AU740916B2 - Induction of viral mutation by incorporation of miscoding ribonucleoside analogs into viral RNA - Google Patents
Induction of viral mutation by incorporation of miscoding ribonucleoside analogs into viral RNA Download PDFInfo
- Publication number
- AU740916B2 AU740916B2 AU50959/98A AU5095998A AU740916B2 AU 740916 B2 AU740916 B2 AU 740916B2 AU 50959/98 A AU50959/98 A AU 50959/98A AU 5095998 A AU5095998 A AU 5095998A AU 740916 B2 AU740916 B2 AU 740916B2
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- Australia
- Prior art keywords
- analog
- ribonucleoside
- virus
- rna
- cytidine
- Prior art date
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Landscapes
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Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US2940496P | 1996-10-28 | 1996-10-28 | |
| US60/029404 | 1996-10-28 | ||
| US4053597P | 1997-02-27 | 1997-02-27 | |
| US60/040535 | 1997-02-27 | ||
| PCT/US1997/019670 WO1998018324A1 (en) | 1996-10-28 | 1997-10-27 | Induction of viral mutation by incorporation of miscoding ribonucleoside analogs into viral rna |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU5095998A AU5095998A (en) | 1998-05-22 |
| AU740916B2 true AU740916B2 (en) | 2001-11-15 |
Family
ID=26704916
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU50959/98A Ceased AU740916B2 (en) | 1996-10-28 | 1997-10-27 | Induction of viral mutation by incorporation of miscoding ribonucleoside analogs into viral RNA |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US6063628A (https=) |
| EP (1) | EP0948256A4 (https=) |
| JP (1) | JP2001525797A (https=) |
| AU (1) | AU740916B2 (https=) |
| CA (1) | CA2269213A1 (https=) |
| NZ (2) | NZ507848A (https=) |
| WO (1) | WO1998018324A1 (https=) |
Families Citing this family (51)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6887707B2 (en) * | 1996-10-28 | 2005-05-03 | University Of Washington | Induction of viral mutation by incorporation of miscoding ribonucleoside analogs into viral RNA |
| NZ507848A (en) * | 1996-10-28 | 2005-01-28 | Univ Washington | Method of increasing the mutation rate of a virus in a non-human by administering an RNA nucleoside analogue to a virally infected cell |
| US6423695B1 (en) * | 1998-01-13 | 2002-07-23 | Ribapharm, Inc. | Cytokine related treatments of disease |
| EP1165127B1 (en) * | 1999-03-26 | 2008-12-31 | Walter Reed Army Institute of Research | Multivalent dengue virus vaccine |
| AU8038400A (en) * | 1999-09-09 | 2001-04-10 | Zymetx, Inc. | Method of treatment of influenza |
| WO2001030989A2 (en) * | 1999-10-27 | 2001-05-03 | Cytos Biotechnology Ag | Method for creating divergent populations of nucleic acid molecules and proteins |
| US7638496B2 (en) | 2000-02-15 | 2009-12-29 | Valeant Pharmaceuticals North America | Nucleoside analogs with carboxamidine modified monocyclic base |
| KR20030005197A (ko) | 2000-02-18 | 2003-01-17 | 샤이어 바이오켐 인코포레이티드 | 뉴클레오시드유도체를 이용한 플라비바이러스 감염의 치료또는 예방 방법 |
| MY164523A (en) * | 2000-05-23 | 2017-12-29 | Univ Degli Studi Cagliari | Methods and compositions for treating hepatitis c virus |
| EP1736478B1 (en) * | 2000-05-26 | 2015-07-22 | IDENIX Pharmaceuticals, Inc. | Methods and compositions for treating flaviviruses and pestiviruses |
| WO2002032920A2 (en) | 2000-10-18 | 2002-04-25 | Pharmasset Limited | Modified nucleosides for treatment of viral infections and abnormal cellular proliferation |
| SK286630B6 (sk) * | 2001-01-22 | 2009-02-05 | Merck & Co., Inc. | Nukleozidové deriváty, farmaceutický prostriedok s ich obsahom a ich použitie |
| US8481712B2 (en) | 2001-01-22 | 2013-07-09 | Merck Sharp & Dohme Corp. | Nucleoside derivatives as inhibitors of RNA-dependent RNA viral polymerase |
