JP2017509354A5 - - Google Patents

Info

Publication number

JP2017509354A5

JP2017509354A5 JP2016568484A JP2016568484A JP2017509354A5 JP 2017509354 A5 JP2017509354 A5 JP 2017509354A5 JP 2016568484 A JP2016568484 A JP 2016568484A JP 2016568484 A JP2016568484 A JP 2016568484A JP 2017509354 A5 JP2017509354 A5 JP 2017509354A5

Authority

JP

Japan

Prior art keywords

double

rnai agent

stranded rnai

nucleotide

nucleotides

Prior art date

2015-02-11

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 46
• 108091030071 RNAI Proteins 0.000 claims 39
• 239000003795 chemical substances by application Substances 0.000 claims 39
• 230000009368 gene silencing by RNA Effects 0.000 claims 39
• 239000002773 nucleotide Substances 0.000 claims 35
• 239000008194 pharmaceutical composition Substances 0.000 claims 19
• 102100023418 Ketohexokinase Human genes 0.000 claims 12
• 108010062852 Ketohexokinase Proteins 0.000 claims 12
• 230000000692 anti-sense effect Effects 0.000 claims 10
• 238000012986 modification Methods 0.000 claims 8
• 230000004048 modification Effects 0.000 claims 8
• 108091081021 Sense strand Proteins 0.000 claims 7
• 210000004027 cell Anatomy 0.000 claims 6
• 239000003446 ligand Substances 0.000 claims 6
• 230000002401 inhibitory effect Effects 0.000 claims 5
• 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 4
• 108091032973 (ribonucleotides)n+m Proteins 0.000 claims 3
• 102000040650 (ribonucleotides)n+m Human genes 0.000 claims 3
• 229910019142 PO4 Inorganic materials 0.000 claims 3
• 239000000872 buffer Substances 0.000 claims 3
• 230000000295 complement effect Effects 0.000 claims 3
• 150000002632 lipids Chemical class 0.000 claims 3
• 208000024172 Cardiovascular disease Diseases 0.000 claims 2
• 208000032928 Dyslipidaemia Diseases 0.000 claims 2
• 208000004930 Fatty Liver Diseases 0.000 claims 2
• 101150063450 Khk gene Proteins 0.000 claims 2
• 208000017170 Lipid metabolism disease Diseases 0.000 claims 2
• 108091034117 Oligonucleotide Proteins 0.000 claims 2
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical group P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 claims 2
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
• 230000004064 dysfunction Effects 0.000 claims 2
• 238000009472 formulation Methods 0.000 claims 2
• 230000002641 glycemic effect Effects 0.000 claims 2
• 208000006575 hypertriglyceridemia Diseases 0.000 claims 2
• 208000017169 kidney disease Diseases 0.000 claims 2
• 208000019423 liver disease Diseases 0.000 claims 2
• 238000000034 method Methods 0.000 claims 2
• 239000000203 mixture Substances 0.000 claims 2
• ONKSSDKXDIVIHK-UHFFFAOYSA-N n,n-didecyldodecanamide Chemical group CCCCCCCCCCCC(=O)N(CCCCCCCCCC)CCCCCCCCCC ONKSSDKXDIVIHK-UHFFFAOYSA-N 0.000 claims 2
• 239000010452 phosphate Substances 0.000 claims 2
• 239000002953 phosphate buffered saline Substances 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
• 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
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims 1
• 208000009304 Acute Kidney Injury Diseases 0.000 claims 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims 1
• 208000030814 Eating disease Diseases 0.000 claims 1
• 206010048554 Endothelial dysfunction Diseases 0.000 claims 1
• 208000019454 Feeding and Eating disease Diseases 0.000 claims 1
• 201000005569 Gout Diseases 0.000 claims 1
• 206010019708 Hepatic steatosis Diseases 0.000 claims 1
• 208000031226 Hyperlipidaemia Diseases 0.000 claims 1
• 206010020772 Hypertension Diseases 0.000 claims 1
• 201000001431 Hyperuricemia Diseases 0.000 claims 1
• 206010022489 Insulin Resistance Diseases 0.000 claims 1
• 238000008214 LDL Cholesterol Methods 0.000 claims 1
• 208000001145 Metabolic Syndrome Diseases 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
• 108091028043 Nucleic acid sequence Proteins 0.000 claims 1
• 208000008589 Obesity Diseases 0.000 claims 1
• 208000033626 Renal failure acute Diseases 0.000 claims 1
• RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical group OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 claims 1
• 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims 1
• 230000002159 abnormal effect Effects 0.000 claims 1
• 230000005856 abnormality Effects 0.000 claims 1
• 238000009825 accumulation Methods 0.000 claims 1
• 201000011040 acute kidney failure Diseases 0.000 claims 1
• 210000001789 adipocyte Anatomy 0.000 claims 1
• 239000007853 buffer solution Substances 0.000 claims 1
• 239000008366 buffered solution Substances 0.000 claims 1
• 230000015556 catabolic process Effects 0.000 claims 1
• 235000012000 cholesterol Nutrition 0.000 claims 1
• 238000003776 cleavage reaction Methods 0.000 claims 1
• 235000019788 craving Nutrition 0.000 claims 1
• 238000006731 degradation reaction Methods 0.000 claims 1
• 206010012601 diabetes mellitus Diseases 0.000 claims 1
• 201000010099 disease Diseases 0.000 claims 1
• 235000014632 disordered eating Nutrition 0.000 claims 1
• 230000008694 endothelial dysfunction Effects 0.000 claims 1
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
• 208000010706 fatty liver disease Diseases 0.000 claims 1
• 230000002757 inflammatory effect Effects 0.000 claims 1
• 210000001596 intra-abdominal fat Anatomy 0.000 claims 1
• 108020004999 messenger RNA Proteins 0.000 claims 1
• YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical group CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 claims 1
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 1
• 239000002105 nanoparticle Substances 0.000 claims 1
• 235000020824 obesity Nutrition 0.000 claims 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims 1
• PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 claims 1
• 239000002504 physiological saline solution Substances 0.000 claims 1
• 230000000291 postprandial effect Effects 0.000 claims 1
• 108060006613 prolamin Proteins 0.000 claims 1
• 210000000512 proximal kidney tubule Anatomy 0.000 claims 1
• 230000007017 scission Effects 0.000 claims 1
• 231100000240 steatosis hepatitis Toxicity 0.000 claims 1
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims 1
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 1