MX2011005851A - Composiciones y metodos para la inhibicion selectiva de isoformas vegf proangiogenicas. - Google Patents
Composiciones y metodos para la inhibicion selectiva de isoformas vegf proangiogenicas.Info
- Publication number
- MX2011005851A MX2011005851A MX2011005851A MX2011005851A MX2011005851A MX 2011005851 A MX2011005851 A MX 2011005851A MX 2011005851 A MX2011005851 A MX 2011005851A MX 2011005851 A MX2011005851 A MX 2011005851A MX 2011005851 A MX2011005851 A MX 2011005851A
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- seq
- sirna
- vegf
- rna
- human
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| US11977908P | 2008-12-04 | 2008-12-04 | |
| US17157109P | 2009-04-22 | 2009-04-22 | |
| US21980809P | 2009-06-24 | 2009-06-24 | |
| PCT/US2009/066741 WO2010065834A1 (en) | 2008-12-04 | 2009-12-04 | Compositions and methods for selective inhibition of pro-angiogenic vegf isoforms |
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| MX2011005851A true MX2011005851A (es) | 2011-07-29 |
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| MX2011005851A MX2011005851A (es) | 2008-12-04 | 2009-12-04 | Composiciones y metodos para la inhibicion selectiva de isoformas vegf proangiogenicas. |
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| US (1) | US8470792B2 (https=) |
| EP (1) | EP2361306A1 (https=) |
| JP (1) | JP5832293B2 (https=) |
| KR (1) | KR20110094323A (https=) |
| AU (1) | AU2009322279A1 (https=) |
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| MX (1) | MX2011005851A (https=) |
| NZ (1) | NZ593743A (https=) |
| SG (1) | SG171952A1 (https=) |
| WO (1) | WO2010065834A1 (https=) |
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| CA2746527A1 (en) | 2008-09-22 | 2010-03-25 | Rxi Pharmaceuticals Corporation | Rna interference in skin indications |
| US9745574B2 (en) | 2009-02-04 | 2017-08-29 | Rxi Pharmaceuticals Corporation | RNA duplexes with single stranded phosphorothioate nucleotide regions for additional functionality |
| RU2012127772A (ru) * | 2009-12-04 | 2014-01-10 | ОПКО ОФТЭЛМИКС, ЭлЭлСи | Композиции и способы для ингибирования vegf |
| US9080171B2 (en) | 2010-03-24 | 2015-07-14 | RXi Parmaceuticals Corporation | Reduced size self-delivering RNAi compounds |
| CN106074591B (zh) | 2010-03-24 | 2020-01-14 | 菲奥医药公司 | 眼部症候中的rna干扰 |
| RU2013102545A (ru) * | 2010-07-28 | 2014-09-10 | Алкон Ресерч, Лтд. | Связывающая vegfa си-рнк и способы лечения in vivo |
| EP2628482A1 (en) * | 2012-02-17 | 2013-08-21 | Academisch Medisch Centrum | Rho kinase inhiitors for use in the treatment of neuroblastoma |
| KR102083700B1 (ko) * | 2012-08-21 | 2020-03-02 | 옵코 파마슈티칼스, 엘엘씨 | 리포좀 제제 |
| CN105143450A (zh) | 2013-01-08 | 2015-12-09 | 贝尼泰克生物制药有限公司 | 年龄相关性黄斑变性治疗 |
| WO2015084897A2 (en) | 2013-12-02 | 2015-06-11 | Mirimmune, Llc | Immunotherapy of cancer |
| US11279934B2 (en) | 2014-04-28 | 2022-03-22 | Phio Pharmaceuticals Corp. | Methods for treating cancer using nucleic acids targeting MDM2 or MYCN |
| CN104267188B (zh) * | 2014-08-28 | 2015-12-30 | 汪建平 | 针对msk1基因的相关制剂在制备5-fu耐药性检测试剂及5-fu耐药逆转剂方面的应用 |
| KR102506169B1 (ko) | 2014-09-05 | 2023-03-08 | 피오 파마슈티칼스 코프. | Tyr 또는 mmp1을 표적화하는 핵산을 사용한 노화 및 피부 장애의 치료 방법 |
| WO2018195355A1 (en) | 2017-04-19 | 2018-10-25 | Rxi Pharmaceuticals Corporation | Topical delivery of nucleic acid compounds |
