JP2020528910A5 - - Google Patents
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- JP2020528910A5 JP2020528910A5 JP2020504133A JP2020504133A JP2020528910A5 JP 2020528910 A5 JP2020528910 A5 JP 2020528910A5 JP 2020504133 A JP2020504133 A JP 2020504133A JP 2020504133 A JP2020504133 A JP 2020504133A JP 2020528910 A5 JP2020528910 A5 JP 2020528910A5
- Authority
- JP
- Japan
- Prior art keywords
- oligonucleotide
- aspects
- composition according
- tablets
- series
- 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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- 238000000034 method Methods 0.000 claims description 14
- 238000004519 manufacturing process Methods 0.000 claims 1
- 108091034117 Oligonucleotide Proteins 0.000 description 97
- 239000000203 mixture Substances 0.000 description 67
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 14
- 239000008194 pharmaceutical composition Substances 0.000 description 14
- LUCHPKXVUGJYGU-XLPZGREQSA-N 5-methyl-2'-deoxycytidine Chemical group O=C1N=C(N)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 LUCHPKXVUGJYGU-XLPZGREQSA-N 0.000 description 11
- 150000007523 nucleic acids Chemical group 0.000 description 11
- 239000002777 nucleoside Substances 0.000 description 10
- 108091028043 Nucleic acid sequence Proteins 0.000 description 9
- 238000004255 ion exchange chromatography Methods 0.000 description 9
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 238000010828 elution Methods 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 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 description 5
- 125000003835 nucleoside group Chemical group 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 239000002671 adjuvant Substances 0.000 description 4
- -1 nucleoside phosphoramidite Chemical class 0.000 description 4
- 239000002773 nucleotide Substances 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 238000000502 dialysis Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 150000003833 nucleoside derivatives Chemical class 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 238000000108 ultra-filtration Methods 0.000 description 3
- MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 description 2
- 206010009900 Colitis ulcerative Diseases 0.000 description 2
- 208000011231 Crohn disease Diseases 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 2
- 201000006704 Ulcerative Colitis Diseases 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 239000006186 oral dosage form Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000010409 thin film Substances 0.000 description 2
- GNFTZDOKVXKIBK-UHFFFAOYSA-N 3-(2-methoxyethoxy)benzohydrazide Chemical compound COCCOC1=CC=CC(C(=O)NN)=C1 GNFTZDOKVXKIBK-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 238000005571 anion exchange chromatography Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000011033 desalting Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- LSACYLWPPQLVSM-UHFFFAOYSA-N isobutyric acid anhydride Chemical group CC(C)C(=O)OC(=O)C(C)C LSACYLWPPQLVSM-UHFFFAOYSA-N 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 150000008300 phosphoramidites Chemical class 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000006177 thiolation reaction Methods 0.000 description 1
- 235000011178 triphosphate Nutrition 0.000 description 1
- 239000001226 triphosphate Substances 0.000 description 1
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762538504P | 2017-07-28 | 2017-07-28 | |
| US62/538,504 | 2017-07-28 | ||
| PCT/US2018/043867 WO2019023439A1 (en) | 2017-07-28 | 2018-07-26 | PROCESS FOR THE PREPARATION OF OLIGONUCLEOTIDE COMPOUNDS |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2020528910A JP2020528910A (ja) | 2020-10-01 |
| JP2020528910A5 true JP2020528910A5 (enExample) | 2021-09-09 |
Family
ID=65041406
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020504133A Pending JP2020528910A (ja) | 2017-07-28 | 2018-07-26 | オリゴヌクレオチド化合物の調製方法 |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US20200392491A1 (enExample) |
| EP (1) | EP3658155A4 (enExample) |
| JP (1) | JP2020528910A (enExample) |
| KR (1) | KR20200042902A (enExample) |
| CN (1) | CN111148519A (enExample) |
| WO (1) | WO2019023439A1 (enExample) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11162097B2 (en) | 2016-02-23 | 2021-11-02 | Nogra Pharma Limited | Methods of treating intestinal fibrosis using SMAD7 inhibition |
| EP3931348B1 (en) * | 2019-02-26 | 2023-08-09 | Roche Innovation Center Copenhagen A/S | Oligonucleotide formulation method |
| KR102746639B1 (ko) * | 2019-07-09 | 2024-12-24 | 에프. 호프만-라 로슈 아게 | 올리고뉴클레오타이드의 탈보호 방법 |
| CN110468171B (zh) * | 2019-09-20 | 2021-10-29 | 凯莱英医药集团（天津）股份有限公司 | 核酸的合成方法 |
| BR112022016598A2 (pt) * | 2020-02-21 | 2022-11-08 | Biogen Ma Inc | Métodos de preparação de composições de oligonucleotídeo utilizando ultrafiltração/diafiltração |
| WO2024138152A1 (en) * | 2022-12-23 | 2024-06-27 | Asahi Kasei Bioprocess America, Inc. | System for performing cleavage, deprotection, ultrafiltration, and diafiltration operations |
| CN117143165A (zh) * | 2023-08-30 | 2023-12-01 | 上海奥锐特生物科技有限公司 | 一种寡核苷酸的纯化方法 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007050789A2 (en) * | 2005-10-25 | 2007-05-03 | Nëdken Corporation | Glycosyl-oligonucleotide conjugates and methods |
| US9701708B2 (en) * | 2013-01-31 | 2017-07-11 | Ionis Pharmaceuticals, Inc. | Method of preparing oligomeric compounds using modified coupling protocols |
| CN106573065A (zh) * | 2014-05-09 | 2017-04-19 | 诺格尔制药有限公司 | 用于治疗炎症性肠病的方法 |
| US20170247695A1 (en) * | 2014-10-17 | 2017-08-31 | Celgene Corporation | Isotopologues of smad7 antisense oligonucleotides |
| EP3355896A2 (en) * | 2015-09-30 | 2018-08-08 | Nogra Pharma Limited | Methods of using smad7 antisense oligonucleotides based on biomarker expression |
-
2018
- 2018-07-26 US US16/634,078 patent/US20200392491A1/en not_active Abandoned
- 2018-07-26 KR KR1020207004894A patent/KR20200042902A/ko not_active Withdrawn
- 2018-07-26 JP JP2020504133A patent/JP2020528910A/ja active Pending
- 2018-07-26 EP EP18837870.7A patent/EP3658155A4/en not_active Withdrawn
- 2018-07-26 WO PCT/US2018/043867 patent/WO2019023439A1/en not_active Ceased
- 2018-07-26 CN CN201880062621.9A patent/CN111148519A/zh active Pending
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