CA3153026A1 - Chemical modifications of small interfering rna with minimal fluorine content - Google Patents
Chemical modifications of small interfering rna with minimal fluorine content Download PDFInfo
- Publication number
- CA3153026A1 CA3153026A1 CA3153026A CA3153026A CA3153026A1 CA 3153026 A1 CA3153026 A1 CA 3153026A1 CA 3153026 A CA3153026 A CA 3153026A CA 3153026 A CA3153026 A CA 3153026A CA 3153026 A1 CA3153026 A1 CA 3153026A1
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- Prior art keywords
- modified
- nucleotides
- oligonucleotide
- antisense strand
- positions
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- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 125000004055 thiomethyl group Chemical group [H]SC([H])([H])* 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 230000036642 wellbeing Effects 0.000 description 1
Classifications
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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
-
- 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
-
- 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
- A61K31/712—Nucleic acids or oligonucleotides having modified sugars, i.e. other than ribose or 2'-deoxyribose
-
- 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
- C12N2310/32—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
- C12N2310/344—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
- C12N2310/30—Chemical structure
- C12N2310/35—Nature of the modification
- C12N2310/351—Conjugate
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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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/35—Nature of the modification
- C12N2310/351—Conjugate
- C12N2310/3515—Lipophilic moiety, e.g. cholesterol
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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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/35—Nature of the modification
- C12N2310/353—Nature of the modification linked to the nucleic acid via an atom other than carbon
- C12N2310/3533—Halogen
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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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
- C12N2310/531—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
- 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
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Wood Science & Technology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Plant Pathology (AREA)
- Biophysics (AREA)
- Virology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201962909278P | 2019-10-02 | 2019-10-02 | |
| US62/909,278 | 2019-10-02 | ||
| PCT/US2020/053999 WO2021067744A1 (en) | 2019-10-02 | 2020-10-02 | Chemical modifications of small interfering rna with minimal fluorine content |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3153026A1 true CA3153026A1 (en) | 2021-04-08 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3153026A Pending CA3153026A1 (en) | 2019-10-02 | 2020-10-02 | Chemical modifications of small interfering rna with minimal fluorine content |
Country Status (12)
| Country | Link |
|---|---|
| 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=) |
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| 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 |
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| 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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- 2020-10-02 EP EP20799874.1A patent/EP4038191A1/en not_active Withdrawn
- 2020-10-02 CN CN202080082980.8A patent/CN114761557B/zh active Active
- 2020-10-02 MX MX2022004032A patent/MX2022004032A/es unknown
- 2020-10-02 JP JP2022520472A patent/JP2022551269A/ja not_active Withdrawn
- 2020-10-02 WO PCT/US2020/053999 patent/WO2021067744A1/en not_active Ceased
- 2020-10-02 CA CA3153026A patent/CA3153026A1/en active Pending
- 2020-10-02 US US17/766,153 patent/US20220389430A1/en not_active Abandoned
- 2020-10-02 KR KR1020227014229A patent/KR20220069103A/ko not_active Withdrawn
- 2020-10-02 IL IL291841A patent/IL291841A/en unknown
- 2020-10-05 TW TW109134478A patent/TW202126809A/zh unknown
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2022
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Also Published As
| Publication number | Publication date |
|---|---|
| WO2021067744A1 (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 |
| TW202126809A (zh) | 2021-07-16 |
| IL291841A (en) | 2022-06-01 |
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