DE60105424T2 - Methoden zur behandlung von delta hepatitis virus infektionen mit beta-l-2' deoxy-nucleosiden - Google Patents
Methoden zur behandlung von delta hepatitis virus infektionen mit beta-l-2' deoxy-nucleosiden Download PDFInfo
- Publication number
- DE60105424T2 DE60105424T2 DE60105424T DE60105424T DE60105424T2 DE 60105424 T2 DE60105424 T2 DE 60105424T2 DE 60105424 T DE60105424 T DE 60105424T DE 60105424 T DE60105424 T DE 60105424T DE 60105424 T2 DE60105424 T2 DE 60105424T2
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- Prior art keywords
- deoxy
- alkyl
- pharmaceutically acceptable
- triphosphate
- mono
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Classifications
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
- A61K31/7072—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
- A61K31/708—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid having oxo groups directly attached to the purine ring system, e.g. guanosine, guanylic acid
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
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- 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
- A61P31/20—Antivirals for DNA viruses
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
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- General Health & Medical Sciences (AREA)
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- Animal Behavior & Ethology (AREA)
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- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Biotechnology (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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| US20753800P | 2000-05-26 | 2000-05-26 | |
| US207538P | 2000-05-26 | ||
| PCT/US2001/017301 WO2001091737A2 (en) | 2000-05-26 | 2001-05-29 | Methods for treating hepatitis delta virus infection with beta-l-2' deoxy-nucleosides |
Publications (2)
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| DE60105424D1 DE60105424D1 (de) | 2004-10-14 |
| DE60105424T2 true DE60105424T2 (de) | 2005-09-22 |
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| DE60105424T Expired - Fee Related DE60105424T2 (de) | 2000-05-26 | 2001-05-29 | Methoden zur behandlung von delta hepatitis virus infektionen mit beta-l-2' deoxy-nucleosiden |
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| EP (1) | EP1292313B1 (enExample) |
| JP (1) | JP2004513070A (enExample) |
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| AU (3) | AU6348401A (enExample) |
| BR (1) | BR0111195A (enExample) |
| CA (1) | CA2410488C (enExample) |
| DE (1) | DE60105424T2 (enExample) |
| EA (1) | EA005890B1 (enExample) |
| ES (1) | ES2227203T3 (enExample) |
| IL (1) | IL153078A0 (enExample) |
| MX (1) | MXPA02011641A (enExample) |
| TR (1) | TR200402565T4 (enExample) |
| WO (1) | WO2001091737A2 (enExample) |
| ZA (2) | ZA200210100B (enExample) |
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| ZA986614B (en) * | 1997-07-25 | 1999-01-27 | Gilead Sciences | Nucleotide analog composition |
| US6444652B1 (en) * | 1998-08-10 | 2002-09-03 | Novirio Pharmaceuticals Limited | β-L-2'-deoxy-nucleosides for the treatment of hepatitis B |
| KR100691737B1 (ko) * | 1998-08-10 | 2007-03-12 | 이데닉스(케이만)리미티드 | Ｂ형 간염의 치료용 β-Ｌ-2'-데옥시-뉴클레오시드 |
