CN114040778A - 一种细胞结合分子-Tubulysin衍生物偶联物及其制备方法 - Google Patents

一种细胞结合分子-Tubulysin衍生物偶联物及其制备方法 Download PDF

Info

Publication number
CN114040778A
CN114040778A CN201980095886.3A CN201980095886A CN114040778A CN 114040778 A CN114040778 A CN 114040778A CN 201980095886 A CN201980095886 A CN 201980095886A CN 114040778 A CN114040778 A CN 114040778A
Authority
CN
China
Prior art keywords
compound
acid
reaction
conjugate
under
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.)
Pending
Application number
CN201980095886.3A
Other languages
English (en)
Inventor
赵珞博
杨庆良
赵林尧
黄圆圆
叶杭波
盖顺
李雯君
白露
其他发明人请求不公开姓名
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.)
Hangzhou Dac Biotech Co Ltd
Original Assignee
Hangzhou Dac Biotech 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 Hangzhou Dac Biotech Co Ltd filed Critical Hangzhou Dac Biotech Co Ltd
Publication of CN114040778A publication Critical patent/CN114040778A/zh
Pending legal-status Critical Current

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
    • A61K47/6811—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A01N25/32—Ingredients for reducing the noxious effect of the active substances to organisms other than pests, e.g. toxicity reducing compositions, self-destructing compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/05—Dipeptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/641—Branched, dendritic or hypercomb peptides
    • 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
    • A61K47/6863—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 the tumour determinant being from stomach or intestines cancer 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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • 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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Oncology (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Cell Biology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Communicable Diseases (AREA)
  • Agronomy & Crop Science (AREA)
  • Pest Control & Pesticides (AREA)
  • Environmental Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Dentistry (AREA)
  • Toxicology (AREA)
  • Plant Pathology (AREA)
  • Zoology (AREA)
  • Peptides Or Proteins (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicinal Preparation (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)

Abstract

本发明涉及以含支链(侧链)连接体偶联Tubulysin衍生物(同系物)与细胞结合分子，产生的偶联物具有更好的药代动力学性质、从而能更精确地靶向杀死异常细胞。本发明还涉及Tubulysin同系物与细胞结合剂的偶联及其所含分子的合成方法，以及使用该偶联物靶向治疗癌症、感染和自身免疫疾病的方法。本发明中的含有长支链连接体的Tubulysin偶联物在靶向传送期间半衰期增加，在血液循环中对非靶细胞、组织或器官的暴露最小，导致脱靶毒性降低。

Description

PCT国内申请，说明书已公开。

Claims (54)

  1. PCT国内申请，权利要求书已公开。
CN201980095886.3A 2019-06-29 2019-06-29 一种细胞结合分子-Tubulysin衍生物偶联物及其制备方法 Pending CN114040778A (zh)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/CN2019/093946 WO2021000067A1 (zh) 2019-06-29 2019-06-29 一种细胞结合分子-Tubulysin衍生物偶联物及其制备方法

Publications (1)

Publication Number Publication Date
CN114040778A true CN114040778A (zh) 2022-02-11

Family

ID=74100095

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201980095886.3A Pending CN114040778A (zh) 2019-06-29 2019-06-29 一种细胞结合分子-Tubulysin衍生物偶联物及其制备方法

Country Status (12)

Country Link
US (1) US20230025327A1 (zh)
EP (1) EP3991752A4 (zh)
JP (1) JP2022540395A (zh)
KR (1) KR20220029725A (zh)
CN (1) CN114040778A (zh)
AU (1) AU2019452577B2 (zh)
BR (1) BR112021025984A2 (zh)
CA (1) CA3145050A1 (zh)
IL (1) IL289458A (zh)
TW (1) TWI785334B (zh)
WO (1) WO2021000067A1 (zh)
ZA (1) ZA202201370B (zh)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115536530A (zh) * 2022-10-10 2022-12-30 浙江大学 一种Vulgarisin型四环二萜化合物的化学全合成方法
CN116199746A (zh) * 2022-11-29 2023-06-02 厦门大学 高亲和力靶向Trop2的多元环肽分子框架

