Deprecated: The each() function is deprecated. This message will be suppressed on further calls in /home/zhenxiangba/zhenxiangba.com/public_html/phproxy-improved-master/index.php on line 456
NZ730014B2 - Compound targeting il-23a and tnf-alpha and uses thereof - Google Patents
[go: Go Back, main page]

NZ730014B2 - Compound targeting il-23a and tnf-alpha and uses thereof - Google Patents

Compound targeting il-23a and tnf-alpha and uses thereof Download PDF

Info

Publication number
NZ730014B2
NZ730014B2 NZ730014A NZ73001415A NZ730014B2 NZ 730014 B2 NZ730014 B2 NZ 730014B2 NZ 730014 A NZ730014 A NZ 730014A NZ 73001415 A NZ73001415 A NZ 73001415A NZ 730014 B2 NZ730014 B2 NZ 730014B2
Authority
NZ
New Zealand
Prior art keywords
target protein
seq
polypeptide
linker
comprises seq
Prior art date
Application number
NZ730014A
Other versions
NZ730014A (en
Inventor
Rachel Rebecca Barrett
Scott Brodeur
Patricia Giblin
Leslie S Johnson
Barney Kathleen Last
Nelamangala Nagaraja
Daw Tsun Shih
Sanjaya Singh
Original Assignee
Boehringer Ingelheim International Gmbh
Macrogenics Inc
Filing date
Publication date
Application filed by Boehringer Ingelheim International Gmbh, Macrogenics Inc filed Critical Boehringer Ingelheim International Gmbh
Priority to NZ766849A priority Critical patent/NZ766849B2/en
Priority claimed from PCT/US2015/048260 external-priority patent/WO2016036918A1/en
Publication of NZ730014A publication Critical patent/NZ730014A/en
Publication of NZ730014B2 publication Critical patent/NZ730014B2/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/24—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/24—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
    • C07K16/241—Tumor Necrosis Factors
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/24—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
    • C07K16/244—Interleukins [IL]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0634—Cells from the blood or the immune system
    • C12N5/0636—T lymphocytes
    • C12N5/0638—Cytotoxic T lymphocytes [CTL] or lymphokine activated killer cells [LAK]
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P15/00—Preparation of compounds containing at least three condensed carbocyclic rings
    • G01N33/574—

Abstract

The disclosure relates to compounds, in particular, bispecific diabodies specific for IL23A and TNF-alpha, compositions comprising the compounds, and methods of use thereof. Nucleic acids, cells, and methods of production related to the compounds and compositions are also disclosed.

Claims (1)

What is claimed is:
1. A compound comprising a first polypeptide and a second polypeptide, wherein: 5 (A) said first polypeptide comprises in the direction from the N-terminus to the C- terminus: (i) a light chain variable domain of a first immunoglobulin (VL1) specific for a first target protein; (ii) a heavy chain variable domain of a second immunoglobulin (VH2) specific 10 for a second target protein; and (iii) a heavy chain constant region (CH1) from an IgG1 or IgG4; (iv) a hinge region from an IgG1 or IgG4, (v) a heavy chain constant region 2 (CH2) from an IgG1 or IgG4 ; and (vi) a heavy chain constant region 3 (CH3) from an IgG1 or IgG4; and 15 (B) said second polypeptide comprises in the direction from the N-terminus to the C- terminus: (i) a light chain variable domain of the second immunoglobulin (VL2) specific for said second target protein; (ii) a heavy chain variable domain of the first immunoglobulin (VH1) specific for 20 said first target protein; and (iii) a light chain constant region (CL) from an IgG1 or IgG4; wherein: (viii) said VL1 and VH1 associate to form a binding site that binds said first 25 target protein; (ix) said VL2 and VH2 associate to form a binding site that binds said second target protein; (x) said IgG1 or IgG4 heavy chain constant region 2 (CH2) comprises a tyrosine at position 252, a threonine at position 254 and a glutamic acid a position 256, numbered according to the EU index as in Kabat; and (xi) said first target protein is TNF-alpha and said second target protein is IL-23A 5 or said first target protein is IL-23A and said second target protein is TNF- alpha, (xii) said CH1 of the first polypeptide and the CL of said second polypeptide are associated together via a disulfide bond to form a C1 domain; 10 (xiii) said first polypeptide comprises a first linker between said VL1 and said VH2 and said second polypeptide further comprises a second linker between said VL2 and said VH1, wherein said first linker and said second linker do not comprise the amino acid sequence GGGSGGG (SEQ ID NO:9); 15 (xiv) said first polypeptide comprises a third linker between said VH2 and said CH1 and said second polypeptide further comprises a fourth linker between said VH1 and said CL, wherein said third linker and/or said fourth linker comprises the amino acid sequence FNRGES (SEQ ID NO:11) or the amino acid sequence VEPKSS (SEQ ID NO:12) or the 20 amino acid sequence LGGGSG (SEQ ID NO:10); wherein: (i) said VL1 comprises SEQ ID NO:2, said VH1 comprises SEQ ID NO:1, said VL2 comprises SEQ ID NO:8 and said VH2 comprises SEQ ID NO:7; or 25 (ii) said VL1 comprises SEQ ID NO:4 or 6, said VH1 comprises SEQ ID NO:3 or 5, said VL2 comprises SEQ ID NO:8 and said VH2 comprises SEQ ID NO:7; (iii) said VL1 comprises SEQ ID NO:8, said VH1 comprises SEQ ID NO:7, said VL2 comprises SEQ ID NO:2 and said VH2 comprises SEQ ID NO:1; or
NZ730014A 2015-09-03 Compound targeting il-23a and tnf-alpha and uses thereof NZ730014B2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
NZ766849A NZ766849B2 (en) 2015-09-03 Compound targeting il-23a and tnf-alpha and uses thereof

