CN103764170A - 新的结合剂-药物缀合物(adc)及其用途 - Google Patents

新的结合剂-药物缀合物(adc)及其用途 Download PDF

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Publication number
CN103764170A
CN103764170A CN201280028243.5A CN201280028243A CN103764170A CN 103764170 A CN103764170 A CN 103764170A CN 201280028243 A CN201280028243 A CN 201280028243A CN 103764170 A CN103764170 A CN 103764170A
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group
methyl
represents hydrogen
formula
site
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CN201280028243.5A
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Chinese (zh)
Inventor
H-G.勒亨
S.埃尔谢赫
R.贝尔
S.布鲁德
B.斯特尔特-路德维希
H.耶里森
C.马勒特
S.格勒文
H.佩特鲁尔
J.舒马赫
L.林登
J.威卢达
C.C.科皮茨
S.戈尔菲尔
I.黑斯勒
A.哈伦加
K-H.蒂劳赫
S.博尔科夫斯基
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Seagen Inc
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Seattle Genetics Inc
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Publication of CN103764170A publication Critical patent/CN103764170A/zh
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111712264A (zh) * 2017-12-19 2020-09-25 拜斯科阿迪有限公司 特异于epha2的双环肽配体
WO2022105878A1 (en) * 2020-11-20 2022-05-27 Bliss Biopharmaceutical (Hangzhou) Co., Ltd. Modified egfr antibody with reduced affinity, drug conjugate, and use thereof

Families Citing this family (70)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AR076284A1 (es) 2009-04-29 2011-06-01 Bayer Schering Pharma Ag Inmunoconjugados de antimesotelina y usos de los mismos
MX2012006593A (es) * 2009-12-09 2012-06-28 Bayer Pharma AG Anticuerpos anti-c4.4a y usos de los mismos.
CN103200950B (zh) * 2010-06-10 2016-03-16 西雅图基因公司 新颖的耳他汀衍生物及其用途
US8987209B2 (en) 2010-09-29 2015-03-24 Seattle Genetics, Inc. N-carboxyalkyl-auristatin and the use thereof
ES2543888T3 (es) 2011-03-16 2015-08-25 Seattle Genetics, Inc. N-carboxialquil-auristatinas y su utilización
SG194567A1 (en) 2011-04-21 2013-12-30 Seattle Genetics Inc Novel binder-drug conjugates (adcs) and their use
MX2014007121A (es) * 2011-12-14 2014-09-04 Seattle Genetics Inc Nuevos conjugados de principio activo-ligante (adc) y su uso.
US10226535B2 (en) 2012-12-10 2019-03-12 Mersana Therapeutics, Inc. Auristatin compounds and conjugates thereof
EP2927227A4 (en) * 2013-01-03 2015-12-30 Celltrion Inc ANTIBODY CONCENTRATOR REMEDY CONJUGATE, METHOD OF MANUFACTURING THEREOF, AND ANTIBODY TOGETHER THEREWITH
HK1220626A1 (zh) 2013-03-15 2017-05-12 The Centre For Drug Research And Development 具细胞毒性和抗有丝分裂的化合物以及其使用方法
FR3005051A1 (fr) * 2013-04-25 2014-10-31 Pf Medicament Derives de la dolastatine 10 et d'auristatines
BR112015030514A2 (pt) 2013-06-04 2017-08-29 Cytomx Therapeutics Inc Composições e métodos para conjugação de anticorpos ativáveis
TR201909034T4 (tr) * 2013-10-25 2019-07-22 Bayer Pharma AG Yeni bir stabil formülasyon.
BR112016012410A2 (pt) * 2013-12-16 2017-09-26 Genentech Inc conjugado de droga e anticorpo, composto conjugado de droga e anticorpo, composto não-peptídico, método de tratamento de doenças em seres humanos e composição farmacêutica
WO2015095301A2 (en) 2013-12-17 2015-06-25 Irm Llc Cytotoxic peptides and conjugates thereof
AU2014372833B2 (en) 2013-12-23 2019-08-22 Bayer Pharma Aktiengesellschaft Antibody drug conjugates (ADCs) with kinesin spindel protein (KSP)
MX2016008448A (es) 2013-12-27 2017-01-09 Zymeworks Inc Conjugados de var2csa-farmaco.