| AU2001245575A1 (en) * | 2000-03-09 | 2001-09-17 | Videoshare, Inc. | Sharing a streaming video |
| ATE414520T1 (de) | 2000-04-13 | 2008-12-15 | Pharmasset Inc | 3 oder 2 hydroxymethyl substituierte nucleoside derivate und ihre verwendung zur behandlung von virusinfektionen |
| MY164523A (en) * | 2000-05-23 | 2017-12-29 | Univ Degli Studi Cagliari | Methods and compositions for treating hepatitis c virus |
| US6787526B1 (en) * | 2000-05-26 | 2004-09-07 | Idenix Pharmaceuticals, Inc. | Methods of treating hepatitis delta virus infection with β-L-2′-deoxy-nucleosides |
| MXPA02011691A (es) | 2000-05-26 | 2004-05-17 | Idenix Cayman Ltd | Metodos y composiciones para el tratamiento de flavivirus y pestivirus. |
| KR20040028657A (ko) * | 2000-10-18 | 2004-04-03 | 파마셋, 리미티드 | 바이러스 감염 및 비정상적인 세포 증식의 치료를 위한변형된 뉴클레오시드 |
| KR20050048544A (ko) * | 2002-06-28 | 2005-05-24 | 이데닉스 (케이만) 리미티드 | 플라비비리다에 감염 치료용의 변형된 2' 및3'-뉴클레오사이드 프로드럭 |
| 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 |
| 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. |
| US7608600B2 (en) | 2002-06-28 | 2009-10-27 | Idenix Pharmaceuticals, Inc. | Modified 2′ and 3′-nucleoside prodrugs for treating Flaviviridae infections |
| JP5087211B2 (ja) * | 2002-06-28 | 2012-12-05 | イデニクス（ケイマン）リミテツド | フラビウィルス感染治療のための２′および３′−ヌクレオシドプロドラッグ |
| KR20080053419A (ko) * | 2002-09-13 | 2008-06-12 | 이데닉스 (케이만) 리미티드 | 내성 ＨＢＶ 균주 치료용 β-Ｌ-2'-데옥시뉴클레오시드 및병용 요법 |
| WO2004041834A2 (en) * | 2002-10-31 | 2004-05-21 | Metabasis Therapeutics, Inc. | Novel cyclic phosphate diesters of 1,3-propane-1-aryl diols and their use in preparing prodrugs |
| ES2624353T3 (es) * | 2002-11-15 | 2017-07-13 | Idenix Pharmaceuticals Llc | 2'-Metil nucleósidos en combinación con interferón y mutación de Flaviviridae |
| CN1303089C (zh) * | 2002-11-19 | 2007-03-07 | 天津药物研究院 | 阿德福韦酯结晶形态及其制备方法 |
| CN1330373C (zh) * | 2002-12-02 | 2007-08-08 | 美德（江西）生物科技有限公司 | 含alfa－干扰素，阿地福韦和二脱氧氟硫代胞嘧啶的药物组合物 |
| RU2005121904A (ru) * | 2002-12-12 | 2006-01-20 | Айденикс (Кайман) Лимитед (Ky) | Способ получения 2`-разветвленных нуклеозидов |
| EP2345658A1 (en) | 2003-05-30 | 2011-07-20 | Pharmasset, Inc. | Modified fluorinated nucleoside analogues |
| 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 |
| KR20080033274A (ko) | 2005-06-17 | 2008-04-16 | 노파르티스 아게 | Ｈｃｖ에서 상글리페린의 용도 |
| WO2007075876A2 (en) * | 2005-12-23 | 2007-07-05 | Idenix Pharmaceuticals, Inc. | Process for preparing a synthetic intermediate for preparation of branched nucleosides |
| GB0623493D0 (en) | 2006-11-24 | 2007-01-03 | Univ Cardiff | Chemical compounds |
| US7964580B2 (en) | 2007-03-30 | 2011-06-21 | Pharmasset, Inc. | Nucleoside phosphoramidate prodrugs |
| CA2748057C (en) | 2008-12-23 | 2018-07-03 | Pharmasset, Inc. | Nucleoside phosphoramidates |
| EA019295B1 (ru) | 2008-12-23 | 2014-02-28 | Джилид Фармассет, Ллс. | Соединения пуриновых нуклеозидов и способ их получения |
| BRPI0922508A8 (pt) | 2008-12-23 | 2016-01-19 | Pharmasset Inc | Análogos de nucleosídeo |
| 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 |
| US9676797B2 (en) | 2015-09-02 | 2017-06-13 | Abbvie Inc. | Anti-viral compounds |
| TWI498117B (zh) | 2010-03-31 | 2015-09-01 | Gilead Pharmasset Llc | 核苷氨基磷酸酯 |