| WO2002069903A2 (en) * | 2001-03-06 | 2002-09-12 | Biocryst Pharmaceuticals, Inc. | Nucleosides, preparation thereof and use as inhibitors of rna viral polymerases |
| WO2003018030A1 (en) * | 2001-08-24 | 2003-03-06 | Koronis Pharmaceuticals, Inc. | Mutagenic nucleoside analogs for the treatment of viral disease |
| US20040006002A1 (en) * | 2001-09-28 | 2004-01-08 | Jean-Pierre Sommadossi | Methods and compositions for treating flaviviruses and pestiviruses using 4'-modified nucleoside |
| US7049303B2 (en) * | 2001-11-07 | 2006-05-23 | Medical Research Council | Inhibition of viruses |
| US20040138170A1 (en) * | 2002-03-06 | 2004-07-15 | Montgomery John A. | Nucleosides, preparation thereof and use as inhibitors of rna viral polymerases |
| 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 |
| US7608600B2 (en) | 2002-06-28 | 2009-10-27 | Idenix Pharmaceuticals, Inc. | Modified 2′ and 3′-nucleoside prodrugs for treating Flaviviridae infections |
| 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 |
| AU2003261231A1 (en) | 2002-07-26 | 2004-02-16 | Chiron Corporation | Modified small interfering rna molecules and methods of use |
| LT1576138T (lt) | 2002-11-15 | 2017-06-26 | Idenix Pharmaceuticals Llc | 2`-šakoti nukleozidai derinyje su interferonu ir flaviviridae mutacija |
| AU2003300901A1 (en) * | 2002-12-12 | 2004-06-30 | Idenix (Cayman) Limited | Process for the production of 2'-branched nucleosides |
| WO2004084796A2 (en) * | 2003-03-28 | 2004-10-07 | Pharmasset Ltd. | Compounds for the treatment of flaviviridae infections |
| WO2005018330A1 (en) * | 2003-08-18 | 2005-03-03 | Pharmasset, Inc. | Dosing regimen for flaviviridae therapy |
| WO2005019424A2 (en) * | 2003-08-18 | 2005-03-03 | Wright State University | Retroviral vector and cell-based assay for measuring the mutation rate of retroviruses employing same |
| CA2600886A1 (en) | 2005-03-08 | 2006-09-14 | Biota Scientific Management Pty Ltd. | Bicyclic nucleosides and nucleotides as therapeutic agents |
| JP4516863B2 (ja) * | 2005-03-11 | 2010-08-04 | 株式会社ケンウッド | 音声合成装置、音声合成方法及びプログラム |
| EP1869012A1 (en) * | 2005-04-05 | 2007-12-26 | Boehringer Ingelheim International Gmbh | Substituted benzylimidazoles useful for the treatment of inflammatory diseases |
| ES2422290T3 (es) * | 2005-12-23 | 2013-09-10 | Idenix Pharmaceuticals Inc | Procedimiento para preparar un producto intermedio sintético para la preparación de nucleósidos ramificados |
| EP1859690A1 (en) | 2006-05-26 | 2007-11-28 | Health Concern B.V. | Premix for cholesterol lowering food products |
| WO2009043096A1 (en) * | 2007-10-05 | 2009-04-09 | Arana Therapeutics (Vic) Pty Ltd | Improved method for mutagenesis |
| MX2010004995A (es) * | 2007-11-29 | 2010-05-20 | Boehringer Ingelheim Int | Derivados de amidas del acido 6,7-dihidro-5h-imidazo[1,2-a]imidazo l-3-carboxilico. |
| JP4621926B2 (ja) * | 2008-07-24 | 2011-02-02 | 国立大学法人九州大学 | 酵素基質修飾ヌクレオシド三リン酸、核酸プローブ、マルチラベル化核酸プローブ、マルチラベル化核酸プローブの製造方法および標的核酸の検出方法 |
| JP5146785B2 (ja) * | 2008-07-24 | 2013-02-20 | 国立大学法人九州大学 | 酵素基質修飾ヌクレオシド三リン酸誘導体 |
| JP2012521359A (ja) * | 2009-03-20 | 2012-09-13 | アリオス バイオファーマ インク． | 置換されたヌクレオシドアナログおよびヌクレオチドアナログ |
| BRPI1012581A2 (pt) | 2009-06-02 | 2016-03-29 | Boehringer Ingelheim Int | derivados de amidas de ácido 6, 7-di-hidro-5h-imidazol[1,2-a]imidazol-3-carboxílico |
| WO2010141330A1 (en) | 2009-06-02 | 2010-12-09 | Boehringer Ingelheim International Gmbh | DERIVATIVES OF 6,7-DIHYDRO-5H-IMIDAZO[1,2-a]IMIDAZOLE-3-CARBOXYLIC ACID AMIDES |
| JP5704481B2 (ja) * | 2010-01-22 | 2015-04-22 | 国立大学法人九州大学 | 核酸検出用キット |
| NZ607996A (en) | 2010-09-22 | 2014-07-25 | Alios Biopharma Inc | Substituted nucleotide analogs |
| EP2697242B1 (en) | 2011-04-13 | 2018-10-03 | Merck Sharp & Dohme Corp. | 2'-azido substituted nucleoside derivatives and methods of use thereof for the treatment of viral diseases |
