BR112017014599A2 - dímeros de benzodiazepina, conjugados dos mesmos, e métodos de preparação e uso - Google Patents

dímeros de benzodiazepina, conjugados dos mesmos, e métodos de preparação e uso

Info

Publication number
BR112017014599A2
BR112017014599A2 BR112017014599A BR112017014599A BR112017014599A2 BR 112017014599 A2 BR112017014599 A2 BR 112017014599A2 BR 112017014599 A BR112017014599 A BR 112017014599A BR 112017014599 A BR112017014599 A BR 112017014599A BR 112017014599 A2 BR112017014599 A2 BR 112017014599A2
Authority
BR
Brazil
Prior art keywords
conjugates
preparation
methods
benzodiazepine dimers
dimers
Prior art date
Application number
BR112017014599A
Other languages
English (en)
Portuguese (pt)
Inventor
Zhang Yong
M. Mcdonald Ivar
S. Chowdari Naidu
N. Huynh Tram
M. Borzilleri Robert
Gangwar Sanjeev
Original Assignee
Bristol-Myers Squibb Company
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Bristol-Myers Squibb Company filed Critical Bristol-Myers Squibb Company
Publication of BR112017014599A2 publication Critical patent/BR112017014599A2/pt

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic 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
    • C07D487/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D519/00Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K5/00Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06Dipeptides
    • C07K5/06008Dipeptides with the first amino acid being neutral
    • C07K5/06017Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/06034Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
    • C07K5/06052Val-amino acid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/68Medicinal 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
    • A61K47/6835Medicinal 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
    • A61K47/6843Medicinal 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 material from animals or humans
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/68Medicinal 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
    • A61K47/6835Medicinal 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
    • A61K47/6849Medicinal 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 receptor, a cell surface antigen or a cell surface determinant
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76Antagonist effect on antigen, e.g. neutralization or inhibition of binding

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Cell Biology (AREA)
  • Zoology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Peptides Or Proteins (AREA)
  • Medicinal Preparation (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
BR112017014599A 2015-01-14 2016-01-13 dímeros de benzodiazepina, conjugados dos mesmos, e métodos de preparação e uso BR112017014599A2 (pt)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201562103157P 2015-01-14 2015-01-14
US201562215928P 2015-09-09 2015-09-09
PCT/US2016/013136 WO2016115191A1 (en) 2015-01-14 2016-01-13 Benzodiazepine dimers, conjugates thereof, and methods of making and using

Publications (1)

Publication Number Publication Date
BR112017014599A2 true BR112017014599A2 (pt) 2018-01-16

Family

ID=55305072

Family Applications (1)

Application Number Title Priority Date Filing Date
BR112017014599A BR112017014599A2 (pt) 2015-01-14 2016-01-13 dímeros de benzodiazepina, conjugados dos mesmos, e métodos de preparação e uso

Country Status (19)

Country Link
US (4) US9527871B2 (https=)
EP (1) EP3245213B1 (https=)
JP (1) JP6498773B2 (https=)
KR (1) KR20170102980A (https=)
CN (1) CN107428780B (https=)
AU (1) AU2016206798A1 (https=)
BR (1) BR112017014599A2 (https=)
CA (1) CA2973354A1 (https=)
CL (1) CL2017001824A1 (https=)
CO (1) CO2017008078A2 (https=)
EA (1) EA201791550A1 (https=)
ES (1) ES2783624T3 (https=)
IL (1) IL253402A0 (https=)
MX (1) MX2017009145A (https=)
PE (1) PE20171184A1 (https=)
SG (1) SG11201705646XA (https=)
TW (1) TW201632531A (https=)
WO (1) WO2016115191A1 (https=)
ZA (1) ZA201704738B (https=)

