CN103997893B - 吡咯并苯并二氮杂卓和靶向结合物 - Google Patents
吡咯并苯并二氮杂卓和靶向结合物 Download PDFInfo
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- CN103997893B CN103997893B CN201280062297.3A CN201280062297A CN103997893B CN 103997893 B CN103997893 B CN 103997893B CN 201280062297 A CN201280062297 A CN 201280062297A CN 103997893 B CN103997893 B CN 103997893B
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Classifications
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- C—CHEMISTRY; METALLURGY
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
- A61K31/5513—1,4-Benzodiazepines, e.g. diazepam or clozapine
- A61K31/5517—1,4-Benzodiazepines, e.g. diazepam or clozapine condensed with five-membered rings having nitrogen as a ring hetero atom, e.g. imidazobenzodiazepines, triazolam
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
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- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- C—CHEMISTRY; METALLURGY
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- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2875—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the NGF/TNF superfamily, e.g. CD70, CD95L, CD153, CD154
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Health & Medical Sciences (AREA)
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- Life Sciences & Earth Sciences (AREA)
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- Transplantation (AREA)
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- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Peptides Or Proteins (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
Description
化合物 | 786-O | Caki-1 | HL60 | HEL9217 |
4 | 50 | 20 | 8 | 8 |
14 | 200 | 400 | 30 | 50 |
Claims (21)
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US201161547195P | 2011-10-14 | 2011-10-14 | |
US61/547,195 | 2011-10-14 | ||
PCT/US2012/059870 WO2013055993A1 (en) | 2011-10-14 | 2012-10-12 | Pyrrolobenzodiazepines and targeted conjugates |
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CN103997893A CN103997893A (zh) | 2014-08-20 |
CN103997893B true CN103997893B (zh) | 2019-04-12 |
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CN201280062297.3A Active CN103997893B (zh) | 2011-10-14 | 2012-10-12 | 吡咯并苯并二氮杂卓和靶向结合物 |
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US (3) | US9387259B2 (zh) |
EP (2) | EP3309162A1 (zh) |
JP (2) | JP6399930B2 (zh) |
KR (1) | KR101961976B1 (zh) |
CN (1) | CN103997893B (zh) |
AU (1) | AU2012322613B2 (zh) |
BR (2) | BR122021017842B1 (zh) |
CA (1) | CA2850375C (zh) |
EA (2) | EA036202B1 (zh) |
ES (1) | ES2660233T3 (zh) |
HK (1) | HK1253715A1 (zh) |
IL (1) | IL231797A (zh) |
MX (2) | MX358757B (zh) |
WO (1) | WO2013055993A1 (zh) |
ZA (1) | ZA201402404B (zh) |
Families Citing this family (121)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB0819095D0 (en) | 2008-10-17 | 2008-11-26 | Spirogen Ltd | Pyrrolobenzodiazepines |
AU2011239525B2 (en) | 2010-04-15 | 2015-04-09 | Medimmune Limited | Pyrrolobenzodiazepines used to treat proliferative diseases |
AU2011239522B2 (en) | 2010-04-15 | 2014-10-23 | Medimmune Limited | Targeted pyrrolobenzodiazapine conjugates |
CA2849039C (en) | 2011-09-20 | 2018-09-18 | Spirogen Sarl | Pyrrolobenzodiazepines as unsymmetrical dimeric pbd compounds for inclusion in targeted conjugates |
BR112014008888A2 (pt) | 2011-10-14 | 2017-04-18 | Seattle Genetics Inc | pirrolobenzodiazepinas |
EP3388435B1 (en) | 2011-10-14 | 2023-05-03 | Seagen Inc. | Pyrrolobenzodiazepines and targeted conjugates |
EA036202B1 (ru) | 2011-10-14 | 2020-10-14 | Сиэтл Дженетикс, Инк. | Пирролбензодиазепины и конъюгаты направленного действия |
US9388187B2 (en) | 2011-10-14 | 2016-07-12 | Medimmune Limited | Pyrrolobenzodiazepines |
CA3060520C (en) | 2012-10-12 | 2022-05-17 | Medimmune Limited | Pyrrolobenzodiazepines and conjugates thereof |
AU2013328673B2 (en) | 2012-10-12 | 2017-07-13 | Medimmune Limited | Synthesis and intermediates of pyrrolobenzodiazepine derivatives for conjugation |
WO2014057114A1 (en) | 2012-10-12 | 2014-04-17 | Adc Therapeutics Sàrl | Pyrrolobenzodiazepine-anti-psma antibody conjugates |