Family Cites Families (114)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4235871A (en) | 1978-02-24 | 1980-11-25 | Papahadjopoulos Demetrios P | Method of encapsulating biologically active materials in lipid vesicles |
| US4394448A (en) | 1978-02-24 | 1983-07-19 | Szoka Jr Francis C | Method of inserting DNA into living cells |
| US4670388A (en) | 1982-12-30 | 1987-06-02 | Carnegie Institution Of Washington | Method of incorporating DNA into genome of drosophila |
| US4501728A (en) | 1983-01-06 | 1985-02-26 | Technology Unlimited, Inc. | Masking of liposomes from RES recognition |
| US5019369A (en) | 1984-10-22 | 1991-05-28 | Vestar, Inc. | Method of targeting tumors in humans |
| US5545412A (en) | 1985-01-07 | 1996-08-13 | Syntex (U.S.A.) Inc. | N-[1, (1-1)-dialkyloxy]-and N-[1, (1-1)-dialkenyloxy]-alk-1-yl-n,n,n-tetrasubstituted ammonium lipids and uses therefor |
| US5139941A (en) | 1985-10-31 | 1992-08-18 | University Of Florida Research Foundation, Inc. | AAV transduction vectors |
| US4837028A (en) | 1986-12-24 | 1989-06-06 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
| US4920016A (en) | 1986-12-24 | 1990-04-24 | Linear Technology, Inc. | Liposomes with enhanced circulation time |
| US5712257A (en) | 1987-08-12 | 1998-01-27 | Hem Research, Inc. | Topically active compositions of mismatched dsRNAs |
| IE72103B1 (en) | 1987-08-12 | 1997-03-12 | Hem Res Inc | Promotion of host defense by systemic dsRNA treatment |
| US5683986A (en) | 1987-08-12 | 1997-11-04 | Hemispherx Biopharma Inc. | Elaboration of host defense mediators into biological fluids by systemic dsRNA treatment |
| US5703055A (en) | 1989-03-21 | 1997-12-30 | Wisconsin Alumni Research Foundation | Generation of antibodies through lipid mediated DNA delivery |
| US5498521A (en) | 1990-01-24 | 1996-03-12 | President And Fellows Of Harvard College | Diagnosis of hereditary retinal degenerative diseases |
| US5843738A (en) | 1990-08-14 | 1998-12-01 | Isis Pharmaceuticals, Inc. | Oligonucleotide modulation of cell adhesion |
| US5252479A (en) | 1991-11-08 | 1993-10-12 | Research Corporation Technologies, Inc. | Safe vector for gene therapy |
| US5322933A (en) | 1992-05-07 | 1994-06-21 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Crystal structure of TGF-β-2 |
| US5587308A (en) | 1992-06-02 | 1996-12-24 | The United States Of America As Represented By The Department Of Health & Human Services | Modified adeno-associated virus vector capable of expression from a novel promoter |
| EP0669987B1 (en) | 1992-09-25 | 2008-08-13 | Aventis Pharma S.A. | Adenovirus vectors for the transfer of foreign genes into cells of the central nervous system, particularly in brain |
| US6177401B1 (en) | 1992-11-13 | 2001-01-23 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften | Use of organic compounds for the inhibition of Flk-1 mediated vasculogenesis and angiogenesis |
| US5478745A (en) | 1992-12-04 | 1995-12-26 | University Of Pittsburgh | Recombinant viral vector system |
| GB9308271D0 (en) | 1993-04-21 | 1993-06-02 | Univ Edinburgh | Method of isolating and/or enriching and/or selectively propagating pluripotential animal cells and animals for use in said method |
| CA2164088C (en) | 1993-06-07 | 2005-06-14 | Gary J. Nabel | Plasmids suitable for gene therapy |
