JP7384833B2 - オフターゲット効果が低下した修飾ｒｎａ剤 - Google Patents

オフターゲット効果が低下した修飾ｒｎａ剤 Download PDF

Info

Publication number
JP7384833B2
JP7384833B2 JP2020564156A JP2020564156A JP7384833B2 JP 7384833 B2 JP7384833 B2 JP 7384833B2 JP 2020564156 A JP2020564156 A JP 2020564156A JP 2020564156 A JP2020564156 A JP 2020564156A JP 7384833 B2 JP7384833 B2 JP 7384833B2
Authority
JP
Japan
Prior art keywords
muna
gna
dsrna
antisense strand
strand
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
JP2020564156A
Other languages
English (en)
Japanese (ja)
Other versions
JP2021523720A (ja
JP2021523720A5 (enExample
Inventor
成夫 松田
マーク・ケー・シュレーゲル
マジャ・ジャナス
ヴァサント・アール・ジャダヴ
マーティン・メイヤー
クラウス・チャリシー
ムティアー・マノハラン
カラントッタティル・ジー・ラジーヴ
ジャヤプラカシュ・ケー・ナイール
Original Assignee
アルニラム・ファーマシューティカルズ・インコーポレーテッド
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 アルニラム・ファーマシューティカルズ・インコーポレーテッド filed Critical アルニラム・ファーマシューティカルズ・インコーポレーテッド
Publication of JP2021523720A publication Critical patent/JP2021523720A/ja
Publication of JP2021523720A5 publication Critical patent/JP2021523720A5/ja
Priority to JP2023189998A priority Critical patent/JP7684373B2/ja
Application granted granted Critical
Publication of JP7384833B2 publication Critical patent/JP7384833B2/ja
Priority to JP2025076285A priority patent/JP2025113272A/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
    • C12N15/111—General methods applicable to biologically active non-coding 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
    • 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
    • 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
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/318—Chemical structure of the backbone where the PO2 is completely replaced, e.g. MMI or formacetal
    • 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
    • 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
    • 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
    • C12N2310/344—Position-specific modifications, e.g. on every purine, at the 3'-end
    • 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
    • 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
    • C12N2320/53—Methods for regulating/modulating their activity reducing unwanted side-effects

Landscapes

  • Engineering & Computer Science (AREA)
  • Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Wood Science & Technology (AREA)
  • Organic Chemistry (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • Physics & Mathematics (AREA)
  • Microbiology (AREA)
  • Plant Pathology (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Biophysics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)
  • Peptides Or Proteins (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Saccharide Compounds (AREA)
JP2020564156A 2018-05-16 2019-05-16 オフターゲット効果が低下した修飾ｒｎａ剤 Active JP7384833B2 (ja)

Priority Applications (2)

Application Number Priority Date Filing Date Title
JP2023189998A JP7684373B2 (ja) 2018-05-16 2023-11-07 オフターゲット効果が低下した修飾ｒｎａ剤
JP2025076285A JP2025113272A (ja) 2018-05-16 2025-05-01 オフターゲット効果が低下した修飾ｒｎａ剤

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201862672405P 2018-05-16 2018-05-16
US62/672,405 2018-05-16
US201862719291P 2018-08-17 2018-08-17
US62/719,291 2018-08-17
PCT/US2019/032633 WO2019222479A1 (en) 2018-05-16 2019-05-16 Modified rna agents with reduced off-target effect

Related Child Applications (1)

Application Number Title Priority Date Filing Date
JP2023189998A Division JP7684373B2 (ja) 2018-05-16 2023-11-07 オフターゲット効果が低下した修飾ｒｎａ剤

Publications (3)

Publication Number Publication Date
JP2021523720A JP2021523720A (ja) 2021-09-09
JP2021523720A5 JP2021523720A5 (enExample) 2022-05-24
JP7384833B2 true JP7384833B2 (ja) 2023-11-21

Family

ID=68540971

Family Applications (3)

