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)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Biochemistry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Microbiology (AREA)
  • Epidemiology (AREA)
  • Neurology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (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
EP2451461A4 (en) 2009-07-06 2013-05-29 Ontorii Inc NOVEL NUCLEIC ACID PRODRUGS AND METHOD OF USE THEREOF
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
US10837014B2 (en) 2012-05-16 2020-11-17 Translate Bio Ma, Inc. Compositions and methods for modulating SMN gene family expression
AU2013262709A1 (en) 2012-05-16 2015-01-22 Rana Therapeutics, Inc. Compositions and methods for modulating MECP2 expression
KR20150030205A (ko) 2012-05-16 2015-03-19 라나 테라퓨틱스, 인크. Smn 유전자 패밀리 발현을 조절하기 위한 조성물 및 방법
DK2872485T3 (da) 2012-07-13 2021-03-08 Wave Life Sciences Ltd Asymmetrisk hjælpegruppe
JP2016534035A (ja) 2013-10-04 2016-11-04 ラナ セラピューティクス インコーポレイテッド 筋萎縮性側索硬化症を治療するための組成物及び方法
ES2810375T3 (es) 2014-12-17 2021-03-08 Proqr Therapeutics Ii Bv Edición direccionada de ARN
WO2016161388A1 (en) 2015-04-03 2016-10-06 University Of Massachusetts Fully stabilized asymmetric sirna
WO2017030973A1 (en) 2015-08-14 2017-02-23 University Of Massachusetts Bioactive conjugates for oligonucleotide delivery
JP2018528783A (ja) 2015-09-25 2018-10-04 アイオーニス ファーマシューティカルズ， インコーポレーテッドＩｏｎｉｓ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ，Ｉｎｃ． コンジュゲートアンチセンス化合物及びその使用
US10478503B2 (en) 2016-01-31 2019-11-19 University Of Massachusetts Branched oligonucleotides
KR102706686B1 (ko) * 2016-05-06 2024-09-19 아이오니스 파마수티컬즈, 인코포레이티드 Glp-1 수용체 리간드 모이어티 컨쥬게이트된 올리고뉴클레오티드 및 이의 용도
EP3475424A1 (en) 2016-06-22 2019-05-01 ProQR Therapeutics II B.V. Single-stranded rna-editing oligonucleotides
US20180028554A1 (en) * 2016-07-05 2018-02-01 Biomarin Technologies B.V. Oligomers Having Bicyclic Scaffold Moeities
US11753638B2 (en) 2016-08-12 2023-09-12 University Of Massachusetts Conjugated oligonucleotides
CA3035293A1 (en) 2016-09-01 2018-03-08 Proqr Therapeutics Ii B.V. Chemically modified single-stranded rna-editing oligonucleotides
US11433089B2 (en) 2016-09-23 2022-09-06 National University Corporation Tokyo Medical And Dental University Blood-brain barrier permeable heteroduplex nucleic acid
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
CA3064590A1 (en) 2017-06-23 2018-12-27 University Of Massachusetts Two-tailed self-delivering sirna and related methods
EP3647423A4 (en) 2017-06-30 2021-03-24 National University Corporation Tokyo Medical and Dental University DOUBLE STRANDED HETERO-ANTI-MIRNA
WO2019092618A2 (en) * 2017-11-08 2019-05-16 Ionis Pharmaceuticals, Inc Glp-1 receptor ligand moiety conjugated oligonucleotides and uses thereof
JP7360170B2 (ja) 2018-02-28 2023-10-12 国立大学法人 東京医科歯科大学 虚血病変部位特異的な遺伝子治療法
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
WO2020033899A1 (en) 2018-08-10 2020-02-13 University Of Massachusetts Modified oligonucleotides targeting snps
JP7627042B2 (ja) 2018-08-23 2025-02-05 ユニバーシティー オブ マサチューセッツ Ｏ－メチルリッチ完全安定化オリゴヌクレオチド
WO2020150636A1 (en) * 2019-01-18 2020-07-23 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
CA3149835A1 (en) 2019-08-09 2021-02-18 University Of Massachusetts Chemically modified oligonucleotides targeting snps
US12365894B2 (en) 2019-09-16 2025-07-22 University Of Massachusetts Branched lipid conjugates of siRNA for specific tissue delivery
US20240117346A1 (en) * 2019-10-11 2024-04-11 National University Corporation Tokyo Medical And Dental University Modified hetero nucleic acids
EP4090744A4 (en) * 2020-01-17 2024-04-10 Anastasia Khvorova UNIVERSAL DYNAMIC PHARMACOKINETIC MODIFYING ANCHORS
EP4123023A4 (en) * 2020-03-16 2024-07-17 National University Corporation Tokyo Medical and Dental University Heteronucleic acid containing morpholino nucleic acid
