CA2876105A1 - Inhibitors of the mir-15 family of micro-rnas - Google Patents
Inhibitors of the mir-15 family of micro-rnas Download PDFInfo
- Publication number
- CA2876105A1 CA2876105A1 CA2876105A CA2876105A CA2876105A1 CA 2876105 A1 CA2876105 A1 CA 2876105A1 CA 2876105 A CA2876105 A CA 2876105A CA 2876105 A CA2876105 A CA 2876105A CA 2876105 A1 CA2876105 A1 CA 2876105A1
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- Prior art keywords
- oligonucleotide
- mir
- nucleotides
- seq
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- Prior art date
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- Abandoned
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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| US10443044B2 (en) | 2014-04-17 | 2019-10-15 | Ips Heart | Generating cardiac progenitor cells from pluripotent stem cells using isoxazole or isoxazole like compounds |
| AU2015301221B2 (en) | 2014-08-04 | 2020-07-02 | MiRagen Therapeutics, Inc. | Inhibitors of MYH7B and uses thereof |
| RU2017105342A (ru) | 2014-08-07 | 2018-09-13 | Регулус Терапьютикс Инк. | НАЦЕЛИВАНИЕ НА микроРНК ПРИ РАССТРОЙСТВАХ ОБМЕНА ВЕЩЕСТВ |
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| WO2017219170A1 (zh) * | 2016-06-19 | 2017-12-28 | 毛侃琅 | 特异抑制人 miRNA-29a 和 miR-424 表达的慢病毒载体的构建及其应用 |
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| CN106692175A (zh) * | 2016-12-26 | 2017-05-24 | 大连医科大学附属第二医院 | miR‑665‑3p抑制物在制备防治缺血再灌注损伤药物中的应用 |
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| WO2005028648A1 (ja) | 2003-09-22 | 2005-03-31 | Aichi Prefecture | リンパ腫の病型および予後診断方法 |
| MXPA06004103A (es) | 2003-10-14 | 2006-06-27 | Novartis Ag | Microarreglo de oligonucleotido. |
| JP2007511528A (ja) | 2003-11-13 | 2007-05-10 | ボード・オブ・リージエンツ，ザ・ユニバーシテイ・オブ・テキサス・システム | 心肥大および心不全の処置としてのｔｒｐチャネル阻害方法 |
| WO2005056797A1 (en) | 2003-12-15 | 2005-06-23 | Kye-Seong Kim | Novel mirna molecules isolated from human embryonic stem cell |
| CA2554818A1 (en) | 2004-02-09 | 2005-08-25 | Thomas Jefferson University | Diagnosis and treatment of cancers with microrna located in or near cancer-associated chromosomal features |
| US20050256072A1 (en) | 2004-02-09 | 2005-11-17 | University Of Massachusetts | Dual functional oligonucleotides for use in repressing mutant gene expression |
| CA2556435C (en) | 2004-02-13 | 2014-08-12 | The Rockefeller University | Anti-microrna oligonucleotide molecules |
| US8088902B2 (en) | 2004-04-05 | 2012-01-03 | The Rockefeller University | DNA virus microRNA and methods for inhibiting same |
| US20050260648A1 (en) | 2004-04-06 | 2005-11-24 | Huffel Christophe V | Method for the determination of cellular transcriptional |
| US20060134639A1 (en) | 2004-04-06 | 2006-06-22 | Huffel Christophe V | Method for the determination of cellular transcriptional regulation |
| EP1735459B1 (en) | 2004-04-07 | 2012-01-25 | Exiqon A/S | Methods for quantification of micrornas and small interfering rnas |
