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RU2016132759A - Дуокармициновые adc, демонстрирующие улучшенную противоопухолевую активность in vivo - Google Patents

Дуокармициновые adc, демонстрирующие улучшенную противоопухолевую активность in vivo Download PDF

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Publication number
RU2016132759A
RU2016132759A RU2016132759A RU2016132759A RU2016132759A RU 2016132759 A RU2016132759 A RU 2016132759A RU 2016132759 A RU2016132759 A RU 2016132759A RU 2016132759 A RU2016132759 A RU 2016132759A RU 2016132759 A RU2016132759 A RU 2016132759A
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use according
compound
her2
cancer
human solid
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RU2016132759A
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RU2016132759A3 (ru
RU2689779C2 (ru
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Виллем ДОКТЕР
Патрик Хенри БЕСКЕР
Петер Йоханнес ГУДИНГС
Гейсбертус Франсискус Мария Верхейден
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Синтон Байофармасьютикалс Б. В.
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Claims (34)

1. Соединение формулы (I):
Figure 00000001
в которой Ат анти-HER2 представляет собой анти-HER2 антитело или фрагмент антитела,
n составляет 0-3,
m представляет собой среднее DAR (соотношение лекарственное средство/антитело) из 1 до 4,
R1 выбран из
Figure 00000002
y составляет 1-16, и
R2 выбран из
Figure 00000003
для применения в лечении человеческих солидных опухолей и гематологических злокачественных новообразований, экспрессирующих HER2.
2. Соединение для применения по п.1, при этом
Ат анти-HER2 представляет собой анти-HER2 антитело или фрагмент антитела,
n составляет 0-1,
m представляет собой среднее DAR от 1 до 4,
R1 выбран из
Figure 00000004
y составляет 1-16, и
R2 выбран из
Figure 00000005
3. Соединение для применения по п.1 или 2 формулы (II):
Figure 00000006
4. Соединение для применения по любому из пп.1-3, для применения в лечении человеческих солидных опухолей.
5. Соединение для применения по любому из пп.1-4, при этом экспрессирующая HER2 человеческая солидная опухоль представляет собой рак молочной железы, рак желудка, рак мочевого пузыря, рак яичников, рак легких, рак простаты, рак поджелудочной железы, колоректальный рак, плоскоклеточный рак головы и шеи или остеосаркому, и гематологическая злокачественная опухоль представляет собой острый лимфобластный лейкоз.
6. Соединение для применения по любому из пп.1-5, при этом экспрессирующая HER2 человеческая солидная опухоль представляет собой рак молочной железы или рак желудка.
7. Соединение для применения по любому из пп.1-6, при этом рак молочной железы является гормон-рецептор позитивным или негативным.
8. Соединение для применения по любому из пп.1-7, при этом человеческая солидная опухоль представляет собой HER2 IHC 2+ или 1+.
9. Соединение для применения по любому из пп.1-8, при этом человеческая солидная опухоль является HER2 FISH негативной.
10. Соединение для применения по любому из пп.1-9, при этом человеческая солидная опухоль представляет собой трижды негативный рак молочной железы.
11. Комбинация соединения для применения по любому из пп.1-10 с терапевтическим антителом и/или химиотерапевтическим агентом, для применения в лечении человеческих солидных опухолей и гематологических злокачественных опухолей, экспрессирующих HER2.
12. Комбинация для применения по п.11, для применения в лечении рака молочной железы, в частности трижды негативного рака молочной железы.
13. Комбинация для применения по п.11 или 12, при этом терапевтическое антитело представляет собой пертузумаб и химиотерапевтический агент представляет собой таксан, в частности доцетаксел или паклитаксел, или антрациклин, в частности доксорубицин, эпирубицин, даунорубицин или валрубицин.
14. Фармацевтическая композиция, содержащая соединение для применения по любому из пп.1-10 или комбинацию для применения по любому из пп.11-13 и одно или более фармацевтически приемлемых вспомогательных веществ.
15. Фармацевтическая композиция по п.14 в форме лиофилизированного порошка или замороженного раствора.
