JP6604544B2 - エクソンスキッピング効果を有する二本鎖アンチセンス核酸 - Google Patents

エクソンスキッピング効果を有する二本鎖アンチセンス核酸 Download PDF

Info

Publication number
JP6604544B2
JP6604544B2 JP2015560881A JP2015560881A JP6604544B2 JP 6604544 B2 JP6604544 B2 JP 6604544B2 JP 2015560881 A JP2015560881 A JP 2015560881A JP 2015560881 A JP2015560881 A JP 2015560881A JP 6604544 B2 JP6604544 B2 JP 6604544B2
Authority
JP
Japan
Prior art keywords
nucleic acid
nucleotides
acid strand
pharmaceutical composition
nucleotide
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.)
Active
Application number
JP2015560881A
Other languages
English (en)
Japanese (ja)
Other versions
JP2016526529A (ja
JP2016526529A5 (enExample
Inventor
隆徳 横田
一隆 仁科
耕太郎 吉岡
聡 小比賀
剛典 下
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
University of Osaka NUC
Original Assignee
Osaka University NUC
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Osaka University NUC filed Critical Osaka University NUC
Publication of JP2016526529A publication Critical patent/JP2016526529A/ja
Publication of JP2016526529A5 publication Critical patent/JP2016526529A5/ja
Application granted granted Critical
Publication of JP6604544B2 publication Critical patent/JP6604544B2/ja
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • 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
    • A—HUMAN NECESSITIES
    • 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
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • 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
    • C12N2310/315—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
    • C12N2310/323—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
    • 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
    • C12N2310/35—Nature of the modification
    • C12N2310/351—Conjugate
    • 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
    • C12N2310/35—Nature of the modification
    • C12N2310/351—Conjugate
    • C12N2310/3513—Protein; Peptide
    • 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
    • C12N2310/50—Physical structure
    • C12N2310/53—Physical structure partially self-complementary or closed
    • C12N2310/533—Physical structure partially self-complementary or closed having a mismatch or nick in at least one of the strands
    • 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
    • C12N2320/00—Applications; Uses
    • C12N2320/30—Special therapeutic applications
    • C12N2320/33—Alteration of splicing

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Biochemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Microbiology (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Neurology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
JP2015560881A 2013-06-16 2014-06-16 エクソンスキッピング効果を有する二本鎖アンチセンス核酸 Active JP6604544B2 (ja)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201361835634P 2013-06-16 2013-06-16
US61/835,634 2013-06-16
US201361836672P 2013-06-19 2013-06-19
US61/836,672 2013-06-19
PCT/JP2014/003208 WO2014203518A1 (en) 2013-06-16 2014-06-16 Double-stranded antisense nucleic acid with exon-skipping effect

Publications (3)

Publication Number Publication Date
JP2016526529A JP2016526529A (ja) 2016-09-05
JP2016526529A5 JP2016526529A5 (enExample) 2017-08-17
JP6604544B2 true JP6604544B2 (ja) 2019-11-13

Family

ID=52104269

Family Applications (1)

Application Number Title Priority Date Filing Date
JP2015560881A Active JP6604544B2 (ja) 2013-06-16 2014-06-16 エクソンスキッピング効果を有する二本鎖アンチセンス核酸

Country Status (7)

Country Link
US (1) US10190117B2 (enExample)
EP (1) EP3010514B1 (enExample)
JP (1) JP6604544B2 (enExample)
CN (1) CN105324119A (enExample)
AU (1) AU2014282666A1 (enExample)
CA (1) CA2915443A1 (enExample)
WO (1) WO2014203518A1 (enExample)

