AU2006235489A1 - Composition and methods of RNAi therapeutics for treatment of cancer and other neovascularization diseases - Google Patents
Composition and methods of RNAi therapeutics for treatment of cancer and other neovascularization diseases Download PDFInfo
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- AU2006235489A1 AU2006235489A1 AU2006235489A AU2006235489A AU2006235489A1 AU 2006235489 A1 AU2006235489 A1 AU 2006235489A1 AU 2006235489 A AU2006235489 A AU 2006235489A AU 2006235489 A AU2006235489 A AU 2006235489A AU 2006235489 A1 AU2006235489 A1 AU 2006235489A1
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| CA2482904A1 (en) | 2002-04-18 | 2003-10-23 | Lynkeus Biotech Gmbh | Means and methods for the specific modulation of target genes in the cns and the eye and methods for their identification |
| US7148342B2 (en) | 2002-07-24 | 2006-12-12 | The Trustees Of The University Of Pennyslvania | Compositions and methods for sirna inhibition of angiogenesis |
| US10011836B2 (en) | 2002-11-14 | 2018-07-03 | Thermo Fisher Scientific Inc. | Methods and compositions for selecting siRNA of improved functionality |
| US9839649B2 (en) | 2002-11-14 | 2017-12-12 | Thermo Fisher Scientific Inc. | Methods and compositions for selecting siRNA of improved functionality |
| US7592442B2 (en) | 2002-11-14 | 2009-09-22 | Dharmacon, Inc. | siRNA targeting ribonucleotide reductase M2 polypeptide (RRM2 or RNR-R2) |
| US7951935B2 (en) | 2002-11-14 | 2011-05-31 | Dharmacon, Inc. | siRNA targeting v-myc myelocytomatosis viral oncogene homolog (MYC) |
| US7635770B2 (en) | 2002-11-14 | 2009-12-22 | Dharmacon, Inc. | siRNA targeting protein kinase N-3 (PKN-3) |
| US9719094B2 (en) | 2002-11-14 | 2017-08-01 | Thermo Fisher Scientific Inc. | RNAi targeting SEC61G |
| US7691998B2 (en) | 2002-11-14 | 2010-04-06 | Dharmacon, Inc. | siRNA targeting nucleoporin 62kDa (Nup62) |
| US9771586B2 (en) | 2002-11-14 | 2017-09-26 | Thermo Fisher Scientific Inc. | RNAi targeting ZNF205 |
| US9228186B2 (en) | 2002-11-14 | 2016-01-05 | Thermo Fisher Scientific Inc. | Methods and compositions for selecting siRNA of improved functionality |
| US9719092B2 (en) | 2002-11-14 | 2017-08-01 | Thermo Fisher Scientific Inc. | RNAi targeting CNTD2 |
| US7619081B2 (en) | 2002-11-14 | 2009-11-17 | Dharmacon, Inc. | siRNA targeting coatomer protein complex, subunit beta 2 (COPB2) |
| US7977471B2 (en) | 2002-11-14 | 2011-07-12 | Dharmacon, Inc. | siRNA targeting TNFα |
| US9879266B2 (en) | 2002-11-14 | 2018-01-30 | Thermo Fisher Scientific Inc. | Methods and compositions for selecting siRNA of improved functionality |
| EP2305812A3 (en) | 2002-11-14 | 2012-06-06 | Dharmacon, Inc. | Fuctional and hyperfunctional sirna |
| US8198427B1 (en) | 2002-11-14 | 2012-06-12 | Dharmacon, Inc. | SiRNA targeting catenin, beta-1 (CTNNB1) |
| WO2006006948A2 (en) | 2002-11-14 | 2006-01-19 | Dharmacon, Inc. | METHODS AND COMPOSITIONS FOR SELECTING siRNA OF IMPROVED FUNCTIONALITY |
| US7612196B2 (en) | 2002-11-14 | 2009-11-03 | Dharmacon, Inc. | siRNA targeting cyclin-dependent kinase inhibitor 1B (p27, Kip1) (CDKN1B) |
| EP1711172A4 (en) | 2003-12-23 | 2008-07-16 | Univ Pennsylvania | COMPOSITIONS AND METHODS FOR COMBINATION THERAPY OF ILLNESSES |
