JP2012525852A5 - - Google Patents

Info

Publication number

JP2012525852A5

JP2012525852A5 JP2012510006A JP2012510006A JP2012525852A5 JP 2012525852 A5 JP2012525852 A5 JP 2012525852A5 JP 2012510006 A JP2012510006 A JP 2012510006A JP 2012510006 A JP2012510006 A JP 2012510006A JP 2012525852 A5 JP2012525852 A5 JP 2012525852A5

Authority

JP

Japan

Prior art keywords

oligonucleotide

composition

polynucleotide

antisense

dystrophin family

Prior art date

2010-05-07

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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• 108091034117 Oligonucleotide Proteins 0.000 claims 37
• 108091033319 polynucleotide Proteins 0.000 claims 32
• 102000040430 polynucleotide Human genes 0.000 claims 32
• 239000002157 polynucleotide Substances 0.000 claims 32
• 102000001039 Dystrophin Human genes 0.000 claims 30
• 108010069091 Dystrophin Proteins 0.000 claims 30
• 239000000203 mixture Substances 0.000 claims 30
• 125000003729 nucleotide group Chemical group 0.000 claims 19
• 230000004048 modification Effects 0.000 claims 15
• 238000012986 modification Methods 0.000 claims 15
• 150000007523 nucleic acids Chemical group 0.000 claims 15
• 230000000692 anti-sense effect Effects 0.000 claims 14
• 239000002773 nucleotide Substances 0.000 claims 14
• 239000000074 antisense oligonucleotide Substances 0.000 claims 11
• 238000012230 antisense oligonucleotides Methods 0.000 claims 11
• 238000001727 in vivo Methods 0.000 claims 11
• 102000039446 nucleic acids Human genes 0.000 claims 10
• 108020004707 nucleic acids Proteins 0.000 claims 10
• 230000006870 function Effects 0.000 claims 9
• 238000000338 in vitro Methods 0.000 claims 9
• 230000000295 complement effect Effects 0.000 claims 8
• 108091093037 Peptide nucleic acid Proteins 0.000 claims 7
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 6
• RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims 6
• 108091028043 Nucleic acid sequence Proteins 0.000 claims 5
• -1 phosphate triester Chemical class 0.000 claims 5
• 206010013801 Duchenne Muscular Dystrophy Diseases 0.000 claims 4
• 210000004027 cell Anatomy 0.000 claims 4
• 201000010099 disease Diseases 0.000 claims 4
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical class CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims 3
• 125000005600 alkyl phosphonate group Chemical group 0.000 claims 3
• 125000002619 bicyclic group Chemical group 0.000 claims 3
• BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 claims 3
• KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 claims 3
• NAGJZTKCGNOGPW-UHFFFAOYSA-K dioxido-sulfanylidene-sulfido-$l^{5}-phosphane Chemical compound [O-]P([O-])([S-])=S NAGJZTKCGNOGPW-UHFFFAOYSA-K 0.000 claims 3
• 238000000034 method Methods 0.000 claims 3
• 201000006938 muscular dystrophy Diseases 0.000 claims 3
• PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 claims 3
• 108090000623 proteins and genes Proteins 0.000 claims 3
• KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 claims 3
• 201000006935 Becker muscular dystrophy Diseases 0.000 claims 2
• 208000021642 Muscular disease Diseases 0.000 claims 2
• 208000012902 Nervous system disease Diseases 0.000 claims 2
• 208000025966 Neurological disease Diseases 0.000 claims 2
• 229910019142 PO4 Inorganic materials 0.000 claims 2
• 108020004459 Small interfering RNA Proteins 0.000 claims 2
• 201000011212 X-linked dilated cardiomyopathy Diseases 0.000 claims 2
• 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 2
• 208000035475 disorder Diseases 0.000 claims 2
• 210000004962 mammalian cell Anatomy 0.000 claims 2
• 208000018360 neuromuscular disease Diseases 0.000 claims 2
• 239000010452 phosphate Substances 0.000 claims 2
• 239000004055 small Interfering RNA Substances 0.000 claims 2
• 108700028369 Alleles Proteins 0.000 claims 1
• 108020000948 Antisense Oligonucleotides Proteins 0.000 claims 1
• 201000001320 Atherosclerosis Diseases 0.000 claims 1
• 208000031229 Cardiomyopathies Diseases 0.000 claims 1
• 208000024172 Cardiovascular disease Diseases 0.000 claims 1
• 108091026890 Coding region Proteins 0.000 claims 1
• 206010010356 Congenital anomaly Diseases 0.000 claims 1
• 206010056370 Congestive cardiomyopathy Diseases 0.000 claims 1
• 206010011878 Deafness Diseases 0.000 claims 1
• 201000010046 Dilated cardiomyopathy Diseases 0.000 claims 1
• 208000014094 Dystonic disease Diseases 0.000 claims 1
• 102100022745 Laminin subunit alpha-2 Human genes 0.000 claims 1
• 208000011093 Myoclonus-dystonia syndrome Diseases 0.000 claims 1
• 208000010316 Myotonia congenita Diseases 0.000 claims 1
• 206010028980 Neoplasm Diseases 0.000 claims 1
• 208000001140 Night Blindness Diseases 0.000 claims 1
• 108010029485 Protein Isoforms Proteins 0.000 claims 1
• 102000001708 Protein Isoforms Human genes 0.000 claims 1
• 208000037328 Qualitative or quantitative defects of sarcoglycan Diseases 0.000 claims 1
• 108091081021 Sense strand Proteins 0.000 claims 1
• 201000011510 cancer Diseases 0.000 claims 1
• 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims 1
• 150000001875 compounds Chemical class 0.000 claims 1
• 201000006815 congenital muscular dystrophy Diseases 0.000 claims 1
• 201000011474 congenital myopathy Diseases 0.000 claims 1
• 230000008602 contraction Effects 0.000 claims 1
• 230000003436 cytoskeletal effect Effects 0.000 claims 1
• 208000010118 dystonia Diseases 0.000 claims 1
• 150000002148 esters Chemical class 0.000 claims 1
• 125000001153 fluoro group Chemical group F* 0.000 claims 1
• 239000012634 fragment Substances 0.000 claims 1
• 230000010370 hearing loss Effects 0.000 claims 1
• 231100000888 hearing loss Toxicity 0.000 claims 1
• 208000016354 hearing loss disease Diseases 0.000 claims 1
• 238000009396 hybridization Methods 0.000 claims 1
• 210000005240 left ventricle Anatomy 0.000 claims 1
• 230000014759 maintenance of location Effects 0.000 claims 1
• 238000002844 melting Methods 0.000 claims 1
• 230000008018 melting Effects 0.000 claims 1
• YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical compound CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 claims 1
• 208000029264 myotonic syndrome Diseases 0.000 claims 1
• 230000002093 peripheral effect Effects 0.000 claims 1
• 208000022587 qualitative or quantitative defects of dystrophin Diseases 0.000 claims 1
• 208000010532 sarcoglycanopathy Diseases 0.000 claims 1
• 230000001568 sexual effect Effects 0.000 claims 1
• 208000002320 spinal muscular atrophy Diseases 0.000 claims 1
• 238000006467 substitution reaction Methods 0.000 claims 1
• 230000008685 targeting Effects 0.000 claims 1
• 235000011178 triphosphate Nutrition 0.000 claims 1
• 239000001226 triphosphate Substances 0.000 claims 1
• UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 claims 1