| EP2290071B1 (en) | 2004-05-28 | 2014-12-31 | Asuragen, Inc. | Methods and compositions involving microRNA |
| EP2990410A1 (en) | 2004-08-10 | 2016-03-02 | Alnylam Pharmaceuticals Inc. | Chemically modified oligonucleotides |
| US7893034B2 (en) | 2004-09-02 | 2011-02-22 | Yale University | Regulation of oncogenes by microRNAs |
| FR2877350B1 (fr) | 2004-11-03 | 2010-08-27 | Centre Nat Rech Scient | IDENTIFICATION ET UTILISATION DE miRNAs IMPLIQUES DANS LA DIFFERENCIATION DE CELLULES ISSUES D'UNE LEUCEMIE MYELOIDE |
| EP2314688B1 (en) | 2004-11-12 | 2014-07-16 | Asuragen, Inc. | Methods and compositions involving miRNA and miRNA inhibitor molecules |
| US9550990B2 (en) | 2004-12-10 | 2017-01-24 | Ionis Pharmaceuticals, Inc. | Regulation of epigenetic control of gene expression |
| US20060185027A1 (en) | 2004-12-23 | 2006-08-17 | David Bartel | Systems and methods for identifying miRNA targets and for altering miRNA and target expression |
| WO2006071884A2 (en) | 2004-12-27 | 2006-07-06 | The Regents Of The University Of Michigan | Oligonucleotide based therapeutics |
| US20070099196A1 (en) | 2004-12-29 | 2007-05-03 | Sakari Kauppinen | Novel oligonucleotide compositions and probe sequences useful for detection and analysis of micrornas and their target mRNAs |
| US8071306B2 (en) | 2005-01-25 | 2011-12-06 | Merck Sharp & Dohme Corp. | Methods for quantitating small RNA molecules |
| US20070065840A1 (en) | 2005-03-23 | 2007-03-22 | Irena Naguibneva | Novel oligonucleotide compositions and probe sequences useful for detection and analysis of microRNAS and their target mRNAS |
| JP2006292367A (ja) | 2005-04-05 | 2006-10-26 | Mitsubishi Rayon Co Ltd | ｍｉＲＮＡ検出用マイクロアレイ |
| WO2006108584A2 (en) | 2005-04-15 | 2006-10-19 | Cenix Bioscience Gmbh | Human marker genes and agents for cardiovascular disorders and artherosclerosis |
| WO2006111512A1 (en) | 2005-04-19 | 2006-10-26 | Basf Plant Science Gmbh | Improved methods controlling gene expression |
| PL2002003T3 (pl) | 2005-05-27 | 2016-06-30 | Ospedale San Raffaele Srl | Wektor genetyczny zawierający mi-RNA |
| US20070054287A1 (en) | 2005-05-31 | 2007-03-08 | Applera Corporation | Method for identifying medically important cell populations using micro rna as tissue specific biomarkers |
| US20070044164A1 (en) | 2005-05-31 | 2007-02-22 | Cold Spring Harbor Laboratory | Methods for producing microRNAs |
| EP1904111A4 (en) | 2005-06-03 | 2009-08-19 | Univ Johns Hopkins | COMPOSITIONS AND METHODS FOR REDUCING MICRORNA EXPRESSION FOR THE TREATMENT OF NEOPLASIA |
| AU2006279906B2 (en) | 2005-08-10 | 2012-05-10 | Alnylam Pharmaceuticals, Inc. | Chemically modified oligonucleotides for use in modulating micro RNA and uses thereof |
| US20070213292A1 (en) | 2005-08-10 | 2007-09-13 | The Rockefeller University | Chemically modified oligonucleotides for use in modulating micro RNA and uses thereof |
| CN101426912A (zh) | 2005-08-17 | 2009-05-06 | 瑟纳治疗公司 | 介导rna干扰的化学修饰短干扰核酸分子 |
| CN103028120B (zh) | 2005-09-12 | 2015-08-12 | 俄亥俄州立大学研究基金会 | 用于诊断或治疗bcl2相关癌症的组合物和方法 |
