CN114302893B - 用于细胞靶向的多特异性抗原结合分子及其用途 - Google Patents

用于细胞靶向的多特异性抗原结合分子及其用途 Download PDF

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Publication number
CN114302893B
CN114302893B CN202080061412.XA CN202080061412A CN114302893B CN 114302893 B CN114302893 B CN 114302893B CN 202080061412 A CN202080061412 A CN 202080061412A CN 114302893 B CN114302893 B CN 114302893B
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antigen
domain
molecule
binding
cell
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CN114302893A (zh
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L·哈伯
J·A·芬尼
R·麦凯
E·史密斯
C-Y·林
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Regeneron Pharmaceuticals Inc
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Regeneron Pharmaceuticals Inc
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    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • 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
    • 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
    • C07K14/70539—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
    • C07K16/2803—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
    • C07K16/2809—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 the 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
    • C07K16/2818—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 CD28 or CD152
    • 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
    • C07K16/2863—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/46—Hybrid immunoglobulins
    • C07K16/468—Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional 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
    • C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/55—Fab or Fab'
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/622—Single chain antibody (scFv)
    • 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

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Cell Biology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Zoology (AREA)
  • Toxicology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
CN202080061412.XA 2019-08-15 2020-08-14 用于细胞靶向的多特异性抗原结合分子及其用途 Active CN114302893B (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202510048366.4A CN119954933A (zh) 2019-08-15 2020-08-14 用于细胞靶向的多特异性抗原结合分子及其用途

Applications Claiming Priority (9)

Application Number Priority Date Filing Date Title
US201962887411P 2019-08-15 2019-08-15
US62/887,411 2019-08-15
US201962924435P 2019-10-22 2019-10-22
US62/924,435 2019-10-22
US202062978584P 2020-02-19 2020-02-19
US62/978,584 2020-02-19
US202063057824P 2020-07-28 2020-07-28
US63/057,824 2020-07-28
PCT/US2020/046352 WO2021030680A1 (en) 2019-08-15 2020-08-14 Multispecific antigen-binding molecules for cell targeting and uses thereof

Related Child Applications (1)

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CN202510048366.4A Division CN119954933A (zh) 2019-08-15 2020-08-14 用于细胞靶向的多特异性抗原结合分子及其用途

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CN114302893A CN114302893A (zh) 2022-04-08
CN114302893B true CN114302893B (zh) 2025-01-28

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CN202510048366.4A Pending CN119954933A (zh) 2019-08-15 2020-08-14 用于细胞靶向的多特异性抗原结合分子及其用途

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US (4) US12077603B2 (enExample)
EP (1) EP4013797A1 (enExample)
JP (2) JP7629906B2 (enExample)
KR (1) KR20220044821A (enExample)
CN (2) CN114302893B (enExample)
AU (1) AU2020330063A1 (enExample)
BR (1) BR112022002012A2 (enExample)
CA (1) CA3147791A1 (enExample)
IL (1) IL290299A (enExample)
MX (1) MX2022001942A (enExample)
TW (2) TW202542199A (enExample)
WO (1) WO2021030680A1 (enExample)

Families Citing this family (12)

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DK3277725T3 (da) 2015-03-30 2021-01-11 Regeneron Pharma Konstante tungkædeområder med reduceret binding til FC-gammareceptorer
MY195059A (en) * 2015-09-23 2023-01-05 Regeneron Pharma Optimized Anti-CD3 Bispecific Antibodies and Uses Thereof
BR112022001194A2 (pt) 2019-07-24 2022-06-07 Regeneron Pharma Receptores de antígeno quimérico com especificidade de mage a4 e usos dos mesmos
IL303675A (en) 2020-12-17 2023-08-01 Regeneron Pharma Production of protein thermal microgels
MX2023008527A (es) 2021-01-20 2023-07-28 Regeneron Pharma Metodos para mejorar el valor proteico en cultivo celular.
JP2024516308A (ja) * 2021-05-04 2024-04-12 リジェネロン・ファーマシューティカルズ・インコーポレイテッド Ｍａｇｅ－ａ４特異性を有するキメラ抗原受容体及びその使用
AU2022318255A1 (en) * 2021-07-27 2024-01-18 Morphosys Ag Combinations of antigen binding molecules
WO2023183758A2 (en) * 2022-03-19 2023-09-28 Regeneron Pharmaceuticals, Inc. Multispecific molecules targeting cd3 and mage-a4 and uses thereof
EP4565610A1 (en) * 2022-08-02 2025-06-11 Ose Immunotherapeutics Multifunctional molecule directed against cd28
IL322890A (en) * 2023-02-28 2025-10-01 Regeneron Pharma Multispecific molecules containing an MHC-peptide complex containing an MHC domain and an antigenic peptide and a partially targeted immune cell antigen
WO2025199278A2 (en) 2024-03-20 2025-09-25 Regeneron Pharmaceuticals, Inc. Masked multispecific antigen-binding molecules with cleavable linkers
WO2025255480A1 (en) * 2024-06-07 2025-12-11 Regeneron Pharmaceuticals, Inc. Tetravalent multispecific binding molecules and methods of use thereof

