CN113164621A - 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

Info

Publication number
CN113164621A
CN113164621A CN202180000978.6A CN202180000978A CN113164621A CN 113164621 A CN113164621 A CN 113164621A CN 202180000978 A CN202180000978 A CN 202180000978A CN 113164621 A CN113164621 A CN 113164621A
Authority
CN
China
Prior art keywords
protein
drug conjugate
antigen
cys1
peptide
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN202180000978.6A
Other languages
English (en)
Other versions
CN113164621B (zh
Inventor
何云
石磊
曹旸
王明
张云
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Harbour Biomed Shanghai Co Ltd
Original Assignee
Harbour Biomed Shanghai Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Harbour Biomed Shanghai Co Ltd filed Critical Harbour Biomed Shanghai Co Ltd
Publication of CN113164621A publication Critical patent/CN113164621A/zh
Application granted granted Critical
Publication of CN113164621B publication Critical patent/CN113164621B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • 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

Landscapes

  • 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。

Description

PCT国内申请，说明书已公开。

Claims (73)

  1. PCT国内申请，权利要求书已公开。
CN202180000978.6A 2020-12-08 2021-03-25 蛋白-药物偶联物和定点偶联方法 Active CN113164621B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
CN2020114238326 2020-12-08
CN202011423832 2020-12-08
PCT/CN2021/083024 WO2021115497A2 (zh) 2020-12-08 2021-03-25 蛋白-药物偶联物和定点偶联方法

Publications (2)

Publication Number Publication Date
CN113164621A true CN113164621A (zh) 2021-07-23
CN113164621B CN113164621B (zh) 2022-02-18

Family

ID=76330846

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202180000978.6A Active CN113164621B (zh) 2020-12-08 2021-03-25 蛋白-药物偶联物和定点偶联方法

Country Status (5)

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

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
WO2023125619A1 (zh) * 2021-12-28 2023-07-06 江苏恒瑞医药股份有限公司 抗ror1抗体和抗ror1抗体药物偶联物及其医药用途
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

Families Citing this family (5)

* 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
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
WO2024077174A1 (en) 2022-10-05 2024-04-11 Lyell Immunopharma, Inc. Methods for culturing nr4a-deficient cells

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104379178A (zh) * 2012-06-19 2015-02-25 宝力泰锐克斯有限公司 用于制备抗体缀合物的新方法以及新的抗体缀合物
CN108136043A (zh) * 2015-10-01 2018-06-08 诺和诺德股份有限公司 蛋白质缀合物
US20180280531A1 (en) * 2014-12-08 2018-10-04 Sorrento Therapeutics, Inc. C-met antibody drug conjugate
CN110575547A (zh) * 2018-06-07 2019-12-17 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
CN110997009A (zh) * 2017-06-20 2020-04-10 索伦托治疗有限公司 Cd38抗体药物缀合物

Family Cites Families (5)

* 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
CA2948082A1 (en) * 2014-05-09 2015-11-12 Bayer Pharma Aktiengesellschaft Method for targeted conjugation of peptides and proteins by paired c2 bridging of cysteine amino acids
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
US11596693B2 (en) * 2019-08-07 2023-03-07 Mabplex International Co., Ltd Antibody-drug conjugates and uses thereof
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 (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104379178A (zh) * 2012-06-19 2015-02-25 宝力泰锐克斯有限公司 用于制备抗体缀合物的新方法以及新的抗体缀合物
US20180280531A1 (en) * 2014-12-08 2018-10-04 Sorrento Therapeutics, Inc. C-met antibody drug conjugate
CN108136043A (zh) * 2015-10-01 2018-06-08 诺和诺德股份有限公司 蛋白质缀合物
CN110997009A (zh) * 2017-06-20 2020-04-10 索伦托治疗有限公司 Cd38抗体药物缀合物
CN110575547A (zh) * 2018-06-07 2019-12-17 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

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
IRENE A. PIKULEVA ET AL.: ""CHEMICAL MODIFICATION OF RABBIT IgG WITH N-DANSYLAZIRIDINE. INVESTIGATION OF THE PROPERTIES OF DANSYLATED ANTIBODIES"", 《MOLECULAR IMMUNOLOGY》 *
ZHAN ZHOU ET AL.: ""Specific Conjugation of the Hinge Region for Homogeneous Preparation of Antibody Fragment-Drug Conjugate: A Case Study for Doxorubicin-PEG-anti-CD20 Fab′ Synthesis"", 《BIOCONJUGATE CHEMISTRY》 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023125619A1 (zh) * 2021-12-28 2023-07-06 江苏恒瑞医药股份有限公司 抗ror1抗体和抗ror1抗体药物偶联物及其医药用途
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
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

Also Published As

Publication number Publication date
WO2021115497A3 (zh) 2021-10-21
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

Similar Documents

Publication Publication Date Title
CN113164621B (zh) 蛋白-药物偶联物和定点偶联方法
JP6728264B2 (ja) 抗ｈｅｒ２抗体及びその結合体
AU2019272250B2 (en) Anti-mesothelin antibody and antibody-drug conjugate thereof
US20240075154A1 (en) Engineered antibody, antibody-drug conjugate, and use thereof
CN110869394A (zh) 工程改造的抗体化合物及其缀合物
CN111819200B (zh) 抗c-met抗体
US20210061916A1 (en) Anti-prlr antibody-drug conjugates (adc) and uses thereof
CN114127117B (zh) 用于偶联的多肽复合物及其应用
WO2019068758A1 (en) MODIFIED CYSTEINE MOLECULES BINDING TO ANTIGEN
JP2024509891A (ja) 抗ｈｅｒ２抗体－免疫アゴニストコンジュゲート及びその使用
JP2021528973A (ja) 抗ｓｔｅａｐ１抗原結合タンパク質
EP3675907A1 (en) Anti-egfr antibody drug conjugates (adc) and uses thereof
JP2024510526A (ja) システイン操作された抗体コンストラクト、コンジュゲート、及び使用方法
US20200297863A1 (en) Anti-egfr antibody drug conjugates (adc) and uses thereof
WO2023178451A1 (en) Anti-folate receptor alpha antibodies and methods of use

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
REG Reference to a national code

Ref country code: HK

Ref legal event code: DE

Ref document number: 40047122

Country of ref document: HK

GR01 Patent grant
GR01 Patent grant