JPWO2020198509A5 - - Google Patents
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- JPWO2020198509A5 JPWO2020198509A5 JP2021557374A JP2021557374A JPWO2020198509A5 JP WO2020198509 A5 JPWO2020198509 A5 JP WO2020198509A5 JP 2021557374 A JP2021557374 A JP 2021557374A JP 2021557374 A JP2021557374 A JP 2021557374A JP WO2020198509 A5 JPWO2020198509 A5 JP WO2020198509A5
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- 108020004459 Small interfering RNA Proteins 0.000 claims description 179
- 108091034117 Oligonucleotide Proteins 0.000 claims description 82
- 150000001875 compounds Chemical class 0.000 claims description 72
- 229910052760 oxygen Inorganic materials 0.000 claims description 69
- 230000000692 anti-sense effect Effects 0.000 claims description 60
- 125000003729 nucleotide group Chemical group 0.000 claims description 39
- 239000002773 nucleotide Substances 0.000 claims description 35
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 31
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 30
- 125000003545 alkoxy group Chemical group 0.000 claims description 30
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 claims description 30
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims description 26
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 claims description 24
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 claims description 24
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 claims description 24
- 108020004707 nucleic acids Proteins 0.000 claims description 21
- 102000039446 nucleic acids Human genes 0.000 claims description 21
- 150000007523 nucleic acids Chemical class 0.000 claims description 21
- 125000005843 halogen group Chemical group 0.000 claims description 19
- 125000006239 protecting group Chemical group 0.000 claims description 19
- 108091081021 Sense strand Proteins 0.000 claims description 16
- 230000004048 modification Effects 0.000 claims description 16
- 238000012986 modification Methods 0.000 claims description 16
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 15
- 229930024421 Adenine Natural products 0.000 claims description 15
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 claims description 15
- 229960000643 adenine Drugs 0.000 claims description 15
- 125000001153 fluoro group Chemical group F* 0.000 claims description 15
- 229940035893 uracil Drugs 0.000 claims description 15
- 108020004414 DNA Proteins 0.000 claims description 14
- -1 dimethoxytrityl Chemical group 0.000 claims description 14
- 230000000295 complement effect Effects 0.000 claims description 13
- 229940104302 cytosine Drugs 0.000 claims description 13
- UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 claims description 12
- HCKNRHBSGZMOOF-UHFFFAOYSA-N 1-methoxy-2-methylperoxyethane Chemical compound COCCOOC HCKNRHBSGZMOOF-UHFFFAOYSA-N 0.000 claims description 12
- 239000002126 C01EB10 - Adenosine Substances 0.000 claims description 12
- MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 claims description 12
- UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 claims description 12
- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 claims description 12
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical group OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 12
- 229910019142 PO4 Inorganic materials 0.000 claims description 12
- 229960005305 adenosine Drugs 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- 150000001408 amides Chemical class 0.000 claims description 12
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 claims description 12
- UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 claims description 12
- 150000002148 esters Chemical class 0.000 claims description 12
- 229940029575 guanosine Drugs 0.000 claims description 12
- 235000021317 phosphate Nutrition 0.000 claims description 12
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 12
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 12
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 12
- 150000003852 triazoles Chemical class 0.000 claims description 12
- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 claims description 12
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 claims description 12
- 229940045145 uridine Drugs 0.000 claims description 12
