SG11201705646XA - Benzodiazepine dimers, conjugates thereof, and methods of making and using - Google Patents
Benzodiazepine dimers, conjugates thereof, and methods of making and usingInfo
- Publication number
- SG11201705646XA SG11201705646XA SG11201705646XA SG11201705646XA SG11201705646XA SG 11201705646X A SG11201705646X A SG 11201705646XA SG 11201705646X A SG11201705646X A SG 11201705646XA SG 11201705646X A SG11201705646X A SG 11201705646XA SG 11201705646X A SG11201705646X A SG 11201705646XA
- Authority
- SG
- Singapore
- Prior art keywords
- conjugates
- making
- methods
- benzodiazepine dimers
- benzodiazepine
- Prior art date
Links
- 125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 title 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
- C07K5/06052—Val-amino acid
-
- 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
- A61K47/00—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
- 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
- A61K47/6835—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
- A61K47/6843—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 material from animals or humans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—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
- 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
- A61K47/6835—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
- A61K47/6849—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 receptor, a cell surface antigen or a cell surface determinant
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- C07K—PEPTIDES
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- 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
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist 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)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Cell Biology (AREA)
- Zoology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (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)
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 |
|---|---|
| SG11201705646XA true SG11201705646XA (en) | 2017-08-30 |
Family
ID=55305072
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SG11201705646XA SG11201705646XA (en) | 2015-01-14 | 2016-01-13 | Benzodiazepine dimers, conjugates thereof, and methods of making and using |
Country Status (19)
| Country | Link |
|---|---|
| US (4) | US9527871B2 (enExample) |
| EP (1) | EP3245213B1 (enExample) |
| JP (1) | JP6498773B2 (enExample) |
| KR (1) | KR20170102980A (enExample) |
| CN (1) | CN107428780B (enExample) |
| AU (1) | AU2016206798A1 (enExample) |
| BR (1) | BR112017014599A2 (enExample) |
| CA (1) | CA2973354A1 (enExample) |
| CL (1) | CL2017001824A1 (enExample) |
| CO (1) | CO2017008078A2 (enExample) |
| EA (1) | EA201791550A1 (enExample) |
| ES (1) | ES2783624T3 (enExample) |
| IL (1) | IL253402A0 (enExample) |
| MX (1) | MX2017009145A (enExample) |
| PE (1) | PE20171184A1 (enExample) |
| SG (1) | SG11201705646XA (enExample) |