KR102384740B1 (ko) 2013-12-27 2022-04-07 자임워크스 인코포레이티드 약물 접합체를 위한 설폰아마이드-함유 연결 시스템
JP6417421B2 (ja) 2014-02-28 2018-11-07 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.Hangzhou Dac Biotech Co.,Ltd. 荷電連結体及び共役体のためのその使用
US9260478B2 (en) 2014-04-04 2016-02-16 Shanghui Hu Potent and efficient cytotoxic peptides and antibody-drug conjugates thereof and their synthesis
RU2747989C2 (ru) * 2014-05-28 2021-05-18 Эдженсис, Инк. Производные пептидов долапроин-долаизолейина
US9884817B2 (en) 2014-06-13 2018-02-06 Novartis Ag Auristatin derivatives and conjugates thereof
ES2905569T3 (es) 2014-09-17 2022-04-11 Zymeworks Inc Compuestos citotóxicos y antimitóticos y métodos para utilizarlos
CN105820248A (zh) * 2015-01-07 2016-08-03 上海张江生物技术有限公司 一种新型抗egfr单克隆抗体的制备方法及应用
CN111150851A (zh) * 2015-02-15 2020-05-15 江苏恒瑞医药股份有限公司 配体-细胞毒性药物偶联物、其制备方法及其应用
PT3271329T (pt) * 2015-03-19 2021-10-25 Hangzhou Dac Biotech Co Ltd Novos ligantes hidrofílicos e conjugados ligando-fármaco dos mesmos
CA2982536C (en) 2015-04-17 2023-04-18 Spring Bioscience Corporation Antibodies, compositions, and immunohistochemistry methods for detecting c4.4a
EP3286172B1 (en) 2015-04-23 2019-06-12 Constellation Pharmaceuticals, Inc. Lsd1 inhibitors and uses thereof
CN116726190A (zh) * 2015-06-20 2023-09-12 杭州多禧生物科技有限公司 澳瑞他汀类似物及其与细胞结合分子的共轭偶联物
SG11201710639YA (en) 2015-06-22 2018-01-30 Bayer Pharma AG Antibody drug conjugates (adcs) and antibody prodrug conjugates (apdcs) with enzymatically cleavable groups
EP3325497B1 (en) * 2015-07-24 2020-09-02 Arizona Board of Regents on behalf of Arizona State University Quinstatin compounds
WO2017058808A1 (en) 2015-10-02 2017-04-06 Sirenas Llc Anti-cancer compounds and conjugates thereof
WO2017060322A2 (en) 2015-10-10 2017-04-13 Bayer Pharma Aktiengesellschaft Ptefb-inhibitor-adc
JP2019510000A (ja) * 2016-02-26 2019-04-11 ジエンス ヘンルイ メデイシンカンパニー リミテッドJiangsu Hengrui Medicine Co.,Ltd. 新規トキシン及びその中間体の製造方法
WO2017161206A1 (en) 2016-03-16 2017-09-21 Halozyme, Inc. Conjugates containing conditionally active antibodies or antigen-binding fragments thereof, and methods of use
SG10202008909VA (en) 2016-03-24 2020-10-29 Bayer Pharma AG Prodrugs of cytotoxic active agents having enzymatically cleavable groups
WO2017216028A1 (en) 2016-06-15 2017-12-21 Bayer Pharma Aktiengesellschaft Specific antibody-drug-conjugates (adcs) with ksp inhibitors and anti-cd123-antibodies
TWI750194B (zh) * 2016-07-05 2021-12-21 大陸商江蘇恆瑞醫藥股份有限公司 Egfr抗體-藥物偶聯物及其在醫藥上的應用
US10517958B2 (en) 2016-10-04 2019-12-31 Zymeworks Inc. Compositions and methods for the treatment of platinum-drug resistant cancer
LT3532459T (lt) 2016-10-26 2023-11-10 Constellation Pharmaceuticals, Inc. Lsd1 inhibitoriai ir jų medicininis panaudojimas
EP3554544A4 (en) 2016-12-16 2020-07-29 Bluefin Biomedicine, Inc. ANTI-PROTEIN 1 ANTIBODY CONTAINING AN ANTI-CUB DOMAIN (CDCP1), ANTIBODY-DRUG CONJUGATES AND THEIR METHODS OF USE
