JP4471650B2 - アポリポタンパク質b発現のアンチセンス調節 - Google Patents
アポリポタンパク質b発現のアンチセンス調節 Download PDFInfo
- Publication number
- JP4471650B2 JP4471650B2 JP2003517078A JP2003517078A JP4471650B2 JP 4471650 B2 JP4471650 B2 JP 4471650B2 JP 2003517078 A JP2003517078 A JP 2003517078A JP 2003517078 A JP2003517078 A JP 2003517078A JP 4471650 B2 JP4471650 B2 JP 4471650B2
- Authority
- JP
- Japan
- Prior art keywords
- sugar moiety
- acid
- apolipoprotein
- composition
- seq
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Classifications
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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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
-
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- 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
-
- 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
- C12N2310/314—Phosphoramidates
-
- 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
-
- 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
-
- 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
- C12N2310/33—Chemical structure of the base
- C12N2310/334—Modified C
- C12N2310/3341—5-Methylcytosine
-
- 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
- C12N2310/34—Spatial arrangement of the modifications
- C12N2310/341—Gapmers, i.e. of the type ===---===
-
- 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
- C12N2310/34—Spatial arrangement of the modifications
- C12N2310/346—Spatial arrangement of the modifications having a combination of backbone and sugar modifications
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/582—Recycling of unreacted starting or intermediate materials
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Diabetes (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Plant Pathology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/920,033 US7888324B2 (en) | 2001-08-01 | 2001-08-01 | Antisense modulation of apolipoprotein B expression |
| US13598502A | 2002-04-30 | 2002-04-30 | |
| US10/147,196 US7407943B2 (en) | 2001-08-01 | 2002-05-15 | Antisense modulation of apolipoprotein B expression |
| PCT/US2002/024247 WO2003011887A2 (en) | 2001-08-01 | 2002-07-30 | Antisense modulation of apolipoprotein b expression |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2008298818A Division JP5797875B2 (ja) | 2001-08-01 | 2008-11-21 | アポリポタンパク質b発現のアンチセンス調節 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2005503142A JP2005503142A (ja) | 2005-02-03 |
| JP2005503142A5 JP2005503142A5 (enExample) | 2006-01-05 |
| JP4471650B2 true JP4471650B2 (ja) | 2010-06-02 |
Family
ID=27384801
Family Applications (5)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2003517078A Expired - Fee Related JP4471650B2 (ja) | 2001-08-01 | 2002-07-30 | アポリポタンパク質b発現のアンチセンス調節 |
| JP2008298818A Expired - Fee Related JP5797875B2 (ja) | 2001-08-01 | 2008-11-21 | アポリポタンパク質b発現のアンチセンス調節 |
| JP2012271532A Pending JP2013066480A (ja) | 2001-08-01 | 2012-12-12 | アポリポタンパク質b発現のアンチセンス調節 |
| JP2015123537A Withdrawn JP2015198669A (ja) | 2001-08-01 | 2015-06-19 | アポリポタンパク質b発現のアンチセンス調節 |
| JP2017042765A Pending JP2017127311A (ja) | 2001-08-01 | 2017-03-07 | アポリポタンパク質b発現のアンチセンス調節 |
Family Applications After (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2008298818A Expired - Fee Related JP5797875B2 (ja) | 2001-08-01 | 2008-11-21 | アポリポタンパク質b発現のアンチセンス調節 |
| JP2012271532A Pending JP2013066480A (ja) | 2001-08-01 | 2012-12-12 | アポリポタンパク質b発現のアンチセンス調節 |
| JP2015123537A Withdrawn JP2015198669A (ja) | 2001-08-01 | 2015-06-19 | アポリポタンパク質b発現のアンチセンス調節 |
| JP2017042765A Pending JP2017127311A (ja) | 2001-08-01 | 2017-03-07 | アポリポタンパク質b発現のアンチセンス調節 |
Country Status (10)
| Country | Link |
|---|---|
| US (4) | US7407943B2 (enExample) |
| EP (3) | EP2336145A1 (enExample) |
| JP (5) | JP4471650B2 (enExample) |
| AU (1) | AU2002326481B2 (enExample) |
| CA (1) | CA2455228A1 (enExample) |
| CY (1) | CY1116385T1 (enExample) |
| DK (1) | DK2174945T3 (enExample) |
| ES (1) | ES2546360T3 (enExample) |
