EA034992B1 - Комбинации лекарственных средств для лечения множественной миеломы - Google Patents
Комбинации лекарственных средств для лечения множественной миеломы Download PDFInfo
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- EA034992B1 EA034992B1 EA201790312A EA201790312A EA034992B1 EA 034992 B1 EA034992 B1 EA 034992B1 EA 201790312 A EA201790312 A EA 201790312A EA 201790312 A EA201790312 A EA 201790312A EA 034992 B1 EA034992 B1 EA 034992B1
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| UA108618C2 (uk) | 2009-08-07 | 2015-05-25 | Застосування c-met-модуляторів в комбінації з темозоломідом та/або променевою терапією для лікування раку | |
| BR112016018450A2 (pt) | 2014-02-14 | 2018-09-18 | Exelixis Inc | formas sólidas cristalinas de n-{4-[(6,7-dimetoxiquinolin-4-il)oxi]fenil}-n'-(4-fluorofenil)ciclopropano-1,1-dicarboxamida, processos de preparo e métodos de uso |
| EP3119476A1 (en) | 2014-03-17 | 2017-01-25 | Exelixis, Inc. | Dosing of cabozantinib formulations |
| EP3174854B1 (en) | 2014-07-31 | 2022-08-24 | Exelixis, Inc. | Method of preparing fluorine-18 labeled cabozantinib and its analogs |
| MX382904B (es) | 2014-08-05 | 2025-03-13 | Exelixis Inc | Combinaciones de fármacos para tratar mieloma múltiple. |
| EP3442531A1 (en) | 2016-04-15 | 2019-02-20 | Exelixis, Inc. | Method of treating renal cell carcinoma using n-(4-(6,7-dimethoxyquinolin-4-yloxy) phenyl)-n'-(4-fluoropheny)cyclopropane-1,1-dicarboxamide, (2s)-hydroxybutanedioate |
| JP2020533382A (ja) * | 2017-09-14 | 2020-11-19 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドＧｌａｘｏｓｍｉｔｈｋｌｉｎｅ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ Ｄｅｖｅｌｏｐｍｅｎｔ Ｌｉｍｉｔｅｄ | 癌の組合せ治療 |
| CN117402114A (zh) | 2018-01-26 | 2024-01-16 | 埃克塞里艾克西斯公司 | 用于治疗激酶依赖性病症的化合物 |
| TWI831259B (zh) | 2018-06-15 | 2024-02-01 | 漢達生技醫藥股份有限公司 | 包含達沙替尼十二烷基硫酸鹽組合物的膠囊 |
| WO2023222946A1 (en) | 2022-05-18 | 2023-11-23 | Fermion Oy | Process for the preparation of cabozantinib |
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Family Cites Families (43)
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|---|---|---|---|---|
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| EP2210607B1 (en) | 2003-09-26 | 2011-08-17 | Exelixis Inc. | N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinolin-4-yl}oxy)phenyl]-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide for the treatment of cancer |
| US7977345B2 (en) | 2004-07-02 | 2011-07-12 | Exelixis, Inc. | c-MET modulators and method of use |
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| PL2101759T3 (pl) | 2006-12-14 | 2019-05-31 | Exelixis Inc | Sposoby stosowania inhibitorów MEK |
| UY31800A (es) | 2008-05-05 | 2009-11-10 | Smithkline Beckman Corp | Metodo de tratamiento de cancer usando un inhibidor de cmet y axl y un inhibidor de erbb |
| AR075084A1 (es) | 2008-09-26 | 2011-03-09 | Smithkline Beecham Corp | Metodo de preparacion de quinolinil -oxidifenil - ciclopropanodicarboxamidas e intermediarios correspondientes |
| JP5486606B2 (ja) | 2008-11-13 | 2014-05-07 | エクセリクシス， インク． | キノリン誘導体の調製方法 |
| US20130030172A1 (en) | 2008-12-04 | 2013-01-31 | Exelixis, Inc. | Methods of Preparing Quinoline Derivatives |
| NZ779754A (en) | 2009-01-16 | 2023-04-28 | Exelixis Inc | Malate salt of n-(4-{ [6,7-bis(methyloxy)quinolin-4-yl] oxy} phenyl)-n’-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, and crystalline forms thereof for the treatment of cancer |