| TW (1) | TW201632531A (enExample) |
| WO (1) | WO2016115191A1 (enExample) |
| ZA (1) | ZA201704738B (enExample) |
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| JP6676058B2 (ja) * | 2015-01-14 | 2020-04-08 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | ヘテロアリーレン架橋したベンゾジアゼピン二量体、そのコンジュゲート、ならびに製造および使用方法 |
| US9504694B2 (en) * | 2015-03-19 | 2016-11-29 | Cellerant Therapeutics, Inc. | Isoquinolidinobenzodiazepines |
| WO2018048975A1 (en) | 2016-09-09 | 2018-03-15 | 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 |
| EP3522932A4 (en) * | 2016-10-10 | 2020-06-24 | Cellerant Therapeutics, Inc. | ISOCHINOLIDINOBENZODIAZEPINE (IQB) -1 (CHLORMETHYL) -2,3-DIHYDRO-1-H-BENZO [E] INDOL (CBI) DIMERS |
| 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 |
| WO2018075842A1 (en) | 2016-10-20 | 2018-04-26 | Bristol-Myers Squibb Company | Condensed benzodiazepine derivatives and conjugates made therefrom |
| CN110225904B (zh) * | 2017-01-25 | 2023-10-27 | 伊缪诺金公司 | 制备细胞毒性苯二氮䓬衍生物的方法 |
| WO2018195243A1 (en) * | 2017-04-20 | 2018-10-25 | Immunogen, Inc. | Cytotoxic benzodiazepine derivatives and conjugates thereof |
| WO2019036433A2 (en) | 2017-08-16 | 2019-02-21 | Bristol-Myers Squibb Company | ANTIBODIES IN THE FORM OF PRODRUGS, PRODRUGS BASED THEREON, THEIR METHODS OF USE AND PREPARATION |
| GB201714115D0 (en) | 2017-09-04 | 2017-10-18 | Femtogenix Ltd | Cytotoxic agents |
| MX2020003125A (es) | 2017-09-29 | 2020-10-01 | Daiichi Sankyo Co Ltd | Conjugado de anticuerpo-derivado de pirrolobenzodiazepina. |
| US11084801B2 (en) * | 2018-05-29 | 2021-08-10 | Intocell, Inc. | Benzodiazepine derivatives and uses thereof |
| US12274898B2 (en) * | 2018-10-31 | 2025-04-15 | Intocell, Inc. | Substituted benzodiazepines as antibody-drug conjugates |
| WO2020100954A1 (ja) | 2018-11-14 | 2020-05-22 | 第一三共株式会社 | 抗ｃｄｈ６抗体－ピロロベンゾジアゼピン誘導体コンジュゲート |
| HRP20230500T1 (hr) | 2018-11-30 | 2023-07-21 | Bristol-Myers Squibb Company | Antitijelo koje sadrži c-terminalnu ekstenziju lakog lanca koja sadrži glutamin, njegovi konjugati, i postupci i primjene |
| KR20210102334A (ko) | 2018-12-12 | 2021-08-19 | 브리스톨-마이어스 스큅 컴퍼니 | 트랜스글루타미나제 접합을 위해 변형된 항체, 그의 접합체, 및 방법 및 용도 |
| GB201901197D0 (en) | 2019-01-29 | 2019-03-20 | Femtogenix Ltd | G-A Crosslinking cytotoxic agents |
| TWI856078B (zh) | 2019-03-25 | 2024-09-21 | 日商第一三共股份有限公司 | 抗體–吡咯并苯二氮呯衍生物結合物、其製造方法及其用途 |
| KR20210141630A (ko) | 2019-03-25 | 2021-11-23 | 다이이찌 산쿄 가부시키가이샤 | 항 her2 항체-피롤로벤조디아제핀 유도체 콘주게이트 |
| 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 |
| US20240377413A1 (en) | 2019-09-16 | 2024-11-14 | Bristol-Myers Squibb Company | Dual capture method for analysis of antibody-drug conjugates |
| KR20230146521A (ko) | 2021-01-13 | 2023-10-19 | 메모리얼 슬로안 케터링 캔서 센터 | 항체-피롤로벤조디아제핀 유도체 접합체 |
| 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 |
| WO2023054706A1 (ja) * | 2021-09-30 | 2023-04-06 | 味の素株式会社 | 抗体および機能性物質のコンジュゲートまたはその塩、ならびにその製造に用いられる抗体誘導体および化合物またはそれらの塩 |
