JPWO2019200124A5 - - Google Patents
Download PDFInfo
- Publication number
- JPWO2019200124A5 JPWO2019200124A5 JP2020554092A JP2020554092A JPWO2019200124A5 JP WO2019200124 A5 JPWO2019200124 A5 JP WO2019200124A5 JP 2020554092 A JP2020554092 A JP 2020554092A JP 2020554092 A JP2020554092 A JP 2020554092A JP WO2019200124 A5 JPWO2019200124 A5 JP WO2019200124A5
- Authority
- JP
- Japan
- Prior art keywords
- double
- nucleic acid
- stranded nucleic
- acid inhibitor
- inhibitor molecule
- 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.)
- Pending
Links
- 108020004707 nucleic acids Proteins 0.000 claims description 76
- 102000039446 nucleic acids Human genes 0.000 claims description 76
- 150000007523 nucleic acids Chemical class 0.000 claims description 76
- 239000003112 inhibitor Substances 0.000 claims description 72
- 125000003729 nucleotide group Chemical group 0.000 claims description 70
- 239000002773 nucleotide Substances 0.000 claims description 64
- 125000002619 bicyclic group Chemical group 0.000 claims description 27
- 108091081021 Sense strand Proteins 0.000 claims description 25
- 230000000692 anti-sense effect Effects 0.000 claims description 19
- 150000002632 lipids Chemical class 0.000 claims description 13
- 108091034117 Oligonucleotide Proteins 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 125000003843 furanosyl group Chemical group 0.000 claims description 6
- 125000006239 protecting group Chemical group 0.000 claims description 6
- 239000003446 ligand Substances 0.000 claims description 5
- OVRNDRQMDRJTHS-KEWYIRBNSA-N N-acetyl-D-galactosamine Chemical compound CC(=O)N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-KEWYIRBNSA-N 0.000 claims description 4
- MBLBDJOUHNCFQT-UHFFFAOYSA-N N-acetyl-D-galactosamine Natural products CC(=O)NC(C=O)C(O)C(O)C(O)CO MBLBDJOUHNCFQT-UHFFFAOYSA-N 0.000 claims description 4
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical group [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 239000002105 nanoparticle Substances 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- GJTBSTBJLVYKAU-XVFCMESISA-N 2-thiouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=S)NC(=O)C=C1 GJTBSTBJLVYKAU-XVFCMESISA-N 0.000 claims description 2
- LQLQRFGHAALLLE-UHFFFAOYSA-N 5-bromouracil Chemical compound BrC1=CNC(=O)NC1=O LQLQRFGHAALLLE-UHFFFAOYSA-N 0.000 claims description 2
- KSNXJLQDQOIRIP-UHFFFAOYSA-N 5-iodouracil Chemical compound IC1=CNC(=O)NC1=O KSNXJLQDQOIRIP-UHFFFAOYSA-N 0.000 claims description 2
- MSSXOMSJDRHRMC-UHFFFAOYSA-N 9H-purine-2,6-diamine Chemical compound NC1=NC(N)=C2NC=NC2=N1 MSSXOMSJDRHRMC-UHFFFAOYSA-N 0.000 claims description 2
- 108020004414 DNA Proteins 0.000 claims description 2
- 229930185560 Pseudouridine Natural products 0.000 claims description 2
- PTJWIQPHWPFNBW-UHFFFAOYSA-N Pseudouridine C Natural products OC1C(O)C(CO)OC1C1=CNC(=O)NC1=O PTJWIQPHWPFNBW-UHFFFAOYSA-N 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- WGDUUQDYDIIBKT-UHFFFAOYSA-N beta-Pseudouridine Natural products OC1OC(CN2C=CC(=O)NC2=O)C(O)C1O WGDUUQDYDIIBKT-UHFFFAOYSA-N 0.000 claims description 2
- FBPFZTCFMRRESA-UHFFFAOYSA-N hexane-1,2,3,4,5,6-hexol Chemical class OCC(O)C(O)C(O)C(O)CO FBPFZTCFMRRESA-UHFFFAOYSA-N 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 230000003278 mimic effect Effects 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- PTJWIQPHWPFNBW-GBNDHIKLSA-N pseudouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1C1=CNC(=O)NC1=O PTJWIQPHWPFNBW-GBNDHIKLSA-N 0.000 claims description 2
- 150000003230 pyrimidines Chemical class 0.000 claims description 2
- 229910019142 PO4 Inorganic materials 0.000 claims 1