| PT (1) | PT2174945E (enExample) |
| WO (1) | WO2003011887A2 (enExample) |
Families Citing this family (89)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7407943B2 (en) | 2001-08-01 | 2008-08-05 | Isis Pharmaceuticals, Inc. | Antisense modulation of apolipoprotein B expression |
| US7888324B2 (en) * | 2001-08-01 | 2011-02-15 | Genzyme Corporation | Antisense modulation of apolipoprotein B expression |
| US20060009410A1 (en) * | 2002-11-13 | 2006-01-12 | Crooke Rosanne M | Effects of apolipoprotein B inhibition on gene expression profiles in animals |
| US7511131B2 (en) | 2002-11-13 | 2009-03-31 | Genzyme Corporation | Antisense modulation of apolipoprotein B expression |
| EP2336318B1 (en) * | 2002-11-13 | 2013-04-24 | Genzyme Corporation | Antisense modulation of apolipoprotein b expression |
| ES2417879T3 (es) * | 2002-11-13 | 2013-08-09 | Genzyme Corporation | Modulación antisentido de la expresión de la apolipoproteína B |
| US9045518B2 (en) | 2002-11-18 | 2015-06-02 | Santaris Pharma A/S | Amino-LNA, thio-LNA and alpha-L-oxy-LN |
| WO2004080406A2 (en) | 2003-03-07 | 2004-09-23 | Alnylam Pharmaceuticals | Therapeutic compositions |
| JP4912873B2 (ja) * | 2003-04-09 | 2012-04-11 | アルナイラム ファーマシューティカルズ, インコーポレイテッド | iRNA複合体 |
| EP1615611B1 (en) * | 2003-04-09 | 2013-02-13 | Alnylam Pharmaceuticals Inc. | iRNA CONJUGATES |
| CA2521464C (en) * | 2003-04-09 | 2013-02-05 | Alnylam Pharmaceuticals, Inc. | Irna conjugates |
| US7598227B2 (en) * | 2003-04-16 | 2009-10-06 | Isis Pharmaceuticals Inc. | Modulation of apolipoprotein C-III expression |
| US7399853B2 (en) * | 2003-04-28 | 2008-07-15 | Isis Pharmaceuticals | Modulation of glucagon receptor expression |
| EP2530157B1 (en) | 2003-07-31 | 2016-09-28 | Regulus Therapeutics Inc. | Oligomeric compounds and compositions for use in modulation of miRNAs |
| US20050261233A1 (en) * | 2004-04-21 | 2005-11-24 | Sanjay Bhanot | Modulation of glucose-6-phosphatase translocase expression |
| US20050287558A1 (en) * | 2004-05-05 | 2005-12-29 | Crooke Rosanne M | SNPs of apolipoprotein B and modulation of their expression |
| AU2011254024B2 (en) * | 2004-08-10 | 2014-08-07 | Kastle Therapeutics, Llc | Antisense Modulation of Apolipoprotein B Expression |
| DK1786472T3 (da) * | 2004-08-10 | 2013-04-15 | Genzyme Corp | Antisense-modulering af apolipoprotein B-ekspression |
| NZ572403A (en) * | 2004-09-24 | 2010-03-26 | Alnylam Pharmaceuticals Inc | Rnai modulation of apob and uses thereof |
| JP2008544742A (ja) * | 2005-02-25 | 2008-12-11 | アイシス ファーマシューティカルズ, インコーポレーテッド | IL4R−αに対する組成物およびその使用 |
| WO2007027775A2 (en) | 2005-08-29 | 2007-03-08 | Isis Pharmaceuticals, Inc. | Methods for use in modulating mir-122a |
| WO2007031081A2 (en) * | 2005-09-15 | 2007-03-22 | Santaris Pharma A/S | RNA ANTAGONIST COMPOUNDS FOR THE INHIBITION OF APO-Bl00 EXPRESSION |
| DK2666859T3 (en) | 2006-04-03 | 2019-04-08 | Roche Innovation Ct Copenhagen As | PHARMACEUTICAL COMPOSITION CONTAINING ANTI-miRNA ANTISENSE OLIGONUCLEOTIDES |
| EP2261333B1 (en) | 2006-04-03 | 2016-03-30 | Roche Innovation Center Copenhagen A/S | Pharmaceutical composition comprising anti-miRNA antisense oligonucleotides |
| DK2021472T3 (da) | 2006-05-05 | 2011-09-19 | Isis Pharmaceuticals Inc | Forbindelser og fremgangsmåder til modulering af genekspression |
| EP2076597A2 (en) | 2006-10-09 | 2009-07-08 | Santaris Pharma A/S | Rna antagonist compounds for the modulation of pcsk9 |
| AU2007310982A1 (en) * | 2006-10-18 | 2008-04-24 | Marina Biotech, Inc. | Nicked or gapped nucleic acid molecules and uses thereof |
| CA2667055C (en) * | 2006-10-18 | 2017-05-09 | Isis Pharmaceuticals, Inc. | Antisense compounds |
| US8093222B2 (en) | 2006-11-27 | 2012-01-10 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
| EP2455471A3 (en) * | 2006-11-27 | 2012-09-12 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
| AU2008228243B2 (en) * | 2007-03-22 | 2014-05-15 | Santaris Pharma A/S | RNA antagonist compounds for the inhibition of Apo-B100 expression |
