JP2017532961A5 - - Google Patents

Info

Publication number

JP2017532961A5

JP2017532961A5 JP2017520449A JP2017520449A JP2017532961A5 JP 2017532961 A5 JP2017532961 A5 JP 2017532961A5 JP 2017520449 A JP2017520449 A JP 2017520449A JP 2017520449 A JP2017520449 A JP 2017520449A JP 2017532961 A5 JP2017532961 A5 JP 2017532961A5

Authority

JP

Japan

Prior art keywords

smad7

composition

antisense oligonucleotide

item

ibd

Prior art date

2015-10-16

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.)

Pending

Links

• Espacenet
• Global Dossier
• Discuss

• 101700026522 SMAD7 Proteins 0.000 claims description 69
• 102000049873 Smad7 Human genes 0.000 claims description 69
• 239000000074 antisense oligonucleotide Substances 0.000 claims description 44
• 238000012230 antisense oligonucleotides Methods 0.000 claims description 44
• 108091034117 Oligonucleotide Proteins 0.000 claims description 40
• 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 22
• 239000002773 nucleotide Substances 0.000 claims description 22
• 125000003729 nucleotide group Chemical group 0.000 claims description 22
• RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims description 11
• 102000054765 polymorphisms of proteins Human genes 0.000 claims description 9
• LUCHPKXVUGJYGU-XLPZGREQSA-N 5-methyl-2'-deoxycytidine Chemical compound O=C1N=C(N)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 LUCHPKXVUGJYGU-XLPZGREQSA-N 0.000 claims description 8
• 150000007523 nucleic acids Chemical group 0.000 claims description 7
• 108020000948 Antisense Oligonucleotides Proteins 0.000 claims description 6
• 206010009900 Colitis ulcerative Diseases 0.000 claims description 4
• 208000011231 Crohn disease Diseases 0.000 claims description 4
• 108091028043 Nucleic acid sequence Proteins 0.000 claims description 4
• 201000006704 Ulcerative Colitis Diseases 0.000 claims description 4
• 239000008194 pharmaceutical composition Substances 0.000 claims description 4
• 102000039446 nucleic acids Human genes 0.000 claims description 3
• 108020004707 nucleic acids Proteins 0.000 claims description 3
• 108091028664 Ribonucleotide Proteins 0.000 claims description 2
• 239000002671 adjuvant Substances 0.000 claims description 2
• 230000000295 complement effect Effects 0.000 claims description 2
• 239000005547 deoxyribonucleotide Substances 0.000 claims description 2
• 239000008203 oral pharmaceutical composition Substances 0.000 claims description 2
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
• 239000002336 ribonucleotide Substances 0.000 claims description 2
• 125000002652 ribonucleotide group Chemical group 0.000 claims description 2
• 239000000203 mixture Substances 0.000 claims 16
• 239000003814 drug Substances 0.000 claims 4
• 238000000034 method Methods 0.000 description 36
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 9
• 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 8
• 102100040247 Tumor necrosis factor Human genes 0.000 description 3
• 229930024421 Adenine Natural products 0.000 description 2
• GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 2
• 229960000643 adenine Drugs 0.000 description 2
• UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
• MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
• 102000052567 Anaphase-Promoting Complex-Cyclosome Apc1 Subunit Human genes 0.000 description 1
• 238000001712 DNA sequencing Methods 0.000 description 1
• 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 1
• 108090000144 Human Proteins Proteins 0.000 description 1
• 102000003839 Human Proteins Human genes 0.000 description 1
• 108091006463 SLC25A24 Proteins 0.000 description 1
• 206010054094 Tumour necrosis Diseases 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
• 238000001574 biopsy Methods 0.000 description 1
• 230000014509 gene expression Effects 0.000 description 1
• 238000011223 gene expression profiling Methods 0.000 description 1
• 239000007788 liquid Substances 0.000 description 1
• 108020004999 messenger RNA Proteins 0.000 description 1
• 238000010208 microarray analysis Methods 0.000 description 1
• 238000007481 next generation sequencing Methods 0.000 description 1
• 108090000623 proteins and genes Proteins 0.000 description 1
• 230000008685 targeting Effects 0.000 description 1