ES2834093T3 - Inhibidores de proteína quinasa heterocíclicos - Google Patents
Inhibidores de proteína quinasa heterocíclicos Download PDFInfo
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- ES2834093T3 ES2834093T3 ES18162853T ES18162853T ES2834093T3 ES 2834093 T3 ES2834093 T3 ES 2834093T3 ES 18162853 T ES18162853 T ES 18162853T ES 18162853 T ES18162853 T ES 18162853T ES 2834093 T3 ES2834093 T3 ES 2834093T3
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Classifications
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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
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
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- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Transplantation (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
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| US201161632834P | 2011-07-21 | 2011-07-21 | |
| US201261632826P | 2012-03-01 | 2012-03-01 | |
| US201261608028P | 2012-03-07 | 2012-03-07 |
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| ES2834093T3 (es) | 2011-07-21 | 2021-06-16 | Sumitomo Dainippon Pharma Oncology Inc | Inhibidores de proteína quinasa heterocíclicos |
| RU2014140735A (ru) * | 2012-03-09 | 2016-04-27 | Лексикон Фармасьютикалз, Инк. | ПРОИЗВОДНЫЕ ПИРАЗОЛО[1, 5-a]ПИРИМИДИНА, КОМПОЗИЦИИ, СОДЕРЖАЩИЕ УКАЗАННЫЕ СОЕДИНЕНИЯ, И СПОСОБЫ ИХ ПРИМЕНЕНИЯ |
| CA2867061A1 (en) * | 2012-03-14 | 2013-09-19 | Bayer Intellectual Property Gmbh | Substituted imidazopyridazines |
| US9573954B2 (en) | 2012-11-16 | 2017-02-21 | University Health Network | Pyrazolopyrimidine compounds |
| EP2943485B1 (en) | 2013-01-14 | 2017-09-20 | Incyte Holdings Corporation | Bicyclic aromatic carboxamide compounds useful as pim kinase inhibitors |
| HUE050215T2 (hu) | 2013-01-15 | 2020-11-30 | Incyte Holdings Corp | Pim kináz inhibitorokként hasznos tiazolkarboxamid és piridinkarboxamid vegyületek |
| JP2016509036A (ja) | 2013-02-20 | 2016-03-24 | バイエル・ファルマ・アクティエンゲゼルシャフト | Ｍｋｎｋ１阻害剤としての置換イミダゾ［１，２−ｂ］ピリダジン |
| EP2964230A4 (en) * | 2013-03-07 | 2016-10-26 | Califia Bio Inc | KINASEHEMMER WITH MIXED ABSTRACT AND TREATMENT PROCESS THEREWITH |
| TW201605866A (zh) | 2013-08-23 | 2016-02-16 | 英塞特公司 | 可用作ｐｉｍ激酶抑制劑之呋喃并－及噻吩并－吡啶甲醯胺化合物 |
| EP3092242A1 (en) | 2014-01-09 | 2016-11-16 | Bayer Pharma Aktiengesellschaft | Amido-substituted imidazopyridazines useful in the treatment of hyper-proliferative and/or angiogenesis disorders |
| GB201403093D0 (en) * | 2014-02-21 | 2014-04-09 | Cancer Rec Tech Ltd | Therapeutic compounds and their use |
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| WO2016010897A1 (en) | 2014-07-14 | 2016-01-21 | Incyte Corporation | Bicyclic heteroaromatic carboxamide compounds useful as pim kinase inhibitors |
| US9540347B2 (en) | 2015-05-29 | 2017-01-10 | Incyte Corporation | Pyridineamine compounds useful as Pim kinase inhibitors |
| CN105061188B (zh) * | 2015-08-11 | 2017-03-08 | 艾琪康医药科技（上海）有限公司 | 一种4,4‑二氟环己基甲酸的制备方法 |
| TWI734699B (zh) | 2015-09-09 | 2021-08-01 | 美商英塞特公司 | Ｐｉｍ激酶抑制劑之鹽 |
| WO2017059251A1 (en) | 2015-10-02 | 2017-04-06 | Incyte Corporation | Heterocyclic compounds useful as pim kinase inhibitors |
| WO2019113487A1 (en) | 2017-12-08 | 2019-06-13 | Incyte Corporation | Low dose combination therapy for treatment of myeloproliferative neoplasms |
| CA3095580A1 (en) * | 2018-04-13 | 2019-10-17 | Sumitomo Dainippon Pharma Oncology, Inc. | Pim kinase inhibitors for treatment of myeloproliferative neoplasms and fibrosis associated with cancer |
| US11028351B2 (en) | 2018-06-27 | 2021-06-08 | Henkel IP & Holding GmbH | Unit dose detergent packs with anti-yellowing and anti-efflorescence formulations |
| HUE072069T2 (hu) | 2019-02-12 | 2025-10-28 | Sumitomo Pharma America Inc | 2-((1R,4R)-4-((3-(3-(trifluormetil)fenil)imidazo[1,2- b]piridazin-6-il)amino)ciklohexil)propán-2-ol sósavas sójának kristályos formája |
| MX2022012437A (es) * | 2020-04-15 | 2022-10-27 | Pyramid Biosciences Inc | Metodos para preparar inhibidores del receptor de la tirosina quinasa. |
| CN112430632B (zh) * | 2020-11-18 | 2022-09-13 | 上海合全药物研发有限公司 | 2-((反式)-4-氨基环己烷基)异丙醇的制备方法 |
| CN115991706A (zh) * | 2021-02-08 | 2023-04-21 | 杭州邦顺制药有限公司 | Pim激酶抑制剂 |
| CA3239257A1 (en) * | 2021-12-01 | 2023-06-08 | Joaquin Pastor Fernandez | Compounds |