| DK2149605T3 (da) * | 2007-03-22 | 2013-09-30 | Santaris Pharma As | Korte RNA antagonist forbindelser til modulering af det ønskede mRNA |
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| WO2009043759A2 (en) * | 2007-10-04 | 2009-04-09 | Santaris Pharma A/S | Short rna antagonist compounds for the modulation of hif1alpha |
| ES2463665T3 (es) | 2007-10-04 | 2014-05-28 | Stella Aps | Tratamiento de combinación para el tratamiento de infección por virus de la hepatitis C |
| JP2009171895A (ja) * | 2008-01-24 | 2009-08-06 | Hitachi Software Eng Co Ltd | 核内ノンコーディングrnaの機能解析方法 |
| EP2268811A1 (en) | 2008-03-07 | 2011-01-05 | Santaris Pharma A/S | Pharmaceutical compositions for treatment of microrna related diseases |
| WO2009148605A2 (en) * | 2008-06-04 | 2009-12-10 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
| US20110172292A1 (en) * | 2008-06-30 | 2011-07-14 | Hansen Jens Bo Rode | Antidote oligomers |
| US8492357B2 (en) | 2008-08-01 | 2013-07-23 | Santaris Pharma A/S | Micro-RNA mediated modulation of colony stimulating factors |
| SG171914A1 (en) | 2008-12-02 | 2011-07-28 | Chiralgen Ltd | Method for the synthesis of phosphorus atom modified nucleic acids |
| WO2010076248A1 (en) * | 2008-12-31 | 2010-07-08 | Santaris Pharma A/S | Use of lna apob antisense oligomers for the treatment of acute coronary syndromes |
| US9107933B2 (en) | 2009-03-16 | 2015-08-18 | Isis Pharmaceuticals, Inc. | Compositions and methods of targeting apolipoprotein B for the reduction of apolipoprotein C-III |
| JP5773535B2 (ja) | 2009-04-24 | 2015-09-02 | ロシュ・イノベーション・センター・コペンハーゲン・アクティーゼルスカブRoche Innovation Center Copenhagen A/S | インターフェロンに非応答性のhcv患者の治療のための医薬組成物 |
| NZ596608A (en) | 2009-06-12 | 2014-01-31 | Santaris Pharma As | New potent anti apob antisense compounds |
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| US8563528B2 (en) | 2009-07-21 | 2013-10-22 | Santaris Pharma A/S | Antisense oligomers targeting PCSK9 |
| DK3252068T3 (da) | 2009-10-12 | 2025-08-25 | Larry J Smith | Metoder og sammensætninger til modulering af genekspression ved anvendelse af oligonukleotidbaserede lægemidler administreret in vivo eller in vitro |
| WO2012027033A1 (en) * | 2010-07-19 | 2012-03-01 | Isis Pharmaceuticals, Inc. | Compounds and methods for modulating target nuclear and sub-nuclear nucleic acid molecules in cells and animals |
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| JP6246121B2 (ja) | 2012-07-13 | 2017-12-13 | 株式会社新日本科学 | キラル核酸アジュバント |
| DK2872485T3 (da) | 2012-07-13 | 2021-03-08 | Wave Life Sciences Ltd | Asymmetrisk hjælpegruppe |
| CN112007045B (zh) | 2012-07-13 | 2026-01-06 | 波涛生命科学有限公司 | 手性控制 |
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| WO2014112144A1 (ja) * | 2013-01-15 | 2014-07-24 | 国立大学法人熊本大学 | 染色体セントロメア由来のサテライトノンコーディングrnaを標的とした核酸抗癌剤、及び該抗癌剤を用いる方法 |
| US20150368642A1 (en) | 2013-01-30 | 2015-12-24 | Hoffmann-La Roche Inc. | Lna oligonucleotide carbohydrate conjugates |
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| US20080242629A1 (en) | 2008-10-02 |
| EP2174945B1 (en) | 2015-04-08 |
| JP2015198669A (ja) | 2015-11-12 |
| CA2455228A1 (en) | 2003-02-13 |
| DK2174945T3 (en) | 2015-05-26 |
| PT2174945E (pt) | 2015-06-25 |
| US20030215943A1 (en) | 2003-11-20 |
| JP2009055925A (ja) | 2009-03-19 |
| JP2005503142A (ja) | 2005-02-03 |
| EP1419168A4 (en) | 2006-11-15 |
| US20150105440A1 (en) | 2015-04-16 |
| EP2336145A1 (en) | 2011-06-22 |
| EP2174945A1 (en) | 2010-04-14 |
| US8735364B2 (en) | 2014-05-27 |
| CY1116385T1 (el) | 2017-02-08 |
| US7407943B2 (en) | 2008-08-05 |
| ES2546360T3 (es) | 2015-09-22 |
| AU2002326481B2 (en) | 2008-11-13 |
| EP1419168A2 (en) | 2004-05-19 |
| JP2017127311A (ja) | 2017-07-27 |
| JP5797875B2 (ja) | 2015-10-21 |
| JP2013066480A (ja) | 2013-04-18 |
| US20170355986A1 (en) | 2017-12-14 |
| WO2003011887A2 (en) | 2003-02-13 |
| WO2003011887A3 (en) | 2003-04-24 |
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