TW202126809A - 具有最小氟含量之小干擾rna的化學修飾 - Google Patents

具有最小氟含量之小干擾rna的化學修飾 Download PDF

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TW202126809A
TW202126809A TW109134478A TW109134478A TW202126809A TW 202126809 A TW202126809 A TW 202126809A TW 109134478 A TW109134478 A TW 109134478A TW 109134478 A TW109134478 A TW 109134478A TW 202126809 A TW202126809 A TW 202126809A
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nucleotides
modified
galnac
oligonucleotide
peg
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TW109134478A
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為民 王
奈姆 納澤夫
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美商戴瑟納製藥股份有限公司
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    • 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
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    • 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

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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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TW109134478A 2019-10-02 2020-10-05 具有最小氟含量之小干擾rna的化學修飾 TW202126809A (zh)

Applications Claiming Priority (2)

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US201962909278P 2019-10-02 2019-10-02
US62/909,278 2019-10-02

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TW202126809A true TW202126809A (zh) 2021-07-16

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US (1) US20220389430A1 (https=)
EP (1) EP4038191A1 (https=)
JP (1) JP2022551269A (https=)
KR (1) KR20220069103A (https=)
CN (1) CN114761557B (https=)
AU (1) AU2020358016A1 (https=)
CA (1) CA3153026A1 (https=)
CL (1) CL2022000825A1 (https=)
IL (1) IL291841A (https=)
MX (1) MX2022004032A (https=)
TW (1) TW202126809A (https=)
WO (1) WO2021067744A1 (https=)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PE20250400A1 (es) 2021-04-12 2025-02-11 Dicerna Pharmaceuticals Inc Composiciones y metodos para inhibir cetohexoquinasa
CA3209418A1 (en) * 2021-04-14 2022-10-20 Utsav SAXENA Compositions and methods for modulating pnpla3 expression
EP4372085A4 (en) * 2021-07-16 2026-01-21 Suzhou Ribo Life Science Co Ltd Nucleic acid, composition and conjugate, container, preparation process and use
EP4405368A1 (en) * 2021-09-22 2024-07-31 Sanegene Bio USA Inc. 2'-alkyl or 3'- alkyl modified ribose derivatives for use in the in-vivo delivery of oligonucleotides
WO2023069495A1 (en) * 2021-10-19 2023-04-27 Alnylam Pharmaceuticals, Inc. Oligonucleotides with 2'-deoxy-2'-f-2'-c-methyl nucleotides
JP2024543195A (ja) 2021-12-01 2024-11-19 ディセルナ ファーマシューティカルズ インコーポレイテッド Ａｐｏｃ３発現を調節するための組成物及び方法
CN119183476A (zh) * 2022-04-26 2024-12-24 上海拓界生物医药科技有限公司 氘代化学修饰和包含其的寡核苷酸
TW202526017A (zh) * 2023-09-14 2025-07-01 美商Ionis製藥公司 用於減少ａｐｏｃｉｉｉ表現的化合物及方法
WO2025191337A2 (en) * 2024-03-11 2025-09-18 Synerk Biotech Limited Oligonucleotide terminal phosphate derivatives and method of use

Family Cites Families (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2429814C (en) 2000-12-01 2014-02-18 Thomas Tuschl Rna interference mediating small rna molecules
WO2003040395A2 (en) 2001-11-07 2003-05-15 Applera Corporation Universal nucleotides for nucleic acid analysis
US20070265220A1 (en) 2004-03-15 2007-11-15 City Of Hope Methods and compositions for the specific inhibition of gene expression by double-stranded RNA
WO2007030167A1 (en) 2005-09-02 2007-03-15 Nastech Pharmaceutical Company Inc. Modification of double-stranded ribonucleic acid molecules
DK2341943T3 (en) 2008-09-22 2019-02-25 Dicerna Pharmaceuticals Inc COMPOSITIONS AND METHODS OF SPECIFIC INHIBITION OF DSRNA REPRINT WITH MODIFICATIONS
US8691971B2 (en) 2008-09-23 2014-04-08 Scott G. Petersen Self delivering bio-labile phosphate protected pro-oligos for oligonucleotide based therapeutics and mediating RNA interference
US20100249214A1 (en) 2009-02-11 2010-09-30 Dicerna Pharmaceuticals Multiplex dicer substrate rna interference molecules having joining sequences
KR101728655B1 (ko) 2008-12-18 2017-04-19 다이서나 파마수이티컬, 인크. 유전자 발현의 특이적 억제를 위한 연장된 다이서 기질 제제 및 방법
WO2011005860A2 (en) 2009-07-07 2011-01-13 Alnylam Pharmaceuticals, Inc. 5' phosphate mimics
WO2011133871A2 (en) 2010-04-22 2011-10-27 Alnylam Pharmaceuticals, Inc. 5'-end derivatives
EP2928877B1 (en) 2012-12-06 2020-01-22 Merck Sharp & Dohme Corp. Disulfide masked prodrug compositions and methods
CA2950960A1 (en) 2014-06-06 2015-12-10 Solstice Biologics, Ltd. Polynucleotide constructs having bioreversible and non-bioreversible groups
DK3569711T3 (da) 2014-12-15 2021-02-22 Dicerna Pharmaceuticals Inc Ligandmodificerede dobbeltstrengede nukleinsyrer
WO2019075419A1 (en) * 2017-10-13 2019-04-18 Dicerna Pharmaceuticals, Inc. METHODS AND COMPOSITIONS FOR INHIBITING LDHA EXPRESSION
UA128786C2 (uk) * 2017-10-20 2024-10-23 Дайсерна Фармасьютикалз, Інк Олігонуклеотид для лікування інфекції гепатиту в

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WO2021067744A1 (en) 2021-04-08
CA3153026A1 (en) 2021-04-08
AU2020358016A1 (en) 2022-04-21
CN114761557B (zh) 2024-11-15
CL2022000825A1 (es) 2023-01-27
CN114761557A (zh) 2022-07-15
JP2022551269A (ja) 2022-12-08
US20220389430A1 (en) 2022-12-08
KR20220069103A (ko) 2022-05-26
EP4038191A1 (en) 2022-08-10
MX2022004032A (es) 2022-09-21
IL291841A (en) 2022-06-01

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