| SI2595980T1 (sl) | 2010-07-22 | 2014-11-28 | Gilead Sciences, Inc. | Postopki in sestavki za zdravljenje paramyxoviridae virusnih infekcij |
| PE20171640A1 (es) | 2010-09-22 | 2017-11-09 | Alios Biopharma Inc | Analogos de nucleotidos sustituidos |
| US8841275B2 (en) | 2010-11-30 | 2014-09-23 | Gilead Pharmasset Llc | 2′-spiro-nucleosides and derivatives thereof useful for treating hepatitis C virus and dengue virus infections |
| RU2606845C2 (ru) * | 2010-12-10 | 2017-01-10 | СИГМАФАРМ ЛЭБОРЭТОРИЗ, ЭлЭлСи | Высокостабильные композиции перорально активных аналогов нуклеотидов или перорально активных пролекарств аналогов нуклеотидов |
| DE202012013074U1 (de) | 2011-09-16 | 2014-10-29 | Gilead Pharmasset Lcc | Zusammensetzungen zur Behandlung von HCV |
| US8889159B2 (en) | 2011-11-29 | 2014-11-18 | Gilead Pharmasset Llc | Compositions and methods for treating hepatitis C virus |
| CA2860234A1 (en) | 2011-12-22 | 2013-06-27 | Alios Biopharma, Inc. | Substituted phosphorothioate nucleotide analogs |
| CN104321333A (zh) | 2012-03-21 | 2015-01-28 | 沃泰克斯药物股份有限公司 | 硫代氨基磷酸酯核苷酸前药的固体形式 |
| HK1203356A1 (en) | 2012-03-22 | 2015-10-30 | 艾丽奥斯生物制药有限公司 | Pharmaceutical combinations comprising a thionucleotide analog |
| EP2950786B1 (en) | 2013-01-31 | 2019-11-27 | Gilead Pharmasset LLC | Combination formulation of two antiviral compounds |
| CA2919905C (en) * | 2013-07-31 | 2021-08-10 | Merck Patent Gmbh | Oxoquinazolinyl-butanamide derivatives |
| 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 |
| WO2015123352A1 (en) | 2014-02-13 | 2015-08-20 | Ligand Pharmaceuticals, Inc. | Prodrug compounds and their uses |
| CN106687118A (zh) | 2014-07-02 | 2017-05-17 | 配体药物公司 | 前药化合物及其用途 |
| DK3310362T3 (da) | 2015-06-17 | 2019-10-07 | Univ Columbia | Deoxynukleosidterapi mod sygdomme forårsaget af ubalancerede nukleotid-pools, herunder mitokondrielt dna-depletionssyndromer |
| CN108264524A (zh) * | 2016-12-31 | 2018-07-10 | 正大天晴药业集团股份有限公司 | 恩曲他滨膦酸酯化合物 |
| RU2644156C1 (ru) | 2017-02-28 | 2018-02-08 | Александр Васильевич Иващенко | Пролекарство ингибитора NS5B HCV полимеразы, способ его получения и применения |
| KR20190141747A (ko) | 2017-05-01 | 2019-12-24 | 길리애드 사이언시즈, 인코포레이티드 | (S)-2-에틸부틸 2-(((S)-(((2R,3S,4R,5R)-5-(4-아미노피롤로[2,1-f] [1,2,4]트리아진-7-일)-5-시아노-3,4-디히드록시테트라히드로푸란-2-일)메톡시)(페녹시) 포스포릴)아미노)프로파노에이트의 결정질 형태 |
| RU2662160C9 (ru) * | 2017-07-03 | 2018-10-22 | Александрович Иващенко Андрей | Комбинированный лекарственный препарат для терапии вирусных инфекций |
| CN111093627B (zh) | 2017-07-11 | 2024-03-08 | 吉利德科学公司 | 用于治疗病毒感染的包含rna聚合酶抑制剂和环糊精的组合物 |
| RU2662161C1 (ru) * | 2017-08-11 | 2018-07-24 | Васильевич Иващенко Александр | Ингибитор входа вируса гепатита и фармацевтическая композиция для лечения гепатита |
| RU2020126177A (ru) | 2018-01-09 | 2022-02-10 | Лиганд Фармасьютикалз, Инк. | Ацетальные соединения и их терапевтическое применение |
| CN114641299A (zh) | 2020-01-27 | 2022-06-17 | 吉利德科学公司 | 用于治疗SARS CoV-2感染的方法 |
| CN118994170A (zh) | 2020-03-12 | 2024-11-22 | 吉利德科学公司 | 制备1'-氰基核苷的方法 |
| WO2021207049A1 (en) | 2020-04-06 | 2021-10-14 | Gilead Sciences, Inc. | Inhalation formulations of 1'-cyano substituted carbanucleoside analogs |
| EP4157272B1 (en) | 2020-05-29 | 2025-07-02 | Gilead Sciences, Inc. | Remdesivir for the treatment of viral infections |