MX364328B (es) | 2012-10-12 | 2019-04-23 | Medimmune Ltd | Conjugados del anticuerpo pirrolobenzodiazepina. |
DK2906251T3 (da) | 2012-10-12 | 2017-11-20 | Adc Therapeutics Sa | Pyrrolobenzodiazepin-anti-CD22-antistofkonjugater |
NZ707486A (en) | 2012-10-12 | 2018-09-28 | Adc Therapeutics Sa | Pyrrolobenzodiazepine - anti-psma antibody conjugates |
EP2906297B1 (en) | 2012-10-12 | 2017-12-06 | ADC Therapeutics SA | Pyrrolobenzodiazepine-antibody conjugates |
NZ707534A (en) | 2012-10-12 | 2018-08-31 | Adc Therapeutics Sa | Pyrrolobenzodiazepine-antibody conjugates |
PL2766048T3 (pl) | 2012-10-12 | 2015-05-29 | Medimmune Ltd | Pirolobenzodiazepiny i ich koniugaty |
US9353150B2 (en) | 2012-12-04 | 2016-05-31 | Massachusetts Institute Of Technology | Substituted pyrazino[1′,2′:1 ,5]pyrrolo[2,3-b]-indole-1,4-diones for cancer treatment |
CN110452242A (zh) | 2012-12-21 | 2019-11-15 | 麦迪穆有限责任公司 | 吡咯并苯并二氮杂卓及其结合物 |
CA2894959C (en) | 2012-12-21 | 2022-01-11 | Spirogen Sarl | Unsymmetrical pyrrolobenzodiazepines-dimers for use in the treatment of proliferative and autoimmune diseases |
CN105189546B (zh) | 2013-03-13 | 2022-09-02 | 西雅图基因公司 | 环糊精和抗体-药物偶联物制剂 |
CN105142674B (zh) | 2013-03-13 | 2018-11-13 | 麦迪穆有限责任公司 | 吡咯并苯并二氮杂卓和其结合物 |
AU2014244245C1 (en) | 2013-03-13 | 2018-04-19 | Genentech, Inc. | Pyrrolobenzodiazepines and conjugates thereof |
CA2901312C (en) | 2013-03-13 | 2022-09-06 | Seattle Genetics, Inc. | Activated carbon filtration for purification of benzodiazepine adcs |
CN105188766B (zh) | 2013-03-15 | 2019-07-12 | 瑞泽恩制药公司 | 生物活性分子、其偶联物及治疗用途 |
US10208125B2 (en) | 2013-07-15 | 2019-02-19 | University of Pittsburgh—of the Commonwealth System of Higher Education | Anti-mucin 1 binding agents and uses thereof |
JP6608823B2 (ja) | 2013-08-26 | 2019-11-20 | レゲネロン ファーマシューティカルス,インコーポレーテッド | マクロライドジアステレオマーを含む医薬組成物、その合成方法、及び治療上の使用 |
EP3054986B1 (en) | 2013-10-11 | 2019-03-20 | Medimmune Limited | Pyrrolobenzodiazepine-antibody conjugates |
US10010624B2 (en) | 2013-10-11 | 2018-07-03 | Medimmune Limited | Pyrrolobenzodiazepine-antibody conjugates |
WO2015052534A1 (en) | 2013-10-11 | 2015-04-16 | Spirogen Sàrl | Pyrrolobenzodiazepine-antibody conjugates |
GB201317981D0 (en) | 2013-10-11 | 2013-11-27 | Spirogen Sarl | Pyrrolobenzodiazepines and conjugates thereof |
GB201317982D0 (en) | 2013-10-11 | 2013-11-27 | Spirogen Sarl | Pyrrolobenzodiazepines and conjugates thereof |
CA2921707C (en) | 2013-10-15 | 2023-03-28 | Seattle Genetics, Inc. | Pegylated drug-linkers for improved ligand-drug conjugate pharmacokinetics |
IL290330B2 (en) | 2013-12-19 | 2023-09-01 | Seagen Inc | Methylene carbamate binders for use with drug-targeting conjugates |
EA035809B1 (ru) | 2014-03-11 | 2020-08-14 | Регенерон Фармасьютикалс, Инк. | АНТИТЕЛА ПРОТИВ EGFRvIII И ИХ ПРИМЕНЕНИЯ |
GB201409653D0 (en) * | 2014-05-30 | 2014-07-16 | Stell Dr Anneliese | Pyrrolobenzodiazepine therapeutic agents |
EP3193940A1 (en) | 2014-09-10 | 2017-07-26 | Medimmune Limited | Pyrrolobenzodiazepines and conjugates thereof |
GB201416112D0 (en) | 2014-09-12 | 2014-10-29 | Medimmune Ltd | Pyrrolobenzodiazepines and conjugates thereof |
TWI758784B (zh) | 2014-09-12 | 2022-03-21 | 美商建南德克公司 | 抗her2抗體及免疫結合物 |
KR20170101895A (ko) | 2014-11-25 | 2017-09-06 | 에이디씨 테라퓨틱스 에스에이 | 피롤로벤조디아제핀-항체 접합체 |
WO2016115201A1 (en) | 2015-01-14 | 2016-07-21 | Bristol-Myers Squibb Company | Heteroarylene-bridged benzodiazepine dimers, conjugates thereof, and methods of making and using |
CN107428780B (zh) | 2015-01-14 | 2020-09-04 | 百时美施贵宝公司 | 苯并二氮杂*二聚体、其缀合物及制备和使用方法 |
CA2980819C (en) * | 2015-03-05 | 2024-03-05 | Peter Und Traudl Engelhorn-Stiftung Zur Forderung Der Lebenswissenschaften | System for the presentation of peptides on the cell surface |
JP6948950B2 (ja) | 2015-03-27 | 2021-10-13 | レゲネロン ファーマシューティカルス,インコーポレーテッド | メイタンシノイド誘導体、そのコンジュゲート、及び使用方法 |
GB201506411D0 (en) | 2015-04-15 | 2015-05-27 | Bergenbio As | Humanized anti-axl antibodies |
GB201506402D0 (en) | 2015-04-15 | 2015-05-27 | Berkel Patricius H C Van And Howard Philip W | Site-specific antibody-drug conjugates |
