SK288038B6 - Use of ribavirin and interferon alpha for manufacture pharmaceutical compositions for treating chronic hepatitis C infection - Google Patents
Use of ribavirin and interferon alpha for manufacture pharmaceutical compositions for treating chronic hepatitis C infection Download PDFInfo
- Publication number
- SK288038B6 SK288038B6 SK1710-2000A SK17102000A SK288038B6 SK 288038 B6 SK288038 B6 SK 288038B6 SK 17102000 A SK17102000 A SK 17102000A SK 288038 B6 SK288038 B6 SK 288038B6
- Authority
- SK
- Slovakia
- Prior art keywords
- weeks
- patients
- interferon alpha
- hcv
- treatment
- Prior art date
Links
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 title claims abstract description 96
- 229960000329 ribavirin Drugs 0.000 title claims abstract description 96
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 title claims abstract description 96
- 108010047761 Interferon-alpha Proteins 0.000 title claims abstract description 85
- 102000006992 Interferon-alpha Human genes 0.000 title claims abstract description 85
- 208000020403 chronic hepatitis C virus infection Diseases 0.000 title claims abstract description 20
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 18
- 238000004519 manufacturing process Methods 0.000 title abstract description 3
- 238000011282 treatment Methods 0.000 claims abstract description 130
- 230000000840 anti-viral effect Effects 0.000 claims abstract description 30
- 230000003612 virological effect Effects 0.000 claims description 77
- 102000014150 Interferons Human genes 0.000 claims description 44
- 108010050904 Interferons Proteins 0.000 claims description 44
- 229940079322 interferon Drugs 0.000 claims description 42
- 210000002966 serum Anatomy 0.000 claims description 35
- 102100040018 Interferon alpha-2 Human genes 0.000 claims description 19
- 108010079944 Interferon-alpha2b Proteins 0.000 claims description 19
- 208000015181 infectious disease Diseases 0.000 claims description 15
- 238000002360 preparation method Methods 0.000 claims description 15
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- 238000003753 real-time PCR Methods 0.000 claims description 4
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- MIXCUJKCXRNYFM-UHFFFAOYSA-M sodium;diiodomethanesulfonate;n-propyl-n-[2-(2,4,6-trichlorophenoxy)ethyl]imidazole-1-carboxamide Chemical compound [Na+].[O-]S(=O)(=O)C(I)I.C1=CN=CN1C(=O)N(CCC)CCOC1=C(Cl)C=C(Cl)C=C1Cl MIXCUJKCXRNYFM-UHFFFAOYSA-M 0.000 description 7
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- QTWJRLJHJPIABL-UHFFFAOYSA-N 2-methylphenol;3-methylphenol;4-methylphenol Chemical compound CC1=CC=C(O)C=C1.CC1=CC=CC(O)=C1.CC1=CC=CC=C1O QTWJRLJHJPIABL-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
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- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
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- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
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- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
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- 108010092851 peginterferon alfa-2b Proteins 0.000 description 1
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- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
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- 239000011780 sodium chloride Substances 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- 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]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- 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]
- A61K38/212—IFN-alpha
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Virology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Gastroenterology & Hepatology (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US7956698A | 1998-05-15 | 1998-05-15 | |
| PCT/US1999/007037 WO1999059621A1 (en) | 1998-05-15 | 1999-05-13 | Combination therapy comprising ribavirin and interferon alpha in antiviral treatment naive patients having g chronic hepatitis c infection |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SK17102000A3 SK17102000A3 (sk) | 2001-05-10 |
| SK288038B6 true SK288038B6 (en) | 2013-01-02 |
Family
ID=22151354
