CN106714909A - 布鲁顿氏酪氨酸激酶抑制剂组合及其用途 - Google Patents
布鲁顿氏酪氨酸激酶抑制剂组合及其用途 Download PDFInfo
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Classifications
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- A61K31/33—Heterocyclic compounds
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
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- A61K31/4196—1,2,4-Triazoles
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- A61K31/425—Thiazoles
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
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- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/191—Tumor necrosis factors [TNF], e.g. lymphotoxin [LT], i.e. TNF-beta
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- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/20—Interleukins [IL]
- A61K38/2013—IL-2
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- A—HUMAN NECESSITIES
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- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/21—Interferons [IFN]
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- 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
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Endocrinology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (9)
| Application Number | Priority Date | Filing Date | Title |
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| US201462034997P | 2014-08-08 | 2014-08-08 | |
| US62/034,997 | 2014-08-08 | ||
| US201462082972P | 2014-11-21 | 2014-11-21 | |
| US62/082,972 | 2014-11-21 | ||
| US201462086162P | 2014-12-01 | 2014-12-01 | |
| US62/086,162 | 2014-12-01 | ||
| US201562196251P | 2015-07-23 | 2015-07-23 | |
| US62/196,251 | 2015-07-23 | ||
| PCT/US2015/044095 WO2016022853A1 (en) | 2014-08-08 | 2015-08-06 | Bruton's tyrosine kinase inhibitor combinations and uses thereof |
Publications (1)
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| CN106714909A true CN106714909A (zh) | 2017-05-24 |
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| EP (1) | EP3177366A4 (enExample) |
| JP (1) | JP2017523207A (enExample) |
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| BR (1) | BR112017002232A2 (enExample) |
| CA (1) | CA2956550A1 (enExample) |
| MX (1) | MX2017001656A (enExample) |
| TW (1) | TWI586354B (enExample) |
| WO (1) | WO2016022853A1 (enExample) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111053777A (zh) * | 2018-10-16 | 2020-04-24 | 正大天晴药业集团股份有限公司 | 伊布替尼的药物组合物及其应用 |
| WO2025002340A1 (zh) * | 2023-06-29 | 2025-01-02 | 上海翰森生物医药科技有限公司 | 三并环类抑制剂与抗癌剂在制备抗肿瘤药物中的联合应用 |
Families Citing this family (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX380504B (es) | 2010-06-03 | 2025-03-12 | Pharmacyclics Llc | El uso de inhibidores de la tirosina quinasa de bruton (btk). |
| HK1206073A1 (en) | 2012-07-24 | 2015-12-31 | 药品循环有限责任公司 | Mutations associated with resistance to inhibitors of bruton's tyrosine kinase (btk) |
| SMT202100674T1 (it) | 2014-08-11 | 2022-01-10 | Acerta Pharma Bv | Combinazioni terapeutiche di un inibitore di btk e un inibitore di bcl-2 |
| WO2016071770A2 (en) * | 2014-11-05 | 2016-05-12 | Janssen Pharmaceutica Nv | Biological markers for identifying ibrutinib resistance in patients having mantle cell lymphoma and methods of using the same |
| IL315294A (en) | 2015-03-03 | 2024-10-01 | Pharmacyclics Llc | Pharmaceutical formulations of proton tyrosine kinase inhibitor |
| MX2018014577A (es) | 2016-05-27 | 2019-05-20 | Tg Therapeutics Inc | Combinacion de anticuerpo anti-cd20, inhibidor selectivo de quinasa p13-delta, e inhibidor de btk para tratar trastornos proliferativos de celulas b. |
| TWI795381B (zh) | 2016-12-21 | 2023-03-11 | 比利時商健生藥品公司 | 作為ｍａｌｔ１抑制劑之吡唑衍生物 |