| US8491914B2 (en) * | 2004-02-13 | 2013-07-23 | Ibc Pharmaceuticals, Inc. | Dock-and-lock (DNL) complexes for delivery of interference RNA |
| US7605250B2 (en) | 2004-05-12 | 2009-10-20 | Dharmacon, Inc. | siRNA targeting cAMP-specific phosphodiesterase 4D |
| US7893244B2 (en) * | 2005-04-12 | 2011-02-22 | Intradigm Corporation | Composition and methods of RNAi therapeutics for treatment of cancer and other neovascularization diseases |
| JP2008537752A (ja) * | 2005-04-12 | 2008-09-25 | イントラディグム コーポレイション | がんおよび他の新血管形成疾患を処置するためのＲＮＡｉ治療用の組成物および方法 |
| US20070082845A1 (en) * | 2005-07-15 | 2007-04-12 | The Penn State Research Foundation | Ferritin as a therapeutic target in abnormal cells |
| KR20080061397A (ko) * | 2005-10-14 | 2008-07-02 | 나스텍 파마수티컬 컴퍼니 인코포레이티드 | Ｒｎａ 치료제용 펩티드 리보핵산 축합물 입자들의화합물들과 방법들 |
| WO2007080902A1 (ja) * | 2006-01-11 | 2007-07-19 | Kyowa Hakko Kogyo Co., Ltd. | 眼球において標的遺伝子の発現を抑制する組成物および眼球における疾患の治療剤 |
| EP3342415B1 (en) | 2006-08-08 | 2022-01-26 | Rheinische Friedrich-Wilhelms-Universität Bonn | Structure and use of 5' phosphate oligonucleotides |
| WO2008045576A2 (en) * | 2006-10-12 | 2008-04-17 | Yijia Liu | Compositions and methods of rnai therapeutics for treatment of cancer and other neovascularization diseases |
| US20080274121A1 (en) * | 2007-04-30 | 2008-11-06 | Yao James C | Inhibition of Angiogenesis by Mithramycin |
| CN101363027B (zh) * | 2007-08-06 | 2011-07-27 | 武汉大学 | 携带短发夹rna的重组质粒的制备方法及用途 |
| JP5273740B2 (ja) * | 2007-09-07 | 2013-08-28 | 国立大学法人徳島大学 | ｐ５３の発現促進方法およびそれに用いるｐ５３発現促進剤 |
| WO2009051659A2 (en) * | 2007-10-12 | 2009-04-23 | Intradigm Corporation | Therapeutic sirna molecules for reducing vegfr1 expression in vitro and in vivo |
| DK2217062T3 (en) | 2007-11-06 | 2015-08-24 | Sirnaomics Inc | MULTI-TARGET READY RNAi therapeutics TO ARFRI WOUND HEALING OF SKIN |
| CN103351597A (zh) * | 2007-11-07 | 2013-10-16 | 犹他大学研究基金会 | 可还原聚（酰胺乙烯亚胺）的可切割修饰以增强核苷酸递送 |
| US20110312877A1 (en) * | 2008-02-26 | 2011-12-22 | Aparna Biosceiences | Engineered tunable nanoparticles for delivery of therapeutics, diagnostics, and experimental compounds and related compositions for therapeutic use |
| ES2338400B1 (es) | 2008-05-06 | 2011-09-14 | David Benet Ferrus | Conjunto de moleculas antiangiogenicas y su uso. |
| EP2297323A1 (en) | 2008-05-21 | 2011-03-23 | Hartmann, Gunther | 5' triphosphate oligonucleotide with blunt end and uses thereof |
| WO2009151539A1 (en) * | 2008-05-24 | 2009-12-17 | Sirnaomics, Inc. | COMPOSITIONS AND METHODS USING siRNA MOLECULES FOR TREATMENT OF GLIOMAS |
| JP5832293B2 (ja) | 2008-12-04 | 2015-12-16 | オプコ ファーマシューティカルズ、エルエルシー | 血管新生促進ｖｅｇｆイソ型を選択的に抑制する組成物および方法 |
| WO2010078517A2 (en) * | 2008-12-31 | 2010-07-08 | Sirnaomics, Inc. | Compositions and methods using sirna molecules and sirna cocktails for the treatment of breast cancer |
| DE102009006606A1 (de) * | 2009-01-29 | 2010-08-05 | Philipps-Universität Marburg | Nicht-virales Transfektionsmittel |
| US20120114710A1 (en) * | 2009-05-18 | 2012-05-10 | Lynn Kirkpatrick | Carbon nanotubes complexed with multiple bioactive agents and methods related thereto |
| WO2011011061A2 (en) * | 2009-07-21 | 2011-01-27 | The Board Of Trustees Of The Leland Stanford Junior University | Method of regulating angiogenesis and lymphangiogenesis, and a pharmaceutical composition for effecting anti-angiogenic and anti-lymphangiogenic cancer therapy |
