CA2795353C - Pyrrolobenzodiazepines used to treat proliferative diseases - Google Patents

Pyrrolobenzodiazepines used to treat proliferative diseases Download PDF

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Publication number
CA2795353C
CA2795353C CA2795353A CA2795353A CA2795353C CA 2795353 C CA2795353 C CA 2795353C CA 2795353 A CA2795353 A CA 2795353A CA 2795353 A CA2795353 A CA 2795353A CA 2795353 C CA2795353 C CA 2795353C
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group
compound according
alkyl
attachment
methyl
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CA2795353A
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English (en)
French (fr)
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CA2795353A1 (en
Inventor
Philip Wilson Howard
Luke Masterson
Arnaud Tiberghien
Scott Jeffrey
Patrick Burke
Peter Senter
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MedImmune Ltd
Seagen Inc
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MedImmune Ltd
Seattle Genetics Inc
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • 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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    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • A61K47/68035—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a pyrrolobenzodiazepine
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    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
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    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
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    • A61K47/6851—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
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    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/10—Compounds having one or more C—Si linkages containing nitrogen having a Si-N linkage

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Immunology (AREA)
  • Epidemiology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Diabetes (AREA)
  • Pulmonology (AREA)
  • Cell Biology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Rheumatology (AREA)
  • Hematology (AREA)
  • Dermatology (AREA)
  • Endocrinology (AREA)
  • Neurology (AREA)
  • Urology & Nephrology (AREA)
  • Reproductive Health (AREA)
  • Neurosurgery (AREA)
  • Otolaryngology (AREA)
  • Pain & Pain Management (AREA)
  • Transplantation (AREA)
  • Ophthalmology & Optometry (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Oncology (AREA)
  • Emergency Medicine (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Biomedical Technology (AREA)
  • Gynecology & Obstetrics (AREA)
CA2795353A 2010-04-15 2011-04-15 Pyrrolobenzodiazepines used to treat proliferative diseases Active CA2795353C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US32445310P 2010-04-15 2010-04-15
US61/324,453 2010-04-15
PCT/US2011/032668 WO2011130616A1 (en) 2010-04-15 2011-04-15 Pyrrolobenzodiazepines used to treat proliferative diseases

Publications (2)

Publication Number Publication Date
CA2795353A1 CA2795353A1 (en) 2011-10-20
CA2795353C true CA2795353C (en) 2018-01-09

Family

ID=43971498

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2795353A Active CA2795353C (en) 2010-04-15 2011-04-15 Pyrrolobenzodiazepines used to treat proliferative diseases

Country Status (13)

Country Link
US (2) US8697688B2 (https=)
EP (2) EP2558475A1 (https=)
JP (1) JP5875083B2 (https=)
KR (1) KR101687054B1 (https=)
CN (1) CN102971329B (https=)
AU (1) AU2011239525B2 (https=)
BR (1) BR112012026410B8 (https=)
CA (1) CA2795353C (https=)
ES (1) ES2623057T3 (https=)
MX (2) MX368648B (https=)
NZ (1) NZ602933A (https=)
WO (1) WO2011130616A1 (https=)
ZA (1) ZA201207357B (https=)

Families Citing this family (174)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB0819095D0 (en) 2008-10-17 2008-11-26 Spirogen Ltd Pyrrolobenzodiazepines
RU2683325C2 (ru) 2009-02-05 2019-03-28 Иммьюноджен, Инк. Новые производные бензодиазепина
CA2795349C (en) 2010-04-15 2016-11-29 Seattle Genetics, Inc. Targeted pyrrolobenzodiazepine conjugates
JP5875083B2 (ja) 2010-04-15 2016-03-02 メディミューン リミテッド 増殖性疾患治療用ピロロベンゾジアゼピン
JP5826863B2 (ja) 2011-02-15 2015-12-02 イミュノジェン・インコーポレーテッド 細胞傷害性ベンゾジアゼピン誘導体
US20130058947A1 (en) 2011-09-02 2013-03-07 Stem Centrx, Inc Novel Modulators and Methods of Use
SG11201400770SA (en) * 2011-09-20 2014-04-28 Spirogen Sarl Pyrrolobenzodiazepines as unsymmetrical dimeric pbd compounds for inclusion in targeted conjugates
CA2850373C (en) 2011-10-14 2019-07-16 Seattle Genetics, Inc. Pyrrolobenzodiazepines and targeted conjugates
AU2012322932B2 (en) 2011-10-14 2016-11-10 Medimmune Limited Pyrrolobenzodiazepines
CN103997893B (zh) 2011-10-14 2019-04-12 西雅图基因公司 吡咯并苯并二氮杂卓和靶向结合物
EP2751111B1 (en) 2011-10-14 2017-04-26 MedImmune Limited Asymmetrical bis-(5H-Pyrrolo[2,1-c][1,4]benzodiazepin-5-one) derivatives for the treatment of proliferative or autoimmune diseases
EP2793947B1 (en) 2011-12-23 2021-02-03 Innate Pharma Enzymatic conjugation of polypeptides
BR112014020826A8 (pt) 2012-02-24 2017-09-19 Stem Centrx Inc Anticorpo que se liga especificamente a um epítopo, ácido nucleico, vetor ou célula hospedeira, conjugado de fármaco – anticorpo, composição farmacêutica compreendendo o referido anticorpo, uso do mesmo, kit e método de preparação do conjugado
EP3539985A1 (en) 2012-02-24 2019-09-18 AbbVie Stemcentrx LLC Anti sez6 antibodies and methods of use
CA2873793C (en) 2012-05-18 2022-02-22 Medical Research Council Methods of incorporating an amino acid comprising a bcn group into a polypeptide using an orthogonal codon encoding it and an orthorgonal pylrs synthase
US10132799B2 (en) 2012-07-13 2018-11-20 Innate Pharma Screening of conjugated antibodies
RS57694B1 (sr) 2012-10-12 2018-11-30 Adc Therapeutics Sa Pirolobenzodiazepin - anti-psma konjugati antitela
MX338711B (es) 2012-10-12 2016-04-28 Medimmune Ltd Pirrolobenzodiazepinas y conjugados de las mismas.