| CN116262753A (zh) * | 2021-12-13 | 2023-06-16 | 杭州邦顺制药有限公司 | 一种新颖的pim激酶抑制剂 |
| AU2023372386A1 (en) | 2022-10-31 | 2025-05-08 | Sumitomo Pharma America, Inc. | Pim1 inhibitor for treating myeloproliferative neoplasms |
| CN116836168A (zh) * | 2023-05-24 | 2023-10-03 | 浙江大学 | 7-二氟甲基-5-芳基吡唑并嘧啶类化合物及制备与应用 |
Family Cites Families (238)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SU6668A1 (ru) | 1921-07-19 | 1924-09-15 | А.Д. Несмеянов | Центробежный распылитель дл жидкости |
| SU5416A1 (ru) | 1926-06-03 | 1928-05-31 | Тормейер Г. | Двигатель компаунд внутреннего горени |
| US2779780A (en) | 1955-03-01 | 1957-01-29 | Du Pont | 1, 4-diamino-2, 3-dicyano-1, 4-bis (substituted mercapto) butadienes and their preparation |
| US3935230A (en) | 1972-10-24 | 1976-01-27 | E. R. Squibb & Sons, Inc. | α, α, α, α', α', α'-Hexafluorodi-m-tolylamine derivatives |
| GB8827305D0 (en) | 1988-11-23 | 1988-12-29 | British Bio Technology | Compounds |
| DE4134467A1 (de) | 1991-10-18 | 1993-04-22 | Thomae Gmbh Dr K | Heterobiarylderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| FI941572L (fi) | 1991-10-07 | 1994-05-27 | Oncologix Inc | Anti-erbB-2-monoklonaalisten vasta-aineiden yhdistelmä ja käyttömenetelmä |
| EP1514934B1 (en) | 1992-02-06 | 2008-12-31 | Novartis Vaccines and Diagnostics, Inc. | Biosynthetic binding protein for cancer marker |
| US6177401B1 (en) | 1992-11-13 | 2001-01-23 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften | Use of organic compounds for the inhibition of Flk-1 mediated vasculogenesis and angiogenesis |
| US5455258A (en) | 1993-01-06 | 1995-10-03 | Ciba-Geigy Corporation | Arylsulfonamido-substituted hydroxamic acids |
| US5441952A (en) | 1993-04-05 | 1995-08-15 | Merck & Co., Inc. | Fibrinogen receptor antagonists |
| EP0647450A1 (en) | 1993-09-09 | 1995-04-12 | BEHRINGWERKE Aktiengesellschaft | Improved prodrugs for enzyme mediated activation |
| IL112248A0 (en) | 1994-01-25 | 1995-03-30 | Warner Lambert Co | Tricyclic heteroaromatic compounds and pharmaceutical compositions containing them |
| US5863949A (en) | 1995-03-08 | 1999-01-26 | Pfizer Inc | Arylsulfonylamino hydroxamic acid derivatives |
| SK133297A3 (en) | 1995-04-04 | 1998-07-08 | Glaxo Group Ltd | Imidazo[1,2-a]pyridine derivatives, pharmaceutical composition containing same and their use |
| FI973974A7 (fi) | 1995-04-20 | 1997-10-16 | Pfizer | Aryylisulfonyylihydroksaamihappojohdannaisia MMP- ja TNF-inhibiittorei na |
| US5747498A (en) | 1996-05-28 | 1998-05-05 | Pfizer Inc. | Alkynyl and azido-substituted 4-anilinoquinazolines |
| US5880141A (en) | 1995-06-07 | 1999-03-09 | Sugen, Inc. | Benzylidene-Z-indoline compounds for the treatment of disease |
| GB9520822D0 (en) | 1995-10-11 | 1995-12-13 | Wellcome Found | Therapeutically active compounds |
| GB9523675D0 (en) | 1995-11-20 | 1996-01-24 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9624482D0 (en) | 1995-12-18 | 1997-01-15 | Zeneca Phaema S A | Chemical compounds |
| DE69624081T2 (de) | 1995-12-20 | 2003-06-12 | Agouron Pharmaceuticals, Inc. | Matrix-metalloprotease Inhibitoren |
| DE69637855D1 (de) | 1995-12-22 | 2009-04-16 | Novo Nordisk As | Verbindungen mit wachstumshormon-freisetzenden eigenschaften |
| JP4464466B2 (ja) | 1996-03-05 | 2010-05-19 | アストラゼネカ・ユーケイ・リミテッド | ４―アニリノキナゾリン誘導体 |
| EP0818442A3 (en) | 1996-07-12 | 1998-12-30 | Pfizer Inc. | Cyclic sulphone derivatives as inhibitors of metalloproteinases and of the production of tumour necrosis factor |
| CA2260058A1 (en) | 1996-07-13 | 1998-01-22 | Kathryn Jane Smith | Bicyclic heteroaromatic compounds as protein tyrosine kinase inhibitors |
| HRP970371A2 (en) | 1996-07-13 | 1998-08-31 | Kathryn Jane Smith | Heterocyclic compounds |
| AR007857A1 (es) | 1996-07-13 | 1999-11-24 | Glaxo Group Ltd | Compuestos heterociclicos fusionados como inhibidores de proteina tirosina quinasa, sus metodos de preparacion, intermediarios uso en medicina ycomposiciones farmaceuticas que los contienen. |
| HUP9903014A3 (en) | 1996-07-18 | 2000-08-28 | Pfizer | Phosphinate derivatives having matrix metalloprotease inhibitor effect and medicaments containing the same |
| IL128189A0 (en) | 1996-08-23 | 1999-11-30 | Pfizer | Arylsulfonylamino hydroxamic acid derivatives |
| JP4073961B2 (ja) | 1996-10-01 | 2008-04-09 | 協和醗酵工業株式会社 | 含窒素複素環化合物 |