Application Number Title Priority Date Filing Date
JP2020564156A Active JP7384833B2 (ja) 2018-05-16 2019-05-16 オフターゲット効果が低下した修飾ｒｎａ剤
JP2023189998A Active JP7684373B2 (ja) 2018-05-16 2023-11-07 オフターゲット効果が低下した修飾ｒｎａ剤
JP2025076285A Pending JP2025113272A (ja) 2018-05-16 2025-05-01 オフターゲット効果が低下した修飾ｒｎａ剤

Family Applications After (2)

Application Number Title Priority Date Filing Date
JP2023189998A Active JP7684373B2 (ja) 2018-05-16 2023-11-07 オフターゲット効果が低下した修飾ｒｎａ剤
JP2025076285A Pending JP2025113272A (ja) 2018-05-16 2025-05-01 オフターゲット効果が低下した修飾ｒｎａ剤

Country Status (6)

Country Link
US (3) US12247203B2 (enExample)
EP (1) EP3802827A4 (enExample)
JP (3) JP7384833B2 (enExample)
AU (2) AU2019270152B2 (enExample)
CA (1) CA3099930A1 (enExample)
WO (1) WO2019222479A1 (enExample)

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11597744B2 (en) 2017-06-30 2023-03-07 Sirius Therapeutics, Inc. Chiral phosphoramidite auxiliaries and methods of their use
CA3098623A1 (en) 2018-05-07 2019-11-14 Alnylam Pharmaceuticals, Inc. Extrahepatic delivery
EP4114947A1 (en) 2020-03-05 2023-01-11 Alnylam Pharmaceuticals, Inc. Complement component c3 irna compositions and methods of use thereof for treating or preventing complement component c3-associated diseases
KR20230043195A (ko) * 2020-08-04 2023-03-30 투오지에 바이오텍 (상하이) 컴퍼니 리미티드 오프-타겟 활성이 감소된 변형된 siRNA
EP4291654A2 (en) 2021-02-12 2023-12-20 Alnylam Pharmaceuticals, Inc. Superoxide dismutase 1 (sod1) irna compositions and methods of use thereof for treating or preventing superoxide dismutase 1- (sod1-) associated neurodegenerative diseases
CN113073098B (zh) * 2021-02-20 2024-08-20 北京理工大学 抑制BACE1基因表达的siRNA修饰物及其应用
BR112023019981A2 (pt) 2021-03-29 2023-12-12 Alnylam Pharmaceuticals Inc Composições do agente irna de huntingtina (htt) e métodos de uso das mesmas
WO2022206946A1 (zh) * 2021-04-02 2022-10-06 上海拓界生物医药科技有限公司 乙型肝炎病毒siRNA和siRNA缀合物
KR20240067943A (ko) 2021-09-24 2024-05-17 알닐람 파마슈티칼스 인코포레이티드 미소관 연관 단백질 타우(MAPT) iRNA 제제 조성물 및 이의 사용 방법
IL315546A (en) 2022-03-16 2024-11-01 Empirico Inc GALNAC compositions to improve siRNA bioavailability
EP4499834A2 (en) 2022-03-28 2025-02-05 Empirico Inc. Modified oligonucleotides
WO2024023256A1 (en) * 2022-07-27 2024-02-01 E-Therapeutics Plc Nucleic acid compounds
JP2025532985A (ja) * 2022-09-30 2025-10-03 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 修飾二本鎖ｒｎａ剤
AU2024258620A1 (en) * 2023-04-21 2025-11-06 Suzhou Siran Biotechnology Co., Ltd. Oligomeric nucleic acid, and preparation method therefore and use thereof
UY40897A (es) 2023-09-21 2025-03-31 Ionis Pharmaceuticals Inc Compuestos y métodos para inhibir lpa
US12454693B1 (en) * 2024-09-27 2025-10-28 Dexcel Pharma Technologies Ltd. Nucleic acids for inhibiting expression of transferrin receptor 2

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015106128A2 (en) 2014-01-09 2015-07-16 Alnylam Pharmaceuticals, Inc. MODIFIED RNAi AGENTS
JP2017525705A (ja) 2014-08-20 2017-09-07 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Ａｌｎｙｌａｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． 修飾二本鎖ｒｎａ剤

