JP2021500016A5 - - Google Patents

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Publication number

JP2021500016A5

JP2021500016A5 JP2020520487A JP2020520487A JP2021500016A5 JP 2021500016 A5 JP2021500016 A5 JP 2021500016A5 JP 2020520487 A JP2020520487 A JP 2020520487A JP 2020520487 A JP2020520487 A JP 2020520487A JP 2021500016 A5 JP2021500016 A5 JP 2021500016A5

Authority

JP

Japan

Prior art keywords

antisense oligonucleotide

modified antisense

pharmaceutically acceptable

acceptable salt

sequence

Prior art date

2018-10-18

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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• 108091034117 Oligonucleotide Proteins 0.000 claims description 40
• 239000000074 antisense oligonucleotide Substances 0.000 claims description 40
• 238000012230 antisense oligonucleotides Methods 0.000 claims description 40
• 230000008685 targeting Effects 0.000 claims description 18
• 108020004999 messenger RNA Proteins 0.000 claims description 7
• 230000000295 complement effect Effects 0.000 claims description 6
• 208000002320 spinal muscular atrophy Diseases 0.000 claims description 5
• 101100203485 Homo sapiens SMN2 gene Proteins 0.000 claims description 4
• 102000053564 human SMN2 Human genes 0.000 claims description 4
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 2
• 150000003839 salts Chemical class 0.000 claims 15
• 230000000692 anti-sense effect Effects 0.000 claims 3
• 239000003937 drug carrier Substances 0.000 claims 2
• 239000000203 mixture Substances 0.000 claims 2
• 239000008194 pharmaceutical composition Substances 0.000 claims 2
• 108020000948 Antisense Oligonucleotides Proteins 0.000 claims 1
• 206010028289 Muscle atrophy Diseases 0.000 claims 1
• 108091028043 Nucleic acid sequence Proteins 0.000 claims 1
• 239000003814 drug Substances 0.000 claims 1
• 230000020763 muscle atrophy Effects 0.000 claims 1
• 201000000585 muscular atrophy Diseases 0.000 claims 1
• 108020004707 nucleic acids Proteins 0.000 claims 1
• 150000007523 nucleic acids Chemical class 0.000 claims 1
• 102000039446 nucleic acids Human genes 0.000 claims 1
• 238000012217 deletion Methods 0.000 description 5
• 230000037430 deletion Effects 0.000 description 5
• 108700024394 Exon Proteins 0.000 description 2
• 101001053946 Homo sapiens Dystrophin Proteins 0.000 description 2
• UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
• 206010013801 Duchenne Muscular Dystrophy Diseases 0.000 description 1
• 208000032007 Glycogen storage disease due to acid maltase deficiency Diseases 0.000 description 1
• 206010053185 Glycogen storage disease type II Diseases 0.000 description 1
• 102100024295 Maltase-glucoamylase Human genes 0.000 description 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 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 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 108010028144 alpha-Glucosidases Proteins 0.000 description 1
• 201000004502 glycogen storage disease II Diseases 0.000 description 1