Families Citing this family (30)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
US9504694B2 (en) * 2015-03-19 2016-11-29 Cellerant Therapeutics, Inc. Isoquinolidinobenzodiazepines
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
WO2018053552A2 (en) * 2016-09-19 2018-03-22 Cellerant Therapeutics, Inc. Isoquinolidinobenzodiazepines
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
US10738338B2 (en) 2016-10-18 2020-08-11 The Research Foundation for the State University Method and composition for biocatalytic protein-oligonucleotide conjugation and protein-oligonucleotide conjugate
US10398783B2 (en) 2016-10-20 2019-09-03 Bristol-Myers Squibb Company Antiproliferative compounds and conjugates made therefrom
EP4148044A1 (en) 2017-01-25 2023-03-15 ImmunoGen, Inc. Methods of preparing cytotoxic benzodiazepine derivatives
WO2018195243A1 (en) * 2017-04-20 2018-10-25 Immunogen, Inc. Cytotoxic benzodiazepine derivatives and conjugates thereof
JP2020531430A (ja) 2017-08-16 2020-11-05 ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company 抗体を標的とする抗ctla4プロボディ療法
GB201714115D0 (en) 2017-09-04 2017-10-18 Femtogenix Ltd Cytotoxic agents
NZ762505A (en) 2017-09-29 2026-03-27 Daiichi Sankyo Co Ltd Antibody-pyrrolobenzodiazepine derivative conjugate
MX2020012718A (es) * 2018-05-29 2021-02-16 Intocell Inc Derivados de benzodiazepinas novedosos y usos de los mismos.
CN112930350A (zh) * 2018-10-31 2021-06-08 尹图赛利有限公司 稠合杂环苯并二氮杂䓬衍生物及其用途
SG11202104993SA (en) 2018-11-14 2021-06-29 Daiichi Sankyo Co Ltd Anti-cdh6 antibody-pyrrolobenzodiazepine derivative conjugate
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
GB201901197D0 (en) 2019-01-29 2019-03-20 Femtogenix Ltd G-A Crosslinking cytotoxic agents
CN113631229B (zh) 2019-03-25 2025-09-23 第一三共株式会社 抗体-吡咯并苯并二氮杂卓衍生物偶联物
WO2020196475A1 (ja) 2019-03-25 2020-10-01 第一三共株式会社 抗her2抗体-ピロロベンゾジアゼピン誘導体コンジュゲート
CA3139180A1 (en) 2019-03-27 2020-10-01 Daiichi Sankyo Company, Limited Combination of antibody-pyrrolobenzodiazepine derivative conjugate and parp inhibitor
WO2020251878A1 (en) 2019-06-11 2020-12-17 Bristol-Myers Squibb Company Anti-ctla4 antibody prodruggable (probody) at a cdr position
WO2021055306A1 (en) 2019-09-16 2021-03-25 Bristol-Myers Squibb Company Dual capture method for analysis of antibody-drug conjugates
CA3204628A1 (en) 2021-01-13 2022-07-21 John T. POIRIER Antibody-pyrrolobenzodiazepine derivative conjugate
CN113372245B (zh) * 2021-06-17 2023-01-13 仪征市海帆化工有限公司 一种n-苯甲酰基-o,o-对甲苯磺酰基-二乙醇胺的合成方法
WO2023037237A1 (en) * 2021-09-09 2023-03-16 Wavelength Enterprises Ltd Process for the preparation of remimazolam
CA3234692A1 (en) * 2021-09-30 2023-04-06 Ajinomoto Co., Inc. Conjugate of antibody and functional substance or salt thereof, and antibody derivative and compound used in production of the same or salts thereof
IL312728A (en) 2021-11-30 2024-07-01 Daiichi Sankyo Co Ltd Protease-cleavable masked antibodies
TW202342106A (zh) 2022-02-09 2023-11-01 日商第一三共股份有限公司 環境應答性遮蔽抗體及其利用
WO2025214466A1 (en) * 2024-04-12 2025-10-16 BeiGene Guangzhou Biologics Manufacturing Co., Ltd. Targeted pyrrolobenzodiazapine conjugates

