DK3099692T5 - Bifunktionelle cytotoksiske midler - Google Patents

Bifunktionelle cytotoksiske midler Download PDF

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Publication number
DK3099692T5
DK3099692T5 DK15708273.6T DK15708273T DK3099692T5 DK 3099692 T5 DK3099692 T5 DK 3099692T5 DK 15708273 T DK15708273 T DK 15708273T DK 3099692 T5 DK3099692 T5 DK 3099692T5
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cytotoxic agents
bifunctional
bifunctional cytotoxic
agents
cytotoxic
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DK15708273.6T
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English (en)
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DK3099692T3 (da
Inventor
Andreas Maderna
Matthew David Doroski
Zecheng Chen
Hud Lawrence Risley
Jeffrey Michael Casavant
Christopher John O'donnell
Alexander M Porte
Chakrapani Subramanyam
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Pfizer
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    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
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Families Citing this family (35)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SG185428A1 (en) 2010-06-08 2012-12-28 Genentech Inc Cysteine engineered antibodies and conjugates
EP3539982B1 (en) 2011-12-23 2025-02-19 Pfizer Inc. Engineered antibody constant regions for site-specific conjugation and methods and uses therefor
CA2937731C (en) * 2014-01-27 2019-09-24 Pfizer Inc. Bifunctional cytotoxic agents
EP3160513B1 (en) * 2014-06-30 2020-02-12 Glykos Finland Oy Saccharide derivative of a toxic payload and antibody conjugates thereof
KR102051503B1 (ko) 2014-08-28 2019-12-03 화이자 인코포레이티드 항체 약물 접합체에 사용하기 위한 안정성-조정 링커
TW201625688A (zh) 2014-09-12 2016-07-16 建南德克公司 經半胱胺酸改造之抗體及接合物
US11566082B2 (en) 2014-11-17 2023-01-31 Cytiva Bioprocess R&D Ab Mutated immunoglobulin-binding polypeptides
WO2016151432A1 (en) * 2015-03-20 2016-09-29 Pfizer Inc. Bifunctional cytotoxic agents containing the cti pharmacophore
MX383558B (es) 2015-08-12 2025-03-14 Pfizer Cisteinas de anticuerpo con capuchon y sin capuchon y su uso en conjugacion de anticuerpo-farmaco
WO2017064675A1 (en) 2015-10-16 2017-04-20 Genentech, Inc. Hindered disulfide drug conjugates
DE102016105449A1 (de) * 2015-10-29 2017-05-04 Georg-August-Universität Göttingen Stiftung Öffentlichen Rechts Bifunktionale Prodrugs
US10689458B2 (en) 2015-11-30 2020-06-23 Pfizer Inc. Site specific HER2 antibody drug conjugates
ES2916099T3 (es) * 2016-03-14 2022-06-28 Spirochem Ag Método de preparación de biciclo[1.1.1]pentanos sustituidos
US10703774B2 (en) 2016-09-30 2020-07-07 Ge Healthcare Bioprocess R&D Ab Separation method
US10654887B2 (en) 2016-05-11 2020-05-19 Ge Healthcare Bio-Process R&D Ab Separation matrix
ES2909833T3 (es) 2016-05-11 2022-05-10 Cytiva Bioprocess R & D Ab Método de limpieza y/o desinfección de una matriz de separación
US10889615B2 (en) 2016-05-11 2021-01-12 Cytiva Bioprocess R&D Ab Mutated immunoglobulin-binding polypeptides
JP7106187B2 (ja) 2016-05-11 2022-07-26 サイティバ・バイオプロセス・アールアンドディ・アクチボラグ 分離マトリックスを保存する方法
US10730908B2 (en) 2016-05-11 2020-08-04 Ge Healthcare Bioprocess R&D Ab Separation method
ES2874974T3 (es) 2016-05-11 2021-11-05 Cytiva Bioprocess R & D Ab Matriz de separación
JP7031934B2 (ja) 2016-05-11 2022-03-08 サイティバ・バイオプロセス・アールアンドディ・アクチボラグ 分離マトリックス
EP3493853A1 (en) 2016-08-03 2019-06-12 Pfizer Inc Heteroaryl sulfone-based conjugation handles, methods for their preparation, and their use in synthesizing antibody drug conjugates
US12448411B2 (en) 2016-09-30 2025-10-21 Cytiva Bioprocess R&D Ab Separation method
EP3525826B1 (en) 2016-10-11 2020-07-22 Byondis B.V Non-linear self-immolative linkers and conjugates thereof
EP3525828B1 (en) 2016-10-17 2024-12-25 Pfizer Inc. Anti-edb antibodies and antibody-drug conjugates
SG10202110184XA (en) * 2017-03-15 2021-10-28 Silverback Therapeutics Inc Benzazepine compounds, conjugates, and uses thereof
US11364303B2 (en) 2017-09-29 2022-06-21 Pfizer Inc. Cysteine engineered antibody drug conjugates
MX2020004381A (es) * 2017-10-27 2020-08-20 Pfizer Anticuerpos y conjugados de anticuerpo-farmaco especificos para cd123 y usos de los mismos.
WO2019113227A1 (en) * 2017-12-06 2019-06-13 Yale University Prodrugs activated by reduction in the cytosol
SG11202105175WA (en) * 2018-11-20 2021-06-29 Regeneron Pharma Bis-octahydrophenanthrene carboxamide derivatives and protein conjugates thereof for use as lxr agonists
CN112986575B (zh) * 2020-12-29 2023-03-17 上海药明康德新药开发有限公司 一种串联式验证dna编码苗头化合物修饰抗体的方法
GB202306325D0 (en) * 2023-04-28 2023-06-14 Iksuda Therapeutics Ltd Antibody-drug conjugate compounds, and methods of use and treatment
EP4494656A1 (en) * 2023-07-21 2025-01-22 Simris Biologics GmbH Organic cytotoxin oligomers and uses thereof as a payload in antibody-drug conjugates
GB202415789D0 (en) * 2024-10-25 2024-12-11 Iksuda Therapeutics Ltd Antibody-drug conjugate compounds, and methods of use and treatment
WO2026093752A1 (en) * 2024-10-30 2026-05-07 Iksuda Therapeutics Limited Antibody conjugates targeting b7-h3

