JPWO2021232099A5 - - Google Patents
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- JPWO2021232099A5 JPWO2021232099A5 JP2022570608A JP2022570608A JPWO2021232099A5 JP WO2021232099 A5 JPWO2021232099 A5 JP WO2021232099A5 JP 2022570608 A JP2022570608 A JP 2022570608A JP 2022570608 A JP2022570608 A JP 2022570608A JP WO2021232099 A5 JPWO2021232099 A5 JP WO2021232099A5
- Authority
- JP
- Japan
- Prior art keywords
- oligonucleotide
- bases
- activity
- region
- tlr8
- 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
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- 108091034117 Oligonucleotide Proteins 0.000 claims 31
- 108010060752 Toll-Like Receptor 8 Proteins 0.000 claims 8
- 102100033110 Toll-like receptor 8 Human genes 0.000 claims 8
- 230000000694 effects Effects 0.000 claims 7
- 239000002773 nucleotide Substances 0.000 claims 5
- 125000003729 nucleotide group Chemical group 0.000 claims 5
- 239000008194 pharmaceutical composition Substances 0.000 claims 5
- 238000000034 method Methods 0.000 claims 4
- 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 3
- 230000028993 immune response Effects 0.000 claims 3
- 239000003607 modifier Substances 0.000 claims 3
- 239000000074 antisense oligonucleotide Substances 0.000 claims 2
- 238000012230 antisense oligonucleotides Methods 0.000 claims 2
- 201000010099 disease Diseases 0.000 claims 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
- 230000030279 gene silencing Effects 0.000 claims 2
- 238000012226 gene silencing method Methods 0.000 claims 2
- -1 hydroxyadenine compound Chemical class 0.000 claims 2
- 239000000203 mixture Substances 0.000 claims 2
- 108090000623 proteins and genes Proteins 0.000 claims 2
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims 1
- DEVCLHVFELRPIU-UHFFFAOYSA-N 2-(ethoxymethyl)-3h-imidazo[4,5-c]quinolin-4-amine Chemical compound NC1=NC2=CC=CC=C2C2=C1NC(COCC)=N2 DEVCLHVFELRPIU-UHFFFAOYSA-N 0.000 claims 1
- BXJWQQWEBUICHY-UHFFFAOYSA-N 2-[[4-[[6-amino-2-(butylamino)-8-oxo-7h-purin-9-yl]methyl]benzoyl]amino]acetic acid Chemical compound C12=NC(NCCCC)=NC(N)=C2N=C(O)N1CC1=CC=C(C(=O)NCC(O)=O)C=C1 BXJWQQWEBUICHY-UHFFFAOYSA-N 0.000 claims 1
- VDCRFBBZFHHYGT-IOSLPCCCSA-N 2-amino-9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-enyl-3h-purine-6,8-dione Chemical compound O=C1N(CC=C)C=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O VDCRFBBZFHHYGT-IOSLPCCCSA-N 0.000 claims 1
- NFYMGJSUKCDVJR-UHFFFAOYSA-N 2-propyl-[1,3]thiazolo[4,5-c]quinolin-4-amine Chemical compound C1=CC=CC2=C(SC(CCC)=N3)C3=C(N)N=C21 NFYMGJSUKCDVJR-UHFFFAOYSA-N 0.000 claims 1
- WROTXLSEMHAZEA-UHFFFAOYSA-N 4-diaminophosphoryloxymorpholine Chemical compound NP(N)(=O)ON1CCOCC1 WROTXLSEMHAZEA-UHFFFAOYSA-N 0.000 claims 1
- TZYVRXZQAWPIAB-FCLHUMLKSA-N 5-amino-3-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-4h-[1,3]thiazolo[4,5-d]pyrimidine-2,7-dione Chemical compound O=C1SC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O TZYVRXZQAWPIAB-FCLHUMLKSA-N 0.000 claims 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 claims 1
