CN102988365A - 含有vx-950的剂型及其给药方案 - Google Patents
含有vx-950的剂型及其给药方案 Download PDFInfo
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Applications Claiming Priority (8)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US62354204P | 2004-10-29 | 2004-10-29 | |
| US60/623,542 | 2004-10-29 | ||
| US67940205P | 2005-05-09 | 2005-05-09 | |
| US60/679,402 | 2005-05-09 | ||
| US68209105P | 2005-05-17 | 2005-05-17 | |
| US60/682,091 | 2005-05-17 | ||
| US72274605P | 2005-09-30 | 2005-09-30 | |
| US60/722,746 | 2005-09-30 |
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Families Citing this family (49)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100509388B1 (ko) * | 1996-10-18 | 2005-08-23 | 버텍스 파마슈티칼스 인코포레이티드 | 세린 프로테아제, 특히 간염 ｃ 바이러스 ｎｓ３ 프로테아제의 저해제 |
| TWI359147B (en) * | 2003-09-05 | 2012-03-01 | Vertex Pharma | Inhibitors of serine proteases, particularly hcv n |
| US20120201883A1 (en) * | 2004-05-21 | 2012-08-09 | Accu-Break Technologies, Inc | Antiviral compositons |
| AR049297A1 (es) * | 2004-06-08 | 2006-07-12 | Vertex Pharma | Una composicion farmaceutica y dispersiones solidas de vx-950 (inhibidor de la proteasa de hcv ns3/4a) y proceso de obtencion |
| NZ563365A (en) * | 2005-06-02 | 2011-02-25 | Schering Corp | Combination of HCV protease inhibitors with a surfactant |
| AU2006252519B2 (en) * | 2005-06-02 | 2012-08-30 | Merck Sharp & Dohme Corp. | HCV protease inhibitors in combination with food |
| US20060287248A1 (en) * | 2005-06-02 | 2006-12-21 | Schering Corporation | Asymmetric dosing methods |
| KR20080033481A (ko) * | 2005-08-02 | 2008-04-16 | 버텍스 파마슈티칼스 인코포레이티드 | 세린 프로테아제의 억제제 |
| US8399615B2 (en) | 2005-08-19 | 2013-03-19 | Vertex Pharmaceuticals Incorporated | Processes and intermediates |
| US7964624B1 (en) | 2005-08-26 | 2011-06-21 | Vertex Pharmaceuticals Incorporated | Inhibitors of serine proteases |
| AR055395A1 (es) * | 2005-08-26 | 2007-08-22 | Vertex Pharma | Compuestos inhibidores de la actividad de la serina proteasa ns3-ns4a del virus de la hepatitis c |
| EP1991229A2 (en) | 2006-02-27 | 2008-11-19 | Vertex Pharmaceuticals Incorporated | Co-crystals and pharmaceutical compositions comprising the same |
| EP1993994A2 (en) | 2006-03-16 | 2008-11-26 | Vertex Pharmceuticals Incorporated | Deuterated hepatitis c protease inhibitors |
| EP2007789B1 (en) | 2006-04-11 | 2015-05-20 | Novartis AG | Spirocyclic HCV/HIV inhibitors and their uses |
| KR20090057035A (ko) * | 2006-08-21 | 2009-06-03 | 유나이티드 세러퓨틱스 코오포레이션 | 바이러스 감염의 치료를 위한 병용 요법 |
| JP2010519329A (ja) * | 2007-02-27 | 2010-06-03 | バーテックス ファーマシューティカルズ インコーポレイテッド | セリンプロテアーゼ阻害剤 |
| DK2114924T3 (da) * | 2007-02-27 | 2012-04-10 | Vertex Pharma | Co-krystaller og farmaceutiske sammensætninger omfattende disse |
| JP2010528013A (ja) * | 2007-05-21 | 2010-08-19 | バーテックス ファーマシューティカルズ インコーポレイテッド | Ｖｘ−９５０を含む用量形態およびそれらの投与レジメン |
| CN101835774B (zh) * | 2007-08-30 | 2014-09-17 | 弗特克斯药品有限公司 | 共晶体和包含该共晶体的药物组合物 |
| AR068756A1 (es) * | 2007-10-10 | 2009-12-02 | Novartis Ag | Compuestos peptidicos, formulacion farmaceutica y sus usos como moduladores del virus de la hepatitis c |