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK1710-2000A SK288038B6 (en) | 1998-05-15 | 1999-05-13 | Use of ribavirin and interferon alpha for manufacture pharmaceutical compositions for treating chronic hepatitis C infection |
Country Status (22)
| Country | Link |
|---|---|
| EP (3) | EP1213029A1 (enExample) |
| JP (2) | JP5281726B2 (enExample) |
| KR (1) | KR100694345B1 (enExample) |
| CN (1) | CN1230198C (enExample) |
| AR (1) | AR019551A1 (enExample) |
| AT (1) | ATE216591T1 (enExample) |
| AU (2) | AU766597B2 (enExample) |
| BR (1) | BR9910505A (enExample) |
| CA (1) | CA2331823A1 (enExample) |
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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. |
| WO2000037110A2 (en) * | 1998-12-18 | 2000-06-29 | Schering Corporation | Ribavirin-pegylated interferon alfa induction hcv combination therapy |
| BR0016162A (pt) * | 1999-12-23 | 2002-08-13 | Ribapharm | Composições e métodos para l-nucleosìdeos, lnucleotìdeos e seus análogos |
| 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 |
| AU2001261024A1 (en) | 2000-04-12 | 2001-10-30 | Delta Biotechnology Limited | Albumin fusion proteins |
| MY164523A (en) | 2000-05-23 | 2017-12-29 | Univ Degli Studi Cagliari | Methods and compositions for treating hepatitis c virus |
| CA2410579C (en) | 2000-05-26 | 2010-04-20 | Jean-Pierre Sommadossi | Methods and compositions for treating flaviviruses and pestiviruses |
| AU2002213343A1 (en) * | 2000-10-18 | 2002-04-29 | Schering Corporation | Ribavirin-pegylated interferon alfa HCV combination therapy |
| AU2002330154A1 (en) | 2001-09-28 | 2003-04-07 | Centre National De La Recherche Scientifique | Methods and compositions for treating hepatitis c virus using 4'-modified nucleosides |
| EP1536839B1 (en) * | 2001-11-09 | 2010-09-15 | Intarcia Therapeutics, Inc | Combination therapy comprising omega-interferon for treating infection with hepatitis c virus or yellow fever virus |
| EP2277910A1 (en) | 2001-12-21 | 2011-01-26 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| US7608600B2 (en) | 2002-06-28 | 2009-10-27 | Idenix Pharmaceuticals, Inc. | Modified 2′ and 3′-nucleoside prodrugs for treating Flaviviridae infections |
| CN101172993A (zh) | 2002-06-28 | 2008-05-07 | 埃迪尼克斯(开曼)有限公司 | 用于治疗黄病毒感染的2′－c－甲基－3′－o－l－缬氨酸酯核糖呋喃基胞苷 |
| CN1678326A (zh) | 2002-06-28 | 2005-10-05 | 埃迪尼克斯(开曼)有限公司 | 用于治疗黄病毒感染的2'－c－甲基－3'－o－l－缬氨酸酯核糖呋喃基胞苷 |
| RS114004A (sr) | 2002-06-28 | 2007-02-05 | Idenix (Cayman) Limited, | Modifikovani 2'i 3'-nukleozid prolekovi za lečenje flaviridae infekcija |
| JP2006519753A (ja) | 2002-11-15 | 2006-08-31 | イデニクス（ケイマン）リミテツド | ２’−分枝ヌクレオシドおよびフラビウイルス科ウイルス突然変異 |
| MXPA05006230A (es) | 2002-12-12 | 2005-09-20 | Idenix Cayman Ltd | Proceso para la produccion de nucleosidos ramificados-2'. |
| EP1594530A4 (en) | 2003-01-22 | 2006-10-11 | Human Genome Sciences Inc | HYBRID PROTEINS OF ALBUMIN |
| CA2529311A1 (en) * | 2003-03-28 | 2004-10-07 | Pharmasset, Inc. | Compounds for the treatment of flaviviridae infections |
| CA2520148A1 (en) * | 2003-04-01 | 2004-12-23 | Intermune, Inc. | Compositions and methods for treating coronavirus infection and sars |
| CN1798572A (zh) * | 2003-04-17 | 2006-07-05 | 阿雷斯贸易股份有限公司 | 用于严重急性呼吸道综合征(SARS)的干扰素β |
| PL3521297T3 (pl) | 2003-05-30 | 2022-04-04 | Gilead Pharmasset Llc | Zmodyfikowane fluorowane analogi nukleozydów |
| US7482149B2 (en) * | 2003-06-09 | 2009-01-27 | Genome Institute Of Singapore | Inhibition of SARS coronavirus infection with clinically approved antiviral drugs |
| US20070202078A1 (en) * | 2003-08-13 | 2007-08-30 | Smith Howard J | 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 |
| JP5001842B2 (ja) | 2004-09-14 | 2012-08-15 | ギリアド ファーマセット エルエルシー | ２’−フルオロ−２’−アルキル−置換又は他の置換されていてもよいリボフラノシルピリミジン類及びプリン類並びにそれらの誘導体の製造 |
| TWI437990B (zh) * | 2004-10-29 | 2014-05-21 | Vertex Pharma | Vx-950之醫藥用途 |
| EP1976516B9 (en) | 2006-01-09 | 2013-10-30 | Romark Laboratories, L.C. | Viral hepatitis treatment |
| US7964580B2 (en) | 2007-03-30 | 2011-06-21 | Pharmasset, Inc. | Nucleoside phosphoramidate prodrugs |
| CN101820887A (zh) | 2007-07-25 | 2010-09-01 | 拜奥雷克斯治疗公司 | 干扰素控释药品以及使用相同药品治疗hcv感染 |
| 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 |
| CL2009002207A1 (es) | 2008-12-23 | 2011-02-18 | Gilead Pharmasset Llc | Compuestos derivados de 3-hidroxi-5-(9h-purin-9-il)tetrahidrofuran-2-il, inhibidor de la replicacion de arn viral dependiente de arn; composicion farmaceutica; uso para el tratamiento de hepatitis c. |