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical class 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 1
- 101000669402 Homo sapiens Toll-like receptor 7 Proteins 0.000 claims 1
- 101000800483 Homo sapiens Toll-like receptor 8 Proteins 0.000 claims 1
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 1
- 108091093037 Peptide nucleic acid Proteins 0.000 claims 1
- 108091027967 Small hairpin RNA Proteins 0.000 claims 1
- 108020004459 Small interfering RNA Proteins 0.000 claims 1
- 108091046915 Threose nucleic acid Proteins 0.000 claims 1
- 102000002689 Toll-like receptor Human genes 0.000 claims 1
- 108020000411 Toll-like receptor Proteins 0.000 claims 1
- 229940123384 Toll-like receptor (TLR) agonist Drugs 0.000 claims 1
- 102100039390 Toll-like receptor 7 Human genes 0.000 claims 1
- 239000000556 agonist Substances 0.000 claims 1
- 150000001408 amides Chemical class 0.000 claims 1
- SQQXRXKYTKFFSM-UHFFFAOYSA-N chembl1992147 Chemical compound OC1=C(OC)C(OC)=CC=C1C1=C(C)C(C(O)=O)=NC(C=2N=C3C4=NC(C)(C)N=C4C(OC)=C(O)C3=CC=2)=C1N SQQXRXKYTKFFSM-UHFFFAOYSA-N 0.000 claims 1
- 230000000295 complement effect Effects 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 claims 1
- 230000002708 enhancing effect Effects 0.000 claims 1
- 102000045720 human TLR8 Human genes 0.000 claims 1
- 229940124669 imidazoquinoline Drugs 0.000 claims 1
- 229960002751 imiquimod Drugs 0.000 claims 1
- DOUYETYNHWVLEO-UHFFFAOYSA-N imiquimod Chemical compound C1=CC=CC2=C3N(CC(C)C)C=NC3=C(N)N=C21 DOUYETYNHWVLEO-UHFFFAOYSA-N 0.000 claims 1
- 229950003954 isatoribine Drugs 0.000 claims 1
- 229950005634 loxoribine Drugs 0.000 claims 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 1
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical compound CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 claims 1
- 150000007523 nucleic acids Chemical group 0.000 claims 1
- 125000004430 oxygen atom Chemical group O* 0.000 claims 1
- 150000004713 phosphodiesters Chemical class 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
- 150000008300 phosphoramidites Chemical class 0.000 claims 1
- 108091033319 polynucleotide Proteins 0.000 claims 1
- 102000040430 polynucleotide Human genes 0.000 claims 1
- 239000002157 polynucleotide Substances 0.000 claims 1
- BXNMTOQRYBFHNZ-UHFFFAOYSA-N resiquimod Chemical group C1=CC=CC2=C(N(C(COCC)=N3)CC(C)(C)O)C3=C(N)N=C21 BXNMTOQRYBFHNZ-UHFFFAOYSA-N 0.000 claims 1
- 239000004055 small Interfering RNA Substances 0.000 claims 1
- 229910052717 sulfur Inorganic materials 0.000 claims 1
- 125000004434 sulfur atom Chemical group 0.000 claims 1
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical class CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 claims 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2020901606 | 2020-05-19 | ||
| AU2020901606A AU2020901606A0 (en) | 2020-05-19 | Oligonucleotides | |
| PCT/AU2021/050469 WO2021232099A1 (en) | 2020-05-19 | 2021-05-19 | Oligonucleotides |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2023526090A JP2023526090A (ja) | 2023-06-20 |