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050032069A1 (en) 2002-11-05 2005-02-10 Muthiah Manoharan Oligomeric compounds having modified bases for binding to adenine and guanine and their use in gene modulation
US7812149B2 (en) * 1996-06-06 2010-10-12 Isis Pharmaceuticals, Inc. 2′-Fluoro substituted oligomeric compounds and compositions for use in gene modulations
EP2152877A2 (en) * 2007-05-02 2010-02-17 Sirna Therapeutics Inc. RNA INTERFERENCE MEDIATED INHIBITION OF CYCLIC NUCLEOTIDE TYPE 4 PHOSPHODIESTERASE ( PDE4B) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
CN102753187A (zh) * 2009-06-03 2012-10-24 戴瑟纳制药公司 肽-dicer底物试剂及其特异性抑制基因表达的方法
WO2011133876A2 (en) 2010-04-22 2011-10-27 Alnylam Pharmaceuticals, Inc. Oligonucleotides comprising acyclic and abasic nucleosides and analogs
US20130190383A1 (en) * 2010-04-26 2013-07-25 Marina Biotech, Inc. Nucleic acid compounds with conformationally restricted monomers and uses thereof
EP3865576A1 (en) 2014-12-15 2021-08-18 Dicerna Pharmaceuticals, Inc. Ligand-modified double-stranded nucleic acids
WO2016209862A1 (en) 2015-06-23 2016-12-29 Alnylam Pharmaceuticals, Inc. Glucokinase (gck) irna compositions and methods of use thereof
JP6924744B2 (ja) * 2015-07-17 2021-08-25 アークトゥラス・セラピューティクス・インコーポレイテッドＡｒｃｔｕｒｕｓ Ｔｈｅｒａｐｅｕｔｉｃｓ，Ｉｎｃ． Ｂ型肝炎ウイルスに対する組成物および薬剤ならびにその使用
WO2018098328A1 (en) * 2016-11-23 2018-05-31 Alnylam Pharmaceuticals, Inc. Modified rna agents with reduced off-target effect

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015106128A2 (en) 2014-01-09 2015-07-16 Alnylam Pharmaceuticals, Inc. MODIFIED RNAi AGENTS
JP2017525705A (ja) 2014-08-20 2017-09-07 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Ａｌｎｙｌａｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． 修飾二本鎖ｒｎａ剤

Also Published As

Publication number Publication date
EP3802827A1 (en) 2021-04-14
US20250207131A1 (en) 2025-06-26
CA3099930A1 (en) 2019-11-21
JP2024014905A (ja) 2024-02-01
US12247203B2 (en) 2025-03-11
US20210238595A1 (en) 2021-08-05
JP2025113272A (ja) 2025-08-01
AU2025206406A1 (en) 2025-08-14
JP7684373B2 (ja) 2025-05-27
WO2019222479A1 (en) 2019-11-21
US12275938B2 (en) 2025-04-15
JP2021523720A (ja) 2021-09-09
AU2019270152A1 (en) 2020-12-10
AU2019270152B2 (en) 2025-05-08
EP3802827A4 (en) 2022-08-03
US20220290145A1 (en) 2022-09-15

Similar Documents

Publication Publication Date Title
JP7684373B2 (ja) オフターゲット効果が低下した修飾ｒｎａ剤
JP7672220B2 (ja) 修飾二本鎖ｒｎａ剤
JP2025168400A (ja) オフターゲット効果が低下した修飾ｒｎａ剤
US20250163417A1 (en) Compositions and methods for improving strand biased
WO2021072395A1 (en) Modified oligonucleotides
HK40121704A (en) Modified double-stranded rna agents
HK40051291A (en) Modified double-stranded rna agents
HK40051656A (en) Modified double-stranded rna agents
EA043057B1 (ru) Средства, представляющие собой модифицированную двухнитевую рнк
EA052885B1 (ru) Средства, представляющие собой модифицированную двухнитевую рнк

Legal Events

Date Code Title Description
A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20220513

A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20220513

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20230522

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20230803

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: 20231010

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20231109

R150 Certificate of patent or registration of utility model

Ref document number: 7384833

Country of ref document: JP

Free format text: JAPANESE INTERMEDIATE CODE: R150