| US5639872A (en) | 1993-07-27 | 1997-06-17 | Hybridon, Inc. | Human VEGF-specific oligonucleotides |
| US6410322B1 (en) | 1993-07-27 | 2002-06-25 | Hybridon Inc | Antisense oligonucleotide inhibition of vascular endothelial growth factor expression |
| US5731294A (en) | 1993-07-27 | 1998-03-24 | Hybridon, Inc. | Inhibition of neovasularization using VEGF-specific oligonucleotides |
| US5624803A (en) | 1993-10-14 | 1997-04-29 | The Regents Of The University Of California | In vivo oligonucleotide generator, and methods of testing the binding affinity of triplex forming oligonucleotides derived therefrom |
| US6037329A (en) | 1994-03-15 | 2000-03-14 | Selective Genetics, Inc. | Compositions containing nucleic acids and ligands for therapeutic treatment |
| US5728068A (en) | 1994-06-14 | 1998-03-17 | Cordis Corporation | Multi-purpose balloon catheter |
| US5505700A (en) | 1994-06-14 | 1996-04-09 | Cordis Corporation | Electro-osmotic infusion catheter |
| US6057119A (en) | 1994-06-17 | 2000-05-02 | Vertex Pharmaceuticals, Incorporated | Crystal structure and mutants of interleukin-1β converting enzyme |
| US6150092A (en) | 1994-06-27 | 2000-11-21 | Taogosei Company, Ltd. | Antisense nucleic acid compound targeted to VEGF |
| US5882914A (en) | 1995-06-06 | 1999-03-16 | The Johns Hopkins University School Of Medicine | Nucleic acids encoding the hypoxia inducible factor-1 |
| CA2225460A1 (en) | 1995-06-23 | 1997-01-09 | Winston Campbell Patterson | Transcriptional regulation of genes encoding vascular endothelial growth factor receptors |
| US20030216335A1 (en) | 2001-11-30 | 2003-11-20 | Jennifer Lockridge | Method and reagent for the modulation of female reproductive diseases and conditions |
| WO1997018855A1 (en) | 1995-11-21 | 1997-05-29 | Eduard Naumovich Lerner | Device for enhanced delivery of biologically active substances and compounds in an organism |
| GB9524807D0 (en) | 1995-12-05 | 1996-02-07 | Smithkline Beecham Plc | Novel compounds |
| WO1998019847A1 (de) | 1996-11-01 | 1998-05-14 | Stern Christian Rene | Spritzgussdüse |
| US5843016A (en) | 1996-03-18 | 1998-12-01 | Physion S.R.L. | Electromotive drug administration for treatment of acute urinary outflow obstruction |
| US7033598B2 (en) | 1996-11-19 | 2006-04-25 | Intrabrain International N.V. | Methods and apparatus for enhanced and controlled delivery of a biologically active agent into the central nervous system of a mammal |
| US6165709A (en) | 1997-02-28 | 2000-12-26 | Fred Hutchinson Cancer Research Center | Methods for drug target screening |
| US6225291B1 (en) | 1997-04-21 | 2001-05-01 | University Of Florida | Rod opsin mRNA-specific ribozyme compositions and methods for the treatment of retinal diseases |
| US20050096282A1 (en) | 1997-04-21 | 2005-05-05 | Lewin Alfred S. | Adeno-associated virus-delivered ribozyme compositions and methods for the treatment of retinal diseases |
| AU3176097A (en) | 1997-06-13 | 1998-12-30 | Medinova Medical Consulting Gmbh | Drug targeting system, method of its preparation and its use |
| US5902598A (en) | 1997-08-28 | 1999-05-11 | Control Delivery Systems, Inc. | Sustained release drug delivery devices |
| US6440933B1 (en) | 1997-09-10 | 2002-08-27 | University Of Florida | Compounds and method for the prevention and treatment of diabetic retinopathy |