Family Cites Families (41)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE69925133T2 (de) 1998-08-27 2006-01-19 Spirogen Ltd., Ryde Pyrrolobenzodiazepine
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
GB0226593D0 (en) 2002-11-14 2002-12-24 Consultants Ltd Compounds
GB0416511D0 (en) 2003-10-22 2004-08-25 Spirogen Ltd Pyrrolobenzodiazepines
GB0404578D0 (en) 2004-03-01 2004-04-07 Spirogen Ltd Pyrrolobenzodiazepines
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
WO2005085260A1 (en) 2004-03-09 2005-09-15 Spirogen Limited Pyrrolobenzodiazepines
US7612062B2 (en) 2005-04-21 2009-11-03 Spirogen Limited Pyrrolobenzodiazepines
NZ566395A (en) 2005-09-26 2012-03-30 Medarex Inc Human monoclonal antibodies to CD70
US8383118B2 (en) 2005-12-08 2013-02-26 Medarex, Inc. Human monoclonal antibodies to fucosyl-GM1 and methods for using anti-fucosyl-GM1
RS52060B (sr) 2006-01-25 2012-04-30 Sanofi Citotoksični agensi koji sadrže nove derivate tomaimicina
ME02345B (me) 2007-07-17 2016-08-31 Squibb & Sons Llc MONOKLONSKA ANTlTELA PROTIV GLIPIKANA-3
SI2019104T1 (sl) 2007-07-19 2013-12-31 Sanofi Citotoksična sredstva, ki obsegajo nove tomaimicinske derivate, in njihova terapevtska uporaba
ES2526355T3 (es) 2007-10-01 2015-01-09 Bristol-Myers Squibb Company Anticuerpos humanos que se adhieren a mesotelina, y usos de los mismos
GB0813432D0 (en) 2008-07-22 2008-08-27 Spirogen Ltd Pyrrolobenzodiazepines
GB0819095D0 (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
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
SI2528625T1 (sl) 2010-04-15 2013-11-29 Spirogen Sarl Pirolobenzodiazepini in njihovi konjugati
FR2963007B1 (fr) 2010-07-26 2013-04-05 Sanofi Aventis Derives anticancereux, leur preparation et leur application therapeutique
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
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
CA2850373C (en) 2011-10-14 2019-07-16 Seattle Genetics, Inc. Pyrrolobenzodiazepines and targeted conjugates
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
WO2013177481A1 (en) * 2012-05-25 2013-11-28 Immunogen, Inc. Benzodiazepines and conjugates thereof
HK1211208A1 (zh) 2012-08-22 2016-05-20 Immunogen, Inc. 細胞毒性苯並二氮呯衍生物
MX338711B (es) 2012-10-12 2016-04-28 Medimmune Ltd Pirrolobenzodiazepinas y conjugados de las mismas.
HRP20190366T1 (hr) 2012-10-12 2019-04-19 Medimmune Limited Pirolobenzodiazepini i njihovi konjugati
CA2891280C (en) 2012-11-24 2018-03-20 Hangzhou Dac Biotech Co., Ltd. Hydrophilic linkers and their uses for conjugation of drugs to cell binding molecules
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
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
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.
US20160106861A1 (en) 2013-04-26 2016-04-21 Spirogen Sarl Axl antibody-drug conjugate and its use for the treatment of cancer

