JP2019527549A5 - - Google Patents
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- Publication number
- JP2019527549A5 JP2019527549A5 JP2019501570A JP2019501570A JP2019527549A5 JP 2019527549 A5 JP2019527549 A5 JP 2019527549A5 JP 2019501570 A JP2019501570 A JP 2019501570A JP 2019501570 A JP2019501570 A JP 2019501570A JP 2019527549 A5 JP2019527549 A5 JP 2019527549A5
- Authority
- JP
- Japan
- Prior art keywords
- modified oligonucleotide
- oligomeric compound
- compound according
- modified
- aspects
- 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
- 150000001875 compounds Chemical class 0.000 claims description 163
- 108091034117 Oligonucleotide Proteins 0.000 claims description 121
- 239000002777 nucleoside Substances 0.000 claims description 88
- 125000003835 nucleoside group Chemical group 0.000 claims description 62
- 239000002243 precursor Substances 0.000 claims description 41
- 108020004999 messenger RNA Proteins 0.000 claims description 37
- 230000000295 complement effect Effects 0.000 claims description 31
- 150000003833 nucleoside derivatives Chemical class 0.000 claims description 24
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 239000001257 hydrogen Substances 0.000 claims description 17
- 150000002632 lipids Chemical class 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical compound CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 claims description 8
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 claims description 8
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical group CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 claims description 8
- 125000002619 bicyclic group Chemical group 0.000 claims description 7
- 201000010099 disease Diseases 0.000 claims description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 7
- 210000003205 muscle Anatomy 0.000 claims description 7
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 7
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims description 7
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 6
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 6
- 108700024394 Exon Proteins 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 229930024421 Adenine Natural products 0.000 claims description 4
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 claims description 4
- 229960000643 adenine Drugs 0.000 claims description 4
- 229940104302 cytosine Drugs 0.000 claims description 4
- 229940113082 thymine Drugs 0.000 claims description 4
- 101000617738 Homo sapiens Survival motor neuron protein Proteins 0.000 claims description 3
- 102100021947 Survival motor neuron protein Human genes 0.000 claims description 3
- 230000002159 abnormal effect Effects 0.000 claims description 3
- 235000012000 cholesterol Nutrition 0.000 claims description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 3
- 229960001295 tocopherol Drugs 0.000 claims description 3
- 229930003799 tocopherol Natural products 0.000 claims description 3
- 235000010384 tocopherol Nutrition 0.000 claims description 3
- 239000011732 tocopherol Substances 0.000 claims description 3
- 229940035893 uracil Drugs 0.000 claims description 3
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 claims description 3
- BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 claims description 2
- 239000004380 Cholic acid Substances 0.000 claims description 2
- OVRNDRQMDRJTHS-KEWYIRBNSA-N N-acetyl-D-galactosamine Chemical group CC(=O)N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-KEWYIRBNSA-N 0.000 claims description 2
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 claims description 2
- 229960002471 cholic acid Drugs 0.000 claims description 2
- 235000019416 cholic acid Nutrition 0.000 claims description 2
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 150000004713 phosphodiesters Chemical class 0.000 claims description 2
- 150000004671 saturated fatty acids Chemical class 0.000 claims description 2
- 150000004670 unsaturated fatty acids Chemical class 0.000 claims description 2
- 108091092195 Intron Proteins 0.000 claims 1
- 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 1
- 150000003869 acetamides Chemical class 0.000 claims 1
- 230000001268 conjugating effect Effects 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 125000006239 protecting group Chemical group 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 claims 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims 1
- 238000000034 method Methods 0.000 description 28
- 239000000203 mixture Substances 0.000 description 10
- 210000001519 tissue Anatomy 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 7
- 210000003169 central nervous system Anatomy 0.000 description 5
- 108020004705 Codon Proteins 0.000 description 4
- 102100040243 Microtubule-associated protein tau Human genes 0.000 description 4
