JP2021500025A5 - - Google Patents
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- JP2021500025A5 JP2021500025A5 JP2020521880A JP2020521880A JP2021500025A5 JP 2021500025 A5 JP2021500025 A5 JP 2021500025A5 JP 2020521880 A JP2020521880 A JP 2020521880A JP 2020521880 A JP2020521880 A JP 2020521880A JP 2021500025 A5 JP2021500025 A5 JP 2021500025A5
- Authority
- JP
- Japan
- Prior art keywords
- oligonucleotide
- galnac
- composition
- nucleotides
- positions
- 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.)
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- 108091034117 Oligonucleotide Proteins 0.000 claims 27
- 239000000203 mixture Substances 0.000 claims 15
- 239000002773 nucleotide Substances 0.000 claims 10
- 230000000692 anti-sense effect Effects 0.000 claims 9
- 125000003729 nucleotide group Chemical group 0.000 claims 9
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound 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 8
- 108091081021 Sense strand Proteins 0.000 claims 8
- 210000004027 cell Anatomy 0.000 claims 8
- 239000005549 deoxyribonucleoside Substances 0.000 claims 8
- 238000000034 method Methods 0.000 claims 8
- 239000002777 nucleoside Substances 0.000 claims 8
- 125000003835 nucleoside group Chemical group 0.000 claims 8
- 239000002342 ribonucleoside Substances 0.000 claims 8
- 241000700721 Hepatitis B virus Species 0.000 claims 5
- 239000003937 drug carrier Substances 0.000 claims 5
- SXUXMRMBWZCMEN-UHFFFAOYSA-N 2'-O-methyl uridine Natural products COC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 SXUXMRMBWZCMEN-UHFFFAOYSA-N 0.000 claims 4
- 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 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 4
- 239000000427 antigen Substances 0.000 claims 4
- FPUGCISOLXNPPC-IOSLPCCCSA-N cordysinin B Chemical compound CO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(N)=C2N=C1 FPUGCISOLXNPPC-IOSLPCCCSA-N 0.000 claims 4
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 claims 3
- 108091007433 antigens Proteins 0.000 claims 3
- 102000036639 antigens Human genes 0.000 claims 3
- 210000002966 serum Anatomy 0.000 claims 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 3
- UUDVSZSQPFXQQM-GIWSHQQXSA-N (2r,3s,4r,5r)-2-(6-aminopurin-9-yl)-3-fluoro-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@]1(O)F UUDVSZSQPFXQQM-GIWSHQQXSA-N 0.000 claims 2
- QPHRQMAYYMYWFW-FJGDRVTGSA-N 1-[(2r,3s,4r,5r)-3-fluoro-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione Chemical compound O[C@]1(F)[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 QPHRQMAYYMYWFW-FJGDRVTGSA-N 0.000 claims 2
- FPUGCISOLXNPPC-UHFFFAOYSA-N 2'-O-Methyladenosine Natural products COC1C(O)C(CO)OC1N1C2=NC=NC(N)=C2N=C1 FPUGCISOLXNPPC-UHFFFAOYSA-N 0.000 claims 2
- RFCQJGFZUQFYRF-UHFFFAOYSA-N 2'-O-Methylcytidine Natural products COC1C(O)C(CO)OC1N1C(=O)N=C(N)C=C1 RFCQJGFZUQFYRF-UHFFFAOYSA-N 0.000 claims 2
- OVYNGSFVYRPRCG-UHFFFAOYSA-N 2'-O-Methylguanosine Natural products COC1C(O)C(CO)OC1N1C(NC(N)=NC2=O)=C2N=C1 OVYNGSFVYRPRCG-UHFFFAOYSA-N 0.000 claims 2
- RFCQJGFZUQFYRF-ZOQUXTDFSA-N 2'-O-methylcytidine Chemical compound CO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)N=C(N)C=C1 RFCQJGFZUQFYRF-ZOQUXTDFSA-N 0.000 claims 2
- OVYNGSFVYRPRCG-KQYNXXCUSA-N 2'-O-methylguanosine Chemical compound CO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=C(N)NC2=O)=C2N=C1 OVYNGSFVYRPRCG-KQYNXXCUSA-N 0.000 claims 2
- SXUXMRMBWZCMEN-ZOQUXTDFSA-N 2'-O-methyluridine Chemical compound CO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 SXUXMRMBWZCMEN-ZOQUXTDFSA-N 0.000 claims 2
- BGTXMQUSDNMLDW-AEHJODJJSA-N 2-amino-9-[(2r,3s,4r,5r)-3-fluoro-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-3h-purin-6-one Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](CO)[C@@H](O)[C@]1(O)F BGTXMQUSDNMLDW-AEHJODJJSA-N 0.000 claims 2
