JPWO2020041769A5 - - Google Patents

Info

Publication number

JPWO2020041769A5

JPWO2020041769A5 JP2021509991A JP2021509991A JPWO2020041769A5 JP WO2020041769 A5 JPWO2020041769 A5 JP WO2020041769A5 JP 2021509991 A JP2021509991 A JP 2021509991A JP 2021509991 A JP2021509991 A JP 2021509991A JP WO2020041769 A5 JPWO2020041769 A5 JP WO2020041769A5

Authority

JP

Japan

Prior art keywords

nucleotides

optionally

oligonucleotide

positions

antisense strand

Prior art date

2022-08-31

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

• Espacenet
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• 239000002773 nucleotide Substances 0.000 claims description 150
• 125000003729 nucleotide group Chemical group 0.000 claims description 150
• 108091034117 Oligonucleotide Proteins 0.000 claims description 122
• 230000000692 anti-sense effect Effects 0.000 claims description 76
• 238000012986 modification Methods 0.000 claims description 61
• 230000004048 modification Effects 0.000 claims description 61
• 150000007523 nucleic acids Chemical group 0.000 claims description 59
• 108091081021 Sense strand Proteins 0.000 claims description 55
• 108020004707 nucleic acids Proteins 0.000 claims description 52
• 102000039446 nucleic acids Human genes 0.000 claims description 52
• 150000001875 compounds Chemical class 0.000 claims description 27
• RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims description 23
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
• 230000002209 hydrophobic effect Effects 0.000 claims description 8
• 125000005647 linker group Chemical group 0.000 claims description 8
• 229910019142 PO4 Inorganic materials 0.000 claims description 4
• 125000000217 alkyl group Chemical group 0.000 claims description 4
• -1 alkylene phosphonate Chemical compound 0.000 claims description 4
• 239000000074 antisense oligonucleotide Substances 0.000 claims description 4
• 238000012230 antisense oligonucleotides Methods 0.000 claims description 4
• 201000010099 disease Diseases 0.000 claims description 4
• 208000035475 disorder Diseases 0.000 claims description 4
• 108020004999 messenger RNA Proteins 0.000 claims description 4
• 235000021317 phosphate Nutrition 0.000 claims description 4
• 125000006850 spacer group Chemical group 0.000 claims description 4
• 230000003612 virological effect Effects 0.000 claims description 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 description 3
• 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 2
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
• 108020004414 DNA Proteins 0.000 claims description 2
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical group OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 2
• ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims description 2
• 125000003342 alkenyl group Chemical group 0.000 claims description 2
• 150000001408 amides Chemical class 0.000 claims description 2
• 150000001413 amino acids Chemical class 0.000 claims description 2
• 125000003118 aryl group Chemical group 0.000 claims description 2
• 229910052799 carbon Inorganic materials 0.000 claims description 2
• 150000001841 cholesterols Chemical class 0.000 claims description 2
• 230000000295 complement effect Effects 0.000 claims description 2
• 150000002148 esters Chemical class 0.000 claims description 2
• ZTWTYVWXUKTLCP-UHFFFAOYSA-L ethenyl-dioxido-oxo-$l^{5}-phosphane Chemical compound [O-]P([O-])(=O)C=C ZTWTYVWXUKTLCP-UHFFFAOYSA-L 0.000 claims description 2
• 230000009368 gene silencing by RNA Effects 0.000 claims description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
• 229910052757 nitrogen Inorganic materials 0.000 claims description 2
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 2
• 239000010452 phosphate Substances 0.000 claims description 2
• 150000008298 phosphoramidates Chemical class 0.000 claims description 2
• 150000003013 phosphoric acid derivatives Chemical class 0.000 claims description 2
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 2
• 102000004196 processed proteins & peptides Human genes 0.000 claims description 2
• 150000003852 triazoles Chemical class 0.000 claims description 2
• 239000011782 vitamin Substances 0.000 claims description 2
• 229940088594 vitamin Drugs 0.000 claims description 2
• 229930003231 vitamin Natural products 0.000 claims description 2
• 235000013343 vitamin Nutrition 0.000 claims description 2
• 150000003722 vitamin derivatives Chemical class 0.000 claims description 2
• 239000003814 drug Substances 0.000 claims 3
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
• 238000000034 method Methods 0.000 description 5
• 239000008194 pharmaceutical composition Substances 0.000 description 4
• 239000003937 drug carrier Substances 0.000 description 2