JPWO2020160163A5 - - Google Patents
Download PDFInfo
- Publication number
- 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
Links
- 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 (4)
| Publication Number | Publication Date |
|---|---|
| JP2022518929A JP2022518929A (ja) | 2022-03-17 |
| JP2022518929A5 JP2022518929A5 (https=) | 2023-02-02 |
| JPWO2020160163A5 true JPWO2020160163A5 (https=) | 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 (https=) |
| EP (1) | EP3918073A4 (https=) |
| JP (2) | JP7557469B2 (https=) |
| TW (1) | TW202043472A (https=) |
| UY (1) | UY38562A (https=) |
| WO (1) | WO2020160163A1 (https=) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EA202091693A1 (ru) | 2018-01-12 | 2021-04-14 | Бристол-Маерс Сквибб Компани | Антисмысловые олигонуклеотиды, целенаправленно воздействующие на альфа-синуклеин, и их применения |
| BR112020013994A2 (pt) | 2018-01-12 | 2020-12-08 | Bristol-Myers Squibb Company | Oligonucleotídeos antissenso que direcionam alfa-sinucleína e seus usos |
| EP3759127A4 (en) | 2018-03-02 | 2022-03-30 | Ionis Pharmaceuticals, Inc. | COMPOUNDS AND METHODS FOR MODULATING AMYLOID BETA PRECURSOR PROTEIN |
| TW202039844A (zh) * | 2018-12-19 | 2020-11-01 | 美商阿尼拉製藥公司 | 類澱粉前驅蛋白（ＡＰＰ）ＲＮＡｉ劑組成物及其使用方法 |
| KR20210149107A (ko) * | 2019-04-03 | 2021-12-08 | 브리스톨-마이어스 스큅 컴퍼니 | Angptl2 안티센스 올리고뉴클레오티드 및 그의 용도 |
| EP4013767A4 (en) | 2019-08-15 | 2023-10-25 | Ionis Pharmaceuticals, Inc. | Linkage modified oligomeric compounds and uses thereof |
| AU2021315992A1 (en) | 2020-07-28 | 2023-02-09 | Ionis Pharmaceuticals, Inc. | Compounds and methods for reducing app expression |
| EP4284390A4 (en) * | 2021-01-29 | 2025-10-29 | Alnylam Pharmaceuticals Inc | ARNI COMPOSITIONS AND METHODS FOR SILENCER OF AMYLOID PRECURSOR PROTEIN (APP) |
| MX2024004437A (es) * | 2021-10-15 | 2024-07-01 | Alnylam Pharmaceuticals Inc | Composiciones de inhibidor de la angiotensina-receptor neprilisina (arni) de administracion extrahepatica y metodos de uso de las mismas. |
| WO2025045195A1 (zh) * | 2023-08-31 | 2025-03-06 | 上海拓界生物医药科技有限公司 | 靶向APP的RNAi剂及其医药用途 |
| 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 |
| WO2025261396A1 (zh) * | 2024-06-18 | 2025-12-26 | 艾码生物科技(南京)有限公司 | 靶向app的rna干扰方法、核酸及其应用 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2126451A1 (en) * | 1991-12-24 | 1993-07-08 | Brett P. Monia | Compositions and methods for modulating .beta.-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 |
| JP2011514158A (ja) * | 2008-02-19 | 2011-05-06 | エダン・バイオテクノロジー・インコーポレイテッド | アミロイドベータタンパク質発現のアンチセンス調節 |
| 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 |
| AU2014274730A1 (en) * | 2013-06-07 | 2016-01-21 | Rana Therapeutics, Inc. | Compositions and methods for modulating FOXP3 expression |
| JP2016531570A (ja) * | 2013-08-16 | 2016-10-13 | ラナ セラピューティクス インコーポレイテッド | ユークロマチン領域を標的とするオリゴヌクレオチド |
| EP4166667A3 (en) * | 2013-10-11 | 2023-08-02 | Ionis Pharmaceuticals, Inc. | Compositions for modulating c9orf72 expression |
| DK3137476T3 (da) * | 2014-04-28 | 2019-11-18 | Ionis Pharmaceuticals Inc | Linker-modificerede oligomerforbindelser |
| EP3759127A4 (en) * | 2018-03-02 | 2022-03-30 | Ionis Pharmaceuticals, Inc. | COMPOUNDS AND METHODS FOR MODULATING AMYLOID BETA PRECURSOR PROTEIN |
-
2020
- 2020-01-29 UY UY0001038562A patent/UY38562A/es not_active Application Discontinuation
- 2020-01-29 US US17/424,672 patent/US20220380773A1/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 EP EP20749114.3A patent/EP3918073A4/en active Pending
- 2020-01-30 TW TW109102899A patent/TW202043472A/zh unknown
-
2024
- 2024-09-13 JP JP2024158813A patent/JP2025000693A/ja active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7354342B2 (ja) | タウ発現を調節するための組成物 | |
| JP7198298B2 (ja) | Ｓｏｄ－１発現を調節するための組成物 | |
| US20230020192A1 (en) | Compounds and methods for modulating c90rf72 | |
| JP6126009B2 (ja) | α−シヌクレイン発現の調節 | |
| US20250313842A1 (en) | Compounds and Methods for Reducing LRRK2 Expression | |
| JP7557469B2 (ja) | Ａｐｐの発現を低減するための化合物及び方法 | |
| JP7446443B2 (ja) | Ｓｍｎ２を調節するための化合物及び方法 | |
| JP2021072862A (ja) | Ｂ型肝炎感染の治療用のＰＡＰＤ５及びＰＡＰＤ７ ｍＲＮＡを低減させるための核酸分子 | |
| CN120475978A (zh) | 用于抑制DM1蛋白激酶(DMPK)表达的RNAi剂、其组合物和使用方法 | |
| JPWO2020160163A5 (https=) | ||
| JP2023536472A (ja) | Ａｐｐの発現を低減するための化合物及び方法 | |
| US20250270556A1 (en) | Compounds and methods for modulating scn2a | |
| KR20240049349A (ko) | Scn1a 발현을 조절하기 위한 화합물 및 방법 | |
| JPWO2020023737A5 (https=) | ||
| WO2021153747A1 (ja) | Ａｔｎ１のアンチセンスオリゴヌクレオチド | |
| JP2024523363A (ja) | Ｉｆｎａｒ１の発現を低減するための化合物及び方法 | |
| US12502402B2 (en) | Compounds and methods for modulating GFAP | |
| JP2019527549A (ja) | 転写プロセシングの調節のための化合物及び方法 | |
| WO2022211129A1 (ja) | Ａｔｎ１のアンチセンスオリゴヌクレオチド誘導体 | |
| JP2023543215A (ja) | Ａｐｏｅの発現を低減するための化合物及び方法 | |
| JPWO2020172559A5 (https=) | ||
| JP2026507572A (ja) | アルファ－シヌクレイン発現を調節するための化合物および方法 | |
| US11732263B2 (en) | Compounds and methods for modulating PLP1 | |
| JP2026506091A (ja) | ハンチンチン発現を調節するための対立遺伝子選択的化合物及び方法 | |
| JP2026506010A (ja) | Ａｐｐ発現を低減するための化合物及び方法 |