| WO2011039646A2 (en) | 2009-09-30 | 2011-04-07 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Papilloma virus -like particles for targeted gene delivery |
| JP2013523651A (ja) * | 2010-03-24 | 2013-06-17 | ノースイースタン ユニヴァーシティ | 多重コンパートメントのマクロファージ送達 |
| US8349308B2 (en) | 2010-03-26 | 2013-01-08 | Mersana Therapeutics, Inc. | Modified polymers for delivery of polynucleotides, method of manufacture, and methods of use thereof |
| WO2011140285A2 (en) | 2010-05-04 | 2011-11-10 | Sirnaomics, Inc. | Combinations of tgfbeta and cox-2 inhibitors and methods for their therapeutic application |
| WO2012016139A2 (en) | 2010-07-29 | 2012-02-02 | Sirnaomics, Inc. | Sirna compositions and methods for treatment of hpv and other infections |
| EP2508530A1 (en) | 2011-03-28 | 2012-10-10 | Rheinische Friedrich-Wilhelms-Universität Bonn | Purification of triphosphorylated oligonucleotides using capture tags |
| CN102727513B (zh) * | 2011-04-15 | 2014-07-09 | 百奥迈科生物技术有限公司 | 靶向于组织因子基因的小核酸及其用途 |
| US8592572B2 (en) * | 2011-05-23 | 2013-11-26 | Delta-Fly Pharma, Inc. | Liposome containing shRNA molecule targeting a thymidylate synthase and use thereof |
| US20120301537A1 (en) * | 2011-05-23 | 2012-11-29 | Delta-Fly Pharma, Inc. | LIPOSOME CONTAINING shRNA MOLECULE TARGETING A THYMIDYLATE SYNTHASE AND USE THEREOF |
| WO2013114339A1 (en) | 2012-02-02 | 2013-08-08 | The Universityof British Columbia | Combination therapy for cancer using hsp27 inhibitor and egfr tyrosine kinase inhibitors or anti-folates |
| EP2712870A1 (en) | 2012-09-27 | 2014-04-02 | Rheinische Friedrich-Wilhelms-Universität Bonn | Novel RIG-I ligands and methods for producing them |
| US9801953B2 (en) | 2012-10-15 | 2017-10-31 | Emory University | Nanoparticles carrying nucleic acid cassettes for expressing RNA |
| US9228189B2 (en) | 2012-10-26 | 2016-01-05 | Geron Corporation | C-myc antisense oligonucleotides and methods for using the same to treat cell-proliferative disorders |
| WO2015021092A1 (en) * | 2013-08-07 | 2015-02-12 | Arrowhead Research Corporation | Polyconjugates for delivery of rnai triggers to tumor cells in vivo |
| CN104635967B (zh) * | 2013-11-12 | 2018-04-10 | 宸鸿光电科技股份有限公司 | 有机发光二极管触控显示设备 |
| US20170143848A1 (en) * | 2014-03-24 | 2017-05-25 | Shire Human Genetic Therapies, Inc. | Mrna therapy for the treatment of ocular diseases |
| EP3265107B1 (en) | 2015-03-02 | 2024-10-02 | 180 Therapeutics LP | Method of treating a localized fibrotic disorder using a tnf receptor 2 antagonist |
| EP4035659A1 (en) | 2016-11-29 | 2022-08-03 | PureTech LYT, Inc. | Exosomes for delivery of therapeutic agents |
| GB201904337D0 (en) * | 2019-03-28 | 2019-05-15 | Sisaf Ltd | A delivery system |
| CN111298129B (zh) * | 2019-08-28 | 2023-05-09 | 中国人民解放军陆军军医大学第二附属医院 | 二甲双胍介导核酸纳米材料自组装方法及采用该方法制备的纳米制剂和应用 |
| KR20240004316A (ko) | 2021-04-27 | 2024-01-11 | 4디 몰레큘러 테라퓨틱스 아이엔씨. | 혈관신생과 관련된 안구 질환의 치료를 위한 조성물 및 방법 |
| WO2025247332A1 (zh) * | 2024-05-31 | 2025-12-04 | 石药集团中奇制药技术（石家庄）有限公司 | 一种抑制vegfa基因和ang-2基因表达的双靶核酸分子 |
Family Cites Families (88)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5240848A (en) * | 1988-11-21 | 1993-08-31 | Monsanto Company | Dna sequences encoding human vascular permeability factor having 189 amino acids |