| KR20190141695A (ko) | 2017-04-13 | 2019-12-24 | 센티 바이오사이언시스, 인코포레이티드 | 병용 암 면역요법 |
| AU2018298855B2 (en) | 2017-07-14 | 2024-07-18 | Janssen Pharmaceutica Nv | Long-acting formulations |
| WO2019070777A2 (en) * | 2017-10-04 | 2019-04-11 | University Of Maryland, Baltimore County | PIM KINASE INHIBITORS IN COMBINATION WITH AUTOPHAGIA INHIBITORS FOR THE TREATMENT OF CANCERS |
| TW202014184A (zh) * | 2018-04-30 | 2020-04-16 | 瑞典商阿斯特捷利康公司 | 用於治療癌症之組合 |
| BR112020022185A2 (pt) | 2018-05-03 | 2021-02-02 | Juno Therapeutics Inc | terapia de combinação de uma terapia de células t do receptor de antígeno quimérico (car) e um inibidor de quinase |
| CA3116138A1 (en) | 2018-10-17 | 2020-04-23 | Senti Biosciences, Inc. | Combinatorial cancer immunotherapy |
| US11419898B2 (en) | 2018-10-17 | 2022-08-23 | Senti Biosciences, Inc. | Combinatorial cancer immunotherapy |
| DK3908281T3 (da) | 2019-01-09 | 2024-10-21 | Celgene Corp | Antiproliferative forbindelser og sekundære aktive midler til anvendelse til behandling af multipelt myelom |
| BR112021016400A2 (pt) | 2019-02-22 | 2021-10-13 | Janssen Pharmaceutica N.V. | Forma cristalina de mono-hidrato de 1-(1-oxo-1,2-di-hidroisoquinolin-5-il)-5-(trifluorometil.)-n-(2-(trifluorometil)piridin-4-il)-1h-pirazol-4-carboxamida |
| US12404260B2 (en) | 2019-04-11 | 2025-09-02 | Janssen Pharmaceutica Nv | Pyridine rings containing derivatives as MALT1 inhibitors |
| EP3871665B1 (en) | 2020-02-28 | 2025-12-24 | Martin-Luther-Universität Halle-Wittenberg | Inhibitors of rna-binding proteins as anti-cancer drugs |
| US20240139205A1 (en) * | 2020-03-05 | 2024-05-02 | Universite De Lausanne | Modulators of aralar for treating neurological disorders |
| JP2023533014A (ja) * | 2020-07-09 | 2023-08-01 | ヤンセン ファーマシューティカ エヌ．ベー． | 長時間作用型配合物 |
| JP2023539729A (ja) * | 2020-08-21 | 2023-09-19 | ヤンセン ファーマシューティカ エヌ．ベー． | Ｍａｌｔ１阻害剤の非晶質形態及びその製剤 |
| EP3967307A1 (en) * | 2020-09-15 | 2022-03-16 | Instytut Hematologii I Transfuzologii | Use of pim kinase inhibitors to augment the efficacy of anti-cd20 antibody-based therapies in hematologic malignancies and non-malignant conditions |
| CN114469949A (zh) * | 2020-10-27 | 2022-05-13 | 正大天晴药业集团股份有限公司 | 用于治疗弥漫大b细胞淋巴瘤的喹啉衍生物 |
| EP4301365A1 (en) * | 2021-03-03 | 2024-01-10 | Janssen Pharmaceutica NV | Combination therapy using a malt1 inhibitor and a btk inhibitor |
| US20250302954A1 (en) | 2022-05-11 | 2025-10-02 | Celgene Corporation | Methods to overcome drug resistance by re-sensitizing cancer cells to treatment with a prior therapy via treatment with a t cell therapy |
| US11807689B1 (en) | 2022-06-01 | 2023-11-07 | Tg Therapeutics, Inc. | Anti-CD20 antibody compositions |
| US11884740B1 (en) | 2022-06-01 | 2024-01-30 | Tg Therapeutics, Inc. | Anti-CD20 antibody compositions |
| US11965032B1 (en) | 2022-06-01 | 2024-04-23 | Tg Therapeutics, Inc. | Anti-CD20 antibody compositions |
| US11814439B1 (en) | 2022-06-01 | 2023-11-14 | Tg Therapeutics, Inc. | Anti-CD20 antibody compositions |
| WO2025262118A1 (en) * | 2024-06-20 | 2025-12-26 | Janssen Pharmaceutica Nv | Combination therapy using a malt1 inhibitor and a btk inhibitor |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090149389A1 (en) * | 2007-01-10 | 2009-06-11 | Purdue Research Foundation | Kinase Inhibitors And Uses Thereof |
| WO2013059738A2 (en) * | 2011-10-19 | 2013-04-25 | Pharmacyclics, Inc. | Use of inhibitors of bruton's tyrosine kinase (btk) |
| WO2013184572A1 (en) * | 2012-06-04 | 2013-12-12 | Pharmacyclics, Inc. | Crystalline forms of a bruton's tyrosine kinase inhibitor |
