JP2005500025A - 女性生殖疾病及び状態の核酸に基づく調節 - Google Patents
女性生殖疾病及び状態の核酸に基づく調節 Download PDFInfo
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- C12N2310/00—Structure or type of the nucleic acid
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- C12N2310/14—Type of nucleic acid interfering nucleic acids [NA]
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- C12N2310/00—Structure or type of the nucleic acid
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- C12N2310/00—Structure or type of the nucleic acid
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- C12N2310/31—Chemical structure of the backbone
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- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/32—Chemical structure of the sugar
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- C12N2310/00—Structure or type of the nucleic acid
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- C12N2310/00—Structure or type of the nucleic acid
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- C12N2310/33—Chemical structure of the base
- C12N2310/332—Abasic residue
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Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US87016101A | 2001-05-29 | 2001-05-29 | |
| US33446101P | 2001-11-30 | 2001-11-30 | |
| US10/138,674 US7034009B2 (en) | 1995-10-26 | 2002-05-03 | Enzymatic nucleic acid-mediated treatment of ocular diseases or conditions related to levels of vascular endothelial growth factor receptor (VEGF-R) |
| PCT/US2002/017674 WO2002096927A2 (en) | 2001-05-29 | 2002-05-29 | Ribozyme based treatment of female reproductive diseases |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2008149684A Division JP2009000106A (ja) | 2001-05-29 | 2008-06-06 | 女性生殖疾病及び状態の核酸に基づく調節 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2005500025A true JP2005500025A (ja) | 2005-01-06 |
| JP2005500025A5 JP2005500025A5 (https=) | 2005-09-15 |
Family
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Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
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| JP2003500106A Pending JP2005500025A (ja) | 2001-05-29 | 2002-05-29 | 女性生殖疾病及び状態の核酸に基づく調節 |
| JP2008149684A Pending JP2009000106A (ja) | 2001-05-29 | 2008-06-06 | 女性生殖疾病及び状態の核酸に基づく調節 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
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| JP2008149684A Pending JP2009000106A (ja) | 2001-05-29 | 2008-06-06 | 女性生殖疾病及び状態の核酸に基づく調節 |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP1390385A4 (https=) |
| JP (2) | JP2005500025A (https=) |
| AU (1) | AU2002344237B8 (https=) |
| CA (1) | CA2448320A1 (https=) |
| GB (1) | GB0404461D0 (https=) |
| WO (1) | WO2002096927A2 (https=) |
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| JP2013189443A (ja) * | 2006-05-25 | 2013-09-26 | Novartis Ag | チロシンキナーゼ阻害剤 |
| JP2016520089A (ja) * | 2013-05-22 | 2016-07-11 | ゼンサン （シャンハイ） サイエンス アンド テクノロジー リミテッド | 心不全を治療するためのニューレグリンの徐放 |
| US11253573B2 (en) | 2011-10-10 | 2022-02-22 | Zensun (Shanghai) Science & Technology, Co., Ltd. | Compositions and methods for treating heart failure |
Families Citing this family (52)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030216335A1 (en) * | 2001-11-30 | 2003-11-20 | Jennifer Lockridge | Method and reagent for the modulation of female reproductive diseases and conditions |
| US7491805B2 (en) * | 2001-05-18 | 2009-02-17 | Sirna Therapeutics, Inc. | Conjugates and compositions for cellular delivery |
| US7833992B2 (en) * | 2001-05-18 | 2010-11-16 | Merck Sharpe & Dohme | Conjugates and compositions for cellular delivery |
| EP1386004A4 (en) | 2001-04-05 | 2005-02-16 | Ribozyme Pharm Inc | MODULATION OF GENE EXPRESSION ASSOCIATED WITH INFLAMMATORY PROLIFERATION AND GROWTH OF NEURITIES BY METHODS INVOLVING NUCLEIC ACID |
| US9994853B2 (en) | 2001-05-18 | 2018-06-12 | Sirna Therapeutics, Inc. | Chemically modified multifunctional short interfering nucleic acid molecules that mediate RNA interference |
| US20050014172A1 (en) | 2002-02-20 | 2005-01-20 | Ivan Richards | RNA interference mediated inhibition of muscarinic cholinergic receptor gene expression using short interfering nucleic acid (siNA) |
| US20050148530A1 (en) * | 2002-02-20 | 2005-07-07 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor gene expression using short interfering nucleic acid (siNA) |
| US7517864B2 (en) | 2001-05-18 | 2009-04-14 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor gene expression using short interfering nucleic acid (siNA) |