JP6392765B2 (ja) 2012-10-12 2018-09-19 エイディーシー・セラピューティクス・エス・アーＡｄｃ Ｔｈｅｒａｐｅｕｔｉｃｓ Ｓａ ピロロベンゾジアゼピン−抗体結合体
HRP20190366T1 (hr) * 2012-10-12 2019-04-19 Medimmune Limited Pirolobenzodiazepini i njihovi konjugati
HRP20182129T1 (hr) * 2012-10-12 2019-02-08 Adc Therapeutics Sa Konjugati protutijelo - pirolobenzodiazepin
EP2906297B1 (en) 2012-10-12 2017-12-06 ADC Therapeutics SA Pyrrolobenzodiazepine-antibody conjugates
SI2906252T1 (sl) * 2012-10-12 2017-10-30 Adc Therapeutics Sa Pirolobenzodiazepin-anti-HER2 protitelesni konjugati
EP2906296B1 (en) 2012-10-12 2018-03-21 ADC Therapeutics SA Pyrrolobenzodiazepine-antibody conjugates
WO2014057118A1 (en) * 2012-10-12 2014-04-17 Adc Therapeutics Sarl Pyrrolobenzodiazepine-anti-cd22 antibody conjugates
EP2906249B1 (en) 2012-10-12 2018-06-27 MedImmune Limited Synthesis and intermediates of pyrrolobenzodiazepine derivatives for conjugation
ES2680153T3 (es) * 2012-10-12 2018-09-04 Adc Therapeutics Sa Conjugados de anticuerpos anti-PSMA-pirrolobenzodiazepinas
EP3564259A3 (en) 2012-11-09 2020-02-12 Innate Pharma Recognition tags for tgase-mediated conjugation
CN110627797A (zh) 2012-12-21 2019-12-31 麦迪穆有限责任公司 用于治疗增殖性和自身免疫疾病的非对称吡咯并苯并二氮杂卓二聚物
CN105189507A (zh) 2012-12-21 2015-12-23 斯皮罗根有限公司 吡咯并苯并二氮杂卓及其结合物
CN103933575B (zh) 2013-01-23 2017-09-29 上海新理念生物医药科技有限公司 一种三齿型连接子及其应用
ES2731681T3 (es) 2013-02-22 2019-11-18 Abbvie Stemcentrx Llc Conjugados de anticuerpo anti-DLL3 y PBD y usos de los mismos
AU2014248640B2 (en) * 2013-03-13 2018-03-01 Seagen Inc. Cyclodextrin and antibody-drug conjugate formulations
AU2014229529B2 (en) 2013-03-13 2018-02-15 Medimmune Limited Pyrrolobenzodiazepines and conjugates thereof
MX362970B (es) * 2013-03-13 2019-02-28 Medimmune Ltd Pirrolobenzodiazepinas y conjugados de las mismas.
DK2968494T3 (en) 2013-03-13 2019-03-04 Seattle Genetics Inc ACTIVATED CARBON FILTERING FOR CLEANING BENZODIAZEPINE ADCs
TWI680766B (zh) * 2013-03-13 2020-01-01 英商梅迪繆思有限公司 吡咯并苯并二氮呯及其共軛物
US10611824B2 (en) 2013-03-15 2020-04-07 Innate Pharma Solid phase TGase-mediated conjugation of antibodies
EP3010547B1 (en) 2013-06-20 2021-04-21 Innate Pharma Enzymatic conjugation of polypeptides
CN105517577A (zh) 2013-06-21 2016-04-20 先天制药公司 多肽的酶促偶联
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
BR112016002829A2 (pt) 2013-08-12 2017-09-19 Genentech Inc Composto e processo para preparar o composto de conjugado anticorpo-¿droga, composição farmacêutica, método de tratamento do câncer, kit para o tratamento do câncer, intermediário ligante¿-droga, porção e composto de porção droga de dímero cbi
CN105792836A (zh) 2013-08-28 2016-07-20 施特姆森特克斯股份有限公司 新型sez6调节剂以及应用方法
SG11201601424PA (en) 2013-08-28 2016-03-30 Stemcentrx Inc Site-specific antibody conjugation methods and compositions
WO2015052534A1 (en) 2013-10-11 2015-04-16 Spirogen Sàrl Pyrrolobenzodiazepine-antibody conjugates
EP3054983B1 (en) 2013-10-11 2019-03-20 Medimmune Limited Pyrrolobenzodiazepine-antibody conjugates
GB201317981D0 (en) 2013-10-11 2013-11-27 Spirogen Sarl Pyrrolobenzodiazepines and conjugates thereof
CN105745224B (zh) 2013-10-11 2019-11-05 牛津生物疗法有限公司 用于治疗癌症的针对ly75的偶联抗体
GB201317982D0 (en) 2013-10-11 2013-11-27 Spirogen Sarl Pyrrolobenzodiazepines and conjugates thereof
WO2015052535A1 (en) 2013-10-11 2015-04-16 Spirogen Sàrl Pyrrolobenzodiazepine-antibody conjugates
NZ758049A (en) 2013-10-15 2024-03-22 Seagen Inc Pegylated drug-linkers for improved ligand-drug conjugate pharmacokinetics
RU2016122041A (ru) 2013-11-06 2017-12-11 ЭББВИ СТЕМСЕНТРКС ЭлЭлСи Новые анти-клаудин антитела и способы их применения
