TWI515294B - A single stranded nucleic acid molecule having a nitrogen-containing lipid ring skeleton - Google Patents

A single stranded nucleic acid molecule having a nitrogen-containing lipid ring skeleton Download PDF

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Publication number
TWI515294B
TWI515294B TW100127384A TW100127384A TWI515294B TW I515294 B TWI515294 B TW I515294B TW 100127384 A TW100127384 A TW 100127384A TW 100127384 A TW100127384 A TW 100127384A TW I515294 B TWI515294 B TW I515294B
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Taiwan
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region
aforementioned
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nucleic acid
acid molecule
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TW100127384A
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Chinese (zh)
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TW201219570A (en
Inventor
大木忠明
林宏剛
白水久男
濱崎智洋
伊藤彰浩
鈴木寬
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伯納克股份有限公司
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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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
    • 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
    • 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
    • C12N2310/10—Type of nucleic acid
    • C12N2310/14—Type of nucleic acid interfering nucleic acids [NA]
    • 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
    • C12N2310/3519—Fusion with another nucleic acid
    • 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
    • C12N2310/531—Stem-loop; Hairpin
    • 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
    • C12N2320/50—Methods for regulating/modulating their activity
    • C12N2320/51—Methods for regulating/modulating their activity modulating the chemical stability, e.g. nuclease-resistance
    • 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
    • C12N2330/00—Production
    • C12N2330/30—Production chemically synthesised

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Microbiology (AREA)
  • Plant Pathology (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Public Health (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pyrrole Compounds (AREA)
  • Hydrogenated Pyridines (AREA)
  • Medicinal Preparation (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
TW100127384A 2010-08-03 2011-08-02 A single stranded nucleic acid molecule having a nitrogen-containing lipid ring skeleton TWI515294B (zh)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
JP2010174915 2010-08-03
JP2010230806 2010-10-13
JP2010269823 2010-12-02
JP2011152381 2011-07-08

Publications (2)

Publication Number Publication Date
TW201219570A TW201219570A (en) 2012-05-16
TWI515294B true TWI515294B (zh) 2016-01-01

Family

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Family Applications (2)

Application Number Title Priority Date Filing Date
TW100127384A TWI515294B (zh) 2010-08-03 2011-08-02 A single stranded nucleic acid molecule having a nitrogen-containing lipid ring skeleton
TW104132132A TWI572716B (zh) 2010-08-03 2011-08-02 Mononuclear Nucleic Acid Molecules with Nitrogen-Containing Liposomes

Family Applications After (1)

Application Number Title Priority Date Filing Date
TW104132132A TWI572716B (zh) 2010-08-03 2011-08-02 Mononuclear Nucleic Acid Molecules with Nitrogen-Containing Liposomes

Country Status (9)

Country Link
EP (4) EP2628801B1 (https=)
JP (3) JP4965745B2 (https=)
KR (3) KR101894701B1 (https=)
CN (3) CN103052711B (https=)
DK (1) DK2674494T3 (https=)
ES (4) ES2527660T3 (https=)
PT (1) PT2674494E (https=)
TW (2) TWI515294B (https=)
WO (1) WO2012017919A1 (https=)