| WO2014004376A2 (en) * | 2012-06-26 | 2014-01-03 | Del Mar Pharmaceuticals | Methods for treating tyrosine-kinase-inhibitor-resistant malignancies in patients with genetic polymorphisms or ahi1 dysregulations or mutations employing dianhydrogalactitol, diacetyldianhydrogalactitol, dibromodulcitol, or analogs or derivatives thereof |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6113898A (en) * | 1995-06-07 | 2000-09-05 | Idec Pharmaceuticals Corporation | Human B7.1-specific primatized antibodies and transfectomas expressing said antibodies |
| US7832117B2 (en) * | 2006-07-17 | 2010-11-16 | Nike, Inc. | Article of footwear including full length composite plate |
| EP2529621B1 (en) | 2006-09-22 | 2016-10-05 | Pharmacyclics LLC | Inhibitors of bruton's tyrosine kinase |
| MX380504B (es) | 2010-06-03 | 2025-03-12 | Pharmacyclics Llc | El uso de inhibidores de la tirosina quinasa de bruton (btk). |
| US9580418B2 (en) | 2014-07-14 | 2017-02-28 | Incyte Corporation | Bicyclic aromatic carboxamide compounds useful as Pim kinase inhibitors |
-
2015
- 2015-08-06 MX MX2017001656A patent/MX2017001656A/es unknown
- 2015-08-06 CA CA2956550A patent/CA2956550A1/en not_active Abandoned
- 2015-08-06 AU AU2015300966A patent/AU2015300966A1/en not_active Abandoned
- 2015-08-06 BR BR112017002232A patent/BR112017002232A2/pt not_active Application Discontinuation
- 2015-08-06 US US14/820,434 patent/US9730938B2/en active Active
- 2015-08-06 JP JP2017505609A patent/JP2017523207A/ja active Pending
- 2015-08-06 CN CN201580047327.7A patent/CN106714909A/zh active Pending
- 2015-08-06 WO PCT/US2015/044095 patent/WO2016022853A1/en not_active Ceased
- 2015-08-06 EP EP15829601.2A patent/EP3177366A4/en not_active Withdrawn
- 2015-08-07 TW TW104125847A patent/TWI586354B/zh not_active IP Right Cessation
-
2017
- 2017-07-21 US US15/656,394 patent/US20180071295A1/en not_active Abandoned
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090149389A1 (en) * | 2007-01-10 | 2009-06-11 | Purdue Research Foundation | Kinase Inhibitors And Uses Thereof |
| WO2013059738A2 (en) * | 2011-10-19 | 2013-04-25 | Pharmacyclics, Inc. | Use of inhibitors of bruton's tyrosine kinase (btk) |
| WO2013184572A1 (en) * | 2012-06-04 | 2013-12-12 | Pharmacyclics, Inc. | Crystalline forms of a bruton's tyrosine kinase inhibitor |
| WO2014004376A2 (en) * | 2012-06-26 | 2014-01-03 | Del Mar Pharmaceuticals | Methods for treating tyrosine-kinase-inhibitor-resistant malignancies in patients with genetic polymorphisms or ahi1 dysregulations or mutations employing dianhydrogalactitol, diacetyldianhydrogalactitol, dibromodulcitol, or analogs or derivatives thereof |
Non-Patent Citations (3)
| Title |
|---|
| ERIKA K. KEETON ET AL: "AZD1208, a potent and selective pan-Pim kinase inhibitor, demonstrates efficacy in preclinical models of acute myeloid leukemia", 《BLOOD》 * |
| HSU-PING KUO ET AL: "The role of PIM1 in the ibrutinib-resistant ABC subtype of diffuse large B-cell lymphoma", 《AM J CANCER RES》 * |
| LISA S. CHEN ET AL: "Pim kinase inhibitor, SGI-1776, induces apoptosis in chronic lymphocytic leukemia cells", 《BLOOD》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111053777A (zh) * | 2018-10-16 | 2020-04-24 | 正大天晴药业集团股份有限公司 | 伊布替尼的药物组合物及其应用 |
| WO2025002340A1 (zh) * | 2023-06-29 | 2025-01-02 | 上海翰森生物医药科技有限公司 | 三并环类抑制剂与抗癌剂在制备抗肿瘤药物中的联合应用 |
Also Published As
| Publication number | Publication date |
|---|---|
| TW201609107A (zh) | 2016-03-16 |
| US9730938B2 (en) | 2017-08-15 |
| TWI586354B (zh) | 2017-06-11 |
| US20160038495A1 (en) | 2016-02-11 |
| WO2016022853A1 (en) | 2016-02-11 |
| EP3177366A4 (en) | 2018-04-04 |
| CA2956550A1 (en) | 2016-02-11 |
| JP2017523207A (ja) | 2017-08-17 |
| AU2015300966A1 (en) | 2017-02-16 |
| BR112017002232A2 (pt) | 2018-07-24 |
| MX2017001656A (es) | 2017-07-24 |
| US20180071295A1 (en) | 2018-03-15 |
| EP3177366A1 (en) | 2017-06-14 |
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