JP2001525797A - ウイルスｒｎａへのミスコーディングリボヌクレオシドアナログの組込みによるウイルス変異の誘導 - Google Patents
ウイルスｒｎａへのミスコーディングリボヌクレオシドアナログの組込みによるウイルス変異の誘導Info
- Publication number
- JP2001525797A JP2001525797A JP52073998A JP52073998A JP2001525797A JP 2001525797 A JP2001525797 A JP 2001525797A JP 52073998 A JP52073998 A JP 52073998A JP 52073998 A JP52073998 A JP 52073998A JP 2001525797 A JP2001525797 A JP 2001525797A
- Authority
- JP
- Japan
- Prior art keywords
- virus
- rna
- analog
- cytidine
- uridine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
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- C12N2770/24161—Methods of inactivation or attenuation
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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Landscapes
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- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
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Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
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| US2940496P | 1996-10-28 | 1996-10-28 | |
| US60/029,404 | 1996-10-28 | ||
| US4053597P | 1997-02-27 | 1997-02-27 | |
| US60/040,535 | 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 |
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| JP2001525797A true JP2001525797A (ja) | 2001-12-11 |
| JP2001525797A5 JP2001525797A5 (enExample) | 2005-06-16 |
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| Application Number | Title | Priority Date | Filing Date |
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| JP52073998A Pending JP2001525797A (ja) | 1996-10-28 | 1997-10-27 | ウイルスｒｎａへのミスコーディングリボヌクレオシドアナログの組込みによるウイルス変異の誘導 |
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| Country | Link |
|---|---|
| US (1) | US6063628A (enExample) |
| EP (1) | EP0948256A4 (enExample) |
| JP (1) | JP2001525797A (enExample) |
| AU (1) | AU740916B2 (enExample) |
| CA (1) | CA2269213A1 (enExample) |
| NZ (2) | NZ335000A (enExample) |
| WO (1) | WO1998018324A1 (enExample) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010010966A1 (ja) * | 2008-07-24 | 2010-01-28 | 国立大学法人九州大学 | ヌクレオシド三リン酸誘導体、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 |
| JP2011026324A (ja) * | 2008-07-24 | 2011-02-10 | Kyushu Univ | 酵素基質修飾ヌクレオシド三リン酸誘導体 |
| JP2011169878A (ja) * | 2010-01-22 | 2011-09-01 | Kyushu Univ | 核酸検出用キット |
Families Citing this family (48)
| 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 |
| NZ335000A (en) * | 1996-10-28 | 2000-12-22 | Univ Washington | Induction of viral mutation by incorporation of miscoding ribonucleoside analogs into viral RNA |
| US6423695B1 (en) * | 1998-01-13 | 2002-07-23 | Ribapharm, Inc. | Cytokine related treatments of disease |
| ATE419006T1 (de) * | 1999-03-26 | 2009-01-15 | Us Army | Multivalenter dengue-virus impfstoff |
| AU8038400A (en) * | 1999-09-09 | 2001-04-10 | Zymetx, Inc. | Method of treatment of influenza |
| AU7938900A (en) * | 1999-10-27 | 2001-05-08 | 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 |
| MXPA02008078A (es) | 2000-02-18 | 2002-11-29 | Julio Javier Cristiani | Metodo para el tratamiento o prevencion de infecciones por flavivirus utilizando analogos de nucleosidos. |
| MY164523A (en) | 2000-05-23 | 2017-12-29 | Univ Degli Studi Cagliari | Methods and compositions for treating hepatitis c virus |
| YU92202A (sh) | 2000-05-26 | 2006-01-16 | Idenix (Cayman) Limited | Metode i smeše za lečenje flavi virusa i pesti virusa |
| CA2426187C (en) * | 2000-10-18 | 2011-08-16 | Pharmasset Limited | Modified nucleosides for the treatment of viral infections and abnormal cellular proliferation |
| CN1267446C (zh) * | 2001-01-22 | 2006-08-02 | 默克公司 | 作为依赖于rna的rna病毒聚合酶的抑制剂的核苷衍生物 |
| US8481712B2 (en) | 2001-01-22 | 2013-07-09 | Merck Sharp & Dohme Corp. | Nucleoside derivatives as inhibitors of RNA-dependent RNA viral polymerase |
| AU2002252183A1 (en) * | 2001-03-06 | 2002-09-19 | Biocryst Pharmaceuticals, Inc. | Nucleosides, preparation thereof and use as inhibitors of rna viral polymerases |
| US7244717B2 (en) * | 2001-08-24 | 2007-07-17 | Koronis Pharmaceuticals, Incorporated | Mutagenic nucleoside analogs for the treatment of viral disease |
| WO2003026675A1 (en) * | 2001-09-28 | 2003-04-03 | Idenix (Cayman) Limited | 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 |
| 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 |
| AU2003248748A1 (en) * | 2002-06-28 | 2004-01-19 | Idenix (Cayman) Limited | 2'-c-methyl-3'-o-l-valine ester ribofuranosyl cytidine for treatment of flaviviridae infections |
| ES2322145T3 (es) | 2002-07-26 | 2009-06-17 | Novartis Vaccines And Diagnostics, Inc. | Moleculas pequeñas modificadas de adn inerferente y procedimiento de uso. |
