CZ300540B6 - Farmaceutický prostredek obsahující ribavirin v kombinaci s interferonem alfa pro lécbu pacientu s chronickou infekcí hepatitidy C genotypu 1 - Google Patents
Farmaceutický prostredek obsahující ribavirin v kombinaci s interferonem alfa pro lécbu pacientu s chronickou infekcí hepatitidy C genotypu 1 Download PDFInfo
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- CZ300540B6 CZ300540B6 CZ20004177A CZ20004177A CZ300540B6 CZ 300540 B6 CZ300540 B6 CZ 300540B6 CZ 20004177 A CZ20004177 A CZ 20004177A CZ 20004177 A CZ20004177 A CZ 20004177A CZ 300540 B6 CZ300540 B6 CZ 300540B6
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- weeks
- patients
- interferon alpha
- hcv
- rna
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Classifications
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- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Pulmonology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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| US7956698A | 1998-05-15 | 1998-05-15 |
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| SK (1) | SK288038B6 (enExample) |
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| WO (1) | WO1999059621A1 (enExample) |
Families Citing this family (47)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2686899B1 (fr) | 1992-01-31 | 1995-09-01 | Rhone Poulenc Rorer Sa | Nouveaux polypeptides biologiquement actifs, leur preparation et compositions pharmaceutiques les contenant. |
| AR021876A1 (es) * | 1998-12-18 | 2002-08-07 | Schering Corp | Terapia de combinacion para vhc por induccion de ribavirina - interferon alfa pegilado |
| CA2384326A1 (en) * | 1999-12-23 | 2001-06-28 | Johnson Lau | Compositions and methods for l-nucleosides, l-nucleotides, and their analogs |
| JP4536194B2 (ja) * | 2000-02-17 | 2010-09-01 | 大日本住友製薬株式会社 | 安定な注射用製剤 |
| AU2001266557A1 (en) | 2000-04-12 | 2001-10-23 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| MY164523A (en) | 2000-05-23 | 2017-12-29 | Univ Degli Studi Cagliari | Methods and compositions for treating hepatitis c virus |
| CZ301182B6 (cs) | 2000-05-26 | 2009-12-02 | Idenix (Cayman) Limited | Použití nukleosidových derivátu pro výrobu farmaceutických prostredku pro lécení infekcí vyvolaných flaviviry a pestiviry |
| HK1052878A1 (zh) * | 2000-10-18 | 2003-10-03 | Schering Corporation | 利巴传林-聚乙二醇化干扰素α：丙型肝炎病毒的联合治疗 |
| EP1435974A4 (en) | 2001-09-28 | 2006-09-06 | Idenix Cayman Ltd | METHODS AND COMPOSITIONS FOR THE TREATMENT OF HEPATITIS C VIRUS USING 4 'MODIFIED NUCLEOSIDES |
| AU2002365436B8 (en) * | 2001-11-09 | 2008-04-03 | Intarcia Therapeutics, Inc. | Method for treating diseases with omega interferon |
| JP5424521B2 (ja) | 2001-12-21 | 2014-02-26 | ヒューマン ジノーム サイエンシーズ， インコーポレイテッド | アルブミン融合タンパク質 |
| US7608600B2 (en) | 2002-06-28 | 2009-10-27 | Idenix Pharmaceuticals, Inc. | Modified 2′ and 3′-nucleoside prodrugs for treating Flaviviridae infections |
| NZ537662A (en) | 2002-06-28 | 2007-10-26 | Idenix Cayman Ltd | 2'-C-methyl-3'-O-L-valine ester ribofuranosyl cytidine for treatment of flaviviridae infections |
| MXPA04012802A (es) | 2002-06-28 | 2005-04-19 | Idenix Cayman Ltd | Ester 2'-c-metil-3'-o-l-valina de ribofuranosil-citidina para el tratamiento de infecciones por flaviviridae. |
| CN104193791A (zh) | 2002-06-28 | 2014-12-10 | 埃迪尼克斯医药公司 | 用于治疗黄病毒感染的修饰的2’和3’-核苷前药 |
| WO2004046331A2 (en) | 2002-11-15 | 2004-06-03 | Idenix (Cayman) Limited | 2’-branched nucleosides and flaviviridae mutation |
| US7598373B2 (en) | 2002-12-12 | 2009-10-06 | Idenix Pharmaceuticals, Inc. | Process for the production of 2-C-methyl-D-ribonolactone |