| US5332671A (en) * | 1989-05-12 | 1994-07-26 | Genetech, Inc. | Production of vascular endothelial cell growth factor and DNA encoding same |
| US5726152A (en) * | 1990-09-21 | 1998-03-10 | Merck & Co., Inc. | Vascular endothelial cell growth factor II |
| DE69229454T2 (de) * | 1991-03-28 | 2000-01-05 | Merck & Co., Inc. | Untereinheit-C des vaskulären endothelialen Zellwachstumsfaktors |
| US6710174B2 (en) | 2001-09-13 | 2004-03-23 | Isis Pharmaceuticals, Inc. | Antisense inhibition of vascular endothelial growth factor receptor-1 expression |
| US6743909B2 (en) * | 2002-06-17 | 2004-06-01 | Isis Pharmaceuticals, Inc. | Antisense modulation of PTPN12 expression |
| US6037329A (en) * | 1994-03-15 | 2000-03-14 | Selective Genetics, Inc. | Compositions containing nucleic acids and ligands for therapeutic treatment |
| US6150092A (en) * | 1994-06-27 | 2000-11-21 | Taogosei Company, Ltd. | Antisense nucleic acid compound targeted to VEGF |
| AU3374795A (en) | 1994-08-29 | 1996-03-22 | Prizm Pharmaceuticals, Inc. | Conjugates of vascular endothelial growth factor with targeted agents |
| NZ328371A (en) | 1994-12-23 | 1999-05-28 | Ludwig Inst Cancer Res | Method of detecting a ligand capable of binding the receptor protein neuroepithelial tyrosine kinase (nyk) and its use in therapeutic compositions |
| US5607918A (en) * | 1995-03-01 | 1997-03-04 | Ludwig Institute For Cancer Research | Vascular endothelial growth factor-B and DNA coding therefor |
| US5928939A (en) * | 1995-03-01 | 1999-07-27 | Ludwig Institute For Cancer Research | Vascular endothelial growth factor-b and dna coding therefor |
| EP0845992B1 (en) * | 1995-08-15 | 2002-11-20 | Connetics Corporation | Use of relaxin for promoting angiogenesis |
| US7005505B1 (en) * | 1995-08-25 | 2006-02-28 | Genentech, Inc. | Variants of vascular endothelial cell growth factor |
| US20040142895A1 (en) * | 1995-10-26 | 2004-07-22 | Sirna Therapeutics, Inc. | Nucleic acid-based modulation of gene expression in the vascular endothelial growth factor pathway |
| 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 |
| US6013780A (en) * | 1996-09-06 | 2000-01-11 | Technion Research & Development Co. Ltd. | VEGF145 expression vectors |
| EP1426444A3 (en) | 1996-09-06 | 2004-06-16 | Technion Research & Development Co., Ltd. | Use of the angiogenic factor VEGF145 in treating cardiovascular diseases |
| US6750044B1 (en) * | 1996-10-17 | 2004-06-15 | Genentech, Inc. | Variants of vascular endothelial cell growth factor having antagonistic properties, nucleic acids encoding the same and host cells comprising those nucleic acids |
| US6395707B1 (en) * | 1997-02-14 | 2002-05-28 | Genentech, Inc. | Methods of treatment utilizing variants of vascular endothelial cell growth factor |
| US6485942B1 (en) * | 1997-02-14 | 2002-11-26 | Genentech, Inc. | Variants of vascular endothelial cell growth factor having altered pharmacological properties, and recombinant methods of production |
| US6479729B1 (en) * | 1998-02-06 | 2002-11-12 | The Johns Hopkins University | Mouse model for ocular neovascularization |
| JP2002502608A (ja) * | 1998-02-06 | 2002-01-29 | コラテラル・セラピューティックス・インコーポレイテッド | 血管新生促進因子である血管内皮細胞成長因子：ｖｅｇｆの変異体 |
| US6783961B1 (en) * | 1999-02-26 | 2004-08-31 | Genset S.A. | Expressed sequence tags and encoded human proteins |