| US6506559B1 (en) | 1997-12-23 | 2003-01-14 | Carnegie Institute Of Washington | Genetic inhibition by double-stranded RNA |
| US6479729B1 (en) * | 1998-02-06 | 2002-11-12 | The Johns Hopkins University | Mouse model for ocular neovascularization |
| US20030096775A1 (en) | 2001-10-23 | 2003-05-22 | Isis Pharmaceuticals Inc. | Antisense modulation of complement component C3 expression |
| US6433145B1 (en) | 1998-07-21 | 2002-08-13 | Human Genome Sciences, Inc. | Keratinocyte derived interferon |
| EP0979869A1 (en) | 1998-08-07 | 2000-02-16 | Hoechst Marion Roussel Deutschland GmbH | Short oligonucleotides for the inhibition of VEGF expression |
| US6219557B1 (en) | 1998-12-11 | 2001-04-17 | Ericsson Inc. | System and method for providing location services in parallel to existing services in general packet radio services architecture |
| EP2314700A1 (en) | 1999-01-28 | 2011-04-27 | Medical College of Georgia Research Institute, Inc | Composition and method for in vivo and in vitro attenuation of gene expression using double stranded RNA |
| DE19956568A1 (de) | 1999-01-30 | 2000-08-17 | Roland Kreutzer | Verfahren und Medikament zur Hemmung der Expression eines vorgegebenen Gens |
| CA2361421A1 (en) | 1999-02-03 | 2000-08-10 | Biosante Pharmaceuticals, Inc. | Therapeutic calcium phosphate particles and methods of manufacture and use |
| US6121000A (en) | 1999-02-11 | 2000-09-19 | Genesense Technologies, Inc. | Antitumor antisense sequences directed against R1 and R2 components of ribonucleotide reductase |
| WO2000063364A2 (en) | 1999-04-21 | 2000-10-26 | American Home Products Corporation | Methods and compositions for inhibiting the function of polynucleotide sequences |
| US6331313B1 (en) | 1999-10-22 | 2001-12-18 | Oculex Pharmaceticals, Inc. | Controlled-release biocompatible ocular drug delivery implant devices and methods |
| GB9927444D0 (en) | 1999-11-19 | 2000-01-19 | Cancer Res Campaign Tech | Inhibiting gene expression |
| DE10160151A1 (de) | 2001-01-09 | 2003-06-26 | Ribopharma Ag | Verfahren zur Hemmung der Expression eines vorgegebenen Zielgens |
| DE10100586C1 (de) | 2001-01-09 | 2002-04-11 | Ribopharma Ag | Verfahren zur Hemmung der Expression eines Ziegens |
| 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 |
| WO2001057206A2 (en) | 2000-02-03 | 2001-08-09 | Ribozyme Pharmaceuticals, Inc. | Method and reagent for the inhibition of checkpoint kinase-1 (chk 1) enzyme |
| EP1272630A2 (en) | 2000-03-16 | 2003-01-08 | Genetica, Inc. | Methods and compositions for rna interference |
| PT1309726E (pt) | 2000-03-30 | 2010-03-08 | Whitehead Biomedical Inst | Mediadores de interferência por rna específicos de sequência de rna |
| WO2001077350A2 (en) | 2000-04-07 | 2001-10-18 | Large Scale Biology Corporation | Compositions and methods for inhibiting gene expression |
| US6372250B1 (en) | 2000-04-25 | 2002-04-16 | The Regents Of The University Of California | Non-invasive gene targeting to the brain |
| US6375972B1 (en) | 2000-04-26 | 2002-04-23 | Control Delivery Systems, Inc. | Sustained release drug delivery devices, methods of use, and methods of manufacturing thereof |
| WO2001083729A2 (en) | 2000-05-01 | 2001-11-08 | Novartis Ag | Vectors for ocular transduction and use thereof for genetic therapy |
