WO2018006785A1 - Conjugué anticorps anti-egfr-médicament et son utilisation pharmaceutique - Google Patents

Conjugué anticorps anti-egfr-médicament et son utilisation pharmaceutique Download PDF

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Publication number
WO2018006785A1
WO2018006785A1 PCT/CN2017/091586 CN2017091586W WO2018006785A1 WO 2018006785 A1 WO2018006785 A1 WO 2018006785A1 CN 2017091586 W CN2017091586 W CN 2017091586W WO 2018006785 A1 WO2018006785 A1 WO 2018006785A1
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WIPO (PCT)
Prior art keywords
cancer
antibody
egfr
pharmaceutically acceptable
formula
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.)
Ceased
Application number
PCT/CN2017/091586
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English (en)
Chinese (zh)
Inventor
何开杰
叶鑫
梁金栋
陶维康
王亚里
杨昌永
张连山
孙飘扬
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.)
Jiangsu Hengrui Medicine Co Ltd
Shanghai Hengrui Pharmaceutical Co Ltd
Original Assignee
Jiangsu Hengrui Medicine Co Ltd
Shanghai Hengrui Pharmaceutical 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 Jiangsu Hengrui Medicine Co Ltd, Shanghai Hengrui Pharmaceutical Co Ltd filed Critical Jiangsu Hengrui Medicine Co Ltd
Priority to CN201780004770.5A priority Critical patent/CN108472371B/zh
Publication of WO2018006785A1 publication Critical patent/WO2018006785A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • 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
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • 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
    • 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

Definitions

  • small molecule tyrosine kinase inhibitors of EGFR such as Gefitinib, Erlotinib
  • EGFR monoclonal antibodies such as Cetuximab
  • Panidan Panitumumab nimotuzumab Namotuzumab, EP0699755, EP0712863
  • these EGFR-targeted drugs are not perfect and are only suitable for smaller patient populations.
  • n is 0-5, preferably 1-3; S is a sulfur atom.
  • alkyl refers to a saturated aliphatic hydrocarbon group which is a straight or branched chain group containing from 1 to 20 carbon atoms, preferably an alkyl group having from 1 to 12 carbon atoms, more preferably from 1 to 10 carbons.
  • the alkyl group of the atom is most preferably an alkyl group having 1 to 6 carbon atoms.
  • cycloalkyl refers to a saturated or partially unsaturated monocyclic or polycyclic cyclic hydrocarbon substituent containing from 3 to 20 carbon atoms, preferably from 3 to 12 carbon atoms, more preferably from 3 to 10 carbon atoms. One carbon atom, most preferably from 3 to 8 carbon atoms.
  • alkoxy refers to -O-(alkyl) and -O-(unsubstituted cycloalkyl), wherein alkyl is as defined above.
  • alkoxy groups include: methoxy, ethoxy, propoxy, butoxy, cyclopropoxy, cyclobutoxy, cyclopentyloxy, cyclohexyloxy.
  • the progress of the reaction in the examples was monitored by thin layer chromatography (TLC).
  • TLC thin layer chromatography
  • the system used for the reaction was: A: dichloromethane and methanol system, B: n-hexane and ethyl acetate system, C: petroleum ether And the ethyl acetate system, D: acetone, the volume ratio of the solvent is adjusted depending on the polarity of the compound.
  • Human IgG purchased from R&D; article number 1-001-A
  • ELISA is a method commonly used to detect pharmacokinetics in biological serum samples. In this study, the concentration of the antibody to be tested in the serum of cynomolgus monkeys was determined by ELISA.
  • V 1/2 ⁇ L length ⁇ L short 2

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Immunology (AREA)
  • General Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Genetics & Genomics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Molecular Biology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Epidemiology (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Peptides Or Proteins (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne un conjugué anticorps anti-EGFR-médicament cytotoxique, ou un sel ou un composé solvant de qualité pharmaceutique de celui-ci, une composition pharmaceutique comprenant le conjugué ou le sel ou le composé solvant de qualité pharmaceutique de celui-ci, et leur utilisation en tant que médicament anticancéreux, plus particulièrement leur utilisation pour la préparation de médicaments pour le traitement de symptômes ou de maladies à médiation par l'EGFR.
PCT/CN2017/091586 2016-07-05 2017-07-04 Conjugué anticorps anti-egfr-médicament et son utilisation pharmaceutique Ceased WO2018006785A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201780004770.5A CN108472371B (zh) 2016-07-05 2017-07-04 Egfr抗体-药物偶联物及其在医药上的应用

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201610526367 2016-07-05
CN201610526367.6 2016-07-05

Publications (1)

Publication Number Publication Date
WO2018006785A1 true WO2018006785A1 (fr) 2018-01-11

Family

ID=60911997

Family Applications (1)

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PCT/CN2017/091586 Ceased WO2018006785A1 (fr) 2016-07-05 2017-07-04 Conjugué anticorps anti-egfr-médicament et son utilisation pharmaceutique

Country Status (3)