| CL2009002208A1 (es) | 2008-12-23 | 2010-10-29 | Gilead Pharmasset Llc | Un compuesto (2s)-2-((((2r,3r,4r,5r)-5-(2-amino-6-etoxi-9h-purin-9-il)-4-fluoro-3-hidroxi-4-metiltetrahidrofuran-2-il)metoxi)(hidroxi)fosforilamino)propanoico, inhibidores de la replicacion de arn viral; composicion farmaceutica; y su uso en el tratamiento de infeccion por hepatitis c, virus del nilo occidental, entre otras. |
| KR20110104074A (ko) | 2008-12-23 | 2011-09-21 | 파마셋 인코포레이티드 | 퓨린 뉴클레오시드의 합성 |
| WO2010129947A2 (en) | 2009-05-08 | 2010-11-11 | Sciclone Pharmaceuticals, Inc. | Alpha thymosin peptides as vaccine enhancers |
| 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 |
| US8618076B2 (en) | 2009-05-20 | 2013-12-31 | Gilead Pharmasset Llc | Nucleoside phosphoramidates |
| MX2012011171A (es) | 2010-03-31 | 2013-02-01 | Gilead Pharmasset Llc | Fosforamidatos de nucleosido. |
| KR20140035305A (ko) * | 2010-10-05 | 2014-03-21 | 노파르티스 아게 | C형 간염 바이러스 감염의 새로운 치료법 |
| AU2011336632B2 (en) | 2010-11-30 | 2015-09-03 | Gilead Pharmasset Llc | Compounds |
| EA201391262A1 (ru) * | 2011-03-02 | 2014-03-31 | Джером Шентаг | Композиция, способ лечения и диагностики стеатоза печени как самостоятельного заболевания или в комбинации с инфекцией гепатита с |
| AP2014007575A0 (en) | 2011-09-16 | 2012-04-30 | 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 |
| SG11201506021XA (en) | 2013-01-31 | 2015-08-28 | Gilead Pharmasset Llc | Combination formulation of two antiviral compounds |
| JP2016529293A (ja) | 2013-08-27 | 2016-09-23 | ギリアド ファーマセット エルエルシー | ２つの抗ウイルス化合物の組合せ製剤 |
Family Cites Families (19)
| 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 |
| KR960705579A (ko) | 1993-11-10 | 1996-11-08 | 에릭에스. 딕커 | 개선된 인터페론 중합체 결합체(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 |
| TW426523B (en) | 1995-04-06 | 2001-03-21 | Hoffmann La Roche | Interferon solution |
| US6387365B1 (en) * | 1995-05-19 | 2002-05-14 | Schering Corporation | Combination therapy for chronic hepatitis C infection |
| US5908621A (en) * | 1995-11-02 | 1999-06-01 | Schering Corporation | Polyethylene glycol modified interferon therapy |
| JP2000507917A (ja) * | 1995-11-02 | 2000-06-27 | シェーリング コーポレイション | 持続的低用量サイトカイン注入治療 |
| TW517067B (en) | 1996-05-31 | 2003-01-11 | Hoffmann La Roche | Interferon conjugates |
| EP1011743B1 (en) | 1997-08-13 | 2011-07-27 | Boston Scientific Limited | Loading and release of water-insoluble drugs |
| EP1317929A3 (en) * | 1997-09-21 | 2003-07-02 | Schering Corporation | Combination therapy for eradicating detectable HCV-RNA in patients having chronic hepatitis c infection |
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1999
- 1999-05-13 AU AU38600/99A patent/AU766597B2/en not_active Withdrawn - After Issue
- 1999-05-13 HU HU0103423A patent/HU230432B1/hu unknown
- 1999-05-13 CZ CZ20004177A patent/CZ300540B6/cs not_active IP Right Cessation
- 1999-05-13 CA CA002331823A patent/CA2331823A1/en not_active Abandoned
- 1999-05-13 EP EP01130613A patent/EP1213029A1/en not_active Withdrawn
- 1999-05-13 CN CNB998085960A patent/CN1230198C/zh not_active Expired - Lifetime
- 1999-05-13 JP JP2000549285A patent/JP5281726B2/ja not_active Expired - Lifetime
- 1999-05-13 EP EP10181927A patent/EP2305287A1/en not_active Withdrawn
- 1999-05-13 DE DE69901321T patent/DE69901321T2/de not_active Expired - Lifetime
- 1999-05-13 PT PT99303729T patent/PT956861E/pt unknown
- 1999-05-13 BR BR9910505-5A patent/BR9910505A/pt not_active Application Discontinuation
- 1999-05-13 TW TW088107774A patent/TWI277424B/zh not_active IP Right Cessation
- 1999-05-13 IL IL13922099A patent/IL139220A0/xx unknown
- 1999-05-13 WO PCT/US1999/007037 patent/WO1999059621A1/en not_active Ceased
- 1999-05-13 EP EP99303729A patent/EP0956861B1/en not_active Expired - Lifetime
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- 1999-05-13 SK SK1710-2000A patent/SK288038B6/sk not_active IP Right Cessation
- 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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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| TC4A | Change of owner's name |
Owner name: MERCK SHARP & DOHME CORP., RAHWAY, NJ, US Effective date: 20121108 |
|
| MK4A | Patent expired |
Expiry date: 20190513 |