JP2023502625A - 共有新抗原を標的にする抗原結合タンパク質 - Google Patents

共有新抗原を標的にする抗原結合タンパク質 Download PDF

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JP2023502625A
JP2023502625A JP2022527937A JP2022527937A JP2023502625A JP 2023502625 A JP2023502625 A JP 2023502625A JP 2022527937 A JP2022527937 A JP 2022527937A JP 2022527937 A JP2022527937 A JP 2022527937A JP 2023502625 A JP2023502625 A JP 2023502625A
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hla
mutation
molecule
ras
class
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JP2023502625A5 (enExample
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カリン ヨース
アレクサンドラ カタジナ ノビツカ
アブバカル ジャロ
ロマン イェレンスキー
ジェームス シン サン
ジェニファー バズビー
マシュー ジョセフ デイビス
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グリットストーン バイオ インコーポレイテッド
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Publication of JP2023502625A5 publication Critical patent/JP2023502625A5/ja
Priority to JP2025140331A priority Critical patent/JP2025176716A/ja
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/7051—T-cell receptor (TcR)-CD3 complex
    • 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
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/2833—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against MHC-molecules, e.g. HLA-molecules
    • 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
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • 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
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • 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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • 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
    • 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
    • C07K2317/32—Immunoglobulins specific features characterized by aspects of specificity or valency specific for a neo-epitope on a complex, e.g. antibody-antigen or ligand-receptor
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565—Complementarity determining region [CDR]
    • 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
    • C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • 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
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/03—Fusion polypeptide containing a localisation/targetting motif containing a transmembrane segment
    • 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
    • C12N2510/00—Genetically modified cells
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
    • G01N2333/70503—Immunoglobulin superfamily, e.g. VCAMs, PECAM, LFA-3
    • G01N2333/70539—MHC-molecules, e.g. HLA-molecules

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Biomedical Technology (AREA)
  • Biochemistry (AREA)
  • Zoology (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Medicinal Chemistry (AREA)
  • Wood Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biophysics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Cell Biology (AREA)
  • General Engineering & Computer Science (AREA)
  • Microbiology (AREA)
  • Hematology (AREA)
  • Physics & Mathematics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Toxicology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Urology & Nephrology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Plant Pathology (AREA)
  • Food Science & Technology (AREA)
  • Pathology (AREA)
  • General Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Peptides Or Proteins (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
JP2022527937A 2019-11-15 2020-11-13 共有新抗原を標的にする抗原結合タンパク質 Pending JP2023502625A (ja)

Priority Applications (1)

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JP2025140331A JP2025176716A (ja) 2019-11-15 2025-08-26 共有新抗原を標的にする抗原結合タンパク質

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US201962936303P 2019-11-15 2019-11-15
US62/936,303 2019-11-15
US202063030774P 2020-05-27 2020-05-27
US63/030,774 2020-05-27
PCT/US2020/060605 WO2021097365A2 (en) 2019-11-15 2020-11-13 Antigen-binding proteins targeting shared neoantigens

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JP2023502625A true JP2023502625A (ja) 2023-01-25
JP2023502625A5 JP2023502625A5 (enExample) 2023-11-21

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JP2025140331A Pending JP2025176716A (ja) 2019-11-15 2025-08-26 共有新抗原を標的にする抗原結合タンパク質

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US (1) US20230041030A1 (enExample)
EP (1) EP4058484A4 (enExample)
JP (2) JP2023502625A (enExample)
KR (1) KR20220098379A (enExample)
CN (1) CN115175934A (enExample)
AU (1) AU2020384374A1 (enExample)
CA (1) CA3157411A1 (enExample)
IL (1) IL292535A (enExample)
WO (1) WO2021097365A2 (enExample)