| PT1576138T (pt) * | 2002-11-15 | 2017-05-03 | Idenix Pharmaceuticals Llc | 2'-metil-nucleósidos em combinação com interferão e mutação de flaviviridae |
| RU2005121904A (ru) * | 2002-12-12 | 2006-01-20 | Айденикс (Кайман) Лимитед (Ky) | Способ получения 2`-разветвленных нуклеозидов |
| US20050049204A1 (en) * | 2003-03-28 | 2005-03-03 | Otto Michael J. | Compounds for the treatment of flaviviridae infections |
| WO2005018330A1 (en) * | 2003-08-18 | 2005-03-03 | Pharmasset, Inc. | Dosing regimen for flaviviridae therapy |
| US20070042352A1 (en) * | 2003-08-18 | 2007-02-22 | Dawn Patricia Wooley | Retroviral vector and cell-based assay for measuring the mutations 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 |
| WO2007075876A2 (en) * | 2005-12-23 | 2007-07-05 | Idenix Pharmaceuticals, Inc. | Process for preparing a synthetic intermediate for preparation of branched nucleosides |
| 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. |
| EP2623104A1 (en) * | 2009-03-20 | 2013-08-07 | Alios Biopharma, Inc. | Substituted nucleoside and nucleotide analogs |
| JP5384732B2 (ja) | 2009-06-02 | 2014-01-08 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | ６，７−ジヒドロ−５Ｈ−イミダゾ［１，２−ａ］イミダゾール−３−カルボン酸アミドの誘導体 |
| JP5384733B2 (ja) | 2009-06-02 | 2014-01-08 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | ６，７−ジヒドロ−５Ｈ−イミダゾ［１，２−ａ］イミダゾール−３−カルボン酸アミドの誘導体 |
| US8871737B2 (en) | 2010-09-22 | 2014-10-28 | Alios Biopharma, Inc. | Substituted nucleotide analogs |
| EA201391519A1 (ru) | 2011-04-13 | 2014-03-31 | Мерк Шарп И Доум Корп. | 2'-замещенные нуклеозидные производные и способы их применения для лечения вирусных заболеваний |
| WO2012142075A1 (en) | 2011-04-13 | 2012-10-18 | Merck Sharp & Dohme Corp. | 2'-azido substituted nucleoside derivatives and methods of use thereof for the treatment of viral diseases |
| JP2014511875A (ja) | 2011-04-13 | 2014-05-19 | メルク・シャープ・アンド・ドーム・コーポレーション | ２’−シアノ置換ヌクレオシド誘導体およびウイルス疾患の治療のためのその使用方法 |
| EP2731433A4 (en) | 2011-07-13 | 2014-12-31 | Merck Sharp & Dohme | 5'-SUBSTITUTED NUCLEOSIDE ANALOGA AND METHOD FOR THEIR USE FOR THE TREATMENT OF VIRUS DISEASES |
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| US8980865B2 (en) | 2011-12-22 | 2015-03-17 | Alios Biopharma, Inc. | Substituted 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 |
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| US12227769B2 (en) | 2018-10-19 | 2025-02-18 | The University Of Chicago | Methods and compositions for treating negative-sense single-stranded RNA virus |
Family Cites Families (3)
| 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 |
| 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 |
| NZ335000A (en) * | 1996-10-28 | 2000-12-22 | Univ Washington | Induction of viral mutation by incorporation of miscoding ribonucleoside analogs into viral RNA |
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1997
- 1997-10-27 NZ NZ33500097A patent/NZ335000A/xx unknown
- 1997-10-27 CA CA 2269213 patent/CA2269213A1/en not_active Abandoned
- 1997-10-27 EP EP97913882A patent/EP0948256A4/en not_active Withdrawn
- 1997-10-27 WO PCT/US1997/019670 patent/WO1998018324A1/en not_active Ceased
- 1997-10-27 NZ NZ507848A patent/NZ507848A/en not_active IP Right Cessation
- 1997-10-27 US US08/958,065 patent/US6063628A/en not_active Expired - Lifetime
- 1997-10-27 AU AU50959/98A patent/AU740916B2/en not_active Ceased
- 1997-10-27 JP JP52073998A patent/JP2001525797A/ja active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010010966A1 (ja) * | 2008-07-24 | 2010-01-28 | 国立大学法人九州大学 | ヌクレオシド三リン酸誘導体、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 |
| JP2010047559A (ja) * | 2008-07-24 | 2010-03-04 | Kyushu Univ | 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 |
| JP2011026324A (ja) * | 2008-07-24 | 2011-02-10 | Kyushu Univ | 酵素基質修飾ヌクレオシド三リン酸誘導体 |
| US8198418B2 (en) | 2008-07-24 | 2012-06-12 | Kyushu University, National University Corporation | Nucleoside triphosphate derivative, nucleic acid probe, multilabeled nucleic acid probe, method for production of multilabeled nucleic acid probe, and method for detection of target nucleic acid |
| JP2011169878A (ja) * | 2010-01-22 | 2011-09-01 | Kyushu Univ | 核酸検出用キット |
Also Published As
| Publication number | Publication date |
|---|---|
| AU740916B2 (en) | 2001-11-15 |
| EP0948256A4 (en) | 2007-10-24 |
| AU5095998A (en) | 1998-05-22 |
| CA2269213A1 (en) | 1998-05-07 |
| NZ507848A (en) | 2005-01-28 |
| NZ335000A (en) | 2000-12-22 |
| US6063628A (en) | 2000-05-16 |
| WO1998018324A1 (en) | 1998-05-07 |
| EP0948256A1 (en) | 1999-10-13 |
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