLE 17. Domain antibodies that had improved potency in the B-cell
proliferation assay were also tested in a variety of other in vitro cell assays.
Affinity maturation by triplet scanning diversification
Five improved-potency dAbs isolated from the error-prone maturation, BMS3h2, -
38-2, 2, 25 and 23, were chosen to be further affinity matured by triplet
scanning diversification. Phage libraries were constructed based on these parents as described
above for the error-prone libraries except that, instead of using error-prone PCR, a series of
overlapping degenerate triplet oligonucleotides were used to diversify the complementarity
determining (CDR) regions of each dAb. For each dAb to be affinity matured,
oligonucleotides containing NNS codon triplets (see Arkin et al. (1992) Proc. Nat’l Acad. Sci.
USA 89:7811-7815) were used to make a number of libraries for each CDR by slicing by
overlap extension (SOE) PCR. The triplets diversified by the oligonucleotides for a given
CDR overlapped by two codons, resulting in two to four libraries per CDR. The amino acid
residues diversified in the BMS3h2 libraries were at positions 30, 31, 32, 33, 35, 50, 52,
53, 55, 56, 95, 96, 97, and 98 (Kabat numbering). The residues diversified in the BMS3h2
libraries were as for 37-2, but with the addition of position 100. The residues diversified in the
BMS3h2 libraries were as for 37-2, but with the addition of positions 100 and 101. The
residues diversified in the BMS3h25 and 23 libraries were at positions 27, 28, 30,
31, 32, 34, 49, 50, 51, 53, 89, 91, 92, 93, 94, and 96.
Phage generated from these libraries were pooled by CDR and selections performed as
described above, except that, for BMS3h2, 2, 2 and 25, the concentrations of
antigen used were 10, 1 and 0.1 nM for rounds one, two and three, respectively. For BMS3h-
217-23 the concentrations of antigen used were 20, 2 and 0.2 nM for rounds one, two and
three, respectively. For BMS3h25, which is cross-reactive for cynomolgus CD40,
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selections were also performed against cyno CD40 in parallel. Additionally, selection rounds
two and three were performed in the presence and absence of 100- or 1000-fold excess
unlabelled CD40, respectively. The addition of this competitor was made after the initial one
hour incubation of the phage with the biotinylated antigen and the mixture was then incubated,
as before, for a further hour. This competition step was included with the aim of enhancing
selection of dAbs with a slower off-rate. Round one titres were in the range 1.4×10 to
9 5 8 4
1.4×10 . Titres in round 2 were 1.3×10 to 4.0×10 without competition and 8.6×10 to
8 5 8
1.3×10 with competition. Titres in round 3 were 1.2×10 to 1.9×10 without competition and
6.0×10 to 1.2×10 with competition.
These selection outputs were sub-cloned and screened as described for the error-prone
affinity maturation. Clones with improved off-rates were identified for all lineages except
BMS3h25. Clones with improved off-rates were tested in the ELISA receptor-binding
assay (RBA) to assess for improved potency. The potency measurements obtained from the
RBA are given in the Tables labeled “Further-Matured Clones.” Clones that were more potent
in the RBA were subsequently tested in a B-cell proliferation assay to assess for enhanced
biological potency and these measurements obtained are given in TABLE 17. Domain
antibodies that had improved potency in the B-cell proliferation assay were also tested in a
variety of other in vitro cell assays.
Example 2
Screening Using Receptor Binding Assays (RBA)
Several in vitro receptor binding assays (RBA) were used to determined CD40 affinity
of the anti-human CD40 variable domain amino acid sequences generated in Example 1.
Three RBA formats were used: (1) a bead RBA, (2) an ELISA RBA, and (3) a CHO cell RBA.
Bead RBA:
Phosphate buffered saline (PBS) washed Sphero streptavidin polystyrene particles
(Saxon Europe, UK) were coated with 0.5µg/ml biotinylated human IZ-CD40L (BMS). After
coating, biotinylated CD40L particles were washed in PBS and diluted 1:10 in 0.1% (w/v)
bovine serum albumin (BSA) (Sigma-Aldrich, UK) in PBS assay buffer. In a 384-well clear
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bottom, black walled plate (Applied Biosystems) a dilution range of purified dAb, 0.25 µg/ml
human CD40 (BMS, CY24FEB06-01), 1 in 5000 mouse anti-human IgG (Fc) mAb clone GG-
7 (Sigma-Aldrich, UK), 0.25 µg/ml goat anti-mouse ALEXA Fluor 647 (Invitrogen, Molecular
probes, UK) and the biotinylated CD40L polystyrene particles were combined equally and
allowed to incubate at room temperature for 6 hours in the absence of light. Following
incubation, competitive binding of dAb vs. human CD40 to biotinylated CD40L particles was
assessed using relative fluorescence with the AB8200 cellular detection mechanism (Applied
Biosystems).
ELISA RBA:
Clear walled High Bind, 384-well plates (Corning, UK) were coated with 25 µl of
1 µg/ml Neutravidin in 0.2 M carbonate-bicarbonate buffer, pH 9.4 overnight at 4 C. The
following day, assay plates were washed with 0.1% (v/v) Tween PBS buffer, blocked with 1%
(w/v) BSA in PBS for 1 hour at room temperature and washed again. Following removal of
excess washing buffer, 25 µl 1 µg/ml of biotinylated human IZ-CD40L (BMS) was incubated
with the assay plates for 1 hour at room temperature. Simultaneously, a dilution range of
purified dAb and 1 µg/ml of human CD40 (BMS, CY24FEB06-01) were complexed in a 1:1
ratio. Following washing of the assay plate, the dAb:human CD40 complex was incubated in
the assay plate at room temperature for 2 hours with gentle agitation. Competitive binding of
dAb vs. human CD40 to biotinylated CD40L was detected with sequential incubations of 1 in
5000 mouse anti-human IgG (Fc) mAb clone GG-7 (Sigma-Aldrich, UK) followed by 1 in
,000 horse radish peroxidase (HRP) conjugated goat anti-mouse IgG (Fc) secondary
detection antibody (Sigma-Aldrich, UK). Absorbance signal was measured using a
SpectraMax M5 plate reader (Molecular Devices) at 450 nm following neutralization with 1M
HCl solution.
Cell assays: CD40 CHO cell RBA:
Stably transfected human CD40 expressing CHO-DG44 cells or native CHO-DG44
cells (both BMS) were detached from cell culture flasks using Versene (Invitrogen). Forty
thousand cells per well were seeded into 96-well High Bind, black walled, clear bottom plates
(Corning, UK) in 0.1% (w/v) BSA PBS assay buffer with a dilution range of dAb, 0.25 µg/ml
of biotinylated human IZ-CD40L (BMS), and 0.25 µg/ml of streptavidin Alexa Fluor 647
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(Invitrogen, Molecular probes, UK). The mixture was incubated in the absence of light for 6
hours. Following incubation, competitive binding of dAb vs. human CD40 CHO cells to
soluble biotinylated IZ-CD40L was assessed using relative fluorescence with the AB8200
cellular detection mechanism (Applied Biosystems).
TABLES 5-7 respectively show the results from a primary screening effort (“naïve
clones”) and subsequent rounds of affinity maturation (“error-prone matured clones” and
“further-matured clones”) for the tested anti-human CD40 dAbs.
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TABLE 5
Primary Screening Effort:
Naïve Clone EC Bead RBA EC ELISA EC cell RBA
50 50 50
(nM) RBA- (nM) (CHO-CD40)
(nM)
BMS3h-37 100, 200
BMS3h-38 600, 650 >10000
BMS3h-41 2000, 1600 >10000
BMS3h-43 100, 50, 50 5000
BMS3h-56 1000, 500
BMS3h-106 300, 1000, 500, >10000
BMS3h-129 5000
BMS3h-131 500, >1000
BMS3h-193 1000
BMS3h-197 30
BMS3h-198 80 600
BMS3h-202 3000, 3700 >10000
BMS3h-217 800 1400
BMS3h-231 670, 870
BMS3h-233 2770
BMS3h-257 3210, 1340
BMS3h-242 390, 210
BMS3h-262 1770, 1160
BMS3h-263 3130
BMS3h-271 370, 210
BMS3h-285 168, 258
BMS3h-287 >10000, 6758
BMS3h-289 2390, >10000
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TABLE 6
Error-Prone-Matured Clones:
Clone EC ELISA RBA EC cell RBA
50 50
(nM) (CHO-CD40)
(nM)
BMS3h2 32
BMS3h4 45
BMS3h11 27
BMS3h5 1000
BMS3h8 2800
BMS3h3 200
BMS3h10 4300
BMS3h3 320
BMS3h5 90
BMS3h1 7.1
BMS3h2 17.0
BMS3h5 4.9, 7.5, 4.7 18, 28
BMS3h7 5.5
BMS3h8 6.2
BMS3h9 4.4, 5.5
BMS3h16 7.0
BMS3h17 66
BMS3h18 6.5
BMS3h19 5.5, 5.1
BMS3h20 6.8
BMS3h21 6.5, 6.2
BMS3h22 6.5
BMS3h23 24.5
BMS3h24 11.7
BMS3h25 5.5
BMS3h26 5.0
BMS3h27 16.3
BMS3h28 8.9
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Clone EC ELISA RBA EC cell RBA
50 50
(nM) (CHO-CD40)
(nM)
BMS3h29 9.7
BMS3h30 24.2
BMS3h31 61.0
BMS3h5 >300
BMS3h7 300
BMS3h10 200
BMS3h11 300
BMS3h12 200
BMS3h15 300
BMS3h18 100
BMS3h19 100
BMS3h25 140
BMS3h26 100
BMS3h27 100
BMS3h29 360, 114
BMS3h30 290, 116
BMS3h1 12 70
BMS3h2 115
BMS3h3 330
BMS3h9 20
BMS3h10 35
BMS3h11 20
BMS3h14 9
BMS3h17 20
BMS3h19 7.9
BMS3h22 10
BMS3h31 6.1
BMS3h32 24.7
BMS3h33 8.7
BMS3h34 32.6
BMS3h37 15.1
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Clone EC ELISA RBA EC cell RBA
50 50
(nM) (CHO-CD40)
(nM)
BMS3h38 7.2
BMS3h10 7200
BMS3h11 8300
BMS3h1 23
BMS3h2 78
BMS3h3 32
BMS3h4 partial, 15
BMS3h5 65
BMS3h6 26
BMS3h7 39
BMS3h8 6
BMS3h9 53
BMS3h14 8
BMS3h15 21
BMS3h16 9
BMS3h17 60
BMS3h23 16
TABLE 7
Further-Matured Clones:
Clone EC ELISA EC EC cell
50 50 50
RBA (nM) ICAM1 cell RBA (CHO-
assay (nM) CD40) (nM)
BMS3h202 4.1, 35
BMS3h205 3.1, 4.4
BMS3h206 3.2, 8.9
BMS3h207 2.5, 6.6
BMS3h212 24
BMS3h213 16
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Clone EC ELISA EC EC cell
50 50 50
RBA (nM) ICAM1 cell RBA (CHO-
assay (nM) CD40) (nM)
BMS3h201 3.4, inactive
BMS3h202 4.8
BMS3h203 5.5
BMS3h204 4.8
BMS3h205 4.5, 11.1
BMS3h209 10.2
BMS3h211 2.3, 13.8
BMS3h215 2.3, 3.6
BMS3h217 1.8, 2.2
BMS3h218 3.0
BMS3h219 1.8, 7.1
BMS3h223 5.7
BMS3h224 6.3
BMS3h225 8.8
BMS3h226 18.1
BMS3h228 4
BMS3h231 4.4
BMS3h235 1.5
BMS3h237 2
BMS3h238 5.1
BMS3h201 3.7, 2.3 10.0
BMS3h202 3.4, 3.2 80.0
BMS3h203 5.2, 4.3 70.0
BMS3h204 4.5
BMS3h205 9.0
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Clone EC ELISA EC EC cell
50 50 50
RBA (nM) ICAM1 cell RBA (CHO-
assay (nM) CD40) (nM)
BMS3h206 2.9, 2.3 5.0
BMS3h207 7.3
BMS3h215 3.2, 4.6 40.0
BMS3h217 2.1, 12.6
BMS3h220 4.2
BMS3h223 5.0
BMS3h224 2.1, 4.2
BMS3h225 2.9
BMS3h229 4.1
BMS3h232 2.8, 3.7
BMS3h239 2.7
BMS3h243 9.9
BMS3h244 6.0
BMS3h246 11.1
BMS3h248 0.7
BMS3h253 1.3
BMS3h258 5.2 23.0 15
BMS3h261 5.7 42.4 17
BMS3h262 4.0 135.0 42
BMS3h265 18.8 289.0 88
BMS3h266 3.8 31.9 27
BMS3h269 3.3 34.2 24
BMS3h270 11.3 93.8 91
BMS3h2501 114
BMS3h2502 170
BMS3h2503 3000
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Clone EC ELISA EC EC cell
50 50 50
RBA (nM) ICAM1 cell RBA (CHO-
assay (nM) CD40) (nM)
BMS3h2504 140
BMS3h2505 500
BMS3h2506 180
BMS3h2507 160
BMS3h2510 170
BMS3h2511 270
BMS3h2512 600
BMS3h2513 130
BMS3h2514 525
BMS3h2515 100
BMS3h2516 100
Example 3
CD40 Binding Kinetics
The binding kinetics were determined for anti-human CD40 dAbs identified in the
primary screening effort (“naïve clones”) and subsequent rounds of affinity maturation (“error-
prone matured clones”). The methods used directly measure the affinity of the dAbs for CD40.
A BIAcore 3000 instrument (GE Healthcare) was used to analyze the binding
kinetics of CD40-specific dAbs to CD40. Approximately 600 response units (RU) of
biotinylated human CD40 (BMS) were immobilized on one flow-cell of a streptavidin (SA)
BIAcore chip. A second flow cell without any ligand immobilized served as a reference
flow-cell for inline referencing. An appropriate doubling dilution series of each dAb to be
analyzed was prepared in HBS-EP buffer (0.01 M HEPES pH 7.4 with 0.15 M NaCl, 3 mM
EDTA and 0.005% v/v Surfactant P20, GE Healthcare). One hundred and eighty microlitres of
each dAb were injected in duplicate using the instrument’s KINJECT function. Each dAb was
injected across the CD40-immobilised and reference flow-cells in series with inline subtraction
of the signal from the reference cell. The experiment was performed at 25°C and a flow rate of
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µl/min of HBS-EP. After each injection had been completed, the dAb was allowed to
dissociate from the ligand in buffer for 300 s before regeneration with a 10 µl injection of
mM glycine pH 2.0. A reference injection of HBS-EP buffer blank (containing no analyte)
was also injected under the same conditions, to serve as a second reference for subtraction
from each analyte trace. BIAevaluation 4.1 software (GE Healthcare) was used to subtract
both the reference flow-cell trace and the buffer blank trace from each analyte trace. The same
software was used to perform a simultaneous, global fit of a 1:1 (Langmuir) kinetic model to
the association and dissociation phases of the analyte dilution series traces. This model yielded
association and dissociation rate constants (k and k , respectively) and the equilibrium
dissociation constant (K ) of the interaction; these are detailed in TABLES 8 and 9.
TABLE 8
Naïve Clones:
TM TM TM
Clone BIAcore BIAcore BIAcore
-1 -1 -1
k (M s ) k (s ) K (M)
a d D
BMS3h-37 1.9E+04 3.6E-03 1.9E-07
BMS3h-38 2.1E+04 6.2E-03 3.0E-07
BMS3h-41 9.9E+03 8.3E-03 8.4E-07
BMS3h-43 1.4E+03 3.1E-03 2.1E-06
BMS3h-56 2.3E+04 4.0E-03 1.8E-07
BMS3h-106 1.3E+05 4.6E-02 3.5E-07
BMS3h-107 2.0E+05 1.7E-01 8.5E-07
BMS3h-129 4.7E+05 5.1E-01 1.1E-06
BMS3h-131 2.4E+04 2.2E-02 9.3E-07
BMS3h-197 8.1E+04 1.4E-02 1.8E-07
BMS3h-198 1.6E+03 3.8E-04 2.4E-07
BMS3h-202 1.7E+03 3.5E-03 2.0E-06
TABLE 9
Error-Prone Matured Clones:
TM TM TM
Clone BIAcore BIAcore BIAcore
-1 -1 -1
k (M s ) k (s ) K (M)
a d D
BMS3h2 1.0E+05 4.1E-04 4.0E-09
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BMS3h5 3.9E+04 2.2E-04 5.5E-09
BMS3h9 1.5E+04 1.8E-04 1.2E-08
BMS3h1 3.2E+04 1.1E-03 3.3E-08
BMS3h2 6.1E+04 7.5E-04 1.2E-08
BMS3h3 7.5E+04 4.1E-04 5.5E-09
BMS3h1 5.1E+04 5.6E-04 1.1E-08
BMS3h1 4.4E+03 6.3E-04 1.4E-07
BMS3h3 3.1E+04 5.9E-04 1.9E-08
BMS3h1 9.8E+04 5.4E-04 5.5E-09
BMS3h2 1.1E+05 6.0E-04 5.3E-09
BMS3h5 1.1E+05 6.3E-04 5.9E-09
BMS3h7 1.3E+05 4.7E-04 3.5E-09
BMS3h9 1.5E+05 3.9E-04 2.6E-09
BMS3h2 7.9E+04 1.7E-03 2.1E-08
BMS3h 4.6E+05 3.7E-02 8.1E-08
BMS3h1 1.5E+04 1.8E-04 1.3E-08
BMS3h5 4.4E+03 1.3E-03 3.0E-07
Example 4
Biophysical Characterization
Anti-human CD40 dAbs identified in the primary screening effort (“naïve clones”) and
subsequent rounds of affinity maturation (“error-prone matured clones” and “further-matured
clones”) were further characterized by analysis of biophysical parameters. To measure the
relative stability of the dAbs, their melting point was determined by differential scanning
calorimetry (DSC). dAbs with a higher melting temperature are more stable. To determine
whether the dAbs form multimeric aggregates in solution, the dAbs were assayed by size
exclusion chromatography/multiangle laser light scattering (SEC-MALLS). The results are
shown in TABLES 10-12.
