CN113766933A - 一种抗体偶联药物、其中间体、制备方法及应用 - Google Patents

一种抗体偶联药物、其中间体、制备方法及应用 Download PDF

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CN113766933A
CN113766933A CN202080030918.4A CN202080030918A CN113766933A CN 113766933 A CN113766933 A CN 113766933A CN 202080030918 A CN202080030918 A CN 202080030918A CN 113766933 A CN113766933 A CN 113766933A
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antibody
seq
amino acid
acid sequence
alkyl
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CN113766933B (zh
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鲍彬
郭青松
高贝
张一帆
邱雪飞
杨彤
沈毅珺
张文伯
吕伟
王磊
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SHANGHAI FUDAN-ZHANGJIANG BIO-PHARMACEUTICAL CO LTD
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    • 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
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    • A—HUMAN NECESSITIES
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
    • A—HUMAN NECESSITIES
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    • 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
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    • 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
    • A61K47/68037—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a camptothecin [CPT] or derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • 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
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    • C07K16/2803—Immunoglobulins [IGs], 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
    • C07K16/2827—Immunoglobulins [IGs], 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 B7 molecules, e.g. CD80, CD86
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/32—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products of oncogenes

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Abstract

本发明公开了一种抗体偶联药物、其中间体、制备方法及应用。本发明提供了抗体偶联药物，其结构通式为Ab‑(L3‑L2‑L1‑D)m。该抗体偶联药物具有更好的生物学活性、稳定性和均一性，具有降低的毒副作用，且在肿瘤细胞内有更快的酶切释放速率。采用这种新型的抗体偶联药物可以实现细胞毒性药物，特别是喜树碱在ADC领域的广泛应用，治疗对于微管类ADC耐药的肿瘤病人。

Description

PCT国内申请，说明书已公开。

Claims (17)

  1. PCT国内申请，权利要求书已公开。
CN202080030918.4A 2019-06-28 2020-06-05 一种抗体偶联药物、其中间体、制备方法及应用 Active CN113766933B (zh)

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CN201910577909 2019-06-28
CN2019105779096 2019-06-28
PCT/CN2020/094767 WO2020259258A1 (zh) 2019-06-28 2020-06-05 一种抗体偶联药物、其中间体、制备方法及应用

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US (1) US20220233708A1 (zh)
EP (1) EP3991754A4 (zh)
JP (1) JP7407845B2 (zh)
KR (1) KR20220025861A (zh)
CN (1) CN113766933B (zh)
AU (1) AU2020301289A1 (zh)
BR (1) BR112021026580A2 (zh)
CA (1) CA3144790A1 (zh)
WO (1) WO2020259258A1 (zh)

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CN116789733A (zh) * 2022-07-05 2023-09-22 上海药明合联生物技术有限公司 偶联连接子
WO2024109949A1 (zh) * 2022-11-25 2024-05-30 明慧医药（杭州）有限公司 一种抗肿瘤化合物及其应用
WO2024114667A1 (zh) * 2022-11-30 2024-06-06 正大天晴药业集团股份有限公司 抗cldn18.2抗体药物偶联物及其药物组合物和用途