SG11201604664PA (en) 2013-12-12 2016-07-28 Stemcentrx Inc Novel anti-dpep3 antibodies and methods of use
EP3082876B1 (en) 2013-12-16 2018-01-17 Genentech, Inc. 1-(chloromethyl)-2,3-dihydro-1h-benzo[e]indole dimer antibody-drug conjugate compounds, and methods of use and treatment
KR102442906B1 (ko) 2013-12-19 2022-09-14 씨젠 인크. 표적화된-약물 컨쥬게이트와 함께 사용되는 메틸렌 카바메이트 링커
CA2939941A1 (en) 2014-02-21 2015-08-27 Abbvie Stemcentrx Llc Anti-dll3 antibodies and drug conjugates for use in melanoma
GB2528227A (en) * 2014-03-14 2016-01-20 Medical Res Council Cyclopropene amino acids and methods
CA2943228C (en) 2014-03-20 2023-03-14 Bristol-Myers Squibb Company Stabilized fibronectin based scaffold molecules
GB201406767D0 (en) 2014-04-15 2014-05-28 Cancer Rec Tech Ltd Humanized anti-Tn-MUC1 antibodies anf their conjugates
TW201617368A (zh) 2014-09-05 2016-05-16 史坦森特瑞斯公司 新穎抗ｍｆｉ２抗體及使用方法
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
LT3191135T (lt) 2014-09-12 2020-11-25 Genentech, Inc. Anti-her2 antikūnai ir imunokonjugatai
AU2015349878A1 (en) 2014-11-21 2017-05-25 Bristol-Myers Squibb Company Antibodies against CD73 and uses thereof
JP6668345B2 (ja) 2014-11-21 2020-03-18 ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ 修飾された重鎖定常領域を含む抗体
CN107148285B (zh) 2014-11-25 2022-01-04 Adc治疗股份有限公司 吡咯并苯并二氮杂䓬-抗体缀合物
CA2969067A1 (en) 2014-11-25 2016-06-02 Bristol-Myers Squibb Company Novel pd-l1 binding polypeptides for imaging
JP6800853B2 (ja) 2014-12-11 2020-12-16 ピエール、ファーブル、メディカマン 抗ｃ１０ｏｒｆ５４抗体およびその使用
MX2017009145A (es) 2015-01-14 2017-11-22 Bristol Myers Squibb Co Dimeros de benzodiazepina, conjugados de estos, y sus metodos de preparacion y uso.
BR112017014937A2 (pt) 2015-01-14 2018-03-13 Bristol-Myers Squibb Company dímeros de benzodiazepina ligados em ponte a heteroarileno, conjugados dos mesmos, e métodos de preparação e uso
JP2018510864A (ja) 2015-03-10 2018-04-19 ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ トランスグルタミナーゼによって結合可能な抗体およびそれによって製造される結合体
CA2982205A1 (en) 2015-04-10 2016-10-13 David W. Andrews Methods and compositions for treating cancers and enhancing therapeutic immunity by selectively reducing immunomodulatory m2 monocytes
GB201506411D0 (en) 2015-04-15 2015-05-27 Bergenbio As Humanized anti-axl antibodies
GB201506389D0 (en) 2015-04-15 2015-05-27 Berkel Patricius H C Van And Howard Philip W Site-specific antibody-drug conjugates
GB201506402D0 (en) 2015-04-15 2015-05-27 Berkel Patricius H C Van And Howard Philip W Site-specific antibody-drug conjugates
DK3303396T5 (da) 2015-05-29 2024-10-07 Bristol Myers Squibb Co Antistoffer mod ox40 og anvendelser deraf
CN106279352B (zh) 2015-05-29 2020-05-22 上海新理念生物医药科技有限公司 海兔毒素10的衍生物及其应用
CN106267225B (zh) 2015-05-29 2020-03-06 上海新理念生物医药科技有限公司 三马来酰亚胺型连接子及其应用
CA2990030A1 (en) * 2015-06-23 2016-12-29 Bristol-Myers Squibb Company Macrocyclic benzodiazepine dimers, conjugates thereof, preparation and uses
EP3325482B1 (en) 2015-07-21 2020-06-24 ImmunoGen, Inc. Methods of preparing cytotoxic benzodiazepine derivatives
CN108884147B (zh) 2015-09-23 2024-02-27 百时美施贵宝公司 结合磷脂酰肌醇蛋白聚糖3的基于纤连蛋白的支架分子
CR20180243A (es) 2015-10-02 2018-07-31 Genentech Inc Conjugados de anticuerpo-fármaco de pirrolobenzodiazepina y métodos de uso
KR20180090290A (ko) 2015-12-04 2018-08-10 시애틀 지네틱스, 인크. 사차화 튜불리신 화합물들의 컨쥬게이트들
US11793880B2 (en) 2015-12-04 2023-10-24 Seagen Inc. Conjugates of quaternized tubulysin compounds
CA3008678A1 (en) 2015-12-21 2017-06-29 Bristol-Myers Squibb Company Variant antibodies for site-specific conjugation
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
