CA2902623A1 - Locked nucleic acid inhibitor of mir-145 and uses thereof - Google Patents
Locked nucleic acid inhibitor of mir-145 and uses thereof Download PDFInfo
- Publication number
- CA2902623A1 CA2902623A1 CA2902623A CA2902623A CA2902623A1 CA 2902623 A1 CA2902623 A1 CA 2902623A1 CA 2902623 A CA2902623 A CA 2902623A CA 2902623 A CA2902623 A CA 2902623A CA 2902623 A1 CA2902623 A1 CA 2902623A1
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- Prior art keywords
- oligonucleotide
- mir
- mer
- cell
- lnas
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- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/32—Chemical structure of the sugar
- C12N2310/322—2'-R Modification
-
- C—CHEMISTRY; METALLURGY
- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/32—Chemical structure of the sugar
- C12N2310/323—Chemical structure of the sugar modified ring structure
- C12N2310/3231—Chemical structure of the sugar modified ring structure having an additional ring, e.g. LNA, ENA
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Engineering & Computer Science (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Microbiology (AREA)
- Epidemiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pulmonology (AREA)
- Cardiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361800755P | 2013-03-15 | 2013-03-15 | |
| US61/800,755 | 2013-03-15 | ||
| PCT/US2014/026538 WO2014151835A1 (en) | 2013-03-15 | 2014-03-13 | Locked nucleic acid inhibitor of mir-145 and uses thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2902623A1 true CA2902623A1 (en) | 2014-09-25 |
Family
ID=51581048
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2902623A Abandoned CA2902623A1 (en) | 2013-03-15 | 2014-03-13 | Locked nucleic acid inhibitor of mir-145 and uses thereof |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US9752143B2 (enExample) |
| EP (1) | EP2968396B1 (enExample) |
| JP (1) | JP6410791B2 (enExample) |
| CN (1) | CN105188715B (enExample) |
| CA (1) | CA2902623A1 (enExample) |
| WO (1) | WO2014151835A1 (enExample) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US11241296B2 (en) | 2005-11-17 | 2022-02-08 | Breast-Med, Inc. | Imaging fiducial markers and methods |
| WO2017184751A1 (en) * | 2016-04-20 | 2017-10-26 | Arizona Board Of Regents On Behalf Of The University Of Arizona | Compositions and methods for treating and preventing hypertension |
| CN110088278B (zh) * | 2016-10-31 | 2023-08-11 | e-NA生物科技公司 | 双链核酸分子及其用途 |
| JP2024504679A (ja) * | 2021-01-18 | 2024-02-01 | リジェン イノファーム インコーポレイテッド | ｍｉＲ１４５阻害剤を有効成分として含む心筋梗塞の治療用組成物 |
| WO2025008641A2 (en) * | 2023-07-06 | 2025-01-09 | Imperial College Innovations Limited | Rna molecule |
Family Cites Families (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995003843A1 (en) | 1993-07-30 | 1995-02-09 | The Regents Of The University Of California | Endocardial infusion catheter |
| US5837533A (en) | 1994-09-28 | 1998-11-17 | American Home Products Corporation | Complexes comprising a nucleic acid bound to a cationic polyamine having an endosome disruption agent |
| US7803782B2 (en) | 2003-05-28 | 2010-09-28 | Roche Madison Inc. | Intravenous delivery of polynucleotides to cells in mammalian limb |
| JP3756313B2 (ja) | 1997-03-07 | 2006-03-15 | 武 今西 | 新規ビシクロヌクレオシド及びオリゴヌクレオチド類縁体 |
| US6770748B2 (en) | 1997-03-07 | 2004-08-03 | Takeshi Imanishi | Bicyclonucleoside and oligonucleotide analogue |
| US6416510B1 (en) | 1997-03-13 | 2002-07-09 | Biocardia, Inc. | Drug delivery catheters that attach to tissue and methods for their use |
| US6794499B2 (en) | 1997-09-12 | 2004-09-21 | Exiqon A/S | Oligonucleotide analogues |
| US6749617B1 (en) | 1997-11-04 | 2004-06-15 | Scimed Life Systems, Inc. | Catheter and implants for the delivery of therapeutic agents to tissues |
| SI20474A (sl) | 1998-05-26 | 2001-08-31 | Icn Pharmaceuticals, Inc. | Novi nukleozidi, ki imajo bicikličen sladkorni del |
| US6833361B2 (en) | 1998-05-26 | 2004-12-21 | Ribapharm, Inc. | Nucleosides having bicyclic sugar moiety |
| HK1048339A1 (zh) | 1999-03-18 | 2003-03-28 | 埃克西库恩公司 | 利用特异性lna引物检测基因突变 |
| DK1334109T3 (da) | 2000-10-04 | 2006-10-09 | Santaris Pharma As | Forbedret syntese af purin-blokerede nukleinsyre-analoger |
| US20050124566A1 (en) | 2001-05-18 | 2005-06-09 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of myostatin gene expression using short interfering nucleic acid (siNA) |