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TW202128227A (zh) * 2019-12-12 2021-08-01 大陸商江蘇恆瑞醫藥股份有限公司 抗密蛋白抗體藥物偶聯物及其醫藥用途
CN113943310A (zh) * 2020-10-12 2022-01-18 四川百利药业有限责任公司 一种氘代的喜树碱衍生物及其抗体药物偶联物
JP7454110B2 (ja) * 2020-12-04 2024-03-21 シャンハイ フダン－チャンジャン バイオ－ファーマシューティカル カンパニー リミテッド 抗体薬物複合体、その中間体、製造方法及び使用
CA3200649A1 (en) * 2020-12-11 2022-06-16 Yuli Xie Novel camptothecin derivative, composition containing same, and use thereof
JP2023550532A (ja) * 2020-12-18 2023-12-01 シャンハイ フダン－チャンジャン バイオ－ファーマシューティカル カンパニー リミテッド Ｔｒｏｐ２を標的とする抗体薬物複合体、その製造方法及び使用
EP4265274A4 (en) * 2020-12-18 2024-03-20 Shanghai Fudan-Zhangjiang Bio-Pharmaceutical Co., Ltd. ANTIBODY-ACTIVE CONJUGATE DIRECTED AGAINST B7-H3 AND PRODUCTION METHOD THEREOF AND USE THEREOF
CN114805377A (zh) * 2021-01-29 2022-07-29 明慧医药（杭州）有限公司 适用于抗体-药物偶联物的毒素分子
WO2022171115A1 (zh) * 2021-02-09 2022-08-18 微境生物医药科技(上海)有限公司 用于adc制备的喜树碱衍生物
WO2022204947A1 (zh) * 2021-03-30 2022-10-06 上海复旦张江生物医药股份有限公司 一种连接基药物偶联物的制备方法及其中间体
WO2022205111A1 (zh) * 2021-03-31 2022-10-06 上海复旦张江生物医药股份有限公司 一种伊喜替康衍生物的制备方法及其中间体
JP2024523422A (ja) * 2021-06-17 2024-06-28 ミンフイ ファーマシューティカル （ハンチョウ） リミテッド 抗腫瘍化合物およびその応用
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KR20240040090A (ko) 2021-07-30 2024-03-27 상하이 후단-장지앙 바이오-파마슈티컬 컴퍼니 리미티드 항-dll3 항체 및 이의 제조 방법, 이의 약물 접합체 및 용도
WO2023042097A1 (en) * 2021-09-15 2023-03-23 Daiichi Sankyo Company, Limited Antibody-drug conjugate for use in methods of treating chemotherapy-resistant cancer
WO2023103854A1 (zh) * 2021-12-09 2023-06-15 昆山新蕴达生物科技有限公司 一种亲和力改善的抗体-药物偶联物、其制备方法及应用
WO2024020536A1 (en) * 2022-07-22 2024-01-25 Nj Bio, Inc. Hexacyclic topoisomerase inhibitors having cytotoxic activity on cancer cells
WO2024026323A1 (en) * 2022-07-26 2024-02-01 Zeno Management, Inc. Immunoconjugates and methods
WO2024022372A1 (zh) * 2022-07-27 2024-02-01 明慧医药（杭州）有限公司 抗体药物偶联物及其应用
CN117510515A (zh) * 2022-07-28 2024-02-06 明慧医药（杭州）有限公司 适用于抗体-药物偶联物的毒素分子
WO2024109840A1 (zh) * 2022-11-22 2024-05-30 康诺亚生物医药科技（成都）有限公司 稠环类化合物及其偶联物和用途
CN116178386A (zh) * 2022-12-30 2023-05-30 上海复旦张江生物医药股份有限公司 一种连接基药物偶联物的制备方法及其中间体

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116789733A (zh) * 2022-07-05 2023-09-22 上海药明合联生物技术有限公司 偶联连接子
WO2024109949A1 (zh) * 2022-11-25 2024-05-30 明慧医药（杭州）有限公司 一种抗肿瘤化合物及其应用
WO2024114667A1 (zh) * 2022-11-30 2024-06-06 正大天晴药业集团股份有限公司 抗cldn18.2抗体药物偶联物及其药物组合物和用途

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JP7407845B2 (ja) 2024-01-04
KR20220025861A (ko) 2022-03-03
US20220233708A1 (en) 2022-07-28
WO2020259258A1 (zh) 2020-12-30
CA3144790A1 (en) 2020-12-30
AU2020301289A1 (en) 2022-02-24
CN113766933B (zh) 2024-09-06
BR112021026580A2 (pt) 2022-05-03
EP3991754A4 (en) 2023-05-17
EP3991754A1 (en) 2022-05-04

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