- 239000010452 phosphate Substances 0.000 claims 1
- 101150006308 botA gene Proteins 0.000 description 12
- 102100030970 Apolipoprotein C-III Human genes 0.000 description 5
- 101000793223 Homo sapiens Apolipoprotein C-III Proteins 0.000 description 5
- -1 cationic lipid Chemical class 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 229930182558 Sterol Natural products 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 150000003432 sterols Chemical class 0.000 description 2
- 235000003702 sterols Nutrition 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- NRJAVPSFFCBXDT-HUESYALOSA-N 1,2-distearoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCCCC NRJAVPSFFCBXDT-HUESYALOSA-N 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 230000003028 elevating effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201862657428P | 2018-04-13 | 2018-04-13 | |
| US62/657,428 | 2018-04-13 | ||
| US201862778755P | 2018-12-12 | 2018-12-12 | |
| US62/778,755 | 2018-12-12 | ||
| PCT/US2019/027021 WO2019200124A1 (en) | 2018-04-13 | 2019-04-11 | Double-stranded nucleic acid inhibitor molecules modified with tm-increasing nucleotides |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2021520355A JP2021520355A (ja) | 2021-08-19 |
| JPWO2019200124A5 true JPWO2019200124A5 (https=) | 2022-04-14 |
| JP2021520355A5 JP2021520355A5 (https=) | 2022-04-14 |
Family
ID=68161339
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020554092A Withdrawn JP2021520355A (ja) | 2018-04-13 | 2019-04-11 | Ｔｍ上昇ヌクレオチドで修飾された二本鎖核酸阻害剤分子 |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US11873488B2 (https=) |
| EP (1) | EP3773609A4 (https=) |
| JP (1) | JP2021520355A (https=) |
| KR (1) | KR20200144100A (https=) |
| CN (1) | CN111971051A (https=) |
| AU (1) | AU2019252529A1 (https=) |
| CA (1) | CA3094008A1 (https=) |
| IL (1) | IL277813A (https=) |
| MX (1) | MX2020010802A (https=) |
| WO (1) | WO2019200124A1 (https=) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2019397247A1 (en) * | 2018-12-12 | 2021-06-24 | Dicerna Pharmaceuticals, Inc. | Double-stranded nucleic acid inhibitor molecules containing a triloop |
| WO2020226960A1 (en) * | 2019-05-03 | 2020-11-12 | Dicerna Pharmaceuticals, Inc. | Double-stranded nucleic acid inhibitor molecules with shortened sense strands |
| US20240287512A1 (en) * | 2021-05-11 | 2024-08-29 | Dicerna Pharmaceuticals, Inc. | Lipid conjugation for targeting neurons of the central nervous system |
| WO2023069707A2 (en) * | 2021-10-22 | 2023-04-27 | Sirnaomics, Inc. | Products and compositions |
| JPWO2023176863A1 (https=) * | 2022-03-16 | 2023-09-21 |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8273866B2 (en) * | 2002-02-20 | 2012-09-25 | Merck Sharp & Dohme Corp. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (SINA) |
| WO2009117589A1 (en) | 2008-03-21 | 2009-09-24 | Isis Pharmaceuticals, Inc. | Oligomeric compounds comprising tricyclic nucleosides and methods for their use |
| JP2012504389A (ja) * | 2008-09-22 | 2012-02-23 | 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 | 修飾を有するｄｓＲＮＡによる遺伝子発現の特異的な阻害のための組成物および方法 |
| US20110288147A1 (en) | 2008-09-22 | 2011-11-24 | Bob Dale Brown | Compositions and methods for the specific inhibition of gene expression by DSRNA containing a tetraloop |
| AU2009336191B2 (en) * | 2008-12-18 | 2017-08-24 | Novo Nordisk A/S | Extended dicer substrate agents and methods for the specific inhibition of gene expression |
| CN104651362A (zh) * | 2009-04-03 | 2015-05-27 | 戴瑟纳制药公司 | 利用不对称双链rna特异性抑制kras的方法和组合物 |
