JP2020505032A5 - - Google Patents
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- Publication number
- JP2020505032A5 JP2020505032A5 JP2019538617A JP2019538617A JP2020505032A5 JP 2020505032 A5 JP2020505032 A5 JP 2020505032A5 JP 2019538617 A JP2019538617 A JP 2019538617A JP 2019538617 A JP2019538617 A JP 2019538617A JP 2020505032 A5 JP2020505032 A5 JP 2020505032A5
- Authority
- JP
- Japan
- Prior art keywords
- target molecule
- molecule
- target
- sirna
- effector
- 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.)
- Granted
Links
- 108020004459 Small interfering RNA Proteins 0.000 claims description 26
- 239000012636 effector Substances 0.000 claims description 22
- 150000007523 nucleic acids Chemical class 0.000 claims description 18
- 108020004707 nucleic acids Proteins 0.000 claims description 17
- 102000039446 nucleic acids Human genes 0.000 claims description 17
- 239000003446 ligand Substances 0.000 claims description 15
- 108091034117 Oligonucleotide Proteins 0.000 claims description 14
- 230000000692 anti-sense effect Effects 0.000 claims description 11
- 108091081021 Sense strand Proteins 0.000 claims description 10
- 230000014509 gene expression Effects 0.000 claims description 8
- 238000000338 in vitro Methods 0.000 claims description 6
- 230000003278 mimic effect Effects 0.000 claims description 6
- 108091027967 Small hairpin RNA Proteins 0.000 claims description 5
- 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 Polymers 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 5
- 230000004048 modification Effects 0.000 claims description 5
- 238000012986 modification Methods 0.000 claims description 5
- 239000004055 small Interfering RNA Substances 0.000 claims description 5
- 230000003834 intracellular effect Effects 0.000 claims description 4
- 239000002679 microRNA Substances 0.000 claims description 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 3
- 108090000994 Catalytic RNA Proteins 0.000 claims description 3
- 102000053642 Catalytic RNA Human genes 0.000 claims description 3
- 108700011259 MicroRNAs Proteins 0.000 claims description 3
- 239000012190 activator Substances 0.000 claims description 3
- 239000000074 antisense oligonucleotide Substances 0.000 claims description 3
- 238000012230 antisense oligonucleotides Methods 0.000 claims description 3
- 210000004369 blood Anatomy 0.000 claims description 3
- 239000008280 blood Substances 0.000 claims description 3
- 235000014633 carbohydrates Nutrition 0.000 claims description 3
- 230000003308 immunostimulating effect Effects 0.000 claims description 3
- 108091092562 ribozyme Proteins 0.000 claims description 3
- 210000002966 serum Anatomy 0.000 claims description 3
- 239000002924 silencing RNA Substances 0.000 claims description 3
- 239000002777 nucleoside Substances 0.000 claims description 2
- 150000003833 nucleoside derivatives Chemical class 0.000 claims description 2
- 125000003835 nucleoside group Chemical group 0.000 claims description 2
- 235000000346 sugar Nutrition 0.000 claims description 2
- 150000008163 sugars Chemical class 0.000 claims description 2
- 108091033409 CRISPR Proteins 0.000 claims 1
- 238000010354 CRISPR gene editing Methods 0.000 claims 1
