JPWO2020160163A5 - - Google Patents
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- JPWO2020160163A5 JPWO2020160163A5 JP2021544144A JP2021544144A JPWO2020160163A5 JP WO2020160163 A5 JPWO2020160163 A5 JP WO2020160163A5 JP 2021544144 A JP2021544144 A JP 2021544144A JP 2021544144 A JP2021544144 A JP 2021544144A JP WO2020160163 A5 JPWO2020160163 A5 JP WO2020160163A5
- Authority
- JP
- Japan
- Prior art keywords
- nucleobases
- seq
- modified
- oligonucleotide
- isometric portion
- 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
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- 108091034117 Oligonucleotide Proteins 0.000 claims description 129
- 239000002777 nucleoside Substances 0.000 claims description 114
- 150000001875 compounds Chemical class 0.000 claims description 99
- 125000003835 nucleoside group Chemical group 0.000 claims description 73
- 235000000346 sugar Nutrition 0.000 claims description 72
- 108091030071 RNAI Proteins 0.000 claims description 63
- 230000009368 gene silencing by RNA Effects 0.000 claims description 63
- 230000000692 anti-sense effect Effects 0.000 claims description 34
- 150000003833 nucleoside derivatives Chemical class 0.000 claims description 34
- 230000001268 conjugating effect Effects 0.000 claims description 14
- 125000002619 bicyclic group Chemical group 0.000 claims description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 235000021092 sugar substitutes Nutrition 0.000 claims description 11
- 239000003765 sweetening agent Substances 0.000 claims description 11
- 230000000295 complement effect Effects 0.000 claims description 10
- 201000010099 disease Diseases 0.000 claims description 10
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 9
- 238000012986 modification Methods 0.000 claims description 7
- 230000004048 modification Effects 0.000 claims description 7
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims description 7
- 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 6
- 150000004713 phosphodiesters Chemical class 0.000 claims description 5
- 208000024827 Alzheimer disease Diseases 0.000 claims description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 claims description 4
- 239000011780 sodium chloride Substances 0.000 claims description 4
- 208000024891 symptom Diseases 0.000 claims description 4
- YIMATHOGWXZHFX-WCTZXXKLSA-N (2r,3r,4r,5r)-5-(hydroxymethyl)-3-(2-methoxyethoxy)oxolane-2,4-diol Chemical compound COCCO[C@H]1[C@H](O)O[C@H](CO)[C@H]1O YIMATHOGWXZHFX-WCTZXXKLSA-N 0.000 claims description 3
- LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical group CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 claims description 3
- 210000001175 cerebrospinal fluid Anatomy 0.000 claims description 3
- 208000035657 Abasia Diseases 0.000 claims description 2
- 208000005145 Cerebral amyloid angiopathy Diseases 0.000 claims description 2
- 125000000824 D-ribofuranosyl group Chemical group [H]OC([H])([H])[C@@]1([H])OC([H])(*)[C@]([H])(O[H])[C@]1([H])O[H] 0.000 claims description 2
- 201000010374 Down Syndrome Diseases 0.000 claims description 2
- 102100034343 Integrase Human genes 0.000 claims description 2
- 101710203526 Integrase Proteins 0.000 claims description 2
- 241001465754 Metazoa Species 0.000 claims description 2
- 206010044688 Trisomy 21 Diseases 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 230000001668 ameliorated effect Effects 0.000 claims description 2