| US20140011860A1 (en) | 2010-07-19 | 2014-01-09 | Isis Pharmaceuticals, Inc. | Compounds and methods for modulating target nuclear and sub-nuclear nucleic acid molecules in cells and animals |
| EP2850092B1 (en) | 2012-04-09 | 2017-03-01 | Ionis Pharmaceuticals, Inc. | Tricyclic nucleic acid analogs |
| CA2902571A1 (en) * | 2013-03-15 | 2014-09-18 | MiRagen Therapeutics, Inc. | Bridged bicyclic nucleosides |
| WO2014140348A1 (en) | 2013-03-15 | 2014-09-18 | Universität Bern | Tricyclic nucleosides and oligomeric compounds prepared therefrom |
| DK3444350T3 (da) * | 2013-07-03 | 2022-02-07 | Dicerna Pharmaceuticals Inc | Fremgangsmåder og sammensætninger til specifik hæmning af alpha-1 antitrypsin ved dobbeltstrenget rna |
| US10150965B2 (en) * | 2013-12-06 | 2018-12-11 | Dicerna Pharmaceuticals, Inc. | Methods and compositions for the specific inhibition of transthyretin (TTR) by double-stranded RNA |
| EP3119789B1 (en) | 2014-03-17 | 2020-04-22 | Ionis Pharmaceuticals, Inc. | Bicyclic carbocyclic nucleosides and oligomeric compounds prepared therefrom |
| AU2015330670B2 (en) * | 2014-10-10 | 2022-01-06 | Novo Nordisk Health Care Ag | Therapeutic inhibition of lactate dehydrogenase and agents therefor |
| 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 |
| US10036017B2 (en) * | 2015-02-17 | 2018-07-31 | Dicerna Pharmaceuticals, Inc. | Methods and compositions for the specific inhibition of complement component 5(C5) by double-stranded RNA |
| KR102350647B1 (ko) | 2016-09-02 | 2022-01-14 | 다이서나 파마수이티컬, 인크. | 4'-포스페이트 유사체 및 이를 포함하는 올리고뉴클레오타이드 |
| KR20200023427A (ko) * | 2017-06-29 | 2020-03-04 | 다이서나 파마수이티컬, 인크. | Hmgb1 발현을 억제하기 위한 조성물 및 방법 |
-
2019
- 2019-04-11 CA CA3094008A patent/CA3094008A1/en active Pending
- 2019-04-11 WO PCT/US2019/027021 patent/WO2019200124A1/en not_active Ceased
- 2019-04-11 JP JP2020554092A patent/JP2021520355A/ja not_active Withdrawn
- 2019-04-11 EP EP19784831.0A patent/EP3773609A4/en active Pending
- 2019-04-11 KR KR1020207029911A patent/KR20200144100A/ko not_active Ceased
- 2019-04-11 MX MX2020010802A patent/MX2020010802A/es unknown
- 2019-04-11 AU AU2019252529A patent/AU2019252529A1/en not_active Abandoned
- 2019-04-11 CN CN201980025615.0A patent/CN111971051A/zh active Pending
- 2019-04-11 US US16/381,931 patent/US11873488B2/en active Active
-
2020
- 2020-10-05 IL IL277813A patent/IL277813A/en unknown
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2021520355A5 (https=) | ||
| TWI784934B (zh) | 抑制lpa之基因表現之組合物及方法 | |
| TWI680767B (zh) | 用於增強的細胞攝取之化合物及方法 | |
| JP7535047B2 (ja) | トリループを含む二本鎖核酸インヒビター分子 | |
| JP7197463B2 (ja) | Ｓｍｎ２の調節のための化合物及び方法 | |
| EP1675954B1 (en) | Nucleic acids useful for triggering tumor cell lethality | |
| US11873488B2 (en) | Double-stranded nucleic acid inhibitor molecules modified with Tm-increasing nucleotides | |
| CA3224145A1 (en) | Novel rna therapeutics and uses thereof | |
| CN111902537A (zh) | Dnm2表达的调节剂 | |
| JPWO2020041769A5 (https=) | ||
| CN119403927A (zh) | 用于抑制跨膜丝氨酸蛋白酶6（tmprss6）表达的组合物和方法 | |
| JPWO2019200124A5 (https=) | ||
| JP2022530678A (ja) | 短縮センス鎖を有する二本鎖核酸阻害剤分子 | |
| KR20240168424A (ko) | 앤지오텐시노겐 조절 조성물 및 이의 사용 방법 | |
| JP2025081562A (ja) | アンチセンス核酸の毒性を軽減する方法 | |
| JP2023530072A (ja) | Ｐｍｐ２２を調節するための化合物及び方法 | |
| JPWO2022187435A5 (https=) | ||
| CN118979036A (zh) | 抑制APP基因表达的siRNA及其缀合物和应用 | |
| CA3250061A1 (en) | Compositions and methods for inhibiting the expression of SNCA | |
| CN115279904A (zh) | 抑制asah1基因表达的组合物和方法 | |
| JPWO2023278607A5 (https=) | ||
| WO2026087871A1 (en) | Gene silencing of cardiovascular genes | |
| KR20260049590A (ko) | Tubb4a 발현을 감소시키기 위한 화합물 및 방법 | |
| KR20240110595A (ko) | 안정화된 rna 제제 | |
| JPWO2023003995A5 (https=) |