KR20180019592A (ko) | 2015-06-23 | 2018-02-26 | 브리스톨-마이어스 스큅 컴퍼니 | 마크로시클릭 벤조디아제핀 이량체, 그의 접합체, 제조법 및 용도 |
IL296285A (en) | 2015-07-06 | 2022-11-01 | Regeneron Pharma | Multispecific antigen binding molecules and their uses |
MA43345A (fr) | 2015-10-02 | 2018-08-08 | Hoffmann La Roche | Conjugués anticorps-médicaments de pyrrolobenzodiazépine et méthodes d'utilisation |
US11793880B2 (en) | 2015-12-04 | 2023-10-24 | Seagen Inc. | Conjugates of quaternized tubulysin compounds |
MX2018006218A (es) | 2015-12-04 | 2018-09-05 | Seattle Genetics Inc | Conjugados de compuestos de tubulisina cuaternizada. |
JP2018536682A (ja) | 2015-12-11 | 2018-12-13 | リジェネロン・ファーマシューティカルズ・インコーポレイテッドRegeneron Pharmaceuticals, Inc. | Egfr及び/またはerbb3遮断に耐性のある腫瘍の成長を低減または防止するための方法 |
EP3408271B1 (en) | 2016-01-25 | 2023-01-11 | Regeneron Pharmaceuticals, Inc. | Maytansinoid derivatives, conjugates thereof, and methods of use |
GB201601431D0 (en) | 2016-01-26 | 2016-03-09 | Medimmune Ltd | Pyrrolobenzodiazepines |
GB201602356D0 (en) | 2016-02-10 | 2016-03-23 | Medimmune Ltd | Pyrrolobenzodiazepine Conjugates |
GB201602359D0 (en) | 2016-02-10 | 2016-03-23 | Medimmune Ltd | Pyrrolobenzodiazepine Conjugates |
UA125510C2 (uk) | 2016-03-25 | 2022-04-13 | Сіджен Інк. | Спосіб отримання пегильованої сполуки лікарський препарат-лінкер, де лікарським препаратом є ауристатин, та її проміжних сполук |
EP3448891A1 (en) | 2016-04-28 | 2019-03-06 | Regeneron Pharmaceuticals, Inc. | Methods of making multispecific antigen-binding molecules |
GB201607478D0 (en) | 2016-04-29 | 2016-06-15 | Medimmune Ltd | Pyrrolobenzodiazepine Conjugates |
US10918627B2 (en) | 2016-05-11 | 2021-02-16 | Massachusetts Institute Of Technology | Convergent and enantioselective total synthesis of Communesin analogs |
TW201808936A (zh) | 2016-05-18 | 2018-03-16 | 美商梅爾莎納醫療公司 | 吡咯并苯并二氮呯類及其共軛物 |
JP2019522050A (ja) | 2016-06-17 | 2019-08-08 | マジェンタ セラピューティクス インコーポレイテッドMagenta Therapeutics, Inc. | 細胞の枯渇のための組成物および方法 |
US10526294B2 (en) | 2016-06-24 | 2020-01-07 | Mersana Therapeutics, Inc. | Pyrrolobenzodiazepines and conjugates thereof |
WO2018002902A1 (en) | 2016-07-01 | 2018-01-04 | Glaxosmithkline Intellectual Property (No.2) Limited | Antibody-drug conjugates and therapeutic methods using the same |
SI3515487T1 (sl) | 2016-09-23 | 2023-09-29 | Regeneron Pharmaceuticals, Inc. | Bispecifična protitelesa proti-MUC16-CD3 in konjugati zdravil proti-MUC16 |
US10772972B2 (en) | 2016-09-23 | 2020-09-15 | Regeneron Pharmaceuticals, Inc. | Anti-STEAP2 antibody drug conjugates, and compositions and uses thereof |
CN110049780A (zh) | 2016-10-10 | 2019-07-23 | 塞勒兰特治疗公司 | 异喹啉并苯并二氮杂卓(iqb)-1(氯甲基)-2,3-二氢-1h-苯并[e]吲哚(cbi)二聚体 |
GB201617466D0 (en) | 2016-10-14 | 2016-11-30 | Medimmune Ltd | Pyrrolobenzodiazepine conjugates |
KR20190074310A (ko) | 2016-11-08 | 2019-06-27 | 리제너론 파마슈티칼스 인코포레이티드 | 스테로이드 및 이의 단백질-접합체 |
TWI782930B (zh) | 2016-11-16 | 2022-11-11 | 美商再生元醫藥公司 | 抗met抗體,結合met之雙特異性抗原結合分子及其使用方法 |
GB201619490D0 (en) * | 2016-11-17 | 2017-01-04 | Medimmune Ltd | Pyrrolobenzodiazepine conjugates |
WO2018134787A2 (en) | 2017-01-20 | 2018-07-26 | Magenta Therapeutics, Inc. | Compositions and methods for the depletion of cd137+ cells |
GB201702031D0 (en) | 2017-02-08 | 2017-03-22 | Medlmmune Ltd | Pyrrolobenzodiazepine-antibody conjugates |
AU2018217926B2 (en) | 2017-02-08 | 2019-10-03 | Adc Therapeutics Sa | Pyrrolobenzodiazepine-antibody conjugates |
BR112019015915A2 (pt) | 2017-02-28 | 2020-04-07 | Daiichi Sankyo Co Ltd | método para o tratamento de câncer de pulmão de células não pequenas resistentes a egfr-tki através da administração do conjugado de anticorpo anti-her3-fármaco |
US11730822B2 (en) | 2017-03-24 | 2023-08-22 | Seagen Inc. | Process for the preparation of glucuronide drug-linkers and intermediates thereof |
EP3612537B1 (en) | 2017-04-18 | 2022-07-13 | Medimmune Limited | Pyrrolobenzodiazepine conjugates |
US20200129637A1 (en) | 2017-04-20 | 2020-04-30 | Adc Therapeutics Sa | Combination therapy with an anti-axl antibody-drug conjugate |