| WO2009061395A2 (en) * | 2007-11-05 | 2009-05-14 | Vertex Pharmaceuticals Incorporated | Hcv combination therapies |
| ES2607814T3 (es) * | 2008-02-28 | 2017-04-04 | Abbvie Inc. | Preparación de tabletas |
| MX2010011580A (es) * | 2008-04-23 | 2010-11-09 | Vertex Pharma | Tratamiento de infecciones por virus de hepatitis c con telaprevir (vx-950) en pacientes que no responden al tratamiento con interferon-alfa-2a-2b pegilado y ribavirina. |
| US20100069821A1 (en) * | 2008-09-16 | 2010-03-18 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Ex vivo modifiable medicament release-sites final dosage form |
| US20100068235A1 (en) * | 2008-09-16 | 2010-03-18 | Searete LLC, a limited liability corporation of Deleware | Individualizable dosage form |
| US20100068275A1 (en) * | 2008-09-16 | 2010-03-18 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Personalizable dosage form |
| US20100069887A1 (en) * | 2008-09-16 | 2010-03-18 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Multiple chamber ex vivo adjustable-release final dosage form |
| US20100068266A1 (en) * | 2008-09-16 | 2010-03-18 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Ex vivo-modifiable multiple-release state final dosage form |
| US20100068153A1 (en) * | 2008-09-16 | 2010-03-18 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Ex vivo activatable final dosage form |
| US20100068233A1 (en) * | 2008-09-16 | 2010-03-18 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Modifiable dosage form |
| US20100068254A1 (en) * | 2008-09-16 | 2010-03-18 | Mahalaxmi Gita Bangera | Modifying a medicament availability state of a final dosage form |
| US20100068152A1 (en) * | 2008-09-16 | 2010-03-18 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Ex vivo modifiable particle or polymeric based final dosage form |
| JP2012503669A (ja) * | 2008-09-24 | 2012-02-09 | バーテックス ファーマシューティカルズ インコーポレイテッド | 肝炎を治療するためのｐｅｇ−インターフェロン、リバビリンおよびｖｘ−９５０を含む治療レジメ |
| WO2010053942A1 (en) * | 2008-11-05 | 2010-05-14 | Vertex Pharmaceuticals Incorporated | Methods for treating hepatitis c virus infection |
| DE102008064038A1 (de) * | 2008-12-22 | 2010-07-01 | Ksb Aktiengesellschaft | Vorrichtung und Verfahren zur Detektion von Belägen |
| WO2010093843A2 (en) | 2009-02-12 | 2010-08-19 | Vertex Pharmaceuticals Incorporated | Hcv combination therapies |
| US8512690B2 (en) | 2009-04-10 | 2013-08-20 | Novartis Ag | Derivatised proline containing peptide compounds as protease inhibitors |
| RU2012136824A (ru) | 2010-01-29 | 2014-03-10 | Вертекс Фармасьютикалз Инкорпорейтед | Способы лечения вирусной инфекции гепатита с |
| WO2011156545A1 (en) | 2010-06-09 | 2011-12-15 | Vertex Pharmaceuticals Incorporated | Viral dynamic model for hcv combination therapy |
| US20120014912A1 (en) | 2010-07-14 | 2012-01-19 | Vertex Pharmaceuticals Incorporated | Palatable pharmaceutical composition |
| CA2815416A1 (en) | 2010-10-21 | 2012-04-26 | Vertex Pharmaceuticals Incorporated | Biomarkers for hcv infected patients |
| WO2012109646A1 (en) | 2011-02-11 | 2012-08-16 | Vertex Pharmaceuticals Incorporated | Treatment of hcv in hiv infection patients |