| WO2012142093A2 (en) | 2011-04-13 | 2012-10-18 | Merck Sharp & Dohme Corp. | 2'-cyano substituted nucleoside derivatives and methods of use thereof for the treatment of viral diseases |
| BR112013026345A2 (pt) | 2011-04-13 | 2019-04-24 | Merck Sharp & Dohe Corp. | composto, composição farmacêutica, uso de um composto, e, método para tratar um paciente infectado com hcv |
| WO2013009735A1 (en) | 2011-07-13 | 2013-01-17 | Merck Sharp & Dohme Corp. | 5'-substituted nucleoside derivatives and methods of use thereof for the treatment of viral diseases |
| US9408863B2 (en) | 2011-07-13 | 2016-08-09 | Merck Sharp & Dohme Corp. | 5′-substituted nucleoside analogs and methods of use thereof for the treatment of viral diseases |
| CA2860234A1 (en) | 2011-12-22 | 2013-06-27 | Alios Biopharma, Inc. | Substituted phosphorothioate nucleotide analogs |
| HK1206362A1 (zh) | 2012-03-21 | 2016-01-08 | Alios Biopharma, Inc. | 硫代氨基磷酸酯核苷酸前藥的固體形式 |
| WO2013142157A1 (en) | 2012-03-22 | 2013-09-26 | Alios Biopharma, Inc. | Pharmaceutical combinations comprising a thionucleotide analog |
| US10278984B2 (en) * | 2014-05-02 | 2019-05-07 | Nitor Therapeutics | Guanosine as an immune potentiator mediated through toll receptors |
| WO2020081937A1 (en) * | 2018-10-19 | 2020-04-23 | The University Of Chicago | Methods and compositions for treating negative-sense single-stranded rna virus |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5512431A (en) * | 1994-06-29 | 1996-04-30 | Darwin Molecular Corporation | Methods of screening for nucleoside analogs that are incorporated by HIV reverse transcriptase and cause incorrect base pairing |
| US6063628A (en) * | 1996-10-28 | 2000-05-16 | University Of Washington | Induction of viral mutation by incorporation of miscoding ribonucleoside analogs into viral RNA |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4072574A (en) * | 1976-07-30 | 1978-02-07 | The Institute For Cancer Research | System for in vitro assay for mutagenicity and/or carcinogenicity of chemicals or other exogenous agents |
-
1997
- 1997-10-27 NZ NZ507848A patent/NZ507848A/en not_active IP Right Cessation
- 1997-10-27 AU AU50959/98A patent/AU740916B2/en not_active Ceased
- 1997-10-27 US US08/958,065 patent/US6063628A/en not_active Expired - Lifetime
- 1997-10-27 JP JP52073998A patent/JP2001525797A/ja active Pending
- 1997-10-27 NZ NZ33500097A patent/NZ335000A/xx unknown
- 1997-10-27 WO PCT/US1997/019670 patent/WO1998018324A1/en not_active Ceased
- 1997-10-27 EP EP97913882A patent/EP0948256A4/en not_active Withdrawn
- 1997-10-27 CA CA 2269213 patent/CA2269213A1/en not_active Abandoned
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5512431A (en) * | 1994-06-29 | 1996-04-30 | Darwin Molecular Corporation | Methods of screening for nucleoside analogs that are incorporated by HIV reverse transcriptase and cause incorrect base pairing |
| US6132776A (en) * | 1994-06-29 | 2000-10-17 | University Of Washington | Methods of screening for nucleoside analogs that are incorporated by HIV reverse transcriptase and cause incorrect base pairing |
| US6063628A (en) * | 1996-10-28 | 2000-05-16 | University Of Washington | Induction of viral mutation by incorporation of miscoding ribonucleoside analogs into viral RNA |
Also Published As
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| EP0948256A4 (en) | 2007-10-24 |
| AU5095998A (en) | 1998-05-22 |
| NZ335000A (en) | 2000-12-22 |
| US6063628A (en) | 2000-05-16 |
| JP2001525797A (ja) | 2001-12-11 |
| WO1998018324A1 (en) | 1998-05-07 |
| EP0948256A1 (en) | 1999-10-13 |
| NZ507848A (en) | 2005-01-28 |
| CA2269213A1 (en) | 1998-05-07 |
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