Families Citing this family (45)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8691782B2 (en) 2010-08-03 2014-04-08 Bonac Corporation Single-stranded nucleic acid molecule having nitrogen-containing alicyclic skeleton
WO2013077446A1 (ja) * 2011-11-26 2013-05-30 株式会社ボナック 遺伝子発現制御のための一本鎖核酸分子
US9404108B2 (en) 2012-03-04 2016-08-02 Bonac Corporation Micro-RMA inhibitor
WO2013133393A1 (ja) * 2012-03-07 2013-09-12 学校法人東京医科大学 Ｖｅｇｆ遺伝子の発現抑制用一本鎖核酸分子
EP2832860A4 (en) * 2012-03-29 2016-01-27 Univ Kyushu Nat Univ Corp NUCLEIC ACID MOLECULAR FOR INHIBITING EXPRESSION OF PERIOSTATING, METHOD FOR RESTRICTING THE EXPRESSION OF PERIOSTATING AND USE OF THE SAID NUCLEIC ACID MOLECULE
CN109810977A (zh) 2012-05-26 2019-05-28 株式会社博纳克 具有递送功能的基因表达调控用单链核酸分子
WO2015046451A1 (ja) * 2013-09-27 2015-04-02 株式会社アクアセラピューティクス 眼科疾患を除くペリオスチン発現に起因する疾患用医薬、およびその用途
WO2015093495A1 (ja) * 2013-12-16 2015-06-25 株式会社ボナック ＴＧＦ－β１遺伝子発現制御のための一本鎖核酸分子
CN105899663B (zh) 2013-12-26 2019-07-26 学校法人东京医科大学 用于基因表达控制的人工模拟miRNA及其用途
SG10201913570XA (en) 2013-12-27 2020-03-30 Bonac Corp Artificial match-type mirna for controlling gene expression and use therefor
JP6492014B2 (ja) * 2013-12-27 2019-03-27 株式会社ボナック 遺伝子発現制御のための人工マッチ型ｍｉＲＮＡおよびその用途
JP6726105B2 (ja) * 2014-12-15 2020-07-22 株式会社ボナック ＴＧＦ−β１発現抑制のための一本鎖核酸分子
SG11201705223XA (en) * 2014-12-27 2017-07-28 Bonac Corp NATURALLY OCCURING miRNA FOR CONTROLLING GENE EXPRESSION, AND USE OF SAME
JP6602847B2 (ja) 2015-03-27 2019-11-06 株式会社ボナック デリバリー機能と遺伝子発現制御能を有する一本鎖核酸分子
JPWO2016167366A1 (ja) * 2015-04-17 2018-04-05 国立大学法人 東京大学 眼疾患治療剤
MX2018005146A (es) * 2015-10-30 2018-08-23 Bonac Corp Composicion que contiene de manera estable molecula de acido nucleico de un solo filamento que suprime la expresion de gen tgf-b1.
CN108473988A (zh) * 2015-12-29 2018-08-31 国立大学法人北海道大学 抑制肾素原基因或肾素原受体基因表达的单链核酸分子及其用途
WO2017131124A1 (ja) * 2016-01-26 2017-08-03 日産化学工業株式会社 一本鎖オリゴヌクレオチド
US11518994B2 (en) 2016-01-30 2022-12-06 Bonac Corporation Artificial single guide RNA and use thereof
JP6787398B2 (ja) * 2016-04-26 2020-11-18 住友化学株式会社 一本鎖核酸分子用モノマーの製造方法
CN110337495B (zh) 2017-02-06 2024-03-29 日产化学株式会社 单链寡核苷酸
EP3604528A4 (en) 2017-03-31 2021-01-13 Bonac Corporation CYCLIC NUCLEIC ACID MOLECULE WITH GENE EXPRESSION CONTROL FUNCTION
JPWO2018199338A1 (ja) * 2017-04-27 2020-03-12 国立大学法人広島大学 Ｂ型肝炎治療用核酸分子
JP7204649B2 (ja) 2017-07-28 2023-01-16 杏林製薬株式会社 線維症治療剤
US20210188895A1 (en) * 2017-10-13 2021-06-24 Bonac Corporation Single-stranded nucleic acid molecule, and production method therefor
TWI830718B (zh) 2018-02-09 2024-02-01 日商住友化學股份有限公司 核酸分子之製造方法
MX2020009765A (es) 2018-03-20 2021-01-08 Tokyo Inst Tech Oligonucleotido antisentido reducido en toxicidad.
CN111819280A (zh) 2018-03-30 2020-10-23 东丽株式会社 发夹型单链rna分子的制备方法
EP3778914A4 (en) * 2018-03-30 2022-01-19 Sumitomo Chemical Company, Ltd. Method for producing single-strand rna
TWI848981B (zh) * 2018-10-02 2024-07-21 日商東麗股份有限公司 新穎亞磷醯胺、及髮夾型單股ｒｎａ分子之製造方法
JP7241098B2 (ja) 2019-01-25 2023-03-16 杏林製薬株式会社 線維症治療剤
US12378275B2 (en) 2019-03-29 2025-08-05 Sumitomo Chemical Company, Limited Porous inorganic carrier and method for producing nucleic acid using same
JP7510919B2 (ja) 2019-03-29 2024-07-04 住友化学株式会社 無機多孔質担体及びこれを用いた核酸の製造方法
WO2020202953A1 (ja) 2019-03-29 2020-10-08 住友化学株式会社 無機多孔質担体、及びこれを用いた核酸の製造方法
US12377409B2 (en) 2019-03-29 2025-08-05 Sumitomo Chemical Company, Limited Inorganic porous carrier, and production method for nucleic acid using same
WO2020202949A1 (ja) 2019-03-29 2020-10-08 住友化学株式会社 Ｒｎａの製造方法
US12509483B2 (en) 2019-10-11 2025-12-30 Sumitomo Chemical Company, Limited Method for producing nucleic acid oligomers
US20230312635A1 (en) 2020-01-29 2023-10-05 Sumitomo Chemical Company, Limited Method for producing nucleic acid oligomer
WO2021153770A1 (en) 2020-01-29 2021-08-05 Sumitomo Chemical Company, Limited Process of preparing nucleic acid oligomer
US12522629B2 (en) 2020-03-27 2026-01-13 Sumitomo Chemical Company, Limited Method for producing nucleic acid oligomer
KR102925978B1 (ko) 2020-05-13 2026-02-10 스미또모 가가꾸 가부시끼가이샤 무기 다공질 기재, 무기 다공질 담체, 및 핵산의 제조 방법
US20230242570A1 (en) 2020-07-09 2023-08-03 Sumitomo Chemical Company, Limited Method for producing nucleic acid oligomer
JP7719788B2 (ja) * 2020-09-24 2025-08-06 住友化学株式会社 核酸オリゴマーの製造方法
KR20240082343A (ko) 2021-09-28 2024-06-10 스미또모 가가꾸 가부시끼가이샤 정제 디클로로아세트산의 제조 방법
KR20240162536A (ko) 2022-03-23 2024-11-15 스미또모 가가꾸 가부시끼가이샤 핵산 올리고머의 제조 방법

