JP7357002B2 - 高コレステロール血症及び関連状態を治療するための、ｐｃｓｋ９を標的とするオリゴヌクレオチド - Google Patents

高コレステロール血症及び関連状態を治療するための、ｐｃｓｋ９を標的とするオリゴヌクレオチド Download PDF

Info

Publication number
JP7357002B2
JP7357002B2 JP2020557924A JP2020557924A JP7357002B2 JP 7357002 B2 JP7357002 B2 JP 7357002B2 JP 2020557924 A JP2020557924 A JP 2020557924A JP 2020557924 A JP2020557924 A JP 2020557924A JP 7357002 B2 JP7357002 B2 JP 7357002B2
Authority
JP
Japan
Prior art keywords
oligonucleotide
nucleotides
oligonucleotides
pcsk9
antisense 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
JP2020557924A
Other languages
English (en)
Japanese (ja)
Other versions
JPWO2019204021A5 (https=
JP2021521796A5 (https=
JP2021521796A (ja
Inventor
ヘンリク ティー デュデック
ジヘ パク
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.)
Dicerna Pharmaceuticals Inc
Original Assignee
Dicerna Pharmaceuticals Inc
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 Dicerna Pharmaceuticals Inc filed Critical Dicerna Pharmaceuticals Inc
Publication of JP2021521796A publication Critical patent/JP2021521796A/ja
Publication of JPWO2019204021A5 publication Critical patent/JPWO2019204021A5/ja
Publication of JP2021521796A5 publication Critical patent/JP2021521796A5/ja
Priority to JP2023159941A priority Critical patent/JP2023174697A/ja
Application granted granted Critical
Publication of JP7357002B2 publication Critical patent/JP7357002B2/ja
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

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
    • C12N15/1137—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 against enzymes
    • 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
    • C12N2310/31—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
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/322—2'-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
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/346—Spatial arrangement of the modifications having a combination of backbone and sugar modifications
    • 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
    • C12N2310/50—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
    • C12Y—ENZYMES
    • C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
    • C12Y304/21—Serine endopeptidases (3.4.21)
    • C12Y304/21061—Kexin (3.4.21.61), i.e. proprotein convertase subtilisin/kexin type 9

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Biomedical Technology (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Plant Pathology (AREA)
  • Microbiology (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Virology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Saccharide Compounds (AREA)
  • Medicinal Preparation (AREA)
JP2020557924A 2018-04-18 2019-04-01 高コレステロール血症及び関連状態を治療するための、ｐｃｓｋ９を標的とするオリゴヌクレオチド Active JP7357002B2 (ja)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2023159941A JP2023174697A (ja) 2018-04-18 2023-09-25 高コレステロール血症及び関連状態を治療するための、ｐｃｓｋ９を標的とするオリゴヌクレオチド

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201862659693P 2018-04-18 2018-04-18
US62/659,693 2018-04-18
US201962820558P 2019-03-19 2019-03-19
US62/820,558 2019-03-19
PCT/US2019/025253 WO2019204021A1 (en) 2018-04-18 2019-04-01 Pcsk9 targeting oligonucleotides for treating hypercholesterolemia and related conditions

Related Child Applications (1)

Application Number Title Priority Date Filing Date
JP2023159941A Division JP2023174697A (ja) 2018-04-18 2023-09-25 高コレステロール血症及び関連状態を治療するための、ｐｃｓｋ９を標的とするオリゴヌクレオチド

Publications (4)

Publication Number Publication Date
JP2021521796A JP2021521796A (ja) 2021-08-30
JPWO2019204021A5 JPWO2019204021A5 (https=) 2022-04-07
JP2021521796A5 JP2021521796A5 (https=) 2022-04-07
JP7357002B2 true JP7357002B2 (ja) 2023-10-05

Family

ID=68239855

Family Applications (2)

Application Number Title Priority Date Filing Date
JP2020557924A Active JP7357002B2 (ja) 2018-04-18 2019-04-01 高コレステロール血症及び関連状態を治療するための、ｐｃｓｋ９を標的とするオリゴヌクレオチド
JP2023159941A Withdrawn JP2023174697A (ja) 2018-04-18 2023-09-25 高コレステロール血症及び関連状態を治療するための、ｐｃｓｋ９を標的とするオリゴヌクレオチド

Family Applications After (1)

Application Number Title Priority Date Filing Date
JP2023159941A Withdrawn JP2023174697A (ja) 2018-04-18 2023-09-25 高コレステロール血症及び関連状態を治療するための、ｐｃｓｋ９を標的とするオリゴヌクレオチド