AU2017380871C1 (en) 2016-12-21 2025-05-15 Bayer Aktiengesellschaft Antibody drug conjugates (ADCs) having enzymatically cleavable groups
US12059472B2 (en) 2016-12-21 2024-08-13 Bayer Aktiengesellschaft Prodrugs of cytotoxic active agents having enzymatically cleavable groups
US11433140B2 (en) 2016-12-21 2022-09-06 Bayer Pharma Aktiengesellschaft Specific antibody drug conjugates (ADCs) having KSP inhibitors
CN110325205B (zh) 2016-12-22 2023-08-15 库尔生物制药有限公司 T细胞调节性多聚体多肽及其使用方法
KR20210125094A (ko) * 2017-04-06 2021-10-15 항저우 디에이씨 바이오테크 씨오, 엘티디 비스-링키지를 사용한 세포독성 약물의 접합
US20200230220A1 (en) * 2017-07-12 2020-07-23 Nouscom Ag Neoantigen vaccine composition for treatment of cancer
US10646585B2 (en) 2017-09-15 2020-05-12 Hangzhou Dac Biotech Co., Ltd. Hydrophilic linkers and ligand-drug conjugates thereof
CN107998453B (zh) * 2017-12-12 2020-09-25 中山大学附属第一医院 一种表面改性的脱细胞基质及其改性方法
EP3746079A1 (en) 2018-01-31 2020-12-09 Bayer Aktiengesellschaft Antibody drug conjugates (adcs) with nampt inhibitors
WO2019183438A1 (en) 2018-03-23 2019-09-26 Seattle Genetics, Inc. Use of antibody drug conjugates comprising tubulin disrupting agents to treat solid tumor
WO2021013693A1 (en) 2019-07-23 2021-01-28 Bayer Pharma Aktiengesellschaft Antibody drug conjugates (adcs) with nampt inhibitors
WO2021081232A1 (en) 2019-10-23 2021-04-29 Cue Biopharma, Inc. Modified cytotoxic t cells and methods of use thereof
EP4054602A4 (en) 2019-11-08 2023-12-06 Mayo Foundation for Medical Education and Research EPHA3 TARGETED CAR-T CELLS FOR TREATING TUMORS
AU2021206218A1 (en) * 2020-01-06 2022-07-07 Cytomx Therapeutics, Inc. Auristatin-related compounds, conjugated auristatin-related compounds, and methods of use thereof
IL296209A (en) 2020-05-12 2022-11-01 Cue Biopharma Inc Multimeric t-cell modulatory polypeptides and methods of using them
JP2023552290A (ja) * 2020-11-19 2023-12-15 アーディアジェン コーポレーション Gpc3結合剤、そのコンジュゲートおよびその使用方法
WO2022216848A1 (en) * 2021-04-06 2022-10-13 Hemoshear Therapeutics, Inc. Methods of treating methylmalonic acidemia and propionic acidemia
CA3230737A1 (en) 2021-09-03 2023-03-09 Toray Industries, Inc. Pharmaceutical composition for cancer treatment and/or prevention
WO2023061405A1 (zh) * 2021-10-12 2023-04-20 成都科岭源医药技术有限公司 一种高稳定性的靶向接头-药物偶联物
EP4433096A1 (en) 2021-11-19 2024-09-25 Ardeagen Corporation Gpc3 binding agents, conjugates thereof and methods of using the same
CN114149343B (zh) * 2021-12-06 2023-10-20 中节能万润股份有限公司 一种高纯度1,4-二氰基-2-丁烯的制备方法
EP4536278A4 (en) 2022-06-07 2026-08-12 Actinium Pharmaceuticals Inc CHELETARIANS AND BIFUNCTIONAL CONJUGATES
JP2025519421A (ja) * 2022-06-09 2025-06-26 ベイジーン スイッツァランド ゲーエムベーハー 抗体薬物複合体
AU2023313117A1 (en) * 2022-07-27 2025-02-13 Mediboston Limited Auristatin derivatives and conjugates thereof
EP4653017A1 (en) 2023-01-18 2025-11-26 Tyligand Bioscience (Shanghai) Limited Antibody-drug conjugate and use thereof
CN116239513B (zh) * 2023-05-05 2023-08-18 天津凯莱英制药有限公司 Mmae关键中间体的制备方法、mmae的制备方法和抗体偶联药物