| US20070092882A1 (en) | 2005-10-21 | 2007-04-26 | Hui Wang | Analysis of microRNA |
| EP1951263A4 (en) | 2005-11-21 | 2009-11-18 | Johnson & Johnson Res Pty Ltd | MULTITARGETING DISTURBING RNAS WITH TWO ACTIVE STRANDS AND DESIGN AND APPLICATION METHODS |
| US20070259827A1 (en) | 2006-01-25 | 2007-11-08 | University Of Massachusetts | Compositions and methods for enhancing discriminatory RNA interference |
| WO2007092181A2 (en) | 2006-01-26 | 2007-08-16 | Unversity Of Massachusetts | Compositions and methods for modulating translational repression |
| CA2638906A1 (en) | 2006-01-26 | 2007-08-16 | University Of Massachusetts | Rna interference agents for therapeutic use |
| EP2388327A1 (en) | 2006-01-27 | 2011-11-23 | Isis Pharmaceuticals, Inc. | Oligomeric compounds and compositions for the use in modulation of micrornas |
| WO2007095387A2 (en) | 2006-02-17 | 2007-08-23 | Dharmacon, Inc. | Compositions and methods for inhibiting gene silencing by rna interference |
| EP2522747A1 (en) | 2006-03-02 | 2012-11-14 | The Ohio State University | MicroRNA expression profile associated with pancreatic cancer |
| KR101407707B1 (ko) * | 2006-04-03 | 2014-06-19 | 산타리스 팔마 에이/에스 | Ａｎｔｉ-ｍｉｒｎａ 안티센스 올리고뉴클레오타이드를 함유하는 약학적 조성물 |
| US20080220423A1 (en) | 2006-05-19 | 2008-09-11 | Soren Moller | Oligonucleotide probes useful for detection and analysis of microRNA precursors |
| WO2007147067A2 (en) | 2006-06-14 | 2007-12-21 | Rosetta Inpharmatics Llc | Methods and compositions for regulating cell cycle progression |
| EP2035446A2 (en) | 2006-06-19 | 2009-03-18 | Københavns Universitet (University of Copenhagen) | Ribozyme mediated stabilization of polynucleotides |
| EP2054529B1 (en) | 2006-08-25 | 2014-03-26 | Duke University | Methods for in vivo identification of endogenous mrna targets of micrornas |
| JP2010510964A (ja) | 2006-09-19 | 2010-04-08 | アシュラジェン インコーポレイテッド | 治療的介入の標的としての、ｍｉＲ−１５、ｍｉＲ−２６、ｍｉＲ−３１、ｍｉＲ−１４５、ｍｉＲ−１４７、ｍｉＲ−１８８、ｍｉＲ−２１５、ｍｉＲ−２１６、ｍｉＲ−３３１、ｍｍｕ−ｍｉＲ−２９２−３ｐによって調節される遺伝子および経路 |
| WO2008042231A2 (en) | 2006-09-29 | 2008-04-10 | Children's Medical Center Corporation | Compositions and methods for evaluating and treating heart failure |
| WO2008043521A2 (de) | 2006-10-09 | 2008-04-17 | Julius-Maximilians-Universität Würzburg | Microrna (mirna) zur diagnose und therapie von herzerkrankungen |
| WO2008147430A2 (en) | 2006-10-11 | 2008-12-04 | Nucleonics, Inc. | Microrna-formatted multitarget interfering rna vector constructs and methods of using the same |
| AU2007323469B2 (en) | 2006-11-23 | 2014-07-24 | Guangdong Maijinjia Biotechnology Co., Ltd | Oligonucleotides for modulating target RNA activity |
| CA2671299A1 (en) | 2006-12-08 | 2008-06-19 | Asuragen, Inc. | Functions and targets of let-7 micro rnas |
| EP2104736B1 (en) | 2006-12-08 | 2011-11-23 | Asuragen, INC. | Mir-126 regulated genes and pathways as targets for therapeutic intervention |
| CA2671294A1 (en) | 2006-12-08 | 2008-06-19 | Asuragen, Inc. | Mir-21 regulated genes and pathways as targets for therapeutic intervention |