| US8492386B2 (en) | 2011-10-21 | 2013-07-23 | Abbvie Inc. | Methods for treating HCV |
| US8466159B2 (en) | 2011-10-21 | 2013-06-18 | Abbvie Inc. | Methods for treating HCV |
| DE202012012955U1 (de) | 2011-10-21 | 2014-07-14 | Abbvie Inc. | Eine Kombination aus mindestens zwei direkt wirkenden antiviralen Wirkstoffen (DAAs) für die Verwendung zur Behandlung von HCV |
| EP2583677A3 (en) | 2011-10-21 | 2013-07-03 | Abbvie Inc. | Methods for treating HCV comprising at least two direct acting antiviral agent, ribavirin but not interferon. |
| US20130195797A1 (en) | 2012-01-31 | 2013-08-01 | Vertex Pharmaceuticals Incorporated | High potency formulations of vx-950 |
| WO2014015217A1 (en) | 2012-07-19 | 2014-01-23 | Vertex Pharmaceuticals Incorporated | Biomarkers for hcv infected patients |
| EA201892448A1 (ru) | 2016-04-28 | 2019-06-28 | Эмори Юниверсити | Алкинсодержащие нуклеотидные и нуклеозидные терапевтические композиции и связанные с ними способы применения |
Family Cites Families (43)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2170020C (en) | 1992-12-29 | 2005-08-02 | Dale J. Kempf | Retroviral protease inhibiting compounds |
| IL110752A (en) | 1993-09-13 | 2000-07-26 | Abbott Lab | Liquid semi-solid or solid pharmaceutical composition for an HIV protease inhibitor |
| US5559158A (en) | 1993-10-01 | 1996-09-24 | Abbott Laboratories | Pharmaceutical composition |
| IL111991A (en) | 1994-01-28 | 2000-07-26 | Abbott Lab | Liquid pharmaceutical composition of HIV protease inhibitors in organic solvent |
| US6037157A (en) | 1995-06-29 | 2000-03-14 | Abbott Laboratories | Method for improving pharmacokinetics |
| US6054472A (en) | 1996-04-23 | 2000-04-25 | Vertex Pharmaceuticals, Incorporated | Inhibitors of IMPDH enzyme |
| US5807876A (en) | 1996-04-23 | 1998-09-15 | Vertex Pharmaceuticals Incorporated | Inhibitors of IMPDH enzyme |
| HUP0004421A3 (en) | 1996-04-23 | 2002-10-28 | Vertex Pharmaceuticals Inc Cam | Urea derivatives and pharmaceutical compositions containing them, use thereof for the treatment of deseases mediated by impdh enzyme |
| EP0966465B1 (en) | 1997-03-14 | 2003-07-09 | Vertex Pharmaceuticals Incorporated | Inhibitors of impdh enzyme |
| US20040058982A1 (en) | 1999-02-17 | 2004-03-25 | Bioavailability System, Llc | Pharmaceutical compositions |
| AU766597B2 (en) * | 1998-05-15 | 2003-10-16 | Schering Corporation | Combination therapy comprising ribavirin and interferon alpha in antiviral treatment naive patients having chronic hepatitis C infection |
| AP1498A (en) | 1999-03-19 | 2005-11-21 | Vertex Pharma | Inhibitors of impdh enzyme. |
| ID30355A (id) | 1999-04-07 | 2001-11-22 | Pfizer Prod Inc | Penggunaan inhibitor-inhibitor cyp2d6 dalam terapi kombinasi |
| ATE255203T1 (de) * | 1999-09-06 | 2003-12-15 | Innovationen Zur Verbrennungst | Verfahren zum betreiben eines kraftfahrzeug- verbrennungsmotors |
| SV2003000617A (es) * | 2000-08-31 | 2003-01-13 | Lilly Co Eli | Inhibidores de la proteasa peptidomimetica ref. x-14912m |
| SK286630B6 (sk) | 2001-01-22 | 2009-02-05 | Merck & Co., Inc. | Nukleozidové deriváty, farmaceutický prostriedok s ich obsahom a ich použitie |