EP3423494A1 (en) 2016-03-04 2019-01-09 Bristol-Myers Squibb Company Combination therapy with anti-cd73 antibodies
JP6937773B2 (ja) 2016-03-07 2021-09-22 ハンミ ファーマシューティカル カンパニー リミテッド ポリエチレングリコール誘導体及びその用途
CN109843919A (zh) 2016-03-25 2019-06-04 西雅图基因公司 用于制备聚乙二醇化的药物-接头及其中间体的方法
JP2019513371A (ja) 2016-04-01 2019-05-30 アビディティー バイオサイエンシーズ エルエルシー 核酸ポリペプチド組成物とその使用
JP2019522960A (ja) 2016-04-21 2019-08-22 アッヴィ・ステムセントルクス・エル・エル・シー 新規の抗ｂｍｐｒ１ｂ抗体及び使用方法
GB201607478D0 (en) 2016-04-29 2016-06-15 Medimmune Ltd Pyrrolobenzodiazepine Conjugates
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
CN109641910A (zh) 2016-06-24 2019-04-16 梅尔莎纳医疗公司 吡咯并苯二氮*及其缀合物
US20190218294A1 (en) 2016-09-09 2019-07-18 Bristol-Myers Squibb Company Use of an anti-pd-1 antibody in combination with an anti-mesothelin antibody in cancer treatment
JP2019530707A (ja) 2016-10-10 2019-10-24 セレラント セラピューティクス インコーポレイテッド イソキノリジノベンゾジアゼピン（ｉｑｂ）−１（クロロメチル）−２，３−ジヒドロ−１ｈ−ベンゾ［ｅ］インドール（ｃｂｉ）二量体
GB201617466D0 (en) 2016-10-14 2016-11-30 Medimmune Ltd Pyrrolobenzodiazepine conjugates
GB201619490D0 (en) * 2016-11-17 2017-01-04 Medimmune Ltd Pyrrolobenzodiazepine conjugates
WO2018098258A2 (en) 2016-11-23 2018-05-31 Immunogen, Inc. Selective sulfonation of benzodiazepine derivatives
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
PL3558391T3 (pl) 2016-12-23 2022-05-16 Immunogen, Inc. Immunokoniugaty skierowane wobec białka adam9 i sposoby ich stosowania
US20180230218A1 (en) 2017-01-04 2018-08-16 Immunogen, Inc. Met antibodies and immunoconjugates and uses thereof
MX2019008199A (es) 2017-01-06 2019-11-25 Avidity Biosciences Llc Composiciones de acido nucleico polipeptido y metodos de induccion de la omision de exon.
CN110300765B (zh) 2017-01-24 2024-08-23 依奈特制药公司 Nkp46结合剂
EP3577138A1 (en) 2017-02-06 2019-12-11 Innate Pharma Immunomodulatory antibody drug conjugates binding to a human mica polypeptide
GB201702031D0 (en) 2017-02-08 2017-03-22 Medlmmune Ltd Pyrrolobenzodiazepine-antibody conjugates
HUE056289T2 (hu) 2017-02-08 2022-02-28 Adc Therapeutics Sa Pirrolobenzodiazepin-antitest konjugátumok
RS61795B1 (sr) 2017-02-08 2021-06-30 Adc Therapeutics Sa Konjugati pirolobenzodiazepin antitela
CN117982673A (zh) 2017-02-28 2024-05-07 第一三共株式会社 抗her3抗体-药物偶联物的应用
KR102648564B1 (ko) 2017-03-24 2024-03-19 씨젠 인크. 글루쿠로니드 약물-링커의 제조 공정 및 그 중간물
CA3058360A1 (en) 2017-03-29 2018-10-04 Legochem Biosciences, Inc. Pyrrolobenzodiazepine dimer prodrug and ligand-linker conjugate compound of the same
CN110582505B (zh) 2017-04-18 2021-04-02 免疫医疗有限公司 吡咯并苯并二氮杂*缀合物
WO2018193102A1 (en) 2017-04-20 2018-10-25 Adc Therapeutics Sa Combination therapy with an anti-axl antibody-drug conjugate
US20200299400A1 (en) 2017-05-25 2020-09-24 Bristol-Myers Squibb Company Antibodies comprising modified heavy constant regions
CA3064804A1 (en) 2017-06-14 2018-12-20 Adc Therapeutics Sa Dosage regimes for the administration of an anti-cd19 adc
AU2018289581C1 (en) 2017-06-23 2025-01-30 VelosBio Inc. ROR1 antibody immunoconjugates
GB201711809D0 (en) 2017-07-21 2017-09-06 Governors Of The Univ Of Alberta Antisense oligonucleotide
CN111201030B (zh) 2017-07-25 2024-11-01 真和制药有限公司 通过阻断tim-3和其配体的相互作用治疗癌症
CN107652219B (zh) 2017-08-14 2021-06-08 上海新理念生物医药科技有限公司 四马来酰亚胺型连接子及其应用
KR102270107B1 (ko) 2017-08-18 2021-06-30 메디뮨 리미티드 피롤로벤조디아제핀 컨쥬게이트
NZ762505A (en) 2017-09-29 2026-03-27 Daiichi Sankyo Co Ltd Antibody-pyrrolobenzodiazepine derivative conjugate
EP3691657A4 (en) 2017-10-04 2021-07-21 Avidity Biosciences, Inc. NUCLEIC ACID POLYPEPTIDE COMPOSITIONS AND USES THEREOF