Families Citing this family (44)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MX342945B (es) 2009-07-06 2016-10-18 Ontorii Inc * Profármacos de ácido nucleico novedosos y métodos de uso de los mismos.
DK2620428T3 (da) 2010-09-24 2019-07-01 Wave Life Sciences Ltd Asymmetrisk hjælpegruppe
US9605019B2 (en) 2011-07-19 2017-03-28 Wave Life Sciences Ltd. Methods for the synthesis of functionalized nucleic acids
AU2013262709A1 (en) 2012-05-16 2015-01-22 Rana Therapeutics, Inc. Compositions and methods for modulating MECP2 expression
US10837014B2 (en) 2012-05-16 2020-11-17 Translate Bio Ma, Inc. Compositions and methods for modulating SMN gene family expression
SG11201407483YA (en) 2012-05-16 2014-12-30 Rana Therapeutics Inc Compositions and methods for modulating smn gene family expression
SG11201500239VA (en) 2012-07-13 2015-03-30 Wave Life Sciences Japan Asymmetric auxiliary group
WO2015051283A1 (en) 2013-10-04 2015-04-09 Rana Therapeutics, Inc. Compositions and methods for treating amyotrophic lateral sclerosis
CA2968336C (en) 2014-12-17 2021-11-23 Proqr Therapeutics Ii B.V. Construct for site directed editing of an adenosine nucleotide in target rna
WO2016161388A1 (en) 2015-04-03 2016-10-06 University Of Massachusetts Fully stabilized asymmetric sirna
EP3334499A4 (en) 2015-08-14 2019-04-17 University of Massachusetts BIOACTIVE CONJUGATES FOR THE RELEASE OF OLIGONUCLEOTIDES
US11116843B2 (en) 2015-09-25 2021-09-14 Ionis Pharmaceuticals, Inc. Conjugated antisense compounds and their use
US10478503B2 (en) 2016-01-31 2019-11-19 University Of Massachusetts Branched oligonucleotides
IL299516A (en) 2016-05-06 2023-02-01 Astrazeneca Ab Oligonucleotides conjugated to the GLP-1 receptor ligand complex and their uses
CN109477103A (zh) 2016-06-22 2019-03-15 ProQR治疗上市公司Ⅱ 单链rna-编辑寡核苷酸
CN109757108A (zh) * 2016-07-05 2019-05-14 比奥马林技术公司 具有治疗遗传疾病的改善特征的包含双环支架部分的前体mRNA剪接转换或调节寡核苷酸
WO2018031933A2 (en) 2016-08-12 2018-02-15 University Of Massachusetts Conjugated oligonucleotides
EP3507366B1 (en) 2016-09-01 2020-10-07 ProQR Therapeutics II B.V. Chemically modified single-stranded rna-editing oligonucleotides
JP7043078B2 (ja) 2016-09-23 2022-03-29 国立大学法人 東京医科歯科大学 血液脳関門通過型ヘテロ２本鎖核酸
JP7129702B2 (ja) 2016-09-29 2022-09-02 国立大学法人 東京医科歯科大学 オーバーハングを有する二本鎖核酸複合体
EP3571300A1 (en) 2017-01-19 2019-11-27 ProQR Therapeutics II B.V. Oligonucleotide complexes for use in rna editing
CN110799647A (zh) 2017-06-23 2020-02-14 马萨诸塞大学 双尾自递送sirna及相关的方法
WO2019004420A1 (ja) 2017-06-30 2019-01-03 国立大学法人東京医科歯科大学 ヘテロ二本鎖型ａｎｔｉｍｉＲ
JP7503492B2 (ja) * 2017-11-08 2024-06-20 アイオニス・ファーマシューティカルズ・インコーポレイテッド Ｇｌｐ－１受容体リガンド部分コンジュゲート化オリゴヌクレオチド及びその使用
US11674141B2 (en) 2018-02-28 2023-06-13 National University Corporation Tokyo Medical And Dental University Ischemic-lesion-site-specific gene therapy
WO2019177061A1 (ja) * 2018-03-14 2019-09-19 国立大学法人東京医科歯科大学 核酸複合体
JP7333079B2 (ja) 2018-03-19 2023-08-24 国立大学法人 東京医科歯科大学 毒性が軽減した核酸
GB201808146D0 (en) 2018-05-18 2018-07-11 Proqr Therapeutics Ii Bv Stereospecific Linkages in RNA Editing Oligonucleotides
AU2019316640B2 (en) 2018-08-10 2026-03-12 University Of Massachusetts Modified oligonucleotides targeting SNPs
EP3840759A4 (en) 2018-08-23 2022-06-01 University Of Massachusetts O-METHYL RICH FULLY STABILIZED OLIGONUCLEOTIDES
AU2020207935A1 (en) 2019-01-18 2021-08-26 University Of Massachusetts Dynamic pharmacokinetic-modifying anchors
WO2020209285A1 (ja) 2019-04-08 2020-10-15 国立大学法人東京医科歯科大学 筋疾患治療用医薬組成物
KR20220047989A (ko) 2019-08-09 2022-04-19 유니버시티 오브 매사추세츠 Snp를 표적화하는 화학적으로 변형된 올리고뉴클레오타이드
US12365894B2 (en) 2019-09-16 2025-07-22 University Of Massachusetts Branched lipid conjugates of siRNA for specific tissue delivery
JP7793144B2 (ja) * 2019-10-11 2026-01-05 国立大学法人東京科学大学 修飾ヘテロ核酸
EP4090744A4 (en) * 2020-01-17 2024-04-10 Anastasia Khvorova UNIVERSAL DYNAMIC PHARMACOKINETIC MODIFYING ANCHORS
WO2021187392A1 (ja) * 2020-03-16 2021-09-23 国立大学法人東京医科歯科大学 モルホリノ核酸を含むヘテロ核酸
US12534724B2 (en) 2020-05-26 2026-01-27 University Of Massachusetts Synthetic oligonucleotides having regions of block and cluster modifications
WO2022106695A1 (en) 2020-11-23 2022-05-27 Alpha Anomeric Sas Nucleic acid duplexes
IL309334A (en) 2021-06-23 2024-02-01 Univ Massachusetts Anti-FLT1 optimized oligonucleotide compounds for the treatment of preeclampsia and other angiogenic disorders
WO2023022229A1 (ja) * 2021-08-19 2023-02-23 国立大学法人東京医科歯科大学 モルホリノ核酸を含む修飾ヘテロ核酸
JP7412668B2 (ja) * 2021-12-07 2024-01-15 リードファーマ株式会社 アンチセンスオリゴヌクレオチド複合体
CN115806984B (zh) * 2022-10-18 2023-10-10 昆明理工大学 环状rna及载体和载体的应用
GB202215614D0 (en) 2022-10-21 2022-12-07 Proqr Therapeutics Ii Bv Heteroduplex rna editing oligonucleotide complexes