| DE69919869T2 (de) * | 1998-06-10 | 2005-09-29 | Biognostik Gesellschaft für Biomolekulare Diagnostik mbH | Stimulierung des immunsystems |
| CA2329160A1 (en) | 1998-06-11 | 1999-12-16 | University Of Medicine & Dentistry Of New Jersey | Wound treatment through inhibition of adenosine diphosphate ribosyl transferase |
| EP0979869A1 (en) * | 1998-08-07 | 2000-02-16 | Hoechst Marion Roussel Deutschland GmbH | Short oligonucleotides for the inhibition of VEGF expression |
| ES2216630T3 (es) * | 1998-09-09 | 2004-10-16 | Scios Inc | Metodos de tratar la hipertension dependiente de la sal. |
| US6677300B1 (en) * | 1998-09-09 | 2004-01-13 | Scios, Inc. | Treatment of microvascular angiopathies |
| EP1417971A3 (en) | 1998-09-09 | 2004-06-30 | Scios Inc. | Use of an angiogenic factor for the treatment of microvascular angiopathies |
| US7030083B2 (en) * | 1998-09-09 | 2006-04-18 | University Of Washington | Treatment of eclampsia and preeclampsia |
| US6916915B1 (en) * | 1998-11-20 | 2005-07-12 | Duke University | Stressor regulated genes |
| CA2296792A1 (en) | 1999-02-26 | 2000-08-26 | Genset S.A. | Expressed sequence tags and encoded human proteins |
| IL128852A0 (en) * | 1999-03-05 | 2000-01-31 | Compugen Ltd | Novel nucleic acid and amino acid sequences |
| US6783954B2 (en) * | 1999-03-05 | 2004-08-31 | Compugen Ltd. | VEGF nucleic acid and amino acid sequences |
| DE19910419A1 (de) | 1999-03-10 | 2000-09-21 | Aventis Pharma Gmbh | Zielzellspezifische, multivalente Proteine (MVP) |
| US6943153B1 (en) * | 1999-03-15 | 2005-09-13 | The Regents Of The University Of California | Use of recombinant gene delivery vectors for treating or preventing diseases of the eye |
| US6475796B1 (en) * | 1999-05-20 | 2002-11-05 | Scios, Inc. | Vascular endothelial growth factor variants |
| US6187822B1 (en) * | 1999-06-11 | 2001-02-13 | University Of Medicine & Dentistry Of Nj | Wound treatment through inhibition of adenosine diphosphate ribosyl transferase |
| WO2001027292A2 (en) | 1999-10-08 | 2001-04-19 | Biofocus Discovery Limited | Methods and compositions for targeting a cell |
| US6770633B1 (en) * | 1999-10-26 | 2004-08-03 | Immusol, Inc. | Ribozyme therapy for the treatment of proliferative skin and eye diseases |
| US7078382B1 (en) * | 1999-11-02 | 2006-07-18 | Genentech, Inc. | Modulation of eNOS activity and therapeutic uses thereof |
| CN1307303C (zh) * | 2000-01-19 | 2007-03-28 | 帕卡什·S·吉尔 | 针对反义vegf寡核苷酸的方法和组合物 |
| WO2001058468A1 (en) | 2000-02-09 | 2001-08-16 | Connetics Corporation | Use of relaxin to treat diseases related to vasoconstriction |
| WO2005019453A2 (en) * | 2001-05-18 | 2005-03-03 | Sirna Therapeutics, Inc. | RNA INTERFERENCE MEDIATED INHIBITION OF GENE EXPRESSION USING CHEMICALLY MODIFIED SHORT INTERFERING NUCLEIC ACID (siNA) |
| AU3988401A (en) * | 2000-02-25 | 2001-09-03 | Ludwig Inst Cancer Res | Materials and methods involving hybrid vascular endothelial growth factor dnas and proteins |
| US6974667B2 (en) * | 2000-06-14 | 2005-12-13 | Gene Logic, Inc. | Gene expression profiles in liver cancer |
| US6727066B2 (en) * | 2000-07-28 | 2004-04-27 | Incyte Corporation | Genes expressed in treated human C3A liver cell cultures |
| US6673549B1 (en) * | 2000-10-12 | 2004-01-06 | Incyte Corporation | Genes expressed in C3A liver cell cultures treated with steroids |