| CA2513213C (en) | 2003-01-22 | 2013-07-30 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| CN1980678A (zh) * | 2003-03-28 | 2007-06-13 | 法莫赛特股份有限公司 | 治疗黄病毒感染的化合物 |
| CA2520148A1 (en) * | 2003-04-01 | 2004-12-23 | Intermune, Inc. | Compositions and methods for treating coronavirus infection and sars |
| MXPA05011170A (es) * | 2003-04-17 | 2005-12-14 | Ares Trading Sa | Interferon beta en el sindrome respiratorio agudo severo. |
| EP2345659A1 (en) | 2003-05-30 | 2011-07-20 | Pharmasset, Inc. | Modified fluorinated nucleoside analogues |
| WO2004108151A1 (en) * | 2003-06-09 | 2004-12-16 | Genome Institute Of Singapore | Inhibition of sars coronavirus infection with clinically approved antiviral drugs |
| AU2004264255A1 (en) * | 2003-08-13 | 2005-02-24 | Howard J. Smith & Associates Pty Ltd | Method of treating viral infections |
| AR045870A1 (es) * | 2003-10-11 | 2005-11-16 | Vertex Pharma | Terapia de combinacion para la infeccion de virus de hepatitis c |
| CN101023094B (zh) | 2004-07-21 | 2011-05-18 | 法莫赛特股份有限公司 | 烷基取代的2-脱氧-2-氟代-d-呋喃核糖基嘧啶和嘌呤及其衍生物的制备 |
| ES2769377T3 (es) | 2004-09-14 | 2020-06-25 | Gilead Pharmasset Llc | Intermedios de D-ribonolactona con sustitución de 2-fluoro-2-alquilo |
| MY141025A (en) * | 2004-10-29 | 2010-02-25 | Vertex Pharma | Dose forms |
| ES2422556T3 (es) * | 2006-01-09 | 2013-09-12 | Romark Lab Lc | Tratamiento de hepatitis vírica |
| US7964580B2 (en) | 2007-03-30 | 2011-06-21 | Pharmasset, Inc. | Nucleoside phosphoramidate prodrugs |
| KR20100056479A (ko) | 2007-07-25 | 2010-05-27 | 바이오렉스 쎄라퓨틱스, 인코포레이티드 | 제어 방출 인터페론 약물 제품 및 이를 사용한 ｈｃｖ 감염의 치료 |
| TW200946541A (en) | 2008-03-27 | 2009-11-16 | Idenix Pharmaceuticals Inc | Solid forms of an anti-HIV phosphoindole compound |
| RU2369403C1 (ru) * | 2008-05-22 | 2009-10-10 | Сергей Юрьевич Родионов | Способ лечения хронических вирусных гепатитов |
| BRPI0923815A2 (pt) | 2008-12-23 | 2015-07-14 | Pharmasset Inc | Síntese de nucleosídeos de purina |
| CN102695513A (zh) | 2008-12-23 | 2012-09-26 | 吉利德制药有限责任公司 | 核苷氨基磷酸酯 |
| AU2009329917B2 (en) | 2008-12-23 | 2016-03-31 | Gilead Pharmasset Llc | Nucleoside analogs |
| JP2012526149A (ja) | 2009-05-08 | 2012-10-25 | サイクローン・ファーマシューティカルズ・インコーポレイテッド | ワクチン増強剤としてのαチモシンペプチド |
| US8618076B2 (en) | 2009-05-20 | 2013-12-31 | Gilead Pharmasset Llc | Nucleoside phosphoramidates |
| TWI583692B (zh) | 2009-05-20 | 2017-05-21 | 基利法瑪席特有限責任公司 | 核苷磷醯胺 |
| SMT201700412T1 (it) | 2010-03-31 | 2017-11-15 | Gilead Pharmasset Llc | Procedimento per la cristallizzazione di (s)-isopropil 2-(((s)-(perfluorofenossi)(fenossi)fosforil)ammino)propanoato |
| JP2013542206A (ja) * | 2010-10-05 | 2013-11-21 | ノバルティス アーゲー | Ｃ型肝炎ウイルス感染症の新規治療 |
| PT3042910T (pt) | 2010-11-30 | 2019-04-16 | Gilead Pharmasset Llc | 2'-espiro-nucleósidos para utilização na terapia da hepatite c |
| KR20140147657A (ko) * | 2011-03-02 | 2014-12-30 | 제롬 쉔타그 | 단독으로 또는 c형 간염 바이러스 감염과 결합되는 간 지방증의 치료를 위한 조성물, 방법 및 진단 |
| EP2709613B2 (en) | 2011-09-16 | 2020-08-12 | Gilead Pharmasset LLC | Methods for treating hcv |
| US8889159B2 (en) | 2011-11-29 | 2014-11-18 | Gilead Pharmasset Llc | Compositions and methods for treating hepatitis C virus |
| PL2950786T3 (pl) | 2013-01-31 | 2020-05-18 | Gilead Pharmasset Llc | Formulacja skojarzona dwóch związków przeciwwirusowych |
| PL3038601T3 (pl) | 2013-08-27 | 2020-08-24 | Gilead Pharmasset Llc | Formulacja złożona dwóch związków przeciwwirusowych |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0707855A2 (en) * | 1995-05-19 | 1996-04-24 | Schering Corporation | Combination therapy for chronic hepatitis C infection |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4211771A (en) | 1971-06-01 | 1980-07-08 | Robins Ronald K | Treatment of human viral diseases with 1-B-D-ribofuranosyl-1,2,4-triazole-3-carboxamide |