| ID18494A (id) | 1996-10-02 | 1998-04-16 | Novartis Ag | Turunan pirazola leburan dan proses pembuatannya |
| ES2224277T3 (es) | 1997-01-06 | 2005-03-01 | Pfizer Inc. | Derivados de sulfonas ciclicas. |
| PT977733E (pt) | 1997-02-03 | 2003-12-31 | Pfizer Prod Inc | Derivados de acido arilsulfonilamino-hidroxamico |
| JP2000507975A (ja) | 1997-02-07 | 2000-06-27 | ファイザー・インク | Ｎ−ヒドロキシ−β−スルホニルプロピオンアミド誘導体類及びそれらのマトリックスメタロプロテイナーゼ阻害薬としての使用 |
| IL131123A0 (en) | 1997-02-11 | 2001-01-28 | Pfizer | Arylsulfonyl hydroxamic acid derivatives |
| CA2289102A1 (en) | 1997-05-07 | 1998-11-12 | Sugen, Inc. | 2-indolinone derivatives as modulators of protein kinase activity |
| EP0984692A4 (en) | 1997-05-30 | 2001-02-21 | Merck & Co Inc | ANGIOGENESIS INHIBITORS |
| ES2216293T3 (es) | 1997-08-08 | 2004-10-16 | Pfizer Products Inc. | Derivados de acido ariloxiarilsulfonilamino-hidroxamico. |
| US6294532B1 (en) | 1997-08-22 | 2001-09-25 | Zeneca Limited | Oxindolylquinazoline derivatives as angiogenesis inhibitors |
| WO1999016755A1 (en) | 1997-09-26 | 1999-04-08 | Merck & Co., Inc. | Novel angiogenesis inhibitors |
| WO1999024440A1 (en) | 1997-11-11 | 1999-05-20 | Pfizer Products Inc. | Thienopyrimidine and thienopyridine derivatives useful as anticancer agents |
| GB9725782D0 (en) | 1997-12-05 | 1998-02-04 | Pfizer Ltd | Therapeutic agents |
| GB9800575D0 (en) | 1998-01-12 | 1998-03-11 | Glaxo Group Ltd | Heterocyclic compounds |
| RS49779B (sr) | 1998-01-12 | 2008-06-05 | Glaxo Group Limited, | Biciklična heteroaromatična jedinjenja kao inhibitori protein tirozin kinaze |
| GB9801690D0 (en) | 1998-01-27 | 1998-03-25 | Pfizer Ltd | Therapeutic agents |
| PA8469401A1 (es) | 1998-04-10 | 2000-05-24 | Pfizer Prod Inc | Derivados biciclicos del acido hidroxamico |
| EP0952148B1 (en) | 1998-04-10 | 2004-05-12 | Pfizer Products Inc. | Cyclobutyl-aryloxyarylsulfonylamino hydroxamic acid derivatives |
| PA8469501A1 (es) | 1998-04-10 | 2000-09-29 | Pfizer Prod Inc | Hidroxamidas del acido (4-arilsulfonilamino)-tetrahidropiran-4-carboxilico |
| TR200003514T2 (tr) | 1998-05-29 | 2002-05-21 | Sugen Inc. | Pirol ikame edilmiş 2-indolinon protein kinaz inhibitörleri |
| UA60365C2 (uk) | 1998-06-04 | 2003-10-15 | Пфайзер Продактс Інк. | Похідні ізотіазолу, спосіб їх одержання, фармацевтична композиція та спосіб лікування гіперпроліферативного захворювання у ссавця |
| DK1004578T3 (da) | 1998-11-05 | 2004-06-28 | Pfizer Prod Inc | 5-oxo-pyrrolidin-2-carboxylsyrehydroxamidderivater |
| IL143236A0 (en) | 1998-12-16 | 2002-04-21 | Warner Lambert Co | Treatment of arthritis with mek inhibitors |
| UA71945C2 (en) | 1999-01-27 | 2005-01-17 | Pfizer Prod Inc | Substituted bicyclic derivatives being used as anticancer agents |
| CN1340051A (zh) | 1999-02-11 | 2002-03-13 | 辉瑞产品公司 | 可用作抗癌剂的杂芳基取代的喹啉－2－酮衍生物 |
| IL129299A0 (en) | 1999-03-31 | 2000-02-17 | Mor Research Applic Ltd | Monoclonal antibodies antigens and diagnosis of malignant diseases |
| EP3225632B1 (en) | 1999-11-30 | 2020-05-06 | Mayo Foundation for Medical Education and Research | Antibodies binding to b7-h1, a novel immunoregulatory molecule |
| BRPI0117360B8 (pt) | 2000-02-15 | 2021-07-06 | Upjohn Co | inibidores de proteína de quinase de 2-indolinona de pirrol substituído, seus sais e composições farmacêuticas compreendendo os mesmos |
| WO2001060816A1 (en) | 2000-02-17 | 2001-08-23 | Amgen Inc. | Kinase inhibitors |
| EE05450B1 (et) | 2000-07-19 | 2011-08-15 | Warner-Lambert Company | 4-jodofenlaminobenshdroksaamhapete oksgeenitud estrid, nende kristallvormid ja farmatseutilised kompositsioonid ning kasutamine |
| BR0113356A (pt) | 2000-08-18 | 2004-04-20 | Millennium Pharm Inc | Derivados de quinazolina como inibidores de quinase |
| US6995162B2 (en) | 2001-01-12 | 2006-02-07 | Amgen Inc. | Substituted alkylamine derivatives and methods of use |
| JP4575667B2 (ja) | 2002-03-08 | 2010-11-04 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 医薬として有用な大環状化合物 |
| PL401638A1 (pl) | 2002-03-13 | 2013-05-27 | Array Biopharma Inc. | N3 alkilowane pochodne benzimidazolu jako inhibitory MEK |
| AU2003231231A1 (en) | 2002-05-06 | 2003-11-11 | Bayer Pharmaceuticals Corporation | Pyridinyl amino pyrimidine derivatives useful for treating hyper-proliferative disorders |