Family Cites Families (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH09110894A (ja) * 1995-10-17 1997-04-28 Soyaku Gijutsu Kenkyusho:Kk ハイブリッドｄｎａ／ｒｎａオリゴヌクレオチド及び抗ウイルス剤
ATE232880T1 (de) 1996-11-18 2003-03-15 Takeshi Imanishi Neue nucleotidanaloga
JP3781879B2 (ja) 1996-11-18 2006-05-31 武 今西 新規ヌクレオチド類縁体
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
US6794499B2 (en) 1997-09-12 2004-09-21 Exiqon A/S Oligonucleotide analogues
DE69829760T3 (de) 1997-09-12 2016-04-14 Exiqon A/S Bi- und tri-zyklische - nukleosid, nukleotid und oligonukleotid-analoga
US20010024808A1 (en) * 1998-09-10 2001-09-27 Millennium Pharmaceuticals, Inc., A Delaware Corporation Leptin induced genes
AU2001233176A1 (en) * 2000-01-31 2001-08-07 Shengfang Jin Resistance sequences and uses thereof
ES2328448T7 (es) * 2000-03-31 2012-03-16 Millennium Pharmaceuticals Inc. 16836, un miembro de la familia de la fosfolipasa c humana y sus usos.
EP1562971B1 (en) * 2002-11-05 2014-02-12 Isis Pharmaceuticals, Inc. Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation
JP4986109B2 (ja) * 2002-11-13 2012-07-25 ジェンザイム・コーポレーション アポリポタンパク質ｂ発現のアンチセンス調節
DK1661905T3 (da) 2003-08-28 2012-07-23 Takeshi Imanishi Hidtil ukendte syntetiske nukleinsyrer af N-O-krydsbindingstype
US20080199960A1 (en) * 2004-05-13 2008-08-21 Juliano Rudolph L Methods for the Delivery of Oligomeric Compounds
WO2006059507A1 (ja) * 2004-11-30 2006-06-08 Sankyo Company, Limited 11β-HSD1アンチセンス化合物
EP2002004B1 (en) * 2006-03-23 2015-10-14 Roche Innovation Center Copenhagen A/S Small internally segmented interfering rna
CA3044969A1 (en) 2006-05-05 2007-12-21 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating gene expression
WO2008029619A1 (fr) 2006-09-07 2008-03-13 Daiichi Sankyo Company, Limited Oligonucléotide antisens ena ayant une action spécifique de la séquence
CA2666191C (en) 2006-10-09 2017-07-11 Santaris Pharma A/S Rna antagonist compounds for the modulation of pcsk9
EP2126079A1 (en) 2007-03-22 2009-12-02 Santaris Pharma A/S Rna antagonist compounds for the inhibition of apo-b100 expression
WO2008137867A2 (en) * 2007-05-03 2008-11-13 Rosetta Inpharmatics Llc Compositions comprising mir34 therapeutic agents for treating cancer
DE102007021870A1 (de) 2007-05-10 2008-11-20 Clariant International Limited Wässrige Pigmentpräparationen
AU2008292091A1 (en) 2007-08-30 2009-03-05 Santaris Pharma A/S RNA antagonist compounds for the modulation of FABP4/aP2
US20100249214A1 (en) * 2009-02-11 2010-09-30 Dicerna Pharmaceuticals Multiplex dicer substrate rna interference molecules having joining sequences
WO2011139710A1 (en) 2010-04-26 2011-11-10 Marina Biotech, Inc. Nucleic acid compounds with conformationally restricted monomers and uses thereof
WO2012138487A2 (en) * 2011-04-07 2012-10-11 The Board Of Regents Of The University Of Texas System Oligonucleotide modulation of splicing
EP2699269A1 (en) * 2011-04-22 2014-02-26 Prosensa Technologies B.V. New compounds for treating, delaying and/or preventing a human genetic disorder such as myotonic dystrophy type 1 (dm1)
WO2013089283A1 (en) * 2011-12-16 2013-06-20 National University Corporation Tokyo Medical And Dental University Chimeric double-stranded nucleic acid