WO2025148868A1 (zh) 2024-01-08 2025-07-17 泰励生物科技(上海)有限公司 一种抗体偶联药物及其用途
WO2026039642A1 (en) 2024-08-16 2026-02-19 Ardeagen Corporation Anti-mesothelin antibody conjugates and methods of use thereof
WO2026145631A1 (zh) * 2024-12-31 2026-07-09 上海复宏汉霖生物技术股份有限公司 一种配体-药物偶联物及制备方法和应用

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005101017A1 (en) * 2004-04-07 2005-10-27 Genentech, Inc. Mass spectrometry of antibody conjugates
CN1938046A (zh) * 2003-11-06 2007-03-28 西雅图基因公司 能够与配体偶联的单甲基缬氨酸化合物
WO2009099728A1 (en) * 2008-01-31 2009-08-13 Genentech, Inc. Anti-cd79b antibodies and immunoconjugates and methods of use
WO2009140242A1 (en) * 2008-05-13 2009-11-19 Genentech, Inc. Analysis of antibody drug conjugates by bead-based affinity capture and mass spectrometry

Family Cites Families (103)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4463776A (en) 1980-06-13 1984-08-07 Crosby Valve And Engineering Company, Limited Fluid pressure relief system actuator
FR2499737B1 (fr) 1981-02-12 1985-07-05 Laudren Cie Sa Ets M Circuit d'alarme pour systemes de surveillance de postes telephoniques publics a prepaiement
US4714681A (en) 1981-07-01 1987-12-22 The Board Of Reagents, The University Of Texas System Cancer Center Quadroma cells and trioma cells and methods for the production of same
US4474893A (en) 1981-07-01 1984-10-02 The University of Texas System Cancer Center Recombinant monoclonal antibodies
EP0071286B1 (en) 1981-07-30 1985-08-28 Shell Internationale Researchmaatschappij B.V. Process for the preparation of carbonate esters
DE3223868A1 (de) 1982-06-25 1983-12-29 Friedrich 8541 Röttenbach Schweinfurter Turbinenpumpe
GR81257B (enExample) 1982-12-04 1984-12-11 Lilly Industries Ltd
GB8308235D0 (en) 1983-03-25 1983-05-05 Celltech Ltd Polypeptides
US4816567A (en) 1983-04-08 1989-03-28 Genentech, Inc. Recombinant immunoglobin preparations
GB2163883B (en) 1984-08-29 1989-02-01 British Aerospace Data processing arrangement
FR2576708B1 (fr) 1985-01-25 1987-04-30 Novatome Generateur de vapeur dont le fluide caloporteur est du metal liquide et dont la detection des fuites est effectuee par prelevement de ce metal liquide
US4606662A (en) 1985-01-31 1986-08-19 International Business Machines Corporation Single stepping motor ribbon and correction feed and lift system
US4640839A (en) 1985-07-01 1987-02-03 Nestec S.A. Agglomeration process
DE8808645U1 (de) 1988-07-06 1988-08-25 Hofer, Daniel, 7730 Villingen-Schwenningen Anzeigeeinrichtung für Feuerlöscher
US4925648A (en) 1988-07-29 1990-05-15 Immunomedics, Inc. Detection and treatment of infectious and inflammatory lesions
US5601819A (en) 1988-08-11 1997-02-11 The General Hospital Corporation Bispecific antibodies for selective immune regulation and for selective immune cell binding
EP0739904A1 (en) 1989-06-29 1996-10-30 Medarex, Inc. Bispecific reagents for aids therapy
JP3360108B2 (ja) 1989-10-20 2002-12-24 メダレックス インク. 二つのエフェクター機能を有する二元特異性異種抗体