Country Status (10)

Country Link
US (2) US11566248B2 (https=)
EP (1) EP3765611A4 (https=)
JP (2) JP7357002B2 (https=)
KR (1) KR102749200B1 (https=)
CN (1) CN112368381A (https=)
AU (1) AU2019255460A1 (https=)
CA (1) CA3097585A1 (https=)
IL (1) IL278086A (https=)
MX (1) MX2020011006A (https=)
WO (1) WO2019204021A1 (https=)

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019006455A1 (en) 2017-06-30 2019-01-03 Solstice Biologics, Ltd. AUXILIARIES OF CHIRAL PHOSPHORAMIDITIS AND METHODS OF USE THEREOF
US11566248B2 (en) 2018-04-18 2023-01-31 Dicerna Pharmaceuticals, Inc. PCSK9 targeting oligonucleotides for treating hypercholesterolemia and related conditions
WO2020226960A1 (en) 2019-05-03 2020-11-12 Dicerna Pharmaceuticals, Inc. Double-stranded nucleic acid inhibitor molecules with shortened sense strands
US20220290156A1 (en) * 2019-08-27 2022-09-15 Sanofi Compositions and methods for inhibiting pcsk9
WO2022089486A1 (zh) * 2020-10-28 2022-05-05 江苏柯菲平医药股份有限公司 抑制PCSK9基因表达的siRNA及其修饰物与应用
CN114634929A (zh) * 2020-12-16 2022-06-17 施能康生物科技有限公司 靶向前蛋白转化酶枯草杆菌转化酶的核酸及其用途
WO2023017004A1 (en) * 2021-08-09 2023-02-16 Cargene Therapeutics Pte. Ltd. Inhibitory nucleic acids for pcsk9
CN120272480A (zh) * 2021-09-30 2025-07-08 北京安龙生物医药有限公司 用于治疗与pcsk9相关疾病的靶向寡核苷酸
CN118786216A (zh) * 2022-01-13 2024-10-15 石药集团中奇制药技术（石家庄）有限公司 一种抑制PCSK9基因表达的RNAi剂及其应用
JP2025520520A (ja) * 2022-06-14 2025-07-03 大睿生物 ＰＣＳＫ９遺伝子活性を調節するｓｉＲＮＡ分子
CN118086311B (zh) * 2023-05-25 2024-08-09 苏州时安生物技术有限公司 抑制PCSK9基因表达的siRNA、其缀合物和药物组合物及用途
CN121866332A (zh) * 2023-06-21 2026-04-14 美国圣因生物股份有限公司 靶向前蛋白转化酶枯草杆菌蛋白酶kexin 9（pcsk9）的双链rna及其使用方法
CN119040325B (zh) * 2023-09-18 2025-07-18 广州必贝特医药股份有限公司 用于同时抑制两个靶基因表达的siRNA、药物及其应用
CN117106781B (zh) * 2023-10-16 2024-03-22 深圳市茵冠生物科技有限公司 修饰的核酸及其产品和应用
WO2025096355A1 (en) * 2023-10-29 2025-05-08 Corsera Llc Improved sirna for silencing expression of pcsk9 and uses thereof
CN117210468B (zh) * 2023-11-06 2024-02-20 北京悦康科创医药科技股份有限公司 靶向调控PCSK9基因表达的siRNA及其应用
CN117384907B (zh) * 2023-12-11 2024-03-29 上海鼎新基因科技有限公司 抑制PCSK9表达的siRNA分子及其应用
CN118109463B (zh) * 2024-01-31 2025-02-21 北京悦康科创医药科技股份有限公司 靶向PCSK9基因的siRNA及其应用
WO2026026812A1 (zh) * 2024-07-29 2026-02-05 成都先衍生物技术有限公司 一种具有双靶点基因抑制作用的核酸缀合物及其应用
WO2026026811A1 (zh) * 2024-07-29 2026-02-05 成都先衍生物技术有限公司 一种具有双靶点基因抑制作用的核酸缀合物及其应用

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2009536827A (ja) 2006-05-11 2009-10-22 アルニラム ファーマシューティカルズ， インコーポレイテッド Ｐｃｓｋ９遺伝子の発現を阻害するための組成物および方法
JP2010503382A (ja) 2006-07-17 2010-02-04 サーナ・セラピューティクス・インコーポレイテッド 低分子干渉核酸（ｓｉＮＡ）を用いたプロタンパク質転換酵素サブチリシンケクシン９（ＰＣＳＫ９）遺伝子発現のＲＮＡ干渉媒介性阻害
WO2010078536A1 (en) 2009-01-05 2010-07-08 Rxi Pharmaceuticals Corporation Inhibition of pcsk9 through rnai
JP2013545736A (ja) 2010-10-29 2013-12-26 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 Ｐｃｓｋ９遺伝子の阻害のための組成物および方法