| RU2192881C1 (ru) * | 2001-03-01 | 2002-11-20 | Сибирский государственный медицинский университет | Способ лечения хронических вирусных гепатитов |
| JP5024497B2 (ja) * | 2001-03-27 | 2012-09-12 | キユーピー株式会社 | 経口用肌改善剤、肌改善方法及び肌改善用食品組成物 |
| CA2369711A1 (en) | 2002-01-30 | 2003-07-30 | Boehringer Ingelheim (Canada) Ltd. | Macrocyclic peptides active against the hepatitis c virus |
| US7091184B2 (en) | 2002-02-01 | 2006-08-15 | Boehringer Ingelheim International Gmbh | Hepatitis C inhibitor tri-peptides |
| CA2369970A1 (en) | 2002-02-01 | 2003-08-01 | Boehringer Ingelheim (Canada) Ltd. | Hepatitis c inhibitor tri-peptides |
| US6642204B2 (en) | 2002-02-01 | 2003-11-04 | Boehringer Ingelheim International Gmbh | Hepatitis C inhibitor tri-peptides |
| RU2207869C1 (ru) * | 2002-04-04 | 2003-07-10 | Акционерное Курганское общество медицинских препаратов и изделий "Синтез" | Фармацевтическая твердая композиция на основе эналаприла малеата и способ ее получения |
| WO2004000858A2 (en) * | 2002-06-21 | 2003-12-31 | Merck & Co., Inc. | Nucleoside derivatives as inhibitors of rna-dependent rna viral polymerase |
| WO2004013300A2 (en) | 2002-08-01 | 2004-02-12 | Pharmasset Inc. | Compounds with the bicyclo[4.2.1]nonane system for the treatment of flaviviridae infections |
| CA2413705A1 (en) | 2002-12-06 | 2004-06-06 | Raul Altman | Use of meloxicam in combination with an antiplatelet agent for treatment of acute coronary syndrome and related conditions |
| US7223785B2 (en) | 2003-01-22 | 2007-05-29 | Boehringer Ingelheim International Gmbh | Viral polymerase inhibitors |
| US7098231B2 (en) | 2003-01-22 | 2006-08-29 | Boehringer Ingelheim International Gmbh | Viral polymerase inhibitors |
| BRPI0407587A (pt) | 2003-02-18 | 2006-02-14 | Pfizer | inibidores do vìrus da hepatite c, composições e tratamentos que os utilizam |
| US6908901B2 (en) | 2003-03-05 | 2005-06-21 | Boehringer Ingelheim International, Gmbh | Hepatitis C inhibitor peptide analogs |
| CA2516016C (en) | 2003-03-05 | 2012-05-29 | Boehringer Ingelheim International Gmbh | Hepatitis c inhibiting compounds |
| CL2004001161A1 (es) | 2003-05-21 | 2005-04-08 | Boehringer Ingelheim Int | Compuestos describe compuestos derivados de quinolina; composicion farmaceutica; y su uso para tratar una enfermedad causada por el virus de la hepatitis c. |
| WO2005018330A1 (en) | 2003-08-18 | 2005-03-03 | Pharmasset, Inc. | Dosing regimen for flaviviridae therapy |
| EP1670415A4 (en) | 2003-09-12 | 2007-12-05 | Vertex Pharma | ANIMAL MODEL FOR STUDYING PROTEASES ACTIVITY AND HEPATIC DISORDERS |
| US6933760B2 (en) | 2003-09-19 | 2005-08-23 | Intel Corporation | Reference voltage generator for hysteresis circuit |
| ES2361997T3 (es) | 2003-09-22 | 2011-06-27 | Boehringer Ingelheim International Gmbh | Péptidos macrocíclicos activos contra el virus de la hepatitis c. |
| AR045870A1 (es) * | 2003-10-11 | 2005-11-16 | Vertex Pharma | Terapia de combinacion para la infeccion de virus de hepatitis c |
| KR20060120166A (ko) * | 2003-10-27 | 2006-11-24 | 버텍스 파마슈티칼스 인코포레이티드 | Ｈｃｖ ｎｓ３－ｎｓ４ａ 단백질분해효소 저항성 돌연변이 |