| IL149820A0 (en) | 2002-05-23 | 2002-11-10 | Curetech Ltd | Humanized immunomodulatory monoclonal antibodies for the treatment of neoplastic disease or immunodeficiency |
| WO2004004771A1 (ja) | 2002-07-03 | 2004-01-15 | Ono Pharmaceutical Co., Ltd. | 免疫賦活組成物 |
| AU2003272548A1 (en) | 2002-09-16 | 2004-04-30 | Plexxikon, Inc. | Crystal structure of pim-1 kinase |
| NZ541151A (en) | 2002-12-18 | 2008-09-26 | Vertex Pharma | Triazolopyridazines as protein kinase inhibitors |
| MXPA05006828A (es) | 2002-12-23 | 2005-09-08 | Wyeth Corp | Anticuerpos contra pd-1, y sus usos. |
| JP2006151810A (ja) | 2002-12-26 | 2006-06-15 | Daiichi Asubio Pharma Co Ltd | ジヒドロチエノキノリン誘導体及びそれを含む細胞接着阻害剤 |
| ATE334131T1 (de) | 2003-02-14 | 2006-08-15 | Pfizer Prod Inc | Triazolopyridine als entzündungshemmende verbindungen |
| ATE433447T1 (de) | 2003-02-20 | 2009-06-15 | Smithkline Beecham Corp | Pyrimiidinverbindungen |
| CA2538413A1 (en) | 2003-09-18 | 2005-03-24 | Novartis Ag | 2,4-di (phenylamino) pyrimidines useful in the treatment of proliferative disorders |
| ATE437872T1 (de) | 2003-10-14 | 2009-08-15 | Univ Arizona | Proteinkinaseinhibitoren |
| WO2006018718A2 (en) | 2004-08-12 | 2006-02-23 | Pfizer Limited | Triazolopyridinylsulfanyl derivatives as p38 map kinase inhibitors |
| TW200633990A (en) | 2004-11-18 | 2006-10-01 | Takeda Pharmaceuticals Co | Amide compound |
| US7723340B2 (en) | 2005-01-13 | 2010-05-25 | Signal Pharmaceuticals, Llc | Haloaryl substituted aminopurines, compositions thereof, and methods of treatment therewith |
| BRPI0609956A2 (pt) | 2005-04-28 | 2010-05-18 | Supergen Inc | inibidores de proteìna quinase |
| JP4361545B2 (ja) | 2005-05-09 | 2009-11-11 | 小野薬品工業株式会社 | ＰｒｏｇｒａｍｍｅｄＤｅａｔｈ１（ＰＤ−１）に対するヒトモノクローナル抗体および抗ＰＤ−１抗体単独または他の免疫療法と併用した癌治療方法 |
| HRP20151102T1 (xx) | 2005-07-01 | 2015-11-20 | E. R. Squibb & Sons, L.L.C. | Humana monoklonska antitijela za ligand programirane smrti 1 (pd-l1) |
| EP1912636B1 (en) | 2005-07-21 | 2014-06-25 | Ardea Biosciences, Inc. | N-(arylamino)-sulfonamide inhibitors of mek |
| WO2007013673A1 (en) | 2005-07-29 | 2007-02-01 | Astellas Pharma Inc. | Fused heterocycles as lck inhibitors |
| EP1923388A4 (en) | 2005-08-12 | 2011-03-09 | Takeda Pharmaceutical | BRAIN / NEURONAL CELL PROTECTIVE AGENT AND THERAPEUTIC AGENT FOR SLEEP DISORDERS |
| WO2007025090A2 (en) | 2005-08-25 | 2007-03-01 | Kalypsys, Inc. | Heterobicyclic and - tricyclic inhibitors of mapk/erk kinase |
| DE102005042742A1 (de) | 2005-09-02 | 2007-03-08 | Schering Ag | Substituierte Imidazo[1,2b]pyridazine als Kinase-Inhibitoren, deren Herstellung und Verwendung als Arzneimittel |
| US7750000B2 (en) | 2005-09-02 | 2010-07-06 | Bayer Schering Pharma Ag | Substituted imidazo[1,2b]pyridazines as kinase inhibitors, their preparation and use as medicaments |
| US7776865B2 (en) | 2005-10-06 | 2010-08-17 | Schering Corporation | Substituted pyrazolo[1,5-a]pyrimidines as protein kinase inhibitors |
| KR20080098490A (ko) | 2006-01-13 | 2008-11-10 | 파마시클릭스, 인코포레이티드 | 티로신 키나제 억제제 및 이의 용도 |
| JO2660B1 (en) | 2006-01-20 | 2012-06-17 | نوفارتيس ايه جي | Pi-3 inhibitors and methods of use |
| JP2009526037A (ja) * | 2006-02-09 | 2009-07-16 | ファイザー・リミテッド | トリアゾロピリジン化合物 |
| CN101490001A (zh) | 2006-06-09 | 2009-07-22 | Icos股份有限公司 | 用作dp-2拮抗剂的取代的苯乙酸 |
| DE102006029447A1 (de) | 2006-06-21 | 2007-12-27 | Bayer Schering Pharma Ag | Oxo-substituierte Imidazo[1,2b]pyridazine, deren Herstellung und Verwendung als Arzneimittel |
| EP1873157A1 (en) | 2006-06-21 | 2008-01-02 | Bayer Schering Pharma Aktiengesellschaft | Pyrazolopyrimidines and salts thereof, pharmaceutical compositions comprising same, methods of preparing same and uses of same |
| EP1900739A1 (en) | 2006-08-30 | 2008-03-19 | Cellzome Ag | Diazolodiazine derivatives as kinase inhibitors |
| JP2010502716A (ja) | 2006-09-07 | 2010-01-28 | バイオジェン・アイデック・エムエイ・インコーポレイテッド | インターロイキン１受容体関連キナーゼの調節物質 |
| SG166093A1 (en) | 2006-09-22 | 2010-11-29 | Pharmacyclics Inc | Inhibitors of brutonæs tyrosine kinase |
| KR20090073121A (ko) | 2006-09-29 | 2009-07-02 | 노파르티스 아게 | Ｐｉ3ｋ 지질 키나제 억제제로서의 피라졸로피리미딘 |
| CA2667962A1 (en) * | 2006-10-30 | 2008-05-08 | Novartis Ag | Heterocyclic compounds as antiinflammatory agents |
| WO2008055233A1 (en) | 2006-10-31 | 2008-05-08 | Supergen, Inc. | Protein kinase inhibitors |
| US8987233B2 (en) | 2006-11-03 | 2015-03-24 | Pharmacyclics, Inc. | Bruton's tyrosine kinase activity probe and method of using |