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TABLE 10
Naïve clones:
Clone DSC SEC-MALS solution state
(Tm/°C)
BMS3h-38 59 Monomer and dimer (<5%)
BMS3h-41 59 Monomer and monomer-dimer equilibrium (<5%)
BMS3h-43 Dimer and trimer
BMS3h-56 57 Monomer and dimer (<10%)
BMS3h-106 Monomer
BMS3h-107 63 Monomer
BMS3h-129 59 Monomer
BMS3h-193 56 Monomer
BMS3h-197 62 & 53 Monomer and dimer (<5%)
BMS3h-198 61 Monomer
BMS3h-202 60 Monomer and monomer-dimer equilibrium (<2%)
BMS3h-207 Dimer and tetramer
BMS3h-208 Monomer and dimer
BMS3h-217 57 Dimer
BMS3h-233 Monomer
BMS3h-242 Monomer and monomer-dimer
BMS3h-262 Monomer
BMS3h-265 Dimer
BMS3h-271 Dimer
BMS3h-285 Monomer
TABLE 11
Error-Prone-Matured Clones:
Clone DSC SEC-MALS solution state
Tm/°C
BMS3h1 57.2
BMS3h2 56.2
BMS3h9 59.7
BMS3h11 60.0
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Attorney Docket No. 20089600-W0
Clone DSC SEC-MALS solution state
Tm/°C
BMS3h1 49.6 Monomer
BMS3h2 63.0 Monomer and dimer (<2%)
BMS3h3 64.0 Monomer (>98%)
BMS3h5 51.2
BMS3h1 56 Monomer (~99%)
BMS3h2 53.4
BMS3h3 51.8
BMS3h9 61 Monomer and Monomer/Dimer rapid equilibrium
(<2%)
BMS3h12 49.8 Monomer/Dimer
BMS3h13 Monomer/Dimer
BMS3h1 53 Monomer (~99%)
BMS3h3 51.2
BMS3h5 48.2 Monomer/Dimer
BMS3h10 51.8
BMS3h11 54.8
BMS3h12 Dimer (60%) and Monomer (40%)
BMS3h1 59.2 Monomer/Dimer
BMS3h2 60.1 Monomer/Dimer
BMS3h5 57 Monomer (>95%)
BMS3h6 57.5 Monomer/Dimer
BMS3h7 61 Monomer + Monomer/Dimer rapid equilibrium
(<5%)
BMS3h8 58 Monomer (>98%)
BMS3h9 61 Monomer + dimer (<5%)
BMS3h14 60.1 Monomer
BMS3h8 60
BMS3h12 52
BMS3h16 54.5 & Monomer
65.7
BMS3h19 56.8 Monomer
BMS3h25 55.8 Monomer
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Attorney Docket No. 20089600-W0
Clone DSC SEC-MALS solution state
Tm/°C
BMS3h29 60 Monomer
BMS3h30 58
BMS3h1 52.5 Monomer
BMS3h2 Monomer
BMS3h3 59
BMS3h5 55.6
BMS3h19 60.7
BMS3h24 59.9 Monomer
BMS3h28 60.3 Monomer
BMS3h1 56.8 Monomer
BMS3h5 55.5 Trimer (60%) and Monomer/Dimer (40%)
BMS3h10 58.3 Trimer (60%) and Monomer/Dimer (40%)
BMS3h1 Monomer/Dimer
BMS3h2 Dimer
BMS3h3 Dimer
BMS3h4 Monomer/Dimer
BMS3h5 Dimer
BMS3h6 Dimer
BMS3h8 Dimer
BMS3h14 Monomer/Dimer
BMS3h15 Dimer
BMS3h16 Dimer
BMS3h17 Monomer/Dimer
BMS3h23 Dimer
TABLE 12
Further-Matured Clones:
Clone DSC Tm/°C SEC-MALS solution state
BMS3h206 Monomer (73%) and dimer (20%) + HMW
BMS3h212 Dimer
BMS3h201 Monomer (75%) and Dimer (15%)
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Attorney Docket No. 20089600-W0
Clone DSC Tm/°C SEC-MALS solution state
BMS3h228 Monomer (90%) and Trimer (10%)
BMS3h231 Monomer (90%) and Dimer (10%)
BMS3h235 Monomer (90%) and Trimer-Dimer
BMS3h237 Monomer (90%) and Tetramer (10%)
BMS3h238 Monomer (95%) and Dimer-Monomer
BMS3h201 57.4 + 61.8 Monomer and Dimer (15%)
BMS3h202 Monomer
BMS3h203 Monomer and Trimer
BMS3h206 Monomer
BMS3h215 Monomer, Dimer (2%) and Trimer (9%)
BMS3h217 52.8 + 54.6
BMS3h232 51.0 + 56.1 Monomer (95%) and Dimer (5%)
BMS3h239 53.5 Monomer
BMS3h243 51.9 Monomer and Pentamer
BMS3h244 Monomer (90%) and Trimer (10%)
BMS3h248 Monomer (60%), Dimer and Tetramer
BMS3h253 Monomer
BMS3h258 62.5 + 57.5
BMS3h261 58.6 + 61.5
BMS3h266 61.3 + 62.3
BMS3h269 64.5 + 67.2
Example 5
Competition Analysis
A BIAcore 3000 instrument (GE Healthcare) was used to analyze whether CD40-
specific dAbs bound the same CD40 epitope. Approximately 600 response units (RU) of
biotinylated human CD40 (BMS) were immobilized on one flow-cell of a streptavidin (SA)
chip. A second flow-cell without any ligand immobilized served as a reference
BIAcore
flow-cell for inline referencing. An appropriate dilution of each dAb or Fab to be analyzed
was prepared in HBS-EP buffer (0.01 M HEPES pH 7.4 with 0.15 M NaCl, 3 mM EDTA and
0.005% v/v Surfactant P20, GE Healthcare). The dilution chosen was one which when
injected as described below resulted in >80% of the maximum possible bound RU for the
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particular inhibitor, typically 1 - 10 µM. Next, a mixture of the same dAb or Fab as above (at
the same final concentration) was prepared with a second dAb or Fab to be analyzed for
competition. The COINJECT function of the instrument was used to inject 60 µl of the single-
inhibitor dilution across the CD40-immobilized and reference flow-cells in series, followed
immediately by a 60 µl injection of the two-inhibitor mixture. Inline subtraction of the signal
from the reference cell was performed by the instrument’s control software. The experiment
was performed at 25°C and a flow rate of 30 µl/min of HBS-EP. After each co-injection had
been completed, the inhibitors were allowed to dissociate from the ligand in buffer for 60 s
before regeneration with a 10 µl injection of 10 mM glycine pH 2.0. The maximum RU
obtained for the second injection (the mixture of the two inhibitors) was noted and expressed
as a percentage of the RU obtained for the same inhibitor when injected alone.
If the second inhibitor retained at least 100% of the RU usually bound when it was
injected alone, then this implied that the two inhibitors bind to discrete epitopes. If less than
100% binding of the second inhibitor was observed, then this was indicative of competition
between the two inhibitors for binding to CD40. There are several possible reasons for this
competition: the two inhibitors may bind to the same or overlapping epitopes, there may be
steric inhibition of binding, or binding of the first inhibitor may induce a conformational
change in the antigen that prevents or reduces binding of the second inhibitor.
An example clone from each lineage (except BMS3h-217) was tested for competition
with other dAbs in overlapping groups. All the dAbs tested appear to compete with each other
for binding to CD40, as shown in TABLES 13 and 14. This data suggests that all antibody
polypeptides selected from the group consisting of lineage BMS3h-37, BMS3h-38, BMS3h-41,
BMS3h-43, BMS3h-56, BMS3h-131, BMS3h-198, and BMS3h-202 should compete with the
binding of a dAb from any of these lineages to human CD40.
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TABLE 13
Competition BIAcore :
Second Injection (% of single dAb RU)
RU first
First BMS3h- BMS3h- BMS3h- BMS3h- BMS3h-
alone
injection 56-5 37-11 131-2 198-1 202-11
BMS3h-
56-5 245 -15 17 0.6 7.3
BMS3h-
37-11 158 15 25 16 0.3
BMS3h-
131-2 220 22 -3.7 23.2 10.3
BMS3h-
198-1 176 28 6.4 41 18
BMS3h-
202-11 124 50 42 57 39
TABLE 14
Second Injection (% of single dAb RU)
RU first
First
BMS3h- BMS3h- BMS3h- BMS3h-
injection
alone
38-2 41-9 43-1 56-5
BMS3h-
170 11 29 29
38-2
BMS3h-
150 27 44 47
41-9
BMS3h-
210 20 19 39
43-1
BMS3h-
190 4 0 22
56-5
Similarly, various dAbs were tested for competition with Chi220 Fab', as shown in
TABLES 15 and 16. In this case, all the dAbs do not compete with Chi220 Fab', except
BMS3h-217, which shows competition. BMS3h5 and BMS3h12 dAbs bound with at
least 100% of single dAb RU in the presence of bound Chi220 or G28-5 Fab', suggesting that
the Fab's bind a different epitope(s) than the dAbs. Chi220 Fab' showed a reduction of bound
RU in the presence G28-5. The same result was observed in the opposite order of binding.
This suggests that G28-5 Fab' binds the same epitope as Chi220 Fab'.
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TABLE 15
RU first Second Injection (% of single dAb/Fab RU)
dAb/Fab
First injection
BMS3h
alone
BMS3h5 Chi220 Fab G28-5 Fab 12
BMS3h5 193 98 94 64
Chi220 Fab 1089 105 11 109
G28-5 Fab 730 125 39 116
BMS3h12 282 44 98 93
TABLE 16
% of single dAb
µM dAb or Fab
Clone name Single dAb RU
tested
(Chi220+dAb)
BMS3h2 5 156 121
BMS3h13 5 162 109
BMS3h3 5 300 101
BMS3h2 5 175 114
BMS3h5 5 193 105
BMS3h-106 10 165 111
BMS3h-107 10 35 146
BMS3h-129 10 156 121
BMS3h12 5 282 98
BMS3h-197 1 177 116
BMS3h-217 10 85 25
G28-5 Fab 1 730 11
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Example 6
CD40 Activity Assays
Anti-human CD40 dAbs were assayed functionally for their ability to antagonize CD40
activities. The CD40 activities tested were B cell proliferation and cytokine production by
hCD40L-driven activation of primary human monocyte-derived dendritic cells (DCs). Unless
otherwise noted, all assays were performed in RPMI media supplemented with 10% fetal calf
serum (FCS). The results using the various assays are shown in TABLE 17.
Soluble IZ-hCD40L-driven primary human B cell proliferation:
1x10 tonsillar human B cells were incubated with 0.6 μg/ml of IZ-hCD40L along with
varying titrations of antibody polypeptide in a final volume of 200 μl/well in a 96-well round
bottom plate. The plates were incubated at 37°C for 72 hours, then thymidine ( H; 0.5
μci/well) was added for 6 hours. B cell proliferation was quantified based on thymidine
incorporation.
CHO-hCD40L-driven primary human B cell proliferation:
CHO cells were transfected with human CD40L to generate a stable cell line expressing
high levels of CD40L on the cell surface. CHO-CD40L cells were irradiated at 10,000 Rads
before incubation with human B cells. 1x10 tonsillar human B cells were incubated with
1x10 CHO-CD40L cells (1:100 ratio of CHO-CD40L: human B cells) along with varying
titrations of antibody polypeptide in a final volume of 200 μl/well in a 96-well round bottom
plate. The plates were incubated at 37°C for 72 hours following which H-thymidine
(0.5 μci/well) was added for 6 hours. B cell proliferation was quantified based on thymidine
incorporation.
Soluble IZ-hCD40L-driven cyno splenic human B cell proliferation:
1x10 cyno splenic B cells were incubated with 0.5 μg/ml of IZ-hCD40L along with
varying titrations of antibody polypeptide in a final volume of 200μl/well in a 96-well round
bottom plate. The plates were incubated at 37°C for 72 hours following which H-thymidine
(0.5 μci/well) was added for 6 hours. B cell proliferation was quantified based on thymidine
incorporation.
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Primary T cell-driven human B cell proliferation:
T cells were isolated from human peripheral blood mononuclear cells (PBMC) and
enriched using sheep red blood cell (SRBC) rosetting. Human tonsillar B cells were isolated
by homogenizing tonsil tissue to a single-cell suspension. Leukocytes were obtained by ficoll
separation, then B cells were negatively selected busing SRBC resetting and enriched by
discarding the rosetted cells.
Enriched human T cells were cultured with PM-LCLs (an EBV-transformed B cell line;
irradiated at 10,000 Rads) at a 5:1 ratio (T:LCL) for 6 days at 37°C to generate a population of
allogeneic T cells. At day 6, the expanded T cells were isolated and irradiated at 3000 Rads,
and then cultured (5x10 T cells/well) with primary human tonsillar B cells (1x10 B
cells/well) at a 1:2 ratio in 96-well flat bottom plated coated with anti-CD3 mAb (OKT3).
Varying titrations of antibody polypeptides were added to each well; the final volume in each
well was 200 μl. Test plates were incubated at 37°C for 3 days. Human B cell proliferation
was determined via the addition of H-thymidine (0.5 μci/well) to the cultures for the last 18
hours.
CHO-hCD40L-driven activation of primary human monocyte-derived dendritic cells (DCs):
Human PBMCs were enriched for monocytes by depleting T cells via SRBC rosetting.
The monocyte-enriched PBMCs were cultured with 10ng/ml GM-CSF and 5 ng/ml IL-4 in
6-well plates for 6 days at 37°C. The cultured plates were replenished with fresh media (with
GM-CSF and IL-4) on days 2 and 5. The immature dendritic cells (DCs) were used in cell
assays on day 6. 8x10 immature DCs were cultured with 4x10 CHO-hCD40L cells
(irradiated at 10,000 Rads) along with varying titrations of antibody polypeptides in a 96-well
flat bottom plate. After 24 hours, supernatants were harvested and tested for the presence of
various cytokines (IL-12, TNF, IL-23). DC activation was determined by the levels of
cytokine production.
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TABLE 17
CHO- CHO-
hIZCD40L- hIZCD40L-
hCD40L- hCD40L-
driven Human driven Cyno B
driven Human T-B cell MLR driven DC
Clone B Cell Cell
B Cell EC50 (nM) Activation
Proliferation Proliferation
Proliferation IL-12 EC50
EC50 (nM) EC50 (nM)
EC50 (nM)
(nM)
3h-5 >7000 >7000
3h-8 >7000 >7000
3h-28 >7000 >7000
3h-33 >7000 >7000
3h-48 >7000 >7000
>7000 >7000
3h-52
>7000 >7000
3h-57
>7000 >7000
3h-61
3h-88 >7000
3h-102 >7000
3h-106 437.0 ± 214.0 >7000
3h-107 >7000 >7000
3h-112 >7000
2100.0 ±
3h-129 1000.0
3h-197 360.0 ± 500.0 >7000
3h-207 >7000
3h-208 >7000
3400.0 ±
3h-37 2900.0 >7000
3h1 250.0 ± 100.0
3h2 5.0 ± 2.0 >7000 198 ± 35 13.0 ± 7.3
3h202 0.6 ± 0.2 83 ± 18 10.0
3h205 2.0 ± 1.0 6.6
3h206 5.0 ± 0.8 23.0
3h207 4.0 ± 2.0 15.5 ± 8.0
3h212 1.0 ± 0.05
3h213 0.7 ± 0.2
3h11 8.0 ± 7.0
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
CHO- CHO-
hIZCD40L- hIZCD40L-
hCD40L- hCD40L-
driven Human driven Cyno B
driven Human T-B cell MLR driven DC
Clone B Cell Cell
B Cell EC50 (nM) Activation
Proliferation Proliferation
Proliferation IL-12 EC50
EC50 (nM) EC50 (nM)
EC50 (nM) (nM)
3h-38 2800.0 ± 400.0 >7000
3h1 142.0 ± 86.0
3h2 10.0 ± 6.0 >7000 723.0 ± 185.0 986 ± 383 289.0 ± 315.0
3h201 >70.0 >7000 >800.0
3h205 4.0 ± 2.0 1100.0 ± 141.0 29.0
3h211 2.0 ± 1.0 82.0 ± 4.0 200 ± 1 18.0 ± 19.0
3h215 1.0 ± 0.0 65.0 ± 1.0 163 ± 14 6.0 ± 4.0
3h217 0.8 ± 0.2 34.0 ± 6.0 74 ± 22 1.7 ± 0.4
3h219 2.0 ± 0.5 93.0 ± 26.0 164 ± 3 9.0 ± 5.0
3h228 0.7 ± 0.05
3h231 0.66 ± 0.2
3h235 0.4 ± 0.2
3h237 0.4 ± 0.2
3h238 0.7 ± 0.03
3h3 10.0 ± 7.0
3h-41 >7000
3h1 104.0 ± 56.0
3h2 47.0 ± 67.0
3h3 12.0 ± 7.0 >7000
3h9 148.0 ± 98.0
3h12 104.0 ± 50.0
3h13 208.0 ± 90.0
3h-43 83.0 ± 40.0 >7000
3h1 53.0 ± 20.0
3h3 87.0 ± 19.0
3h5 180.0 ± 130.0
3h10 143.0 ± 131.0
3h11 30.0 ± 19.0
3h12 12.0 ± 6.0
3h-56 713.0 ± 133.0 >7000
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
CHO- CHO-
hIZCD40L- hIZCD40L-
hCD40L- hCD40L-
driven Human driven Cyno B
driven Human T-B cell MLR driven DC
Clone B Cell Cell
B Cell EC50 (nM) Activation
Proliferation Proliferation
Proliferation IL-12 EC50
EC50 (nM) EC50 (nM)
EC50 (nM) (nM)
3h1 7.0 ± 5.0
444.0,
3h2 3.0 ± 1.0 326.0 ± 79.0 276 ± 29 >2000.0
3h201 0.12 ± 0.04 11.0 ± 6.0 7.25 ± 0.96 0.93 ± 0.7
3h202 0.6 ± 0.2 39.0 ± 16.0 50 ± 9.8 2.9 ± 2.6
3h203 0.45 ± 0.1 51.0 ± 29.0 52 ± 23 3.7 ± 4.0
3h206 0.1 ± 0.01 6.0 ± 2.0 5.25 ± 0.5 0.7± 0.4
3h215 0.2 ± 0.03 41.0 ± 15.0 31 ± 7 11.0± 12.0
3h217 0.1 ± 0.04 13.0 ± 5.0 16 ± 6.7 9.4 ± 8.0
3h224 0.5 ± 0.2 26.0 ± 5.0 47 ± 11 18.0 ± 22.0
3h232 0.27 ± 0.1 37.0 ± 0.7 42 ± 10 7.3 ± 6.6
3h239 0.11 ± 0.0 18.0 ± 4.0 13.5 ± 4.76 5.8 ± 6.5
3h243 0.15 ± 0.007 13.5 ± 2.0 14.2 ± 4.6 8.8 ± 10.0
3h244 0.17 ± 0.02 26.0 ± 3.0 21 ± 4.1 12.6 ± 16.0
3h246 0.24 ± 0.06 34.0 ± 14.0 23.8 ± 6.2 23.2 ± 22.0
3h248 0.36 ± 0.1
3h253 0.4 ± 0.2
3h258 0.079 ± 0.003 11.0 ± 3.0 8.7 ± 1.9 1.52 ± 1.6
3h261 0.17 ± 0.09 25.5 ± 6.0 17 ± 5.4 3.0 ± 1.8
3h262 0.31 ± 0.007
3h265 0.36 ± 0.06
3h266 0.19 ± 0.04 19.5 ± 6.0 13.8 ± 2.4 2.8 ± 2.3
3h269 0.14 ± 0.02 15.0 ± 5.0 9.7 ± 1.9 1.8 ± 1.2
3h270 0.31 ± 0.1
3h5 6.0 ± 4.0 >7000
3h6 4.0 ± 3.0
3h7 8.0 ± 6.0
3h8 5.0 ± 2.0
3h9 3.0 ± 0.6
3h15 2.0 ± 0.9
3h19 3.0 ± 2.0
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
CHO- CHO-
hIZCD40L- hIZCD40L-
hCD40L- hCD40L-
driven Human driven Cyno B
driven Human T-B cell MLR driven DC
Clone B Cell Cell
B Cell EC50 (nM) Activation
Proliferation Proliferation
Proliferation IL-12 EC50
EC50 (nM) EC50 (nM)
EC50 (nM) (nM)
3h21 2.0 ± 1.0
2700.0 ±
3h-131 1000.0 >7000
3h2 55.0 ± 53.0 >7000
3h6 141.0 ± 37.0
3h14 24.0 ± 4.0
3h-193 >7000
3h12 277.0 ± 167.0
3h16 387.0 ± 173.0
3h19 233.0 ± 110.0
2200.0 ±
3h25 303.0 ± 214.0 1200.0
3h29 1380.0 ± 721.0
3h-198 554.0 ± 186.0 >7000
3h1 64.0 ± 47.0
3h2 207.0 ± 158.0
3h5 9.0 ± 6.0
3h19 19.0 ± 14.0
3h24 34.0 ± 37.0
3h28 20.0 ± 9.0
6400.0 ±
3h-202 1300.0 >7000
3h1 192.0 ± 77.0 >7000
6500.0 ±
3h5 1000.0
3h10 289.0 ± 158.0
3h11 201.0 ± 103.0
3200.0 ± >7000, 5300,
3h-217 2030.0 1690
3h1 45.0 ± 26.0 35.0 ± 8.0
3h2 8.0 ± 4.0 7.0 335.0
3h4 61.0 ± 20.0 27.0
DC01/ 2911446.1
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Attorney Docket No. 20089600-W0
CHO- CHO-
hIZCD40L- hIZCD40L-
hCD40L- hCD40L-
driven Human driven Cyno B
driven Human T-B cell MLR driven DC
Clone B Cell Cell
B Cell EC50 (nM) Activation
Proliferation Proliferation
Proliferation IL-12 EC50
EC50 (nM) EC50 (nM)
EC50 (nM) (nM)
3h5 13.0 ± 5.0 15.0
3h6 11.0 ± 3.0 10.0
3h7 220.0 ± 20.0
3h8 33.0 ± 10.0 14.0
3h9 380.0 ± 170.0
3h14 26.0 ± 10.0 8.0
3h15 47.0 ± 21.0 20.0
3h16 5.0 ± 2.0 7.0 1125.0
3h17 1950.0 ± 110.0
3h23 16.0 ± 6.0 15.0
3h2305 11.0 ± 4.0
3h30 80.0 ± 9.0 >7700
3h31 >700.0
3h-231 328.0 ± 144.0 >7000
3h-233 184.0 ± 75.0 >7000 1492.0, >2000
3h-240 >7000 >7000
3h-242 219.0 ± 53.0 435.0 ± 62.0 2050.0
3h-257 135.0 ± 28.0 >7000 704.0 ± 445.0
3h-262 548.0 ± 121.0 >700 998.0
3h-263 >700.0 >700
3h-264 1200.0 ± 400.0 >7000 >2000
2400.0 ±
3h-265 1000.0 >7000 >2000
3h-271 295.0 ± 92.0 446.0 >2000
3h-274 1200, >7000 >7000
3h-275 157.0 ± 11.0 >7000
3h-285 49.0 ± 0.7 155.0
3h-287 287.0 ± 156.0 918.0
2300.0 ±
3h-289 1200.0 4300.0
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
CHO- CHO-
hIZCD40L- hIZCD40L-
hCD40L- hCD40L-
driven Human driven Cyno B
driven Human T-B cell MLR driven DC
Clone B Cell Cell
B Cell EC50 (nM) Activation
Proliferation Proliferation
Proliferation IL-12 EC50
EC50 (nM) EC50 (nM)
EC50 (nM) (nM)
3h-290 >7000 5650.0
3h-294 >7000 >7000
3h-295 >7000 >7000
3h-296 306.0 ± 55.0 >7000
3h-309 648.0 ± 268.0 838.0
3h-312 1100.0 ± 346.0 >7000
Example 7
Dual Specific dAbs Binding CD40 and Serum Albumin
Dual specific dAbs that specifically bind CD40 and human serum albumin (HSA) or
cynomolgus serum albumin (CSA) were constructed and tested for activity in cell-based
assays. The albumin-specific dAbs are called “AlbudAbs.” In this example, AlbudAb fusions
comprise a BMS3h dAb that binds CD40 and another domain antibody, DOM7h, that
recognizes HSA. The two dAbs are fused in frame to the amino and carboxyl termini of an
amino acid linker to form an inline fusion (ILF) polypeptide. The ILF polypeptide is expressed
recombinantly as a single fusion protein. RBAs demonstrating activity of the AlbudAb ILFs
are described below, and the results are shown in TABLE 18. TABLE 19 summarizes the
linker sequences used in the tested AlbudAb ILFs. Kinetic binding data determined by a
BIAcore assay are shown in TABLE 20.