| JPWO2021232099A5 true JPWO2021232099A5 (https=) | 2024-05-27 |
| JP2023526090A5 JP2023526090A5 (https=) | 2024-05-27 |
Family
ID=78708815
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2022570608A Pending JP2023526090A (ja) | 2020-05-19 | 2021-05-19 | オリゴヌクレオチド |
Country Status (10)
| Country | Link |
|---|---|
| US (2) | US20230348903A1 (https=) |
| EP (1) | EP4153751A4 (https=) |
| JP (1) | JP2023526090A (https=) |
| KR (1) | KR20230013266A (https=) |
| CN (1) | CN115916978A (https=) |
| AU (1) | AU2021276730A1 (https=) |
| BR (1) | BR112022023310A2 (https=) |
| CA (1) | CA3171986A1 (https=) |
| MX (1) | MX2022014495A (https=) |
| WO (1) | WO2021232099A1 (https=) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115916978A (zh) | 2020-05-19 | 2023-04-04 | 哈德森医学研究所 | 寡核苷酸 |
| US20240384268A1 (en) * | 2021-04-08 | 2024-11-21 | Hudson Institute of Medical Research | Oligonucleotides |
| CN118460654B (zh) * | 2024-07-10 | 2025-02-14 | 凯莱英医药集团（天津）股份有限公司 | 一种Givosiran的制备方法 |
| CN119592567B (zh) * | 2024-12-10 | 2025-12-02 | 浙江大学 | 基于肿瘤剪接转换治疗的反义寡核苷酸及其应用 |
Family Cites Families (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6320041B1 (en) | 2001-04-13 | 2001-11-20 | Trilink Biotechnologies, Inc. | Pre-activated carbonyl linkers for the modification of oligonucleotides |
| US8153141B2 (en) | 2002-04-04 | 2012-04-10 | Coley Pharmaceutical Gmbh | Immunostimulatory G, U-containing oligoribonucleotides |
| US20050239733A1 (en) | 2003-10-31 | 2005-10-27 | Coley Pharmaceutical Gmbh | Sequence requirements for inhibitory oligonucleotides |
| WO2005097993A2 (en) * | 2004-02-19 | 2005-10-20 | Coley Pharmaceutical Group, Inc. | Immunostimulatory viral rna oligonucleotides |
| WO2006063152A2 (en) * | 2004-12-08 | 2006-06-15 | 3M Innovative Properties Company | Immunostimulatory combinations and methods |
| EP1819365B1 (en) | 2004-12-09 | 2014-07-02 | Alnylam Pharmaceuticals Inc. | Compositions and methods for inducing an immune response in a mammal and methods of avoiding an immune response to oligonucleotide agents such as short interfering RNAs |
| CN101160401A (zh) * | 2005-02-24 | 2008-04-09 | 科勒制药集团公司 | 免疫刺激寡核苷酸 |
| EP1764107A1 (en) * | 2005-09-14 | 2007-03-21 | Gunther Hartmann | Compositions comprising immunostimulatory RNA oligonucleotides and methods for producing said RNA oligonucleotides |
| US8076068B2 (en) | 2005-09-14 | 2011-12-13 | Gunther Hartmann | Method for determining immunostimulatory activity of RNA oligonucleotides |
| KR20080059595A (ko) * | 2005-09-27 | 2008-06-30 | 콜리 파마슈티칼 게엠베하 | 어댑터 올리고뉴클레오티드를 사용하는 ｔｌｒ-매개 면역반응의 조절 |
| PL1957647T3 (pl) * | 2005-11-25 | 2015-07-31 | Zoetis Belgium S A | Oligorybonukleotydy immunostymulujące |
| CN101331229B (zh) * | 2005-11-25 | 2012-08-29 | 科勒制药股份公司 | 免疫刺激性寡核糖核苷酸 |
| EP2021008B1 (en) * | 2006-04-07 | 2015-12-02 | Idera Pharmaceuticals, Inc. | Stabilized immune modulatory rna (simra) compounds for tlr7 and tlr8 |
| AU2007268075C1 (en) | 2006-06-01 | 2013-03-07 | Trilink Biotechnologies | Chemically modified oligonucleotide primers for nucleic acid amplification |