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PL2872157T3 (pl) 2012-07-12 2020-07-13 Hangzhou Dac Biotech Co., Ltd Koniugaty wiążących komórkę cząsteczek ze środkami cytotoksycznymi
US11873281B2 (en) 2012-07-12 2024-01-16 Hangzhou Dac Biotech Co., Ltd. Conjugates of cell binding molecules with cytotoxic agents
CA3108168A1 (en) * 2020-02-05 2021-08-05 Yue Zhang Conjugates of cell-binding molecules with cytotoxic agents
CN116699116A (zh) * 2023-06-14 2023-09-05 河南省人民医院 检测嗜碱性粒细胞cd284表达水平的物质的应用

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105641707A (zh) * 2014-11-11 2016-06-08 杭州多禧生物科技有限公司 细胞毒素分子同细胞结合受体分子的共轭体
CN109912683A (zh) * 2017-12-13 2019-06-21 杭州多禧生物科技有限公司 一种细胞毒素分子、偶联物及其制备方法和应用
CN111093707A (zh) * 2017-12-31 2020-05-01 杭州多禧生物科技有限公司 含支链连接体的Tubulysin同系物偶联物

Family Cites Families (74)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4491632A (en) 1979-10-22 1985-01-01 The Massachusetts General Hospital Process for producing antibodies to hepatitis virus and cell lines therefor
US4444887A (en) 1979-12-10 1984-04-24 Sloan-Kettering Institute Process for making human antibody producing B-lymphocytes
EP0043718B1 (en) 1980-07-07 1984-11-28 National Research Development Corporation Improvements in or relating to cell lines
US4341761A (en) 1980-07-25 1982-07-27 E. I. Du Pont De Nemours And Company Antibodies to immunogenic peptides and their use to purify human fibroblast interferon
US4466917A (en) 1981-02-12 1984-08-21 New York University Malaria vaccine
US4493890A (en) 1981-03-23 1985-01-15 Miles Laboratories, Inc. Activated apoglucose oxidase and its use in specific binding assays
US4451570A (en) 1981-03-26 1984-05-29 The Regents Of The University Of California Immunoglobulin-secreting human hybridomas from a cultured human lymphoblastoid cell line
US4399121A (en) 1981-11-04 1983-08-16 Miles Laboratories, Inc. Iodothyronine immunogens and antibodies
US4427783A (en) 1981-12-14 1984-01-24 Hoffmann-La Roche Inc. Immunoassay of thymosin α1
US4493795A (en) 1983-10-17 1985-01-15 Syntex (U.S.A.) Inc. Synthetic peptide sequences useful in biological and pharmaceutical applications and methods of manufacture
US5859205A (en) 1989-12-21 1999-01-12 Celltech Limited Humanised antibodies
US6075181A (en) 1990-01-12 2000-06-13 Abgenix, Inc. Human antibodies derived from immunized xenomice
US6150584A (en) 1990-01-12 2000-11-21 Abgenix, Inc. Human antibodies derived from immunized xenomice
US5545806A (en) 1990-08-29 1996-08-13 Genpharm International, Inc. Ransgenic non-human animals for producing heterologous antibodies
US5661016A (en) 1990-08-29 1997-08-26 Genpharm International Inc. Transgenic non-human animals capable of producing heterologous antibodies of various isotypes
EP0546073B1 (en) 1990-08-29 1997-09-10 GenPharm International, Inc. production and use of transgenic non-human animals capable of producing heterologous antibodies
US6797492B2 (en) 1991-05-17 2004-09-28 Merck & Co., Inc. Method for reducing the immunogenicity of antibody variable domains
US5436149A (en) 1993-02-19 1995-07-25 Barnes; Wayne M. Thermostable DNA polymerase with enhanced thermostability and enhanced length and efficiency of primer extension