| EP1292606A4 (en) | 2000-06-23 | 2004-03-24 | Yissum Res Dev Co | POSITIVELY CHARGED PEPTIDIC NUCLEIC ACID ANALOGS WITH IMPROVED PROPERTIES |
| US6852510B2 (en) | 2000-07-03 | 2005-02-08 | Gala Design Inc | Host cells containing multiple integrating vectors |
| CA2416676A1 (en) | 2000-07-21 | 2002-01-31 | The Trustees Of Columbia University In The City Of New York | Nucleic acids comprising regions of the rat peg-3 promoter and uses thereof |
| US20020132788A1 (en) | 2000-11-06 | 2002-09-19 | David Lewis | Inhibition of gene expression by delivery of small interfering RNA to post-embryonic animal cells in vivo |
| US20020173478A1 (en) | 2000-11-14 | 2002-11-21 | The Trustees Of The University Of Pennsylvania | Post-transcriptional gene silencing by RNAi in mammalian cells |
| US20040259247A1 (en) | 2000-12-01 | 2004-12-23 | Thomas Tuschl | Rna interference mediating small rna molecules |
| EP1229134A3 (en) | 2001-01-31 | 2004-01-28 | Nucleonics, Inc | Use of post-transcriptional gene silencing for identifying nucleic acid sequences that modulate the function of a cell |
| US20020165158A1 (en) | 2001-03-27 | 2002-11-07 | King George L. | Methods of modulating angiogenesis |
| JP2002305193A (ja) | 2001-04-05 | 2002-10-18 | Sony Corp | 半導体装置とその製造方法 |
| US20030045830A1 (en) | 2001-04-17 | 2003-03-06 | De Bizemont Therese | Gene therapy with chimeric oligonucleotides delivered by a method comprising a step of iontophoresis |
| 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) |
| 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) |
| 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) |
| US20050159380A1 (en) | 2001-05-18 | 2005-07-21 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of angiopoietin gene expression using short interfering nucleic acid (siNA) |
| US20050048529A1 (en) | 2002-02-20 | 2005-03-03 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of intercellular adhesion molecule (ICAM) gene expression using short interfering nucleic acid (siNA) |
| US20050187174A1 (en) | 2001-05-18 | 2005-08-25 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of intercellular adhesion molecule (ICAM) gene expression using short interfering nucleic acid (siNA) |
| EP1401884A1 (en) | 2001-05-29 | 2004-03-31 | Union Carbide Chemicals & Plastics Technology Corporation | Olefin polymerization catalyst compositions and method of preperation |
| CA2448320A1 (en) | 2001-05-29 | 2002-12-05 | Sirna Therapeutics, Inc. | Ribozyme based treatment of female reproductive diseases |
| US20040028613A1 (en) | 2001-06-25 | 2004-02-12 | Nastech Pharmaceutical Company Inc | Dopamine agonist formulations for enhanced central nervous system delivery |
| ES2386775T3 (es) | 2001-07-23 | 2012-08-30 | The Board Of Trustees Of The Leland Stanford Junior University | Procedimientos y composiciones para la inhibición mediada por ARNi de la expresión génica en mamíferos |
| US7820178B2 (en) | 2001-08-01 | 2010-10-26 | University of Brisol | VEGF isoforms and their use as anti-angiogenic, anti-vasodilatory, anti-permeability and anti-proliferative agents |
| 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 |
| AU2002343792A1 (en) | 2001-11-28 | 2003-06-10 | Center For Advanced Science And Technology Incubation, Ltd. | siRNA EXPRESSION SYSTEM AND PROCESS FOR PRODUCING FUNCTIONAL GENE-KNOCKDOWN CELLS AND THE LIKE USING THE SAME |