| US7750007B2 (en) * | 2006-11-06 | 2010-07-06 | Supergen, Inc. | Imidazo[1,2-beta]pyridazine and pyrazolo[1,5-alpha]pyrimidine derivatives and their use as protein kinase inhibitors |
| US20120058997A1 (en) | 2006-11-06 | 2012-03-08 | Supergen, Inc. | Imidazo[1,2-b]pyridazine and pyrazolo[1,5-a]pyrimidine derivatives and their use as protein kinase inhibitors |
| WO2008082839A2 (en) | 2006-12-29 | 2008-07-10 | Abbott Laboratories | Pim kinase inhibitors as cancer chemotherapeutics |
| WO2008092199A1 (en) | 2007-01-31 | 2008-08-07 | Cytopia Research Pty Ltd | Thiopyrimidine-based compounds and uses thereof |
| EA019951B1 (ru) | 2007-03-01 | 2014-07-30 | Новартис Аг | Ингибиторы киназы pim и способы их применения |
| KR20090129434A (ko) | 2007-03-01 | 2009-12-16 | 수퍼젠, 인크. | 피리미딘-2,4-디아민 유도체 및 ｊａｋ2 키나제 억제제로서의 이의 용도 |
| US7834024B2 (en) | 2007-03-26 | 2010-11-16 | Rigel Pharmaceuticals, Inc. | Compositions and methods for inhibition of the JAK pathway |
| US8809273B2 (en) | 2007-03-28 | 2014-08-19 | Pharmacyclics, Inc. | Inhibitors of Bruton's tyrosine kinase |
| CN101674834B (zh) | 2007-03-28 | 2013-06-12 | 环状药物公司 | 布鲁顿氏酪氨酸激酶(Bruton's tyrosine kinase)抑制剂 |
| US7998966B2 (en) | 2007-04-13 | 2011-08-16 | Supergen, Inc. | Axl kinase inhibitors |
| US9244059B2 (en) | 2007-04-30 | 2016-01-26 | Immutep Parc Club Orsay | Cytotoxic anti-LAG-3 monoclonal antibody and its use in the treatment or prevention of organ transplant rejection and autoimmune disease |
| EP1987839A1 (en) | 2007-04-30 | 2008-11-05 | I.N.S.E.R.M. Institut National de la Sante et de la Recherche Medicale | Cytotoxic anti-LAG-3 monoclonal antibody and its use in the treatment or prevention of organ transplant rejection and autoimmune disease |
| NZ582150A (en) | 2007-06-18 | 2012-08-31 | Msd Oss Bv | Antibodies to human programmed death receptor pd-1 |
| WO2009017954A1 (en) | 2007-08-01 | 2009-02-05 | Phenomix Corporation | Inhibitors of jak2 kinase |
| EP2205242B1 (en) | 2007-09-12 | 2015-04-15 | Genentech, Inc. | Combinations of phosphoinositide 3-kinase inhibitor compounds and chemotherapeutic agents, and methods of use |
| EP2044949A1 (en) | 2007-10-05 | 2009-04-08 | Immutep | Use of recombinant lag-3 or the derivatives thereof for eliciting monocyte immune response |
| JP5348725B2 (ja) | 2007-10-25 | 2013-11-20 | ジェネンテック， インコーポレイテッド | チエノピリミジン化合物の製造方法 |
| EP2217601A1 (en) | 2007-11-08 | 2010-08-18 | Centro Nacional de Investigaciones Oncológicas (CNIO) | Imidazopyridazines for use as protein kinase inhibitors |
| EP2217235A4 (en) | 2007-11-15 | 2011-01-12 | Musc Found For Res Dev | INHIBITORS OF PIM PROTEIN KINASES, COMPOSITIONS AND METHOD FOR THE TREATMENT OF CANCER |
| KR20100108390A (ko) | 2007-12-19 | 2010-10-06 | 버텍스 파마슈티칼스 인코포레이티드 | ＪＡＫ２ 억제제로서 유용한 피라졸로［１，５－ａ］피리미딘 |
| WO2009080638A2 (en) | 2007-12-20 | 2009-07-02 | Cellzome Limited | Sulfamides as zap-70 inhibitors |
| US8168794B2 (en) | 2008-03-03 | 2012-05-01 | Novartis Ag | Pim kinase inhibitors and methods of their use |
| AR070531A1 (es) | 2008-03-03 | 2010-04-14 | Novartis Ag | Inhibidores de cinasa pim y metodos para su uso |
| WO2009114335A2 (en) | 2008-03-12 | 2009-09-17 | Merck & Co., Inc. | Pd-1 binding proteins |
| CN102105150B (zh) | 2008-05-21 | 2014-03-12 | 阿里亚德医药股份有限公司 | 用作激酶抑制剂的磷衍生物 |
| EP2296475A4 (en) | 2008-06-20 | 2014-03-05 | Genentech Inc | TRIAZOLOPYRIDINE COMPOUNDS JAK KINASE INHIBITORS AND METHODS |
| NZ624345A (en) | 2008-06-27 | 2016-07-29 | Celgene Avilomics Res Inc | 2,4-disubstituted pyrimidines useful as kinase inhibitors |
| FR2933409B1 (fr) | 2008-07-03 | 2010-08-27 | Centre Nat Rech Scient | NOUVEAUX PYRROLO °2,3-a! CARBAZOLES ET LEUR UTILISATION COMME INHIBITEURS DES KINASES PIM |
| CA2730930C (en) | 2008-07-16 | 2015-01-13 | Pharmacyclics, Inc. | Inhibitors of bruton's tyrosine kinase for the treatment of solid tumors |
| CN102112131A (zh) | 2008-08-05 | 2011-06-29 | 塔格根公司 | 治疗地中海贫血的方法 |
| AR072999A1 (es) | 2008-08-11 | 2010-10-06 | Medarex Inc | Anticuerpos humanos que se unen al gen 3 de activacion linfocitaria (lag-3) y los usos de estos |
| TWI496779B (zh) | 2008-08-19 | 2015-08-21 | Array Biopharma Inc | 作為ｐｉｍ激酶抑制劑之三唑吡啶化合物 |
| US8557809B2 (en) | 2008-08-19 | 2013-10-15 | Array Biopharma Inc. | Triazolopyridine compounds as PIM kinase inhibitors |