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims description 11
- 150000008298 phosphoramidates Chemical class 0.000 claims description 11
- 150000003013 phosphoric acid derivatives Chemical class 0.000 claims description 11
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 11
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Chemical class Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 claims description 10
- 125000006850 spacer group Chemical group 0.000 claims description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 8
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims description 8
- 238000007385 chemical modification Methods 0.000 claims description 7
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 claims description 6
- YIXYJZHPCDLFAW-UHFFFAOYSA-N [methoxy-[methoxy(phenyl)methoxy]methyl]benzene Chemical compound C=1C=CC=CC=1C(OC)OC(OC)C1=CC=CC=C1 YIXYJZHPCDLFAW-UHFFFAOYSA-N 0.000 claims description 6
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- CPZBTYRIGVOOMI-UHFFFAOYSA-N methylsulfanyl(methylsulfanylmethoxy)methane Chemical compound CSCOCSC CPZBTYRIGVOOMI-UHFFFAOYSA-N 0.000 claims description 6
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical compound C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 claims description 6
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims description 6
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
- 230000003993 interaction Effects 0.000 claims description 4
- 125000003835 nucleoside group Chemical group 0.000 claims description 4
- 150000004713 phosphodiesters Chemical class 0.000 claims description 4
- 230000001225 therapeutic effect Effects 0.000 claims description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
- 108020005004 Guide RNA Proteins 0.000 claims description 2
- 210000004556 brain Anatomy 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 210000001072 colon Anatomy 0.000 claims description 2
- 210000003734 kidney Anatomy 0.000 claims description 2
- 210000004185 liver Anatomy 0.000 claims description 2
- 210000004072 lung Anatomy 0.000 claims description 2
- 108091070501 miRNA Proteins 0.000 claims description 2
- 239000002679 microRNA Substances 0.000 claims description 2
- 210000003205 muscle Anatomy 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 210000000496 pancreas Anatomy 0.000 claims description 2
- 210000003491 skin Anatomy 0.000 claims description 2
- 210000000952 spleen Anatomy 0.000 claims description 2
- 210000001541 thymus gland Anatomy 0.000 claims description 2
- 108020004999 messenger RNA Proteins 0.000 claims 2
- 238000006467 substitution reaction Methods 0.000 claims 2
- 210000003169 central nervous system Anatomy 0.000 claims 1
- 238000002347 injection Methods 0.000 claims 1
- 239000007924 injection Substances 0.000 claims 1
- 238000000185 intracerebroventricular administration Methods 0.000 claims 1
- 238000007913 intrathecal administration Methods 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims 1
- 239000010452 phosphate Substances 0.000 claims 1
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 claims 1
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 239000002777 nucleoside Substances 0.000 description 12
- 150000003833 nucleoside derivatives Chemical class 0.000 description 12
- DVFXLNFDWATPMW-IWOKLKJTSA-N tert-butyldiphenylsilyl Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO[Si](C=2C=CC=CC=2)(C=2C=CC=CC=2)C(C)(C)C)[C@@H](OP(O)(=O)OC[C@@H]2[C@H](C[C@@H](O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=O)OC[C@@H]2[C@H](C[C@@H](O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=O)OC[C@@H]2[C@H](C[C@@H](O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=O)OC[C@@H]2[C@H](CC(O2)N2C3=NC=NC(N)=C3N=C2)OP(O)(=O)OC[C@@H]2[C@H](C[C@@H](O2)N2C3=C(C(NC(N)=N3)=O)N=C2)O)C1 DVFXLNFDWATPMW-IWOKLKJTSA-N 0.000 description 1
- 125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2025015181A JP2025072451A (ja) | 2019-03-26 | 2025-01-31 | 安定性が増加した修飾オリゴヌクレオチド |
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201962824136P | 2019-03-26 | 2019-03-26 | |
| US62/824,136 | 2019-03-26 | ||
| US201962826454P | 2019-03-29 | 2019-03-29 | |
| US62/826,454 | 2019-03-29 | ||
| US201962864792P | 2019-06-21 | 2019-06-21 | |
| US62/864,792 | 2019-06-21 | ||