| US11939347B2 (en) | 2020-06-24 | 2024-03-26 | Gilead Sciences, Inc. | 1′-cyano nucleoside analogs and uses thereof |
| CA3188373A1 (en) | 2020-08-24 | 2022-03-03 | Scott E. Lazerwith | Phospholipid compounds and uses thereof |
| SI4204421T1 (sl) | 2020-08-27 | 2024-07-31 | Gilead Sciences, Inc., | Spojine in postopki za zdravljenje virusnih okužb |
| TW202344257A (zh) | 2020-10-16 | 2023-11-16 | 美商基利科學股份有限公司 | 磷脂化合物及其用途 |
| EP4320128A1 (en) | 2022-03-02 | 2024-02-14 | Gilead Sciences, Inc. | Compounds and methods for treatment of viral infections |
| US12357577B1 (en) | 2024-02-02 | 2025-07-15 | Gilead Sciences, Inc. | Pharmaceutical formulations and uses thereof |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE8802687D0 (sv) | 1988-07-20 | 1988-07-20 | Astra Ab | Nucleoside derivatives |
| JP3693357B2 (ja) * | 1993-04-09 | 2005-09-07 | 峯郎 実吉 | 逆転写酵素阻害剤 |
| WO1996011204A1 (de) | 1994-10-07 | 1996-04-18 | Max-Delbrück-Centrum für Molekulare Medizin | NEUE β-L-NUCLEOSIDE UND IHRE VERWENDUNG |
| KR100691737B1 (ko) * | 1998-08-10 | 2007-03-12 | 이데닉스(케이만)리미티드 | Ｂ형 간염의 치료용 β-Ｌ-2'-데옥시-뉴클레오시드 |
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2001
- 2001-05-29 BR BR0111195-7A patent/BR0111195A/pt not_active Application Discontinuation
- 2001-05-29 EP EP01937785A patent/EP1292313B1/en not_active Expired - Lifetime
- 2001-05-29 DE DE60105424T patent/DE60105424T2/de not_active Expired - Fee Related
- 2001-05-29 ES ES01937785T patent/ES2227203T3/es not_active Expired - Lifetime
- 2001-05-29 WO PCT/US2001/017301 patent/WO2001091737A2/en not_active Ceased
- 2001-05-29 AU AU6348401A patent/AU6348401A/xx active Pending
- 2001-05-29 JP JP2001587753A patent/JP2004513070A/ja active Pending
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- 2001-05-29 MX MXPA02011641A patent/MXPA02011641A/es active IP Right Grant
- 2001-05-29 AT AT01937785T patent/ATE275406T1/de not_active IP Right Cessation
- 2001-05-29 US US09/867,110 patent/US6596700B2/en not_active Expired - Fee Related
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- 2001-05-29 AU AU2001263484A patent/AU2001263484B2/en not_active Ceased
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| DE60105424D1 (de) | 2004-10-14 |
| EA200201263A1 (ru) | 2003-06-26 |
| EP1292313A2 (en) | 2003-03-19 |
| AU2001263484B2 (en) | 2006-12-14 |
| HK1050999A1 (en) | 2003-07-18 |
| IL153078A0 (en) | 2003-06-24 |
| KR20030031487A (ko) | 2003-04-21 |
| CN1444483A (zh) | 2003-09-24 |
| AU6348401A (en) | 2001-12-11 |
| CA2410488C (en) | 2009-10-27 |
| CA2410488A1 (en) | 2001-12-06 |
| US6596700B2 (en) | 2003-07-22 |
| ZA200210100B (en) | 2004-06-22 |
| ZA200404304B (en) | 2005-03-30 |
| BR0111195A (pt) | 2004-07-20 |
| JP2004513070A (ja) | 2004-04-30 |
| MXPA02011641A (es) | 2004-07-30 |
| WO2001091737A2 (en) | 2001-12-06 |
| EP1292313B1 (en) | 2004-09-08 |
| ATE275406T1 (de) | 2004-09-15 |
| WO2001091737A3 (en) | 2002-05-30 |
| TR200402565T4 (tr) | 2004-12-21 |
| KR100854398B1 (ko) | 2008-08-26 |
| CN100490818C (zh) | 2009-05-27 |
| EA005890B1 (ru) | 2005-06-30 |
| AU2006252214A1 (en) | 2007-01-18 |
| US20020035085A1 (en) | 2002-03-21 |
| ES2227203T3 (es) | 2005-04-01 |
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