Also Published As

Publication number Publication date
CA2973354A1 (en) 2016-07-21
CN107428780B (zh) 2020-09-04
US20180079781A1 (en) 2018-03-22
EP3245213A1 (en) 2017-11-22
SG11201705646XA (en) 2017-08-30
TW201632531A (zh) 2016-09-16
US9822144B2 (en) 2017-11-21
AU2016206798A1 (en) 2017-08-31
JP2018503639A (ja) 2018-02-08
MX2017009145A (es) 2017-11-22
CO2017008078A2 (es) 2017-11-10
WO2016115191A1 (en) 2016-07-21
US10112975B2 (en) 2018-10-30
CL2017001824A1 (es) 2018-02-09
EP3245213B1 (en) 2020-03-04
KR20170102980A (ko) 2017-09-12
ZA201704738B (en) 2019-02-27
JP6498773B2 (ja) 2019-04-10
PE20171184A1 (es) 2017-08-22
US9676794B2 (en) 2017-06-13
CN107428780A (zh) 2017-12-01
US20170073357A1 (en) 2017-03-16
US20170233436A1 (en) 2017-08-17
EA201791550A1 (ru) 2017-11-30
US9527871B2 (en) 2016-12-27
IL253402A0 (en) 2017-09-28
US20160200742A1 (en) 2016-07-14
ES2783624T3 (es) 2020-09-17

Similar Documents

Publication Publication Date Title
BR112017014599A2 (pt) dímeros de benzodiazepina, conjugados dos mesmos, e métodos de preparação e uso
BR112017014937A2 (pt) dímeros de benzodiazepina ligados em ponte a heteroarileno, conjugados dos mesmos, e métodos de preparação e uso
BR112015023752A2 (pt) complexos multiespecificos monovalentes e multivalentes e seus usos
CO2017001994A2 (es) Compuestos activos hacia bromodominios
BR112016012146A2 (pt) Compostos derivados de aminopiridina como inibidores quinase da família tam, composição farmacêutica compreendendo ditos compostos e uso terapêutico dos mesmos
CL2017002422A1 (es) Derivados de maitansinoide, conjugados de los mismos, y métodos de uso.
MX2016004596A (es) Conjugados de proteina-polimero-farmaco.
BR112016015105A2 (pt) Conjugados var2csa-droga
CL2016002269A1 (es) Moduladores alostéricos del núcleo proteico de la hepatitis b.
MX2016004659A (es) Conjugados proteina-polimero-farmaco.
UY34605A (es) Derivados de arilalquiloxipirimidina e insecticidas agrohortícolas que comprenden dichos derivados como principios activos, y método de uso de los mismos
BR112018003269A2 (pt) conjugados de fármaco-anticorpo anti-dll3 e métodos de utilização
CL2012002355A1 (es) Compuestos derivados de 1,3,4,8-tetrahidro-2h-pirido[1,2-a]pirazina; composicion farmaceutica que los comprende; kit farmaceutico; y su uso como inhibidores de la integrasa del vih para el tratamiento de una enfermedad infecciosa del vih.
BR112019000693A2 (pt) composições de muc1- car e métodos para uso
BR112017025711A2 (pt) ?composições, processo para preparação de siloxanos modificados por poliéter e uso das composições inovadoras?
BR112018010279A2 (pt) novos anticorpos anti-emr2 e métodos de uso
BR112017027258A2 (pt) dímeros de benzodiazepina macrocíclicos, conjugados dos mesmos, preparação e usos
EP3878445A3 (en) Acamprosate formulations, methods of using the same, and combinations comprising the same
BR112017000246A2 (pt) composto, sal farmaceuticamente aceitável de um composto, composição farmacêutica, e, uso de um composto ou de um sal
BR112017018940A2 (pt) anticorpos sítio-específicos projetados e métodos de uso
CL2018001913A1 (es) Derivados de 3-(carboxietil)-8-amino-2-oxo-1,3-diaza-espiro-[4.5]-decano
BR112018012883A2 (pt) novos anticorpos anti-upk1b e métodos de uso
MX393281B (es) Conjugados y composiciones de texafirina-pt (iv) para su uso para superar la resistencia del platino.
BR112018010456A2 (pt) ?composição, método para limpeza ou desinfecção de uma superfície e uso de uma composição?
BR112016015394A8 (pt) sistemas de geração de pulso elétrico

Legal Events

Date Code Title Description
B11A Dismissal acc. art.33 of ipl - examination not requested within 36 months of filing
B11Y Definitive dismissal - extension of time limit for request of examination expired [chapter 11.1.1 patent gazette]