- 108020004485 Nonsense Codon Proteins 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 230000007717 exclusion Effects 0.000 description 3
- 230000037434 nonsense mutation Effects 0.000 description 3
- 102000001039 Dystrophin Human genes 0.000 description 2
- 108010069091 Dystrophin Proteins 0.000 description 2
- 101000891579 Homo sapiens Microtubule-associated protein tau Proteins 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 125000001183 hydrocarbyl group Chemical group 0.000 description 2
- 238000007910 systemic administration Methods 0.000 description 2
- 108010026424 tau Proteins Proteins 0.000 description 2
- PMDCZENCAXMSOU-UHFFFAOYSA-N N-Ethylacetamide Natural products CCNC(C)=O PMDCZENCAXMSOU-UHFFFAOYSA-N 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- -1 linker nucleoside Chemical class 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2022162447A JP2022188237A (ja) | 2016-07-15 | 2022-10-07 | 転写プロセシングの調節のための化合物及び方法 |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662363193P | 2016-07-15 | 2016-07-15 | |
| US62/363,193 | 2016-07-15 | ||
| PCT/US2017/042465 WO2018014043A1 (en) | 2016-07-15 | 2017-07-17 | Compounds and methods for modulation of transcript processing |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2022162447A Division JP2022188237A (ja) | 2016-07-15 | 2022-10-07 | 転写プロセシングの調節のための化合物及び方法 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2019527549A JP2019527549A (ja) | 2019-10-03 |
| JP2019527549A5 true JP2019527549A5 (enExample) | 2020-08-27 |
| JP7211933B2 JP7211933B2 (ja) | 2023-01-24 |
Family
ID=60952754
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2019501570A Active JP7211933B2 (ja) | 2016-07-15 | 2017-07-17 | 転写プロセシングの調節のための化合物及び方法 |
| JP2022162447A Withdrawn JP2022188237A (ja) | 2016-07-15 | 2022-10-07 | 転写プロセシングの調節のための化合物及び方法 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2022162447A Withdrawn JP2022188237A (ja) | 2016-07-15 | 2022-10-07 | 転写プロセシングの調節のための化合物及び方法 |
Country Status (6)
| Country | Link |
|---|---|
| US (2) | US20190321387A1 (enExample) |
| EP (1) | EP3485016A4 (enExample) |
| JP (2) | JP7211933B2 (enExample) |
| AU (1) | AU2017297624B2 (enExample) |
| CA (1) | CA3027177A1 (enExample) |
| WO (1) | WO2018014043A1 (enExample) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR112017004056A2 (pt) | 2014-09-12 | 2017-12-05 | Biogen Ma Inc | composições e métodos para detecção da proteína smn em um indivíduo e tratamento de um indivíduo |
| EP3485016A4 (en) * | 2016-07-15 | 2020-03-18 | Ionis Pharmaceuticals, Inc. | COMPOUNDS AND METHODS FOR MODULATING TRANSCRIPTION PROCESSING |
| AR121446A1 (es) * | 2020-02-28 | 2022-06-08 | Ionis Pharmaceuticals Inc | Compuestos y métodos para modular smn2 |
| CN119213005A (zh) | 2022-03-16 | 2024-12-27 | 艾姆皮瑞克公司 | 用于提高siRNA生物利用度的GALNAC组合物 |
| WO2023192830A2 (en) | 2022-03-28 | 2023-10-05 | Empirico Inc. | Modified oligonucleotides |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6147200A (en) * | 1999-08-19 | 2000-11-14 | Isis Pharmaceuticals, Inc. | 2'-O-acetamido modified monomers and oligomers |
| PL1910395T3 (pl) * | 2005-06-23 | 2013-03-29 | Cold Spring Harbor Laboratory | Kompozycja i sposób modulacji splicingu SMN2 |
| US20070213292A1 (en) * | 2005-08-10 | 2007-09-13 | The Rockefeller University | Chemically modified oligonucleotides for use in modulating micro RNA and uses thereof |
| WO2011123621A2 (en) * | 2010-04-01 | 2011-10-06 | Alnylam Pharmaceuticals Inc. | 2' and 5' modified monomers and oligonucleotides |
| WO2011159836A2 (en) * | 2010-06-15 | 2011-12-22 | Isis Pharmaceuticals, Inc. | Compounds and methods for modulating interaction between proteins and target nucleic acids |
| DK3031920T3 (da) * | 2010-07-19 | 2019-10-14 | Ionis Pharmaceuticals Inc | Modulation af dystrofi myotonica-protein kinase (dmpk) ekspression |
| GB201410693D0 (en) * | 2014-06-16 | 2014-07-30 | Univ Southampton | Splicing modulation |
| EP3485016A4 (en) * | 2016-07-15 | 2020-03-18 | Ionis Pharmaceuticals, Inc. | COMPOUNDS AND METHODS FOR MODULATING TRANSCRIPTION PROCESSING |
| AR121446A1 (es) * | 2020-02-28 | 2022-06-08 | Ionis Pharmaceuticals Inc | Compuestos y métodos para modular smn2 |
-
2017
- 2017-07-17 EP EP17828627.4A patent/EP3485016A4/en active Pending
- 2017-07-17 WO PCT/US2017/042465 patent/WO2018014043A1/en not_active Ceased
- 2017-07-17 CA CA3027177A patent/CA3027177A1/en not_active Abandoned
- 2017-07-17 JP JP2019501570A patent/JP7211933B2/ja active Active
- 2017-07-17 AU AU2017297624A patent/AU2017297624B2/en active Active
- 2017-07-17 US US16/310,758 patent/US20190321387A1/en not_active Abandoned
-
2020
- 2020-11-18 US US16/951,449 patent/US20210315918A1/en active Pending
-
2022
- 2022-10-07 JP JP2022162447A patent/JP2022188237A/ja not_active Withdrawn
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