| US20030186920A1 (en) | 2000-10-13 | 2003-10-02 | Sirois Martin G. | Antisense oligonucleotide directed toward mammalian vegf receptor genes and uses thereof |
| AU2002305236A1 (en) | 2001-04-24 | 2002-11-05 | Epigenesis Pharmaceuticals, Inc. | Composition, formulations and kits for treatment of respiratory and lung disease with anti-sense oligonucleotides and a bronchodilating agent |
| US20070021360A1 (en) | 2001-04-24 | 2007-01-25 | Nyce Jonathan W | Compositions, formulations and kit with anti-sense oligonucleotide and anti-inflammatory steroid and/or obiquinone for treatment of respiratory and lung disesase |
| 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) |
| US20050222066A1 (en) * | 2001-05-18 | 2005-10-06 | 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) |
| 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) |
| 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) |
| WO2004111237A1 (en) | 2003-04-16 | 2004-12-23 | Sirna Therapeutics, Inc. | RNA INTERFERENCE MEDIATED INHIBITION OF PLATELET-DERIVED ENDOTHELIAL CELL GROWTH FACTOR (ECGF1) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
| EP1262199A1 (en) | 2001-05-23 | 2002-12-04 | Fornix Biosciences N.V. | Vectors for enhanced expression of VEGF for disease treatment |
| CA2448320A1 (en) | 2001-05-29 | 2002-12-05 | Sirna Therapeutics, Inc. | Ribozyme based treatment of female reproductive diseases |
| US7101977B2 (en) * | 2001-07-17 | 2006-09-05 | Research Development Foundation | Therapeutic agents comprising pro-apoptotic proteins |
| JP2003088388A (ja) * | 2001-09-14 | 2003-03-25 | Herikkusu Kenkyusho:Kk | 新規な全長ｃＤＮＡ |
| EP1293569A3 (en) | 2001-09-14 | 2004-03-31 | Research Association for Biotechnology | Full-length cDNAs |
| JP2005508396A (ja) * | 2001-11-02 | 2005-03-31 | イントラディグム、コーポレイション | 核酸送達ビヒクルのための治療方法 |
| FR2832154B1 (fr) | 2001-11-09 | 2007-03-16 | Centre Nat Rech Scient | Oligonucleotides inhibiteurs et leur utilisation pour reprimer specifiquement un gene |
| US20050075304A1 (en) * | 2001-11-30 | 2005-04-07 | Mcswiggen James | RNA interference mediated inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor gene expression using short interfering nucleic acid (siNA) |
| US6927779B2 (en) * | 2002-05-13 | 2005-08-09 | Large Scale Biology Corporation | Web-based well plate information retrieval and display system |
| US7148342B2 (en) * | 2002-07-24 | 2006-12-12 | The Trustees Of The University Of Pennyslvania | Compositions and methods for sirna inhibition of angiogenesis |
| MXPA05003287A (es) * | 2002-09-28 | 2005-07-05 | Massachusetts Inst Technology | Influenza terapeutica. |
| EP2305812A3 (en) | 2002-11-14 | 2012-06-06 | Dharmacon, Inc. | Fuctional and hyperfunctional sirna |
| FR2835838B1 (fr) | 2003-02-06 | 2007-11-16 | Centre Nat Rech Scient | Oligonucleotides inhibiteurs et leur utilisation pour reprimer specifiquement un gene codant pour un facteur de transcription |
| FR2835837B1 (fr) | 2003-02-06 | 2007-03-16 | Centre Nat Rech Scient | Oligonucleotides inhibiteurs et leurs utilisation pour reprimer specifiquement un gene codant pour un facteur de croissance |
| AU2004227414A1 (en) | 2003-04-03 | 2004-10-21 | Alnylam Pharmaceuticals | iRNA conjugates |