| US4530901A (en) | 1980-01-08 | 1985-07-23 | Biogen N.V. | Recombinant DNA molecules and their use in producing human interferon-like polypeptides |
| US6936694B1 (en) | 1982-05-06 | 2005-08-30 | Intermune, Inc. | Manufacture and expression of large structural genes |
| US4492537A (en) | 1982-12-10 | 1985-01-08 | Awerkamp John B | Fluid-operated oil or water well pump |
| US4917888A (en) | 1985-06-26 | 1990-04-17 | Cetus Corporation | Solubilization of immunotoxins for pharmaceutical compositions using polymer conjugation |
| US4766106A (en) | 1985-06-26 | 1988-08-23 | Cetus Corporation | Solubilization of proteins for pharmaceutical compositions using polymer conjugation |
| JP2514950B2 (ja) | 1986-03-10 | 1996-07-10 | エフ・ホフマン―ラ ロシユ アーゲー | 化学修飾蛋白質，その製造法および中間体 |
| US5595732A (en) | 1991-03-25 | 1997-01-21 | Hoffmann-La Roche Inc. | Polyethylene-protein conjugates |
| US5382657A (en) | 1992-08-26 | 1995-01-17 | Hoffmann-La Roche Inc. | Peg-interferon conjugates |
| AU691225B2 (en) * | 1993-11-10 | 1998-05-14 | Schering Corporation | Improved interferon polymer conjugates |
| US5766582A (en) | 1994-10-11 | 1998-06-16 | Schering Corporation | Stable, aqueous alfa interferon solution formulations |
| US5824784A (en) * | 1994-10-12 | 1998-10-20 | Amgen Inc. | N-terminally chemically modified protein compositions and methods |
| JP2758154B2 (ja) | 1995-04-06 | 1998-05-28 | エフ・ホフマン−ラ ロシユ アーゲー | インターフェロンを含む液体製剤 |
| US5908621A (en) * | 1995-11-02 | 1999-06-01 | Schering Corporation | Polyethylene glycol modified interferon therapy |
| CA2329474C (en) * | 1995-11-02 | 2002-02-26 | Schering Corporation | Continuous low-dose cytokine infusion therapy |
| TW517067B (en) | 1996-05-31 | 2003-01-11 | Hoffmann La Roche | Interferon conjugates |
| JP2001514936A (ja) | 1997-08-13 | 2001-09-18 | ボストン サイエンティフィック コーポレイション | 水不溶性薬剤の装填および放出 |
| ES2186660T3 (es) * | 1997-09-21 | 2003-05-16 | Schering Corp | Terapia de combinacion para erradicar hcv-rna detectable en pacientes con infeccion por hepatitis c cronica. |
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1999
- 1999-05-13 CN CNB998085960A patent/CN1230198C/zh not_active Expired - Lifetime
- 1999-05-13 BR BR9910505-5A patent/BR9910505A/pt not_active Application Discontinuation
- 1999-05-13 SK SK1710-2000A patent/SK288038B6/sk not_active IP Right Cessation
- 1999-05-13 PT PT99303729T patent/PT956861E/pt unknown
- 1999-05-13 WO PCT/US1999/007037 patent/WO1999059621A1/en not_active Ceased
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- 1999-05-13 EP EP01130613A patent/EP1213029A1/en not_active Withdrawn
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- 1999-05-13 AT AT99303729T patent/ATE216591T1/de active
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- 1999-05-13 KR KR1020007012784A patent/KR100694345B1/ko not_active Expired - Lifetime
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0707855A2 (en) * | 1995-05-19 | 1996-04-24 | Schering Corporation | Combination therapy for chronic hepatitis C infection |
Non-Patent Citations (9)
| Title |
|---|
| Dig. Dis. Sci 41(12 Suppl) 131S-134S (1996) (abstrakt) * |
| Dig. Dis. Sci. 1996 DEc 41 (12 Suppl) 131S-134S (abstrakt) * |
| Hepatology 26 (2) s. 500- 504 (1997) * |
| Hournal of Hepatology 23 (Suppl. 2) 32-36 (1995) (abstrakt) * |
| Journal of Hepatology 23 (SUP2) s. 17-21 (1995) (abstrakt) * |
| Journal of Hepatology 23 (SUP2) s. 3-7 (1995) (abstrakt) * |
| Pathologie Biologie43 (8 s. 716-724 (1995) (abstrakt) * |
| Scnadinavian Journal of Gastroenterology 32 (Suppl. 223) s. 46-49 (1997) (abstrakt) * |
| The Lacet 351 10.1.1998s. 83-87 * |
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Effective date: 20190513 |