Family Cites Families (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3687808A (en) 1969-08-14 1972-08-29 Univ Leland Stanford Junior Synthetic polynucleotides
GB9621367D0 (en) * 1996-10-14 1996-12-04 Isis Innovation Chiral peptide nucleic acids
US6509323B1 (en) 1998-07-01 2003-01-21 California Institute Of Technology Linear cyclodextrin copolymers
WO2005019453A2 (en) * 2001-05-18 2005-03-03 Sirna Therapeutics, Inc. RNA INTERFERENCE MEDIATED INHIBITION OF GENE EXPRESSION USING CHEMICALLY MODIFIED SHORT INTERFERING NUCLEIC ACID (siNA)
US6962906B2 (en) * 2000-03-14 2005-11-08 Active Motif Oligonucleotide analogues, methods of synthesis and methods of use
TWI321054B (en) 2000-12-19 2010-03-01 California Inst Of Techn Compositions containing inclusion complexes
AU2003219900A1 (en) * 2002-02-22 2003-09-09 James R. Eshleman Antigene locks and therapeutic uses thereof
AU2003256857A1 (en) 2002-08-08 2004-02-25 Dharmacon, Inc. Short interfering rnas having a hairpin structure containing a non-nucleotide loop
NL1022811C2 (nl) * 2003-02-28 2004-08-31 Fountain Patents B V Systeem en werkwijze voor opslag en transport van zeecontainers.
AU2004227414A1 (en) * 2003-04-03 2004-10-21 Alnylam Pharmaceuticals iRNA conjugates
CA2538215A1 (en) * 2003-09-30 2005-04-07 Anges Mg, Inc. Staple oligonucleotides and medicaments comprising the same
CA2572151A1 (en) * 2004-06-30 2006-08-24 Alnylam Pharmaceuticals, Inc. Oligonucleotides comprising a non-phosphate backbone linkage
WO2006074108A2 (en) * 2004-12-30 2006-07-13 Hauser Todd M Compositions and methods for modulating gene expression using self-protected oligonucleotides
PL2129680T3 (pl) * 2007-03-21 2015-10-30 Brookhaven Science Ass Llc Łączone kompozycje cząsteczek antysensownych o strukturze spinki do włosów oraz sposoby modulacji ekspresji
CN101889087B (zh) * 2007-11-29 2013-04-03 苏州瑞博生物技术有限公司 一种干扰靶基因表达的复合分子及其制备方法
WO2009082607A2 (en) * 2007-12-04 2009-07-02 Alnylam Pharmaceuticals, Inc. Targeting lipids
WO2009076321A2 (en) * 2007-12-07 2009-06-18 Halo-Bio Rnai Therapeutics Inc. Compositions and methods for modulating gene expression using asymmetrically-active precursor polynucleotides
JP2010174915A (ja) 2009-01-27 2010-08-12 Toyota Motor Corp 高圧ガスタンク
JP5449815B2 (ja) 2009-03-26 2014-03-19 住友化学株式会社 偏光板の製造方法
JP2010269823A (ja) 2009-05-21 2010-12-02 British American Tobacco Japan Kk 喫煙品用容器
JP2011152381A (ja) 2010-01-25 2011-08-11 Ucom:Kk 箸置き