| US20050096370A1 (en) | 2003-04-07 | 2005-05-05 | Bizbiotech Co., Ltd. | Method for inhibiting tumor angiogenesis and tumor growth |
| DE10316701A1 (de) | 2003-04-09 | 2004-11-04 | Hinzmann, Bernd, Dr. | Humane Nukleinsäuresequenzen aus Bronchialkarzinomen |
| US20050019927A1 (en) * | 2003-07-13 | 2005-01-27 | Markus Hildinger | DECREASING GENE EXPRESSION IN A MAMMALIAN SUBJECT IN VIVO VIA AAV-MEDIATED RNAi EXPRESSION CASSETTE TRANSFER |
| EP1548445A3 (en) | 2003-12-22 | 2005-11-23 | F. Hoffmann-La Roche Ag | Novel targets for obesity from fat tissue |
| EP1713819A4 (en) * | 2004-02-05 | 2007-11-14 | Intradigm Corp | METHOD AND COMPOSITIONS FOR COMBINING RNAI THERAPEUTICS |
| EP1711510A4 (en) * | 2004-02-05 | 2008-11-26 | Intradigm Corp | RNAI THERAPEUTIC FOR THE TREATMENT OF EYE DISEASES WITH VASCULAR REPRODUCTION |
| AU2005222902B2 (en) | 2004-03-12 | 2010-06-10 | Alnylam Pharmaceuticals, Inc. | iRNA agents targeting VEGF |
| EP1752536A4 (en) | 2004-05-11 | 2008-04-16 | Alphagen Co Ltd | POLYNUCLEOTIDE CAUSING RNA INTERFERENCE AND METHOD OF REGULATING GENE EXPRESSION WITH THE USE OF THE SAME |
| EP1607485A1 (en) | 2004-06-14 | 2005-12-21 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Method for quantifying VEGF121 isoform in a biological sample |
| AU2005310131A1 (en) | 2004-11-17 | 2006-06-08 | University Of Maryland, Baltimore | Highly branched HK peptides as effective carriers of siRNA |
| JP2008537752A (ja) * | 2005-04-12 | 2008-09-25 | イントラディグム コーポレイション | がんおよび他の新血管形成疾患を処置するためのＲＮＡｉ治療用の組成物および方法 |
| US7893244B2 (en) * | 2005-04-12 | 2011-02-22 | Intradigm Corporation | Composition and methods of RNAi therapeutics for treatment of cancer and other neovascularization diseases |
| EP1714970A1 (en) | 2005-04-22 | 2006-10-25 | Universität des Saarlandes | Use of inhibitors of RNAse A-family enzymes for stabilizing oligonucleotides having RNA interfering activity |
| CN100374573C (zh) | 2006-04-14 | 2008-03-12 | 中国医学科学院医药生物技术研究所 | 一种可稳定表达VEGF shRNA的载体pCD-VEGF |
| WO2008045576A2 (en) | 2006-10-12 | 2008-04-17 | Yijia Liu | Compositions and methods of rnai therapeutics for treatment of cancer and other neovascularization diseases |
| WO2009051659A2 (en) | 2007-10-12 | 2009-04-23 | Intradigm Corporation | Therapeutic sirna molecules for reducing vegfr1 expression in vitro and in vivo |
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- 2006-04-12 SG SG201002548-4A patent/SG161267A1/en unknown
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| JP2008537752A (ja) | 2008-09-25 |
| CN101277704A (zh) | 2008-10-01 |
| WO2006110813A2 (en) | 2006-10-19 |
| US20090118208A1 (en) | 2009-05-07 |
| US7534878B2 (en) | 2009-05-19 |
| SG161267A1 (en) | 2010-05-27 |
| US20090227657A1 (en) | 2009-09-10 |
| EP1877065A2 (en) | 2008-01-16 |
| US20080220027A1 (en) | 2008-09-11 |
| US7786092B2 (en) | 2010-08-31 |
| US7893243B2 (en) | 2011-02-22 |
| CA2604441A1 (en) | 2006-10-19 |
| US20080153771A1 (en) | 2008-06-26 |
| WO2006110813A3 (en) | 2007-11-15 |
| US7723316B2 (en) | 2010-05-25 |
| US20080241198A1 (en) | 2008-10-02 |
| IL186578A0 (en) | 2008-01-20 |
| BRPI0610499A2 (pt) | 2010-06-22 |
| EP1877065A4 (en) | 2010-12-22 |
| KR20080041145A (ko) | 2008-05-09 |
| MX2007012766A (es) | 2008-10-01 |
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