US11932650B2 (en) | 2017-05-11 | 2024-03-19 | Massachusetts Institute Of Technology | Potent agelastatin derivatives as modulators for cancer invasion and metastasis |
AU2018270784B2 (en) | 2017-05-18 | 2024-05-16 | Regeneron Pharmaceuticals, Inc. | Cyclodextrin protein drug conjugates |
US20180334426A1 (en) | 2017-05-18 | 2018-11-22 | Regeneron Pharmaceutical, Inc. | Bis-octahydrophenanthrene carboxamides and protein conjugates thereof |
KR102442736B1 (ko) | 2017-06-14 | 2022-09-16 | 에이디씨 테라퓨틱스 에스에이 | 항-cd19 adc의 투여를 위한 투약량 체제 |
JP7220203B2 (ja) | 2017-08-18 | 2023-02-09 | メドイミューン・リミテッド | ピロロベンゾジアゼピン複合体 |
US11628223B2 (en) | 2017-09-29 | 2023-04-18 | Daiichi Sankyo Company, Limited | Antibody-drug conjugates comprising substituted benzo[e]pyrrolo[1,2-α][1,4]diazepines |
US10640508B2 (en) | 2017-10-13 | 2020-05-05 | Massachusetts Institute Of Technology | Diazene directed modular synthesis of compounds with quaternary carbon centers |
SG11202004151YA (en) | 2017-11-07 | 2020-06-29 | Regeneron Pharma | Hydrophilic linkers for antibody drug conjugates |
ES2920123T3 (es) * | 2017-11-14 | 2022-08-01 | Medimmune Ltd | Conjugados de pirrolobenzodiazepina |
EP3717021A1 (en) | 2017-11-27 | 2020-10-07 | Mersana Therapeutics, Inc. | Pyrrolobenzodiazepine antibody conjugates |
US20220305127A1 (en) | 2017-12-21 | 2022-09-29 | Mersana Therapeutics, Inc. | Pyrrolobenzodiazepine antibody conjugates |
BR112020013492A2 (pt) | 2018-01-08 | 2020-12-08 | Regeneron Pharmaceuticals, Inc. | Esteroides e conjugados de anticorpo dos mesmos |
GB201803342D0 (en) | 2018-03-01 | 2018-04-18 | Medimmune Ltd | Methods |
GB201806022D0 (en) | 2018-04-12 | 2018-05-30 | Medimmune Ltd | Pyrrolobenzodiazepines and conjugates thereof |
CA3097711A1 (en) | 2018-04-30 | 2019-11-07 | Regeneron Pharmaceuticals, Inc. | Antibodies, and bispecific antigen-binding molecules that bind her2 and/or aplp2, conjugates, and uses thereof |
CA3098453A1 (en) | 2018-05-09 | 2019-11-14 | Regeneron Pharmaceuticals, Inc. | Anti-msr1 antibodies and methods of use thereof |
AU2019269685A1 (en) | 2018-05-17 | 2020-12-03 | Regeneron Pharmaceuticals, Inc. | Anti-CD63 antibodies, conjugates, and uses thereof |
KR20210003938A (ko) | 2018-05-29 | 2021-01-12 | 주식회사 인투셀 | 신규한 벤조다이아제핀 유도체 및 그 용도 |
CA3113207A1 (en) | 2018-09-20 | 2020-03-26 | Daiichi Sankyo Company, Limited | Treatment of her3-mutated cancer by administration of anti-her3 antibody-drug conjugate |
CA3120528A1 (en) | 2018-11-20 | 2020-05-28 | Regeneron Pharmaceuticals, Inc. | Bis-octahydrophenanthrene carboxamide derivatives and protein conjugates thereof for use as lxr agonists |
EA202191769A1 (ru) | 2018-12-21 | 2021-12-08 | Регенерон Фармасьютикалз, Инк. | Тубулизины и конъюгаты белок-тубулизин |
US11666658B2 (en) | 2018-12-21 | 2023-06-06 | Regeneran Pharmaceuticals, Inc. | Rifamycin analogs and antibody-drug conjugates thereof |
MX2021008114A (es) | 2019-01-08 | 2021-08-05 | Regeneron Pharma | Enlazadores sin rastro y conjugados de proteinas de los mismos. |
WO2020172475A1 (en) | 2019-02-21 | 2020-08-27 | Regeneron Pharmaceuticals, Inc. | Methods of treating ocular cancer using anti-met antibodies and bispecific antigen binding molecules that bind met |
WO2020247054A1 (en) | 2019-06-05 | 2020-12-10 | Massachusetts Institute Of Technology | Compounds, conjugates, and compositions of epipolythiodiketopiperazines and polythiodiketopiperazines and uses thereof |
CN114340684A (zh) | 2019-09-16 | 2022-04-12 | 瑞泽恩制药公司 | 用于免疫pet成像的放射性标记的met结合蛋白 |
US11814428B2 (en) | 2019-09-19 | 2023-11-14 | Regeneron Pharmaceuticals, Inc. | Anti-PTCRA antibody-drug conjugates and uses thereof |
WO2021080608A1 (en) | 2019-10-25 | 2021-04-29 | Medimmune, Llc | Branched moiety for use in conjugates |
JP2023511956A (ja) | 2020-01-24 | 2023-03-23 | レゲネロン ファーマシューティカルス,インコーポレーテッド | タンパク質-抗ウイルス化合物コンジュゲート |
AU2021228225A1 (en) | 2020-02-28 | 2022-09-01 | Regeneron Pharmaceuticals, Inc. | Bispecific antigen binding molecules that bind HER2, and methods of use thereof |
WO2021211984A1 (en) | 2020-04-16 | 2021-10-21 | Regeneron Pharmaceuticals, Inc. | Diels-alder conjugation methods |