- 0 CC(C)CC*C(*1*)OC(CO)C(*)C1O*(C(*)C1*C2OC(CO)C(*)C(*)C2*)OC(C*)C1O Chemical compound CC(C)CC*C(*1*)OC(CO)C(*)C1O*(C(*)C1*C2OC(CO)C(*)C(*)C2*)OC(C*)C1O 0.000 description 6
- 210000001163 endosome Anatomy 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- -1 U1 adapters Substances 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2022185398A JP7450008B2 (ja) | 2017-01-18 | 2022-11-21 | エンドソーム切断可能なリンカー |
| JP2024031869A JP2024052946A (ja) | 2017-01-18 | 2024-03-04 | エンドソーム切断可能なリンカー |
| JP2025205386A JP2026020334A (ja) | 2017-01-18 | 2025-11-27 | エンドソーム切断可能なリンカー |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762447786P | 2017-01-18 | 2017-01-18 | |
| US62/447,786 | 2017-01-18 | ||
| PCT/US2018/014213 WO2018136620A2 (en) | 2017-01-18 | 2018-01-18 | Endosomal cleavable linkers |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2022185398A Division JP7450008B2 (ja) | 2017-01-18 | 2022-11-21 | エンドソーム切断可能なリンカー |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2020505032A JP2020505032A (ja) | 2020-02-20 |
| JP2020505032A5 true JP2020505032A5 (https=) | 2021-02-25 |
| JP7244424B2 JP7244424B2 (ja) | 2023-03-22 |
Family
ID=62908671
Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2019538617A Active JP7244424B2 (ja) | 2017-01-18 | 2018-01-18 | エンドソーム切断可能なリンカー |
| JP2022185398A Active JP7450008B2 (ja) | 2017-01-18 | 2022-11-21 | エンドソーム切断可能なリンカー |
| JP2024031869A Pending JP2024052946A (ja) | 2017-01-18 | 2024-03-04 | エンドソーム切断可能なリンカー |
| JP2025205386A Pending JP2026020334A (ja) | 2017-01-18 | 2025-11-27 | エンドソーム切断可能なリンカー |
Family Applications After (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2022185398A Active JP7450008B2 (ja) | 2017-01-18 | 2022-11-21 | エンドソーム切断可能なリンカー |
| JP2024031869A Pending JP2024052946A (ja) | 2017-01-18 | 2024-03-04 | エンドソーム切断可能なリンカー |
| JP2025205386A Pending JP2026020334A (ja) | 2017-01-18 | 2025-11-27 | エンドソーム切断可能なリンカー |
Country Status (6)
| Country | Link |
|---|---|
| US (2) | US11286482B2 (https=) |
| EP (1) | EP3570892A4 (https=) |
| JP (4) | JP7244424B2 (https=) |
| AU (2) | AU2018209934B2 (https=) |
| CA (1) | CA3049133A1 (https=) |
| WO (1) | WO2018136620A2 (https=) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA3049133A1 (en) * | 2017-01-18 | 2018-07-26 | Alnylam Pharmaceuticals, Inc. | Endosomal cleavable linkers |
| WO2019217459A1 (en) | 2018-05-07 | 2019-11-14 | Alnylam Pharmaceuticals, Inc. | Extrahepatic delivery |
| CA3138627A1 (en) * | 2019-06-21 | 2020-12-24 | Alexander V. KEL'IN | Structurally defined sirna-dual variable domain immunoglobulin conjugates |
| WO2021049504A1 (ja) * | 2019-09-10 | 2021-03-18 | 第一三共株式会社 | 肝臓送達用ＧａｌＮＡｃ－オリゴヌクレオチドコンジュゲートおよび製造方法 |
| KR20230011913A (ko) | 2020-03-04 | 2023-01-25 | 버브 테라퓨틱스, 인크. | 표적화된 rna 전달을 위한 조성물 및 방법 |
| US20230257745A1 (en) | 2020-07-10 | 2023-08-17 | Alnylam Pharmaceuticals, Inc. | Circular siRNAs |
| WO2023283403A2 (en) | 2021-07-09 | 2023-01-12 | Alnylam Pharmaceuticals, Inc. | Bis-rnai compounds for cns delivery |
| JP2024530647A (ja) | 2021-08-03 | 2024-08-23 | ヴァーヴ・セラピューティクス，インコーポレーテッド | 標的ｒｎａ送達のための組成物および方法 |
| EP4522742A2 (en) | 2022-05-13 | 2025-03-19 | Alnylam Pharmaceuticals, Inc. | Single-stranded loop oligonucleotides |