| EP2390328A1 (en) | 2001-09-28 | 2011-11-30 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | MicroRNA molecules |
| US7781415B2 (en) | 2003-02-07 | 2010-08-24 | Roche Madison Inc. | Process for delivering sirna to cardiac muscle tissue |
| KR20050115231A (ko) | 2003-02-10 | 2005-12-07 | 내셔날 인스티튜트 오브 어드밴스드 인더스트리얼 사이언스 앤드 테크놀로지 | 포유동물 세포의 조절 |
| EP1648914A4 (en) | 2003-07-31 | 2009-12-16 | Regulus Therapeutics Inc | OLIGOMERIC COMPOUNDS AND COMPOSITIONS USEFUL FOR MODULATING SMALL NON-CODING RNA |
| US7722596B2 (en) | 2004-02-26 | 2010-05-25 | Osprey Medical, Inc. | Regional cardiac tissue treatment |
| US20070203445A1 (en) | 2004-02-26 | 2007-08-30 | V-Kardia Pty Ltd | Isolating cardiac circulation |
| BRPI0508073A (pt) | 2004-02-26 | 2007-07-17 | Kardia Pty Ltd V | método e aparelho para isolar substancialmente circulação cardìaca da circulação sistêmica aparelho para perfundir o coração com um agente terapêutico, cateter de obstrução para obstruir fluxo entre um vaso principal e um ou mais vasos ramificados, método para administrar um agente terapêutico ao coração e estrutura de suporte percutaneamente administrável para manter patência do sinus coronário |
| EP2314688B1 (en) | 2004-11-12 | 2014-07-16 | Asuragen, Inc. | Methods and compositions involving miRNA and miRNA inhibitor molecules |
| US7404969B2 (en) | 2005-02-14 | 2008-07-29 | Sirna Therapeutics, Inc. | Lipid nanoparticle based compositions and methods for the delivery of biologically active molecules |
| WO2006089340A2 (en) | 2005-02-23 | 2006-08-31 | V-Kardia Pty Ltd | Polynucleotide delivery to cardiac tissue |
| WO2006107826A2 (en) | 2005-04-04 | 2006-10-12 | The Board Of Regents Of The University Of Texas System | Micro-rna's that regulate muscle cells |
| WO2006113540A2 (en) | 2005-04-14 | 2006-10-26 | Duke University | Use of ntrosylated hemoglobin |
| CN101448942B (zh) | 2005-12-12 | 2014-04-23 | 北卡罗来纳大学查珀尔希尔分校 | 调节肌细胞增殖和分化的microrna |
| KR101407707B1 (ko) | 2006-04-03 | 2014-06-19 | 산타리스 팔마 에이/에스 | Ａｎｔｉ-ｍｉｒｎａ 안티센스 올리고뉴클레오타이드를 함유하는 약학적 조성물 |
| US20090162240A1 (en) | 2006-04-21 | 2009-06-25 | Jfe Steel Corp. | Brake disk having high temper softening resistance |
| EP2434017A3 (en) | 2006-08-01 | 2012-09-05 | Board of Regents of the University of Texas System | Identification of a micro-RNA that activates expression of beta-myosin heavy chain |
| US8288356B2 (en) * | 2007-10-04 | 2012-10-16 | Santaris Pharma A/S | MicroRNAs |
| 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 |
| US8735568B2 (en) * | 2009-03-09 | 2014-05-27 | The J. David Gladstone Institutes | Methods of modulating smooth muscle cell proliferation and differentiation |
| DK2427472T3 (en) | 2009-05-05 | 2016-09-12 | Miragen Therapeutics | Lipophilic polynukleotidkonjugater |
| SG176716A1 (en) | 2009-06-08 | 2012-01-30 | Miragen Therapeutics | CHEMICAL MODIFICATION MOTIFS FOR miRNA INHIBITORS AND MIMETICS |
| CN102382824A (zh) | 2010-09-01 | 2012-03-21 | 中国科学院上海药物研究所 | 人miR-145反义核酸及其应用 |
| US8642751B2 (en) | 2010-12-15 | 2014-02-04 | Miragen Therapeutics | MicroRNA inhibitors comprising locked nucleotides |
| CN103814131A (zh) * | 2011-05-09 | 2014-05-21 | 格拉斯哥大学理事会 | 在肺动脉高血压的治疗中调控microrna的方法 |
| JP6208228B2 (ja) | 2012-06-21 | 2017-10-04 | ミラゲン セラピューティクス， インコーポレイテッド | ロックド核酸モチーフを含むオリゴヌクレオチドベースの阻害剤 |
-
2014
- 2014-03-13 US US14/777,172 patent/US9752143B2/en not_active Expired - Fee Related
- 2014-03-13 CA CA2902623A patent/CA2902623A1/en not_active Abandoned
- 2014-03-13 JP JP2016502169A patent/JP6410791B2/ja not_active Expired - Fee Related
- 2014-03-13 EP EP14768310.6A patent/EP2968396B1/en not_active Not-in-force
- 2014-03-13 CN CN201480015816.XA patent/CN105188715B/zh not_active Expired - Fee Related
- 2014-03-13 WO PCT/US2014/026538 patent/WO2014151835A1/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| EP2968396B1 (en) | 2018-12-19 |
| WO2014151835A1 (en) | 2014-09-25 |
| CN105188715A (zh) | 2015-12-23 |
| US9752143B2 (en) | 2017-09-05 |
| EP2968396A4 (en) | 2016-08-17 |
| US20160010091A1 (en) | 2016-01-14 |
| JP2016518820A (ja) | 2016-06-30 |
| EP2968396A1 (en) | 2016-01-20 |
| CN105188715B (zh) | 2018-12-25 |
| JP6410791B2 (ja) | 2018-10-24 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20190228 |
|
| FZDE | Discontinued |
Effective date: 20210831 |