| CA2671302A1 (en) | 2006-12-08 | 2008-06-19 | Asuragen, Inc. | Mirna regulated genes and pathways as targets for therapeutic intervention |
| US20090137504A1 (en) | 2006-12-21 | 2009-05-28 | Soren Morgenthaler Echwald | Microrna target site blocking oligos and uses thereof |
| EP3536788A1 (en) | 2006-12-21 | 2019-09-11 | QIAGEN GmbH | Microrna target site blocking oligos and uses thereof |
| US20090175827A1 (en) | 2006-12-29 | 2009-07-09 | Byrom Mike W | miR-16 REGULATED GENES AND PATHWAYS AS TARGETS FOR THERAPEUTIC INTERVENTION |
| WO2008109373A1 (en) | 2007-03-02 | 2008-09-12 | Mdrna, Inc. | Nucleic acid compounds for inhibiting erbb gene expression and uses thereof |
| WO2008112226A2 (en) | 2007-03-13 | 2008-09-18 | Massachusetts Institute Of Technology | Cre-lox based gene knockdown constructs and methods of use thereof |
| US8288358B2 (en) | 2007-03-26 | 2012-10-16 | Newcastle Innovation Ltd. | Therapeutic targets and molecules |
| US8841267B2 (en) | 2007-05-23 | 2014-09-23 | Ge Healthcare Dharmacon, Inc. | Micro-RNA scaffolds, non-naturally occurring micro-RNAs, and methods for optimizing non-naturally occurring micro-RNAs |
| KR20100049079A (ko) | 2007-07-18 | 2010-05-11 | 더 리젠트스 오브 더 유니버시티 오브 콜로라도 | 인간의 정상 심장과 기능부진 심장에서 마이크로 ｒｎａ의 차등 발현 |
| WO2009012263A2 (en) | 2007-07-18 | 2009-01-22 | The Trustees Of Columbia University In The City Of New York | Tissue-specific micrornas and compositions and uses thereof |
| US20090092980A1 (en) | 2007-07-20 | 2009-04-09 | Christoph Arenz | miRNA PROCESSING INHIBITOR EFFICACY ASSAYS AND SUBSTANCES |
| WO2009044895A1 (ja) | 2007-10-03 | 2009-04-09 | Kyowa Hakko Kirin Co., Ltd. | 標的遺伝子の発現を抑制する組成物 |
| US8288356B2 (en) | 2007-10-04 | 2012-10-16 | Santaris Pharma A/S | MicroRNAs |
| WO2009058818A2 (en) | 2007-10-29 | 2009-05-07 | The Board Of Regents Of The University Of Texas System | Compositions comprising a micro-rna and methods of their use in regulating cardiac remodeling |
| JP2011517279A (ja) | 2007-10-29 | 2011-06-02 | ユニバーシティ オブ マサチューセッツ | 核酸（ｓｉＲＮＡ）送達用の酵母細胞壁粒子（ＹＣＷＰ）多層状ナノ粒子 |
| CA2705325C (en) | 2007-11-09 | 2016-11-01 | The Board Of Regents Of The University Of Texas System | Micro-rnas of the mir-15 family modulate cardiomyocyte survival and cardiac repair |
| KR101026502B1 (ko) * | 2007-11-23 | 2011-04-01 | 주식회사 파나진 | 마이크로ｒｎａ 안티센스 ｐｎａ, 그를 포함하는 조성물, 및 그의 사용 및 평가 방법 |
| EP2268811A1 (en) | 2008-03-07 | 2011-01-05 | Santaris Pharma A/S | Pharmaceutical compositions for treatment of microrna related diseases |
| EP2105145A1 (en) | 2008-03-27 | 2009-09-30 | ETH Zürich | Method for muscle-specific delivery lipid-conjugated oligonucleotides |
| WO2009121031A1 (en) | 2008-03-27 | 2009-10-01 | Vascular Biosciences, Inc. | Methods of novel therapeutic candidate identification through gene expression analysis in vascular-related diseases |
| US20090326049A1 (en) | 2008-04-04 | 2009-12-31 | Alexander Aristarkhov | Blocking oligos for inhibition of microrna and sirna activity and uses thereof |