| PCT/US2020/025017 WO2020198509A2 (en) | 2019-03-26 | 2020-03-26 | Modified oligonucleotides with increased stability |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2025015181A Division JP2025072451A (ja) | 2019-03-26 | 2025-01-31 | 安定性が増加した修飾オリゴヌクレオチド |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2022528840A JP2022528840A (ja) | 2022-06-16 |
| JPWO2020198509A5 true JPWO2020198509A5 (https=) | 2023-04-03 |
| JP2022528840A5 JP2022528840A5 (https=) | 2023-04-03 |
Family
ID=72609530
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2021557374A Pending JP2022528840A (ja) | 2019-03-26 | 2020-03-26 | 安定性が増加した修飾オリゴヌクレオチド |
| JP2025015181A Pending JP2025072451A (ja) | 2019-03-26 | 2025-01-31 | 安定性が増加した修飾オリゴヌクレオチド |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2025015181A Pending JP2025072451A (ja) | 2019-03-26 | 2025-01-31 | 安定性が増加した修飾オリゴヌクレオチド |
Country Status (4)
| Country | Link |
|---|---|
| US (2) | US11820985B2 (https=) |
| EP (1) | EP3946369A4 (https=) |
| JP (2) | JP2022528840A (https=) |
| WO (1) | WO2020198509A2 (https=) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3277811B1 (en) | 2015-04-03 | 2020-12-23 | University of Massachusetts | Fully stabilized asymmetric sirna |
| US10633653B2 (en) | 2015-08-14 | 2020-04-28 | University Of Massachusetts | Bioactive conjugates for oligonucleotide delivery |
| WO2017132669A1 (en) | 2016-01-31 | 2017-08-03 | University Of Massachusetts | Branched oligonucleotides |
| CA3033368A1 (en) | 2016-08-12 | 2018-02-15 | University Of Massachusetts | Conjugated oligonucleotides |
| CN106987604B (zh) * | 2017-03-29 | 2021-05-28 | 北京希诺谷生物科技有限公司 | 一种制备动脉粥样硬化疾病模型犬的方法 |
| JP7406793B2 (ja) | 2017-06-23 | 2023-12-28 | ユニバーシティー オブ マサチューセッツ | ２テイル自己デリバリー型ｓｉＲＮＡおよび関連方法 |
| JP7627042B2 (ja) | 2018-08-23 | 2025-02-05 | ユニバーシティー オブ マサチューセッツ | Ｏ－メチルリッチ完全安定化オリゴヌクレオチド |
| CN113614232A (zh) | 2019-01-18 | 2021-11-05 | 马萨诸塞大学 | 动态药代动力学修饰锚 |
| US11820985B2 (en) | 2019-03-26 | 2023-11-21 | University Of Massachusetts | Modified oligonucleotides with increased stability |
| MX2022001710A (es) | 2019-08-09 | 2022-05-10 | Univ Massachusetts | Oligonucleótidos modificados químicamente dirigidos a los snp. |
| US12365894B2 (en) | 2019-09-16 | 2025-07-22 | University Of Massachusetts | Branched lipid conjugates of siRNA for specific tissue delivery |
| JP7505545B2 (ja) | 2020-03-25 | 2024-06-25 | 株式会社プロテリアル | センサ |
| JP7837560B2 (ja) | 2020-03-26 | 2026-03-31 | ユニバーシティー オブ マサチューセッツ | 安定性の向上を有する修飾オリゴヌクレオチドの合成 |
| WO2021242883A1 (en) | 2020-05-26 | 2021-12-02 | University Of Massachusetts | Synthetic oligonucleotides having regions of block and cluster modifications |
| US12077758B2 (en) | 2020-05-28 | 2024-09-03 | University Of Massachusetts | Oligonucleotides for SARS-CoV-2 modulation |
| WO2022212231A2 (en) * | 2021-03-29 | 2022-10-06 | Alnylam Pharmaceuticals, Inc. | Huntingtin (htt) irna agent compositions and methods of use thereof |
| AU2022299169A1 (en) | 2021-06-23 | 2024-02-08 | Beth Israel Deaconess Medical Center, Inc. | Optimized anti-flt1 oligonucleotide compounds for treatment of preeclampsia and other angiogenic disorders |
| US20250223588A1 (en) * | 2021-10-19 | 2025-07-10 | Alnylam Pharmaceuticals, Inc. | Oligonucleotides with 2'-deoxy-2'-f-2'-c-methyl nucleotides |
| US20230313198A1 (en) * | 2021-12-17 | 2023-10-05 | University Of Massachusetts | Oligonucleotides for mlh3 modulation |
| WO2024002007A1 (zh) * | 2022-06-27 | 2024-01-04 | 大睿生物医药科技(上海)有限公司 | 含有可降低脱靶毒性的核苷酸类似物的双链rna |
| WO2025264952A2 (en) * | 2024-06-21 | 2025-12-26 | Eli Lilly And Company | Novel rna therapeutics and uses thereof |
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| JPH08508490A (ja) | 1993-03-31 | 1996-09-10 | スターリング ウィンスロップ インコーポレイティド | 新規５’−置換ヌクレオシド及びそれから得られるオリゴマー |
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2020
- 2020-03-26 US US16/831,470 patent/US11820985B2/en active Active
- 2020-03-26 EP EP20777915.8A patent/EP3946369A4/en active Pending
- 2020-03-26 WO PCT/US2020/025017 patent/WO2020198509A2/en not_active Ceased
- 2020-03-26 JP JP2021557374A patent/JP2022528840A/ja active Pending
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2023
- 2023-09-01 US US18/459,992 patent/US20240141362A1/en active Pending
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2025
- 2025-01-31 JP JP2025015181A patent/JP2025072451A/ja active Pending
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