Citations (3)

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WO1991003493A1 (en) * 1989-08-29 1991-03-21 The University Of Southampton Bi-or trispecific (fab)3 or (fab)4 conjugates
WO2014022540A1 (en) * 2012-08-02 2014-02-06 Regeneron Pharmaceuticals, Inc. Multivalent antigen-binding proteins
WO2018178074A1 (en) * 2017-03-29 2018-10-04 F. Hoffmann-La Roche Ag Trimeric antigen binding molecules specific for a costimulatory tnf receptor

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US7550143B2 (en) * 2005-04-06 2009-06-23 Ibc Pharmaceuticals, Inc. Methods for generating stably linked complexes composed of homodimers, homotetramers or dimers of dimers and uses
EP1740946B1 (en) 2004-04-20 2013-11-06 Genmab A/S Human monoclonal antibodies against cd20
CA2604032C (en) * 2005-04-06 2017-08-22 Ibc Pharmaceuticals, Inc. Methods for generating stably linked complexes composed of homodimers, homotetramers or dimers of dimers and uses
SG176219A1 (en) * 2009-05-27 2011-12-29 Hoffmann La Roche Tri- or tetraspecific antibodies
TWI507525B (zh) 2009-06-26 2015-11-11 Regeneron Pharma 具天然免疫球蛋白形式之易分離的雙專一性抗體
SG183149A1 (en) 2010-02-08 2012-09-27 Regeneron Pharma Common light chain mouse
JOP20200236A1 (ar) 2012-09-21 2017-06-16 Regeneron Pharma الأجسام المضادة لمضاد cd3 وجزيئات ربط الأنتيجين ثنائية التحديد التي تربط cd3 وcd20 واستخداماتها
JP2014124186A (ja) 2012-12-26 2014-07-07 Industrial Technology Research Institute 多価抗体フラグメントおよびその三量体化複合体
TWI682941B (zh) 2013-02-01 2020-01-21 美商再生元醫藥公司 含嵌合恆定區之抗體
US10428155B2 (en) * 2014-12-22 2019-10-01 Xencor, Inc. Trispecific antibodies
DK3277725T3 (da) 2015-03-30 2021-01-11 Regeneron Pharma Konstante tungkædeområder med reduceret binding til FC-gammareceptorer
MY195059A (en) 2015-09-23 2023-01-05 Regeneron Pharma Optimized Anti-CD3 Bispecific Antibodies and Uses Thereof
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WO1991003493A1 (en) * 1989-08-29 1991-03-21 The University Of Southampton Bi-or trispecific (fab)3 or (fab)4 conjugates
WO2014022540A1 (en) * 2012-08-02 2014-02-06 Regeneron Pharmaceuticals, Inc. Multivalent antigen-binding proteins
WO2018178074A1 (en) * 2017-03-29 2018-10-04 F. Hoffmann-La Roche Ag Trimeric antigen binding molecules specific for a costimulatory tnf receptor

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AU2020330063A1 (en) 2022-03-24
US20240368312A1 (en) 2024-11-07
KR20220044821A (ko) 2022-04-11
CA3147791A1 (en) 2021-02-18
JP7629906B2 (ja) 2025-02-14
JP2022545647A (ja) 2022-10-28
IL290299A (en) 2022-04-01
US11952430B2 (en) 2024-04-09
US20220251244A1 (en) 2022-08-11
JP7896097B2 (ja) 2026-07-28
EP4013797A1 (en) 2022-06-22
US12065508B2 (en) 2024-08-20
TW202120553A (zh) 2021-06-01
MX2022001942A (es) 2022-07-27
TWI890689B (zh) 2025-07-21
TW202542199A (zh) 2025-11-01
US20230068129A1 (en) 2023-03-02
JP2025072461A (ja) 2025-05-09
WO2021030680A1 (en) 2021-02-18
BR112022002012A2 (pt) 2022-06-07
CN114302893A (zh) 2022-04-08
US12077603B2 (en) 2024-09-03
US20210047438A1 (en) 2021-02-18
CN119954933A (zh) 2025-05-09

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