- 239000000074 antisense oligonucleotide Substances 0.000 claims description 2
- 238000012230 antisense oligonucleotides Methods 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
- 206010002942 Apathy Diseases 0.000 claims 2
- 108020000948 Antisense Oligonucleotides Proteins 0.000 claims 1
- DEVWEFBXXYMHIL-UHFFFAOYSA-N CCCOP(O)=O Chemical compound CCCOP(O)=O DEVWEFBXXYMHIL-UHFFFAOYSA-N 0.000 claims 1
- 206010010904 Convulsion Diseases 0.000 claims 1
- 206010012289 Dementia Diseases 0.000 claims 1
- 206010017577 Gait disturbance Diseases 0.000 claims 1
- 230000002159 abnormal effect Effects 0.000 claims 1
- 230000003941 amyloidogenesis Effects 0.000 claims 1
- 230000003542 behavioural effect Effects 0.000 claims 1
- 208000010877 cognitive disease Diseases 0.000 claims 1
- 230000006735 deficit Effects 0.000 claims 1
- 108020004707 nucleic acids Proteins 0.000 claims 1
- 150000007523 nucleic acids Chemical class 0.000 claims 1
- 102000039446 nucleic acids Human genes 0.000 claims 1
- 230000000750 progressive effect Effects 0.000 claims 1
- 238000000034 method Methods 0.000 description 6
- 150000008163 sugars Chemical class 0.000 description 4
- 238000011830 transgenic mouse model Methods 0.000 description 3
- 101000823051 Homo sapiens Amyloid-beta precursor protein Proteins 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 102000046783 human APP Human genes 0.000 description 2
- 101100268553 Homo sapiens APP gene Proteins 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- FBWJHGIUUCOZRM-UHFFFAOYSA-N cyclopropylphosphonic acid Chemical compound OP(O)(=O)C1CC1 FBWJHGIUUCOZRM-UHFFFAOYSA-N 0.000 description 1
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical group NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2024158813A JP2025000693A (ja) | 2019-01-29 | 2024-09-13 | Ａｐｐの発現を低減するための化合物及び方法 |
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201962798353P | 2019-01-29 | 2019-01-29 | |
| US62/798,353 | 2019-01-29 | ||
| US201962841169P | 2019-04-30 | 2019-04-30 | |
| US62/841,169 | 2019-04-30 | ||
| US201962915764P | 2019-10-16 | 2019-10-16 | |
| US62/915,764 | 2019-10-16 | ||
| PCT/US2020/015701 WO2020160163A1 (en) | 2019-01-29 | 2020-01-29 | Compounds and methods for reducing app expression |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2024158813A Division JP2025000693A (ja) | 2019-01-29 | 2024-09-13 | Ａｐｐの発現を低減するための化合物及び方法 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2022518929A JP2022518929A (ja) | 2022-03-17 |
| JPWO2020160163A5 true JPWO2020160163A5 (enExample) | 2023-02-02 |
| JP7557469B2 JP7557469B2 (ja) | 2024-09-27 |
Family
ID=71840111
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2021544144A Active JP7557469B2 (ja) | 2019-01-29 | 2020-01-29 | Ａｐｐの発現を低減するための化合物及び方法 |
| JP2024158813A Pending JP2025000693A (ja) | 2019-01-29 | 2024-09-13 | Ａｐｐの発現を低減するための化合物及び方法 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2024158813A Pending JP2025000693A (ja) | 2019-01-29 | 2024-09-13 | Ａｐｐの発現を低減するための化合物及び方法 |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US20220380773A1 (enExample) |
| EP (1) | EP3918073A4 (enExample) |
| JP (2) | JP7557469B2 (enExample) |
| TW (1) | TW202043472A (enExample) |
| UY (1) | UY38562A (enExample) |
| WO (1) | WO2020160163A1 (enExample) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR102839166B1 (ko) | 2018-01-12 | 2025-07-28 | 브리스톨-마이어스 스큅 컴퍼니 | 알파-시누클레인을 표적화하는 안티센스 올리고뉴클레오티드 및 그의 용도 |
