JP6410791B2 - Ｍｉｒ−１４５のロックト核酸阻害剤およびその使用 - Google Patents
Ｍｉｒ−１４５のロックト核酸阻害剤およびその使用 Download PDFInfo
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/713—Double-stranded nucleic acids or oligonucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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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
- A61P9/12—Antihypertensives
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
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- 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
- C12N2310/10—Type of nucleic acid
- C12N2310/11—Antisense
- C12N2310/113—Antisense targeting other non-coding nucleic acids, e.g. antagomirs
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- 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
- C12N2310/31—Chemical structure of the backbone
- C12N2310/315—Phosphorothioates
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- 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
- C12N2310/321—2'-O-R Modification
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- 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
- C12N2310/322—2'-R Modification
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- 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
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- 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 (3)
| Publication Number | Publication Date |
|---|---|
| JP2016518820A JP2016518820A (ja) | 2016-06-30 |
| JP2016518820A5 JP2016518820A5 (https=) | 2017-04-06 |
| JP6410791B2 true JP6410791B2 (ja) | 2018-10-24 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016502169A Expired - Fee Related JP6410791B2 (ja) | 2013-03-15 | 2014-03-13 | Ｍｉｒ−１４５のロックト核酸阻害剤およびその使用 |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US9752143B2 (https=) |
| EP (1) | EP2968396B1 (https=) |
| JP (1) | JP6410791B2 (https=) |
| CN (1) | CN105188715B (https=) |
| CA (1) | CA2902623A1 (https=) |
| WO (1) | WO2014151835A1 (https=) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| US10874688B2 (en) * | 2016-10-31 | 2020-12-29 | Gifu University | Double-stranded nucleic acid molecule and use thereof |
| WO2022154636A1 (ko) * | 2021-01-18 | 2022-07-21 | (주)스템메디텍 | Mir 145 억제제를 유효성분으로 포함하는 심근경색증의 치료용 조성물 |
| 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 |
| CA2333380A1 (en) | 1998-05-26 | 1999-12-02 | Icn Pharmaceuticals, Inc. | Novel nucleosides having bicyclic sugar moiety |
| US6833361B2 (en) | 1998-05-26 | 2004-12-21 | Ribapharm, Inc. | Nucleosides having bicyclic sugar moiety |
| RU2001128165A (ru) | 1999-03-18 | 2004-03-27 | Эксикон А/С (Dk) | Выявление мутаций в генах посредством специфичных lna-праймеров |
| JP4413493B2 (ja) | 2000-10-04 | 2010-02-10 | サンタリス ファーマ アー／エス | プリンｌｎａ類似体の改善された合成方法 |
| 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) |
| EP2390331B1 (en) | 2001-09-28 | 2018-04-25 | 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 |
| JP2006519008A (ja) | 2003-02-10 | 2006-08-24 | 独立行政法人産業技術総合研究所 | 哺乳動物細胞の調節 |
| US7683036B2 (en) | 2003-07-31 | 2010-03-23 | Regulus Therapeutics Inc. | Oligomeric compounds and compositions for use in modulation of small non-coding RNAs |
| US20070203445A1 (en) | 2004-02-26 | 2007-08-30 | V-Kardia Pty Ltd | Isolating cardiac circulation |
| US7722596B2 (en) | 2004-02-26 | 2010-05-25 | Osprey Medical, Inc. | Regional cardiac tissue treatment |
| AU2005216564A1 (en) | 2004-02-26 | 2005-09-09 | Osprey Medical Inc. | Isolating cardiac circulation |
| CA2857881A1 (en) | 2004-11-12 | 2006-12-28 | 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 |
| US7338670B2 (en) | 2005-04-14 | 2008-03-04 | Duke University | Use of an agent that restores tissue perfusion and oxygenation |
| PL1969125T3 (pl) | 2005-12-12 | 2012-11-30 | Univ North Carolina Chapel Hill | Mikrorna, które regulują proliferację i różnicowanie komórek mięśniowych |
| CA2648132C (en) | 2006-04-03 | 2019-05-28 | Santaris Pharma A/S | Pharmaceutical composition comprising anti-mirna antisense oligonucleotides |
| KR20080110623A (ko) | 2006-04-21 | 2008-12-18 | 제이에프이 스틸 가부시키가이샤 | 템퍼링 연화 저항이 큰 브레이크 디스크 |
| KR101485495B1 (ko) | 2006-08-01 | 2015-01-22 | 보드 오브 리전츠 오브 더 유니버시티 오브 텍사스 시스템 | 베타-마이오신 중사슬의 발현을 활성화하는 마이크로-ｒｎａ의 동정 |
| EP2623599B1 (en) * | 2007-10-04 | 2019-01-02 | Roche Innovation Center Copenhagen A/S | Micromirs |
| 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 |
| WO2010104796A2 (en) * | 2009-03-09 | 2010-09-16 | The J. David Gladstone Institutes | Methods of modulating smooth muscle cell proliferation and differentiation |
| JP5883381B2 (ja) | 2009-05-05 | 2016-03-15 | ミラゲン セラピューティクス，インコーポレイテッド | 親油性ポリヌクレオチド接合体 |
| CA2765129A1 (en) * | 2009-06-08 | 2010-12-16 | 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 |
| EA201370139A1 (ru) | 2010-12-15 | 2013-10-30 | Мираген Терапеутикс | Ингибиторы микро-рнк, содержащие закрытые нуклеотиды |
| EP2707485B1 (en) | 2011-05-09 | 2016-12-14 | The University Court of The University Of Glasgow | Methods of modulating micrornas in the treatment of pulmonary arterial hypertension |
| US9388408B2 (en) | 2012-06-21 | 2016-07-12 | MiRagen Therapeutics, Inc. | Oligonucleotide-based inhibitors comprising locked nucleic acid motif |
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2014
- 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
- 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 CA CA2902623A patent/CA2902623A1/en not_active Abandoned
- 2014-03-13 US US14/777,172 patent/US9752143B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| WO2014151835A1 (en) | 2014-09-25 |
| CN105188715A (zh) | 2015-12-23 |
| EP2968396B1 (en) | 2018-12-19 |
| CN105188715B (zh) | 2018-12-25 |
| US20160010091A1 (en) | 2016-01-14 |
| CA2902623A1 (en) | 2014-09-25 |
| US9752143B2 (en) | 2017-09-05 |
| EP2968396A4 (en) | 2016-08-17 |
| EP2968396A1 (en) | 2016-01-20 |
| JP2016518820A (ja) | 2016-06-30 |
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