| IL312728A (en) | 2021-11-30 | 2024-07-01 | Daiichi Sankyo Co Ltd | Protease-cleavable masked antibodies |
| CA3251410A1 (en) | 2022-02-09 | 2025-07-08 | Daiichi Sankyo Co Ltd | Masked antibody sensitive to the environment and its use |
| WO2025214466A1 (en) * | 2024-04-12 | 2025-10-16 | BeiGene Guangzhou Biologics Manufacturing Co., Ltd. | Targeted pyrrolobenzodiazapine conjugates |
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| ATE320436T1 (de) | 1998-08-27 | 2006-04-15 | Spirogen Ltd | Dimere pyrrolobenzodiazepine |
| ES2369542T3 (es) | 2002-07-31 | 2011-12-01 | Seattle Genetics, Inc. | Conjugados de auristatina y su uso para tratar cáncer, una enfermedad autoinmune o una enfermedad infecciosa. |
| GB0226593D0 (en) | 2002-11-14 | 2002-12-24 | Consultants Ltd | Compounds |
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| GB0404578D0 (en) | 2004-03-01 | 2004-04-07 | Spirogen Ltd | Pyrrolobenzodiazepines |
| PT2270010E (pt) | 2004-03-01 | 2012-03-12 | Spirogen Ltd | Derivados de 11-hidroxi-5h-pirrolo[2,1-c][1,4]benzodiazepin- 5-ona como intermediários chave para a preparação de pirrolobenzodiazepinas substituídas em c2 |
| GB0404577D0 (en) | 2004-03-01 | 2004-04-07 | Spirogen Ltd | Pyrrolobenzodiazepines |
| WO2005085260A1 (en) | 2004-03-09 | 2005-09-15 | Spirogen Limited | Pyrrolobenzodiazepines |
| PT1879901E (pt) | 2005-04-21 | 2010-03-29 | Spirogen Ltd | Pirrolobenzodiazepinas |
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| CN101356195B (zh) | 2005-12-08 | 2013-04-03 | 米德列斯公司 | 抗岩藻糖基-gm1的人单克隆抗体及使用抗岩藻糖基-gm1抗体的方法 |
| SI1813614T1 (sl) | 2006-01-25 | 2012-01-31 | Sanofi 174 | Citotoksična sredstva, ki obsegajo nove tomajmicinske derivate |
| RS54624B1 (sr) | 2007-07-17 | 2016-08-31 | E. R. Squibb & Sons, L.L.C. | Monoklonska antitela protiv glipikana-3 |
| ES2435779T3 (es) | 2007-07-19 | 2013-12-23 | Sanofi | Agentes citotóxicos que comprenden nuevos derivados de tomaimicina y su uso terapéutico |
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| GB0813432D0 (en) | 2008-07-22 | 2008-08-27 | Spirogen Ltd | Pyrrolobenzodiazepines |
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| CN105198908B (zh) * | 2009-02-05 | 2019-12-24 | 伊缪诺金公司 | 新型苯并二氮杂*衍生物 |
| FR2949469A1 (fr) | 2009-08-25 | 2011-03-04 | Sanofi Aventis | Derives anticancereux, leur preparation et leur application en therapeutique |
| ES2623057T3 (es) | 2010-04-15 | 2017-07-10 | Medimmune Limited | Pirrolobenzodiazepinas usadas para tratar enfermedades proliferativas |
| CN102933236B (zh) | 2010-04-15 | 2014-10-08 | 斯皮罗根有限公司 | 吡咯并苯二氮卓类及其结合物 |
| CN103068405A (zh) | 2010-04-15 | 2013-04-24 | 西雅图基因公司 | 靶向吡咯并苯并二氮杂卓结合物 |
| FR2963007B1 (fr) | 2010-07-26 | 2013-04-05 | Sanofi Aventis | Derives anticancereux, leur preparation et leur application therapeutique |
| PT2675480T (pt) * | 2011-02-15 | 2019-04-15 | Immunogen Inc | Métodos para preparação de conjugados |
| CN103987718A (zh) | 2011-09-20 | 2014-08-13 | 斯皮罗根有限公司 | 作为非对称二聚体pbd化合物用于内含在靶向结合物中的吡咯并苯并二氮杂卓 |