WO2021262910A2 (en) | 2020-06-24 | 2021-12-30 | Regeneron Pharmaceuticals, Inc. | Tubulysins and protein-tubulysin conjugates |
TW202216212A (zh) | 2020-07-17 | 2022-05-01 | 日商第一三共股份有限公司 | 抗體-藥物結合物之製造方法 |
WO2022056494A1 (en) | 2020-09-14 | 2022-03-17 | Regeneron Pharmaceuticals, Inc. | Antibody-drug conjugates comprising glp1 peptidomimetics and uses thereof |
WO2022087243A1 (en) | 2020-10-22 | 2022-04-28 | Regeneron Pharmaceuticals, Inc. | Anti-fgfr2 antibodies and methods of use thereof |
AU2022320713A1 (en) | 2021-07-28 | 2023-11-09 | Regeneron Pharmaceuticals, Inc. | Protein-antiviral compound conjugates |
WO2023129518A1 (en) | 2021-12-29 | 2023-07-06 | Regeneron Pharmaceuticals, Inc. | Tubulysins and protein-tubulysin conjugates |
US20230287138A1 (en) | 2022-01-12 | 2023-09-14 | Regneron Pharmaceuticals, Inc. | Protein-drug conjugates comprising camptothecin analogs and methods of use thereof |
WO2023137443A1 (en) | 2022-01-14 | 2023-07-20 | Regeneron Pharmaceuticals, Inc. | Verrucarin a derivatives and antibody drug conjugates thereof |
WO2023173132A1 (en) | 2022-03-11 | 2023-09-14 | Regeneron Pharmaceuticals, Inc. | Anti-glp1r antibody-drug conjugates comprising glp1 peptidomimetics and uses thereof |
US20240218011A1 (en) | 2022-07-21 | 2024-07-04 | Firefly Bio, Inc. | Glucocorticoid receptor agonists and conjugates thereof |
WO2024118785A2 (en) | 2022-11-30 | 2024-06-06 | Regeneron Pharmaceuticals, Inc. | Tlr7 agonists and antibody-drug-conjugates thereof |
WO2024138000A1 (en) | 2022-12-21 | 2024-06-27 | Regeneron Pharmaceuticals, Inc. | Prodrugs of topoisomerase i inhibitor for adc conjugations and methods of use thereof |
Family Cites Families (121)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3361742A (en) | 1964-12-07 | 1968-01-02 | Hoffmann La Roche | 5-oxo-1h-pyrrolo-[2, 1-c][1, 4]-benzodiazepin-2-crylamides |
US3523941A (en) | 1967-03-06 | 1970-08-11 | Hoffmann La Roche | Benzodiazepine compounds and process for their preparation |
US3524849A (en) | 1967-10-27 | 1970-08-18 | Hoffmann La Roche | Process for the preparation of pyrrolo-benzodiazepine acrylamides and intermediates useful therein |
DE1965304A1 (de) | 1968-12-30 | 1970-07-23 | Fujisawa Pharmaceutical Co | Benzdiazepinon-Verbindungen und Verfahren zu ihrer Herstellung |
JPS4843755B1 (zh) | 1969-06-26 | 1973-12-20 | ||
IL33558A (en) | 1968-12-30 | 1973-10-25 | Fujisawa Pharmaceutical Co | Antibiotic pyrrolo-benzodiazepine compound,its derivatives and processes for their production |
JPS5382792U (zh) | 1976-12-10 | 1978-07-08 | ||
JPS6053033B2 (ja) | 1976-12-28 | 1985-11-22 | 財団法人微生物化学研究会 | 新制癌抗生物質マゼスラマイシン及びその製造方法 |
JPS585916B2 (ja) | 1977-12-27 | 1983-02-02 | 株式会社ミドリ十字 | 新規ベンゾジアゼピン系化合物 |
JPS5615289A (en) | 1979-07-17 | 1981-02-14 | Green Cross Corp:The | Novel benzodiazepinnbased compound 3 |
JPS57131791A (en) | 1980-12-31 | 1982-08-14 | Fujisawa Pharmaceut Co Ltd | Benzodiazepine derivative and its preparation |
JPH0353356Y2 (zh) | 1981-02-06 | 1991-11-21 | ||
CA1173441A (en) | 1981-02-27 | 1984-08-28 | Hoffmann-La Roche Limited | Imidazodiazepines |
CA1184175A (en) | 1981-02-27 | 1985-03-19 | Walter Hunkeler | Imidazodiazepines |
CA1185602A (en) | 1981-02-27 | 1985-04-16 | Emilio Kyburz | Imidazodiazepines |
JPS58180487A (ja) | 1982-04-16 | 1983-10-21 | Kyowa Hakko Kogyo Co Ltd | 抗生物質dc−81およびその製造法 |
JPS58180487U (ja) | 1982-05-28 | 1983-12-02 | 松下電工株式会社 | 光線式報知器の組立体 |
US4427588A (en) | 1982-11-08 | 1984-01-24 | Bristol-Myers Company | Process for conversion of oxotomaymycin to tomaymycin |
US4427587A (en) | 1982-11-10 | 1984-01-24 | Bristol-Myers Company | Total synthesis of antitumor antibiotics BBM-2040A and BBM-2040B |
JPS59152329A (ja) | 1983-02-17 | 1984-08-31 | Green Cross Corp:The | 局所障害抑制剤 |
FR2586683B1 (fr) | 1985-08-29 | 1988-07-01 | Centre Nat Rech Scient | Nouveaux derives de neothramycine, leur procede de preparation et leur application en tant que medicaments |
JP2660201B2 (ja) | 1988-08-05 | 1997-10-08 | 塩野義製薬株式会社 | 新規ピロロ[1,4]ベンゾジアゼピン誘導体および老人性痴呆薬 |
FR2676230B1 (fr) | 1991-05-07 | 1993-08-27 | Centre Nat Rech Scient | Nouveaux derives de pyrrolo [1,4]-benzodiazepines, leur procede de preparation et medicaments les contenant. |