Human CD40 CHO cell ELISA for the detection of dAbs in a supernatant:
Stably transfected human CD40 expressing CHO-DG44 cells or native CHO-DG44
cells (both BMS) were detached from cell culture flasks using 0.25% trypsin EDTA, and
100,000 cells per well were seeded in growth media into 96 well tissue culture treated plates
(NUNC). The cells were allowed to adhere overnight in a humidified atmosphere at 37°C, 5%
CO . On the day of assay, the cell sheet was washed with PBS prior to being fixed with 2%
paraformaldehyde (Sigma-Aldrich) for 20 minutes. Following fixing, the cell sheet was
washed again in PBS prior to a 1 hr blocking step with 15% fetal bovine serum (FBS, PAA) in
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PBS. Plates were washed once more prior to addition of 100 µl/well of dAb supernatant and
incubated for 2 h at room temperature. Following incubation of dAb supernatants with cells,
the plates were washed and dAb binding was detected with incubation of horse radish
peroxidase (HRP) conjugate anti-protein A or L, depending on whether dAbs are V or V
domains. Absorbance signal was measured using a SpectraMax M5 plate reader (Molecular
Devices) at 450 nm following neutralization with 1 M HCl.
ICAM-1 up-regulation cell assay:
Stably transfected human CD40L expressing COS cells were detached from cell culture
flasks using Versene (Invitrogen). 20,000 cells per well were seeded into 96 well Highbind,
black walled, clear bottom plates (Corning, UK) in assay buffer (RPMI 1640 without phenol
red (Sigma-Aldrich, UK) + 1% penicillin/streptomycin + 10% FBS Gold (both PAA
Laboratories, UK). The cells were left to adhere overnight in a humidified atmosphere at 37°C
with 5% CO . The following day, exhausted assay buffer containing non attached cells was
replenished with 100µl of fresh assay buffer. To this, 20,000 RAMOS cells/well were added
in assay buffer in addition to a dilution range of dAb. The assay plate was returned to a
humidified atmosphere at 37°C with 5% CO for a further 24 hours. For negative control
wells, no RAMOS cells were added. The ability of dAb to inhibit the up-regulation of ICAM-
1 on the cell surface of RAMOS cells in response to exposure to CD40L on the cell surface of
COS cells was assessed by addition of 0.5µg/ml mouse anti human ICAM-1 antibody (R&D
systems) and 0.2µg/ml goat anti mouse ALEXA flour 647(Invitrogen, Molecular probes, UK).
Following a 3hour incubation period in the absence of light, relative fluorescence was detected
as measured by the AB8200 cellular detection platform (Applied Biosystems).
Analysis of inline fusion (ILF) kinetics of binding to serum albumin:
A BIAcore 3000 instrument (GE Healthcare) was used to analyze the binding
kinetics of anti-CD40-AlbudAb ILFs to human and cynomolgus serum albumin.
Approximately 400 response units (RU) of human serum albumin (HSA) or cynomolgus serum
albumin (CSA) were immobilized on a flow-cell of a CM5 BIAcore chip using an Amine
Coupling Kit (GE Healthcare). A second flow cell without any ligand immobilized served as a
reference flow-cell for inline referencing. An appropriate doubling dilution series of each dAb
to be analyzed was prepared in HBS-EP buffer (0.01 M HEPES pH 7.4 with 0.15 M NaCl,
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3 mM EDTA and 0.005% v/v Surfactant P20, GE Healthcare). Two hundred microlitres of
each ILF were injected in duplicate using the instrument’s KINJECT function. The injections
were made across the serum albumin-immobilized and reference flow-cells in series, with
inline subtraction of the signal from the reference cell. The experiment was performed at 25°C
and a flow rate of 40 µl/min of HBS-EP. After each injection had been completed, the dAb
was allowed to dissociate from the ligand in buffer for 120 s before regeneration with a 10 µl
injection of 10 mM glycine pH 2.0. A reference injection of HBS-EP buffer blank (containing
no analyte) was also injected under the same conditions to serve as a second reference for
subtraction from each analyte trace. BIAevaluation 4.1 software (GE Healthcare) was used to
subtract both the reference flow-cell trace and the buffer blank trace from each analyte trace.
The same software was used to perform a simultaneous, global fit of a 1:1 (Langmuir) kinetic
model to the association and dissociation phases of the analyte dilution series traces. This
model yielded association and dissociation rate constants (k and k , respectively) and the
equilibrium dissociation constant (K ) of the interaction. The parameter values are shown in
TABLE 20.
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TABLE 18
Activity Assays
DMS No. N-term. dAb Linker C-term. dAb CHO-CD40 Cell RBA ICAM-1 Cell Assay
EC (nM) EC (nM)
50 50
0.1% 50 µM 10% 10%
BSA HSA bovine human
serum serum
DMS0654 BMS3h201 AST DOM7h3 15 8.6
DMS0655 BMS3h201 AST DOM7h87 6.3 2.7
DMS0656 BMS3h258 AST DOM7h3 11.8 26.8
DMS0657 BMS3h258 AST DOM7h87 6.8 16.6
DMS0658 DOM7h3 TVAAPS BMS3h201 12.2 9.1
DMS0659 DOM7h87 TVAAPS BMS3h201 7.2 3.3
DMS0660 DOM7h3 TVAAPS BMS3h258 21.8 13.1
DMS0661 DOM7h87 TVAAPS BMS3h258 4.1 5.7
DMS0662 DOM7h90 TVAAPS BMS3h201 33.5 >1000
DMS0663 DOM7h86 TVAAPS BMS3h201 21.4 >1000
DMS0664 DOM7h69 TVAAPS BMS3h201 16.5 >1000
DMS0677 DOM7h90 TVA BMS3h258 21.7 20.35
DMS0679 DOM7h90 G S BMS3h258 21.7 39.2
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DMS No. N-term. dAb Linker C-term. dAb CHO-CD40 Cell RBA ICAM-1 Cell Assay
EC (nM) EC (nM)
50 50
0.1% 50 µM 10% 10%
BSA HSA bovine human
serum serum
DMS0680 DOM7h90 (G S) BMS3h258 39.3 74.2
DMS0681 DOM7h90 (G S) BMS3h258 43.6 53.3
DMS0682 BMS3h258 TVA DOM7h90 10.2 94.8
DMS0683 BMS3h258 ASTSGPS DOM7h90 32.4 50.9
DMS0684 BMS3h258 G S DOM7h90 37.9 74.3
DMS0685 BMS3h258 (G S) DOM7h90 31.9 62.4
DMS0686 BMS3h258 (G S) DOM7h90 48.3 66.6
TABLE 19
Representative Linker Sequences
AST SEQ ID NO: 5
TVAAPS SEQ ID NO: 6
TVA SEQ ID NO: 7
GGGGS SEQ ID NO: 1207
(GGGGS) SEQ ID NO: 1208
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(GGGGS) SEQ ID NO: 1209
ASTSGPS SEQ ID NO: 8
TABLE 20
BIAcore Analysis
DMS No. N-Term Linker C-Term Human Serum Albumin Cyno Serum Albumin
dAb dAb
("TVAAPS"
k (1/Ms) k (1/s) K (nM) k (1/Ms) k (1/s) K (nM)
a d D a d D
disclosed as SEQ -6 3 -6 3
×10 ×10 ×10 ×10
ID NO: 6)
DMS0659 DOM7h- TVAAPS BMS3h- 0.85, 1.17, 1.37, 0.85, 2.37, 2.79,
11-87 56-201 2.85, 2.6 1.69, 1.2 0.60, 0.45 2.79, 2.9 3.37, 2.4 1.21, 0.83
DMS0662 DOM7h- TVAAPS BMS3h- 1.1, 1.19 1.33, 1.47 1.21, 1.23 1.01, 1.10 2.52, 2.66 2.5, 2.42
11-90 56-201
DMS0663 DOM7h- TVAAPS BMS3h- 1.25, 1.32 1.40, 1.60 1.12, 1.21 1.18, 1.18 2.81, 2.96 2.38, 2.52
11-86 56-201
DMS0664 DOM7h- TVAAPS BMS3h- 2.5, 0.93 1.42, 1.49 0.57, 1.59 2.51, 0.92 2.73, 2.72 1.09, 2.97
11-69 56-201
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TABLE 21 lists amino acid sequences of representative AlbudAb ILFs that can
specifically bind CD40 and HSA or CSA. The designation of each ILF identifies the
particular linker sequence: “GxS” means the linker has “x” residues of glycine followed
by serine, and “(GxS)y” means the linker has y repeating units of GxS. TABLE 22
discloses representative nucleic acids that encode the ILF sequences listed in TABLE 21.
As is known in the art, multiple codons can encode the same amino acid. Nucleic acids
encoding a protein sequence thus include nucleic acids having codon degeneracy.
TABLE 21
Dual Specificity dAb Amino Acid Sequences
(Table 21 discloses "AST," "TVAAPS," "TVA," "G4S," "(G4S)3," "(G4S)5," and
"ASTSGPS" disclosed as SEQ ID NOS 5-7, 1207-1209 and 8, respectively)
DMS0654 BMS3h201-AST-DOM7h3
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTY
YADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKLPFYFQEWGQGTLVTVSSAS
TDIQMTQSPSSLSASVGDRVTITCRASRPIGTTLSWYQQKPGKAPKLLILWNSRLQSGV
PSRFSGSGSGTDFTLTISSLQPEDFATYYCAQAGTHPTTFGQGTKVEIKR (SEQ ID
NO: 1210)
DMS0655 BMS3h201-AST-DOM7h87
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTY
YADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKLPFYFQEWGQGTLVTVSSAS
TDIQMTQSPSSLSASVGDRVTITCRASRPIGTMLSWYQQKPGKAPKLLILAFSRLQSGV
PSRFSGSGSGTDFTLTISSLQPEDFATYYCAQAGTHHTTFGQGTKVEIKR (SEQ ID
NO: 1211)
DMS0656 BMS3h258-AST-DOM7h3
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTY
YADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKLPFYFHEWGQGTLVTVSSAS
TDIQMTQSPSSLSASVGDRVTITCRASRPIGTTLSWYQQKPGKAPKLLILWNSRLQSGV
PSRFSGSGSGTDFTLTISSLQPEDFATYYCAQAGTHPTTFGQGTKVEIKR (SEQ ID
NO: 1212)
DMS0657 BMS3h258-AST-DOM7h87
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTY
YADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKLPFYFHEWGQGTLVTVSSAS
TDIQMTQSPSSLSASVGDRVTITCRASRPIGTMLSWYQQKPGKAPKLLILAFSRLQSGV
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PATENT
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PSRFSGSGSGTDFTLTISSLQPEDFATYYCAQAGTHHTTFGQGTKVEIKR (SEQ ID
NO: 1213)
DMS0658 DOM7h3-TVAAPS-BMS3h201
DIQMTQSPSSLSASVGDRVTITCRASRPIGTTLSWYQQKPGKAPKLLILWNSRLQSGVP
SRFSGSGSGTDFTLTISSLQPEDFATYYCAQAGTHPTTFGQGTKVEIKRTVAAPSEVQL
LESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADS
VKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKLPFYFQEWGQGTLVTVSS (SEQ
ID NO: 1214)
DMS0659 DOM7h87-TVAAPS-BMS3h201
DIQMTQSPSSLSASVGDRVTITCRASRPIGTMLSWYQQKPGKAPKLLILAFSRLQSGVP
SRFSGSGSGTDFTLTISSLQPEDFATYYCAQAGTHHTTFGQGTKVEIKRTVAAPSEVQL
LESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADS
VKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKLPFYFQEWGQGTLVTVSS (SEQ
ID NO: 1215)
DMS0660 DOM7h3-TVAAPS-BMS3h258
DIQMTQSPSSLSASVGDRVTITCRASRPIGTTLSWYQQKPGKAPKLLILWNSRLQSGVP
SRFSGSGSGTDFTLTISSLQPEDFATYYCAQAGTHPTTFGQGTKVEIKRTVAAPSEVQL
LESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADS
VKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKLPFYFHEWGQGTLVTVSS (SEQ
ID NO: 1216)
DMS0661 DOM7h87-TVAAPS-BMS3h258
DIQMTQSPSSLSASVGDRVTITCRASRPIGTMLSWYQQKPGKAPKLLILAFSRLQSGVP
SRFSGSGSGTDFTLTISSLQPEDFATYYCAQAGTHHTTFGQGTKVEIKRTVAAPSEVQL
LESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADS
VKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKLPFYFHEWGQGTLVTVSS (SEQ
ID NO: 1217)
DMS0662 DOM7h90-TVAAPS-BMS3h201
DIQMTQSPSSLSASVGDRVTITCRASRPIGTMLSWYQQKPGKAPKLLILAFSRLQSGVP
SRFSGSGSGTDFTLTISNLQPEDFATYYCAQAGTHPTTFGQGTKVEIKRTVAAPSEVQL
LESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADS
VKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKLPFYFQEWGQGTLVTVSS (SEQ
ID NO: 1218)
DMS0663 DOM7h86-TVAAPS-BMS3h201
40 DIQMTQSPSSLSASVGDRVTITCRASRPIGTMLSWYQQKPGKAPKLLILAFSRLQSGVP
SRFSGSGSGTDFTLTISSLQPEDVATYYCAQAGTHPTTFGQGTKVEIKRTVAAPSEVQL
LESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADS
VKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKLPFYFQEWGQGTLVTVSS (SEQ
ID NO: 1219)
DMS0664 DOM7h69-TVAAPS-BMS3h201
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PATENT
Attorney Docket No. 20089600-W0
DIQMTQSPSSLSASVGDRVTITCRASRPIGTMLSWYQQKPGKAPKLLILAFSRLQSGVP
SRFSGSGSGTDFTLTISSLQPEDFATYYCAQAGVHPTTFGQGTKVEIKRTVAAPSEVQL
LESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADS
VKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKLPFYFQEWGQGTLVTVSS (SEQ
ID NO: 1220)
DMS0667 DOM7h3-TVAAPS-BMS3h240
DIQMTQSPSSLSASVGDRVTITCRASRPIGTTLSWYQQKPGKAPKLLILWNSRLQSGVP
SRFSGSGSGTDFTLTISSLQPEDFATYYCAQAGTHPTTFGQGTKVEIKRTVAAPSEVQL
LESGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISRNGYSTYYADS
VKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSS (SEQ
ID NO: 1221)
DMS0668 BMS3h240-AST-DOM7h3
EVQLLESGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISRNGYSTY
YADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSSAS
TDIQMTQSPSSLSASVGDRVTITCRASRPIGTTLSWYQQKPGKAPKLLILWNSRLQSGV
PSRFSGSGSGTDFTLTISSLQPEDFATYYCAQAGTHPTTFGQGTKVEIKR (SEQ ID
NO: 1222)
DMS0669 DOM7h10-TVAAPS-BMS3h240
DIQMTQSPSSLSASVGDRVTITCRASQWIGSQLSWYQQKPGKAPKLLIMWRSSLQSGVP
SRFSGSGSGTDFTLTISSLQPEDFATYYCAQGLRHPKTFGQGTKVEIKRTVAAPSEVQL
LESGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISRNGYSTYYADS
VKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSS (SEQ
ID NO: 1223)
DMS0670 BMS3h240-AST-DOM7h10
EVQLLESGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISRNGYSTY
YADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSSAS
TDIQMTQSPSSLSASVGDRVTITCRASQWIGSQLSWYQQKPGKAPKLLIMWRSSLQSGV
PSRFSGSGSGTDFTLTISSLQPEDFATYYCAQGLRHPKTFGQGTKVEIKR (SEQ ID
NO: 1224)
DMS0671 BMS3h235-AST-DOM7h3
EVQLLASGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISRNGYSTY
YADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSSAS
TDIQMTQSPSSLSASVGDRVTITCRASRPIGTTLSWYQQKPGKAPKLLILWNSRLQSGV
PSRFSGSGSGTDFTLTISSLQPEDFATYYCAQAGTHPTTFGQGTKVEIKR (SEQ ID
40 NO: 1225)
DMS0672 BMS3h235-AST-DOM7h90
EVQLLASGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISRNGYSTY
YADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSSAS
45 TDIQMTQSPSSLSASVGDRVTITCRASRPIGTMLSWYQQKPGKAPKLLILAFSRLQSGV
PSRFSGSGSGTDFTLTISNLQPEDFATYYCAQAGTHPTTFGQGTKVEIKR (SEQ ID
NO: 1226)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
DMS0674 DOM7h3-TVAAPS-BMS3h235
DIQMTQSPSSLSASVGDRVTITCRASRPIGTTLSWYQQKPGKAPKLLILWNSRLQSGVP
SRFSGSGSGTDFTLTISSLQPEDFATYYCAQAGTHPTTFGQGTKVEIKRTVAAPSEVQL
LASGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISRNGYSTYYADS
VKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSS (SEQ
ID NO: 1227)
DMS0675 DOM7h90-TVAAPS-BMS3h235
DIQMTQSPSSLSASVGDRVTITCRASRPIGTMLSWYQQKPGKAPKLLILAFSRLQSGVP
SRFSGSGSGTDFTLTISNLQPEDFATYYCAQAGTHPTTFGQGTKVEIKRTVAAPSEVQL
LASGGGLVQPGGSLRLSCAASGFTFEEEEMIWVRQAPGKGLEWVSAISRNGYSTYYADS
VKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCGKEPFRYDYWGQGTLVTVSS (SEQ
ID NO: 1228)
DMS0677 DOM7h90-TVA-BMS3h258
DIQMTQSPSSLSASVGDRVTITCRASRPIGTMLSWYQQKPGKAPKLLILAFSRLQSGVP
SRFSGSGSGTDFTLTISNLQPEDFATYYCAQAGTHPTTFGQGTKVEIKRTVAEVQLLES
GGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSVKG
RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKLPFYFHEWGQGTLVTVSS (SEQ ID
NO: 1229)
DMS0678 DOM7h90-ASTSGPS-BMS3h258
DIQMTQSPSSLSASVGDRVTITCRASRPIGTMLSWYQQKPGKAPKLLILAFSRLQSGVP
SRFSGSGSGTDFTLTISNLQPEDFATYYCAQAGTHPTTFGQGTKVEIKRASTSGPSEVQ
LLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYAD
SVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKLPFYFHEWGQGTLVTVSS (SEQ
ID NO: 1230)
DMS0679 DOM7h90-G4S-BMS3h258
DIQMTQSPSSLSASVGDRVTITCRASRPIGTMLSWYQQKPGKAPKLLILAFSRLQSGVP
SRFSGSGSGTDFTLTISNLQPEDFATYYCAQAGTHPTTFGQGTKVEIKRGGGGSEVQLL
ESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADSV
KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKLPFYFHEWGQGTLVTVSS (SEQ
ID NO: 1231)
DMS0680 DOM7h90-(G4S)3-BMS3h258
DIQMTQSPSSLSASVGDRVTITCRASRPIGTMLSWYQQKPGKAPKLLILAFSRLQSGVP
SRFSGSGSGTDFTLTISNLQPEDFATYYCAQAGTHPTTFGQGTKVEIKRGGGGSGGGGS
40 GGGGSEVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQ
GTRTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKLPFYFHEWGQGTLVT
VSS (SEQ ID NO: 1232)
DMS0681 DOM7h90-(G4S)5-BMS3h258
45 DIQMTQSPSSLSASVGDRVTITCRASRPIGTMLSWYQQKPGKAPKLLILAFSRLQSGVP
SRFSGSGSGTDFTLTISNLQPEDFATYYCAQAGTHPTTFGQGTKVEIKRGGGGSGGGGS
GGGGSGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKG
DC01/ 2911446.1
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LERVSAINPQGTRTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKLPFYF
HEWGQGTLVTVSS (SEQ ID NO: 1233)
DMS0682 BMS3h258-TVA-DOM7h90
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTY
YADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKLPFYFHEWGQGTLVTVSSTV
ADIQMTQSPSSLSASVGDRVTITCRASRPIGTMLSWYQQKPGKAPKLLILAFSRLQSGV
PSRFSGSGSGTDFTLTISNLQPEDFATYYCAQAGTHPTTFGQGTKVEIKR (SEQ ID
NO: 1234)
DMS0683 BMS3h258-ASTSGPS-DOM7h90
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTY
YADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKLPFYFHEWGQGTLVTVSSAS
TSGPSDIQMTQSPSSLSASVGDRVTITCRASRPIGTMLSWYQQKPGKAPKLLILAFSRL
QSGVPSRFSGSGSGTDFTLTISNLQPEDFATYYCAQAGTHPTTFGQGTKVEIKR (SEQ
ID NO: 1235)
DMS0684 BMS3h258-G4S-DOM7h90
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTY
YADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKLPFYFHEWGQGTLVTVSSGG
GGSDIQMTQSPSSLSASVGDRVTITCRASRPIGTMLSWYQQKPGKAPKLLILAFSRLQS
GVPSRFSGSGSGTDFTLTISNLQPEDFATYYCAQAGTHPTTFGQGTKVEIKR (SEQ
ID NO: 1236)
DMS0685 BMS3h258-(G4S)3-DOM7h90
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTY
YADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKLPFYFHEWGQGTLVTVSSGG
GGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASRPIGTMLSWYQQKPGKAPKL
LILAFSRLQSGVPSRFSGSGSGTDFTLTISNLQPEDFATYYCAQAGTHPTTFGQGTKVE
IKR (SEQ ID NO: 1237)
DMS0686 BMS3h258-(G4S)5-DOM7h90
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTY
YADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKLPFYFHEWGQGTLVTVSSGG
GGSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASRPIGTMLSWY
QQKPGKAPKLLILAFSRLQSGVPSRFSGSGSGTDFTLTISNLQPEDFATYYCAQAGTHP
TTFGQGTKVEIKR (SEQ ID NO: 1238)
DMS0688 DOM7h90-TVAAPS-BMS3h258
40 DIQMTQSPSSLSASVGDRVTITCRASRPIGTMLSWYQQKPGKAPKLLILAFSRLQSGVP
SRFSGSGSGTDFTLTISNLQPEDFATYYCAQAGTHPTTFGQGTKVEIKRTVAAPSEVQL
LESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSAINPQGTRTYYADS
VKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKLPFYFHEWGQGTLVTVSS (SEQ
ID NO: 1239)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
TABLE 22
Polynucleotides Encoding Dual Specificity dAbs
(Table 22 discloses "AST," "TVAAPS," "TVA," "G4S," "(G4S)3," "(G4S)5," and
"ASTSGPS" disclosed as SEQ ID NOS 5-7, 1207-1209 and 8, respectively)
DMS0654 BMS3h201-AST-DOM7h3
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTC
TCCTGTGCAGCCTCCGGATTCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCT
CCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCCGCAGGGTACGCGTACATACTAC
GCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTGTAT
CTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCG
TTTTACTTTCAGGAGTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGCGCTAGCACCGAC
ATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATC
ACTTGCCGGGCAAGTCGTCCGATTGGGACGACGTTAAGTTGGTACCAGCAGAAACCAGGG
AAAGCCCCTAAGCTCCTGATCCTTTGGAATTCCCGTTTGCAAAGTGGGGTCCCATCACGT
TTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAA
GATTTTGCTACGTACTACTGTGCGCAGGCTGGGACGCATCCTACGACGTTCGGCCAAGGG
ACCAAGGTGGAAATCAAACGG (SEQ ID NO: 1240)
DMS0655 BMS3h201-AST-DOM7h87
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTC
TCCTGTGCAGCCTCCGGATTCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCT
CCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCCGCAGGGTACGCGTACATACTAC
GCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTGTAT
CTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCG
TTTTACTTTCAGGAGTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGCGCTAGCACCGAC
ATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATC
ACTTGCCGGGCAAGTCGTCCGATTGGGACGATGTTAAGTTGGTACCAGCAGAAACCAGGG
AAAGCCCCTAAGCTCCTGATCCTTGCTTTTTCCCGTTTGCAAAGTGGGGTCCCATCACGT
TTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAA
GATTTTGCTACGTACTACTGTGCGCAGGCTGGGACGCATCATACGACGTTCGGCCAAGGG
ACCAAGGTGGAAATCAAACGG (SEQ ID NO: 1241)
DMS0656 BMS3h258-AST-DOM7h3
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTC
TCCTGTGCAGCCTCCGGATTCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCT
CCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCCGCAGGGTACGCGTACATACTAC
GCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTGTAT
CTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCG
TTTTACTTTCACGAGTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGCGCTAGCACCGAC
40 ATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATC
ACTTGCCGGGCAAGTCGTCCGATTGGGACGACGTTAAGTTGGTACCAGCAGAAACCAGGG
AAAGCCCCTAAGCTCCTGATCCTTTGGAATTCCCGTTTGCAAAGTGGGGTCCCATCACGT
TTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAA
GATTTTGCTACGTACTACTGTGCGCAGGCTGGGACGCATCCTACGACGTTCGGCCAAGGG
45 ACCAAGGTGGAAATCAAACGG (SEQ ID NO: 1242)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
DMS0657 BMS3h258-AST-DOM7h87
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTC
TCCTGTGCAGCCTCCGGATTCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCT
CCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCCGCAGGGTACGCGTACATACTAC
GCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTGTAT
CTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCG
TTTTACTTTCACGAGTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGCGCTAGCACCGAC
ATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATC
ACTTGCCGGGCAAGTCGTCCGATTGGGACGATGTTAAGTTGGTACCAGCAGAAACCAGGG
AAAGCCCCTAAGCTCCTGATCCTTGCTTTTTCCCGTTTGCAAAGTGGGGTCCCATCACGT
TTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAA
GATTTTGCTACGTACTACTGTGCGCAGGCTGGGACGCATCATACGACGTTCGGCCAAGGG
ACCAAGGTGGAAATCAAACGG (SEQ ID NO: 1243)
DMS0658 DOM7h3-TVAAPS-BMS3h201
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACC
ATCACTTGCCGGGCAAGTCGTCCGATTGGGACGACGTTAAGTTGGTACCAGCAGAAACCA
GGGAAAGCCCCTAAGCTCCTGATCCTTTGGAATTCCCGTTTGCAAAGTGGGGTCCCATCA
CGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCT
GAAGATTTTGCTACGTACTACTGTGCGCAGGCTGGGACGCATCCTACGACGTTCGGCCAA
GGGACCAAGGTGGAAATCAAACGTACGGTGGCTGCACCATCTGAGGTGCAGCTGTTGGAG
TCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGA
TTCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAG
CGGGTCTCAGCTATTAATCCGCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGC
CGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTG
CGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCGTTTTACTTTCAGGAGTGG
GGTCAGGGAACCCTGGTCACCGTCTCCAGC (SEQ ID NO: 1244)
DMS0659 DOM7h87-TVAAPS-BMS3h201
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACC
ATCACTTGCCGGGCAAGTCGTCCGATTGGGACGATGTTAAGTTGGTACCAGCAGAAACCA
GGGAAAGCCCCTAAGCTCCTGATCCTTGCTTTTTCCCGTTTGCAAAGTGGGGTCCCATCA
CGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCT
GAAGATTTTGCTACGTACTACTGTGCGCAGGCTGGGACGCATCATACGACGTTCGGCCAA
GGGACCAAGGTGGAAATCAAACGTACGGTGGCTGCACCATCTGAGGTGCAGCTGTTGGAG
TCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGA
TTCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAG
CGGGTCTCAGCTATTAATCCGCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGC
CGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTG
40 CGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCGTTTTACTTTCAGGAGTGG
GGTCAGGGAACCCTGGTCACCGTCTCCAGC (SEQ ID NO: 1245)
DMS0660 DOM7h3-TVAAPS-BMS3h258
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACC
45 ATCACTTGCCGGGCAAGTCGTCCGATTGGGACGACGTTAAGTTGGTACCAGCAGAAACCA
GGGAAAGCCCCTAAGCTCCTGATCCTTTGGAATTCCCGTTTGCAAAGTGGGGTCCCATCA
CGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCT
GAAGATTTTGCTACGTACTACTGTGCGCAGGCTGGGACGCATCCTACGACGTTCGGCCAA
GGGACCAAGGTGGAAATCAAACGTACGGTGGCTGCACCATCTGAGGTGCAGCTGTTGGAG
50 TCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGA
TTCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAG
CGGGTCTCAGCTATTAATCCGCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGC
CGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTG
CGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCGTTTTACTTTCACGAGTGG
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
GGTCAGGGAACCCTGGTCACCGTCTCCAGC (SEQ ID NO: 1246)
DMS0661 DOM7h87-TVAAPS-BMS3h258
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACC
ATCACTTGCCGGGCAAGTCGTCCGATTGGGACGATGTTAAGTTGGTACCAGCAGAAACCA
GGGAAAGCCCCTAAGCTCCTGATCCTTGCTTTTTCCCGTTTGCAAAGTGGGGTCCCATCA
CGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCT
GAAGATTTTGCTACGTACTACTGTGCGCAGGCTGGGACGCATCATACGACGTTCGGCCAA
GGGACCAAGGTGGAAATCAAACGTACGGTGGCTGCACCATCTGAGGTGCAGCTGTTGGAG
TCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGA
TTCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAG
CGGGTCTCAGCTATTAATCCGCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGC
CGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTG
CGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCGTTTTACTTTCACGAGTGG
GGTCAGGGAACCCTGGTCACCGTCTCCAGC (SEQ ID NO: 1247)
DMS0662 DOM7h90-TVAAPS-BMS3h201
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACC
ATCACTTGCCGGGCAAGTCGTCCGATTGGGACGATGTTAAGTTGGTACCAGCAGAAACCA
GGGAAAGCCCCTAAGCTCCTGATCCTTGCTTTTTCCCGTTTGCAAAGTGGGGTCCCATCA
CGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAATCTGCAACCT
GAAGATTTTGCTACGTACTACTGCGCGCAGGCTGGGACGCATCCTACGACGTTCGGCCAA
GGGACCAAGGTGGAAATCAAACGTACGGTGGCTGCACCATCTGAGGTGCAGCTGTTGGAG
TCCGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGA
TTCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAG
CGGGTCTCAGCTATTAATCCGCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGC
CGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTG
CGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCGTTTTACTTTCAGGAGTGG
GGTCAGGGAACCCTGGTCACCGTCTCCAGC (SEQ ID NO: 1248)
DMS0663 DOM7h86-TVAAPS-BMS3h201
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACC
ATCACTTGCCGGGCAAGTCGTCCGATTGGGACGATGTTAAGTTGGTACCAGCAGAAACCA
GGGAAAGCCCCTAAGCTCCTGATCCTTGCTTTTTCCCGTTTGCAAAGTGGGGTCCCATCA
CGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCT
GAAGATGTTGCTACGTACTACTGTGCGCAGGCTGGGACGCATCCTACGACGTTCGGCCAA
GGGACCAAGGTGGAAATCAAACGTACGGTGGCTGCACCATCTGAGGTGCAGCTGTTGGAG
TCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGA
TTCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAG
40 CGGGTCTCAGCTATTAATCCGCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGC
CGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTG
CGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCGTTTTACTTTCAGGAGTGG
GGTCAGGGAACCCTGGTCACCGTCTCCAGC (SEQ ID NO: 1249)
45 DMS0664 DOM7h69-TVAAPS-BMS3h201
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACC
ATCACTTGCCGGGCAAGTCGTCCGATTGGGACGATGTTAAGTTGGTACCAGCAGAAACCA
GGGAAAGCCCCTAAGCTCCTGATCCTTGCTTTTTCCCGTTTGCAAAGTGGGGTCCCATCA
CGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCT
50 GAAGATTTTGCTACGTACTACTGTGCGCAGGCTGGGGTGCATCCTACGACGTTCGGCCAA
GGGACCAAGGTGGAAATCAAACGTACGGTGGCTGCACCATCTGAGGTGCAGCTGTTGGAG
TCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGA
TTCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAG
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
CGGGTCTCAGCTATTAATCCGCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGC
CGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTG
CGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCGTTTTACTTTCAGGAGTGG
GGTCAGGGAACCCTGGTCACCGTCTCCAGC (SEQ ID NO: 1250)
DMS0667 DOM7h3-TVAAPS-BMS3h240
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACC
ATCACTTGCCGGGCAAGTCGTCCGATTGGGACGACGTTAAGTTGGTACCAGCAGAAACCA
GGGAAAGCCCCTAAGCTCCTGATCCTTTGGAATTCCCGTTTGCAAAGTGGGGTCCCATCA
CGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCT
GAAGATTTTGCTACGTACTACTGTGCGCAGGCTGGGACGCATCCTACGACGTTCGGCCAA
GGGACCAAGGTGGAAATCAAACGTACGGTGGCTGCACCATCTGAGGTGCAGCTGTTGGAG
TCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGA
TTCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAG
TGGGTCTCAGCTATTAGTAGGAACGGTTACAGCACATACTACGCAGACTCCGTGAAGGGC
CGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTG
CGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTATGACTACTGG
GGTCAGGGAACCCTGGTCACCGTCTCCAGC (SEQ ID NO: 1251)
DMS0668 BMS3h240-AST-DOM7h3
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTC
TCCTGCGCAGCCTCCGGATTCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCT
CCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTAGGAACGGTTACAGCACATACTAC
GCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTGTAT
CTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCG
TTTCGTTATGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGCGCTAGCACCGAC
ATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATC
ACTTGCCGGGCAAGTCGTCCGATTGGGACGACGTTAAGTTGGTACCAGCAGAAACCAGGG
AAAGCCCCTAAGCTCCTGATCCTTTGGAATTCCCGTTTGCAAAGTGGGGTCCCATCACGT
TTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAA
GATTTTGCTACGTACTACTGTGCGCAGGCTGGGACGCATCCTACGACGTTCGGCCAAGGG
ACCAAGGTGGAAATCAAACGG (SEQ ID NO: 1252)
DMS0669 DOM7h10-TVAAPS-BMS3h240
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACC
ATCACTTGCCGGGCAAGTCAGTGGATTGGGTCTCAGTTATCTTGGTACCAGCAGAAACCA
GGGAAAGCCCCTAAGCTCCTGATCATGTGGCGTTCCTCGTTGCAAAGTGGGGTCCCATCA
CGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCT
GAAGATTTTGCTACGTACTACTGTGCTCAGGGTTTGAGGCATCCTAAGACGTTCGGCCAA
40 GGGACCAAGGTGGAAATCAAACGTACGGTGGCTGCACCATCTGAGGTGCAGCTGTTGGAG
TCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGA
TTCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAG
TGGGTCTCAGCTATTAGTAGGAACGGTTACAGCACATACTACGCAGACTCCGTGAAGGGC
CGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTG
45 CGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTATGACTACTGG
GGTCAGGGAACCCTGGTCACCGTCTCCAGC (SEQ ID NO: 1253)
DMS0670 BMS3h240-AST-DOM7h10
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTC
50 TCCTGCGCAGCCTCCGGATTCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCT
CCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTAGGAACGGTTACAGCACATACTAC
GCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTGTAT
CTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCG
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
TTTCGTTATGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGCGCTAGCACCGAC
ATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATC
ACTTGCCGGGCAAGTCAGTGGATTGGGTCTCAGTTATCTTGGTACCAGCAGAAACCAGGG
AAAGCCCCTAAGCTCCTGATCATGTGGCGTTCCTCGTTGCAAAGTGGGGTCCCATCACGT
TTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAA
GATTTTGCTACGTACTACTGTGCTCAGGGTTTGAGGCATCCTAAGACGTTCGGCCAAGGG
ACCAAGGTGGAAATCAAACGG (SEQ ID NO: 1254)
DMS0671 BMS3h235-AST-DOM7h3
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTC
TCCTGCGCAGCCTCCGGATTCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCT
CCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTAGGAACGGTTACAGCACATACTAC
GCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTGTAT
CTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCG
TTTCGTTATGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGCGCTTCAACCGAC
ATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATC
ACTTGCCGGGCAAGTCGTCCGATTGGGACGACGTTAAGTTGGTACCAGCAGAAACCAGGG
AAAGCCCCTAAGCTCCTGATCCTTTGGAATTCCCGTTTGCAAAGTGGGGTCCCATCACGT
TTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAA
GATTTTGCTACGTACTACTGTGCGCAGGCTGGGACGCATCCTACGACGTTCGGCCAAGGG
ACCAAGGTGGAAATCAAACGG (SEQ ID NO: 1255)
DMS0672 BMS3h235-AST-DOM7h90
GAGGTGCAGCTGTTGGCGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTC
TCCTGCGCAGCCTCCGGATTCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCC
CCAGGGAAGGGTCTAGAGTGGGTCTCAGCTATTAGTAGGAACGGTTACAGCACATACTAC
GCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTGTAT
CTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCG
TTTCGTTATGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGCGCTTCAACCGAC
ATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATC
ACTTGCCGGGCAAGTCGTCCGATTGGGACGATGTTAAGTTGGTACCAGCAGAAACCAGGG
AAAGCCCCTAAGCTCCTGATCCTTGCTTTTTCCCGTTTGCAAAGTGGGGTCCCATCACGT
TTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAATCTGCAACCTGAA
GATTTTGCTACGTACTACTGCGCGCAGGCTGGGACGCATCCTACGACGTTCGGCCAAGGG
ACCAAGGTGGAAATCAAACGG (SEQ ID NO: 1256)
DMS0674 DOM7h3-TVAAPS-BMS3h235
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACC
ATCACTTGCCGGGCAAGTCGTCCGATTGGGACGACGTTAAGTTGGTACCAGCAGAAACCA
40 GGGAAAGCCCCTAAGCTCCTGATCCTTTGGAATTCCCGTTTGCAAAGTGGGGTCCCATCA
CGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCT
GAAGATTTTGCTACGTACTACTGTGCGCAGGCTGGGACGCATCCTACGACGTTCGGCCAA
GGGACCAAGGTGGAAATCAAACGGACCGTGGCGGCGCCGAGTGAGGTGCAGCTGTTGGCG
TCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGA
45 TTCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAG
TGGGTCTCAGCTATTAGTAGGAACGGTTACAGCACATACTACGCAGACTCCGTGAAGGGC
CGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTG
CGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTATGACTACTGG
GGTCAGGGAACCCTGGTCACCGTCTCCAGC (SEQ ID NO: 1257)
DMS0675 DOM7h90-TVAAPS-BMS3h235
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACC
ATCACTTGCCGGGCAAGTCGTCCGATTGGGACGATGTTAAGTTGGTACCAGCAGAAACCA
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
GGGAAAGCCCCTAAGCTCCTGATCCTTGCTTTTTCCCGTTTGCAAAGTGGGGTCCCATCA
CGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAATCTGCAACCT
GAAGATTTTGCTACGTACTACTGCGCGCAGGCTGGGACGCATCCTACGACGTTCGGCCAA
GGGACCAAGGTGGAAATCAAACGGACCGTGGCGGCGCCGAGTGAGGTGCAACTGTTGGCG
TCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAGCCTCCGGA
TTCACCTTTGAGGAGGAGGAGATGATTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAG
TGGGTCTCAGCTATTAGTAGGAACGGTTACAGCACATACTACGCAGACTCCGTGAAGGGC
CGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTG
CGTGCCGAGGATACCGCGGTATATTACTGTGGGAAAGAGCCGTTTCGTTATGACTACTGG
GGTCAGGGAACCCTGGTCACCGTCTCCAGC (SEQ ID NO: 1258)
DMS0677 DOM7h90-TVA-BMS3h258
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACC
ATCACTTGCCGGGCAAGTCGTCCGATTGGGACGATGTTAAGTTGGTACCAGCAGAAACCA
GGGAAAGCCCCTAAGCTCCTGATCCTTGCTTTTTCCCGTTTGCAAAGTGGGGTCCCATCA
CGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAATCTGCAACCT
GAAGATTTTGCTACGTACTACTGCGCGCAGGCTGGGACGCATCCTACGACGTTCGGCCAA
GGGACCAAGGTGGAAATCAAACGTACGGTGGCGGAGGTGCAGCTGTTGGAGTCTGGGGGA
GGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGATTCACCTTT
CGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCA
GCTATTAATCCGCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACC
ATCTCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAG
GACACCGCGGTATATTACTGTGCGAAACTTCCGTTTTACTTTCACGAGTGGGGTCAGGGA
ACCCTGGTCACCGTCTCCAGC (SEQ ID NO: 1259)
DMS0678 DOM7h90-ASTSGPS-BMS3h258
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACC
ATCACTTGCCGGGCAAGTCGTCCGATTGGGACGATGTTAAGTTGGTACCAGCAGAAACCA
GGGAAAGCCCCTAAGCTCCTGATCCTTGCTTTTTCCCGTTTGCAAAGTGGGGTCCCATCA
CGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAATCTGCAACCT
GAAGATTTTGCTACGTACTACTGCGCGCAGGCTGGGACGCATCCTACGACGTTCGGCCAA
GGGACCAAGGTGGAAATCAAACGGGCTAGCACCTCAGGTCCATCGGAGGTGCAGCTGTTG
GAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCC
GGATTCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTA
GAGCGGGTCTCAGCTATTAATCCGCAGGGTACGCGTACATACTACGCAGACTCCGTGAAG
GGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGC
CTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCGTTTTACTTTCACGAG
TGGGGTCAGGGAACCCTGGTCACCGTCTCCAGC (SEQ ID NO: 1260)
40 DMS0679 DOM7h90-G4S-BMS3h258
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACC
ATCACTTGCCGGGCAAGTCGTCCGATTGGGACGATGTTAAGTTGGTACCAGCAGAAACCA
GGGAAAGCCCCTAAGCTCCTGATCCTTGCTTTTTCCCGTTTGCAAAGTGGGGTCCCATCA
CGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAATCTGCAACCT
45 GAAGATTTTGCTACGTACTACTGCGCGCAGGCTGGGACGCATCCTACGACGTTCGGCCAA
GGGACCAAGGTGGAAATCAAACGGGGTGGAGGTGGCTCTGAGGTGCAGCTGTTGGAGTCT
GGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGATTC
ACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGG
GTCTCAGCTATTAATCCGCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGG
50 TTCACCATCTCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGT
GCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCGTTTTACTTTCACGAGTGGGGT
CAGGGAACCCTGGTCACCGTCTCCAGC (SEQ ID NO: 1261)
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
DMS0680 DOM7h90-(G4S)3-BMS3h258
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACC
ATCACTTGCCGGGCAAGTCGTCCGATTGGGACGATGTTAAGTTGGTACCAGCAGAAACCA
GGGAAAGCCCCTAAGCTCCTGATCCTTGCTTTTTCCCGTTTGCAAAGTGGGGTCCCATCA
CGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAATCTGCAACCT
GAAGATTTTGCTACGTACTACTGCGCGCAGGCTGGGACGCATCCTACGACGTTCGGCCAA
GGGACCAAGGTGGAAATCAAACGGGGTGGAGGTGGCTCTGGAGGTGGCGGTAGCGGCGGA
GGCGGTTCAGAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCC
CTGCGTCTCTCCTGTGCAGCCTCCGGATTCACCTTTCGGGATTATGAGATGTGGTGGGTC
CGCCAGGCTCCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCCGCAGGGTACGCGT
ACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAAC
ACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCG
AAACTTCCGTTTTACTTTCACGAGTGGGGTCAGGGAACCCTGGTCACCGTCTCCAGC (SEQ ID
NO: 1262)
DMS0681 DOM7h90-(G4S)5-BMS3h258
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACC
ATCACTTGCCGGGCAAGTCGTCCGATTGGGACGATGTTAAGTTGGTACCAGCAGAAACCA
GGGAAAGCCCCTAAGCTCCTGATCCTTGCTTTTTCCCGTTTGCAAAGTGGGGTCCCATCA
CGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAATCTGCAACCT
GAAGATTTTGCTACGTACTACTGCGCGCAGGCTGGGACGCATCCTACGACGTTCGGCCAA
GGGACCAAGGTGGAAATCAAACGGGGTGGAGGTGGCTCTGGAGGTGGCGGTAGCGGCGGT
GGCGGTTCAGGTGGCGGAGGTTCTGGAGGCGGTGGATCTGAGGTGCAGCTGTTGGAGTCT
GGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGATTC
ACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGCGG
GTCTCAGCTATTAATCCGCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGCCGG
TTCACCATCTCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGT
GCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCGTTTTACTTTCACGAGTGGGGT
CAGGGAACCCTGGTCACCGTCTCCAGC (SEQ ID NO: 1263)
DMS0682 BMS3h258-TVA-DOM7h90
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTC
TCCTGTGCAGCCTCCGGATTCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCT
CCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCCGCAGGGTACGCGTACATACTAC
GCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTGTAT
CTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCG
TTTTACTTTCACGAGTGGGGTCAGGGAACCCTGGTCACCGTTTCGAGCACGGTGGCGGAC
ATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATC
ACTTGCCGGGCAAGTCGTCCGATTGGGACGATGTTAAGTTGGTACCAGCAGAAACCAGGG
40 AAAGCCCCTAAGCTCCTGATCCTTGCTTTTTCCCGTTTGCAAAGTGGGGTCCCATCACGT
TTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAATCTGCAACCTGAA
GATTTTGCTACGTACTACTGCGCGCAGGCTGGGACGCATCCTACGACGTTCGGCCAAGGG
ACCAAGGTGGAAATCAAACGG (SEQ ID NO: 1264)
45 DMS0683 BMS3h258-ASTSGPS-DOM7h90
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTC
TCCTGTGCAGCCTCCGGATTCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCT
CCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCCGCAGGGTACGCGTACATACTAC
GCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTGTAT
50 CTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCG
TTTTACTTTCACGAGTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGCGCTAGCACCTCA
GGTCCATCGGACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGAC
CGTGTCACCATCACTTGCCGGGCAAGTCGTCCGATTGGGACGATGTTAAGTTGGTACCAG
CAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCCTTGCTTTTTCCCGTTTGCAAAGTGGG
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GTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAAT
CTGCAACCTGAAGATTTTGCTACGTACTACTGCGCGCAGGCTGGGACGCATCCTACGACG
TTCGGCCAAGGGACCAAGGTGGAAATCAAACGG (SEQ ID NO: 1265)
DMS0684 BMS3h258-G4S-DOM7h90
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTC
TCCTGTGCAGCCTCCGGATTCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCT
CCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCCGCAGGGTACGCGTACATACTAC
GCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTGTAT
CTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCG
TTTTACTTTCACGAGTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGCGGTGGAGGCGGC
TCTGACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTC
ACCATCACTTGCCGGGCAAGTCGTCCGATTGGGACGATGTTAAGTTGGTACCAGCAGAAA
CCAGGGAAAGCCCCTAAGCTCCTGATCCTTGCTTTTTCCCGTTTGCAAAGTGGGGTCCCA
TCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAATCTGCAA
CCTGAAGATTTTGCTACGTACTACTGCGCGCAGGCTGGGACGCATCCTACGACGTTCGGC
CAAGGGACCAAGGTGGAAATCAAACGG (SEQ ID NO: 1266)
DMS0685 BMS3h258-(G4S)3-DOM7h90
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTC
TCCTGTGCAGCCTCCGGATTCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCT
CCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCCGCAGGGTACGCGTACATACTAC
GCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTGTAT
CTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCG
TTTTACTTTCACGAGTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGCGGTGGAGGTGGC
TCTGGAGGTGGCGGTAGCGGCGGTGGCGGTTCAGACATCCAGATGACCCAGTCTCCATCC
TCCCTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTCGTCCGATT
GGGACGATGTTAAGTTGGTACCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCCTT
GCTTTTTCCCGTTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACA
GATTTCACTCTCACCATCAGCAATCTGCAACCTGAAGATTTTGCTACGTACTACTGCGCG
CAGGCTGGGACGCATCCTACGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACGG (SEQ ID
NO: 1267)
DMS0686 BMS3h258-(G4S)5-DOM7h90
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTC
TCCTGTGCAGCCTCCGGATTCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCT
CCAGGGAAGGGTCTAGAGCGGGTCTCAGCTATTAATCCGCAGGGTACGCGTACATACTAC
GCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTGTAT
CTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCG
40 TTTTACTTTCACGAGTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGCGGTGGAGGTGGC
TCTGGAGGTGGCGGTAGCGGCGGTGGCGGTTCAGGTGGCGGAGGTTCTGGAGGCGGTGGA
TCTGACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTC
ACCATCACTTGCCGGGCAAGTCGTCCGATTGGGACGATGTTAAGTTGGTACCAGCAGAAA
CCAGGGAAAGCCCCTAAGCTCCTGATCCTTGCTTTTTCCCGTTTGCAAAGTGGGGTCCCA
45 TCACGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAATCTGCAA
CCTGAAGATTTTGCTACGTACTACTGCGCGCAGGCTGGGACGCATCCTACGACGTTCGGC
CAAGGGACCAAGGTGGAAATCAAACGG (SEQ ID NO: 1268)
DMS0688 DOM7h90-TVAAPS-BMS3h258
50 GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACCGTGTCACC
ATCACTTGCCGGGCAAGTCGTCCGATTGGGACGATGTTAAGTTGGTACCAGCAGAAACCA
GGGAAAGCCCCTAAGCTCCTGATCCTTGCTTTTTCCCGTTTGCAAAGTGGGGTCCCATCA
CGTTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAATCTGCAACCT
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GAAGATTTTGCTACGTACTACTGCGCGCAGGCTGGGACGCATCCTACGACGTTCGGCCAA
GGGACCAAGGTGGAAATCAAACGGACCGTAGCGGCGCCGAGTGAGGTGCAGCTGTTGGAG
TCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAGCCTCCGGA
TTCACCTTTCGGGATTATGAGATGTGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAG
CGGGTCTCAGCTATTAATCCGCAGGGTACGCGTACATACTACGCAGACTCCGTGAAGGGC
CGGTTCACCATCTCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTG
CGTGCCGAGGACACCGCGGTATATTACTGTGCGAAACTTCCGTTTTACTTTCACGAGTGG
GGTCAGGGAACCCTGGTCACCGTCTCCAGC (SEQ ID NO: 1269)
Example 8
Anti-Cynomolgus CD40 dAbs
The methods disclosed herein to generate antibody polypeptides that specifically
bind human CD40 may be used to generate antibody polypeptides that specifically bind
CD40 of other species. For example, anti-cynomolgus (anti-cyno) CD40 antibody
polypeptides can be produced using the presently disclosed methods. The anti-
cynoCD40 antibody polypeptides can be generated using the same scheme of
initial/primary screening and affinity maturation as anti-human CD40 dAbs, for example.
Methods for obtaining anti-cynoCD40 dAbs are disclosed, and representative examples
of anti-cynoCD40 dAbs are provided in TABLE 23 below.
ELISA RBA:
Clear walled Highbind, 384 well plates (Corning, UK) were coated with 25µl of
1 µg/ml neutravidin in carbonate buffer overnight at 4°C. The following day, assay
plates were washed with 0.1% Tween PBS buffer, blocked with 1% BSA in PBS for
1hour at room temperature, and washed again. Following removal of excess washing
buffer, 25 µl of 1 µg/ml of biotinylated human IZ-CD40L (BMS, 1.2 mg/ml stock
concentration) was incubated with the assay plates for 1 hour at room temperature.
Simultaneously, a dilution range of purified dAb and 1 µg/ml of cynoCD40 (BMS) were
complexed in a 1:1 ratio. Following washing of the assay plate, the dAb:cyno CD40
complex was incubated in the assay plate at room temperature for 2hours with gentle
agitation. Competitive binding of dAb vs. cynoCD40 to biotinylated CD40L was
detected with horse radish peroxidase (HRP) conjugated anti human (Fc) secondary
antibody (Sigma-Aldrich, UK). Absorbance signal was measured using a Spectromax
M5e plate reader (Molecular Devices) at 450 nm following neutralization with 1M HCl.
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cynoCD40 CHO cell RBA using AB8200 FMAT:
Stably transfected cynoCD40-expressing CHO-DG44 cells or native CHO-DG44
cells (BMS) were detached from cell culture flasks using Versene (Invitrogen). 40,000
cells per well were seeded into 96 well Highbind, black walled, clear bottom plates
(Corning, UK) in 0.1% BSA PBS assay buffer with a dilution range of dAb, 0.25 µg/ml
of biotinylated human IZ-CD40L (BMS, 1.2 mg/ml stock concentration), and 0.25 µg/ml
of streptavidin Alexa Fluor 647 (Invitrogen, Molecular probes, UK). The mixture was
incubated in the absence of light for 6hours. Following incubation, competitive binding
of dAb vs. cynoCD40 CHO cells to soluble biotinylated IZ-CD40L was assessed using
relative fluorescence as measured by the AB8200 cellular detection platform (Applied
Biosystems).
CHO-hCD40L-driven primary human B cell proliferation:
CHO cells (ATCC) were transfected with human CD40L to generate a stable cell
line expressing high levels of CD40L on the cell surface. CHO-CD40L cells were
irradiated at 10,000 Rads before incubation with human B cells. 1x10 tonsillar human B
cells were incubated with 1x10 CHO-CD40L cells (1:100 ratio of CHO-CD40L: human
B cells) along with varying titration of dAb or monoclonal antibody in a final volume of
200μl/well in a 96-well round bottom plate. The plates were incubated at 37°C for 72
hours, following which thymidine ( H; 0.5μci/well) was added for 6 hours. B cell
proliferation was quantified based on thymidine incorporation. All assays, unless
otherwise noted, were performed in RPMI media supplemented with 10% fetal calf
serum (FCS).
Soluble IZ-hCD40L-driven cyno splenic B cell proliferation:
1x10 B cells isolated from cynomolgous monkey spleens were incubated with
0.5 μg/ml of IZ-hCD40L along with varying titration of dAb or mAb in a final volume of
200 μl/well in a 96-well round bottom plate. The plates were incubated at 37°C for 72
hours, following which H-thymidine (μci/well) was added for 6 hours. B cell
proliferation was quantified based on thymidine incorporation. All assays, unless
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otherwise noted, were performed in RPMI media supplemented with 10% fetal calf
serum (FCS).