US5270163A (en) 1990-06-11 1993-12-14 University Research Corporation Methods for identifying nucleic acid ligands
DK0553244T4 (da) 1990-10-05 2005-08-01 Celldex Therapeutics Inc Målrettet immunostimulering med bispecifikke reagenser
AU8727291A (en) 1990-10-29 1992-06-11 Cetus Oncology Corporation Bispecific antibodies, method of production, and uses thereof
AU658396B2 (en) 1991-03-06 1995-04-13 Merck Patent Gesellschaft Mit Beschrankter Haftung Humanized and chimeric monoclonal antibodies
EP0582595A1 (en) 1991-04-26 1994-02-16 Surface Active Limited Novel antibodies, and methods for their use
EP1306095A3 (en) 1992-03-05 2003-06-25 Board Of Regents, The University Of Texas System Methods and compositions for targeting the vasculature of solid tumors
ATE244306T1 (de) 1994-12-20 2003-07-15 Merck Patent Gmbh Monoklonaler antikörper gegen das alpha-v- integrin
EP0859841B1 (en) 1995-08-18 2002-06-19 MorphoSys AG Protein/(poly)peptide libraries
US6150508A (en) 1996-03-25 2000-11-21 Northwest Biotherapeutics, Inc. Monoclonal antibodies specific for the extracellular domain of prostate-specific membrane antigen
DE69735294T2 (de) 1996-03-25 2006-09-21 Medarex Inc. Spezifische monoklonale antikörper für die extrazelluläre domäne von protasta-spezifischem membranantigen
EP1098666B1 (en) * 1998-07-17 2013-01-16 The United States of America, represented by the Secretary, Department of Health and Human Services Water-soluble drugs and methods for their production
MXPA01011502A (es) 1999-05-14 2003-08-20 Boehringer Ingelheim Pharma Compuestos de tipo profarmaco anti-tumorigenos, activados por enzimas.
EE200100603A (et) 1999-05-14 2003-02-17 Imclone Systems Incorporated Inimese refraktaarsete kasvajate ravi epidermaalse kasvufaktori retseptori antagonistidega
ES2277846T3 (es) 1999-07-29 2007-08-01 Medarex, Inc. Anticuerpos monoclonales humanos para antigeno prostatico especifico.
US6323315B1 (en) 1999-09-10 2001-11-27 Basf Aktiengesellschaft Dolastatin peptides
EP1220919A2 (en) 1999-09-29 2002-07-10 Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts Metastasis-associated antigen c4.4a
YU63302A (sh) 2000-02-25 2005-09-19 The Government Of The Un.Stat. Anti-egfrv iii scfvs sa pojačanom citotoksičnošću i povećanim prinosom, imunotoksini na bazi istog i metodi za upotrebu na bazi istog
CA2409361A1 (en) 2000-05-19 2001-11-22 Scancell Limited Humanised antibodies to the epidermal growth factor receptor
US7288390B2 (en) 2000-08-07 2007-10-30 Centocor, Inc. Anti-dual integrin antibodies, compositions, methods and uses
AUPR395801A0 (en) 2001-03-26 2001-04-26 Austin Research Institute, The Antibodies against cancer
CZ20033208A3 (en) 2001-04-26 2004-03-17 Biogen, Inc. Cripto blocking antibodies and uses thereof
US6884869B2 (en) 2001-04-30 2005-04-26 Seattle Genetics, Inc. Pentapeptide compounds and uses related thereto
DK1392359T4 (da) 2001-05-11 2013-06-10 Ludwig Inst For Cancer Res Ltd Specifikke bindingsproteiner og deres anvendelser.
