CN113453724B - 基于磺酰基马来酰亚胺的连接子和相应的偶联物 - Google Patents

基于磺酰基马来酰亚胺的连接子和相应的偶联物 Download PDF

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CN113453724B
CN113453724B CN201980077950.5A CN201980077950A CN113453724B CN 113453724 B CN113453724 B CN 113453724B CN 201980077950 A CN201980077950 A CN 201980077950A CN 113453724 B CN113453724 B CN 113453724B
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group
linker
antibody
residue
arylene
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CN113453724A (zh
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M·佩雷斯
F·马里昂
J-F·霍伊乌
C·德雷富斯
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Pierre Fabre Medicament SA
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    • 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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CN201980077950.5A 2018-09-27 2019-09-27 基于磺酰基马来酰亚胺的连接子和相应的偶联物 Active CN113453724B (zh)

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EP18306270.2 2018-09-27
EP18306270 2018-09-27
PCT/IB2019/001114 WO2020065408A1 (en) 2018-09-27 2019-09-27 Sulfomaleimide-based linkers and corresponding conjugates

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CN113453724B true CN113453724B (zh) 2025-02-25

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US (2) US12011485B2 (https=)
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Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB201908886D0 (en) * 2019-06-20 2019-08-07 Almac Discovery Ltd Anthracycline derivatives
WO2024008102A1 (en) * 2022-07-05 2024-01-11 Wuxi Xdc (Shanghai) Co., Ltd. Linker for conjugation
WO2024235120A1 (zh) * 2023-05-12 2024-11-21 四川科伦博泰生物医药股份有限公司 稠环化合物及其制备方法和用途
CN119751374A (zh) * 2024-12-09 2025-04-04 中国科学院水生生物研究所 高抑菌活性、低生态毒性的异噻唑啉酮类化合物及其制备方法和应用

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4127687A (en) * 1976-07-19 1978-11-28 Rohm And Haas Company Prevention of fouling of marine structures such as boat hulls
WO2016064749A2 (en) * 2014-10-20 2016-04-28 Igenica Biotherapeutics, Inc. Novel antibody-drug conjugates and related compounds, compositions, and methods of use

Family Cites Families (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5530101A (en) 1988-12-28 1996-06-25 Protein Design Labs, Inc. Humanized immunoglobulins
IL162181A (en) 1988-12-28 2006-04-10 Pdl Biopharma Inc A method of producing humanized immunoglubulin, and polynucleotides encoding the same
GB9014932D0 (en) 1990-07-05 1990-08-22 Celltech Ltd Recombinant dna product and method
JPH04248881A (ja) 1991-01-25 1992-09-04 Mitsubishi Kasei Corp 顔料分散型水性記録液
JPH04261476A (ja) 1991-02-15 1992-09-17 Mitsubishi Kasei Corp インクジェットプリンター用クリーニング液
WO1994004679A1 (en) 1991-06-14 1994-03-03 Genentech, Inc. Method for making humanized antibodies
JPH05244982A (ja) 1991-12-06 1993-09-24 Sumitomo Chem Co Ltd 擬人化ｂ−ｂ１０
US5639641A (en) 1992-09-09 1997-06-17 Immunogen Inc. Resurfacing of rodent antibodies
TW258789B (https=) 1992-09-28 1995-10-01 Rohm & Haas
KR20070110327A (ko) * 2005-03-08 2007-11-16 미쓰비시 가가꾸 가부시키가이샤 이방성 색소 필름용 조성물, 이방성 색소 필름 및 편광소자
JP2007025635A (ja) * 2005-06-17 2007-02-01 Fujitsu Hitachi Plasma Display Ltd プラズマディスプレイ装置及びその処理方法
US20060293374A1 (en) 2005-06-24 2006-12-28 Beers Scott A Substituted isothiazolones
CN101397280A (zh) 2008-11-04 2009-04-01 东华大学 反应性异噻唑啉酮类抗菌整理剂的制备方法
DE102012213321A1 (de) * 2012-07-30 2014-01-30 Robert Bosch Gmbh Verfahren und Vorrichtung zum Betreiben eines Fahrzeugs
FR3005051A1 (fr) 2013-04-25 2014-10-31 Pf Medicament Derives de la dolastatine 10 et d'auristatines
US9840533B2 (en) 2013-04-29 2017-12-12 Memorial Sloan Kettering Cancer Center Compositions and methods for altering second messenger signaling
US10781259B2 (en) * 2013-06-06 2020-09-22 Magenta Therapeutics, Inc. Modified antibodies and related compounds, compositions, and methods of use
CN106456602B (zh) 2014-03-27 2020-11-24 范德比尔特大学 取代的吲哚mcl-1抑制剂
HRP20190888T8 (hr) 2014-04-25 2019-10-04 Pierre Fabre Médicament Konjugat antitijela za igf-1r i lijeka i njegova upotreba u liječenju karcinoma
HUE047952T2 (hu) 2014-04-25 2020-05-28 Pf Medicament Ellenanyag-drog konjugátum és alkalmazása rák kezelésében történõ alkalmazásra
DK3134438T3 (da) 2014-04-25 2020-12-07 Pf Medicament IGF-1R-antistof og anvendelse heraf som adresseringsvehikel til behandling af cancer
CN104230916B (zh) * 2014-09-30 2020-04-28 上海化学试剂研究所有限公司 一种异噻唑啉酮类化合物及其制备方法和应用
EP3546473B1 (en) 2014-12-16 2025-12-10 Kayla Therapeutics Fluorinated cyclic [(2',5')p(3',5')p]-dinucleotides for cytokine induction
EA035817B1 (ru) 2015-03-10 2020-08-14 Адуро Байотек, Инк. Композиции и способы для активации сигналинга, зависимого от "гена стимулятора интерферона"
CA2989269C (en) * 2015-06-15 2020-09-22 Robert Yongxin Zhao Hydrophilic linkers for conjugation of a cytotoxic agent or chromophore molecule to a cell-binding molecule
WO2017051254A1 (en) * 2015-09-25 2017-03-30 Legochem Biosciences, Inc. Compositions and methods related to anti-egfr antibody drug conjugates
US20180369268A1 (en) 2015-12-16 2018-12-27 Aduro Biotech, Inc. Methods for identifying inhibitors of "stimulator of interferon gene"- dependent interferon production
US11129910B2 (en) * 2016-02-04 2021-09-28 Hangzhou Dac Biotech Co., Ltd. Specific conjugation linkers, specific immunoconjugates thereof, methods of making and uses such conjugates thereof
PE20210255A1 (es) 2016-12-01 2021-02-10 Takeda Pharmaceuticals Co Dinucleotido ciclico como agonistas de sting (estimulador de genes de interferon)

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4127687A (en) * 1976-07-19 1978-11-28 Rohm And Haas Company Prevention of fouling of marine structures such as boat hulls
WO2016064749A2 (en) * 2014-10-20 2016-04-28 Igenica Biotherapeutics, Inc. Novel antibody-drug conjugates and related compounds, compositions, and methods of use

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