Family Cites Families (36)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2036891B (en) 1978-12-05 1983-05-05 Windsor Smith C Change speed gear
GB8308235D0 (en) 1983-03-25 1983-05-05 Celltech Ltd Polypeptides
US4816567A (en) 1983-04-08 1989-03-28 Genentech, Inc. Recombinant immunoglobin preparations
JPS6147500A (ja) 1984-08-15 1986-03-07 Res Dev Corp Of Japan キメラモノクロ−ナル抗体及びその製造法
EP0173494A3 (en) 1984-08-27 1987-11-25 The Board Of Trustees Of The Leland Stanford Junior University Chimeric receptors by dna splicing and expression
GB8422238D0 (en) 1984-09-03 1984-10-10 Neuberger M S Chimeric proteins
JPS61134325A (ja) 1984-12-04 1986-06-21 Teijin Ltd ハイブリツド抗体遺伝子の発現方法
EP0247091B1 (en) 1985-11-01 1993-09-29 Xoma Corporation Modular assembly of antibody genes, antibodies prepared thereby and use
US5225539A (en) 1986-03-27 1993-07-06 Medical Research Council Recombinant altered antibodies and methods of making altered antibodies
MX9203460A (es) * 1988-09-12 1992-09-01 Upjohn Co Nuevos analogos cc-1065 que tienen dos subunidades cpi.
JP3380237B2 (ja) * 1988-09-12 2003-02-24 ファルマシア・アンド・アップジョン・カンパニー ２のｃｐｉサブユニットを有する新規ｃｃ―１０６５アナログ類
US5530101A (en) 1988-12-28 1996-06-25 Protein Design Labs, Inc. Humanized immunoglobulins
DE3920358A1 (de) 1989-06-22 1991-01-17 Behringwerke Ag Bispezifische und oligospezifische, mono- und oligovalente antikoerperkonstrukte, ihre herstellung und verwendung
US5633425A (en) 1990-08-29 1997-05-27 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
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
AU8507191A (en) 1990-08-29 1992-03-30 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US5625126A (en) 1990-08-29 1997-04-29 Genpharm International, Inc. Transgenic non-human animals for producing heterologous antibodies
DE69233528T2 (de) 1991-11-25 2006-03-16 Enzon, Inc. Verfahren zur Herstellung von multivalenten antigenbindenden Proteinen
ATE279947T1 (de) 1996-03-18 2004-11-15 Univ Texas Immunglobulinähnliche domäne mit erhöhten halbwertszeiten
US8088387B2 (en) 2003-10-10 2012-01-03 Immunogen Inc. Method of targeting specific cell populations using cell-binding agent maytansinoid conjugates linked via a non-cleavable linker, said conjugates, and methods of making said conjugates
US7517903B2 (en) 2004-05-19 2009-04-14 Medarex, Inc. Cytotoxic compounds and conjugates
CN101010106A (zh) * 2004-06-30 2007-08-01 诺瓦提斯公司 抗体和Duocarmycin衍生物的缀合物作为抗肿瘤剂
EP1853294A4 (en) 2005-03-03 2010-01-27 Covx Technologies Ireland Ltd ANTIANGIOGENIC COMPOUNDS
AU2006294554B2 (en) * 2005-09-26 2013-03-21 E. R. Squibb & Sons, L.L.C. Antibody-drug conjugates and methods of use
US20090118349A1 (en) * 2007-08-16 2009-05-07 Onco-Pharmakon Incorporated Bis-alkylating agents and their use in cancer therapy
MX2011004625A (es) 2008-11-03 2011-07-20 Syntarga Bv Analogos cc-1065 novedosos y sus conjugados.
DE102009051799B4 (de) 2009-11-03 2021-07-01 Georg-August-Universität Göttingen Stiftung Öffentlichen Rechts Bifunktionale Prodrugs und Drugs
CA2930801C (en) 2010-11-05 2019-05-28 Rinat Neuroscience Corporation Engineered polypeptide conjugates and methods for making thereof using transglutaminase
US8852599B2 (en) * 2011-05-26 2014-10-07 Bristol-Myers Squibb Company Immunoconjugates, compositions for making them, and methods of making and use
SG11201400770SA (en) 2011-09-20 2014-04-28 Spirogen Sarl Pyrrolobenzodiazepines as unsymmetrical dimeric pbd compounds for inclusion in targeted conjugates
US8871908B2 (en) 2011-11-11 2014-10-28 Rinat Neuroscience Corp. Antibodies specific for Trop-2 and their uses
ES2656298T3 (es) 2012-11-05 2018-02-26 Pfizer Inc. Análogos de ayustoestatina
WO2014144878A2 (en) 2013-03-15 2014-09-18 The Scripps Research Institute Novel thiol & amino modifying reagents for protein chemistry and methods of use thereof
JP6993084B2 (ja) * 2013-08-12 2022-02-03 ジェネンテック， インコーポレイテッド １－（クロロメチル）－２，３－ジヒドロ－１ｈ－ベンゾ［ｅ］インドール二量体抗体 － 薬物コンジュゲート化合物、並びに使用及び処置の方法
CA2937731C (en) * 2014-01-27 2019-09-24 Pfizer Inc. Bifunctional cytotoxic agents

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