GB9205051D0 (en) | 1992-03-09 | 1992-04-22 | Cancer Res Campaign Tech | Pyrrolobenzodiazepine derivatives,their preparation,and compositions containing them |
FR2696176B1 (fr) | 1992-09-28 | 1994-11-10 | Synthelabo | Dérivés de pipéridine, leur préparation et leur application en thérapeutique. |
US6214345B1 (en) | 1993-05-14 | 2001-04-10 | Bristol-Myers Squibb Co. | Lysosomal enzyme-cleavable antitumor drug conjugates |
GB9316162D0 (en) | 1993-08-04 | 1993-09-22 | Zeneca Ltd | Fungicides |
ATE349722T1 (de) | 1998-07-08 | 2007-01-15 | E Ink Corp | Verbesserte farbige mikroverkapselte elektrophoretische anzeige |
GB9818730D0 (en) | 1998-08-27 | 1998-10-21 | Univ Portsmouth | Collections of compounds |
GB9818732D0 (en) | 1998-08-27 | 1998-10-21 | Univ Portsmouth | Collection of compounds |
PT1413582E (pt) | 1998-08-27 | 2006-07-31 | Spirogen Ltd | Pirrolobenzodiazepinas dimericas |
GB9818731D0 (en) | 1998-08-27 | 1998-10-21 | Univ Portsmouth | Compounds |
US6909006B1 (en) | 1999-08-27 | 2005-06-21 | Spirogen Limited | Cyclopropylindole derivatives |
DK1320522T3 (da) | 2000-09-19 | 2006-04-03 | Moses Lee | Achirale analoger af CC-1065 og af duocarmyciner samt præparater og metoder til anvendelse deraf |
US6362331B1 (en) | 2001-03-30 | 2002-03-26 | Council Of Scientific And Industrial Research | Process for the preparation of antitumor agents |
US6660856B2 (en) | 2002-03-08 | 2003-12-09 | Kaohsiung Medical University | Synthesis of pyrrolo[2,1-c][1,4]benzodiazepine analogues |
AU2003263964C1 (en) | 2002-07-31 | 2010-08-19 | Seagen Inc. | Drug conjugates and their use for treating cancer, an autoimmune disease or an infectious disease |
US20040138269A1 (en) | 2002-10-11 | 2004-07-15 | Sugen, Inc. | Substituted pyrroles as kinase inhibitors |
FR2846966A1 (fr) | 2002-11-07 | 2004-05-14 | Fournier Lab Sa | Derive du 4-methyl-2-oxo-2h-1-benzopyran-7-yl 5-thio-beta-d- xylopyranoside, son procede de preparation et composition pharmaceutique le contenant |
GB0226593D0 (en) | 2002-11-14 | 2002-12-24 | Consultants Ltd | Compounds |
DE60326060D1 (de) | 2003-03-31 | 2009-03-19 | Council Scient Ind Res | Nichtvernetzende pyrroloä2,1-cüä1,4übenzodiazepine als potentielle antitumor-agentien und ihre herstellung |
GB0321295D0 (en) | 2003-09-11 | 2003-10-15 | Spirogen Ltd | Synthesis of protected pyrrolobenzodiazepines |
GB0416511D0 (en) | 2003-10-22 | 2004-08-25 | Spirogen Ltd | Pyrrolobenzodiazepines |
ATE516288T1 (de) | 2003-10-22 | 2011-07-15 | Us Gov Health & Human Serv | Pyrrolobenzodiazepinderivate, zusammensetzungen, die diese enthalten, und damit in zusammenhang stehende verfahren |
SI1725249T1 (sl) | 2003-11-06 | 2014-04-30 | Seattle Genetics, Inc. | Spojine monometilvalina, sposobne konjugacije na ligande |
WO2005082023A2 (en) | 2004-02-23 | 2005-09-09 | Genentech, Inc. | Heterocyclic self-immolative linkers and conjugates |
SI1720881T1 (sl) | 2004-03-01 | 2013-04-30 | Spirogen Sarl | 11-hidroksi-5H-pirolo(2,1-c)(1,4)benzodiazepin-5onski derivati kot ključni intermediati za pipravo C2 substituiranih pirolobenzodiazepinov |
GB0404577D0 (en) | 2004-03-01 | 2004-04-07 | Spirogen Ltd | Pyrrolobenzodiazepines |
GB0404574D0 (en) | 2004-03-01 | 2004-04-07 | Spirogen Ltd | Amino acids |
GB0404578D0 (en) | 2004-03-01 | 2004-04-07 | Spirogen Ltd | Pyrrolobenzodiazepines |
DE102004010943A1 (de) | 2004-03-03 | 2005-09-29 | Degussa Ag | Verfahren zur Herstellung von N-geschützten 4-Ketprolinderivaten |
JP5166861B2 (ja) | 2004-03-09 | 2013-03-21 | スピロゲン リミティッド | ピロロベンゾジアゼピン |
FR2869231B1 (fr) | 2004-04-27 | 2008-03-14 | Sod Conseils Rech Applic | Composition therapeutique contenant au moins un derive de la pyrrolobenzodiazepine et la fludarabine |
GB0410725D0 (en) | 2004-05-13 | 2004-06-16 | Spirogen Ltd | Pyrrolobenzodiazepine therapeutic agents |
WO2006034488A2 (en) | 2004-09-23 | 2006-03-30 | Genentech, Inc. | Cysteine engineered antibodies and conjugates |
CN101080506B (zh) | 2004-12-24 | 2012-06-13 | 昭和电工株式会社 | 热电半导体合金的制造方法、热电转换模块以及热电发电设备 |