KR100945108B1 (ko) 2001-06-13 2010-03-02 젠맵 에이/에스 표피 성장 인자 수용체 (egfr)에 대한 인간모노클로날 항체
US7595378B2 (en) 2001-06-13 2009-09-29 Genmab A/S Human monoclonal antibodies to epidermal growth factor receptor (EGFR)
US7091186B2 (en) 2001-09-24 2006-08-15 Seattle Genetics, Inc. p-Amidobenzylethers in drug delivery agents
WO2003026577A2 (en) 2001-09-24 2003-04-03 Seattle Genetics, Inc. P-amidobenzylethers in drug delivery agents
MY147019A (en) 2002-03-13 2012-10-15 Biogen Idec Inc Anti-alpha v beta 6 antibodies
EP1494693B1 (en) 2002-03-22 2010-12-08 Biogen Idec MA Inc. Cripto-specific antibodies
ES2524767T3 (es) 2002-06-14 2014-12-12 Immunomedics, Inc. Anticuerpo monoclonal humanizado HPAM4
ES2369542T3 (es) 2002-07-31 2011-12-01 Seattle Genetics, Inc. Conjugados de auristatina y su uso para tratar cáncer, una enfermedad autoinmune o una enfermedad infecciosa.
EP1617864A4 (en) 2003-04-11 2006-06-21 Medimmune Inc EPHA2 AND NON-NEOPLASTIC HYPERPROLIFERATIVE CELL TROUBLESHOOTING
MXPA05014155A (es) 2003-06-27 2006-05-25 Abgenix Inc Anticuerpos dirigidos a los mutantes de delecion de receptor de factor de crecimiento epidermico y sus usos.
EA014640B1 (ru) 2003-07-21 2010-12-30 Иммьюноджен, Инк. Антитело или его эпитоп-связывающий фрагмент, которые связываются с гликотопом са6, и способы их применения
US20050142133A1 (en) 2003-12-03 2005-06-30 Xencor, Inc. Optimized proteins that target the epidermal growth factor receptor
US7767792B2 (en) 2004-02-20 2010-08-03 Ludwig Institute For Cancer Research Ltd. Antibodies to EGF receptor epitope peptides
ES2387809T3 (es) 2004-03-19 2012-10-02 Imclone Llc Anticuerpo frente al receptor del factor de crecimiento epidérmico humano
CA2583137A1 (en) * 2004-10-05 2006-04-20 Genentech, Inc. Therapeutic agents with decreased toxicity
JP2008519863A (ja) 2004-11-12 2008-06-12 シアトル ジェネティクス インコーポレイティッド N末端にアミノ安息香酸単位を有するオーリスタチン
DE602005022928D1 (de) * 2004-11-30 2010-09-23 Abgenix Inc Antikörper gegen gpnmb und ihre verwendungen
KR101281501B1 (ko) 2004-12-09 2013-07-15 얀센 바이오테크 인코포레이티드 항인테그린 면역 컨쥬게이트, 방법 및 용도
DK1841793T3 (da) 2005-01-07 2010-07-19 Diadexus Inc Ovr110-antistofsammensætninger og fremgangsmåder til anvendelse deraf
US7811572B2 (en) 2005-08-24 2010-10-12 Immunogen, Inc. Process for preparing purified drug conjugates
US8207303B2 (en) 2005-02-18 2012-06-26 Medarex, Inc. Monoclonal antibodies against CD30 lacking in fucosyl residues
ES2708763T3 (es) 2005-07-07 2019-04-11 Seattle Genetics Inc Compuestos de monometilvalina que tienen modificaciones de la cadena lateral de fenilalanina en el extremo C
WO2007008848A2 (en) 2005-07-07 2007-01-18 Seattle Genetics, Inc. Monomethylvaline compounds having phenylalanine carboxy modifications at the c-terminus
KR20080080482A (ko) * 2005-09-07 2008-09-04 메디뮨 엘엘씨 독소가 컨쥬게이트된 eph 수용체 항체
EP1934261B1 (en) 2005-09-26 2014-10-29 Medarex, L.L.C. Human monoclonal antibodies to cd70
EP1957115B8 (en) * 2005-11-10 2014-03-05 Celldex Therapeutics, Inc. Method of treating ovarian and renal cancer using antibodies against t cell immunoglobulin domain and mucin domain 1 (tim-1) antigen