| WO2024238385A2 (en) | 2023-05-12 | 2024-11-21 | Alnylam Pharmaceuticals, Inc. | Single-stranded loop oligonucleotides |
| WO2025242235A1 (zh) * | 2024-05-21 | 2025-11-27 | 深圳信立泰药业股份有限公司 | 双链rna缀合物及其制备方法和用途 |
| WO2025259743A1 (en) | 2024-06-12 | 2025-12-18 | Alnylam Pharmaceuticals, Inc. | Dual conjugate compounds for extrahepatic delivery |
| WO2025259747A2 (en) | 2024-06-12 | 2025-12-18 | Alnylam Pharmaceuticals, Inc. | Dystrophy myotonic protein kinase (dmpk) irna compositions and methods of use thereof |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5519134A (en) | 1994-01-11 | 1996-05-21 | Isis Pharmaceuticals, Inc. | Pyrrolidine-containing monomers and oligomers |
| US20070258986A1 (en) * | 2003-11-19 | 2007-11-08 | Govt of the US as represented by the secretary, | Targeted Delivery System for Bioactive Agents |
| US7528118B2 (en) | 2004-09-24 | 2009-05-05 | Alnylam Pharmaceuticals, Inc. | RNAi modulation of ApoB and uses thereof |
| US20060148740A1 (en) * | 2005-01-05 | 2006-07-06 | Prosensa B.V. | Mannose-6-phosphate receptor mediated gene transfer into muscle cells |
| US20080311040A1 (en) * | 2007-03-06 | 2008-12-18 | Flagship Ventures | METHODS AND COMPOSITIONS FOR IMPROVED THERAPEUTIC EFFECTS WITH siRNA |
| WO2009126933A2 (en) * | 2008-04-11 | 2009-10-15 | Alnylam Pharmaceuticals, Inc. | Site-specific delivery of nucleic acids by combining targeting ligands with endosomolytic components |
| EP2364330B1 (en) * | 2008-11-06 | 2015-03-25 | University Of Washington | Multiblock copolymers |
| US20100249214A1 (en) * | 2009-02-11 | 2010-09-30 | Dicerna Pharmaceuticals | Multiplex dicer substrate rna interference molecules having joining sequences |
| EP2780454A2 (en) | 2011-11-18 | 2014-09-24 | Alnylam Pharmaceuticals, Inc. | Modified rnai agents |
| EP2908818A4 (en) * | 2012-10-16 | 2016-07-13 | Endocyte Inc | CONJUGATES OF DRUG DELIVERY CONTAINING ARTIFICIAL AMINO ACIDS AND METHODS OF USE |
| CN105705638B (zh) * | 2013-07-05 | 2019-11-26 | 柏业公司 | 改善的具有高效能的纳米颗粒型寡核苷酸结构及其制备方法 |
| WO2015113922A1 (en) * | 2014-01-30 | 2015-08-06 | Roche Innovation Center Copenhagen A/S | Poly oligomer compound with biocleavable conjugates |
| EP3919619A1 (en) | 2015-07-17 | 2021-12-08 | Alnylam Pharmaceuticals, Inc. | Multi-targeted single entity conjugates |
| CA3049133A1 (en) * | 2017-01-18 | 2018-07-26 | Alnylam Pharmaceuticals, Inc. | Endosomal cleavable linkers |
-
2018
- 2018-01-18 CA CA3049133A patent/CA3049133A1/en active Pending
- 2018-01-18 JP JP2019538617A patent/JP7244424B2/ja active Active
- 2018-01-18 EP EP18741935.3A patent/EP3570892A4/en active Pending
- 2018-01-18 WO PCT/US2018/014213 patent/WO2018136620A2/en not_active Ceased
- 2018-01-18 US US16/474,776 patent/US11286482B2/en active Active
- 2018-01-18 AU AU2018209934A patent/AU2018209934B2/en active Active
-
2022
- 2022-02-10 US US17/668,917 patent/US20220177885A1/en active Pending
- 2022-11-21 JP JP2022185398A patent/JP7450008B2/ja active Active
-
2024
- 2024-02-07 AU AU2024200743A patent/AU2024200743B2/en active Active
- 2024-03-04 JP JP2024031869A patent/JP2024052946A/ja active Pending
-
2025
- 2025-11-27 JP JP2025205386A patent/JP2026020334A/ja active Pending
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