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201462045498P 2014-09-03 2014-09-03
PCT/US2015/048260 WO2016036918A1 (en) 2014-09-03 2015-09-03 Compound targeting il-23a and tnf-alpha and uses thereof

Publications (2)

Publication Number Publication Date
NZ730014A NZ730014A (en) 2024-07-05
NZ730014B2 true NZ730014B2 (en) 2024-10-08

Family

ID=

Similar Documents

Publication Publication Date Title
HRP20210739T1 (en) Antigen binding molecules comprising a tnf family ligand trimer
AR101753A1 (en) COMPOUND OF OBJECTIVE TO IL-23A AND TNF-A AND USE OF THE SAME
RU2019120720A (en) IMPROVED SEPARATE VARIABLE IMMUNOGLOBULIN DOMAINS BINDING WITH SERUM ALBUMIN
NZ715896A (en) Humanized or chimeric cd3 antibodies
TW200745164A (en) Gene recombination antibodies composition
AR108452A1 (en) ANTIGEN UNION MOLECULES THAT INCLUDE A TRIMMER BINDING THE FNT FAMILY AND A FRACTION OF UNION TO TENASCINA
IL259927B2 (en) Humanized anti-cd73 antibodies
IL299282B1 (en) Improved immunoglobulin variable domains
IL274071B1 (en) Method for generating in vivo multispecific antibodies from monospecific antibodies
IL263542B2 (en) Bispecific checkpoint inhibitor antibodies
WO2015138907A3 (en) Hybrid immunoglobulin containing non-peptidyl linkage
HRP20211528T1 (en) Trispecific and/or trivalent binding proteins for prevention or treatment of hiv infection
HRP20201785T1 (en) MULTIVALENT AND MULTISPECIFIC DR5-BINDING FUSION PROTEINS
PE20210554A1 (en) ANTI-CXCR5 ANTIBODIES AND COMPOSITIONS AND USES THEREOF
HRP20221142T1 (en) Modified-igg antibodies that bind transforming growth factor-beta1 with high affinity, avidity and specificity
EA201691782A1 (en) ANTIBODIES SPECIFIC TO THE RECEPTOR OF INSULIN-LIKE GROWTH FACTOR 1, AND THEIR APPLICATION
ZA202000961B (en) Antigen binding proteins binding to 5t4 and 4-1bb and related compositions and methods
NZ730014B2 (en) Compound targeting il-23a and tnf-alpha and uses thereof
NZ766849B2 (en) Compound targeting il-23a and tnf-alpha and uses thereof
NZ738942A (en) Compound targeting il-23a and b-cell activating factor (baff) and uses thereof
NZ738942B2 (en) Compound targeting il-23a and b-cell activating factor (baff) and uses thereof
WO2017142388A3 (en) Pharmaceutical composition of recombinant hybrid proteins that can generate scorpion-venom-neutralising antibodies
NZ778160B2 (en) Compound targeting il-23a and b-cell activating factor (baff) and uses thereof
NZ763848B2 (en) Improved immunoglobulin variable domains
NZ763848A (en) Improved immunoglobulin variable domains