CA2684722A1 - Combination therapy with a compound acting as a platelet adp receptor inhibitor - Google Patents
Combination therapy with a compound acting as a platelet adp receptor inhibitor Download PDFInfo
- Publication number
- CA2684722A1 CA2684722A1 CA002684722A CA2684722A CA2684722A1 CA 2684722 A1 CA2684722 A1 CA 2684722A1 CA 002684722 A CA002684722 A CA 002684722A CA 2684722 A CA2684722 A CA 2684722A CA 2684722 A1 CA2684722 A1 CA 2684722A1
- Authority
- CA
- Canada
- Prior art keywords
- factor
- agent
- pharmaceutically acceptable
- inhibitor
- pharmaceutical composition
- Prior art date
- Legal status (The legal status 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 status listed.)
- Abandoned
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Landscapes
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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| US60/947,921 | 2007-07-03 | ||
| US97870007P | 2007-10-09 | 2007-10-09 | |
| US60/978,700 | 2007-10-09 | ||
| PCT/US2008/062561 WO2008137787A2 (en) | 2007-05-02 | 2008-05-02 | Combination therapy with a compound acting as a platelet adp receptor inhibitor |
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| CA2684722A1 true CA2684722A1 (en) | 2008-11-13 |
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| BRPI0512273A (pt) | 2004-06-18 | 2008-02-19 | Millennium Pharm Inc | inibidores do fator xa |
| US7696352B2 (en) * | 2004-06-18 | 2010-04-13 | Millennium Pharmaceuticals, Inc. | Factor Xa inhibitors |
| DK2774925T3 (en) | 2005-11-08 | 2017-02-27 | Vertex Pharma | Heterocyclic modulators of ATP binding cassette transporters |
| US20090186810A1 (en) * | 2006-03-27 | 2009-07-23 | Portola Pharmaceuticals, Inc. | Potassium channel modulators and platelet procoagulant activity |
| EP2016072B1 (en) | 2006-05-05 | 2014-07-16 | Millennium Pharmaceuticals, Inc. | Factor xa inhibitors |
| WO2008057972A1 (en) * | 2006-11-02 | 2008-05-15 | Millennium Pharmaceuticals, Inc. | Methods of synthesizing pharmaceutical salts of a factor xa inhibitor |
| US20080293704A1 (en) * | 2007-01-05 | 2008-11-27 | Millennium Pharmaceuticals, Inc. | FACTOR Xa INHIBITORS |
| WO2008127682A2 (en) | 2007-04-13 | 2008-10-23 | Millennium Pharmaceuticals, Inc. | Combination anticoagulant therapy with a compound that acts as a factor xa inhibitor |
| CN103626744B (zh) | 2007-12-07 | 2016-05-11 | 沃泰克斯药物股份有限公司 | 3-(6-(1-(2,2-二氟苯并[d][1,3]间二氧杂环戊烯-5-基)环丙烷甲酰氨基)-3-甲基吡啶-2-基)苯甲酸的固体形式 |
| CA2743639A1 (en) * | 2008-11-14 | 2010-05-20 | Patheon Inc. | Solid composition for controlled release of ionizable active agents with poor aqueous solubility at low ph and methods of use thereof |
| JP5796872B2 (ja) | 2009-12-17 | 2015-10-21 | ミレニアム ファーマシューティカルズ， インコーポレイテッドＭｉｌｌｅｎｎｉｕｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． | 第Ｘａ因子阻害剤の結晶性塩 |
| WO2011075602A1 (en) * | 2009-12-17 | 2011-06-23 | Millennium Pharmaceuticals, Inc. | Methods of preparing factor xa inhibitors and salts thereof |