TABLE 23
Clone ELISA RBA Cell RBA B cell proliferation assay
(nM) (nM) (EC50 nM)
Human Cyno
BMS5c8 8,10,12,8,8
BMS3c-85 370 >7000, >7000 747, 2700, 7000,
7000
BMS3c1 52, 8 12 2600, 1100 18, 39, 47
BMS3c2 12, 4 4, 17 1800, 800 2, 5, 6, 1
BMS3c3 7 23 >7000, >7000 33, 31, 21, 31
BMS3c8 22 17.2 >7000, >7000 33, 33, 25
BMS3c9 10 >7000, >7000 >70, >70, 104
BMS3c21 11 18 24
BMS3c24 8 13, 14
BMS3c25 62
BMS3c26 3 3300, 3900 >70, >70, 385
BMS3c27 13 23 39
BMS3c31 13 11, 9
BMS3c32 21 56 111
BMS3c33 15 10, 21.3 17
BMS3c34 48
BMS3c35 - 19, 1.5 >700 2
BMS3c36 - 28
BMS3c37 - 71
BMS3c38 - 17
BMS3c47 - 2.9 >700 <2, 0.5
BMS3c49 - 10 >700 3, 3
BMS3c51 - 2.5 >700 3
BMS3c52 - 8.5
BMS3c55 - 13.3, 6.7 >700 3, 3
BMS3c56 - no convergence
BMS3c57 - 13.8, 5.3 >700 2, 4
BMS3c62 - 9.9, 2.7, 2.0 >700 <2, 0.63
BMS3c63 - 80.9
BMS3c64 - 16.1
BMS3c65 - 13.9, 7.4 >700 3, 2
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Clone ELISA RBA Cell RBA B cell proliferation assay
(nM) (nM) (EC50 nM)
Human Cyno
BMS3c67 - 1.5 0.17
BMS3c69 - 1.8 0.33
BMS3c72 - 2 0.16
BMS3c73 - 2.3
BMS3c77 - 2.3 0.2
BMS3c84 - 1.3 0.21
BMS3c88 - 3 0.25
BMS3c91 - 1.3 0.26
Example 9
Anti-Human CD40 dAbs Do Not Bind CynoCD40
CynoCD40 has a Leu109 residue instead of a Trp109, as in human CD40. The
amino acid sequence of Macaca fascicularis CD40 is reproduced below:
1 MVRLPLQCVL WGCLLTAVYP EPPTACREKQ YLINSQCCSL CQPGQKLVSD
51 CTEFTETECL PCGESEFLDT WNRETRCHQH KYCDPNLGLR VQQKGTSETD
101 TICTCEEGLH CTSESCESCV PHRSCLPGFG VKQIATGVSD TICEPCPVGF
151 FSNVSSAFEK CRPWTSCETK DLVVQQAGTN KTDVVCGPQD RQRALVVIPI
201 CLGILFVILL LVLVFIKKVA KKPNDKVPHP KQEPQEINFP DDLPGSNPAA
251 PVQETLHGCQ PVTQEDGKES RISVQERQ (SEQ ID NO: 2)
Anti-human CD40 dAbs were tested for cross reactivity to B cells in cynomolgus
monkey, rhesus macaque and chimpanzee blood, and lymphocytes from marmoset blood
using flow cytometric methods. The procedures detailed below summarize methods used
for CD40 dAb detection over multiple experiments. The results, shown in TABLE 24,
suggest that anti-human CD40 dAbs do not bind cynoCD40. This is consistent with the
evidence disclosed above (see and 2) that Trp109 in human CD40 (which is absent
in cynoCD40) is important for complex formation between the dAbs and human CD40.
Methods:
PEGylated anti-human CD40 dAbs (BMS3h5C-40L and BMS3h38-2C-
P40Br) or a biotin-conjugated dAb (BMS3h38biotin) were incubated with human and
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primate blood samples on a rotator for 1 hour at 37°C. 100 μl from each blood sample
was aliquoted to 12 x 75mm tubes and washed 3 times with FACS buffer (0.5%
FBS/PBS/0.1% sodium azide). Tubes were centrifuged for 5 minutes at 1500 rpm, and
supernatants were decanted between washes. Following the washes, tubes were placed
on ice and incubated with human IgG for 5 minutes to block non-specific binding via Fc
receptors.
For PEGylated dAb detection, anti-PEG antibodies (clone CH-2074, Silver Lake
Research or clone 2-2, Open Biosystems) were added to tubes and incubated for 30
minutes. Samples were washed once in FACS buffer, then incubated with an APC-
labeled CD20 antibody (clone 2H7, BD Biosciences) and PE labeled-anti-mouse IgG
(Fcγ1 specific; Calbiochem) for an additional 30 minutes on ice.
For biotin-conjugated dAb detection, PE-labeled streptavidin (Invitrogen) and
APC-labeled CD20 antibody (clone 2H7, BD Biosciences) were added to tubes and
incubated 30 minutes at room temperature.
Additionally, to measure CD40 levels on human and primate blood, an aliquot of
each blood sample was incubated with an APC-labeled CD20 antibody (clone 2H7, BD
Biosciences) and a PE-labeled anti-human CD40 antibody that cross reacts with primate
species (clone 5C3, BD Biosciences) for 30 minutes at room temperature.
To lyse red blood cells and fix white blood cells following detection antibody
incubation, FACS Lysing Solution (BD Biosciences) was added to all tubes, and samples
were incubated for 15 minutes at room temperature. Samples were centrifuged and
resuspended in FACS Lysing Solution, and analyzed by flow cytometry on a BD
FACSCanto™, gating on CD20+ B cells for analysis. For marmoset samples, the CD20
antibody was not cross reactive; therefore analysis was performed on all lymphocytes as
identified by forward and side scatter properties (size).
Results:
Binding of PEGylated and biotinylated anti-human CD40 dAbs was tested in
human and primate blood samples according to the method above. Anti-human CD40
dAb binding to CD20+ B cells in human blood samples was detected. In contrast, the
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binding of PEGylated and biotinylated CD40 dAbs was not detected on CD20+ B cells in
cynomolgus, rhesus, or chimp blood samples or on lymphocytes in marmoset blood
samples. Results for BMS3h2C-P40Br dAb are shown in Panels A and B.
Similar results were obtained for the other dAbs. Comparable levels of CD40 on the B
cells of human and primate species were confirmed using an anti-human CD40 antibody
that cross reacts with primate CD40. These data indicate that human CD40 dAbs from
the BMS3h-56 and BMS3h-38 lineages are unable to bind CD40 in primate species. The
data are consistent with the importance of the Trp109 residue in forming a complex
between CD40 and the anti-CD40 dAbs, as shown in FIGS. 1 and 2.
Example 10
X-Ray Crystallography of a Complex Between CD40 and dAb BMS3h5
Data collection and processing:
Two different crystal forms were analyzed during the structure determination of
the human CD40 (SEQ ID NO: 1)/BMS3h5 (SEQ ID NO: 321) complex. Data were
collected from a crystal of the CD40/BMS3h56-5 complex, flash-cooled to and
maintained at 100 K, and mounted on a Rigaku AFC-9 goniometer. The X-ray source
was a Rigaku FR-E using a copper target with MicroMax confocal optics and a Saturn
92 detector. Data were collected at extremely high redundancy to enhance the sulfur
anomalous diffraction signal in the hopes of using that signal to phase the data. Data
were processed with HKL2000 (HKL Research; Otwinowski et al., In Methods Enzymol.
Macromolecular Crystallography part A, Carter et al., eds., vol. 276, p. 307-326,
Academic Press, Inc., New York, NY (1997)). Data collection statistics for this crystal
are summarized below and in Table 24:
Space Group: I222;
Unit Cell: a = 156.6 Å; b = 158.3 Å; c = 200.7 Å;
Mosaicity 0.59-0.84; Rejected observations: 1028; 0.06%.
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TABLE 24
s09-167 Resolution, Measured Unique Redun. %Complete R
Å value
1603547 37772 42.5 99.8 0.137 33.7
Overall 50.00-3.30
First 50.00-8.94 ≥38193 1971 40.1 97.1 0.049 58.7
Shell
Last 3.36-3.30 ≥37054 1861 43.6 99.8 0.439 12.5
Shell
A second crystal form was collected from a crystal flash-cooled to 100 K and
mounted on a Rayonix MX-225 detector at the Canadian Light Source beamline CMCF1
(08-ID-1) and the wavelength was 0.9793 Å. These data were collected by Shamrock
Structures (R. Walter and G. Ranieri) and were processed with HKL2000. Data
collection statistics for this crystal are summarized below and in Table 25:
Space Group: C2;
Unit Cell: a = 199.3 Å; b = 48.7 Å; c = 138.8 Å; β = 118.2°;
Mosaicity 0.62-0.71; Rejected observations: 70; 0.08%.
TABLE 25
x09-275 Resolution, Measured Unique Redun. %Complete R
Å value
Overall 50.00-2.80 92545 29303 3.2 98.6 0.091 14.6
First 50.00-6.03 9265 3060 3.0 98.5 0.052 18.0
Shell
Last 2.90-2.80 8857 2882 3.1 98.0 0.421 3.4
Shell
Molecular Replacement Models:
The model of the dAb, BMS3h5, was derived from PDB ID 2VYR chain E
residues 1-124 with sequential residues corresponding to CDRs 31-35, 50-57, and 99-111
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removed by SPLIT_PDB (which corresponds to Kabat numbering 31-35, 50-56, and 95-
100G) and then run through MUTATE and finally renumbered by RENUMBER.
MUTATE changes non-identical residues to the minimum identical, i.e., normally Ala or
Gly, but, for example Tyr→Phe and Phe→Tyr would result in Phe. It does not build any
atoms, although for Thr→Val, Val→Thr, Cys→Ser, and Ser→Cys, it will substitute the
appropriate atom name, but not change the position. RENUMBER changed the
numbering to Kabat numbering (Kabat et al., Sequences of Immunological Interest, 5
ed., U.S. Dept. Health & Human Services, Washington, D.C. (1991)), which is a standard
numbering system for antibodies that makes description of CDRs and framework
residues straight-forward.
A CD40 model was constructed from PDB IDs 1JMA (chain B), 1NCF (chain A),
1TNR (chain R), 2HEV (chain R), 2HEY (chains R, T), and 2UWI (chains A, B) using
phenix.ensembler (University of Cambridge, UK) to create an ensemble of structures.
The N-termini (residues 24-78) plus a six residue segment (residues 95-100) of these
molecules were superimposable with an acceptable root mean square distance for Cα
atoms, and that was used as a model for the N-terminal region of CD40.
Molecular Replacement Methods:
The program PHASER (McCoy et al., J. Appl. Crystallogr. 40: 658-674 (2007))
was used for molecular replacement. The translation function Z-score (TFZ) and the
increase in the log-likelihood gain were monitored to decide whether real solutions had
been found. TFZ scores of 8 and above generally represent a solution. Lesser TFZ
scores accompanied by substantial increases (>50) in the log-likelihood gain also are
acceptable indicators.
Model building, Density Modification, and Crystallographic Refinement Methods:
Model-building tools for molecular graphics included the COOT program
(Emsley et al., Acta Crystallogr Sect. D 60: 2126-2132 (2004); Emsley et al., “Features
and Development of Coot,” Acta Crystallogr Sect. D 66: 486-501 (2010)). Density
modification using non-crystallographic symmetry map averaging was performed using
known density modification programs and other programs to calculate the Eulerian
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angles and translations between molecules. Refinement was run using autoBUSTER
(GlobalPhasing,Ltd.: Bricogne et al., Acta Crystallogr. Sect. D 60: 2210-2221 (2004);
Tronrud et al., Acta Crystallogr. Sect. A 43: 489-501 (1987)).
Domain Antibody numbering system:
The residue numbering system for the domain antibody follows that of Kabat.
The Kabat numbering is compared to straight sequential numbering below for BMS3h-
56-5:
1
BMS-3h5 ST
CDR1_
Kabat 10 20 30 40
- | - | - | - | -
Sequential 10 20 30 40
- | - | - | - | -
BMS-3h5
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSA
______CDR2______
Kabat 60 70 80 90
A - | - | - | ABC - |
Sequential 60 70 80 90
- | - | - | - | -
BMS-3h5
INPQGTRTYYADSVMGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKLP
CDR3_
Kabat 99101 110 116
|| - | -|
Sequential 110 119
- | - |
BMS-3h5 FTFDDWGQGTLVTVSSAAA (SEQ ID NO: 3)
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In Kabat numbering BMS3h5 has insertion residues 52A, 82A, 82B, 82C and is
missing residue 100. In both numbering systems the Ser and Thr at the N-terminus that
are part of the expression construct are given negative numbers.
Determination of the structure of CD40/BMS3h5 complex:
PHASER was able to locate four BMS3h5 dAb molecules in the I222 crystal
form and three BMS3h5 dAb molecules in the C2 crystal form. In the I222 crystal
form the TFZ scores ranged from 7.6 to 41.0, and the increase in the log-likelihood gain
ranged from 77 to 446. These solutions for the BMS3h5 dAb molecules formed
helical columns of dAb molecules through the I222 crystal that were separated from other
columns by large channels. In the C2 crystal the TFZ scores ranged from 7.7 to 16.5, and
the increase in the log-likelihood gain ranged from 110 to 150. The packing of the dAbs
in this crystal form was not repetitive or symmetric.
Using the ensemble model for the CD40 N-terminal domain, four molecules of
the N-terminal domain of CD40 could be placed in the I222 crystal form with TFZ scores
ranging from 5.7 to 8.5, and the increase in the log-likelihood gain ranged from 83 to
389. The four N-terminal domains of CD40 in the I222 crystal form formed a clump
equally centered between four columns of dAb molecules. However, they did not touch
the BMS3h5 dAb molecules. In the C2 crystal form three molecules of the N-
terminal domain of CD40 could be placed with TFZ scores ranging from 5.8 to 12.1, and
the increase in the log-likelihood gain ranged from 100 to 198. In this crystal form, the
N-terminal domains also did not contact the BMS3h5 dAb molecules.
In the I222 crystal form, the N-terminal domain of the CD40 from the
CD40/Chi220 Fab complex and the N-terminal domain from 2UWI were superimposed
on the CD40 N-terminal domain. The ability to associate the N-terminal with a particular
BMS3h5 dAb allowed the use of non-crystallographic symmetry (NCS) map
averaging. The starting correlation coefficients for NCS averaging gave off-diagonal
values of 0.71-0.81. The final off-diagonal values were 0.88-0.92. The electron density
close to the N-terminal region was clear, and a path could be traced for CDR3 of the
BMS3h5 dAb. Residues 82-94 and 101-121 from the CD40/Chi220 Fab' complex
were superimposed on the corresponding residues on 2UWI and then COOT was used to
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improve the fit manually. This position for the second domain (residues 82-94 and 101-
121) of CD40 was then transformed onto the other three N-terminal domains.
A cycle of refinement was run with R-free decreasing from 0.437 to 0.380 and
R-work from 0.447 to 0.381 with improvement in root mean square bond and angle
deviations from ideal. The resulting electron density map showed that residue 109 had a
side chain that was consistent with Trp and that density existed for at least some residues
in the C-terminal 70 residues of CD40.
Since CD40 has little secondary structure, fitting the C-terminal ~70 residues to
the electron proved difficult, so the Research Collaboratory for Structural Bioinformatics
Protein Data Base was searched for a suitable model to help guide chain tracing. The top
two hits with 16 out of 44 identities and 24 out of 44 matches were 2AW2 and 1JMA,
which have the same sequence:
125 130 140 150 160
_ | _ | _ | _ | _
CD40 CSPGFGVKQIATGVSDTICEPCPVGFFSNVSSAFEKCHPWTSCE
2AW2 CSPGYRVKEACGELTGTVCEPCPPGTYIAHLNGLSKCLQCQMCD
Consensus CSPG* VK* ** T CEGCP G * * KC C*
| . | . | . | . | .|
23 30 40 50 60 66
|. . | . | . | . . |
1JMA 19 30 40 50 62
(SEQ ID NOS 1270-1271)
Identical residues are noted with the appropriate single letter code on the consensus line
and similar residues are noted on the consensus line as asterisks. This was the same
stretch of residues as for residues 41-84 of the N-terminal domain of CD40:
41 50 60 70 80
| _ | _ | _ | _ |
CD40 CQPGQKLVSDCTEFTETECLPCGESEFLDTWNRETHCHQHKYCD
CD40 CSPGFGVKQIATGVSDTICEPCPVGFFSNVSSAFEKCHPWTSCE
Consensus C PG * T **T C PC F * * *CH C*
_ | _ | _ | _ | _
125 130 140 150 160
(SEQ ID NOS 1272 and 1270)
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Identical residues are noted with the appropriate single letter code on the consensus line
and similar residues are noted on the consensus line as asterisks.
Matching disulfide bonds:
Comparison of Disulfide linkages in residues 41-84 and 125-168 of CD40
Residues 41-84 Residues 125-
C41-C59 C125-C143
[C38]-C51
C62-C77 C146-C161
C83[-C103] C167[-C186]
Residues in brackets fall outside of the residue ranges in the sequence repeat.
With the 1JMA/2AW2 model as a guide, the COOT program was used to fit one
of the CD40 chains. This fitted model was then superimposed on one of the other three
CD40 chains. However, it appeared that the position of this new stretch of residues was
differently oriented in the other two CD40 chains, and they were not fitted at this time. A
cycle of refinement was run with R-free decreasing from 0.393 to 0.366 and R-work from
0.400 to 0.349 with considerable improvement in root mean square bond and angle
deviations from ideal.
The BMS3h5 dAb from one of the molecules in the I222 crystal form was
superimposed on each of the three dAbs in the C2 crystal form. That transformation
matrix was used to orient the second and C-terminal domains of the I222 crystal form.
The model was rebuilt using the COOT program. A cycle of refinement was run with R-
free decreasing from 0.361 to 0.334 and R-work from 0.375 to 0.306 with improved root
mean square bond and angle deviations from ideal. The resulting electron density map
provided guidance for placing many more CD40 residues. Another cycle of refinement
was run with R-free decreasing from 0.302 to 0.287 and R-work from 0.299 to 0.270 with
improved root mean square bond and angle deviations from ideal
Conventional model building and refinement then were used to complete the
structure determination. Several more rounds of optimization led to a final refinement
with the following statistics: R-free 0.260, R-work 0.228, root mean square bonds 0.010
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Å, root mean square angles 1.4°. The real space correlation coefficients are 0.92 for
main-chain atoms and 0.80 for side-chain atoms. The final model had 13 water
molecules.
Using the model of the C-terminal domain from the C2 crystal form as a guide,
the CD40 models in I222 crystal form were further refined. Several more cycles of
model building using the COOT program and refinement with the autoBUSTER program
led to the following statistics: R-free 0.323, R-work 0.292, root mean square bonds 0.011
Å, root mean square angles 1.5°. The real space correlation coefficients are 0.91 for
main-chain atoms and 0.80 for side-chain atoms. The model contained no water
molecules.
Overall Structure of the CD40/BMS3h5 complex:
One BMS3h5 dAb binds to one CD40 molecule. As shown in
BMS3h5 binds to an epitope that is distinct from that of the antibody Chi220, which
binds in the N-terminal region. CD40 residues (SEQ ID NO: 1) are shown in green,
except for epitope residues. CD40 epitope residues for Chi220 are shown in blue;
BMS3h5 dAb epitope residues are shown in cyan. Chi220 Fab and BMS3h5 β-
strands are shown in red, CDR residues are shown in magenta, and other loops are shown
in orange. Disulfide bonds are shown for the CD40, Chi220, and BMS3h5 molecules
with the sulfur atoms in yellow.
The I222 crystal form contains four crystallographically independent
CD40/BMS3h5 complexes, and the C2 crystal for contains three crystallographically
independent CD40/BMS3h5 complexes. The CD40 molecule has a certain amount
of flexibility, and the domains are arrayed differently in the seven unique versions of the
complex, but the overall nature of the interaction is retained in all cases.
BMS3h5 dAb epitope residues:
The minimal CD40 epitope for BMS3h5 is defined as CD40 residues
containing at least one atom in van der Waals or hydrogen-bond contact with a BMS3h-
56-5 atom. The minimal epitope in all the complexes contains the following CD40
residues with reference to SEQ ID NO: 1: Trp109, Leu121, His122, Ser124, Ser156,
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Ala157, Phe158, Glu159, and His162. The following additional residues are in van der
Waals or hydrogen-bond contact in some complexes: Pro85, Asn86, Leu87, Gly88,
Glu106, Glu107, Gly108, His110, Thr112, Cys119, Val120, Gln133, Ile134, Ala135,
Thr136, Ser155, Lys160.
A maximal CD40 epitope is defined as residues containing atoms that are buried
by a 1.7 Å probe sphere. These residues include all the residues above, plus Val 154 in
all complexes. In some complexes, additional buried residues are: Ser118, Arg123,
Thr141, Phe151, Asp153, Cys161, and Pro163.
A depiction of the surface of BMS3h5 with contacting residues is shown in
Contacting BMS3h5 residues are shown. Buried residues are.also shown.
