JPWO2021167841A5 - - Google Patents

Info

Publication number

JPWO2021167841A5

JPWO2021167841A5 JP2022549500A JP2022549500A JPWO2021167841A5 JP WO2021167841 A5 JPWO2021167841 A5 JP WO2021167841A5 JP 2022549500 A JP2022549500 A JP 2022549500A JP 2022549500 A JP2022549500 A JP 2022549500A JP WO2021167841 A5 JPWO2021167841 A5 JP WO2021167841A5

Authority

JP

Japan

Prior art keywords

nucleotides

dsrna agent

sense strand

strand

dsrna

Prior art date

2024-02-20

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
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• 125000003729 nucleotide group Chemical group 0.000 claims 61
• 239000003795 chemical substances by application Substances 0.000 claims 53
• 239000002773 nucleotide Substances 0.000 claims 51
• 108091081021 Sense strand Proteins 0.000 claims 30
• 230000000692 anti-sense effect Effects 0.000 claims 26
• 108010056301 Apolipoprotein C-III Proteins 0.000 claims 18
• 102100030970 Apolipoprotein C-III Human genes 0.000 claims 18
• RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims 13
• 239000003446 ligand Substances 0.000 claims 12
• 239000008194 pharmaceutical composition Substances 0.000 claims 12
• 230000002401 inhibitory effect Effects 0.000 claims 9
• YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical compound CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 claims 9
• 230000004048 modification Effects 0.000 claims 8
• 238000012986 modification Methods 0.000 claims 8
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 6
• 229920002477 rna polymer Polymers 0.000 claims 6
• UEUPTUCWIHOIMK-RRKCRQDMSA-N 2'-deoxyadenosine 3'-monophosphate Chemical class 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 4
• 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 4
• 239000003814 drug Substances 0.000 claims 4
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 4
• 239000000872 buffer Substances 0.000 claims 3
• 238000010586 diagram Methods 0.000 claims 3
• 208000006575 hypertriglyceridemia Diseases 0.000 claims 3
• 238000000034 method Methods 0.000 claims 3
• 101150001527 APOC3 gene Proteins 0.000 claims 2
• 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 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 2
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 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
• 238000004519 manufacturing process Methods 0.000 claims 2
• 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims 2
• 239000002953 phosphate buffered saline Substances 0.000 claims 2
• 108090000623 proteins and genes Proteins 0.000 claims 2
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims 2
• 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
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims 1
• 206010003210 Arteriosclerosis Diseases 0.000 claims 1
• 201000001320 Atherosclerosis 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
• 206010018910 Haemolysis Diseases 0.000 claims 1
• 206010020772 Hypertension Diseases 0.000 claims 1
• 206010022489 Insulin Resistance Diseases 0.000 claims 1
• 108091028043 Nucleic acid sequence Proteins 0.000 claims 1
• 208000008589 Obesity Diseases 0.000 claims 1
• 229910019142 PO4 Inorganic materials 0.000 claims 1
• 206010033645 Pancreatitis Diseases 0.000 claims 1
• 238000009825 accumulation Methods 0.000 claims 1
• 208000011775 arteriosclerosis disease Diseases 0.000 claims 1
• 230000008588 hemolysis Effects 0.000 claims 1
• 208000017169 kidney disease Diseases 0.000 claims 1
• 239000007788 liquid Substances 0.000 claims 1
• 206010053219 non-alcoholic steatohepatitis Diseases 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
• 239000010452 phosphate Substances 0.000 claims 1
• 239000002504 physiological saline solution Substances 0.000 claims 1
• 201000010065 polycystic ovary syndrome Diseases 0.000 claims 1
• 230000002265 prevention Effects 0.000 claims 1
• 239000000243 solution Substances 0.000 claims 1
• 238000007920 subcutaneous administration Methods 0.000 claims 1
• 229940124597 therapeutic agent Drugs 0.000 claims 1
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 1