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Families Citing this family (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9901567B2 (en) 2007-08-01 2018-02-27 Syntarga B.V. Substituted CC-1065 analogs and their conjugates
JP5677970B2 (ja) 2008-11-03 2015-02-25 シンタルガ・ビーブイ 新規ｃｃ−１０６５類似体およびその複合体
NO3056203T3 (ru) 2010-04-21 2018-05-12
MX379355B (es) 2012-12-21 2025-03-11 Altrubio Inc Enlazadores autodestructivos hidrofilos y conjugados de los mismos.
ES2668984T3 (es) 2014-01-10 2018-05-23 Synthon Biopharmaceuticals B.V. CAF de duocarmicina para su uso en el tratamiento del cáncer de vejiga
HUE029672T2 (en) * 2014-01-10 2017-03-28 Synthon Biopharmaceuticals Bv Duokarmicin-ADCs for use in the treatment of endometrial cancer
MX373458B (es) 2014-01-10 2020-05-11 Byondis Bv Metodo para purificar conjugados de anticuerpo-farmaco enlazados a cisteina.
MX374342B (es) 2014-05-22 2025-03-06 Byondis Bv Conjugacion especifica de sitio de farmacos enlazadores con anticuerpos y conjugados farmaco-anticuerpo (adc) resultantes.
TWI695011B (zh) 2014-06-18 2020-06-01 美商梅爾莎納醫療公司 抗ｈｅｒ２表位之單株抗體及其使用之方法
WO2015195925A1 (en) 2014-06-18 2015-12-23 Mersana Therapeutics, Inc. Protein-polymer-drug conjugates and methods of using same
EP3157560A4 (en) * 2014-06-20 2018-02-21 Abgenomics International Inc. Her2 antibody-drug conjugates
SG11201610620UA (en) 2014-06-20 2017-01-27 Bioalliance Cv Anti-folate receptor aplha (fra) antibody-drug conjugates and methods of using thereof
JP6522806B2 (ja) 2015-07-10 2019-05-29 シントン・バイオファーマシューティカルズ・ビー．ブイ．Ｓｙｎｔｈｏｎ Ｂｉｏｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｂ．Ｖ． 抗体デュオカルマイシン薬物複合体を含む組成物
LT3352857T (lt) * 2015-09-22 2021-02-25 Byondis B.V. T-dm1 atsparių, vėžiu sergančių pacientų gydymas junginiu syd985
CN106729743B (zh) 2015-11-23 2021-09-21 四川科伦博泰生物医药股份有限公司 抗ErbB2抗体-药物偶联物及其组合物、制备方法和应用
JP2019501139A (ja) * 2015-11-25 2019-01-17 イミュノジェン・インコーポレーテッド 医薬製剤及びその使用
AU2017206074B2 (en) 2016-01-08 2023-09-07 Altrubio Inc. Tetravalent anti-PSGL-1 antibodies and uses thereof
US10961311B2 (en) * 2016-04-15 2021-03-30 Macrogenics, Inc. B7-H3 binding molecules, antibody drug conjugates thereof and methods of use thereof
GB201708909D0 (en) * 2017-06-05 2017-07-19 Orthox Ltd Implantable tissue repair devices and methods for manufacturing the same
AU2018445278B2 (en) * 2018-10-12 2022-07-28 Hangzhou Dac Biotech Co., Ltd Conjugation linkers containing 2,3-diaminosuccinyl group
WO2020078905A1 (en) 2018-10-15 2020-04-23 Merck Patent Gmbh Combination therapy utilizing dna alkylating agents and atr inhibitors
MX2021005484A (es) * 2018-11-09 2021-06-18 Byondis Bv Composiciones de conjugados de anticuerpo-farmaco que contienen duocarmicina filtrable y metodos relacionados.
AU2021216099A1 (en) * 2020-02-06 2022-09-01 Byondis B.V. Combination containing a duocarmycin derivative-comprising antibody-drug conjugate and thiosulfate

Family Cites Families (70)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA1238907A (en) 1984-02-21 1988-07-05 Robert C. Kelly 1,2,8,8a-tetrahydrocyclopropa¬c|pyrrolo(3,2-e)- indol-4(5h)-ones and related compounds
US4771128A (en) 1986-10-10 1988-09-13 Cetus Corporation Method of purifying toxin conjugates using hydrophobic interaction chromatography
MX9203460A (es) 1988-09-12 1992-09-01 Upjohn Co Nuevos analogos cc-1065 que tienen dos subunidades cpi.