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| WO2013055987A1 (en) | 2011-10-14 | 2013-04-18 | Spirogen Sàrl | Pyrrolobenzodiazepines and conjugates thereof |
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| CN103998450B (zh) | 2011-10-14 | 2017-03-08 | 麦迪穆有限责任公司 | 吡咯并苯并二氮杂卓 |
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| JP6133431B2 (ja) | 2012-11-24 | 2017-05-24 | ハンジョウ ディーエーシー バイオテック シーオー．，エルティディ．Ｈａｎｇｚｈｏｕ Ｄａｃ Ｂｉｏｔｅｃｈ Ｃｏ．，Ｌｔｄ． | 親水性連結体及び薬物分子と細胞結合分子との共役反応における親水性連結体の使用 |
| JP6527466B2 (ja) | 2012-12-21 | 2019-06-05 | メドイミューン・リミテッドＭｅｄＩｍｍｕｎｅ Ｌｉｍｉｔｅｄ | 増殖性疾患および自己免疫疾患の治療に使用するための非対称ピロロベンゾジアゼピンニ量体 |
| WO2014096368A1 (en) | 2012-12-21 | 2014-06-26 | Spirogen Sàrl | Pyrrolobenzodiazepines and conjugates thereof |
| KR102066319B1 (ko) | 2013-03-13 | 2020-01-14 | 메디뮨 리미티드 | 피롤로벤조디아제핀 및 그의 컨쥬게이트 |
| WO2014159981A2 (en) | 2013-03-13 | 2014-10-02 | Spirogen Sarl | Pyrrolobenzodiazepines and conjugates thereof |
| NZ710746A (en) | 2013-03-13 | 2018-11-30 | Medimmune Ltd | Pyrrolobenzodiazepines and conjugates thereof |
| US20160106861A1 (en) | 2013-04-26 | 2016-04-21 | Spirogen Sarl | Axl antibody-drug conjugate and its use for the treatment of cancer |
-
2016
- 2016-01-13 JP JP2017537227A patent/JP6498773B2/ja not_active Expired - Fee Related
- 2016-01-13 EA EA201791550A patent/EA201791550A1/ru unknown
- 2016-01-13 EP EP16703196.2A patent/EP3245213B1/en active Active
- 2016-01-13 ES ES16703196T patent/ES2783624T3/es active Active
- 2016-01-13 BR BR112017014599A patent/BR112017014599A2/pt not_active Application Discontinuation
- 2016-01-13 US US14/994,296 patent/US9527871B2/en active Active
- 2016-01-13 AU AU2016206798A patent/AU2016206798A1/en not_active Abandoned
- 2016-01-13 CN CN201680006151.5A patent/CN107428780B/zh active Active
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- 2016-01-13 TW TW105100987A patent/TW201632531A/zh unknown
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| EP3245213B1 (en) | 2020-03-04 |
| IL253402A0 (en) | 2017-09-28 |
| US20180079781A1 (en) | 2018-03-22 |
| US10112975B2 (en) | 2018-10-30 |
| US20160200742A1 (en) | 2016-07-14 |
| US9527871B2 (en) | 2016-12-27 |
| US9676794B2 (en) | 2017-06-13 |
| JP2018503639A (ja) | 2018-02-08 |
| WO2016115191A1 (en) | 2016-07-21 |
| AU2016206798A1 (en) | 2017-08-31 |
| CO2017008078A2 (es) | 2017-11-10 |
| US9822144B2 (en) | 2017-11-21 |
| PE20171184A1 (es) | 2017-08-22 |
| CL2017001824A1 (es) | 2018-02-09 |
| ZA201704738B (en) | 2019-02-27 |
| CN107428780A (zh) | 2017-12-01 |
| CA2973354A1 (en) | 2016-07-21 |
| TW201632531A (zh) | 2016-09-16 |
| ES2783624T3 (es) | 2020-09-17 |
| MX2017009145A (es) | 2017-11-22 |
| BR112017014599A2 (pt) | 2018-01-16 |
| US20170233436A1 (en) | 2017-08-17 |
| EA201791550A1 (ru) | 2017-11-30 |
| JP6498773B2 (ja) | 2019-04-10 |
| EP3245213A1 (en) | 2017-11-22 |
| CN107428780B (zh) | 2020-09-04 |
| US20170073357A1 (en) | 2017-03-16 |
| KR20170102980A (ko) | 2017-09-12 |
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