| JP2012510429A (ja) | 2008-08-25 | 2012-05-10 | アンプリミューン、インコーポレーテッド | Ｐｄ−１アンタゴニストおよびその使用方法 |
| PT2344474E (pt) | 2008-09-02 | 2015-12-28 | Novartis Ag | Derivados de picolinamida como inibidores de cinase |
| US8735424B2 (en) | 2008-09-02 | 2014-05-27 | Novartis Ag | Bicyclic kinase inhibitors |
| CA2735782A1 (en) | 2008-09-02 | 2010-03-11 | Novartis Ag | Heterocyclic pim-kinase inhibitors |
| EP2342229A1 (en) | 2008-09-12 | 2011-07-13 | ISIS Innovation Limited | Pd-1 specific antibodies and uses thereof |
| ES2464461T3 (es) | 2008-09-22 | 2014-06-02 | Array Biopharma, Inc. | Compuestos de imidazo[1,2B]piridazina sustituidos como inhibidores de la TRK cinasa |
| AU2009296392B2 (en) | 2008-09-26 | 2016-06-02 | Dana-Farber Cancer Institute, Inc. | Human anti-PD-1, PD-L1, and PD-L2 antibodies and uses therefor |
| KR20250091300A (ko) | 2008-12-09 | 2025-06-20 | 제넨테크, 인크. | 항-ｐｄ-ｌ１ 항체 및 ｔ 세포 기능을 향상시키기 위한 그의 용도 |
| TW201035100A (en) | 2008-12-19 | 2010-10-01 | Cephalon Inc | Pyrrolotriazines as ALK and JAK2 inhibitors |
| JP2012524106A (ja) | 2009-04-15 | 2012-10-11 | ジ・オハイオ・ステイト・ユニバーシティ・リサーチ・ファウンデイション | 二重ｊａｋ２／ｓｔａｔ３阻害剤としてのクルクミン類似体ならびにその同じ物を作る、および用いる方法 |
| WO2010135581A1 (en) | 2009-05-20 | 2010-11-25 | Cylene Pharmaceuticals, Inc. | Pyrazolopyrimidines and related heterocycles as kinase inhibitors |
| US20100331315A1 (en) | 2009-06-18 | 2010-12-30 | Mustapha Haddach | Rhodanines and related heterocycles as kinase inhibitors |
| TW201107329A (en) | 2009-07-30 | 2011-03-01 | Oncotherapy Science Inc | Fused imidazole derivative having ttk inhibitory action |
| US7741330B1 (en) | 2009-10-12 | 2010-06-22 | Pharmacyclics, Inc. | Pyrazolo-pyrimidine inhibitors of Bruton's tyrosine kinase |
| EP2332917B1 (en) | 2009-11-11 | 2012-08-01 | Sygnis Bioscience GmbH & Co. KG | Compounds for PIM kinase inhibition and for treating malignancy |
| DK2504364T3 (da) | 2009-11-24 | 2017-11-06 | Medimmune Ltd | Målrettede bindemidler mod b7-h1 |
| JP2013512251A (ja) | 2009-11-24 | 2013-04-11 | アンプリミューン、インコーポレーテッド | Ｐｄ−ｌ１／ｐｄ−ｌ２の同時阻害 |
| EP2515665B1 (en) | 2009-12-22 | 2013-08-14 | Unilever NV | A process for preparing a tea product |
| AU2010336386B2 (en) | 2009-12-23 | 2016-01-21 | Jasco Pharmaceuticals, LLC | Aminopyrimidine kinase inhibitors |
| UY33213A (es) | 2010-02-18 | 2011-09-30 | Almirall Sa | Derivados de pirazol como inhibidores de jak |
| CA2791930A1 (en) | 2010-03-11 | 2011-09-15 | Kerry Louise Tyson | Pd-1 antibody |
| NZ717373A (en) | 2010-06-03 | 2017-11-24 | Pharmacyclics Llc | The use of inhibitors of bruton’s tyrosine kinase (btk) |
| HUE040213T2 (hu) | 2010-06-11 | 2019-02-28 | Kyowa Hakko Kirin Co Ltd | Anti-TIM antitest |
| CA2802344C (en) | 2010-06-18 | 2023-06-13 | The Brigham And Women's Hospital, Inc. | Bi-specific antibodies against tim-3 and pd-1 for immunotherapy in chronic immune conditions |
| US8907053B2 (en) | 2010-06-25 | 2014-12-09 | Aurigene Discovery Technologies Limited | Immunosuppression modulating compounds |
| US20130109682A1 (en) | 2010-07-06 | 2013-05-02 | Novartis Ag | Cyclic ether compounds useful as kinase inhibitors |
| TWI541243B (zh) | 2010-09-10 | 2016-07-11 | 拜耳知識產權公司 | 經取代咪唑并嗒 |
| KR101913441B1 (ko) | 2010-12-17 | 2018-10-30 | 네르비아노 메디칼 사이언시스 에스.알.엘. | 키나제 억제제로서 치환된 피라졸로-퀴나졸린 유도체 |
| AU2012254082B2 (en) | 2011-02-25 | 2016-12-08 | Array Biopharma Inc. | Triazolopyridine compounds as PIM kinase inhibitors |
| UY33929A (es) | 2011-03-04 | 2012-10-31 | Novartis Ag | Compuestos de ciclohexilo tetrasustituido como inhibidores de quinasas |
| AU2012230890A1 (en) | 2011-03-22 | 2013-09-26 | Amgen Inc. | Azole compounds as Pim inhibitors |
| MX338353B (es) | 2011-04-20 | 2016-04-13 | Medimmune Llc | Anticuerpos y otras moleculas que se unen a b7 - h1 y pd - 1. |
| SG195141A1 (en) | 2011-06-14 | 2013-12-30 | Novartis Ag | Combination of panobinostat and ruxolitinib in the treatment of cancer suchas a myeloproliferative neoplasm |
| WO2012177606A1 (en) | 2011-06-20 | 2012-12-27 | Incyte Corporation | Azetidinyl phenyl, pyridyl or pyrazinyl carboxamide derivatives as jak inhibitors |
| US8841418B2 (en) | 2011-07-01 | 2014-09-23 | Cellerant Therapeutics, Inc. | Antibodies that specifically bind to TIM3 |
| MX2014000518A (es) | 2011-07-13 | 2014-05-30 | Pharmacyclics Inc | Inhibidores de la tirosina quinasa de bruton. |