| US7132504B2 (en) | 2003-11-12 | 2006-11-07 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| ATE495185T1 (de) | 2004-01-21 | 2011-01-15 | Boehringer Ingelheim Int | Makrocyclische peptide mit wirkung gegen das hepatitis-c-virus |
| CN102911161A (zh) | 2004-02-20 | 2013-02-06 | 贝林格尔.英格海姆国际有限公司 | 病毒聚合酶抑制剂 |
| US20050187192A1 (en) | 2004-02-20 | 2005-08-25 | Kucera Pharmaceutical Company | Phospholipids for the treatment of infection by togaviruses, herpes viruses and coronaviruses |
| AR049297A1 (es) * | 2004-06-08 | 2006-07-12 | Vertex Pharma | Una composicion farmaceutica y dispersiones solidas de vx-950 (inhibidor de la proteasa de hcv ns3/4a) y proceso de obtencion |
-
2005
- 2005-10-28 TW TW103100886A patent/TW201424733A/zh unknown
- 2005-10-28 TW TW094137981A patent/TWI437990B/zh not_active IP Right Cessation
- 2005-10-28 MY MYPI20055106A patent/MY141025A/en unknown
- 2005-10-31 CN CN2012104136092A patent/CN102988365A/zh active Pending
- 2005-10-31 KR KR1020077012147A patent/KR20070085547A/ko not_active Ceased
- 2005-10-31 EP EP05815054A patent/EP1819336A2/en not_active Withdrawn
- 2005-10-31 US US11/264,746 patent/US8431615B2/en not_active Expired - Fee Related
- 2005-10-31 AU AU2005302361A patent/AU2005302361B2/en not_active Ceased
- 2005-10-31 RU RU2007119725/14A patent/RU2393863C2/ru not_active IP Right Cessation
- 2005-10-31 WO PCT/US2005/039240 patent/WO2006050250A2/en not_active Ceased
- 2005-10-31 EP EP11184992A patent/EP2500021A1/en not_active Withdrawn
- 2005-10-31 CA CA002585647A patent/CA2585647A1/en not_active Abandoned
- 2005-10-31 MX MX2007005179A patent/MX2007005179A/es unknown
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- 2005-10-31 JP JP2007539241A patent/JP2008518943A/ja active Pending
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- 2007-05-29 NO NO20072733A patent/NO20072733L/no not_active Application Discontinuation
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2013
- 2013-01-09 JP JP2013001638A patent/JP2013060474A/ja active Pending
Non-Patent Citations (1)
| Title |
|---|
| ANONYMOUS: ""Vertex Pharmaceuticals Reports Completion of dosing in the Phase Ia Clinical Study of VX-950,an Oral HCVprotease Inhibitor for the Treatment of Hepatitis C", 《URL:HTTP://WWW.VPHARM.COM/PRESSRELEASES2004/PR090704.HTML》 * |
Also Published As
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|---|---|
| MX2007005179A (es) | 2008-03-06 |
| TWI437990B (zh) | 2014-05-21 |
| KR20070085547A (ko) | 2007-08-27 |
| AU2005302361A1 (en) | 2006-05-11 |
| RU2007119725A (ru) | 2008-12-20 |
| TW201424733A (zh) | 2014-07-01 |
| NO20072733L (no) | 2007-05-29 |
| JP2013060474A (ja) | 2013-04-04 |
| KR20130063022A (ko) | 2013-06-13 |
| EP2500021A1 (en) | 2012-09-19 |
| EP1819336A2 (en) | 2007-08-22 |
| AU2005302361B2 (en) | 2011-11-17 |
| US20060105978A1 (en) | 2006-05-18 |
| JP2008518943A (ja) | 2008-06-05 |
| RU2393863C2 (ru) | 2010-07-10 |
| MY141025A (en) | 2010-02-25 |
| WO2006050250A2 (en) | 2006-05-11 |
| IL182847A0 (en) | 2007-09-20 |
| CA2585647A1 (en) | 2006-05-11 |
| TW200630093A (en) | 2006-09-01 |
| US8431615B2 (en) | 2013-04-30 |
| WO2006050250A3 (en) | 2006-07-27 |
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