WO2019092148A1 (en) 2017-11-10 2019-05-16 Innate Pharma Antibodies with functionalized glutamine residues
CN111417409B (zh) 2017-11-14 2022-07-08 麦迪穆有限责任公司 吡咯并苯并二氮杂䓬缀合物
WO2019104289A1 (en) 2017-11-27 2019-05-31 Mersana Therapeutics, Inc. Pyrrolobenzodiazepine antibody conjugates
AU2018378812B2 (en) 2017-12-06 2025-05-22 Avidity Biosciences, Inc. Compositions and methods of treating muscle atrophy and myotonic dystrophy
CN111757757A (zh) 2017-12-21 2020-10-09 梅尔莎纳医疗公司 吡咯并苯并二氮呯抗体共轭物
GB201803342D0 (en) 2018-03-01 2018-04-18 Medimmune Ltd Methods
EP3774923A4 (en) 2018-03-28 2021-12-29 Mitsubishi Tanabe Pharma Corporation Drug conjugates of cmet monoclonal binding agents, and uses thereof
GB201806022D0 (en) 2018-04-12 2018-05-30 Medimmune Ltd Pyrrolobenzodiazepines and conjugates thereof
WO2020059772A1 (ja) 2018-09-20 2020-03-26 第一三共株式会社 抗ｈｅｒ３抗体－薬物コンジュゲート投与によるｈｅｒ３変異がんの治療
TWI897855B (zh) 2018-10-26 2025-09-21 美商免疫遺傳股份有限公司 Ｅ ｐ Ｃ Ａ Ｍ 抗體、可活化抗體及免疫偶聯物以及其用途
GB201817444D0 (en) 2018-10-26 2018-12-12 Res & Innovation Uk Methods and compositions
US12583932B2 (en) 2018-11-16 2026-03-24 Virtuoso Binco, Inc. CD38 and ICAM1 antibodies and uses thereof
EP3887397A1 (en) 2018-11-28 2021-10-06 Bristol-Myers Squibb Company Antibodies comprising modified heavy constant regions
KR102861586B1 (ko) 2018-11-30 2025-09-17 브리스톨-마이어스 스큅 컴퍼니 글루타민-함유 경쇄 c-말단 연장부를 포함하는 항체, 그의 접합체, 및 방법 및 용도
US12478686B2 (en) 2018-12-12 2025-11-25 Bristol-Myers Squibb Company Antibodies modified for transglutaminase conjugation, conjugates thereof, and methods and uses
GB201820725D0 (en) 2018-12-19 2019-01-30 Adc Therapeutics Sarl Pyrrolobenzodiazepine resistance
WO2020127573A1 (en) 2018-12-19 2020-06-25 Adc Therapeutics Sa Pyrrolobenzodiazepine resistance
IL312067B2 (en) 2018-12-21 2025-08-01 Avidity Biosciences Inc Anti-transferrin receptor antibodies and uses thereof
KR20200084802A (ko) 2019-01-03 2020-07-13 주식회사 레고켐 바이오사이언스 안전성이 향상된 피롤로벤조디아제핀 이량체 화합물 및 이의 용도
WO2020141923A2 (ko) 2019-01-03 2020-07-09 주식회사 레고켐 바이오사이언스 안전성이 향상된 피롤로벤조디아제핀 이량체 화합물 및 이의 용도
WO2020160156A2 (en) 2019-01-30 2020-08-06 Immutics, Inc. Anti-gal3 antibodies and uses thereof
CN113631560B (zh) 2019-03-15 2025-02-18 麦迪穆有限责任公司 氮杂环丁烷并苯并二氮杂䓬二聚体和用于治疗癌症的包含它们的缀合物
WO2020219820A1 (en) 2019-04-25 2020-10-29 Avidity Biosciences, Inc. Nucleic acid compositions and methods of multi-exon skipping
CN114375296A (zh) 2019-06-06 2022-04-19 艾维迪提生物科学公司 核酸多肽组合物及其用途
US12006499B2 (en) 2019-06-06 2024-06-11 Avidity Biosciences, Inc. Una amidites and uses thereof
GB201908128D0 (en) 2019-06-07 2019-07-24 Adc Therapeutics Sa Pyrrolobenzodiazepine-antibody conjugates
WO2021022678A1 (zh) 2019-08-07 2021-02-11 烟台迈百瑞国际生物医药股份有限公司 一种抗体药物偶联物及其应用
WO2021055306A1 (en) 2019-09-16 2021-03-25 Bristol-Myers Squibb Company Dual capture method for analysis of antibody-drug conjugates
WO2021080608A1 (en) 2019-10-25 2021-04-29 Medimmune, Llc Branched moiety for use in conjugates
JP7835441B2 (ja) 2019-12-06 2026-03-25 トゥルーバインディング，インコーポレイテッド Ｇａｌ３とインスリン受容体又はインテグリンとの相互作用を妨害する抗体及びそれらの使用方法
WO2021188390A1 (en) 2020-03-19 2021-09-23 Avidity Biosciences, Inc. Compositions and methods of treating facioscapulohumeral muscular dystrophy
SI4126066T1 (sl) 2020-03-27 2026-04-30 Avidity Biosciences, Inc. Sestavki in postopki zdravljenja mišične distrofije
EP4157338A4 (en) 2020-05-26 2024-11-13 TrueBinding, Inc. METHOD FOR TREATING INFLAMMATORY DISEASES BY GALECTIN-3 BLOCKING
IL299803A (en) 2020-07-17 2023-03-01 Daiichi Sankyo Co Ltd Production method for antibody-drug conjugate
MX2023005873A (es) 2020-11-25 2023-06-05 Innate Pharma Tratamiento del cancer.