DOP2006000277A (es) 2005-12-12 2007-08-31 Bayer Pharmaceuticals Corp Anticuerpos anti mn y métodos para su utilización
PT2032606E (pt) * 2006-05-30 2014-02-05 Genentech Inc Anticorpos e imunoconjugados e respetivas utilizações
WO2008004834A1 (en) 2006-07-06 2008-01-10 Isu Abxis Co., Ltd Humanized monoclonal antibody highly binding to epidermal growth factor receptor, egf receptor
US8323653B2 (en) 2006-09-08 2012-12-04 Medimmune, Llc Humanized anti-CD19 antibodies and their use in treatment of oncology, transplantation and autoimmune disease
WO2008028686A2 (en) 2006-09-10 2008-03-13 Glycotope Gmbh Use of human cells of myeloid leukaemia origin for expression of antibodies
EP2064240A2 (en) 2006-09-18 2009-06-03 Xencor, Inc. Optimized antibodies that target hm1.24
WO2008133641A2 (en) * 2006-10-11 2008-11-06 Curagen Corporation Antibodies directed to gpnmb and uses thereof
EP1914242A1 (en) 2006-10-19 2008-04-23 Sanofi-Aventis Novel anti-CD38 antibodies for the treatment of cancer
PL2099823T5 (pl) 2006-12-01 2023-02-20 Seagen Inc. Wariant środków wiążących cel i jego zastosowania
US8652466B2 (en) 2006-12-08 2014-02-18 Macrogenics, Inc. Methods for the treatment of disease using immunoglobulins having Fc regions with altered affinities for FcγRactivating and FcγRinhibiting
WO2008092117A2 (en) 2007-01-25 2008-07-31 Xencor, Inc. Immunoglobulins with modifications in the fcr binding region
JP5532486B2 (ja) 2007-08-14 2014-06-25 ルードヴィッヒ インスティテュート フォー キャンサー リサーチ Egf受容体を標的とするモノクローナル抗体175ならびにその誘導体および用途
EP2185188B1 (en) 2007-08-22 2014-08-06 Medarex, L.L.C. Site-specific attachment of drugs or other agents to engineered antibodies with c-terminal extensions
EP2185574B1 (en) 2007-09-07 2013-05-08 Agensys, Inc. Antibodies and related molecules that bind to 24p4c12 proteins
US8039597B2 (en) 2007-09-07 2011-10-18 Agensys, Inc. Antibodies and related molecules that bind to 24P4C12 proteins
HRP20150074T1 (hr) * 2007-10-01 2015-03-13 Bristol-Myers Squibb Company Humana antitijela koja se vežu za mezotelin i njihove uporabe
KR101559599B1 (ko) 2007-11-26 2015-10-12 바이엘 인텔렉쳐 프로퍼티 게엠베하 항-메소텔린 항체 및 이의 용도
PL2242772T3 (pl) 2007-12-26 2015-05-29 Biotest Ag Immunokonjugaty nakierowane na CD138 i ich zastosowanie
ES2475201T3 (es) 2007-12-26 2014-07-10 Biotest Ag Agentes dirigidos contra CD138 y usos de los mismos
CA2716516A1 (en) 2008-02-25 2009-09-03 Prittie Family Trust 89 Raised image plate construction with regions of varying support thickness beneath the image areas
US9879267B2 (en) * 2008-03-14 2018-01-30 Genentech, Inc. Genetic variations associated with drug resistance
WO2009117531A1 (en) 2008-03-18 2009-09-24 Seattle Genetics, Inc. Auristatin drug linker conjugates
SG189730A1 (en) 2008-04-02 2013-05-31 Macrogenics Inc Her2/neu-specific antibodies and methods of using same
MX2011001927A (es) 2008-08-29 2011-04-21 Symphogen As Composiciones de anticuerpo recombinante anti-receptor de factor de crecimiento epidermico.
