JP2016533765A5 - - Google Patents
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- JP2016533765A5 JP2016533765A5 JP2016542824A JP2016542824A JP2016533765A5 JP 2016533765 A5 JP2016533765 A5 JP 2016533765A5 JP 2016542824 A JP2016542824 A JP 2016542824A JP 2016542824 A JP2016542824 A JP 2016542824A JP 2016533765 A5 JP2016533765 A5 JP 2016533765A5
- Authority
- JP
- Japan
- Prior art keywords
- wing segment
- linked nucleosides
- modified oligonucleotide
- segment
- compound
- 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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- 150000001875 compounds Chemical class 0.000 claims description 67
- 239000002777 nucleoside Substances 0.000 claims description 55
- 108091034117 Oligonucleotide Proteins 0.000 claims description 49
- 125000003835 nucleoside group Chemical group 0.000 claims description 45
- 230000000295 complement effect Effects 0.000 claims description 27
- 208000002780 macular degeneration Diseases 0.000 claims description 19
- 208000017169 kidney disease Diseases 0.000 claims description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
- 206010064930 age-related macular degeneration Diseases 0.000 claims description 14
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims description 14
- 201000010099 disease Diseases 0.000 claims description 12
- 230000037361 pathway Effects 0.000 claims description 12
- 208000035913 Atypical hemolytic uremic syndrome Diseases 0.000 claims description 11
- 208000016323 C3 glomerulonephritis Diseases 0.000 claims description 10
- 208000004451 Membranoproliferative Glomerulonephritis Diseases 0.000 claims description 10
- 208000022401 dense deposit disease Diseases 0.000 claims description 10
- 150000003833 nucleoside derivatives Chemical class 0.000 claims description 10
- LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical group CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 claims description 8
- 229940104302 cytosine Drugs 0.000 claims description 7
- 230000008482 dysregulation 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
- 102100035325 Complement factor H-related protein 5 Human genes 0.000 claims description 5
- 101000878134 Homo sapiens Complement factor H-related protein 5 Proteins 0.000 claims description 5
- 208000005777 Lupus Nephritis Diseases 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 4
- 208000000208 Wet Macular Degeneration Diseases 0.000 claims description 3
- 206010003694 Atrophy Diseases 0.000 claims description 2
- 230000037444 atrophy Effects 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- -1 methoxyethyl Chemical group 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 5
- 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 1
- 230000024203 complement activation Effects 0.000 claims 1
- 238000000034 method Methods 0.000 description 54
- 102000003712 Complement factor B Human genes 0.000 description 21
- 108090000056 Complement factor B Proteins 0.000 description 21
- 239000003112 inhibitor Substances 0.000 description 13
- 230000000692 anti-sense effect Effects 0.000 description 12
- 238000009825 accumulation Methods 0.000 description 8
- 230000002401 inhibitory effect Effects 0.000 description 6
- 210000003734 kidney Anatomy 0.000 description 5
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 4
- 230000008685 targeting Effects 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 3
- 108020004707 nucleic acids Proteins 0.000 description 3
- 102000039446 nucleic acids Human genes 0.000 description 3
- 150000007523 nucleic acids Chemical class 0.000 description 3
- 101710131943 40S ribosomal protein S3a Proteins 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- 239000007791 liquid phase Substances 0.000 description 2
- 210000005228 liver tissue Anatomy 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 238000009736 wetting Methods 0.000 description 2
- 108010034753 Complement Membrane Attack Complex Proteins 0.000 description 1
- 206010064571 Gene mutation Diseases 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 108091036066 Three prime untranslated region Proteins 0.000 description 1
- 208000034841 Thrombotic Microangiopathies Diseases 0.000 description 1
