JP2011502501A5 - - Google Patents

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Publication number

JP2011502501A5

JP2011502501A5 JP2010532629A JP2010532629A JP2011502501A5 JP 2011502501 A5 JP2011502501 A5 JP 2011502501A5 JP 2010532629 A JP2010532629 A JP 2010532629A JP 2010532629 A JP2010532629 A JP 2010532629A JP 2011502501 A5 JP2011502501 A5 JP 2011502501A5

Authority

JP

Japan

Prior art keywords

oligonucleotide

nucleobases

modified

nucleobase

virus

Prior art date

2008-11-05

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

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• 108091034117 Oligonucleotide Proteins 0.000 claims 38
• 150000001875 compounds Chemical class 0.000 claims 15
• 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 11
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 10
• 241000700605 Viruses Species 0.000 claims 9
• 230000029812 viral genome replication Effects 0.000 claims 9
• 108020004707 nucleic acids Proteins 0.000 claims 8
• 150000007523 nucleic acids Chemical class 0.000 claims 8
• 102000039446 nucleic acids Human genes 0.000 claims 8
• PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims 8
• 239000002773 nucleotide Substances 0.000 claims 7
• 125000003729 nucleotide group Chemical group 0.000 claims 7
• 230000003612 virological effect Effects 0.000 claims 7
• 230000002401 inhibitory effect Effects 0.000 claims 6
• 230000000295 complement effect Effects 0.000 claims 4
• 239000003814 drug Substances 0.000 claims 4
• 239000003937 drug carrier Substances 0.000 claims 4
• 108020004414 DNA Proteins 0.000 claims 3
• 241001493065 dsRNA viruses Species 0.000 claims 3
• 238000004519 manufacturing process Methods 0.000 claims 3
• 230000010076 replication Effects 0.000 claims 3
• 108091026890 Coding region Proteins 0.000 claims 2
• 101710163270 Nuclease Proteins 0.000 claims 2
• 241001631646 Papillomaviridae Species 0.000 claims 2
• 241000710961 Semliki Forest virus Species 0.000 claims 2
• 108700005077 Viral Genes Proteins 0.000 claims 2
• 238000009396 hybridization Methods 0.000 claims 2
• 238000000034 method Methods 0.000 claims 2
• 239000000546 pharmaceutical excipient Substances 0.000 claims 2
• 238000010839 reverse transcription Methods 0.000 claims 2
• JHEKNTQSGTVPAO-UHFFFAOYSA-N 2-amino-8-sulfanylidene-7,9-dihydro-3h-purin-6-one Chemical compound N1C(N)=NC(=O)C2=C1NC(=S)N2 JHEKNTQSGTVPAO-UHFFFAOYSA-N 0.000 claims 1
• OFJNVANOCZHTMW-UHFFFAOYSA-N 5-hydroxyuracil Chemical compound OC1=CNC(=O)NC1=O OFJNVANOCZHTMW-UHFFFAOYSA-N 0.000 claims 1
• MIHCRNZMESVPJI-UHFFFAOYSA-N 5-sulfanyl-1h-pyrimidine-2,4-dione Chemical compound SC1=CNC(=O)NC1=O MIHCRNZMESVPJI-UHFFFAOYSA-N 0.000 claims 1
• NLLCDONDZDHLCI-UHFFFAOYSA-N 6-amino-5-hydroxy-1h-pyrimidin-2-one Chemical compound NC=1NC(=O)N=CC=1O NLLCDONDZDHLCI-UHFFFAOYSA-N 0.000 claims 1
• UGQXLWWNSMGEBY-UHFFFAOYSA-N 6-amino-5-sulfanyl-1h-pyrimidin-2-one Chemical compound NC1=NC(=O)NC=C1S UGQXLWWNSMGEBY-UHFFFAOYSA-N 0.000 claims 1
• BHVOFCPOXNYVCE-UHFFFAOYSA-N 6-amino-7,9-dihydropurine-8-thione Chemical compound NC1=NC=NC2=C1NC(=S)N2 BHVOFCPOXNYVCE-UHFFFAOYSA-N 0.000 claims 1
• CLGFIVUFZRGQRP-UHFFFAOYSA-N 7,8-dihydro-8-oxoguanine Chemical compound O=C1NC(N)=NC2=C1NC(=O)N2 CLGFIVUFZRGQRP-UHFFFAOYSA-N 0.000 claims 1
• RGKBRPAAQSHTED-UHFFFAOYSA-N 8-oxoadenine Chemical compound NC1=NC=NC2=C1NC(=O)N2 RGKBRPAAQSHTED-UHFFFAOYSA-N 0.000 claims 1
• 241000710929 Alphavirus Species 0.000 claims 1
• 229910052684 Cerium Inorganic materials 0.000 claims 1
• 241000388186 Deltapapillomavirus 4 Species 0.000 claims 1