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2010510807A (ja) * 2006-11-27 2010-04-08 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 高コレステロール血症を治療するための方法
WO2008109369A2 (en) * 2007-03-02 2008-09-12 Mdrna, Inc. Nucleic acid compounds for inhibiting tnf gene expression and uses thereof
WO2009114475A2 (en) * 2008-03-09 2009-09-17 Intradigm Corporation Compositions comprising human pcsk9 and apolipoprotein b sirna and methods of use
NZ597504A (en) * 2009-06-15 2013-10-25 Alnylam Pharmaceuticals Inc Lipid formulated dsrna targeting the pcsk9 gene
JP7105065B2 (ja) * 2014-12-15 2022-07-22 ダイセルナ ファーマシューティカルズ， インコーポレイテッド リガンド修飾二本鎖核酸
US11566248B2 (en) * 2018-04-18 2023-01-31 Dicerna Pharmaceuticals, Inc. PCSK9 targeting oligonucleotides for treating hypercholesterolemia and related conditions

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2009536827A (ja) 2006-05-11 2009-10-22 アルニラム ファーマシューティカルズ， インコーポレイテッド Ｐｃｓｋ９遺伝子の発現を阻害するための組成物および方法
JP2010503382A (ja) 2006-07-17 2010-02-04 サーナ・セラピューティクス・インコーポレイテッド 低分子干渉核酸（ｓｉＮＡ）を用いたプロタンパク質転換酵素サブチリシンケクシン９（ＰＣＳＫ９）遺伝子発現のＲＮＡ干渉媒介性阻害
WO2010078536A1 (en) 2009-01-05 2010-07-08 Rxi Pharmaceuticals Corporation Inhibition of pcsk9 through rnai
JP2013545736A (ja) 2010-10-29 2013-12-26 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 Ｐｃｓｋ９遺伝子の阻害のための組成物および方法

Also Published As

Publication number Publication date
CA3097585A1 (en) 2019-10-24
JP2023174697A (ja) 2023-12-08
KR20210005068A (ko) 2021-01-13
IL278086A (en) 2020-11-30
KR102749200B1 (ko) 2025-01-03
CN112368381A (zh) 2021-02-12
AU2019255460A1 (en) 2020-11-12
MX2020011006A (es) 2021-01-20
US20210238606A1 (en) 2021-08-05
US11566248B2 (en) 2023-01-31
EP3765611A4 (en) 2022-05-04
EP3765611A1 (en) 2021-01-20
WO2019204021A1 (en) 2019-10-24
US20230250435A1 (en) 2023-08-10
JP2021521796A (ja) 2021-08-30

Similar Documents

Publication Publication Date Title
JP7357002B2 (ja) 高コレステロール血症及び関連状態を治療するための、ｐｃｓｋ９を標的とするオリゴヌクレオチド
JP7476422B2 (ja) Ｌｐａ発現を阻害するための組成物及び方法
JP7645323B2 (ja) Ｂ型肝炎感染の治療方法
JP7749645B2 (ja) Ａｎｇｐｔｌ３発現を阻害する組成物及び方法
US11478501B2 (en) Compositions and methods for inhibiting HMGB1 expression
CN111601891A (zh) 用于抑制aldh2表达的组合物和方法
US12534730B2 (en) Compositions and methods for inhibiting GYS2 expression
US20220072024A1 (en) Compositions and methods for inhibiting hmgb1 expression
KR20230171431A (ko) Pnpla3 발현을 조절하기 위한 조성물 및 방법
CA3235941A1 (en) Compositions and methods for modulating apoc3 expression
WO2020167593A1 (en) Methods and compositions for inhibiting expression of cyp27a1
WO2026041910A2 (en) Compositions and methods for inhibiting xdh expression
CA3245064A1 (en) COMPOSITIONS AND METHODS OF MODULATING THE ACTIVITY OF STRUCTURAL AND CYTOSKELETON-ASSOCIATED PROTEINS

Legal Events

Date Code Title Description
A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20220330

A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20220330

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20230215

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20230511

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: 20230727

A601 Written request for extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A601

Effective date: 20230822

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20230925

R150 Certificate of patent or registration of utility model

Ref document number: 7357002

Country of ref document: JP

Free format text: JAPANESE INTERMEDIATE CODE: R150