AR075982A1 (es) 2009-03-31 2011-05-11 Roche Glycart Ag Terapia de combinacion de un anticuerpo afucosilado y una o mas de las citoquinas seleccionadas de gm- csf humano, m -csf humano y/o il-3 humano y composicion
MX2011009620A (es) 2009-03-31 2011-10-19 Roche Glycart Ag Tratamiento de cancer con un anticuerpo de inmunoglobulina g1 (igg1) humanizado anti receptor de factor de crecimiento epidermico (anti-egfr) e irinotecan.
JP2012529895A (ja) 2009-06-19 2012-11-29 メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング 抗egfr抗体の癌療法における有効性を決定するためのバイオマーカーおよび方法
MX2012004029A (es) 2009-10-07 2012-05-08 Macrogenics Inc Polipeptidos que contienen la region fc que exhiben funcion efectora mejorada debido a alteraciones del grado de fucosilacion, y metodos para su uso.
MX2012006593A (es) 2009-12-09 2012-06-28 Bayer Pharma AG Anticuerpos anti-c4.4a y usos de los mismos.
CN103200950B (zh) * 2010-06-10 2016-03-16 西雅图基因公司 新颖的耳他汀衍生物及其用途
US8987209B2 (en) 2010-09-29 2015-03-24 Seattle Genetics, Inc. N-carboxyalkyl-auristatin and the use thereof
AU2011349443B2 (en) * 2010-12-20 2015-12-24 Genentech, Inc. Anti-mesothelin antibodies and immunoconjugates
US9302799B2 (en) * 2011-02-17 2016-04-05 Sabic Global Technologies B.V. Method for bulk transporting 2,6-xylenol susceptible to oxidative discoloration
ES2543888T3 (es) 2011-03-16 2015-08-25 Seattle Genetics, Inc. N-carboxialquil-auristatinas y su utilización
SG194567A1 (en) 2011-04-21 2013-12-30 Seattle Genetics Inc Novel binder-drug conjugates (adcs) and their use
MX2014007121A (es) 2011-12-14 2014-09-04 Seattle Genetics Inc Nuevos conjugados de principio activo-ligante (adc) y su uso.

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1938046A (zh) * 2003-11-06 2007-03-28 西雅图基因公司 能够与配体偶联的单甲基缬氨酸化合物
WO2005101017A1 (en) * 2004-04-07 2005-10-27 Genentech, Inc. Mass spectrometry of antibody conjugates
WO2009099728A1 (en) * 2008-01-31 2009-08-13 Genentech, Inc. Anti-cd79b antibodies and immunoconjugates and methods of use
WO2009140242A1 (en) * 2008-05-13 2009-11-19 Genentech, Inc. Analysis of antibody drug conjugates by bead-based affinity capture and mass spectrometry

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111712264A (zh) * 2017-12-19 2020-09-25 拜斯科阿迪有限公司 特异于epha2的双环肽配体
WO2022105878A1 (en) * 2020-11-20 2022-05-27 Bliss Biopharmaceutical (Hangzhou) Co., Ltd. Modified egfr antibody with reduced affinity, drug conjugate, and use thereof
CN116419929A (zh) * 2020-11-20 2023-07-11 百力司康生物医药(杭州)有限公司 亲和力降低的改造的egfr抗体、药物偶联物及其用途
CN116419929B (zh) * 2020-11-20 2024-03-08 百力司康生物医药(杭州)有限公司 亲和力降低的改造的egfr抗体、药物偶联物及其用途
US12605457B2 (en) 2020-11-20 2026-04-21 Bliss Biopharmaceutical (Hangzhou) Co., Ltd. Modified EGFR antibody with reduced affinity, drug conjugate, and use thereof

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