| ES2550033T3 (es) * | 2009-12-23 | 2015-11-04 | Ratiopharm Gmbh | Forma de dosificación farmacéutica sólida de ticagrelor |
| CA2792993A1 (fr) * | 2010-01-21 | 2011-07-28 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Composition particuliere pour son application comme medicament |
| SI3246021T1 (sl) * | 2010-02-25 | 2020-03-31 | Bristol-Myers Squibb Holdings Ireland Unlimited Company | Formulacije apiksabana |
| EP2555755B2 (en) | 2010-04-07 | 2019-07-10 | Vertex Pharmaceuticals Incorporated | Pharmaceutical compositions of 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyriodin-2-yl)benzoic acid and administration thereof |
| AR082804A1 (es) * | 2010-09-01 | 2013-01-09 | Portola Pharm Inc | Formas cristalinas de un inhibidor del factor xa |
| PT2691371E (pt) * | 2011-03-29 | 2015-07-20 | Sanofi Sa | Sal de ácido benzóico de otamixaban |
| US20150224091A1 (en) * | 2011-08-31 | 2015-08-13 | Portola Pharmaceuticals, Inc. | Prevention and treatment of thrombosis in medically ill patients |
| WO2014099694A1 (en) * | 2012-12-19 | 2014-06-26 | Merck Sharp & Dohme Corp. | FACTOR IXa INHIBITORS |
| EP2934537B1 (en) * | 2012-12-19 | 2018-04-04 | Merck Sharp & Dohme Corp. | Factor ixa inhibitors |
| US9708308B2 (en) | 2012-12-19 | 2017-07-18 | Merck Sharp Dohme Corp. | Factor IXa inhibitors |
| US9200268B2 (en) | 2012-12-27 | 2015-12-01 | Portola Pharmaceuticals, Inc. | Compounds and methods for purification of serine proteases |
| HRP20210516T2 (hr) | 2013-11-12 | 2021-10-01 | Vertex Pharmaceuticals Incorporated | Postupak proizvodnje farmaceutskih pripravaka za liječenje bolesti koje su posredovane putem cftr |
| US9676723B2 (en) * | 2014-02-11 | 2017-06-13 | Merck Sharp & Dohme Corp | Factor XIa inhibitors |
| CN106831553A (zh) * | 2015-09-11 | 2017-06-13 | 天津科伦药物研究有限公司 | 贝曲西班或其类似物的制备方法 |
| CN105250286A (zh) * | 2015-11-13 | 2016-01-20 | 谭惠娟 | 一种抗血栓组合物 |
| EP3254674A1 (en) * | 2016-06-08 | 2017-12-13 | Sandoz Ag | Pharmaceutical compositions of betrixaban maleate |
| WO2018093695A1 (en) | 2016-11-18 | 2018-05-24 | Merck Sharp & Dohme Corp. | FACTOR XIIa INHIBITORS |
| US11654036B2 (en) | 2020-05-26 | 2023-05-23 | Elixir Medical Corporation | Anticoagulant compounds and methods and devices for their use |
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| US6509348B1 (en) * | 1998-11-03 | 2003-01-21 | Bristol-Myers Squibb Company | Combination of an ADP-receptor blocking antiplatelet drug and a thromboxane A2 receptor antagonist and a method for inhibiting thrombus formation employing such combination |
| AU760174B2 (en) | 1999-02-09 | 2003-05-08 | Bristol-Myers Squibb Company | Lactam inhibitors of FXa and method |
| US6844367B1 (en) * | 1999-09-17 | 2005-01-18 | Millennium Pharmaceuticals, Inc. | Benzamides and related inhibitors of factor Xa |
| DE60040676D1 (de) * | 1999-09-17 | 2008-12-11 | Millennium Pharm Inc | BENZAMIDE UND ÄHNLICHE INHIBITOREN VON FAKTOR Xa |