| US7176303B2 (en) * | 2003-11-06 | 2007-02-13 | Isis Pharmaceuticals, Inc. | Modulation of STAT5 expression |
| WO2003085110A2 (en) | 2002-04-05 | 2003-10-16 | Santaris Pharma A/S | Oligomeric compounds for the modulation hif-1alpha expression |
| 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 |
| US7199107B2 (en) * | 2002-05-23 | 2007-04-03 | Isis Pharmaceuticals, Inc. | Antisense modulation of kinesin-like 1 expression |
| WO2003099298A1 (en) | 2002-05-24 | 2003-12-04 | Max-Planck Gesellschaft zur Förderung der Wissenschaften e.V. | Rna interference mediating small rna molecules |
| US20040115640A1 (en) | 2002-12-11 | 2004-06-17 | Isis Pharmaceuticals Inc. | Modulation of angiopoietin-2 expression |
| US7148342B2 (en) | 2002-07-24 | 2006-12-12 | The Trustees Of The University Of Pennyslvania | Compositions and methods for sirna inhibition of angiogenesis |
| CN1720257A (zh) | 2002-08-06 | 2006-01-11 | 因特拉迪格姆公司 | 通过导入干扰rna在体内下调靶基因表达的方法 |
| NZ540779A (en) | 2002-11-01 | 2008-05-30 | Univ Pennsylvania | Compositions and methods for siRNA inhibition of HIF-1 alpha |
| EP2305812A3 (en) | 2002-11-14 | 2012-06-06 | Dharmacon, Inc. | Fuctional and hyperfunctional sirna |
| DE602004028587D1 (de) | 2003-01-16 | 2010-09-23 | Univ Pennsylvania | ZUSAMMENSETZUNGEN UND VERFAHREN ZUR siRNA-HEMMUNG VON ICAM-1 |
| CA2522730A1 (en) | 2003-04-18 | 2004-11-04 | The Trustees Of The University Of Pennsylvania | Compositions and methods for sirna inhibition of angiopoietin 1 and 2 and their receptor tie2 |
| 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 |
| US7468431B2 (en) * | 2004-01-22 | 2008-12-23 | Isis Pharmaceuticals, Inc. | Modulation of eIF4E-BP2 expression |
| AU2005222902B2 (en) | 2004-03-12 | 2010-06-10 | Alnylam Pharmaceuticals, Inc. | iRNA agents targeting VEGF |
| US20060182783A1 (en) | 2004-04-30 | 2006-08-17 | Allergan, Inc. | Sustained release intraocular drug delivery systems |
| 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 |
| ATE466081T1 (de) | 2005-12-22 | 2010-05-15 | Opko Ophthalmics Llc | Zusammensetzungen und verfahren zur regulierung eines komplementsystems |
| EP1982176A1 (en) | 2006-01-30 | 2008-10-22 | Dako Denmark A/S | High-speed quantification of antigen specific t-cells in whole blood by flow cytometry |
| PT2029746E (pt) * | 2006-06-12 | 2012-10-15 | Exegenics Inc D B A Opko Health Inc | Composições e métodos para a inibição do sirna de angiogenese |
| US7872118B2 (en) * | 2006-09-08 | 2011-01-18 | Opko Ophthalmics, Llc | siRNA and methods of manufacture |
| GB0704678D0 (en) * | 2007-03-09 | 2007-04-18 | Univ Bristol | Pro- and anti-angiogenic treatments |
-
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- 2009-12-04 US US12/631,078 patent/US8470792B2/en not_active Expired - Fee Related
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2011
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| EP2361306A1 (en) | 2011-08-31 |
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| AU2009322279A1 (en) | 2011-07-14 |
| JP5832293B2 (ja) | 2015-12-16 |
| US20100151007A1 (en) | 2010-06-17 |
| KR20110094323A (ko) | 2011-08-23 |
| CA2745832A1 (en) | 2010-06-10 |
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