JP5122441B2 (ja) | 2005-04-19 | 2013-01-16 | シアトル ジェネティックス, インコーポレイテッド | ヒト化抗cd70結合剤およびその使用 |
NZ563136A (en) | 2005-04-21 | 2009-11-27 | Spirogen Ltd | Pyrrolobenzodiazepines |
WO2007039752A1 (en) | 2005-10-05 | 2007-04-12 | Spirogen Limited | Alkyl 4- [4- (5-oxo-2, 3, 5, 11a-tetrahyd0-5h-pyrr0l0 [2, 1-c] [1, 4] benzodiazepine-8-yloxy) -butyrylamino]-1h-pyrrole-2-carboxylate derivatives and related compounds for the treatment of a proliferative disease |
US20070154906A1 (en) | 2005-10-05 | 2007-07-05 | Spirogen Ltd. | Methods to identify therapeutic candidates |
ATE527262T1 (de) | 2006-01-25 | 2011-10-15 | Sanofi Sa | Neue tomaymycin derivate enhaltende zytotoxische mittel |
ES2673822T3 (es) | 2006-07-18 | 2018-06-25 | Sanofi | Anticuerpo antagonista contra EphA2 para el tratamiento de cáncer |
EP1914242A1 (en) | 2006-10-19 | 2008-04-23 | Sanofi-Aventis | Novel anti-CD38 antibodies for the treatment of cancer |
WO2008050140A2 (en) | 2006-10-27 | 2008-05-02 | Spirogen Limited | Compounds for treatment of parasitic infection |
PL2099823T5 (pl) | 2006-12-01 | 2023-02-20 | Seagen Inc. | Wariant środków wiążących cel i jego zastosowania |
ES2435779T3 (es) | 2007-07-19 | 2013-12-23 | Sanofi | Agentes citotóxicos que comprenden nuevos derivados de tomaimicina y su uso terapéutico |
JP5485897B2 (ja) * | 2007-10-12 | 2014-05-07 | シアトル ジェネティクス,インコーポレーテッド | 抗体−薬物複合体の併用療法 |
GB0722088D0 (en) | 2007-11-09 | 2007-12-19 | Spirogen Ltd | Pyrrolobenzodiazepines |
GB0722087D0 (en) | 2007-11-09 | 2007-12-19 | Spirogen Ltd | Polyamides |
US8609105B2 (en) | 2008-03-18 | 2013-12-17 | Seattle Genetics, Inc. | Auristatin drug linker conjugates |
WO2009117631A2 (en) | 2008-03-21 | 2009-09-24 | Kingsdown, Inc. | Methods and apparatuses for providing a sleep system having customized zoned support and zoned comfort |
GB0813432D0 (en) | 2008-07-22 | 2008-08-27 | Spirogen Ltd | Pyrrolobenzodiazepines |
GB0819095D0 (en) * | 2008-10-17 | 2008-11-26 | Spirogen Ltd | Pyrrolobenzodiazepines |
GB0819097D0 (en) * | 2008-10-17 | 2008-11-26 | Spirogen Ltd | Pyrrolobenzodiazepines |
IL271761B (en) | 2009-02-05 | 2022-09-01 | Immunogen Inc | (12as)-8-methoxy-9-benzyloxy-11,12,12a,13-tetrahydro-6h-indolo[2,1-c][1,4]benzodiazepine-6-one, 4-benzyloxy-5-methoxy -2-nitrobenzoic acid and a process for their preparation |
FR2949469A1 (fr) | 2009-08-25 | 2011-03-04 | Sanofi Aventis | Derives anticancereux, leur preparation et leur application en therapeutique |
JP2013505944A (ja) | 2009-09-24 | 2013-02-21 | シアトル ジェネティックス, インコーポレイテッド | Dr5リガンド薬物結合体 |
ES2449379T3 (es) | 2010-02-09 | 2014-03-19 | Bristol-Myers Squibb Company | Derivados de bencilpirrolidinona como moduladores de la actividad de receptores de quimiocinas |
PE20130342A1 (es) | 2010-04-15 | 2013-04-20 | Spirogen Sarl | Pirrolobenzodiacepinas y conjugados de las mismas |
GB201006340D0 (en) | 2010-04-15 | 2010-06-02 | Spirogen Ltd | Synthesis method and intermediates |
AU2011239525B2 (en) | 2010-04-15 | 2015-04-09 | Medimmune Limited | Pyrrolobenzodiazepines used to treat proliferative diseases |
AU2011239522B2 (en) | 2010-04-15 | 2014-10-23 | Medimmune Limited | Targeted pyrrolobenzodiazapine conjugates |
US9534000B2 (en) | 2011-02-15 | 2017-01-03 | Immunogen, Inc. | Cytotoxic benzodiazepine derivatives and methods of preparation |
CA2849039C (en) | 2011-09-20 | 2018-09-18 | Spirogen Sarl | Pyrrolobenzodiazepines as unsymmetrical dimeric pbd compounds for inclusion in targeted conjugates |
US9388187B2 (en) | 2011-10-14 | 2016-07-12 | Medimmune Limited | Pyrrolobenzodiazepines |
HUE025661T2 (en) | 2011-10-14 | 2016-04-28 | Medimmune Ltd | Pyrrolobenzodiazepines and their conjugates |
BR112014008888A2 (pt) | 2011-10-14 | 2017-04-18 | Seattle Genetics Inc | pirrolobenzodiazepinas |
EP3388435B1 (en) | 2011-10-14 | 2023-05-03 | Seagen Inc. | Pyrrolobenzodiazepines and targeted conjugates |
EA036202B1 (ru) | 2011-10-14 | 2020-10-14 | Сиэтл Дженетикс, Инк. | Пирролбензодиазепины и конъюгаты направленного действия |
EA029046B1 (ru) | 2011-10-14 | 2018-02-28 | Медимьюн Лимитед | Пирролобензодиазепины и промежуточные соединения для их получения, способы их синтеза |