- PJWBTAIPBFWVHX-FJGDRVTGSA-N 4-amino-1-[(2r,3s,4r,5r)-3-fluoro-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@](F)(O)[C@H](O)[C@@H](CO)O1 PJWBTAIPBFWVHX-FJGDRVTGSA-N 0.000 claims 2
- 108700019146 Transgenes Proteins 0.000 claims 2
- 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 2
- 239000003795 chemical substances by application Substances 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 210000003494 hepatocyte Anatomy 0.000 claims 2
- 238000000338 in vitro Methods 0.000 claims 2
- 125000005647 linker group Chemical group 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 239000011734 sodium Substances 0.000 claims 2
- 159000000000 sodium salts Chemical class 0.000 claims 2
- 108020004414 DNA Proteins 0.000 claims 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims 1
- 125000004450 alkenylene group Chemical group 0.000 claims 1
- 125000002947 alkylene group Chemical group 0.000 claims 1
- 125000004419 alkynylene group Chemical group 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 208000016350 chronic hepatitis B virus infection Diseases 0.000 claims 1
- 230000008878 coupling Effects 0.000 claims 1
- 238000010168 coupling process Methods 0.000 claims 1
- 238000005859 coupling reaction Methods 0.000 claims 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 claims 1
- 239000002612 dispersion medium Substances 0.000 claims 1
- 125000004474 heteroalkylene group Chemical group 0.000 claims 1
- 208000015181 infectious disease Diseases 0.000 claims 1
- CAAULPUQFIIOTL-UHFFFAOYSA-N methyl dihydrogen phosphate Chemical compound COP(O)(O)=O CAAULPUQFIIOTL-UHFFFAOYSA-N 0.000 claims 1
- 229910052757 nitrogen Inorganic materials 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 239000002953 phosphate buffered saline Substances 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 239000000243 solution Substances 0.000 claims 1
- 239000002904 solvent Substances 0.000 claims 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims 1
- 229910052717 sulfur Inorganic materials 0.000 claims 1
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2023151506A JP7645323B2 (ja) | 2017-10-20 | 2023-09-19 | Ｂ型肝炎感染の治療方法 |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762575358P | 2017-10-20 | 2017-10-20 | |
| US62/575,358 | 2017-10-20 | ||
| PCT/US2018/056801 WO2019079781A2 (en) | 2017-10-20 | 2018-10-19 | METHODS OF TREATING HEPATITIS B TYPE INFECTIONS |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2023151506A Division JP7645323B2 (ja) | 2017-10-20 | 2023-09-19 | Ｂ型肝炎感染の治療方法 |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| JP2021500025A JP2021500025A (ja) | 2021-01-07 |
| JP2021500025A5 true JP2021500025A5 (enExample) | 2021-11-25 |
| JPWO2019079781A5 JPWO2019079781A5 (enExample) | 2023-07-21 |
| JP7353276B2 JP7353276B2 (ja) | 2023-09-29 |
Family
ID=66173915
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020521880A Active JP7353276B2 (ja) | 2017-10-20 | 2018-10-19 | Ｂ型肝炎感染の治療方法 |
| JP2023151506A Active JP7645323B2 (ja) | 2017-10-20 | 2023-09-19 | Ｂ型肝炎感染の治療方法 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2023151506A Active JP7645323B2 (ja) | 2017-10-20 | 2023-09-19 | Ｂ型肝炎感染の治療方法 |
Country Status (30)
| Country | Link |
|---|---|
| US (5) | US10799524B2 (enExample) |
| EP (2) | EP4197544A1 (enExample) |
| JP (2) | JP7353276B2 (enExample) |
| KR (1) | KR102783206B1 (enExample) |
| CN (2) | CN118185936A (enExample) |
| AU (1) | AU2018351649B2 (enExample) |
| BR (1) | BR112020007476A2 (enExample) |
| CA (1) | CA3078960A1 (enExample) |
| CL (1) | CL2020001061A1 (enExample) |
| CO (1) | CO2020005135A2 (enExample) |