Also Published As

Publication number Publication date
EP3010514A4 (en) 2017-02-22
CA2915443A1 (en) 2014-12-24
CN105324119A (zh) 2016-02-10
US10190117B2 (en) 2019-01-29
JP2016526529A (ja) 2016-09-05
EP3010514B1 (en) 2021-01-20
AU2014282666A1 (en) 2016-01-07
US20160130583A1 (en) 2016-05-12
EP3010514A1 (en) 2016-04-27
WO2014203518A1 (en) 2014-12-24

Similar Documents

Publication Publication Date Title
JP6604544B2 (ja) エクソンスキッピング効果を有する二本鎖アンチセンス核酸
JP6472087B2 (ja) 治療用オリゴヌクレオチドを送達するための二本鎖剤
JP7174384B2 (ja) キメラ２重鎖核酸
JP6440170B2 (ja) キメラ一本鎖アンチセンスポリヌクレオチドおよび二本鎖アンチセンス剤
EP4706689A2 (en) Compositions for delivery of antisense compounds
US20210052706A1 (en) Compositions and methods for facilitating delivery of synthetic nucleic acids to cells
US10183977B2 (en) Stabilized STAT3 decoy oligonucleotides and uses therefor
JP2022551269A (ja) 最小フッ素含有量を用いた低分子干渉ｒｎａの化学修飾
CN115397436A (zh) 用于抑制PNPLA3表达的RNAi剂、其药物组合物和使用方法
TW202400190A (zh) 活化補體因子h表現的寡核苷酸調節劑
CA3235941A1 (en) Compositions and methods for modulating apoc3 expression
TW202444904A (zh) 用於抑制粒線體醯胺肟還原組分1(MARC1)之表現之RNAi藥劑、其醫藥組合物及使用方法
HK40084771B (zh) 用於抑制PNPLA3表达的RNAi剂、其药物组合物和使用方法
HK40084771A (en) Rnai agents for inhibiting expression of pnpla3, pharmaceutical compositions thereof, and methods of use

Legal Events

Date Code Title Description
A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20170615

A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20170615

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A821

Effective date: 20170615

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20180724

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20180921

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20190305

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20190423

TRDD Decision of grant or rejection written
A01 Written decision to grant a patent or to grant a registration (utility model)

Free format text: JAPANESE INTERMEDIATE CODE: A01

Effective date: 20190903

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20191003

R150 Certificate of patent or registration of utility model

Ref document number: 6604544

Country of ref document: JP

Free format text: JAPANESE INTERMEDIATE CODE: R150

S111 Request for change of ownership or part of ownership

Free format text: JAPANESE INTERMEDIATE CODE: R313115

R350 Written notification of registration of transfer

Free format text: JAPANESE INTERMEDIATE CODE: R350

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250