WO2021115497A3 - 蛋白-药物偶联物和定点偶联方法 - Google Patents

蛋白-药物偶联物和定点偶联方法 Download PDF

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Publication number
WO2021115497A3
WO2021115497A3 PCT/CN2021/083024 CN2021083024W WO2021115497A3 WO 2021115497 A3 WO2021115497 A3 WO 2021115497A3 CN 2021083024 W CN2021083024 W CN 2021083024W WO 2021115497 A3 WO2021115497 A3 WO 2021115497A3
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drug conjugate
protein
antigen binding
site
cys1
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PCT/CN2021/083024
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English (en)
French (fr)
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WO2021115497A2 (zh
Inventor
何云
石磊
曹旸
王明
张云
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和铂医药(上海)有限责任公司
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Priority to EP21731365.9A priority Critical patent/EP4241789A2/en
Priority to US18/256,422 priority patent/US20240050583A1/en
Priority to CN202180000978.6A priority patent/CN113164621B/zh
Publication of WO2021115497A2 publication Critical patent/WO2021115497A2/zh
Publication of WO2021115497A3 publication Critical patent/WO2021115497A3/zh
Priority to TW110145684A priority patent/TW202222349A/zh

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • A61K47/68031—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being an auristatin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/65—Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6851—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6889—Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

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  • Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Immunology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Cell Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)

Abstract

本申请涉及一种蛋白-药物偶联物，其包含抗原结合蛋白部分和药物偶联物部分；所述抗原结合蛋白部分包括一个或多个抗原结合片段，以及与所述抗原结合片段直接或间接连接的至少两个连接肽；所述两个连接肽可各自独立地含有第一半胱氨酸Cys1和第二半胱氨酸Cys2；所述药物偶联物部分共价结合于所述Cys1上。本申请还涉及一种蛋白-药物偶联物的制备方法，以及所述蛋白-药物偶联物在预防或治疗肿瘤或其他疾病中的用途。
PCT/CN2021/083024 2020-12-08 2021-03-25 蛋白-药物偶联物和定点偶联方法 WO2021115497A2 (zh)

Priority Applications (4)

Application Number Priority Date Filing Date Title
EP21731365.9A EP4241789A2 (en) 2020-12-08 2021-03-25 Protein-drug conjugate and site-specific conjugating method
US18/256,422 US20240050583A1 (en) 2020-12-08 2021-03-25 Protein-drug conjugate and site-specific conjugating method
CN202180000978.6A CN113164621B (zh) 2020-12-08 2021-03-25 蛋白-药物偶联物和定点偶联方法
TW110145684A TW202222349A (zh) 2020-12-08 2021-12-07 蛋白－藥物偶聯物和定點偶聯方法

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN202011423832 2020-12-08
CN202011423832.6 2020-12-08

Publications (2)

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WO2021115497A2 WO2021115497A2 (zh) 2021-06-17
WO2021115497A3 true WO2021115497A3 (zh) 2021-10-21

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US (1) US20240050583A1 (zh)
EP (1) EP4241789A2 (zh)
CN (1) CN113164621B (zh)
TW (1) TW202222349A (zh)
WO (1) WO2021115497A2 (zh)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA3234822A1 (en) 2021-10-28 2023-05-04 Suman Kumar VODNALA Methods for culturing cells expressing ror1-binding protein
WO2023116802A1 (zh) * 2021-12-23 2023-06-29 山东先声生物制药有限公司 抗gucy2c纳米抗体及其应用
TW202330619A (zh) * 2021-12-28 2023-08-01 大陸商江蘇恆瑞醫藥股份有限公司 抗ｒｏｒ１抗體和抗ｒｏｒ１抗體藥物偶聯物及其醫藥用途
WO2023125289A1 (zh) * 2021-12-31 2023-07-06 上海宏成药业有限公司 抗pd-1抗体及其用途
WO2023222108A1 (zh) * 2022-05-20 2023-11-23 上海迈晋生物医药科技有限公司 抗体-药物偶联物的制备方法
WO2024064952A1 (en) 2022-09-23 2024-03-28 Lyell Immunopharma, Inc. Methods for culturing nr4a-deficient cells overexpressing c-jun
WO2024064958A1 (en) 2022-09-23 2024-03-28 Lyell Immunopharma, Inc. Methods for culturing nr4a-deficient cells
CN115850449A (zh) * 2022-09-29 2023-03-28 苏州智核生物医药科技有限公司 抗体和缀合物
WO2024077174A1 (en) 2022-10-05 2024-04-11 Lyell Immunopharma, Inc. Methods for culturing nr4a-deficient cells

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106413758A (zh) * 2014-05-09 2017-02-15 拜耳医药股份有限公司 经由半胱氨酸氨基酸的成对c2桥联而使肽和蛋白质定向偶联的方法
CN110997010A (zh) * 2019-08-07 2020-04-10 烟台迈百瑞国际生物医药有限公司 一种抗体药物偶联物及其应用

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB0905023D0 (en) 2009-03-24 2009-05-06 Univ Erasmus Medical Ct Binding molecules
CA2876365A1 (en) * 2012-06-19 2013-12-27 Polytherics Limited Novel process for preparation of antibody conjugates and novel antibody conjugates
JP7235436B2 (ja) 2014-11-10 2023-03-08 ザ ボード オブ トラスティーズ オブ ザ レランド スタンフォード ジュニア ユニバーシティー 細胞の表面上にポリペプチドを発現させるための組成物および方法
SG11201704458SA (en) * 2014-12-08 2017-06-29 Sorrento Therapeutics Inc C-met antibody drug conjugate
MA43348A (fr) * 2015-10-01 2018-08-08 Novo Nordisk As Conjugués de protéines
CA3067311A1 (en) * 2017-06-20 2018-12-27 Sorrento Therapeutics, Inc. Cd38 antibody drug conjugate
CN110575547B (zh) * 2018-06-07 2021-07-30 中国科学院上海药物研究所 靶向于tf的抗体-药物偶联物及其制法和用途
CN111234020B (zh) 2020-01-23 2020-10-23 和铂医药(苏州)有限公司 一种bcma结合蛋白及其制备方法和应用

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106413758A (zh) * 2014-05-09 2017-02-15 拜耳医药股份有限公司 经由半胱氨酸氨基酸的成对c2桥联而使肽和蛋白质定向偶联的方法
CN110997010A (zh) * 2019-08-07 2020-04-10 烟台迈百瑞国际生物医药有限公司 一种抗体药物偶联物及其应用

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Publication number Publication date
CN113164621A (zh) 2021-07-23
CN113164621B (zh) 2022-02-18
WO2021115497A2 (zh) 2021-06-17
TW202222349A (zh) 2022-06-16
EP4241789A2 (en) 2023-09-13
US20240050583A1 (en) 2024-02-15

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