| MY125533A (en) * | 1999-12-06 | 2006-08-30 | Bristol Myers Squibb Co | Heterocyclic dihydropyrimidine compounds |
| US6906063B2 (en) * | 2000-02-04 | 2005-06-14 | Portola Pharmaceuticals, Inc. | Platelet ADP receptor inhibitors |
| CA2401778C (en) * | 2000-02-29 | 2010-12-21 | Cor Therapeutics, Inc. | Benzamides and related inhibitors of factor xa |
| US7235567B2 (en) | 2000-06-15 | 2007-06-26 | Schering Corporation | Crystalline polymorph of a bisulfate salt of a thrombin receptor antagonist |
| US20040192753A1 (en) | 2000-06-15 | 2004-09-30 | Samuel Chackalamannil | Methods of use of thrombin receptor antagonists |
| AU2001296305B2 (en) | 2000-09-26 | 2007-12-06 | Duke University | RNA aptamers and methods for identifying the same |
| US7312235B2 (en) * | 2001-03-30 | 2007-12-25 | Millennium Pharmaceuticals, Inc. | Benzamide inhibitors of factor Xa |
| ZA200508481B (en) * | 2003-04-09 | 2007-04-25 | Japan Tobacco Inc | Heteroaromatic pentacyclic compound and medicinal use thereof |
| US7294635B2 (en) | 2003-10-03 | 2007-11-13 | Portola Pharmaceuticals, Inc. | Substituted isoquinolinones |
| DE602004024910D1 (de) * | 2003-10-09 | 2010-02-11 | Millennium Pharm Inc | Thioethersubstituierte benzamide als inhibitoren von faktor xa |
| BRPI0512273A (pt) * | 2004-06-18 | 2008-02-19 | Millennium Pharm Inc | inibidores do fator xa |
| US7696352B2 (en) * | 2004-06-18 | 2010-04-13 | Millennium Pharmaceuticals, Inc. | Factor Xa inhibitors |
| EP1807086A1 (en) * | 2004-10-25 | 2007-07-18 | Boehringer Ingelheim International GmbH | Use of dipyridamole in combination with antithrombotics for treatment and prevention of thromboembolic diseases |
| WO2006083924A1 (en) | 2005-02-02 | 2006-08-10 | Vitae Pharmaceuticals, Inc. | 1-acylamino-2-hydroxy-3-amino-w-arylalkanes as renin inhibitors |
| US7467697B2 (en) * | 2005-10-07 | 2008-12-23 | Ford Global Technologies, Llc | Electromagnetic coupling device for engine accessories |
| KR101423483B1 (ko) * | 2005-11-03 | 2014-07-28 | 포톨라 파마슈티컬스, 인코포레이티드 | 〔４-(６-할로-７-치환된-２,４-디옥소-１,４-디히드로-２ｈ-퀴나졸린-３-일)-페닐〕-５-클로로티오펜-２-일-설포닐우레아 및 이의 형태 및 이와 관련된 방법 |
| PT1948608E (pt) * | 2005-11-08 | 2012-05-24 | Millennium Pharm Inc | Novos sais farmacêuticos e polimorfos de um inibidor do fator xa |
| US20090186810A1 (en) * | 2006-03-27 | 2009-07-23 | Portola Pharmaceuticals, Inc. | Potassium channel modulators and platelet procoagulant activity |
| EP2016072B1 (en) | 2006-05-05 | 2014-07-16 | Millennium Pharmaceuticals, Inc. | Factor xa inhibitors |
| CA2671502C (en) * | 2006-12-08 | 2017-01-24 | Millennium Pharmaceuticals, Inc. | Unit dose formulations and methods of treating thrombosis with an oral factor xa inhibitor |
| US20080293704A1 (en) * | 2007-01-05 | 2008-11-27 | Millennium Pharmaceuticals, Inc. | FACTOR Xa INHIBITORS |
| WO2008127682A2 (en) * | 2007-04-13 | 2008-10-23 | Millennium Pharmaceuticals, Inc. | Combination anticoagulant therapy with a compound that acts as a factor xa inhibitor |