CD40 is represented as a cartoon with orange representing non-repetitive secondary
structure and magenta representing the epitope residues. Also shown as sticks (carbon
atoms in cyan) are CD40 residues Trp109, Ala115, Leu121, Ser126, and His162, which
are five of the seven residues that differ between human and cynomolgus monkey
(Macaca fascicularis). Ala115 and Ser126 are on the opposite side of CD40 from the
BMS3h5 binding site. Trp109 and Leu121 bind in a cleft of BMS-h5 that lies
between CDR-3 and FR-2 (BMS-3h5 residues Leu45 and Arg47). His162 of CD40
interacts with Arg56 of CDR-2 of the BMS3h5 dAb. Mutation of Trp109
considerably reduces or ablates BMS3h5 activity.
Depending on the crystallographically independent complex, 660-740 Å of CD40
surface area is buried with between 16-21 contacting residues represented at a finer level
with contacting 46-67 atoms. For BMS3h5, 660-780 Å of surface area is buried
with contacting 14-17 residues represented at a finer level with contacting 48-62 atoms.
These contacts yield 3-7 hydrogen bonds and 111-142 van der Waals interactions,
depending on the crystallographically independent complex.
Example 11
Identifying dAb Binding Epitopes on CD40
To identify dAb binding epitopes on CD40, dAb binding was tested against seven
CD40-Fc fusion proteins containing specific amino acid residue substitutions at residues
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76, 109, or 121. These CD40-Fc fusion proteins include wild type human CD40 (wt-
hCD40), wild type cynomolgus monkey CD40 (wt-cCD40), and five mutant human
CD40 proteins (M1-M5) with specific amino acid residues mutated to the corresponding
residue from the sequence of cynomolgus monkey CD40 (M1, M2, M4, M5) or
chimpanzee CD40 (M3). The amino acid substitutions are listed in Table 26.
The sequence of the wild type human CD40 extracellular domain (1-193) is from
REFSEQ:accession NM_001250.3. Cynomolgous and mutant constructs were generated
using site-directed mutagenesis of the wild type sequence at the positions shown in Table
26. The extracellular domains were fused with a thrombin-cleavable linker
DPGGGGGRLVPRGFGTGDP (SEQ ID NO: 1273), which was fused with human IgG1
Fc. The proteins were expressed in HEK6E cells transfected with TIG-pYD7-
GATE Durocher expression vectors. The supernatants were harvested after five days.
Each CD40 protein was purified from conditioned media using protein A fast flow
chromatography. The column was washed with PBS (20 mM sodium phosphate, 0.15 M
NaCl, pH 7.2) and then eluted using 80 mM sodium acetate, pH 3, into 1/5 volume of 1
M Tris-HCl, pH 8. The eluate was run on a Superdex-200 column in PBS.
TABLE 26
Name Short name Residue 76 Residue 109 Residue 121
wild type human CD40 Fc fusion wt-hCD40 H W L
human CD40 (H76R) Fc fusion hCD40-M1 R W L
human CD40 (W109L) Fc fusion hCD40-M2 H L L
human CD40 (W109R) Fc fusion hCD40-M3 H R L
(Chimpanzee CD40)
human CD40 (W109L, L121P) Fc hCD40-M4 H L P
fusion
human CD40 (H76R, W109L, hCD40-M5 R L P
L121P) Fc fusion
wild type cynomolgus monkey wt-cyno- R L P
CD40 Fc fusion CD40
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Representative dAb’s from the 3h217, 3h37, 3h38, and 3h56 lineages were
assayed for their binding to CD40-Fc fusion proteins listed in Table 26. Assays were
performed on a BioRad ProteOn XPR36 SPR instrument. The SPR surfaces were
prepared by immobilizing 8 µg/ml anti-human IgG(Fc) antibody (Biacore/GE
Healthcare) in 10 mM sodium acetate pH 4.5 on a BioRad GLC sensor chip using
standard ethyl(dimethylaminopropyl) carbodiimide (EDC) / N-hydroxysuccinimide
(NHS) chemistry, with ethanolamine blocking. The running buffer for immobilization
and kinetic binding analysis was 10 mM sodium phosphate, 130 mM sodium chloride,
0.05% tween 20, pH 7.1. CD40-Fc fusion proteins at concentrations of 20 µg/ml were
captured in the vertical orientation on these surfaces via the Fc tail, and reference
surfaces lacking CD40-Fc proteins were used for reference subtraction. Kinetic
experiments were performed by flowing 405, 135, 45, 15, and 5nM dAb analytes in the
horizontal orientation over the captured CD40-Fc surfaces at 25°C, using a 240 s
association time, and a 420 s dissociation time, at a flow rate of 30 µl/min. The surfaces
were regenerated in both horizontal and vertical orientations with 30 s pulses of 3 M
MgCl followed by running buffer at 60 µl/min. Sensogram data was double-referenced
and then fitted to a 1:1 Langmuir model using BioRad ProteOn Manager V.2.1.0.38
software, to determine the association rate constant (ka), the dissociation rate constant
(kd), and the equilibrium dissociation constant (K ).
All dAbs of the 3h-37, 3h-38, and 3h-56 lineages were found to bind with high
affinity (K <10 M) to CD40-Fc fusion proteins containing the human CD40 residues
W109 and L121, but binding was significantly reduced or undetectable to CD40-Fc
fusion proteins with the corresponding residues from cynomolgus monkey CD40 (L109,
P121) or chimpanzee CD40 (R109). This indicates that dAbs from each of the 3h37,
3h38--, and 3h56- lineages bind specifically to an epitope that includes residues 109 and
121 of human CD40. In contrast, all tested members of the 3h-217 lineage bound with
similar affinity to all CD40-Fc fusion proteins tested, indicating that the members of the
3h-217 lineage bind to a site on CD40 which does not include residues 76, 109, or 121.
Therefore, the 3h-217 lineage binds to a different epitope than the 3h-37, 3h-38, and 3h-
56 lineages. Table 27 summarizes K values determined for dAb binding to CD40-Fc
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fusion proteins using SPR on a ProteOn XPR36 instrument. An “X” in Table 27 means
that no evidence for binding was found under these conditions.
TABLE 27
wt- hCD40- hCD40- hCD40- hCD40- hCD40- cyno
hCD40 M1 M2 M3 M4 M5 CD40
(H76R) (W109L) (W109R) (W109L, (H76R,
L121P) W109L,
L121P)
3h5 0.47, 0.48 0.94 0.99 0.72 0.93 1.0 0.9
3h16 0.22, 0.26 0.35 0.41 0.27 0.35 0.5 0.4
0.78, 1.5 1.6 2.0 1.2 1.6 2.2 1.9
3h23
3h2 2.0, 2.0 2.6 >1000 X X X X
3h11 1.9, 2.3 2.4 >1000 X X X X
3h2 5.1, 8.0 7.2 X X X X X
3h211 3.3, 6.1 4.0 >1000 X X X X
3h215 2.1, 6.0 3.0 >1000 X X X X
3h217 2.3, 2.4 3.4 >1000 X X X X
3h1 3.0, 5.4 4.2 29 >1000 X X X
3h2 3.8, 3.2 6.1 44 >1000 X X X
3h5 5.3, 4.7 7.2 65 >1000 X X X
3h202 2.3, 1.3 3.3 160 X X X X
0.60, 1.4 1.0 55 X X X X
3h206
3h217 1.0, 1.9 1.4 2.5 23 X X X
Table 28 shows the association rate constant (ka), dissociation rate constant (kd),
and equilibrium dissociation constant (K ) determined for dAb binding to CD40-Fc
fusion proteins using SPR on a ProteOn XPR36 instrument. An “X” in Table 28 means
that no evidence for binding was found under these conditions.
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TABLE 28
Ligand dAb ka kd (1/s) Kd
(1/Ms) (nM)
6 -3
wt-hCD40 3h5 2.71x10 1.27x10 0.47
6 -4
wt-hCD40 (repeat) 3h5 2.03x10 9.81x10 0.48
6 -3
hCD40 M1 (H76R) 3h5 3.17x10 2.99x10 0.94
6 -3
hCD40 M2 (W109L) 3h5 2.55x10 2.51x10 0.99
6 -3
hCD40 M3 (W109R) 3h5 2.73x10 1.96x10 0.72
6 -3
hCD40 M4 (W109L, L121P) 3h5 2.78x10 2.59x10 0.93
6 -3
hCD40-M5 (H76R, W109L, L121P) 3h5 2.44x10 2.42x10 0.99
6 -3
wt-cCD40 3h5 2.46x10 2.12x10 0.86
6 -4
wt-hCD40 3h16 4.47x10 9.91x10 0.22
6 -4
wt-hCD40 (repeat) 3h16 3.30x10 8.47x10 0.26
6 -3
hCD40 M1 (H76R) 3h16 4.83x10 1.68x10 0.35
6 -3
hCD40 M2 (W109L) 3h16 4.06x10 1.67x10 0.41
6 -3
hCD40 M3 (W109R) 3h16 3.78x10 1.04x10 0.27
6 -3
hCD40 M4 (W109L, L121P) 3h16 4.39x10 1.52x10 0.35
6 -3
hCD40-M5 (H76R, W109L, L121P) 3h16 3.65x10 1.70x10 0.47
6 -3
wt-cCD40 3h16 3.44x10 1.47x10 0.43
6 -3
wt-hCD40 3h23 1.64x10 1.27x10 0.78
6 -3
wt-hCD40 (repeat) 3h23 1.07x10 1.63x10 1.52
6 -3
hCD40 M1 (H76R) 3h23 1.64x10 2.62x10 1.59
6 -3
hCD40 M2 (W109L) 3h23 1.49x10 2.91x10 1.95
6 -3
hCD40 M3 (W109R) 3h23 1.53x10 1.86x10 1.22
6 -3
hCD40 M4 (W109L, L121P) 3h23 1.67x10 2.68x10 1.61
6 -3
hCD40-M5 (H76R, W109L, L121P) 3h23 1.30x10 2.87x10 2.21
6 -3
wt-cCD40 3h23 1.24x10 2.35x10 1.90
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-4
wt-hCD40 3h2 2.12x10 4.17x10 1.96
-4
wt-hCD40 (repeat) 3h2 2.13x10 4.26x10 2.00
-4
hCD40 M1 (H76R) 3h2 2.17x10 5.62x10 2.58
hCD40 M2 (W109L) 3h2 >1000
hCD40 M3 (W109R) 3h2 X
hCD40 M4 (W109L, L121P) 3h2 X
hCD40-M5 (H76R, W109L, L121P) 3h2 X
wt-cCD40 3h2 X
-4
wt-hCD40 3h11 2.91x10 5.60x10 1.92
-4
wt-hCD40 (repeat) 3h11 2.81x10 6.40x10 2.28
-4
hCD40 M1 (H76R) 3h11 3.00x10 7.17x10 2.39
hCD40 M2 (W109L) 3h11 >1000
hCD40 M3 (W109R) 3h11 X
hCD40 M4 (W109L, L121P) 3h11 X
hCD40-M5 (H76R, W109L, L121P) 3h11 X
wt-cCD40 3h11 X
-4
wt-hCD40 3h2 1.20x10 6.08x10 5.07
-3
wt-hCD40 (repeat) 3h2 1.42x10 1.14x10 8.04
-3
hCD40 M1 (H76R) 3h2 1.40x10 1.00x10 7.15
hCD40 M2 (W109L) 3h2 X
hCD40 M3 (W109R) 3h2 X
hCD40 M4 (W109L, L121P) 3h2 X
hCD40-M5 (H76R, W109L, L121P) 3h2 X
wt-cCD40 3h2 X
-4
wt-hCD40 3h211 1.11x10 3.62x10 3.26
-4
wt-hCD40 (repeat) 3h211 1.20x10 7.28x10 6.08
-4
hCD40 M1 (H76R) 3h211 1.28x10 5.10x10 3.98
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hCD40 M2 (W109L) 3h211 >1000
hCD40 M3 (W109R) 3h211 X
hCD40 M4 (W109L, L121P) 3h211 X
hCD40-M5 (H76R, W109L, L121P) 3h211 X
wt-cCD40 3h211 X
-4
wt-hCD40 3h215 1.37x10 2.88x10 2.10
-4
wt-hCD40 (repeat) 3h215 1.36x10 8.20x10 6.02
-4
hCD40 M1 (H76R) 3h215 1.75x10 5.30x10 3.03
hCD40 M2 (W109L) 3h215 >1000
hCD40 M3 (W109R) 3h215 X
hCD40 M4 (W109L, L121P) 3h215 X
hCD40-M5 (H76R, W109L, L121P) 3h215 X
wt-cCD40 3h215 X
-4
wt-hCD40 3h217 1.27x10 2.96x10 2.34
-4
wt-hCD40 (repeat) 3h217 1.44x10 3.40x10 2.37
-4
hCD40 M1 (H76R) 3h217 1.41x10 4.81x10 3.41
hCD40 M2 (W109L) 3h217 >1000
hCD40 M3 (W109R) 3h217 X
hCD40 M4 (W109L, L121P) 3h217 X
hCD40-M5 (H76R, W109L, L121P) 3h217 X
wt-cCD40 3h217 X
-4
wt-hCD40 3h1 2.52x10 7.50x10 2.97
-3
wt-hCD40 (repeat) 3h1 1.93x10 1.03x10 5.35
-4
hCD40 M1 (H76R) 3h1 2.31x10 9.67x10 4.18
-3
hCD40 M2 (W109L) 3h1 1.92x10 5.57x10 29.10
hCD40 M3 (W109R) 3h1 >1000
hCD40 M4 (W109L, L121P) 3h1 X
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hCD40-M5 (H76R, W109L, L121P) 3h1 X
wt-cCD40 3h1 X
-4
wt-hCD40 3h2 2.46x10 9.27x10 3.77
-4
wt-hCD40 (repeat) 3h2 1.97x10 6.24x10 3.17
-3
hCD40 M1 (H76R) 3h2 2.20x10 1.33x10 6.05
-3
hCD40 M2 (W109L) 3h2 1.89x10 8.30x10 43.90
hCD40 M3 (W109R) 3h2 >1000
hCD40 M4 (W109L, L121P) 3h2 X
hCD40-M5 (H76R, W109L, L121P) 3h2 X
wt-cCD40 3h2 X
-4
wt-hCD40 3h5 1.78x10 9.38x10 5.26
-4
wt-hCD40 (repeat) 3h5 1.53x10 7.19x10 4.69
-3
hCD40 M1 (H76R) 3h5 1.69x10 1.21x10 7.18
-3
hCD40 M2 (W109L) 3h5 1.38x10 8.89x10 64.60
hCD40 M3 (W109R) 3h5 >1000
hCD40 M4 (W109L, L121P) 3h5 X
hCD40-M5 (H76R, W109L, L121P) 3h5 X
wt-cCD40 3h5 X
wt-hCD40 3h202 1.82E+05 4.15x10 2.27
wt-hCD40 (repeat) 3h202 1.77E+05 2.21x10 1.25
hCD40 M1 (H76R) 3h202 1.76E+05 5.79x10 3.29
hCD40 M2 (W109L) 3h202 1.35E+05 2.00x10 155.00
hCD40 M3 (W109R) 3h202 X
hCD40 M4 (W109L, L121P) 3h202 X
hCD40-M5 (H76R, W109L, L121P) 3h202 X
wt-cCD40 3h202 X
wt-hCD40 3h206 6.48E+05 3.89x10 0.60
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wt-hCD40 (repeat) 3h206 3.27E+05 4.72x10 1.44
hCD40 M1 (H76R) 3h206 5.65E+05 5.45x10 0.96
hCD40 M2 (W109L) 3h206 3.38E+05 2.00x10 54.70
hCD40 M3 (W109R) 3h206 X
hCD40 M4 (W109L, L121P) 3h206 X
hCD40-M5 (H76R, W109L, L121P) 3h206 X
wt-cCD40 3h206 X
wt-hCD40 3h217 4.71E+05 4.70x10 1.00
wt-hCD40 (repeat) 3h217 2.91E+05 5.46x10 1.87
hCD40 M1 (H76R) 3h217 4.45E+05 6.35x10 1.43
hCD40 M2 (W109L) 3h217 4.25E+05 1.05x10 2.48
hCD40 M3 (W109R) 3h217 2.91E+05 6.70x10 23.00
hCD40 M4 (W109L, L121P) 3h217 X
hCD40-M5 (H76R, W109L, L121P) 3h217 X
wt-cCD40 3h217 X
Example 12
Construction of Fc Fusion Polypeptides
Antibody polypeptides comprising dAbs can be constructed in various
configurations, as disclosed herein. In this example, various dAbs were fused with a Fc
domain to generate Fc fusion polypeptides of anti-human CD40 variable domain
constructs such as 3h37-202, 3h37-235, 3h37-258, and 3h37-202.
In one representative example, the dAb BMS3h269 (SEQ ID NO: 417) was
fused with a modified IgG1 (IgG1*) Fc domain (SEQ ID NO: 1284). In the dAb-IgG1*
Fc domain fusion polypeptide, the C-terminus of dAb BMS3h269 was fused to a
linker tripeptide having the sequence Ala-Ser-Thr, which in turn was fused with the
IgG1* Fc domain (SEQ ID NO: 1284). The IgG1* Fc domain contained the modification
C5S, referring to the numbering of positions in SEQ ID NO: 1284. C5 of the IgG1 Fc
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domain normally forms a disulfide bond with a Cys residue in the light chain of an IgG
molecule. The IgG1* Fc domain also contained C11S and C14S mutations to eliminate
interchain disulfide bonds in the IgG1 hinge region. Finally, the IgG1* Fc domain
contained a P23S mutation to lower Fc domain effector function. The dAb-IgG1* Fc
fusion polypeptide has the following sequence, where the Ala-Ser-Thr linker is in bold
font and the modifications to the Fc domain are in bold italics:
1 EVQLLESGGG LVQPGGSLRL SCAASGFTFR DYEMWWVRQA PGKGLERVSA
51 INPQGTRTYY ADSVKGRFTI SRDNSKNTLY LQMNSLRAED TAVYYCAKLP
101 FRFSDRGQGT LVTVSSASTE PKSSDKTHTS PPSPAPELLG GSSVFLFPPK
151 PKDTLMISRT PEVTCVVVDV SHEDPEVKFN WYVDGVEVHN AKTKPREEQY
201 NSTYRVVSVL TVLHQDWLNG KEYKCKVSNK ALPAPIEKTI SKAKGQPREP
251 QVYTLPPSRD ELTKNQVSLT CLVKGFYPSD IAVEWESNGQ PENNYKTTPP
301 VLDSDGSFFL YSKLTVDKSR WQQGNVFSCS VMHEALHNHY TQKSLSLSPG
351 K (SEQ ID NO: 1286)
The dAb-IgG1* Fc fusion polypeptide depicted in SEQ ID NO: 1286 is a monomer
having a calculated molecular weight of 39,127 Da. It can form a dimer having a
calculated molecular weight of 78,254 Da.
dAb BMS3h269 (SEQ ID NO: 417) alternatively was fused with a human
IgG Fc domain (SEQ ID NO: 1285). The C-terminus of dAb BMS3h269 was again
fused to the Ala-Ser-Thr linker, which was fused with the IgG Fc domain (SEQ ID NO:
1285). The IgG Fc domain contained the modification S10P, referring to the numbering
of positions in SEQ ID NO: 1285. The BMS3h269-IgG Fc fusion polypeptide has
the following sequence, where the Ala-Ser-Thr linker is in bold font and the S10P
modification is in bold italics:
1 EVQLLESGGG LVQPGGSLRL SCAASGFTFR DYEMWWVRQA PGKGLERVSA
51 INPQGTRTYY ADSVKGRFTI SRDNSKNTLY LQMNSLRAED TAVYYCAKLP
101 FRFSDRGQGT LVTVSSASTE SKYGPPCPPC PAPEFLGGPS VFLFPPKPKD
151 TLMISRTPEV TCVVVDVSQE DPEVQFNWYV DGVEVHNAKT KPREEQFNST
201 YRVVSVLTVL HQDWLNGKEY KCKVSNKGLP SSIEKTISKA KGQPREPQVY
251 TLPPSQEEMT KNQVSLTCLV KGFYPSDIAV EWESNGQPEN NYKTTPPVLD
301 SDGSFFLYSR LTVDKSRWQE GNVFSCSVMH EALHNHYTQK SLSLSLGK
(SEQ ID NO: 1287)
The BMS3h269-IgG Fc fusion polypeptide depicted in SEQ ID NO: 1287 is a
monomer having a calculated molecular weight of 38,867 Da. It can form a dimer having
a calculated molecular weight of 77,734 Da.
