JP2018512155A5 - - Google Patents

Info

Publication number

JP2018512155A5

JP2018512155A5 JP2017553347A JP2017553347A JP2018512155A5 JP 2018512155 A5 JP2018512155 A5 JP 2018512155A5 JP 2017553347 A JP2017553347 A JP 2017553347A JP 2017553347 A JP2017553347 A JP 2017553347A JP 2018512155 A5 JP2018512155 A5 JP 2018512155A5

Authority

JP

Japan

Prior art keywords

seq

nucleotide

dsrna

nucleotides

modified

Prior art date

2016-04-13

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
• Global Dossier
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• 125000003729 nucleotide group Chemical group 0.000 claims 43
• 239000002773 nucleotide Substances 0.000 claims 32
• 101000693085 Homo sapiens Angiopoietin-related protein 3 Proteins 0.000 claims 12
• 230000000692 anti-sense effect Effects 0.000 claims 12
• 102100025668 Angiopoietin-related protein 3 Human genes 0.000 claims 9
• 108091081021 Sense strand Proteins 0.000 claims 8
• 238000012986 modification Methods 0.000 claims 7
• 230000004048 modification Effects 0.000 claims 7
• 230000002401 inhibitory effect Effects 0.000 claims 6
• 239000003446 ligand Substances 0.000 claims 6
• 229920002477 rna polymer Polymers 0.000 claims 4
• 229910019142 PO4 Inorganic materials 0.000 claims 3
• 108020004707 nucleic acids Proteins 0.000 claims 3
• 102000039446 nucleic acids Human genes 0.000 claims 3
• 239000008194 pharmaceutical composition Substances 0.000 claims 3
• 239000010452 phosphate Substances 0.000 claims 3
• 208000035762 Disorder of lipid metabolism Diseases 0.000 claims 2
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
• 208000035475 disorder Diseases 0.000 claims 2
• 239000003814 drug Substances 0.000 claims 2
• 238000004519 manufacturing process Methods 0.000 claims 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims 2
• RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims 2
• MPCAJMNYNOGXPB-UHFFFAOYSA-N 1,5-Anhydro-mannit Natural products OCC1OCC(O)C(O)C1O MPCAJMNYNOGXPB-UHFFFAOYSA-N 0.000 claims 1
• UEUPTUCWIHOIMK-UHFFFAOYSA-N 2'-deoxy-AMP Natural products C1=NC=2C(N)=NC=NC=2N1C1CC(OP(O)(O)=O)C(CO)O1 UEUPTUCWIHOIMK-UHFFFAOYSA-N 0.000 claims 1
• UEUPTUCWIHOIMK-RRKCRQDMSA-N 2'-deoxyadenosine 3'-monophosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@H]1C[C@H](OP(O)(O)=O)[C@@H](CO)O1 UEUPTUCWIHOIMK-RRKCRQDMSA-N 0.000 claims 1
• QQMSZHORHNORLP-KVQBGUIXSA-N 2'-deoxyguanosine 3'-monophosphate Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](OP(O)(O)=O)[C@@H](CO)O1 QQMSZHORHNORLP-KVQBGUIXSA-N 0.000 claims 1
• QQMSZHORHNORLP-UHFFFAOYSA-N 2'-deoxyguanosine 3'-monophosphate Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1CC(OP(O)(O)=O)C(CO)O1 QQMSZHORHNORLP-UHFFFAOYSA-N 0.000 claims 1
• FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims 1
• KBDWGFZSICOZSJ-UHFFFAOYSA-N 5-methyl-2,3-dihydro-1H-pyrimidin-4-one Chemical group N1CNC=C(C1=O)C KBDWGFZSICOZSJ-UHFFFAOYSA-N 0.000 claims 1
• 208000035657 Abasia Diseases 0.000 claims 1
• 208000031226 Hyperlipidaemia Diseases 0.000 claims 1
• OVRNDRQMDRJTHS-CBQIKETKSA-N N-Acetyl-D-Galactosamine Chemical compound CC(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-CBQIKETKSA-N 0.000 claims 1
• OVRNDRQMDRJTHS-KEWYIRBNSA-N N-acetyl-D-galactosamine Chemical class CC(=O)N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-KEWYIRBNSA-N 0.000 claims 1
• MBLBDJOUHNCFQT-UHFFFAOYSA-N N-acetyl-D-galactosamine Natural products CC(=O)NC(C=O)C(O)C(O)C(O)CO MBLBDJOUHNCFQT-UHFFFAOYSA-N 0.000 claims 1
• 108091034117 Oligonucleotide Proteins 0.000 claims 1
• 108091030071 RNAI Proteins 0.000 claims 1
• RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 claims 1
• 238000009825 accumulation Methods 0.000 claims 1
• 230000015556 catabolic process Effects 0.000 claims 1
• 239000003795 chemical substances by application Substances 0.000 claims 1
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol group Chemical group [C@@H]1(CC[C@H]2[C@@H]3CC=C4C[C@@H](O)CC[C@]4(C)[C@H]3CC[C@]12C)[C@H](C)CCCC(C)C HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims 1
• 238000003776 cleavage reaction Methods 0.000 claims 1
• 230000000295 complement effect Effects 0.000 claims 1
• 230000008878 coupling Effects 0.000 claims 1
• 238000010168 coupling process Methods 0.000 claims 1
• 238000005859 coupling reaction Methods 0.000 claims 1
• 238000006731 degradation reaction Methods 0.000 claims 1
• 238000010586 diagram Methods 0.000 claims 1
• BNKAXGCRDYRABM-UHFFFAOYSA-N ethenyl dihydrogen phosphate Chemical compound OP(O)(=O)OC=C BNKAXGCRDYRABM-UHFFFAOYSA-N 0.000 claims 1
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
• 125000001153 fluoro group Chemical group F* 0.000 claims 1
• 230000009368 gene silencing by RNA Effects 0.000 claims 1
• 208000006575 hypertriglyceridemia Diseases 0.000 claims 1
• 238000000338 in vitro Methods 0.000 claims 1
• 150000002632 lipids Chemical class 0.000 claims 1
• 125000001921 locked nucleotide group Chemical group 0.000 claims 1
• 108020004999 messenger RNA Proteins 0.000 claims 1
• 238000000034 method Methods 0.000 claims 1
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
• 230000003278 mimic effect Effects 0.000 claims 1
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 1
• ONKSSDKXDIVIHK-UHFFFAOYSA-N n,n-didecyldodecanamide Chemical group CCCCCCCCCCCC(=O)N(CCCCCCCCCC)CCCCCCCCCC ONKSSDKXDIVIHK-UHFFFAOYSA-N 0.000 claims 1
• PTMHPRAIXMAOOB-UHFFFAOYSA-N phosphoramidic acid Chemical compound NP(O)(O)=O PTMHPRAIXMAOOB-UHFFFAOYSA-N 0.000 claims 1
• 230000007017 scission Effects 0.000 claims 1
• 210000002966 serum Anatomy 0.000 claims 1
• -1 thymidine-glycol nucleic acid Chemical class 0.000 claims 1