| BR112020013994A2 (pt) | 2018-01-12 | 2020-12-08 | Bristol-Myers Squibb Company | Oligonucleotídeos antissenso que direcionam alfa-sinucleína e seus usos |
| WO2019169243A1 (en) | 2018-03-02 | 2019-09-06 | Ionis Pharmaceuticals, Inc. | Compounds and methods for the modulation of amyloid-beta precursor protein |
| EP3898979A4 (en) * | 2018-12-19 | 2022-10-12 | Alnylam Pharmaceuticals, Inc. | Amyloid precursor protein (app) rnai agent compositions and methods of use thereof |
| MX2021012098A (es) * | 2019-04-03 | 2021-11-03 | Bristol Myers Squibb Co | Oligonucleotidos antisentido del transcrito tipo 2 de angiopoyetina (angptl2) y sus usos. |
| CN114555621B (zh) | 2019-08-15 | 2025-10-28 | Ionis制药公司 | 键修饰的寡聚化合物及其用途 |
| WO2022026589A1 (en) | 2020-07-28 | 2022-02-03 | Ionis Pharmaceuticals, Inc. | Compounds and methods for reducing app expression |
| WO2022165172A1 (en) * | 2021-01-29 | 2022-08-04 | Alnylam Pharmaceuticals, Inc. | Irna compositions and methods for silencing amyloid precursor protein (app) |
| EP4416284A1 (en) * | 2021-10-15 | 2024-08-21 | Alnylam Pharmaceuticals, Inc. | Extra-hepatic delivery irna compositions and methods of use thereof |
| TW202511488A (zh) * | 2023-08-31 | 2025-03-16 | 大陸商上海拓界生物醫藥科技有限公司 | 靶向ＡＰＰ的ＲＮＡｉ劑及其醫藥用途 |
| WO2025228429A1 (zh) * | 2024-04-30 | 2025-11-06 | 北京安龙生物医药有限公司 | 靶向淀粉样前体蛋白基因的寡核苷酸及其用途 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0644889A4 (en) * | 1991-12-24 | 1996-01-10 | Isis Pharmaceuticals Inc | COMPOSITIONS AND METHODS FOR MODULATION OF -g (b) -AMYLOID. |
| US20030232435A1 (en) * | 2002-06-14 | 2003-12-18 | Isis Pharmaceuticals Inc. | Antisense modulation of amyloid beta protein precursor expression |
| GB0324854D0 (en) * | 2003-10-24 | 2003-11-26 | Expresson Biosystems Ltd | App/ena antisense |
| WO2009105572A2 (en) * | 2008-02-19 | 2009-08-27 | Edunn Biotechonology Inc. | Antisense modulation of amyloid beta protein expression |
| US20100190807A1 (en) * | 2008-08-26 | 2010-07-29 | Senex Biotechnology, Inc. | CDKI Pathway inhibitors and uses thereof to regulate expression to TAU protein |
| US20110301052A1 (en) * | 2010-04-16 | 2011-12-08 | Mcneel Douglas G | Diagnostic evaluation of antibody responses to commonly recognized prostate cancer-associated antigens |
| WO2014197826A1 (en) * | 2013-06-07 | 2014-12-11 | Rana Therapeutics, Inc. | Compositions and methods for modulating foxp3 expression |
| WO2015023941A1 (en) * | 2013-08-16 | 2015-02-19 | Rana Therapeutics, Inc. | Oligonucleotides targeting euchromatin regions of genes |
| EP3055414A4 (en) * | 2013-10-11 | 2017-07-19 | Ionis Pharmaceuticals, Inc. | Compositions for modulating c9orf72 expression |
| DK3137476T3 (da) * | 2014-04-28 | 2019-11-18 | Ionis Pharmaceuticals Inc | Linker-modificerede oligomerforbindelser |
| WO2019169243A1 (en) * | 2018-03-02 | 2019-09-06 | Ionis Pharmaceuticals, Inc. | Compounds and methods for the modulation of amyloid-beta precursor protein |
-
2020
- 2020-01-29 UY UY0001038562A patent/UY38562A/es not_active Application Discontinuation
- 2020-01-29 EP EP20749114.3A patent/EP3918073A4/en active Pending
- 2020-01-29 WO PCT/US2020/015701 patent/WO2020160163A1/en not_active Ceased
- 2020-01-29 JP JP2021544144A patent/JP7557469B2/ja active Active
- 2020-01-29 US US17/424,672 patent/US20220380773A1/en active Pending
- 2020-01-30 TW TW109102899A patent/TW202043472A/zh unknown
-
2024
- 2024-09-13 JP JP2024158813A patent/JP2025000693A/ja active Pending
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