JP2024526764A (ja) 2021-07-13 2024-07-19 トゥルーバインディング，インコーポレイテッド タンパク質凝集を防止する方法
CN118265544A (zh) 2021-09-16 2024-06-28 艾维迪提生物科学公司 治疗面肩肱型肌营养不良的组合物和方法
CN118524852A (zh) 2021-11-09 2024-08-20 真和制药有限公司 治疗或抑制心血管疾病的方法
AU2022422149A1 (en) 2021-12-23 2024-08-01 Mirecule, Inc. Compositions for delivery of polynucleotides
US12071621B2 (en) 2022-04-05 2024-08-27 Avidity Biosciences, Inc. Anti-transferrin receptor antibody-PMO conjugates for inducing DMD exon 44 skipping
CA3247699A1 (en) 2022-04-07 2025-02-03 Twinpig Biolab Inc. ITGB2 MEDIAD DRUG DISTRIBUTION SYSTEM
JP2025517476A (ja) 2022-05-25 2025-06-05 イナート・ファルマ・ソシエテ・アノニム ネクチン－４結合剤
EP4548932A1 (en) 2022-06-30 2025-05-07 Toray Industries, Inc. Pharmaceutical composition for treating and/or preventing cancer
CN120659627A (zh) 2022-07-29 2025-09-16 瑞泽恩制药公司 用于转铁蛋白受体（tfr）介导的脑和肌肉递送的组合物和方法
KR20250116795A (ko) 2022-11-14 2025-08-01 리제너론 파마슈티칼스 인코포레이티드 별아교세포로의 섬유아세포 성장 인자 수용체 3-매개된 전달을 위한 조성물 및 방법
EP4721766A1 (en) 2023-06-02 2026-04-08 Daiichi Sankyo Company, Limited Combination of (anti-her3 antibody)-drug conjugate and rasg12c inhibitor
EP4735602A2 (en) 2023-06-27 2026-05-06 Atrium Therapeutics, Inc. Compositions and methods of using prkag2-targeting antibody-oligonucleotide conjugates abstract
AU2024308906A1 (en) 2023-06-30 2026-02-05 Atrium Therapeutics, Inc. Compositions and methods of using pln-targeting antibody-oligonucleotide conjugates
CN119424671A (zh) 2023-08-01 2025-02-14 上海新理念生物医药科技有限公司 含糖基吡啶型连接子的抗体药物偶联物
WO2025096716A1 (en) 2023-11-01 2025-05-08 Incyte Corporation Anti-mutant calreticulin (calr) antibody-drug conjugates and uses thereof

Family Cites Families (116)

* Cited by examiner, † Cited by third party
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
IL33558A (en) 1968-12-30 1973-10-25 Fujisawa Pharmaceutical Co Antibiotic pyrrolo-benzodiazepine compound,its derivatives and processes for their production
DE1965304A1 (de) 1968-12-30 1970-07-23 Fujisawa Pharmaceutical Co Benzdiazepinon-Verbindungen und Verfahren zu ihrer Herstellung
JPS4843755B1 (https=) 1969-06-26 1973-12-20
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
CA1173441A (en) 1981-02-27 1984-08-28 Hoffmann-La Roche Limited Imidazodiazepines
CA1185602A (en) 1981-02-27 1985-04-16 Emilio Kyburz Imidazodiazepines
CA1184175A (en) 1981-02-27 1985-03-19 Walter Hunkeler 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
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
EP1093600B1 (en) 1998-07-08 2004-09-15 E Ink Corporation Methods for achieving improved color in microencapsulated electrophoretic devices
GB9818732D0 (en) 1998-08-27 1998-10-21 Univ Portsmouth Collection of compounds
DE69925133T2 (de) 1998-08-27 2006-01-19 Spirogen Ltd., Ryde Pyrrolobenzodiazepine
GB9818730D0 (en) 1998-08-27 1998-10-21 Univ Portsmouth Collections of compounds
GB9818731D0 (en) 1998-08-27 1998-10-21 Univ Portsmouth Compounds
US6909006B1 (en) 1999-08-27 2005-06-21 Spirogen Limited Cyclopropylindole derivatives
WO2002030894A2 (en) 2000-09-19 2002-04-18 Taiho Pharmaceutical Co., Ltd. Compositions and methods of the use thereof achiral analogues of cc-1065 and the duocarmycins
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
DK1545613T3 (da) 2002-07-31 2011-11-14 Seattle Genetics Inc Auristatinkonjugater og deres anvendelse til behandling af cancer, en autoimmun sygdom eller en infektiøs sygdom
US20040138269A1 (en) 2002-10-11 2004-07-15 Sugen, Inc. Substituted pyrroles as kinase inhibitors
GB0226593D0 (en) * 2002-11-14 2002-12-24 Consultants Ltd Compounds
ATE421967T1 (de) 2003-03-31 2009-02-15 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