| CR (1) | CR20200163A (enExample) |
| DK (1) | DK3684377T3 (enExample) |
| ES (1) | ES2936863T3 (enExample) |
| FI (1) | FI3684377T3 (enExample) |
| HR (1) | HRP20230023T1 (enExample) |
| HU (1) | HUE061122T2 (enExample) |
| IL (4) | IL274040B2 (enExample) |
| LT (1) | LT3684377T (enExample) |
| MA (1) | MA50264B1 (enExample) |
| MX (1) | MX2020004060A (enExample) |
| MY (1) | MY201698A (enExample) |
| PE (1) | PE20220561A1 (enExample) |
| PH (1) | PH12020550591A1 (enExample) |
| PL (1) | PL3684377T3 (enExample) |
| PT (1) | PT3684377T (enExample) |
| RS (1) | RS64001B1 (enExample) |
| SG (1) | SG11202003488WA (enExample) |
| SI (1) | SI3684377T1 (enExample) |
| UA (1) | UA128786C2 (enExample) |
| WO (1) | WO2019079781A2 (enExample) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL3684377T3 (pl) | 2017-10-20 | 2023-04-17 | Dicerna Pharmaceuticals, Inc. | Sposoby leczenia zakażenia wirusem zapalenia wątroby typu b |
| CR20210015A (es) | 2018-07-13 | 2021-03-22 | Hoffmann La Roche | Oligonucleótidos para modular la expresión de rtel 1 |
| WO2021067744A1 (en) * | 2019-10-02 | 2021-04-08 | Dicerna Pharmaceuticals, Inc. | Chemical modifications of small interfering rna with minimal fluorine content |
| EP4077671A1 (en) * | 2019-12-19 | 2022-10-26 | F. Hoffmann-La Roche AG | Use of saraf inhibitors for treating hepatitis b virus infection |
| EP4081639A1 (en) * | 2019-12-24 | 2022-11-02 | F. Hoffmann-La Roche AG | Pharmaceutical combination of a therapeutic oligonucleotide targeting hbv and a tlr7 agonist for treatment of hbv |
| AU2020415322A1 (en) * | 2019-12-24 | 2022-06-16 | F. Hoffmann-La Roche Ag | Pharmaceutical combination of antiviral agents targeting HBV and/or an immune modulator for treatment of HBV |
| EP4189089A1 (en) * | 2020-07-27 | 2023-06-07 | Aligos Therapeutics, Inc. | Hbv binding oligonucleotides and methods of use |
| WO2022029209A1 (en) | 2020-08-05 | 2022-02-10 | F. Hoffmann-La Roche Ag | Oligonucleotide treatment of hepatitis b patients |
| KR102798766B1 (ko) * | 2020-12-18 | 2025-04-23 | 올릭스 주식회사 | HBV 발현을 억제하는 RNAi 제제 및 이의 용도 |
| CN114853829A (zh) * | 2021-02-05 | 2022-08-05 | 上海拓界生物医药科技有限公司 | 一种核酸配体、其缀合物、制备方法及用途 |
| CN114940991B (zh) * | 2021-04-13 | 2023-02-03 | 厦门甘宝利生物医药有限公司 | 一种抑制乙型肝炎病毒基因表达的rna抑制剂及其应用 |
| JP7536187B2 (ja) * | 2021-04-19 | 2024-08-19 | ノヴォ ノルディスク アー／エス | 核内受容体サブファミリー１グループｈメンバー３（ｎｒ１ｈ３）発現を阻害するための組成物および方法 |
| WO2023083906A2 (en) | 2021-11-11 | 2023-05-19 | F. Hoffmann-La Roche Ag | Pharmaceutical combinations for treatment of hbv |
| TW202329987A (zh) * | 2021-11-29 | 2023-08-01 | 大陸商上海舶望製藥有限公司 | 用於抑制乙型肝炎病毒（hbv）蛋白表達的組合物和方法 |
| EP4201947A1 (en) | 2021-12-22 | 2023-06-28 | F. Hoffmann-La Roche AG | Process for the backbone deprotection of oligonucleotides containing a terminal alkyl phosphonate group |
| WO2023116764A1 (zh) * | 2021-12-23 | 2023-06-29 | 苏州瑞博生物技术股份有限公司 | 一种核酸、含有该核酸的组合物与缀合物及其用途 |
| US20240309383A1 (en) * | 2023-02-24 | 2024-09-19 | Suzhou Sanegene Bio Inc. | Small interfering rna targeting hbv and uses thereof |
| WO2025199466A1 (en) | 2024-03-22 | 2025-09-25 | Purdue Research Foundation | Liver-specific asialoglycoprotein receptor targeting ligands, conjugates comprising same, and related compositions and methods of use |
| WO2025242321A1 (en) | 2024-05-24 | 2025-11-27 | Glaxosmithkline Intellectual Property (No.3) Limited | Novel use |
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| US20040127446A1 (en) | 1992-05-14 | 2004-07-01 | Lawrence Blatt | Oligonucleotide mediated inhibition of hepatitis B virus and hepatitis C virus replication |
| KR20080023768A (ko) | 2000-03-30 | 2008-03-14 | 화이트헤드 인스티튜트 포 바이오메디칼 리서치 | Ｒｎａ 간섭의 ｒｎａ 서열 특이적인 매개체 |
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