Families Citing this family (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20190016802A1 (en) 2017-07-14 2019-01-17 Immatics Biotechnologies Gmbh Dual specificity polypeptide molecule
CA3127673A1 (en) * 2019-01-25 2020-07-30 The Trustees Of The University Of Pennsylvania Compositions and methods for targeting mutant ras
GB2613715B (en) 2019-02-20 2023-12-06 Fred Hutchinson Cancer Center Binding proteins specific for RAS neoantigens and uses thereof
WO2022082030A2 (en) 2020-10-15 2022-04-21 Gritstone Bio, Inc. Antigen-binding proteins and related methods of use
WO2022155503A1 (en) 2021-01-14 2022-07-21 Gritstone Bio, Inc. Multi-specific antibodies and methods of use
WO2022233956A1 (en) 2021-05-05 2022-11-10 Immatics Biotechnologies Gmbh Antigen binding proteins specifically binding prame
WO2023288203A2 (en) * 2021-07-12 2023-01-19 Ludwig Institute For Cancer Research Ltd T cell receptors specific for tumor-associated antigens and methods of use thereof
EP4401766A4 (en) * 2021-09-17 2025-10-29 Seattle Project Corp Neo-antigenic anti-Kras therapies
CN118525037A (zh) * 2021-10-29 2024-08-20 侯亚非 识别ctnnb1中s37f突变的t细胞受体及其应用
WO2023086435A1 (en) * 2021-11-10 2023-05-19 Memorial Sloan-Kettering Cancer Center T cell receptors targeting q61-comprising ras mutations and uses thereof
EP4466283A1 (en) * 2022-01-21 2024-11-27 T-Knife GmbH Antigen recognizing construct that binds specific peptide with determinable affinity and t cell receptor having antigenic specificity for kras as well as corresponding nucleic acid sequence, vector, host cell, pharmaceutical composition and kit
WO2023173024A2 (en) * 2022-03-10 2023-09-14 The Board Of Trustees Of The Leland Stanford Junior University Treatment of coronary artery disease by reducing activity of cross-reactive t cells
WO2023220718A1 (en) * 2022-05-13 2023-11-16 Fred Hutchinson Cancer Center Binding proteins specific for ras neoantigens and uses thereof
WO2024036166A1 (en) * 2022-08-08 2024-02-15 The University Of North Carolina At Chapel Hill Bioorthogonal t cell receptor molecules and methods of making and using the same
EP4573114A4 (en) * 2022-08-19 2026-07-29 Memorial Sloan Kettering Cancer Center T-LYMPHOCYTE RECEPTORS TARGETTING RAS MUTATIONS AND ASSOCIATED USES
US20260232734A1 (en) * 2023-02-27 2026-08-13 Adaptive Biotechnologies Corporation Therapeutic T-Cell Receptors Targeting KRAS G12D
CN118924886A (zh) * 2023-03-16 2024-11-12 郑州大学 肿瘤共享新抗原表位肽或其编码核酸的新用途
CN118909132A (zh) * 2023-05-06 2024-11-08 北京鼎成肽源生物技术有限公司 靶向kras g12v突变的tcr分子和细胞及其应用
IL304887A (en) * 2023-07-31 2025-02-01 Yeda Res & Dev T-cell receptor directed against RAS neoantigen
WO2025056659A1 (en) * 2023-09-15 2025-03-20 Medigene Immunotherapies Gmbh T-CELL RECEPTOR VARIANT AGAINST mKRAS7-16 G12V AND G12C
WO2025056656A1 (en) * 2023-09-15 2025-03-20 Medigene Immunotherapies Gmbh T-CELL RECEPTOR VARIANT AGAINST mKRAS7-16 G12V
WO2025189363A1 (zh) * 2024-03-12 2025-09-18 广州医科大学 一种t细胞受体(tcr)及其用途
WO2025240737A1 (en) * 2024-05-16 2025-11-20 Rutgers, The State University Of New Jersey Methods of producing memory t cells in vitro and their use in immunotherapy
WO2025259799A2 (en) * 2024-06-12 2025-12-18 Biontech Us Inc. T cell receptor compositions and methods of use thereof
EP4737476A1 (en) * 2024-09-12 2026-05-06 Medigene Immunotherapies GmbH T-cell receptor variant against mkras 7-16 g12d
WO2026125390A1 (en) 2024-12-09 2026-06-18 Vib Vzw Fthl17 immunogen and tcr

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016191246A2 (en) * 2015-05-22 2016-12-01 Memorial Sloan-Kettering Cancer Center T cell receptor-like antibodies specific for a prame peptide
JP2017536825A (ja) * 2014-11-26 2017-12-14 アメリカ合衆国 抗突然変異ｋｒａｓ ｔ細胞受容体
JP2018522822A (ja) * 2015-05-20 2018-08-16 ザ・ブロード・インスティテュート・インコーポレイテッド 共通ネオ抗原

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2771349B1 (en) * 2011-09-16 2020-02-26 Iogenetics, LLC. Bioinformatic processes for determination of peptide binding
WO2013190090A1 (en) * 2012-06-21 2013-12-27 Philip Morris Products S.A. Gene signatures for classifying and grading lung cancer
WO2016154047A2 (en) * 2015-03-20 2016-09-29 Memorial Sloan-Kettering Cancer Center Monoclonal antigen-binding proteins to intracellular oncogene products
EP3286222A4 (en) * 2015-03-23 2018-08-08 The Johns Hopkins University Hla-restricted epitopes encoded by somatically mutated genes
SG11201808196UA (en) * 2016-03-31 2018-10-30 Neon Therapeutics Inc Neoantigens and methods of their use
MX2020001879A (es) * 2017-08-18 2020-07-29 Gritstone Oncology Inc Proteínas de fijación al antígeno que se dirigen a antígenos compartidos.
SG11202003798TA (en) * 2017-10-27 2020-05-28 Univ California Targeted replacement of endogenous t cell receptors
TW202000907A (zh) * 2018-05-23 2020-01-01 美商葛利史東腫瘤科技公司 共有抗原

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2017536825A (ja) * 2014-11-26 2017-12-14 アメリカ合衆国 抗突然変異ｋｒａｓ ｔ細胞受容体
JP2018522822A (ja) * 2015-05-20 2018-08-16 ザ・ブロード・インスティテュート・インコーポレイテッド 共通ネオ抗原
WO2016191246A2 (en) * 2015-05-22 2016-12-01 Memorial Sloan-Kettering Cancer Center T cell receptor-like antibodies specific for a prame peptide

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
EXPERT OPIN BIOL THER., vol. 16(8), JPN6022052358, 2016, pages 979 - 987, ISSN: 0005429929 *
THE JOURNAL OF IMMUNOLOGY, vol. 169, JPN6022052360, 2002, pages 1110 - 1118, ISSN: 0005429928 *

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AU2020384374A1 (en) 2022-06-09
KR20220098379A (ko) 2022-07-12
WO2021097365A2 (en) 2021-05-20
US20230041030A1 (en) 2023-02-09
CA3157411A1 (en) 2021-05-20
CN115175934A (zh) 2022-10-11
EP4058484A4 (en) 2024-04-03
EP4058484A2 (en) 2022-09-21
IL292535A (en) 2022-06-01
JP2025176716A (ja) 2025-12-04
WO2021097365A3 (en) 2021-07-08

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