| AU2007280690C1 (en) * | 2006-07-31 | 2012-08-23 | Curevac Gmbh | Nucleic acid of formula (I): GIXmGn, or (II): CIXmCn, in particular as an immune-stimulating agent/adjuvant |
| EP3342415B1 (en) * | 2006-08-08 | 2022-01-26 | Rheinische Friedrich-Wilhelms-Universität Bonn | Structure and use of 5' phosphate oligonucleotides |
| WO2008019486A1 (en) | 2006-08-16 | 2008-02-21 | Protiva Biotherapeutics, Inc. | Nucleic acid modulation of toll-like receptor-mediated immune stimulation |
| CA2692161C (en) * | 2007-07-09 | 2015-09-29 | Idera Pharmaceuticals, Inc. | Stabilized immune modulatory rna (simra) compounds |
| JP5753382B2 (ja) * | 2007-11-06 | 2015-07-22 | アディウティーダ ファーマシューティカルズ ゲーエムベーハー | 修飾されたオリゴリン酸基を含有する免疫賦活オリゴリボヌクレオチドアナログ |
| US20100047188A1 (en) * | 2008-08-04 | 2010-02-25 | Idera Pharmaceuticals, Inc. | Modulation of toll-like receptor 8 expression by antisense oligonucleotides |
| US9631227B2 (en) | 2009-07-06 | 2017-04-25 | Trilink Biotechnologies, Inc. | Chemically modified ligase cofactors, donors and acceptors |
| EP3191591A1 (en) * | 2014-09-12 | 2017-07-19 | Alnylam Pharmaceuticals, Inc. | Polynucleotide agents targeting complement component c5 and methods of use thereof |
| WO2016205323A1 (en) * | 2015-06-18 | 2016-12-22 | Alnylam Pharmaceuticals, Inc. | Polynucleotde agents targeting hydroxyacid oxidase (glycolate oxidase, hao1) and methods of use thereof |
| ES2964690T3 (es) | 2015-09-21 | 2024-04-09 | Trilink Biotechnologies Llc | Método para sintetizar ARN con caperuza 5' |
| WO2017100587A1 (en) * | 2015-12-09 | 2017-06-15 | Alnylam Pharmaceuticals, Inc. | Polynucleotide agents targeting programmed cell death 1 ligand 1 (pd-l1) and methods of use thereof |
| WO2018184003A1 (en) | 2017-03-31 | 2018-10-04 | Dana-Farber Cancer Institute, Inc. | Modulating dsrna editing, sensing, and metabolism to increase tumor immunity and improve the efficacy of cancer immunotherapy and/or modulators of intratumoral interferon |
| US11603532B2 (en) * | 2017-06-02 | 2023-03-14 | Wave Life Sciences Ltd. | Oligonucleotide compositions and methods of use thereof |
| CN115916978A (zh) | 2020-05-19 | 2023-04-04 | 哈德森医学研究所 | 寡核苷酸 |
-
2021
- 2021-05-19 CN CN202180049291.1A patent/CN115916978A/zh active Pending
- 2021-05-19 EP EP21807588.5A patent/EP4153751A4/en active Pending
- 2021-05-19 WO PCT/AU2021/050469 patent/WO2021232099A1/en not_active Ceased
- 2021-05-19 US US17/926,383 patent/US20230348903A1/en not_active Abandoned
- 2021-05-19 BR BR112022023310A patent/BR112022023310A2/pt unknown
- 2021-05-19 AU AU2021276730A patent/AU2021276730A1/en active Pending
- 2021-05-19 JP JP2022570608A patent/JP2023526090A/ja active Pending
- 2021-05-19 MX MX2022014495A patent/MX2022014495A/es unknown
- 2021-05-19 KR KR1020227044467A patent/KR20230013266A/ko active Pending
- 2021-05-19 CA CA3171986A patent/CA3171986A1/en active Pending
-
2023
- 2023-06-22 US US18/213,116 patent/US12448622B2/en active Active
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