Country Link
CN (1) CN108472371B (fr)
TW (1) TWI750194B (fr)
WO (1) WO2018006785A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110960490A (zh) * 2018-09-28 2020-04-07 江苏恒瑞医药股份有限公司 一种抗egfr抗体偶联药物组合物及其用途
WO2025131053A1 (fr) * 2023-12-22 2025-06-26 Fortvita Biologics Inc. Conjugués anticorps-médicament bispécifiques ciblant b7h3 et egfr et leur utilisation

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2025025434A1 (fr) * 2023-08-02 2025-02-06 百泰生物药业有限公司 Anticorps bispécifique egfr/c-met et son utilisation

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5891996A (en) * 1972-09-17 1999-04-06 Centro De Inmunologia Molecular Humanized and chimeric monoclonal antibodies that recognize epidermal growth factor receptor (EGF-R); diagnostic and therapeutic use
WO2005081711A2 (fr) * 2003-11-06 2005-09-09 Seattle Genetics, Inc. Composes de monomethylvaline capables de conjugaison aux ligands
CN103333246A (zh) * 2012-12-21 2013-10-02 百奥泰生物科技(广州)有限公司 一种抗egfr受体的肿瘤生长抑制剂及其制备方法和用途
CN103333179A (zh) * 2012-12-21 2013-10-02 百奥泰生物科技(广州)有限公司 类美登素衍生物及其制备方法和用途
CN103429261A (zh) * 2010-12-22 2013-12-04 塞法隆澳大利亚股份有限公司 半寿期改进的修饰抗体
CN103781494A (zh) * 2011-07-05 2014-05-07 梅里麦克制药股份有限公司 针对表皮生长因子受体(egfr)的抗体及其用途
CN103826661A (zh) * 2011-04-21 2014-05-28 西雅图基因公司 新的结合剂-药物缀合物(adc)及其用途
WO2015177360A1 (fr) * 2014-05-22 2015-11-26 Synthon Biopharmaceuticals B.V. Médicaments lieurs conjugués en un site spécifique à des anticorps et cam résultants
WO2016064749A2 (fr) * 2014-10-20 2016-04-28 Igenica Biotherapeutics, Inc. Nouveaux conjugués anticorps-médicament et composés, compositions et procédés d'utilisation s'y rapportant
WO2016065456A1 (fr) * 2014-10-31 2016-05-06 Formation Biologics Inc. Polythérapie à base d'anticorps anti-egfr

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AR099812A1 (es) * 2014-03-21 2016-08-17 Abbvie Inc Anticuerpos y conjugados de anticuerpo y fármaco anti-egfr
KR102508023B1 (ko) * 2014-09-03 2023-03-10 이뮤노젠 아이엔씨 세포-결합제 및 세포독성 약물을 포함하는 콘주게이트

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5891996A (en) * 1972-09-17 1999-04-06 Centro De Inmunologia Molecular Humanized and chimeric monoclonal antibodies that recognize epidermal growth factor receptor (EGF-R); diagnostic and therapeutic use
WO2005081711A2 (fr) * 2003-11-06 2005-09-09 Seattle Genetics, Inc. Composes de monomethylvaline capables de conjugaison aux ligands
CN103429261A (zh) * 2010-12-22 2013-12-04 塞法隆澳大利亚股份有限公司 半寿期改进的修饰抗体
CN103826661A (zh) * 2011-04-21 2014-05-28 西雅图基因公司 新的结合剂-药物缀合物(adc)及其用途
CN103781494A (zh) * 2011-07-05 2014-05-07 梅里麦克制药股份有限公司 针对表皮生长因子受体(egfr)的抗体及其用途
CN103333246A (zh) * 2012-12-21 2013-10-02 百奥泰生物科技(广州)有限公司 一种抗egfr受体的肿瘤生长抑制剂及其制备方法和用途
CN103333179A (zh) * 2012-12-21 2013-10-02 百奥泰生物科技(广州)有限公司 类美登素衍生物及其制备方法和用途
WO2015177360A1 (fr) * 2014-05-22 2015-11-26 Synthon Biopharmaceuticals B.V. Médicaments lieurs conjugués en un site spécifique à des anticorps et cam résultants
WO2016064749A2 (fr) * 2014-10-20 2016-04-28 Igenica Biotherapeutics, Inc. Nouveaux conjugués anticorps-médicament et composés, compositions et procédés d'utilisation s'y rapportant
WO2016065456A1 (fr) * 2014-10-31 2016-05-06 Formation Biologics Inc. Polythérapie à base d'anticorps anti-egfr

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110960490A (zh) * 2018-09-28 2020-04-07 江苏恒瑞医药股份有限公司 一种抗egfr抗体偶联药物组合物及其用途
WO2025131053A1 (fr) * 2023-12-22 2025-06-26 Fortvita Biologics Inc. Conjugués anticorps-médicament bispécifiques ciblant b7h3 et egfr et leur utilisation

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Publication number Publication date
TW201801752A (zh) 2018-01-16
TWI750194B (zh) 2021-12-21
CN108472371A (zh) 2018-08-31
CN108472371B (zh) 2022-05-24

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