Also Published As

Publication number Publication date
WO2012017919A1 (ja) 2012-02-09
ES2443346T3 (es) 2014-02-19
TWI572716B (zh) 2017-03-01
KR101894702B1 (ko) 2018-09-04
EP2639307A8 (en) 2014-04-30
KR20180040728A (ko) 2018-04-20
CN103052711B (zh) 2016-08-03
KR20130095738A (ko) 2013-08-28
KR20180040727A (ko) 2018-04-20
ES2528285T3 (es) 2015-02-06
ES2533129T3 (es) 2015-04-07
JP4965745B2 (ja) 2012-07-04
KR101849801B1 (ko) 2018-04-17
EP2436767B1 (en) 2013-11-20
EP2628801B1 (en) 2015-01-07
TW201219570A (en) 2012-05-16
JP2013138681A (ja) 2013-07-18
EP2674494A1 (en) 2013-12-18
CN104004018A (zh) 2014-08-27
PT2674494E (pt) 2015-02-27
JP5261677B2 (ja) 2013-08-14
CN104004018B (zh) 2017-01-04
EP2639307B1 (en) 2015-03-04
CN103052711A (zh) 2013-04-17
EP2639307A2 (en) 2013-09-18
CN104059911B (zh) 2017-01-04
JPWO2012017919A1 (ja) 2013-10-03
EP2639307A3 (en) 2014-02-05
ES2527660T3 (es) 2015-01-28
TW201615835A (zh) 2016-05-01
CN104059911A (zh) 2014-09-24
KR101894701B1 (ko) 2018-09-04
DK2674494T3 (en) 2015-02-23
JP2013034470A (ja) 2013-02-21
JP5555346B2 (ja) 2014-07-23
EP2436767A1 (en) 2012-04-04
EP2674494B1 (en) 2014-12-17
EP2436767A4 (en) 2012-05-09
HK1189910A1 (en) 2014-06-20
EP2628801A1 (en) 2013-08-21
HK1200460A1 (en) 2015-08-07

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