US5922545A (en) 1993-10-29 1999-07-13 Affymax Technologies N.V. In vitro peptide and antibody display libraries
US6111166A (en) 1994-09-19 2000-08-29 Medarex, Incorporated Transgenic mice expressing human Fcα and β receptors
DE19638870B4 (de) 1996-09-23 2009-05-14 Helmholtz-Zentrum für Infektionsforschung GmbH Tubulysine, Verfahren zu ihrer Gewinnung und sie enthaltende Mittel
US5916771A (en) 1996-10-11 1999-06-29 Abgenix, Inc. Production of a multimeric protein by cell fusion method
DE10008089A1 (de) 2000-02-22 2001-10-31 Biotechnolog Forschung Gmbh Syntheseverfahren zur Herstellung von Tubulysinen
US6596541B2 (en) 2000-10-31 2003-07-22 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
US20020169125A1 (en) 2001-03-21 2002-11-14 Cell Therapeutics, Inc. Recombinant production of polyanionic polymers and uses thereof
US20040249130A1 (en) 2002-06-18 2004-12-09 Martin Stanton Aptamer-toxin molecules and methods for using same
US7767803B2 (en) 2002-06-18 2010-08-03 Archemix Corp. Stabilized aptamers to PSMA and their use as prostate cancer therapeutics
EP1521769B1 (de) 2002-07-09 2015-09-09 Dömling, Alexander Tubulysinkonjugate
DE10230872A1 (de) 2002-07-09 2004-01-22 Morphochem AG Aktiengesellschaft für kombinatorische Chemie Verfahren zur Herstellung von substituierten Thiazol-2-ylmethylestern
AU2003266233A1 (en) 2002-07-09 2004-01-23 Morphochem Aktiengesellschaft Fur Kombinatorische Chemie Novel tubulysin analogues
DE10241152A1 (de) 2002-09-05 2004-03-18 GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF) Tubulysin-Biosynthese-Gene
DE10254439A1 (de) 2002-11-21 2004-06-03 GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF) Tubulysine, Herstellungsverfahren und Tubulysin-Mittel
DE102004030227A1 (de) 2004-06-23 2006-01-26 Dömling, Alexander, Dr. Wirkstoffe mit antiangiogenetischen Eigenschaften
US7638299B2 (en) 2004-07-21 2009-12-29 Ambrx, Inc. Biosynthetic polypeptides utilizing non-naturally encoded amino acids
US20060142393A1 (en) 2004-09-16 2006-06-29 Sherman Matthew L Bis(thio-hydrazide amides) for treatment of hyperplasia
ES2579805T3 (es) 2004-09-23 2016-08-16 Genentech, Inc. Anticuerpos y conjugados modificados por ingeniería genética con cisteína
EP2899277A1 (en) 2004-11-26 2015-07-29 Pieris AG Compound with affinity for the cytotoxic T lymphocyte-associated antigen (CTLA-4)
MX2007007590A (es) 2004-12-22 2007-12-10 Ambrx Inc Composiciones que contienen, metodos que involucran y usos de aminoacidos no naturales y polipeptidos.
CA2600418A1 (en) 2005-03-07 2006-09-14 Archemix Corp. Stabilized aptamers to psma and their use as prostate cancer therapeutics
EP2339014B1 (en) 2005-11-16 2015-05-27 Ambrx, Inc. Methods and compositions comprising non-natural amino acids
CA2653748A1 (en) 2006-05-02 2007-11-15 Allozyne, Inc. Non-natural amino acid substituted polypeptides
US20080096819A1 (en) 2006-05-02 2008-04-24 Allozyne, Inc. Amino acid substituted molecules
ITMI20061624A1 (it) 2006-08-11 2008-02-12 Bioker Srl Mono-coniugati sito-specifici di g-csf
US7985783B2 (en) 2006-09-21 2011-07-26 The Regents Of The University Of California Aldehyde tags, uses thereof in site-specific protein modification
TW201509433A (zh) 2006-12-13 2015-03-16 Cerulean Pharma Inc 用於醫物傳遞之以環糊精為基之聚合物
CN101678124A (zh) 2007-03-14 2010-03-24 恩多塞特公司 结合配体连接的微管溶素递药缀合物