EP4157289A4 (en) 2020-05-26 2024-06-26 University Of Massachusetts Synthetic oligonucleotides having regions of block and cluster modifications
CA3202708A1 (en) 2020-11-23 2022-05-27 Alpha Anomeric Sas Nucleic acid duplexes
AR126207A1 (es) 2021-06-23 2023-09-27 Univ Massachusetts Compuestos de oligonucleotidos anti-flt1 optimizados para el tratamiento de la preeclampsia y otros desordenes angiogénicos
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
US20250297249A1 (en) * 2021-12-07 2025-09-25 Liid Pharmaceuticals, Inc. Antisense oligonucleotide complex
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
US6043060A (en) 1996-11-18 2000-03-28 Imanishi; Takeshi Nucleotide analogues
JP3781879B2 (ja) 1996-11-18 2006-05-31 武 今西 新規ヌクレオチド類縁体
US6770748B2 (en) 1997-03-07 2004-08-03 Takeshi Imanishi Bicyclonucleoside and oligonucleotide analogue
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
CA2303299C (en) 1997-09-12 2016-02-23 Exiqon A/S Oligonucleotide analogues
US6794499B2 (en) 1997-09-12 2004-09-21 Exiqon A/S Oligonucleotide analogues
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
AU2001249649A1 (en) * 2000-03-31 2001-10-15 Millennium Pharmaceuticals, Inc. 16836, a novel human phospholipase c family member and uses thereof
WO2004041889A2 (en) * 2002-11-05 2004-05-21 Isis Pharmaceuticals, Inc. Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation
EP2336318B1 (en) * 2002-11-13 2013-04-24 Genzyme Corporation Antisense modulation of apolipoprotein b expression
EP1661905B9 (en) 2003-08-28 2012-12-19 IMANISHI, Takeshi Novel artificial nucleic acids of n-o bond crosslinkage type
WO2005113571A2 (en) * 2004-05-13 2005-12-01 The University Of North Carolina At Chapel Hill 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
AU2007229161B2 (en) * 2006-03-23 2012-07-12 Roche Innovation Center Copenhagen A/S Small internally segmented interfering RNA
DK2021472T3 (da) 2006-05-05 2011-09-19 Isis Pharmaceuticals Inc Forbindelser og fremgangsmåder til modulering af genekspression
WO2008029619A1 (fr) 2006-09-07 2008-03-13 Daiichi Sankyo Company, Limited Oligonucléotide antisens ena ayant une action spécifique de la séquence
EP2076597A2 (en) 2006-10-09 2009-07-08 Santaris Pharma A/S Rna antagonist compounds for the modulation of pcsk9
AU2008228243B2 (en) 2007-03-22 2014-05-15 Santaris Pharma A/S RNA antagonist compounds for the inhibition of Apo-B100 expression
EP2152722B1 (en) * 2007-05-03 2016-04-27 Merck Sharp & Dohme Corp. Compositions comprising mir34 therapeutic agents for treating cancer
DE102007021870A1 (de) 2007-05-10 2008-11-20 Clariant International Limited Wässrige Pigmentpräparationen
WO2009027527A2 (en) 2007-08-30 2009-03-05 Santaris Pharma A/S Rna antagonist compounds for the modulation of fabp4/ap2
WO2010093788A2 (en) * 2009-02-11 2010-08-19 Dicerna Pharmaceuticals, Inc. 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
US20140128449A1 (en) * 2011-04-07 2014-05-08 The Board Of Regents Of The University Of Texas System Oligonucleotide modulation of splicing
CA2833223A1 (en) * 2011-04-22 2012-10-26 Prosensa Technologies B.V. New compounds for treating, delaying and/or preventing a human genetic disorder such as myotonic dystrophy type 1 (dm1)
ES2707232T3 (es) * 2011-12-16 2019-04-03 Univ Nat Corp Tokyo Medical & Dental Acido nucleico bicatenario quimérico

Also Published As

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

Similar Documents

Publication Publication Date Title
US10190117B2 (en) Double-stranded antisense nucleic acid with exon-skipping effect
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
JP6826984B2 (ja) アシル−アミノ−ｌｎａオリゴヌクレオチドおよび／またはヒドロカルビル−アミノ−ｌｎａオリゴヌクレオチド
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
JP2026068029A (ja) 一本鎖核酸及びその用途
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