| ES2834093T3 (es) | 2011-07-21 | 2021-06-16 | Sumitomo Dainippon Pharma Oncology Inc | Inhibidores de proteína quinasa heterocíclicos |
| CA2840018C (en) | 2011-07-24 | 2019-07-16 | Curetech Ltd. | Variants of humanized immunomodulatory monoclonal antibodies |
| CN102924444B (zh) | 2011-08-11 | 2015-07-08 | 上海吉铠医药科技有限公司 | Pim激酶抑制剂及其制备方法与在制药中的应用 |
| US20140303191A1 (en) | 2011-10-19 | 2014-10-09 | Pharmacyclics, Inc. | Use of inhibitors of bruton's tyrosine kinase (btk) |
| SMT202000561T1 (it) | 2011-11-28 | 2021-01-05 | Merck Patent Gmbh | Anticorpi anti-pd-l1 e usi relativi |
| US8377946B1 (en) | 2011-12-30 | 2013-02-19 | Pharmacyclics, Inc. | Pyrazolo[3,4-d]pyrimidine and pyrrolo[2,3-d]pyrimidine compounds as kinase inhibitors |
| US8501724B1 (en) | 2012-01-31 | 2013-08-06 | Pharmacyclics, Inc. | Purinone compounds as kinase inhibitors |
| KR102085121B1 (ko) | 2012-03-09 | 2020-03-05 | 렉시컨 파마슈티컬스 인코퍼레이티드 | 이미다조[1,2-b]피리다진계 화합물, 그를 포함하는 조성물 및 그의 용도 |
| WO2013173518A1 (en) | 2012-05-16 | 2013-11-21 | Pharmacyclics, Inc. | Inhibitors of bruton's tyrosine kinase |
| KR20150013548A (ko) | 2012-05-21 | 2015-02-05 | 노파르티스 아게 | 키나제 억제제로서의 신규 고리-치환된 n-피리디닐 아미드 |
| WO2013181634A2 (en) | 2012-05-31 | 2013-12-05 | Sorrento Therapeutics Inc. | Antigen binding proteins that bind pd-l1 |
| TWI662963B (zh) | 2012-06-04 | 2019-06-21 | 美商製藥有限責任公司 | 布魯頓氏酪胺酸激酶抑制劑之結晶形式 |
| UY34887A (es) | 2012-07-02 | 2013-12-31 | Bristol Myers Squibb Company Una Corporacion Del Estado De Delaware | Optimización de anticuerpos que se fijan al gen de activación de linfocitos 3 (lag-3) y sus usos |
| US10954567B2 (en) | 2012-07-24 | 2021-03-23 | Pharmacyclics Llc | Mutations associated with resistance to inhibitors of Bruton's Tyrosine Kinase (BTK) |
| CN111499755A (zh) | 2012-08-03 | 2020-08-07 | 丹娜法伯癌症研究院 | 抗-pd-l1和pd-l2双结合抗体单一试剂及其使用方法 |
| US8703981B2 (en) | 2012-08-03 | 2014-04-22 | Xerox Corporation | Lignosulfonate compounds for solid ink applications |
| RU2645672C2 (ru) | 2012-08-06 | 2018-02-27 | Ацея Байосайенсиз Инк. | Новые соединения пирролопиримидина в качестве ингибиторов протеинкиназ |
| KR101446742B1 (ko) | 2012-08-10 | 2014-10-01 | 한국화학연구원 | Ｎ2,ｎ4-비스(4-(피페라진-1-일)페닐)피리미딘-2,4-디아민 유도체 또는 이의 약학적으로 허용가능한 염 및 이를 유효성분으로 함유하는 암의 예방 또는 치료용 약학적 조성물 |
| CN102880459A (zh) | 2012-08-14 | 2013-01-16 | 张涛 | 基于VisualLisp编程语言下的编译实现方法及系统 |
| US9315514B2 (en) | 2012-08-27 | 2016-04-19 | Rhodes Technologies | 1,3-dioxanomorphides and 1,3-dioxanocodides |
| WO2014033631A1 (en) | 2012-08-31 | 2014-03-06 | Novartis Ag | N-(3-pyridyl) biarylamides as kinase inhibitors |
| CA2886275A1 (en) | 2012-09-26 | 2014-04-03 | Mannkind Corporation | Multiple kinase pathway inhibitors |
| US9828434B2 (en) | 2012-10-04 | 2017-11-28 | Dana-Farber Cancer Institute, Inc. | Human monoclonal anti-PD-L1 antibodies and methods of use |
| MX2015006168A (es) | 2012-11-15 | 2015-08-10 | Pharmacyclics Inc | Compuestos de pirrolopirimidina como inhibidores de quinasas. |
| AR093984A1 (es) | 2012-12-21 | 2015-07-01 | Merck Sharp & Dohme | Anticuerpos que se unen a ligando 1 de muerte programada (pd-l1) humano |
| HUE050215T2 (hu) | 2013-01-15 | 2020-11-30 | Incyte Holdings Corp | Pim kináz inhibitorokként hasznos tiazolkarboxamid és piridinkarboxamid vegyületek |
| EA201591051A1 (ru) | 2013-02-08 | 2016-06-30 | Селджен Авиломикс Рисерч, Инк. | Ингибиторы erk и варианты их применения |
| US10322125B2 (en) | 2013-02-22 | 2019-06-18 | Emory University | TGF-beta enhancing compositions for cartilage repair and methods related thereto |
| WO2014130693A1 (en) | 2013-02-25 | 2014-08-28 | Pharmacyclics, Inc. | Inhibitors of bruton's tyrosine kinase |
| AU2014236820B2 (en) | 2013-03-14 | 2018-08-02 | Sumitomo Pharma Oncology, Inc. | JAK2 and ALK2 inhibitors and methods for their use |
| JP2016512549A (ja) | 2013-03-14 | 2016-04-28 | ファーマサイクリックス エルエルシー | ブルトン型チロシンキナーゼ阻害剤及びｃｙｐ３ａ４阻害剤の組み合わせ |
| HRP20201113T1 (hr) | 2013-03-15 | 2020-10-30 | Glaxosmithkline Intellectual Property Development Limited | Vežući proteini protiv lag-3 |
| EP2983670A4 (en) | 2013-04-08 | 2017-03-08 | Pharmacyclics LLC | Ibrutinib combination therapy |
| JP6742903B2 (ja) | 2013-05-02 | 2020-08-19 | アナプティスバイオ インコーポレイティッド | プログラム死−１（ｐｄ−１）に対する抗体 |
| CA2913977C (en) | 2013-05-31 | 2022-11-29 | Sorrento Therapeutics, Inc. | Antigen binding proteins that bind pd-1 |