WO2008125116A2 (en) 2007-03-31 2008-10-23 Aarhus Universitet Upar inhibition
WO2008122039A2 (en) 2007-04-02 2008-10-09 The Government Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Selenocysteine mediated hybrid antibody molecules
AR066476A1 (es) 2007-05-08 2009-08-19 Genentech Inc Anticuerpos anti-muc16 disenados con cisteina y conjugaods de anticuerpos y farmacos
US8980833B2 (en) 2007-05-10 2015-03-17 R&D-Biopharmaceuticals Gmbh Tubulysine derivatives
EP3569251A1 (en) 2007-06-25 2019-11-20 Endocyte, Inc. Conjugates containing hydrophilic spacer linkers
US8476451B2 (en) 2007-07-20 2013-07-02 The Regents Of The University Of California Tubulysin D analogues
EP2181101A2 (en) 2007-07-20 2010-05-05 Helmholtz-Zentrum für Infektionsforschung GmbH Tubulysin d analogues
EP3656403B1 (en) 2007-08-17 2022-05-11 Purdue Research Foundation Preparation process of psma binding ligand-linker conjugates
CA2703491C (en) 2007-10-25 2017-06-13 Endocyte, Inc. Tubulysins and processes for preparing
CN106986926A (zh) 2008-01-30 2017-07-28 皮里斯股份公司 具有对人c‑met受体酪氨酸激酶的亲和性的泪脂质运载蛋白的突变蛋白及其获得方法
EP2349274A4 (en) 2008-09-17 2014-12-17 Endocyte Inc CONJUGATES OF ANTIFOLATES BINDING THE FOLATE RECEPTOR
EP2174947A1 (en) 2008-09-25 2010-04-14 Universität des Saarlandes Bioactive pre-tubulysins and use thereof
EP2379578A4 (en) 2009-01-12 2012-05-02 Sutro Biopharma Inc DOUBLE-LOADING SYSTEM FOR THE SELECTIVE INTRODUCTION OF NON-NITIVE AMINO ACIDS IN PROTEINS DUE TO AN IN VITRO-SYNTHESIS PROCESS
US9238878B2 (en) 2009-02-17 2016-01-19 Redwood Bioscience, Inc. Aldehyde-tagged protein-based drug carriers and methods of use
IT1394860B1 (it) 2009-07-22 2012-07-20 Kemotech S R L Composti farmaceutici
US8394922B2 (en) 2009-08-03 2013-03-12 Medarex, Inc. Antiproliferative compounds, conjugates thereof, methods therefor, and uses thereof
SG11201401699WA (en) 2011-11-11 2014-09-26 Rinat Neuroscience Corp Antibodies specific for trop-2 and their uses
US9717803B2 (en) 2011-12-23 2017-08-01 Innate Pharma Enzymatic conjugation of polypeptides
GB201210770D0 (en) 2012-06-18 2012-08-01 Polytherics Ltd Novel conjugation reagents
PL2872157T3 (pl) 2012-07-12 2020-07-13 Hangzhou Dac Biotech Co., Ltd Koniugaty wiążących komórkę cząsteczek ze środkami cytotoksycznymi
NO2789793T3 (zh) 2012-10-24 2018-01-27
US9310374B2 (en) 2012-11-16 2016-04-12 Redwood Bioscience, Inc. Hydrazinyl-indole compounds and methods for producing a conjugate
EP4063389A3 (en) 2013-03-11 2022-12-28 Genzyme Corporation Site-specific antibody-drug conjugation through glycoengineering
WO2016059628A1 (en) 2014-10-12 2016-04-21 Korol Oleg System and method for determining watering needs for field or landscape irrigation
CA2991384C (en) 2015-07-04 2022-11-08 Suzhou M-Conj Biotech Co., Ltd Bridge linkers for conjugation of a cell-binding molecule
EP3319936A4 (en) 2015-07-12 2019-02-06 Suzhou M-conj Biotech Co., Ltd. PLACES OF CONDUCT FOR THE CONJUGATION OF CELL BINDING MOLECULES
CA2991975C (en) 2015-08-10 2021-04-06 Suzhou M-Conj Biotech Co., Ltd. Novel linkers and their uses in specific conjugation of drugs to a biological molecule
JP7138350B2 (ja) * 2016-11-14 2022-09-16 ハンジョウ ディーエーシー バイオテック シーオー．，エルティディ． 共役連結体、該連結体を含有する細胞結合分子－薬物共役体、並びに該共役体及び連結体の使用及び製造方法