- 230000001668 ameliorated effect Effects 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000002414 normal-phase solid-phase extraction Methods 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 210000005084 renal tissue Anatomy 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361877624P | 2013-09-13 | 2013-09-13 | |
| US61/877,624 | 2013-09-13 | ||
| PCT/US2014/055458 WO2015038939A2 (en) | 2013-09-13 | 2014-09-12 | Modulators of complement factor b |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2019201990A Division JP7158363B2 (ja) | 2013-09-13 | 2019-11-07 | 補体ｂ因子の調節薬 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2016533765A JP2016533765A (ja) | 2016-11-04 |
| JP2016533765A5 true JP2016533765A5 (enExample) | 2017-10-19 |
| JP6666250B2 JP6666250B2 (ja) | 2020-03-13 |
Family
ID=52666522
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016542824A Active JP6666250B2 (ja) | 2013-09-13 | 2014-09-12 | 補体ｂ因子の調節薬 |
| JP2019201990A Active JP7158363B2 (ja) | 2013-09-13 | 2019-11-07 | 補体ｂ因子の調節薬 |
| JP2022011551A Active JP7297112B2 (ja) | 2013-09-13 | 2022-01-28 | 補体ｂ因子の調節薬 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2019201990A Active JP7158363B2 (ja) | 2013-09-13 | 2019-11-07 | 補体ｂ因子の調節薬 |
| JP2022011551A Active JP7297112B2 (ja) | 2013-09-13 | 2022-01-28 | 補体ｂ因子の調節薬 |
Country Status (32)
Families Citing this family (34)
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| EP3626823A1 (en) | 2009-09-11 | 2020-03-25 | Ionis Pharmaceuticals, Inc. | Modulation of huntingtin expression |
| US10017764B2 (en) | 2011-02-08 | 2018-07-10 | Ionis Pharmaceuticals, Inc. | Oligomeric compounds comprising bicyclic nucleotides and uses thereof |
| PL2992098T3 (pl) | 2013-05-01 | 2019-09-30 | Ionis Pharmaceuticals, Inc. | Kompozycje i sposoby modulowania ekspresji hbv i ttr |
| PL3043827T3 (pl) * | 2013-09-13 | 2020-03-31 | Ionis Pharmaceuticals, Inc. | Modulatory czynnika b dopełniacza |
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| TW201730341A (zh) * | 2016-02-05 | 2017-09-01 | Kyowa Hakko Kirin Co Ltd | 抑制補體b因子之表現之反義寡核苷酸 |
| MX2018016046A (es) | 2016-06-27 | 2019-05-02 | Achillion Pharmaceuticals Inc | Quinazolina y compuestos indol para tratar trastornos medicos. |
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| WO2018117253A1 (ja) * | 2016-12-23 | 2018-06-28 | 協和発酵キリン株式会社 | 補体ｂ因子の発現を抑制する核酸 |
| WO2019027015A1 (ja) * | 2017-08-02 | 2019-02-07 | 協和発酵キリン株式会社 | 核酸複合体 |
| CA3078971A1 (en) | 2017-11-01 | 2019-05-09 | Alnylam Pharmaceuticals, Inc. | Complement component c3 irna compositions and methods of use thereof |
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| AU2022376760A1 (en) | 2021-10-27 | 2024-05-02 | Hansoh Bio Llc | Piperidinyl indole derivatives, preparation methods and medicinal uses thereof |
| AR127477A1 (es) * | 2021-10-29 | 2024-01-31 | Alnylam Pharmaceuticals Inc | COMPOSICIONES DE ARNi CONTRA EL FACTOR B DEL COMPLEMENTO (CFB) Y MÉTODOS DE USO DE LAS MISMAS |
| EP4437104A4 (en) | 2021-11-24 | 2026-01-21 | Adarx Pharmaceuticals Inc | COMPLEMENT FACTOR B MODULATION COMPOSITIONS AND THEIR METHODS OF USE |
| WO2023129496A2 (en) * | 2021-12-27 | 2023-07-06 | Apellis Pharmaceuticals, Inc. | Rnas for complement inhibition |
| EP4471021A4 (en) | 2022-01-26 | 2025-04-30 | Shanghai Meiyue Biotech Development Co., Ltd. | Salt type and crystal form of complement factor b inhibitor, and preparation method therefor and application thereof |
| JP2025530222A (ja) | 2022-09-10 | 2025-09-11 | 江▲蘇▼豪森▲薬▼▲業▼集▲団▼有限公司 | ２－置換ピペリジン誘導体、その製造方法及び医薬的用途 |
| AU2023372971A1 (en) * | 2022-11-02 | 2025-05-15 | Ionis Pharmaceuticals, Inc. | Methods for modulating complement factor b expression |
| AU2024261191A1 (en) | 2023-04-27 | 2025-11-06 | Jiangsu Hansoh Pharmaceutical Group Co., Ltd. | Salt of piperidylindole compound and preparation method therefor |
| TW202513799A (zh) * | 2023-06-02 | 2025-04-01 | 大陸商維亞臻生物技術（蘇州）有限公司 | 用於免疫類疾病的雙鏈核苷酸化合物及其用途 |
| CN118620964A (zh) * | 2023-06-28 | 2024-09-10 | 百奥赛图(北京)医药科技股份有限公司 | 一种cfb基因修饰的非人动物 |
| KR20260030856A (ko) * | 2023-06-28 | 2026-03-06 | 상하이 아르고 바이오파마슈티칼 씨오., 엘티디. | 보체 인자 b(cfb) 발현을 억제하기 위한 조성물 및 방법 |
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