| CN102510855B (zh) | 2009-07-17 | 2015-11-25 | 埃克塞里艾克西斯公司 | N-[3-氟-4-({6-(甲基氧基)-7-[(3-吗啉-4-基丙基)氧基]-喹啉-4-基}氧基)苯基]-n′-(4-氟苯基)环丙烷-1，1-二甲酰胺的晶形 |
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| MX2012008898A (es) * | 2010-02-03 | 2012-11-06 | Incyte Corp | Imidazo - [1, 2 - b] [1, 2, 4] triazinas como inhibidores de c - met. |
| AU2011224203A1 (en) | 2010-03-12 | 2012-10-04 | Exelixis, Inc | Hydrated crystalline forms of N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin -4-ylpropyl)oxy]-quinolin-4-yl}oxy)phenyl] -N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide |
| US20120070368A1 (en) | 2010-04-16 | 2012-03-22 | Exelixis, Inc. | Methods of Using C-Met Modulators |
| EA030435B1 (ru) | 2010-07-16 | 2018-08-31 | Экселиксис, Инк. | ТАБЛЕТКА, СОДЕРЖАЩАЯ МОДУЛЯТОР c-MET В ФОРМЕ КРИСТАЛЛИЧЕСКОЙ L-МАЛАТНОЙ СОЛИ (ВАРИАНТЫ), СПОСОБ ЕЕ ПРОИЗВОДСТВА И СПОСОБ ЛЕЧЕНИЯ ОНКОЛОГИЧЕСКОГО ЗАБОЛЕВАНИЯ С ЕЕ ИСПОЛЬЗОВАНИЕМ |
| US20140186407A9 (en) | 2010-07-16 | 2014-07-03 | Exelixis Inc. | C-Met Modulator Pharmaceutical Compositions |
| US20140057908A1 (en) | 2010-09-27 | 2014-02-27 | Exelixis, Inc. | Method of Treating Cancer |
| JP2013540759A (ja) | 2010-09-27 | 2013-11-07 | エクセリクシス， インク． | 去勢抵抗性前立腺癌および造骨性転移の治療のためのｍｅｔおよびｖｅｇｆの二元阻害薬 |
| MX352926B (es) | 2010-09-27 | 2017-12-14 | Exelixis Inc | Inhibidores dobles de met y factor de crecimiento endotelial vascular (vegf) para el tratamiento de cancer de prostata resistente a la castracion y metastasis osteoblasticas en los huesos. |
| WO2012064967A2 (en) * | 2010-11-10 | 2012-05-18 | Cedars-Sinai Medical Center | Cancer cell-derived receptor activator of the nf-kb ligand drives bone and soft tissue metastases |
| WO2012071321A1 (en) | 2010-11-22 | 2012-05-31 | Glaxosmithkline Llc | Method of treating cancer |
| BR112013020362A2 (pt) | 2011-02-10 | 2018-05-29 | Exelixis Inc | processos para a preparação de compostos de quinolina, compostos e combinações farmacêuticas que os contem |
| US20120252840A1 (en) | 2011-04-04 | 2012-10-04 | Exelixis, Inc. | Method of Treating Cancer |
| MX2013012695A (es) | 2011-05-02 | 2014-03-27 | Exelixis Inc | Metodo para el tratamiento del cancer y el dolor por cancer de hueso. |
| TW201306842A (zh) | 2011-06-15 | 2013-02-16 | Exelixis Inc | 使用ｐｉ３ｋ／ｍｔｏｒ吡啶並嘧啶酮抑制劑及苯達莫司汀及／或利妥昔單抗治療惡性血液疾病之組合療法 |
| EP2758057B1 (en) | 2011-09-22 | 2017-05-31 | Exelixis, Inc. | Method for treating osteoporosis |
| CN104395284A (zh) | 2011-10-20 | 2015-03-04 | 埃克塞里艾克西斯公司 | 制备喹啉衍生物的方法 |
| IN2014CN04067A (https=) | 2011-11-08 | 2015-10-23 | Exelixis Inc | |
| JP2015508066A (ja) * | 2012-02-06 | 2015-03-16 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | Ｅｍｐ２は、ｖｅｇｆの誘導を通じた癌細胞における血管形成を制御する |
| CN103304552B (zh) * | 2012-03-09 | 2016-12-28 | 广东东阳光药业有限公司 | 取代的吡啶化合物及其使用方法和用途 |
| WO2013166296A1 (en) | 2012-05-02 | 2013-11-07 | Exelixis, Inc. | A dual met - vegf modulator for treating osteolytic bone metastases |
| JP6513567B2 (ja) | 2012-09-07 | 2019-05-15 | エクセリクシス， インク． | 肺腺癌の治療で使用するためのｍｅｔ、ｖｅｇｆｒ、およびｒｅｔの阻害剤 |
| US20140221372A1 (en) | 2013-02-06 | 2014-08-07 | GlaxoSmithKline Intellectual Property (NO 2.) Limited | Method of administration and treatment |
| CA2907334C (en) | 2013-03-15 | 2021-12-07 | Exelixis, Inc. | Metabolites of n-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-n'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide |
| WO2014165779A1 (en) | 2013-04-04 | 2014-10-09 | Exelixis, Inc. | Drug combinations to treat cancer |
| US11564915B2 (en) | 2013-04-04 | 2023-01-31 | Exelixis, Inc. | Cabozantinib dosage form and use in the treatment of cancer |
| BR112016018450A2 (pt) | 2014-02-14 | 2018-09-18 | Exelixis Inc | formas sólidas cristalinas de n-{4-[(6,7-dimetoxiquinolin-4-il)oxi]fenil}-n'-(4-fluorofenil)ciclopropano-1,1-dicarboxamida, processos de preparo e métodos de uso |
| EP3119476A1 (en) | 2014-03-17 | 2017-01-25 | Exelixis, Inc. | Dosing of cabozantinib formulations |
| UA121655C2 (uk) | 2014-04-25 | 2020-07-10 | Екселіксіс, Інк. | Спосіб лікування аденокарциноми легень |
| EP3174854B1 (en) | 2014-07-31 | 2022-08-24 | Exelixis, Inc. | Method of preparing fluorine-18 labeled cabozantinib and its analogs |
| MX382904B (es) | 2014-08-05 | 2025-03-13 | Exelixis Inc | Combinaciones de fármacos para tratar mieloma múltiple. |
| TW201625243A (zh) | 2014-10-14 | 2016-07-16 | 艾克塞里克斯公司 | 用於治療黑素瘤之藥物組合 |
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Non-Patent Citations (3)
| Title |
|---|
| ISRAEL CAÑADAS, FEDERICO ROJO, MONTSERRAT ARUMÍ-URÍA, ANA ROVIRA , JOAN ALBANELL, EDURNE ARRIOLA: "C-MET as a new therapeutic target for the development of novel anticancer drugs", CLINICAL AND TRANSLATIONAL ONCOLOGY, SPRINGER MILAN, MILAN, vol. 12, no. 4, 1 April 2010 (2010-04-01), Milan, pages 253 - 260, XP002745388, ISSN: 1699-3055, DOI: 10.1007/s12094-010-0501-0 * |
| MILLIGAN S A, BURKE P, COLEMAN D T, BIGELOW R L, STEFFAN J J, CARROLL J L, WILLIAMS B J, CARDELLI J A: "The green tea polyphenol EGCG potentiates the antiproliferative activity of c-Met and epidermal growth factor receptor inhibitors in non-small cell lung cancer cells.", CLINICAL CANCER RESEARCH, AMERICAN ASSOCIATION FOR CANCER RESEARCH, US, vol. 15, no. 15, 1 August 2009 (2009-08-01), US, pages 4885 - 4894, XP002745386, ISSN: 1078-0432, DOI: 10.1158/1078-0432.CCR-09-0109 * |
| MOSCHETTA M, BASILE A, FERRUCCI A, FRASSANITO M A, RAO L, RIA R, SOLIMANDO A G, GIULIANI N, BOCCARELLI A, FUMAROLA F, COLUCCIA M, : "Novel targeting of phospho-cMET overcomes drug resistance and induces antitumor activity in multiple myeloma.", CLINICAL CANCER RESEARCH, AMERICAN ASSOCIATION FOR CANCER RESEARCH, US, vol. 19, no. 16, 15 August 2013 (2013-08-15), US, pages 4371 - 4382, XP002745387, ISSN: 1078-0432, DOI: 10.1158/1078-0432.CCR-13-0039 * |
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| Publication number | Publication date |
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| MX2017001490A (es) | 2017-05-11 |
| JP2020002179A (ja) | 2020-01-09 |
| KR20170031786A (ko) | 2017-03-21 |
| EP3177311B1 (en) | 2024-10-30 |
| EP3177311C0 (en) | 2024-10-30 |
| UA121482C2 (uk) | 2020-06-10 |
| CA2957466C (en) | 2023-10-17 |
| CN106573042A (zh) | 2017-04-19 |
| WO2016022697A1 (en) | 2016-02-11 |
| BR112017002318A2 (pt) | 2018-07-17 |
| JP2017526662A (ja) | 2017-09-14 |
| EA201790312A1 (ru) | 2017-06-30 |
| JP6892381B2 (ja) | 2021-06-23 |
| CA2957466A1 (en) | 2016-02-11 |
| AU2015301097B2 (en) | 2021-03-04 |
| EP3177311A1 (en) | 2017-06-14 |
| US20170224672A1 (en) | 2017-08-10 |
| MA40457A (fr) | 2017-06-14 |
| US11065240B2 (en) | 2021-07-20 |
| MX382904B (es) | 2025-03-13 |
| KR102634247B1 (ko) | 2024-02-05 |
| AU2015301097A1 (en) | 2017-03-02 |
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