| US20100113284A1 (en) | 2008-04-04 | 2010-05-06 | Alexander Aristarkhov | Small interfering rna (sirna) target site blocking oligos and uses thereof |
| EP2285960B1 (en) | 2008-05-08 | 2015-07-08 | Asuragen, INC. | Compositions and methods related to mir-184 modulation of neovascularization or angiogenesis |
| CA2726052A1 (en) | 2008-06-04 | 2009-12-10 | The Board Of Regents Of The University Of Texas System | Modulation of gene expression through endogenous small rna targeting of gene promoters |
| WO2010036939A2 (en) | 2008-09-26 | 2010-04-01 | University Of Southern California | A system for synergistic expression of multiple small functional rna elements |
| WO2010048585A2 (en) | 2008-10-24 | 2010-04-29 | Isis Pharmaceuticals, Inc. | Oligomeric compounds and methods |
| WO2010126355A1 (en) | 2009-04-29 | 2010-11-04 | Academisch Medisch Centrum Bij De Universiteit Van Amsterdam | Means and methods for counteracting, preventing and/or determining heart failure, or a risk of heart failure |
| SG176716A1 (en) | 2009-06-08 | 2012-01-30 | Miragen Therapeutics | CHEMICAL MODIFICATION MOTIFS FOR miRNA INHIBITORS AND MIMETICS |
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- 2013-06-19 US US13/921,537 patent/US9163235B2/en not_active Expired - Fee Related
- 2013-06-21 EP EP13806131.2A patent/EP2863956A4/en not_active Withdrawn
- 2013-06-21 MX MX2014015641A patent/MX2014015641A/es unknown
- 2013-06-21 IN IN10899DEN2014 patent/IN2014DN10899A/en unknown
- 2013-06-21 HK HK15110356.0A patent/HK1209621A1/xx unknown
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- 2013-06-21 CN CN201380039961.7A patent/CN104540527A/zh active Pending
- 2013-06-21 CA CA2876105A patent/CA2876105A1/en not_active Abandoned
- 2013-06-21 WO PCT/US2013/046960 patent/WO2013192486A1/en not_active Ceased
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- 2013-06-21 EA EA201590070A patent/EA201590070A1/ru unknown
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- 2013-06-21 SG SG11201408460UA patent/SG11201408460UA/en unknown
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- 2013-06-21 TW TW102122289A patent/TW201406774A/zh unknown
- 2013-06-21 KR KR1020157001535A patent/KR20150036140A/ko not_active Withdrawn
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| BR112014032239A2 (pt) | 2017-08-01 |
| MX2014015641A (es) | 2015-07-14 |
| US20130345288A1 (en) | 2013-12-26 |
| CN104540527A (zh) | 2015-04-22 |
| IN2014DN10899A (enExample) | 2015-09-11 |
| MD20150006A2 (ro) | 2015-06-30 |
| WO2013192486A1 (en) | 2013-12-27 |
| SG11201408460UA (en) | 2015-01-29 |
| AR091539A1 (es) | 2015-02-11 |
| HK1209621A1 (en) | 2016-04-08 |
| EP2863956A1 (en) | 2015-04-29 |
| TW201406774A (zh) | 2014-02-16 |
| EP2863956A4 (en) | 2016-01-20 |
| EA201590070A1 (ru) | 2015-04-30 |
| US9163235B2 (en) | 2015-10-20 |
| AU2013277033A1 (en) | 2015-01-22 |
| KR20150036140A (ko) | 2015-04-07 |
| JP2015525081A (ja) | 2015-09-03 |
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