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105641707A (zh) * 2014-11-11 2016-06-08 杭州多禧生物科技有限公司 细胞毒素分子同细胞结合受体分子的共轭体
CN109912683A (zh) * 2017-12-13 2019-06-21 杭州多禧生物科技有限公司 一种细胞毒素分子、偶联物及其制备方法和应用
CN111093707A (zh) * 2017-12-31 2020-05-01 杭州多禧生物科技有限公司 含支链连接体的Tubulysin同系物偶联物

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115536530A (zh) * 2022-10-10 2022-12-30 浙江大学 一种Vulgarisin型四环二萜化合物的化学全合成方法
CN116199746A (zh) * 2022-11-29 2023-06-02 厦门大学 高亲和力靶向Trop2的多元环肽分子框架

Also Published As

Publication number Publication date
TW202114740A (zh) 2021-04-16
AU2019452577B2 (en) 2023-08-24
EP3991752A1 (en) 2022-05-04
BR112021025984A2 (pt) 2022-04-12
JP2022540395A (ja) 2022-09-15
TWI785334B (zh) 2022-12-01
US20230025327A1 (en) 2023-01-26
AU2019452577A1 (en) 2022-02-24
WO2021000067A1 (zh) 2021-01-07
CA3145050A1 (en) 2021-01-07
ZA202201370B (en) 2022-10-26
KR20220029725A (ko) 2022-03-08
IL289458A (en) 2022-07-01
EP3991752A4 (en) 2023-03-29

Similar Documents

Publication Publication Date Title
CN109912683B (zh) 一种细胞毒素分子、偶联物及其制备方法和应用
US11767294B2 (en) Conjugates of cell binding molecules with cytotoxic agents
CN110099682B (zh) 偶联连接体，含有此连接体的细胞结合分子-药物偶联物及其制备和应用
CN109689107B (zh) 鹅膏毒素的衍生物及其与细胞结合分子的偶联
CN108289964B (zh) 新型连接体及其用于药物和生物分子的特异性偶联
CN108026123B (zh) 用于偶联的亲水链接体
KR102641565B1 (ko) 분지형 링커를 갖는 튜불리신 유사체의 접합체
CN110621673A (zh) 双链连接的细胞毒性药物偶联物
TWI785334B (zh) 一種細胞結合分子-tubulysin衍生物偶聯物及其製備方法
CN112272669A (zh) 横交联吡咯并苯二氮杂*二聚体（pbd）衍生物及其偶联物
CN106414465B (zh) 带电荷链接体及其在共轭反应上的应用
CN113698335A (zh) 细胞结合分子的特异性偶联
CN105641707B (zh) 细胞毒素分子同细胞结合受体分子的共轭体
CN113350518A (zh) 与细胞结合分子的共轭偶联的桥连接体
KR20230034957A (ko) 캄프토테신 유사체를 갖는 세포-결합 분자의 접합체
JP2024028815A (ja) チューブリシン類縁体と細胞結合分子との共役体の製剤
CN113423430A (zh) 含支链连接子的鹅膏毒素偶联物
NZ719369B2 (en) Conjugates of Cell Binding Molecules with Cytotoxic Agents

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