WO1991016324A1 (en) 1990-04-25 1991-10-31 The Upjohn Company Novel cc-1065 analogs
JPH05268205A (ja) 1992-03-19 1993-10-15 Fujitsu Ltd クロック切換え回路
DE69231123T2 (de) 1992-03-25 2001-02-15 Immunogen Inc Konjugaten von Zell-bindender Mittel und Derivaten von CC-1065
JP3514490B2 (ja) 1992-08-21 2004-03-31 杏林製薬株式会社 トリフルオロメチルピロロインドールカルボン酸エステル誘導体及びその製造方法
GB9307491D0 (en) 1993-04-08 1993-06-02 Sandoz Ltd Organic compounds
EP0702014A4 (en) 1994-04-01 1996-08-07 Kyowa Hakko Kogyo Kk DC-89 DERIVATIVES
US5502068A (en) 1995-01-31 1996-03-26 Synphar Laboratories, Inc. Cyclopropylpyrroloindole-oligopeptide anticancer agents
DE19503320A1 (de) 1995-02-02 1996-08-08 Boehringer Mannheim Gmbh Neue Benzodiazepinkonjugate
US5843937A (en) 1996-05-23 1998-12-01 Panorama Research, Inc. DNA-binding indole derivatives, their prodrugs and immunoconjugates as anticancer agents
ES2253786T3 (es) 1996-09-12 2006-06-01 Auckland Uniservices Limited Compuestos de ciclopropilindola y su uso como precursores de medicamentos.
WO1998025900A1 (en) 1996-12-13 1998-06-18 Shionogi & Co., Ltd. Compounds having antitumor activity
US20030036629A1 (en) 1997-12-12 2003-02-20 Barry Foster Novel tgf-beta protein purification methods
US7214685B2 (en) 2000-05-02 2007-05-08 Lutz F. Tietze Prodrugs for a selective cancer therapy
ATE310724T1 (de) 2000-09-19 2005-12-15 Taiho Pharmaceutical Co Ltd Zusammensetzungen und verfahren zur verwendung achirale analoge von cc1065 und den duocarmycinen
WO2002059122A1 (en) 2001-01-24 2002-08-01 Auckland Uniservices Limited ANTI-CANCER 2,3-DIHYDRO-1H-PYRROLO[3,2-f]QUINOLINE COMPLEXES OF COBALT AND CHROMIUM
JP4862120B2 (ja) 2001-02-22 2012-01-25 ユニヴァーシティ オブ ブラッドフォード 腫瘍治療のためのプロドラッグとしてのベンズ−インドールおよびベンゾ−キノリン誘導体
KR20030033007A (ko) * 2001-05-31 2003-04-26 코울터 파머수티컬, 인코포레이티드 세포독소, 약물전구체, 링커 및 이에 유용한 안정화제
US7514078B2 (en) 2001-06-01 2009-04-07 Cornell Research Foundation, Inc. Methods of treating prostate cancer with anti-prostate specific membrane antigen antibodies
US20050014700A1 (en) 2001-09-07 2005-01-20 Boger Dale L. Cbi analogues of cc-1065 and the duocarmycins
WO2003026577A2 (en) * 2001-09-24 2003-04-03 Seattle Genetics, Inc. P-amidobenzylethers in drug delivery agents
US6756397B2 (en) 2002-04-05 2004-06-29 Immunogen, Inc. Prodrugs of CC-1065 analogs
AU2003228173A1 (en) 2002-05-17 2003-12-02 Auckland Uniservices Limited Processes for preparing 3-substituted 1-(chloromethyl)-1,2-dihydro-3h-(ring fused indol-5-yl(amine-derived)) compounds and analogues thereof, and to products obtained therefrom
US20050180972A1 (en) * 2002-07-31 2005-08-18 Wahl Alan F. Anti-CD20 antibody-drug conjugates for the treatment of cancer and immune disorders
JP2006507322A (ja) 2002-11-14 2006-03-02 シンタルガ・ビーブイ 多重自己脱離放出スペーサーとして構築されたプロドラッグ
AR042942A1 (es) 2003-01-27 2005-07-06 Endocyte Inc Conjugados de administracion de drogas de union de receptores de vitaminas
