WO2014194030A3 - Conjugates comprising cell-binding agents and cytotoxic agents - Google Patents

Conjugates comprising cell-binding agents and cytotoxic agents Download PDF

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Publication number
WO2014194030A3
WO2014194030A3 PCT/US2014/039919 US2014039919W WO2014194030A3 WO 2014194030 A3 WO2014194030 A3 WO 2014194030A3 US 2014039919 W US2014039919 W US 2014039919W WO 2014194030 A3 WO2014194030 A3 WO 2014194030A3
Authority
WO
WIPO (PCT)
Prior art keywords
conjugates
cell
cytotoxic
agents
cba
Prior art date
Application number
PCT/US2014/039919
Other languages
French (fr)
Other versions
WO2014194030A2 (en
Inventor
Wayne C. Widdison
Ravi V.J. Chari
Original Assignee
Immunogen, Inc.
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 Immunogen, Inc. filed Critical Immunogen, Inc.
Publication of WO2014194030A2 publication Critical patent/WO2014194030A2/en
Publication of WO2014194030A3 publication Critical patent/WO2014194030A3/en

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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
    • A61K47/6835—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
    • A61K47/6883—Polymer-drug antibody conjugates, e.g. mitomycin-dextran-Ab; DNA-polylysine-antibody complex or conjugate used for therapy
    • 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

Abstract

The invention provides a branched linker compound with reactive moieties for forming covalent bonds with multiple cytotoxic agents (drugs) and/or a cell-binding agent (CBA); a cytotoxic compound comprising a branched linker moiety with a reactive group for forming a CBA-drug conjugates; a modified cell-binding agent comprising a branched linker moiety with a reactive group for forming a CBA-drug conjugates; and conjugates so formed. Such conjugates and/or cytotoxic compounds may be effective for treating a range of diseases, such as cancer, with a relatively high activity at a relatively low, non-toxic dose.
PCT/US2014/039919 2013-05-31 2014-05-29 Conjugates comprising cell-binding agents and cytotoxic agents WO2014194030A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201361829893P 2013-05-31 2013-05-31
US61/829,893 2013-05-31

Publications (2)

Publication Number Publication Date
WO2014194030A2 WO2014194030A2 (en) 2014-12-04
WO2014194030A3 true WO2014194030A3 (en) 2015-01-22

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PCT/US2014/039919 WO2014194030A2 (en) 2013-05-31 2014-05-29 Conjugates comprising cell-binding agents and cytotoxic agents

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CN106267225B (en) * 2015-05-29 2020-03-06 上海新理念生物医药科技有限公司 Trimaleimide-type linker and use thereof
JP6802840B2 (en) 2015-06-09 2020-12-23 エックスディーシーエクスプローラー （シャンハイ） カンパニー リミテッド Antibody-drug conjugates, intermediates, methods for their production, pharmaceutical compositions and applications
US11413353B2 (en) 2015-11-25 2022-08-16 Legochem Biosciences, Inc. Conjugates comprising self-immolative groups and methods related thereto
AU2016359234B2 (en) * 2015-11-25 2022-09-08 Legochem Biosciences, Inc. Conjugates comprising peptide groups and methods related thereto
CN113599533A (en) 2015-11-25 2021-11-05 乐高化学生物科学股份有限公司 Antibody-drug conjugates comprising branched linkers and methods related thereto
CN114478801A (en) 2016-01-25 2022-05-13 里珍纳龙药品有限公司 Maytansinoid derivatives, conjugates thereof, and methods of use
US11654197B2 (en) 2017-03-29 2023-05-23 Legochem Biosciences, Inc. Pyrrolobenzodiazepine dimer prodrug and ligand-linker conjugate compound of the same
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KR20210028544A (en) 2019-09-04 2021-03-12 주식회사 레고켐 바이오사이언스 Antibody-drug conjugate comprising antibody binding to antibody against human ROR1 and its use
KR102465431B1 (en) * 2020-10-21 2022-11-09 순천향대학교 산학협력단 Cell Penetrating Peptide-linker-anti-cancer drug and Pharmaceutical composition for prevention or treatment of colorectal cancer containing the same
WO2022262516A1 (en) * 2021-06-18 2022-12-22 北京海步医药科技有限公司 Linker and conjugate therefor

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