WO2005040170A2 (en) 2003-10-22 2005-05-06 Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services Pyrrolobenzodiazepine derivatives, compositions comprising the same and methods related thereto
EP2478912B1 (en) 2003-11-06 2016-08-31 Seattle Genetics, Inc. Auristatin conjugates with anti-HER2 or anti-CD22 antibodies and their use in therapy
CA2556752C (en) 2004-02-23 2016-02-02 Genentech, Inc. Heterocyclic self-immolative linkers and conjugates
GB0404574D0 (en) 2004-03-01 2004-04-07 Spirogen Ltd Amino acids
GB0404577D0 (en) 2004-03-01 2004-04-07 Spirogen Ltd Pyrrolobenzodiazepines
WO2005085251A1 (en) 2004-03-01 2005-09-15 Spirogen Limited 11-hydroxy-5h-pyrrolo[2,1-c][1,4]benzodiazepin-5-one derivatives as key intermediates for the preparation of c2 substituted pyrrolobenzodiazepines
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
WO2005085260A1 (en) 2004-03-09 2005-09-15 Spirogen Limited Pyrrolobenzodiazepines
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
DK1791565T3 (en) 2004-09-23 2016-08-01 Genentech Inc Cysteingensplejsede antibodies and conjugates
US7849909B2 (en) 2004-12-24 2010-12-14 Showa Denko K.K. Production method of thermoelectric semiconductor alloy, thermoelectric conversion module and thermoelectric power generating device
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
GB0508084D0 (en) * 2005-04-21 2005-06-01 Spirogen Ltd Pyrrolobenzodiazepines
US7612062B2 (en) 2005-04-21 2009-11-03 Spirogen Limited Pyrrolobenzodiazepines
US8637664B2 (en) 2005-10-05 2014-01-28 Spirogen Sarl Alkyl 4- [4- (5-oxo-2,3,5, 11a-tetrahydo-5H-pyrrolo [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
RS52060B (sr) 2006-01-25 2012-04-30 Sanofi Citotoksični agensi koji sadrže nove derivate tomaimicina
MX2009000709A (es) 2006-07-18 2009-02-04 Sanofi Aventis Anticuerpo antagonista contra epha2 para el tratamiento de cancer.
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
PT2099823E (pt) 2006-12-01 2014-12-22 Seattle Genetics Inc Agentes de ligação ao alvo variantes e suas utilizações
WO2009011753A2 (en) 2007-07-11 2009-01-22 The Regents Of The University Of California Nanostructured polymer membranes for proton conduction
SI2019104T1 (sl) 2007-07-19 2013-12-31 Sanofi Citotoksična sredstva, ki obsegajo nove tomaimicinske derivate, in njihova terapevtska uporaba
GB0722087D0 (en) 2007-11-09 2007-12-19 Spirogen Ltd Polyamides
GB0722088D0 (en) 2007-11-09 2007-12-19 Spirogen Ltd Pyrrolobenzodiazepines
DK2265283T3 (da) 2008-03-18 2014-10-20 Seattle Genetics Inc Auristatin-lægemiddel-linker-konjugater
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
RU2683325C2 (ru) 2009-02-05 2019-03-28 Иммьюноджен, Инк. Новые производные бензодиазепина
FR2949469A1 (fr) 2009-08-25 2011-03-04 Sanofi Aventis Derives anticancereux, leur preparation et leur application en therapeutique
US9040526B2 (en) 2010-02-09 2015-05-26 Bristol-Myers Squibb Company Benzylpyrrolidinone derivatives as modulators of chemokine receptor activity
GB201006340D0 (en) 2010-04-15 2010-06-02 Spirogen Ltd Synthesis method and intermediates
SI2528625T1 (sl) 2010-04-15 2013-11-29 Spirogen Sarl Pirolobenzodiazepini in njihovi konjugati
JP5875083B2 (ja) 2010-04-15 2016-03-02 メディミューン リミテッド 増殖性疾患治療用ピロロベンゾジアゼピン
CA2795349C (en) 2010-04-15 2016-11-29 Seattle Genetics, Inc. Targeted pyrrolobenzodiazepine conjugates
JP5826863B2 (ja) 2011-02-15 2015-12-02 イミュノジェン・インコーポレーテッド 細胞傷害性ベンゾジアゼピン誘導体
SG11201400770SA (en) 2011-09-20 2014-04-28 Spirogen Sarl Pyrrolobenzodiazepines as unsymmetrical dimeric pbd compounds for inclusion in targeted conjugates
CA2850373C (en) 2011-10-14 2019-07-16 Seattle Genetics, Inc. Pyrrolobenzodiazepines and targeted conjugates