WO2004069201A2 (en) 2003-02-03 2004-08-19 Medlogics Device Corporation Compounds useful in coating stents to prevent and treat stenosis and restenosis
DK1594542T3 (da) 2003-02-20 2010-10-11 Seattle Genetics Inc Anti-CD70 antistof-lægemiddelkonjugater og deres anvendelse ved behandling af cancer
WO2004101767A2 (en) 2003-05-13 2004-11-25 The Scripps Research Institute Cbi analogues of the duocarmycins and cc-1065
WO2005032594A2 (en) 2003-10-03 2005-04-14 The Government Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Alkylators linked to polyamides as dna binding agents
ES2533695T3 (es) 2004-03-02 2015-04-14 Seattle Genetics, Inc. Anticuerpos cargados parcialmente y métodos para su conjugación
WO2005112919A2 (en) 2004-05-19 2005-12-01 Medarex, Inc. Self-immolative linkers and drug conjugates
EP3088004B1 (en) 2004-09-23 2018-03-28 Genentech, Inc. Cysteine engineered antibodies and conjugates
US20100041617A1 (en) 2004-09-27 2010-02-18 Jane Trepel Modulating mxa expression
NZ536107A (en) 2004-10-22 2007-06-29 Auckland Uniservices Ltd Nitrobenzindoles and their use in cancer therapy
EP1858902A1 (en) 2005-02-24 2007-11-28 Pfizer Products Incorporated Bicyclic heteroaromatic derivatives useful as anticancer agents
CN101312748A (zh) 2005-09-26 2008-11-26 梅达莱克斯公司 抗体-药物轭合物和使用方法
US7847105B2 (en) 2005-10-26 2010-12-07 Medarex, Inc. Methods and compounds for preparing CC-1065 analogs
KR20080114709A (ko) 2006-02-02 2008-12-31 신타가 비.브이. 수용성 ｃｃ-1065 유사체 및 그들의 결합체
EP1832577A1 (en) 2006-03-07 2007-09-12 Sanofi-Aventis Improved prodrugs of CC-1065 analogs
DK3564674T3 (da) 2006-11-01 2021-10-18 Ventana Med Syst Inc Haptener, haptenkonjugater, sammensætninger deraf og fremgangsmåde til fremstilling og anvendelse deraf
NZ578354A (en) 2006-12-14 2012-01-12 Medarex Inc Antibody-partner molecule conjugates that bind cd70 and uses thereof
CA2678514A1 (en) 2007-02-21 2008-08-28 Medarex, Inc. Chemical linkers with single amino acids and conjugates thereof
US9901567B2 (en) 2007-08-01 2018-02-27 Syntarga B.V. Substituted CC-1065 analogs and their conjugates
US8680293B2 (en) 2007-08-01 2014-03-25 Syntarga B.V. Substituted CC-1065 analogs and their conjugates
WO2009064908A1 (en) 2007-11-13 2009-05-22 The Scripps Research Institute Cbi derivatives subject to reductive activation
US20090162372A1 (en) 2007-11-30 2009-06-25 Medarex, Inc. Fibronectin ed-b antibodies, conjugates thereof, and methods of use
NZ571028A (en) 2008-09-03 2011-01-28 Auckland Uniservices Ltd Nitrobenzindole compounds and their use in cancer treatment
AU2009293140A1 (en) 2008-09-17 2010-03-25 Endocyte, Inc. Folate receptor binding conjugates of antifolates
EP2165710A1 (en) * 2008-09-19 2010-03-24 Institut Curie Tyrosine kinase receptor Tyro3 as a therapeutic target in the treatment of a bladder tumor
JP5677970B2 (ja) 2008-11-03 2015-02-25 シンタルガ・ビーブイ 新規ｃｃ−１０６５類似体およびその複合体