BR112014027190B1 (pt) | 2012-04-30 | 2020-03-03 | Medimmune Limited | Composto de pirrolobenzodiazepinas, sua composição farmacêutica e seu uso |
EP2855482B1 (en) | 2012-04-30 | 2017-03-01 | MedImmune Limited | Pyrrolobenzodiazepines |
CA2873889A1 (en) | 2012-07-09 | 2014-01-16 | Genentech, Inc. | Anti-cd22 antibodies and immunoconjugates |
MA37840B1 (fr) | 2012-07-09 | 2020-05-29 | Genentech Inc | Immunoconjugués comprenant des anticorps anti-cd79b |
BR112015002193A2 (pt) | 2012-08-02 | 2017-07-04 | Genentech Inc | anticorpos anti-etbr e imunoconjugados |
EP2906297B1 (en) | 2012-10-12 | 2017-12-06 | ADC Therapeutics SA | Pyrrolobenzodiazepine-antibody conjugates |
WO2014057118A1 (en) | 2012-10-12 | 2014-04-17 | Adc Therapeutics Sarl | Pyrrolobenzodiazepine-anti-cd22 antibody conjugates |
CA3060520C (en) | 2012-10-12 | 2022-05-17 | Medimmune Limited | Pyrrolobenzodiazepines and conjugates thereof |
WO2014057114A1 (en) | 2012-10-12 | 2014-04-17 | Adc Therapeutics Sàrl | Pyrrolobenzodiazepine-anti-psma antibody conjugates |
MX364328B (es) | 2012-10-12 | 2019-04-23 | Medimmune Ltd | Conjugados del anticuerpo pirrolobenzodiazepina. |
DK2906251T3 (da) | 2012-10-12 | 2017-11-20 | Adc Therapeutics Sa | Pyrrolobenzodiazepin-anti-CD22-antistofkonjugater |
PL2766048T3 (pl) | 2012-10-12 | 2015-05-29 | Medimmune Ltd | Pirolobenzodiazepiny i ich koniugaty |
CA2887896A1 (en) | 2012-10-12 | 2014-04-17 | Adc Therapeutics Sarl | Pyrrolobenzodiazepine-anti-her2 antibody conjugates |
NZ707486A (en) | 2012-10-12 | 2018-09-28 | Adc Therapeutics Sa | Pyrrolobenzodiazepine - anti-psma antibody conjugates |
NZ707534A (en) | 2012-10-12 | 2018-08-31 | Adc Therapeutics Sa | Pyrrolobenzodiazepine-antibody conjugates |
AU2013328673B2 (en) | 2012-10-12 | 2017-07-13 | Medimmune Limited | Synthesis and intermediates of pyrrolobenzodiazepine derivatives for conjugation |
CN110452242A (zh) | 2012-12-21 | 2019-11-15 | 麦迪穆有限责任公司 | 吡咯并苯并二氮杂卓及其结合物 |
CA2894959C (en) | 2012-12-21 | 2022-01-11 | Spirogen Sarl | Unsymmetrical pyrrolobenzodiazepines-dimers for use in the treatment of proliferative and autoimmune diseases |
CN105164159A (zh) | 2013-02-22 | 2015-12-16 | 施特姆森特克斯股份有限公司 | 新的抗体缀合物及其用途 |
AU2014244245C1 (en) | 2013-03-13 | 2018-04-19 | Genentech, Inc. | Pyrrolobenzodiazepines and conjugates thereof |
US20160031887A1 (en) | 2013-03-13 | 2016-02-04 | Medimmune Limited | Pyrrolobenzodiazepines and conjugates thereof |
CN105142674B (zh) | 2013-03-13 | 2018-11-13 | 麦迪穆有限责任公司 | 吡咯并苯并二氮杂卓和其结合物 |
WO2014174111A1 (en) | 2013-04-26 | 2014-10-30 | Pierre Fabre Medicament | Axl antibody-drug conjugate and its use for the treatment of cancer |
EP3054986B1 (en) | 2013-10-11 | 2019-03-20 | Medimmune Limited | Pyrrolobenzodiazepine-antibody conjugates |
US10010624B2 (en) | 2013-10-11 | 2018-07-03 | Medimmune Limited | Pyrrolobenzodiazepine-antibody conjugates |
GB201317981D0 (en) | 2013-10-11 | 2013-11-27 | Spirogen Sarl | Pyrrolobenzodiazepines and conjugates thereof |
WO2015052534A1 (en) | 2013-10-11 | 2015-04-16 | Spirogen Sàrl | Pyrrolobenzodiazepine-antibody conjugates |
GB201317982D0 (en) | 2013-10-11 | 2013-11-27 | Spirogen Sarl | Pyrrolobenzodiazepines and conjugates thereof |
US20160256561A1 (en) | 2013-10-11 | 2016-09-08 | Medimmune Limited | Pyrrolobenzodiazepine-antibody conjugates |
BR112016014126B1 (pt) | 2013-12-16 | 2023-02-14 | Medimmune Limited | Composto não-peptídico, conjugados de anticorpo-fármaco do mesmo, uso dos ditos conjugados para o tratamento de câncer e composição farmacêutica que compreende os mesmos |
GB201406767D0 (en) | 2014-04-15 | 2014-05-28 | Cancer Rec Tech Ltd | Humanized anti-Tn-MUC1 antibodies anf their conjugates |
-
2012
- 2012-10-12 EA EA201692215A patent/EA036202B1/ru unknown
- 2012-10-12 WO PCT/US2012/059870 patent/WO2013055993A1/en active Application Filing
- 2012-10-12 KR KR1020147012118A patent/KR101961976B1/ko active IP Right Grant
- 2012-10-12 US US14/351,172 patent/US9387259B2/en active Active
- 2012-10-12 EA EA201490582A patent/EA026643B1/ru unknown
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