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2008
- 2008-05-02 EA EA200901442A patent/EA020045B1/ru not_active IP Right Cessation
- 2008-05-02 ES ES08747590.1T patent/ES2467468T3/es active Active
- 2008-05-02 CA CA002684722A patent/CA2684722A1/en not_active Abandoned
- 2008-05-02 NZ NZ581324A patent/NZ581324A/en not_active IP Right Cessation
- 2008-05-02 KR KR1020097024870A patent/KR101509829B1/ko not_active Expired - Fee Related
- 2008-05-02 NZ NZ599556A patent/NZ599556A/xx not_active IP Right Cessation
- 2008-05-02 BR BRPI0811000-0A2A patent/BRPI0811000A2/pt not_active Application Discontinuation
- 2008-05-02 AU AU2008247435A patent/AU2008247435A1/en not_active Abandoned
- 2008-05-02 MX MX2009011755A patent/MX2009011755A/es active IP Right Grant
- 2008-05-02 PT PT87475901T patent/PT2146705E/pt unknown
- 2008-05-02 WO PCT/US2008/062561 patent/WO2008137787A2/en not_active Ceased
- 2008-05-02 EP EP13151486.1A patent/EP2586439A1/en not_active Withdrawn
- 2008-05-02 CN CN200880021658.3A patent/CN101686959B/zh not_active Expired - Fee Related
- 2008-05-02 JP JP2010506696A patent/JP5439363B2/ja not_active Expired - Fee Related
- 2008-05-02 EP EP08747590.1A patent/EP2146705B1/en not_active Not-in-force
- 2008-05-02 US US12/114,706 patent/US20080279845A1/en not_active Abandoned
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- 2009-10-23 TN TNP2009000444A patent/TN2009000444A1/fr unknown
- 2009-10-29 IL IL201826A patent/IL201826A/en not_active IP Right Cessation
- 2009-10-30 GT GT200900283A patent/GT200900283A/es unknown
- 2009-11-20 CO CO09132196A patent/CO6241105A2/es not_active Application Discontinuation
- 2009-11-26 MA MA32375A patent/MA31396B1/fr unknown
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Also Published As
| Publication number | Publication date |
|---|---|
| NZ581324A (en) | 2012-05-25 |
| HK1138765A1 (en) | 2010-09-03 |
| JP5439363B2 (ja) | 2014-03-12 |
| IL201826A0 (en) | 2010-06-16 |
| EP2146705A2 (en) | 2010-01-27 |
| EA200901442A1 (ru) | 2010-06-30 |
| MX2009011755A (es) | 2010-02-12 |
| TN2009000444A1 (en) | 2011-03-31 |
| CN101686959B (zh) | 2014-05-07 |
| GT200900283A (es) | 2011-10-05 |
| PT2146705E (pt) | 2014-05-23 |
| US8946219B2 (en) | 2015-02-03 |
| US20080279845A1 (en) | 2008-11-13 |
| EP2586439A1 (en) | 2013-05-01 |
| CO6241105A2 (es) | 2011-01-20 |
| ES2467468T3 (es) | 2014-06-12 |
| WO2008137787A3 (en) | 2009-02-05 |
| AU2008247435A1 (en) | 2008-11-13 |
| EA020045B1 (ru) | 2014-08-29 |
| MA31396B1 (fr) | 2010-05-03 |
| NZ599556A (en) | 2013-10-25 |
| IL201826A (en) | 2014-08-31 |
| JP2010526103A (ja) | 2010-07-29 |
| CN101686959A (zh) | 2010-03-31 |
| ECSP099775A (es) | 2010-01-29 |
| KR101509829B1 (ko) | 2015-04-06 |
| US20110033459A1 (en) | 2011-02-10 |
| KR20100023836A (ko) | 2010-03-04 |
| BRPI0811000A2 (pt) | 2015-01-27 |
| EP2146705B1 (en) | 2014-03-05 |
| WO2008137787A2 (en) | 2008-11-13 |
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