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
The sequences of BMS3h269 (SEQ ID NO: 417), BMS3h269-IgG1* Fc
fusion polypeptide (SEQ ID NO: 1286), and BMS3h269-IgG Fc fusion polypeptide
(SEQ ID NO: 1287) are aligned below, where the start of the Fc domain is marked by an
arrow:
BMS3h56-269 (SEQ ID NO:417) (1)
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSA
BMS3h56CTL2 (SEQ ID NO:1286) (1)
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSA
BMS3h56Ig4 (SEQ ID NO:1287) (1)
EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYEMWWVRQAPGKGLERVSA
BMS3h56-269 (SEQ ID NO:417) (34)
INPQGTRTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKLP
BMS3h56CTL2 (SEQ ID NO:1286) (51)
INPQGTRTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKLP
BMS3h56Ig4 (SEQ ID NO:1287) (51)
INPQGTRTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKLP
BMS3h56-269 (SEQ ID NO:417) (84)
FRFSDRGQGTLVTVSS----------------------------------
BMS3h56CTL2 (SEQ ID NO:1286) (101)
FRFSDRGQGTLVTVSSASTEPKSSDKTHTSPPSPAPELLGGSSVFLFPPK
BMS3h56Ig4 (SEQ ID NO:1287) (101)
FRFSDRGQGTLVTVSSASTESKYG---PPCPPCPAPEFLGGPSVFLFPPK
Start of Fc
BMS3h56-269 (SEQ ID NO:417) (117)
--------------------------------------------------
BMS3h56CTL2 (SEQ ID NO:1286) (151)
PKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY
BMS3h56Ig4 (SEQ ID NO:1287) (148)
PKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQF
BMS3h56-269 (SEQ ID NO:417) (117)
--------------------------------------------------
BMS3h56CTL2 (SEQ ID NO:1286) (201)
NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP
40 BMS3h56Ig4 (SEQ ID NO:1287) (198)
NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREP
BMS3h56-269 (SEQ ID NO:417) (117) --------------------
------------------------------
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
BMS3h56CTL2 (SEQ ID NO:1286) (251)
QVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP
BMS3h56Ig4 (SEQ ID NO:1287) (248)
QVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP
BMS3h56-269 (SEQ ID NO:417) (117)
--------------------------------------------------
BMS3h56CTL2 (SEQ ID NO:1286) (301)
VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
BMS3h56Ig4 (SEQ ID NO:1287) (298)
VLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG
BMS3h56-269 (SEQ ID NO:417) (117) -
BMS3h56CTL2 (SEQ ID NO:1286) (351) K
BMS3h56Ig4 (SEQ ID NO:1287) (348) K
The Fc fusion polypeptides were expressed using the cell culture methods
disclosed in Example 11. The column was washed with PBS (20 mM sodium phosphate,
0.15 M NaCl, pH 7.2) and then eluted using 80 mM sodium acetate, pH 3, into 1/5
volume of 1 M Tris-HCl, pH 8. The eluate was run on a Superdex-200 column in PBS.
Example 13
CD40 Fc Fusion Polypeptide Acitivity Assays
Anti-human CD40 Fc Fusion Polypeptides were assayed functionally for their
ability to antagonize CD40 activities. The CD40 activities tested were B cell
proliferation and cytokine production by hCD40L-driven activation of primary human
monocyte-derived dendritic cells (DCs). B cell proliferation and cytokine production
were measured using the assays disclosed in Example 6. Unless otherwise noted, all
assays were performed in RPMI media supplemented with 10% fetal calf serum (FCS).
The dAb-Fc domain fusion polypeptides exhibited potent inhibition (i.e., antagonism) of
CD40-dependent activation. There were no agonistic properties noted among any of the
humanCD40-specific dAb-Fc domain fusion polypeptides. The results using the various
assays are shown in TABLE 29. 3h56IgG4 was assayed for its binding to
immobilized human-CD40 using the assays disclosed in Example 11. For 3h56
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
IgG4, the apparent avidity influenced Kd value for binding immobilized human-CD40 is
measured at 30 pM at 25C and 40 pM at 37C.
TABLE 29
CHO-
hCD40L- CHO- CHO-
hIZCD40L- CHO-
driven hCD40L- hCD40L-
driven T-B cell hCD40L-
Human B driven DC driven DC
Human B MLR driven DC
Cell Activation Activation
dAb-Fc
Cell EC50 Activation
Proliferati TNF IL-6
Proliferation (nM) IL-12
on EC50 EC50
EC50 (nM) EC50 (nM)
EC50 (nM) (nM)
(nM)
3h37-
202-
IgG4 0.16 ± 0.08 5.0, 3.0 5.0, 6.0 0.53 ± 0.1
3h37-
202-
IgG1* 0.27, 0.22 3.0, 7.0 0.74 ± 0.2
3h38-
235-
IgG4 0.20, 0.15 6.0, 10.0 16.7 ± 5.7 0.67 ± 0.3
3h38-
235-
IgG1* 0.25 ± 0.1 4.0 ± 1.0 0.88 ± 0.3
3h56-
258- 0.22 ± 0.11 ±
IgG4 0.16 ± 0.05 1.0 ± 0.8 2.4 ± 0.99 0.08 0.05 0.3 ± 0.2
3h56-
258-
IgG1* 0.063 ± 0.03 0.6 ± 0.4 2.0 ± 0.63 0.31 ± 0.1
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
3h56-
269- 0.27 ± 0.52 ± 0.16 ± 0.09 ±
IgG4 0.028 ± 0.01 0.08 0.07 0.03 0.02 0.092 ± 0.03
3h56-
269- 0.25 ± 0.27 ± 0.15 ±
IgG1* 0.025 ± 0.01 0.04 0.53 ± 0.1 0.06 0.05 0.14 ± 0.06
Although the present embodiments have been described in detail with reference to
examples above, it is understood that various modifications can be made without
departing from the spirit of these embodiments, and would be readily known to the
skilled artisan.
DC01/ 2911446.1
PATENT
Attorney Docket No. 20089600-W0
Claims (28)
1. An antibody polypeptide comprising a first variable domain, wherein said antibody polypeptide specifically binds an epitope of human CD40, wherein the antibody polypeptide competes with the binding of domain antibody (dAb) BMS3h269 (SEQ ID NO: 417) to CD40, wherein CD40 comprises the amino acid sequence of SEQ ID NO: 1, and wherein the epitope comprises at least one CD40 amino acid residue selected from the group consisting of Trp109, Leu121, His122, Ser124, Ser156, Ala157, Phe158, Glu159, and His162, wherein said antibody polypeptide is a domain antibody, and wherein the binding of the antibody polypeptide to CD40 antagonizes CD40 activity.
2. The antibody polypeptide of claim 1, wherein the first variable domain comprises the amino acid sequence of one of the antibody polypeptides of the lineage group of BMS3h-56 selected from the group consisting of SEQ ID NO: 317; SEQ ID NO: 318; SEQ ID NO: 319; SEQ ID NO: 320; SEQ ID NO: 321; SEQ ID NO: 322; SEQ ID NO: 323; SEQ ID NO: 324; SEQ ID NO: 325; SEQ ID NO: 326; SEQ ID NO: 327; SEQ ID NO: 328; SEQ ID NO: 329; SEQ ID NO: 330; SEQ ID NO: 331; SEQ ID NO: 332; SEQ ID NO: 333; SEQ ID NO: 334; SEQ ID NO: 335; SEQ ID NO: 336; SEQ ID NO: 337; SEQ ID NO: 338; SEQ ID NO: 339; SEQ ID NO: 340; SEQ ID NO: 341; SEQ ID NO: 342; SEQ ID NO: 343; SEQ ID NO: 344; SEQ ID NO: 345; SEQ ID NO: 346; SEQ ID NO: 347; SEQ ID NO: 348; SEQ ID NO: 349; SEQ ID NO: 9; SEQ ID NO: 350; SEQ ID NO: 351; SEQ ID NO: 352; SEQ ID NO: 353; SEQ ID NO: 354; SEQ ID NO: 355; SEQ ID NO: 356; SEQ ID NO: 357; SEQ ID NO: 358; SEQ ID NO: 359; SEQ ID NO: 360; SEQ ID NO: 361; SEQ ID NO: 362; SEQ ID NO: 363; SEQ ID NO: 364; SEQ ID NO: 365; SEQ ID NO: 366; SEQ ID NO: 367; SEQ ID NO: 368; SEQ ID NO: 369; SEQ ID NO: 370; SEQ ID NO: 371; SEQ ID NO: 372; SEQ ID NO: 373; SEQ ID NO: 374; SEQ ID NO: 375; SEQ ID NO: 376; SEQ ID NO: 377; SEQ ID NO: 378; SEQ ID NO: 379; SEQ ID NO: 380; SEQ ID NO: 381; SEQ ID NO: 382; SEQ ID NO: 383; SEQ ID NO: 384; SEQ ID NO: 385; SEQ ID NO: 386; SEQ ID NO: 387; SEQ ID NO: 388; SEQ ID NO: 389; SEQ ID NO: 390; SEQ ID NO: 391; SEQ ID NO: 392; SEQ ID NO: DC01/ 2911446.1 PATENT Attorney Docket No. 20089600-W0 393; SEQ ID NO: 394; SEQ ID NO: 395; SEQ ID NO: 396; SEQ ID NO: 397; SEQ ID NO: 398; SEQ ID NO: 399; SEQ ID NO: 400; SEQ ID NO: 401; SEQ ID NO: 402; SEQ ID NO: 403; SEQ ID NO: 404; SEQ ID NO: 405; SEQ ID NO: 406; SEQ ID NO: 407; SEQ ID NO: 408; SEQ ID NO: 409; SEQ ID NO: 410; SEQ ID NO: 411; SEQ ID NO: 412; SEQ ID NO: 413; SEQ ID NO: 414; SEQ ID NO: 415; SEQ ID NO: 416; SEQ IS NO: 417; SEQ ID NO: 418; SEQ ID NO: 419; SEQ ID NO: 420; SEQ ID NO: 421; SEQ ID NO: 422; SEQ ID NO: 423; SEQ ID NO: 424; SEQ ID NO: 425; SEQ ID NO: 426; SEQ ID NO: 427; SEQ ID NO: 428; SEQ ID NO: 429; SEQ ID NO: 430; SEQ ID NO: 431; SEQ ID NO: 432; SEQ ID NO: 433; SEQ ID NO: 434; SEQ ID NO: 435; and SEQ ID NO: 436.
3. The antibody polypeptide of claim 1, wherein the first variable domain comprises: (a) a CDR1 region comprising the CDR1 region of BMS3h269 (amino acids 31 to 35 of SEQ ID NO: 417) or differs from the CDR1 region of BMS3h269 by up to two amino acids, (b) a CDR2 region comprising the CDR2 region of BMS3h269 (amino acids 50 to 66 of SEQ ID NO: 417) or differs from the CDR2 region of BMS3h269 by up to two amino acids, (c) a CDR3 region comprising the CDR3 region of BMS3h269 (amino acids 99 to 105 of SEQ ID NO: 417) or differs from the CDR3 region of BMS3h269 by up to two amino acids.
4. The antibody polypeptide of claim 3, wherein the first variable domain further comprises: (a) a FR1 region comprising the FR1 region of BMS3h269 (amino acids 1 to 30 of SEQ ID NO: 417) or differs from FR1 region of BMS3h269 by up to two amino acids, (b) a FR2 region comprising the FR2 region of BMS3h269 (amino acids 36 to 49 of SEQ ID NO: 417) or differs from the FR2 region of BMS3h269 by up to two amino acids, DC01/ 2911446.1 PATENT Attorney Docket No. 20089600-W0 (c) a FR3 region comprising the FR3 region of BMS3h269 (amino acids 67 to 98 of SEQ ID NO: 417) or differs from the FR3 region of BMS3h269 by up to two amino acids, and (d) a FR4 region comprising the FR4 region of BMS3h269 (amino acids 106 to 116 of SEQ ID NO: 417) or differs from the FR4 region of BMS3h269 by up to two amino acids.
5. The antibody polypeptide of claim 3, wherein the first variable domain comprises: (a) a CDR1 region comprising the CDR1 region of BMS3h269 (SEQ ID NO: 417), (b) a CDR2 region comprising the CDR2 region of BMS3h269 (SEQ ID NO: 417), and (c) a CDR3 region comprising the CDR3 region of BMS3h269 (SEQ ID NO: 417).
6. The antibody polypeptide of claim 4, wherein the first variable domain comprises: (a) a FR1 region comprising the FR1 region of BMS3h269 (SEQ ID NO: 417), (b) a FR2 region comprising the FR2 region of BMS3h269 (SEQ ID NO: 417), (c) a FR3 region comprising the FR3 region of BMS3h269 (SEQ ID NO: 417), and (d) a FR4 region comprising the FR4 region of BMS3h269 (SEQ ID NO: 417).
7. An antibody polypeptide comprising a first variable domain, wherein said antibody polypeptide specifically binds human CD40, wherein CD40 comprises the amino acid sequence of SEQ ID No: 1, wherein the first variable domain comprises the amino acid sequence of BMS3h258 (SEQ ID NO: 10) or BMS3h269 (SEQ ID DC01/ 2911446.1 PATENT Attorney Docket No. 20089600-W0 NO: 417), or differs from the amino acid sequence of BMS3h258 (SEQ ID NO: 10) or BMS3h269 (SEQ ID NO: 417) by up to 10 amino acids.
8. The antibody polypeptide of claim 7, wherein the first variable domain comprises the amino acid sequence of BMS3h258 (SEQ ID NO: 10).
9. The antibody polypeptide of claim 7, wherein the first variable domain comprises the amino acid sequence of BMS3h269 (SEQ ID NO: 417).
10. The antibody polypeptide of claim 1, wherein the first variable domain comprises: (a) a CDR1 region having a sequence X -Tyr-Glu-Y -Trp (SEQ ID NO: 1274), wherein X is Asp or Gly, and Y is Met or Leu; (b) a CDR2 region having a sequence Ala-Ile-Asn-Pro-X -Gly-Y -Z -Thr-Tyr- 2 2 2 Tyr-Ala-Asp-Ser-Val-A -Gly (SEQ ID NO: 1275), wherein X is Gln, Tyr, Pro, Trp, or Ala, Y is Thr, Ser, Asn, Gly, Met, or Gln, Z is Arg, Leu, Tyr, His, or Phe, and A is Lys or Met; and (c) a CDR3 region having a sequence X -Pro-Y -Z -Phe-A -B (SEQ ID NO: 3 3 3 3 3 1276), wherein X is Leu or Pro, Y is Phe, Gln, Thr, or Met, Z is Tyr, Pro, 3 3 3 Leu, Thr, Ile, Phe, or Met, A is Gln, His, Asp, Ser, Lys, Glu, or Gly, and B is Glu, Asp, or Tyr.
11. The antibody polypeptide of any one of claims 1 to 10, wherein the antibody polypeptide is a fusion polypeptide comprising the first variable domain and an Fc domain.
12. The antibody polypeptide of any one of claims 1 to 11, wherein the antibody polypeptide comprises the amino acid sequence of the BMS3h269-IgG1* Fc fusion polypeptide (SEQ ID NO: 1286). DC01/ 2911446.1 PATENT Attorney Docket No. 20089600-W0
13. The antibody polypeptide of any one of claims 1 to 12, wherein the antibody polypeptide comprises the amino acid sequence of the BMS3h269-IgG4 Fc fusion polypeptide (SEQ ID NO: 1287).
14. The antibody polypeptide of any one of claims 1 to 13, wherein the antibody polypeptide further comprises a second variable domain that specifically binds a second antigen, wherein the second antigen is an antigen other than human CD40.
15. A nucleic acid encoding the antibody polypeptide of any one of claims 1 to
16. An isolated host cell comprising the nucleic acid of claim 15.
17. A pharmaceutical composition comprising a therapeutically-effective amount of the antibody polypeptide of any one of claims 1 to 14 and a pharmaceutically acceptable carrier.
18. A pharmaceutical composition of claim 17, wherein the first variable domain of the antibody polypeptide comprises the amino acid sequence of BMS3h269 (SEQ ID NO: 417).
19. The use of an antibody polypeptide of any one of claims 1 to 14 in the manufacture of a medicament for use in the treatment of an immune disease in a patient in need of such treatment, wherein the immune disease is selected from the group consisting of Addison’s disease, allergies, ankylosing spondylitis, asthma, atherosclerosis, autoimmune diseases of the ear, autoimmune diseases of the eye, autoimmune hepatitis, autoimmune parotitis, ulcerative colitis, coronary heart disease, Crohn’s disease, diabetes, epididymitis, glomerulonephritis, Graves’ disease, Guillain- Barre syndrome, Hashimoto’s disease, hemolytic anemia, idiopathic thrombocytopenic purpura, inflammatory bowel disease, immune response to recombinant drug products, systemic lupus erythematosus, male infertility, multiple sclerosis, myasthenia gravis, DC01/ 2911446.1 PATENT Attorney Docket No. 20089600-W0 pemphigus, psoriasis, rheumatic fever, rheumatoid arthritis, sarcoidosis, scleroderma, Sjogren’s syndrome, spondyloarthropathies, thyroiditis, transplant rejection, vasculitis, AIDS, atopic allergy, bronchial asthma, eczema, leprosy, schizophrenia, inherited depression, transplantation of tissues and organs, chronic fatigue syndrome, Alzheimer’s disease, Parkinson’s disease, myocardial infarction, stroke, autism, epilepsy, Arthus’ phenomenon, anaphylaxis, alcohol addiction, and drug addiction.
20. The use according to claim 19, wherein the immune disease is selected from the group consisting of ulcerative colitis, Crohn’s disease, and inflammatory bowel disease.
21. The use according to claim 19, wherein the immune disease is systemic lupus erythematosus.
22. The use according to any one of claims 19 to 21, wherein the antibody polypeptide is present in the medicament in a therapeutically effective amount.
23. The use according to any one of claims 19 to 22, wherein the first variable domain of the antibody polypeptide comprises the amino acid sequence of BMS3h 269 (SEQ ID NO: 417).
24. An antibody polypeptide as claimed in any one of claims 1 to 14, substantially as herein described with reference to any example thereof.
25. A nucleic acid as claimed in claim 15, substantially as herein described with reference to any example thereof.
26. An isolated host cell as claimed in claim 16, substantially as herein described with reference to any example thereof. DC01/ 2911446.1 PATENT Attorney Docket No. 20089600-W0
27. A pharmaceutical composition as claimed in claim 17, substantially as herein described with reference to any example thereof.
28. A use as claimed in any one of claims 19 to 22, substantially as herein described with reference to any example thereof. DC01/ 2911446.1 5812071_1.txt
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161477904P | 2011-04-21 | 2011-04-21 | |
| US61/477,904 | 2011-04-21 | ||
| PCT/US2012/034519 WO2012145673A1 (en) | 2011-04-21 | 2012-04-20 | Antibody polypeptides that antagonize cd40 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NZ618025A NZ618025A (en) | 2015-10-30 |
| NZ618025B2 true NZ618025B2 (en) | 2016-02-02 |
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