• 229910052692 Dysprosium Inorganic materials 0.000 claims 1
• 229910052691 Erbium Inorganic materials 0.000 claims 1
• 229910052693 Europium Inorganic materials 0.000 claims 1
• 229910052688 Gadolinium Inorganic materials 0.000 claims 1
• 241000711549 Hepacivirus C Species 0.000 claims 1
• 229910052689 Holmium Inorganic materials 0.000 claims 1
• 241000713772 Human immunodeficiency virus 1 Species 0.000 claims 1
• 241000701806 Human papillomavirus Species 0.000 claims 1
• 229910052765 Lutetium Inorganic materials 0.000 claims 1
• 229910052779 Neodymium Inorganic materials 0.000 claims 1
• 108091092724 Noncoding DNA Proteins 0.000 claims 1
• 229910052777 Praseodymium Inorganic materials 0.000 claims 1
• 229910052773 Promethium Inorganic materials 0.000 claims 1
• 229910052772 Samarium Inorganic materials 0.000 claims 1
• 229910052771 Terbium Inorganic materials 0.000 claims 1
• 229910052775 Thulium Inorganic materials 0.000 claims 1
• 229910052769 Ytterbium Inorganic materials 0.000 claims 1
• 230000001154 acute effect Effects 0.000 claims 1
• ZMIGMASIKSOYAM-UHFFFAOYSA-N cerium Chemical compound [Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce] ZMIGMASIKSOYAM-UHFFFAOYSA-N 0.000 claims 1
• 230000001684 chronic effect Effects 0.000 claims 1
• 238000003776 cleavage reaction Methods 0.000 claims 1
• KBQHZAAAGSGFKK-UHFFFAOYSA-N dysprosium atom Chemical compound [Dy] KBQHZAAAGSGFKK-UHFFFAOYSA-N 0.000 claims 1
• UYAHIZSMUZPPFV-UHFFFAOYSA-N erbium Chemical compound [Er] UYAHIZSMUZPPFV-UHFFFAOYSA-N 0.000 claims 1
• OGPBJKLSAFTDLK-UHFFFAOYSA-N europium atom Chemical compound [Eu] OGPBJKLSAFTDLK-UHFFFAOYSA-N 0.000 claims 1
• 230000001747 exhibiting effect Effects 0.000 claims 1
• UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 claims 1
• KJZYNXUDTRRSPN-UHFFFAOYSA-N holmium atom Chemical compound [Ho] KJZYNXUDTRRSPN-UHFFFAOYSA-N 0.000 claims 1
• 229910052747 lanthanoid Inorganic materials 0.000 claims 1
• 150000002602 lanthanoids Chemical class 0.000 claims 1
• 229910052746 lanthanum Inorganic materials 0.000 claims 1
• FZLIPJUXYLNCLC-UHFFFAOYSA-N lanthanum atom Chemical compound [La] FZLIPJUXYLNCLC-UHFFFAOYSA-N 0.000 claims 1
• 239000002502 liposome Substances 0.000 claims 1
• OHSVLFRHMCKCQY-UHFFFAOYSA-N lutetium atom Chemical compound [Lu] OHSVLFRHMCKCQY-UHFFFAOYSA-N 0.000 claims 1
• 229910052751 metal Inorganic materials 0.000 claims 1
• 239000002184 metal Substances 0.000 claims 1
• QEFYFXOXNSNQGX-UHFFFAOYSA-N neodymium atom Chemical compound [Nd] QEFYFXOXNSNQGX-UHFFFAOYSA-N 0.000 claims 1
• 230000004962 physiological condition Effects 0.000 claims 1
• PUDIUYLPXJFUGB-UHFFFAOYSA-N praseodymium atom Chemical compound [Pr] PUDIUYLPXJFUGB-UHFFFAOYSA-N 0.000 claims 1
• VQMWBBYLQSCNPO-UHFFFAOYSA-N promethium atom Chemical compound [Pm] VQMWBBYLQSCNPO-UHFFFAOYSA-N 0.000 claims 1
• 230000001105 regulatory effect Effects 0.000 claims 1
• 108091008025 regulatory factors Proteins 0.000 claims 1
• 102000037983 regulatory factors Human genes 0.000 claims 1
• KZUNJOHGWZRPMI-UHFFFAOYSA-N samarium atom Chemical compound [Sm] KZUNJOHGWZRPMI-UHFFFAOYSA-N 0.000 claims 1
• 230000007017 scission Effects 0.000 claims 1
• GZCRRIHWUXGPOV-UHFFFAOYSA-N terbium atom Chemical compound [Tb] GZCRRIHWUXGPOV-UHFFFAOYSA-N 0.000 claims 1
• 238000013518 transcription Methods 0.000 claims 1
• 230000035897 transcription Effects 0.000 claims 1
• 230000002103 transcriptional effect Effects 0.000 claims 1
• 241001430294 unidentified retrovirus Species 0.000 claims 1
• NAWDYIZEMPQZHO-UHFFFAOYSA-N ytterbium Chemical compound [Yb] NAWDYIZEMPQZHO-UHFFFAOYSA-N 0.000 claims 1