| FR2832154B1 (fr) * | 2001-11-09 | 2007-03-16 | Centre Nat Rech Scient | Oligonucleotides inhibiteurs et leur utilisation pour reprimer specifiquement un gene |
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| EP1495120B1 (en) | 2002-04-18 | 2012-10-10 | Acuity Pharmaceuticals, Inc | Means and methods for the specific modulation of target genes in the eye |
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| WO2006006948A2 (en) | 2002-11-14 | 2006-01-19 | Dharmacon, Inc. | METHODS AND COMPOSITIONS FOR SELECTING siRNA OF IMPROVED FUNCTIONALITY |
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| EP1606305A4 (en) * | 2003-03-12 | 2009-06-24 | Vasgene Therapeutics Inc | NUCLEIC ACID COMPOUNDS FOR THE INHIBITION OF ANGIOGENESIS AND TUMOR GROWTH |
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| CA2528372A1 (en) * | 2003-06-06 | 2005-01-27 | Senesco Technologies, Inc. | Inhibition of apoptosis-specific elf-5a ("eif-5a1") with antisense oligonucleotides and sirnas as anti-inflammatory therapeutics |
| EP1660657A1 (en) | 2003-08-28 | 2006-05-31 | Novartis AG | Interfering rna duplex having blunt-ends and 3'-modifications |
| WO2005038013A1 (en) | 2003-10-07 | 2005-04-28 | Isis Pharmaceuticals, Inc. | Artisense oligonucleotides optimized for kidney targeting |
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| WO2005076998A2 (en) * | 2004-02-05 | 2005-08-25 | Intradigm Corporation | Rnai therapeutics for treatment of eye neovascularization diseases |
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| CN101277704A (zh) | 2005-04-12 | 2008-10-01 | 因特拉迪格姆公司 | 用于治疗癌症及其它新血管生成疾病的RNAi治疗剂的组合物和方法 |
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| US7872118B2 (en) | 2006-09-08 | 2011-01-18 | Opko Ophthalmics, Llc | siRNA and methods of manufacture |
| US11078262B2 (en) | 2007-04-30 | 2021-08-03 | Allergan, Inc. | High viscosity macromolecular compositions for treating ocular conditions |
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| WO2011019423A2 (en) | 2009-05-20 | 2011-02-17 | Schering Corporation | Modulation of pilr receptors to treat microbial infections |
| JP5833549B2 (ja) | 2009-06-22 | 2015-12-16 | アンピオ ファーマシューティカルズ，インコーポレイテッド | 血管透過性亢進を抑制するためのダナゾールを含む製薬組成物 |
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Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6346398B1 (en) * | 1995-10-26 | 2002-02-12 | Ribozyme Pharmaceuticals, Inc. | Method and reagent for the treatment of diseases or conditions related to levels of vascular endothelial growth factor receptor |
| WO1999004819A1 (en) * | 1997-07-24 | 1999-02-04 | Inex Pharmaceuticals Corporation | Liposomal compositions for the delivery of nucleic acid catalysts |
| WO2003070910A2 (en) * | 2002-02-20 | 2003-08-28 | Ribozyme Pharmaceuticals, Incorporated | INHIBITION OF VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) AND VEGF RECEPTOR GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
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- 2002-05-29 CA CA002448320A patent/CA2448320A1/en not_active Abandoned
- 2002-05-29 EP EP02752028A patent/EP1390385A4/en not_active Withdrawn
- 2002-05-29 AU AU2002344237A patent/AU2002344237B8/en not_active Ceased
- 2002-05-29 JP JP2003500106A patent/JP2005500025A/ja active Pending
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2008
- 2008-06-06 JP JP2008149684A patent/JP2009000106A/ja active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013189443A (ja) * | 2006-05-25 | 2013-09-26 | Novartis Ag | チロシンキナーゼ阻害剤 |
| US11253573B2 (en) | 2011-10-10 | 2022-02-22 | Zensun (Shanghai) Science & Technology, Co., Ltd. | Compositions and methods for treating heart failure |
| US12076370B2 (en) | 2011-10-10 | 2024-09-03 | Zensun (Shanghai) Science & Technology, Co., Ltd. | Compositions and methods for treating heart failure |
| JP2016520089A (ja) * | 2013-05-22 | 2016-07-11 | ゼンサン （シャンハイ） サイエンス アンド テクノロジー リミテッド | 心不全を治療するためのニューレグリンの徐放 |
| US11179323B2 (en) | 2013-05-22 | 2021-11-23 | Zensun (Shanghai) Science & Technology, Co., Ltd. | Extended release of neuregulin for treating heart failure |
| US12208158B2 (en) | 2013-05-22 | 2025-01-28 | Zensun (Shanghai) Science & Technology, Co., Ltd. | Extended release of neuregulin for treating heart failure |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2002344237B8 (en) | 2008-11-06 |
| GB0404461D0 (en) | 2004-03-31 |
| WO2002096927A3 (en) | 2003-02-20 |
| JP2009000106A (ja) | 2009-01-08 |
| EP1390385A2 (en) | 2004-02-25 |
| WO2002096927A2 (en) | 2002-12-05 |
| AU2002344237B2 (en) | 2008-10-23 |
| EP1390385A4 (en) | 2004-11-24 |
| CA2448320A1 (en) | 2002-12-05 |
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