WO2010070117A1 (en) * 2008-12-18 2010-06-24 Universite Libre De Bruxelles Treatment method by the administration of anti-her2 targeted active compounds to patients with early breast cancer and her2-negative primary tumor
WO2011022316A1 (en) * 2009-08-20 2011-02-24 The Regents Of The University Of Colorado, A Body Corporate Mirnas dysregulated in triple-negative breast cancer
NO3056203T3 (ru) * 2010-04-21 2018-05-12
EP2380909A1 (en) * 2010-04-26 2011-10-26 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. PTK-7 protein involved in breast cancer
CA2800769C (en) * 2010-05-27 2021-11-02 Genmab A/S Monoclonal antibodies against her2 epitope
CA2832387A1 (en) * 2011-04-20 2012-10-26 Genmab A/S Bispecifc antibodies against her2
EP2764351B1 (en) 2011-09-29 2018-11-07 Seattle Genetics, Inc. Intact mass determination of protein conjugated agent compounds
WO2013055874A2 (en) * 2011-10-14 2013-04-18 Genentech, Inc. Uses for and article of manufacture including her2 dimerization inhibitor pertuzumab
CA3111357A1 (en) 2011-12-23 2013-06-27 Pfizer Inc. Engineered antibody constant regions for site-specific conjugation and methods and uses therefor
EP2814512A1 (en) 2012-02-16 2014-12-24 UCL Business Plc. Lysosome-cleavable linker
HUE029672T2 (en) * 2014-01-10 2017-03-28 Synthon Biopharmaceuticals Bv Duokarmicin-ADCs for use in the treatment of endometrial cancer
MX373458B (es) 2014-01-10 2020-05-11 Byondis Bv Metodo para purificar conjugados de anticuerpo-farmaco enlazados a cisteina.
ES2668984T3 (es) 2014-01-10 2018-05-23 Synthon Biopharmaceuticals B.V. CAF de duocarmicina para su uso en el tratamiento del cáncer de vejiga
MX374342B (es) 2014-05-22 2025-03-06 Byondis Bv Conjugacion especifica de sitio de farmacos enlazadores con anticuerpos y conjugados farmaco-anticuerpo (adc) resultantes.
PL3152191T3 (pl) 2014-06-05 2019-10-31 Synthon Biopharmaceuticals Bv Ulepszony sposób wytwarzania proleków duokarmycyny
EP3197919A1 (en) 2014-09-22 2017-08-02 Synthon Biopharmaceuticals B.V. Pan-reactive antibodies to duocarmycins
JP6522806B2 (ja) 2015-07-10 2019-05-29 シントン・バイオファーマシューティカルズ・ビー．ブイ．Ｓｙｎｔｈｏｎ Ｂｉｏｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｂ．Ｖ． 抗体デュオカルマイシン薬物複合体を含む組成物

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CA2935433A1 (en) 2015-07-16
CL2016001760A1 (es) 2017-06-09
HUE029255T2 (en) 2017-02-28
SG10201911860VA (en) 2020-02-27
EP2948184A2 (en) 2015-12-02
MY207293A (en) 2025-02-14
RU2016132759A3 (ru) 2018-08-14
RU2769700C2 (ru) 2022-04-05
RU2019114963A3 (ru) 2021-09-28
LT3069735T (lt) 2018-06-11
JP6342517B2 (ja) 2018-06-13
KR102323302B1 (ko) 2021-11-09
MX368396B (es) 2019-10-01
ES2668984T3 (es) 2018-05-23
CN105899236B (zh) 2019-07-26
WO2015104385A2 (en) 2015-07-16
JP2018039809A (ja) 2018-03-15
US9421278B2 (en) 2016-08-23
PL3069735T3 (pl) 2018-08-31
EP3069735B1 (en) 2018-03-14
US11382982B2 (en) 2022-07-12
NO3069735T3 (ru) 2018-08-11
US20190314513A1 (en) 2019-10-17
RU2689779C2 (ru) 2019-05-29
DK3069735T3 (en) 2018-05-22

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