JP2019524151A5 - - Google Patents

Info

Publication number

JP2019524151A5

JP2019524151A5 JP2019511384A JP2019511384A JP2019524151A5 JP 2019524151 A5 JP2019524151 A5 JP 2019524151A5 JP 2019511384 A JP2019511384 A JP 2019511384A JP 2019511384 A JP2019511384 A JP 2019511384A JP 2019524151 A5 JP2019524151 A5 JP 2019524151A5

Authority

JP

Japan

Prior art keywords

seq

rnai construct

sequence

composition

sense strand

Prior art date

2017-08-25

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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• 108091030071 RNAI Proteins 0.000 claims description 105
• 230000009368 gene silencing by RNA Effects 0.000 claims description 105
• 230000000692 anti-sense effect Effects 0.000 claims description 51
• 108091081021 Sense strand Proteins 0.000 claims description 46
• 125000003729 nucleotide group Chemical group 0.000 claims description 43
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical group C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 30
• 239000002773 nucleotide Substances 0.000 claims description 24
• 101000785944 Homo sapiens Asialoglycoprotein receptor 1 Proteins 0.000 claims description 16
• 102100026292 Asialoglycoprotein receptor 1 Human genes 0.000 claims description 15
• 235000012000 cholesterol Nutrition 0.000 claims description 15
• 239000003446 ligand Substances 0.000 claims description 13
• 208000029078 coronary artery disease Diseases 0.000 claims description 12
• 208000010125 myocardial infarction Diseases 0.000 claims description 12
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 9
• 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 description 5
• 239000000427 antigen Substances 0.000 claims description 5
• 102000036639 antigens Human genes 0.000 claims description 5
• 108091007433 antigens Proteins 0.000 claims description 5
• 230000000295 complement effect Effects 0.000 claims description 5
• 239000012634 fragment Substances 0.000 claims description 5
• RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 claims description 4
• -1 bicyclic nucleic acids Chemical class 0.000 claims description 4
• RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims description 4
• 108020004999 messenger RNA Proteins 0.000 claims description 3
• HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 claims description 2
• MSWZFWKMSRAUBD-GASJEMHNSA-N 2-amino-2-deoxy-D-galactopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O MSWZFWKMSRAUBD-GASJEMHNSA-N 0.000 claims description 2
• 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 description 2
• WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 claims description 2
• MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 claims description 2
• 239000003613 bile acid Substances 0.000 claims description 2
• 150000001720 carbohydrates Chemical class 0.000 claims description 2
• 235000014113 dietary fatty acids Nutrition 0.000 claims description 2
• 239000003085 diluting agent Substances 0.000 claims description 2
• 239000003937 drug carrier Substances 0.000 claims description 2
• 229930195729 fatty acid Natural products 0.000 claims description 2
• 239000000194 fatty acid Substances 0.000 claims description 2
• 150000004665 fatty acids Chemical class 0.000 claims description 2
• 125000003929 folic acid group Chemical group 0.000 claims description 2
• 229930182830 galactose Natural products 0.000 claims description 2
• 229930182470 glycoside Natural products 0.000 claims description 2
• 150000002338 glycosides Chemical class 0.000 claims description 2
• 238000001990 intravenous administration Methods 0.000 claims description 2
• 108020004707 nucleic acids Proteins 0.000 claims description 2
• 102000039446 nucleic acids Human genes 0.000 claims description 2
• 239000008194 pharmaceutical composition Substances 0.000 claims description 2
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
• 230000002265 prevention Effects 0.000 claims description 2
• 150000003431 steroids Chemical class 0.000 claims description 2
• 238000007920 subcutaneous administration Methods 0.000 claims description 2
• 239000011782 vitamin Substances 0.000 claims description 2
• 235000013343 vitamin Nutrition 0.000 claims description 2
• 229940088594 vitamin Drugs 0.000 claims description 2
• 229930003231 vitamin Natural products 0.000 claims description 2
• 150000003722 vitamin derivatives Chemical class 0.000 claims description 2
• 239000000203 mixture Substances 0.000 claims 22
• 230000008878 coupling Effects 0.000 claims 2
• 238000010168 coupling process Methods 0.000 claims 2
• 238000005859 coupling reaction Methods 0.000 claims 2
• 238000000034 method Methods 0.000 description 17
• 239000003814 drug Substances 0.000 description 6
• 238000002360 preparation method Methods 0.000 description 6
• 210000004027 cell Anatomy 0.000 description 5
• 210000003494 hepatocyte Anatomy 0.000 description 4
• 238000008214 LDL Cholesterol Methods 0.000 description 3
• 235000001014 amino acid Nutrition 0.000 description 3
• 235000018417 cysteine Nutrition 0.000 description 2
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
• 210000005229 liver cell Anatomy 0.000 description 2
• 150000001413 amino acids Chemical class 0.000 description 1
• 150000001875 compounds Chemical class 0.000 description 1
• 102000051237 human ASGR1 Human genes 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 238000006467 substitution reaction Methods 0.000 description 1