| KR102094011B1 (ko) | 2013-06-13 | 2020-03-26 | 삼성전자주식회사 | 전자 장치에서 노이즈를 제거하기 위한 장치 및 방법 |
| WO2014209804A1 (en) | 2013-06-24 | 2014-12-31 | Biomed Valley Discoveries, Inc. | Bispecific antibodies |
| EP3016953A4 (en) | 2013-07-02 | 2017-03-01 | Pharmacyclics, LLC | Purinone compounds as kinase inhibitors |
| KR20160040196A (ko) | 2013-08-08 | 2016-04-12 | 노파르티스 아게 | Pim 키나제 억제제 조합물 |
| TW201605866A (zh) | 2013-08-23 | 2016-02-16 | 英塞特公司 | 可用作ｐｉｍ激酶抑制劑之呋喃并－及噻吩并－吡啶甲醯胺化合物 |
| HRP20221262T1 (hr) | 2013-09-13 | 2022-12-09 | Beigene Switzerland Gmbh | Protutijela anti-pd1 i njihova uporaba kao terapeutskih i dijagnostičkih sredstava |
| MA38961A1 (fr) | 2013-09-30 | 2018-05-31 | Pharmacyclics Llc | Composés 3-phenyl-1h-pyrazolo[3,4-d]pyrimidin-4-ylamine substitués inhibiteurs de la tyrosine kinase de bruton utilisés pour traiter par exemple les maladies auto-immunes, respiratoires et inflammatoires, cancer, mastocytose et osteoporose |
| CA2926856A1 (en) | 2013-10-25 | 2015-04-30 | Dana-Farber Cancer Institute, Inc. | Anti-pd-l1 monoclonal antibodies and fragments thereof |
| WO2015081158A1 (en) | 2013-11-26 | 2015-06-04 | Bristol-Myers Squibb Company | Method of treating hiv by disrupting pd-1/pd-l1 signaling |
| SI3081576T1 (sl) | 2013-12-12 | 2019-12-31 | Shanghai Hengrui Pharmaceutical Co., Ltd., | Protitelo PD-1, njegov antigen-vezavni fragment in njegova medicinska uporaba |
| SI3094351T1 (sl) | 2014-01-15 | 2022-05-31 | Kadmon Corporation, Llc | Imunomodulatorna sredstva |
| TWI681969B (zh) | 2014-01-23 | 2020-01-11 | 美商再生元醫藥公司 | 針對ｐｄ-１的人類抗體 |
| TWI680138B (zh) | 2014-01-23 | 2019-12-21 | 美商再生元醫藥公司 | 抗ｐｄ-ｌ１之人類抗體 |
| JOP20200094A1 (ar) | 2014-01-24 | 2017-06-16 | Dana Farber Cancer Inst Inc | جزيئات جسم مضاد لـ pd-1 واستخداماتها |
| HUE057817T2 (hu) | 2014-01-28 | 2022-06-28 | Bristol Myers Squibb Co | Anti-LAG-3 antitestek haematológiai malignitások kezelésére |
| JOP20200096A1 (ar) | 2014-01-31 | 2017-06-16 | Children’S Medical Center Corp | جزيئات جسم مضاد لـ tim-3 واستخداماتها |
| KR20240110004A (ko) | 2014-03-14 | 2024-07-12 | 노파르티스 아게 | Lag-3에 대한 항체 분자 및 그의 용도 |
| MA39984B1 (fr) | 2014-04-08 | 2020-12-31 | Incyte Corp | Traitement d'affections malignes par lymphocytes b par un inhibiteur jak et pi3k combiné |
| TW201545749A (zh) | 2014-04-25 | 2015-12-16 | Univ Nat Cheng Kung | 樟芝酸ａ、一種ｊａｋ２／３酪胺酸激酶抑制劑及有潛力的肝炎治療劑 |
| WO2015181342A1 (en) | 2014-05-29 | 2015-12-03 | Spring Bioscience Corporation | Pd-l1 antibodies and uses thereof |
| WO2015195163A1 (en) | 2014-06-20 | 2015-12-23 | R-Pharm Overseas, Inc. | Pd-l1 antagonist fully human antibody |
| TWI693232B (zh) | 2014-06-26 | 2020-05-11 | 美商宏觀基因股份有限公司 | 與pd-1和lag-3具有免疫反應性的共價結合的雙抗體和其使用方法 |
| CN110156892B (zh) | 2014-07-03 | 2023-05-16 | 百济神州有限公司 | 抗pd-l1抗体及其作为治疗剂及诊断剂的用途 |
| JO3663B1 (ar) | 2014-08-19 | 2020-08-27 | Merck Sharp & Dohme | الأجسام المضادة لمضاد lag3 وأجزاء ربط الأنتيجين |
| US9988452B2 (en) | 2014-10-14 | 2018-06-05 | Novartis Ag | Antibody molecules to PD-L1 and uses thereof |
| MX374788B (es) | 2014-11-06 | 2025-03-06 | Hoffmann La Roche | Anticuerpos anti-tim3 y metodos de uso. |
| TWI595006B (zh) | 2014-12-09 | 2017-08-11 | 禮納特神經系統科學公司 | 抗ｐｄ－１抗體類和使用彼等之方法 |
| US20160200815A1 (en) | 2015-01-05 | 2016-07-14 | Jounce Therapeutics, Inc. | Antibodies that inhibit tim-3:lilrb2 interactions and uses thereof |
| CA2978892A1 (en) | 2015-03-06 | 2016-09-15 | Sorrento Therapeutics, Inc. | Antibody therapeutics that bind tim3 |
| MA41867B1 (fr) | 2015-04-01 | 2024-11-29 | Anaptysbio, Inc. | Anticorps dirigés contre l'immunoglobuline de cellule t et protéine 3 de mucine (tim-3) |
| WO2016161248A1 (en) | 2015-04-02 | 2016-10-06 | Tolero Pharmaceuticals, Inc. | Targeting pim kinases in combination with btk inhibition |
| CN105919955A (zh) | 2016-06-13 | 2016-09-07 | 佛山市腾瑞医药科技有限公司 | 一种鲁索利替尼制剂及其应用 |
| CA3095580A1 (en) | 2018-04-13 | 2019-10-17 | Sumitomo Dainippon Pharma Oncology, Inc. | Pim kinase inhibitors for treatment of myeloproliferative neoplasms and fibrosis associated with cancer |
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| US20250320217A1 (en) | 2025-10-16 |
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| CY1123626T1 (el) | 2022-03-24 |
| DK3409278T3 (da) | 2020-11-09 |
| ES2671748T3 (es) | 2018-06-08 |
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