AU2012322932B2 (en) 2011-10-14 2016-11-10 Medimmune Limited Pyrrolobenzodiazepines
BR112014009050B1 (pt) 2011-10-14 2022-06-21 Medimmune Limited Conjugado anticorpo-fármaco de pirrolbenzodiazepinas, composição farmacêutica que compreende o mesmo, bem como compostos de pirrolbenzodiazepinas
CN103997893B (zh) 2011-10-14 2019-04-12 西雅图基因公司 吡咯并苯并二氮杂卓和靶向结合物
EP2751111B1 (en) 2011-10-14 2017-04-26 MedImmune Limited Asymmetrical bis-(5H-Pyrrolo[2,1-c][1,4]benzodiazepin-5-one) derivatives for the treatment of proliferative or autoimmune diseases
BR112014009070B1 (pt) 2011-10-14 2021-11-23 Medimmune Limited Método de síntese e intermediários úteis na preparação de pirrolobenzo-diazepinas
ES2623042T3 (es) 2012-04-30 2017-07-10 Medimmune Limited Pirrolobenzodiacepinas
AU2013255612B2 (en) 2012-04-30 2017-06-22 Medimmune Limited Pyrrolobenzodiazepines
IN2014DN10652A (https=) 2012-07-09 2015-09-11 Genentech Inc
AR091703A1 (es) 2012-07-09 2015-02-25 Genentech Inc Anticuerpos e inmunoconjugados que comprenden anticuerpos anti-cd22
JP2015528818A (ja) 2012-08-02 2015-10-01 ジェネンテック， インコーポレイテッド 抗ｅｔｂｒ抗体およびイムノコンジュゲート
HRP20182129T1 (hr) 2012-10-12 2019-02-08 Adc Therapeutics Sa Konjugati protutijelo - pirolobenzodiazepin
HRP20190366T1 (hr) 2012-10-12 2019-04-19 Medimmune Limited Pirolobenzodiazepini i njihovi konjugati
MX338711B (es) 2012-10-12 2016-04-28 Medimmune Ltd Pirrolobenzodiazepinas y conjugados de las mismas.
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
EP2906296B1 (en) 2012-10-12 2018-03-21 ADC Therapeutics SA Pyrrolobenzodiazepine-antibody conjugates
RS57694B1 (sr) 2012-10-12 2018-11-30 Adc Therapeutics Sa Pirolobenzodiazepin - anti-psma konjugati antitela
JP6392765B2 (ja) 2012-10-12 2018-09-19 エイディーシー・セラピューティクス・エス・アーＡｄｃ Ｔｈｅｒａｐｅｕｔｉｃｓ Ｓａ ピロロベンゾジアゼピン−抗体結合体
EP2906249B1 (en) 2012-10-12 2018-06-27 MedImmune Limited Synthesis and intermediates of pyrrolobenzodiazepine derivatives for conjugation
SI2906252T1 (sl) 2012-10-12 2017-10-30 Adc Therapeutics Sa Pirolobenzodiazepin-anti-HER2 protitelesni konjugati
ES2680153T3 (es) 2012-10-12 2018-09-04 Adc Therapeutics Sa Conjugados de anticuerpos anti-PSMA-pirrolobenzodiazepinas
CN105189507A (zh) 2012-12-21 2015-12-23 斯皮罗根有限公司 吡咯并苯并二氮杂卓及其结合物
CN110627797A (zh) 2012-12-21 2019-12-31 麦迪穆有限责任公司 用于治疗增殖性和自身免疫疾病的非对称吡咯并苯并二氮杂卓二聚物
ES2731681T3 (es) 2013-02-22 2019-11-18 Abbvie Stemcentrx Llc Conjugados de anticuerpo anti-DLL3 y PBD y usos de los mismos
MX362970B (es) 2013-03-13 2019-02-28 Medimmune Ltd Pirrolobenzodiazepinas y conjugados de las mismas.
AU2014229529B2 (en) 2013-03-13 2018-02-15 Medimmune Limited Pyrrolobenzodiazepines and conjugates thereof
TWI680766B (zh) 2013-03-13 2020-01-01 英商梅迪繆思有限公司 吡咯并苯并二氮呯及其共軛物
US20160106861A1 (en) 2013-04-26 2016-04-21 Spirogen Sarl Axl antibody-drug conjugate and its use for the treatment of cancer
GB201317982D0 (en) 2013-10-11 2013-11-27 Spirogen Sarl Pyrrolobenzodiazepines and conjugates thereof
GB201317981D0 (en) 2013-10-11 2013-11-27 Spirogen Sarl Pyrrolobenzodiazepines and conjugates thereof
EP3054983B1 (en) 2013-10-11 2019-03-20 Medimmune Limited Pyrrolobenzodiazepine-antibody conjugates
US20160256561A1 (en) 2013-10-11 2016-09-08 Medimmune Limited Pyrrolobenzodiazepine-antibody conjugates
WO2015052534A1 (en) 2013-10-11 2015-04-16 Spirogen Sàrl Pyrrolobenzodiazepine-antibody conjugates
WO2015052535A1 (en) 2013-10-11 2015-04-16 Spirogen Sàrl Pyrrolobenzodiazepine-antibody conjugates
KR102337414B1 (ko) 2013-12-16 2021-12-10 제넨테크, 인크. 펩타이드 모방체 화합물 및 이의 항체-약물 컨쥬게이트
GB201406767D0 (en) 2014-04-15 2014-05-28 Cancer Rec Tech Ltd Humanized anti-Tn-MUC1 antibodies anf their conjugates

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