JP2019513372A5 - - Google Patents

Info

Publication number

JP2019513372A5

JP2019513372A5 JP2018551989A JP2018551989A JP2019513372A5 JP 2019513372 A5 JP2019513372 A5 JP 2019513372A5 JP 2018551989 A JP2018551989 A JP 2018551989A JP 2018551989 A JP2018551989 A JP 2018551989A JP 2019513372 A5 JP2019513372 A5 JP 2019513372A5

Authority

JP

Japan

Prior art keywords

mcna

lna

ome

delivery

polynucleotides

Prior art date

2017-04-07

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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• 108091033319 polynucleotide Proteins 0.000 claims description 52
• 102000040430 polynucleotide Human genes 0.000 claims description 52
• 239000002157 polynucleotide Substances 0.000 claims description 48
• 125000003729 nucleotide group Chemical group 0.000 claims description 18
• 108020005345 3' Untranslated Regions Proteins 0.000 claims description 16
• 102000004169 proteins and genes Human genes 0.000 claims description 12
• 108090000623 proteins and genes Proteins 0.000 claims description 12
• 239000000203 mixture Substances 0.000 claims description 10
• 239000002773 nucleotide Substances 0.000 claims description 10
• GJTBSTBJLVYKAU-XVFCMESISA-N 2-thiouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=S)NC(=O)C=C1 GJTBSTBJLVYKAU-XVFCMESISA-N 0.000 claims description 8
• ZAYHVCMSTBRABG-UHFFFAOYSA-N 5-Methylcytidine Natural products O=C1N=C(N)C(C)=CN1C1C(O)C(O)C(CO)O1 ZAYHVCMSTBRABG-UHFFFAOYSA-N 0.000 claims description 8
• ZAYHVCMSTBRABG-JXOAFFINSA-N 5-methylcytidine Chemical compound O=C1N=C(N)C(C)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 ZAYHVCMSTBRABG-JXOAFFINSA-N 0.000 claims description 8
• 150000001875 compounds Chemical class 0.000 claims description 8
• UVBYMVOUBXYSFV-XUTVFYLZSA-N 1-methylpseudouridine Chemical compound O=C1NC(=O)N(C)C=C1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 UVBYMVOUBXYSFV-XUTVFYLZSA-N 0.000 claims description 6
• UVBYMVOUBXYSFV-UHFFFAOYSA-N 1-methylpseudouridine Natural products O=C1NC(=O)N(C)C=C1C1C(O)C(O)C(CO)O1 UVBYMVOUBXYSFV-UHFFFAOYSA-N 0.000 claims description 6
• VQAYFKKCNSOZKM-IOSLPCCCSA-N N(6)-methyladenosine Chemical compound C1=NC=2C(NC)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O VQAYFKKCNSOZKM-IOSLPCCCSA-N 0.000 claims description 6
• VQAYFKKCNSOZKM-UHFFFAOYSA-N NSC 29409 Natural products C1=NC=2C(NC)=NC=NC=2N1C1OC(CO)C(O)C1O VQAYFKKCNSOZKM-UHFFFAOYSA-N 0.000 claims description 6
• 229930185560 Pseudouridine Natural products 0.000 claims description 6
• PTJWIQPHWPFNBW-UHFFFAOYSA-N Pseudouridine C Natural products OC1C(O)C(CO)OC1C1=CNC(=O)NC1=O PTJWIQPHWPFNBW-UHFFFAOYSA-N 0.000 claims description 6
• WGDUUQDYDIIBKT-UHFFFAOYSA-N beta-Pseudouridine Natural products OC1OC(CN2C=CC(=O)NC2=O)C(O)C1O WGDUUQDYDIIBKT-UHFFFAOYSA-N 0.000 claims description 6
• 108020004999 messenger RNA Proteins 0.000 claims description 6
• 102000039446 nucleic acids Human genes 0.000 claims description 6
• 108020004707 nucleic acids Proteins 0.000 claims description 6
• 150000007523 nucleic acids Chemical class 0.000 claims description 6
• PTJWIQPHWPFNBW-GBNDHIKLSA-N pseudouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1C1=CNC(=O)NC1=O PTJWIQPHWPFNBW-GBNDHIKLSA-N 0.000 claims description 6
• 125000006850 spacer group Chemical group 0.000 claims description 6
• 239000003981 vehicle Substances 0.000 claims description 6
• 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 4
• 108020004414 DNA Proteins 0.000 claims description 4
• DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 claims description 4
• 102000028499 poly(A) binding Human genes 0.000 claims description 4
• 108091023021 poly(A) binding Proteins 0.000 claims description 4
• 125000000548 ribosyl group Chemical group C1([C@H](O)[C@H](O)[C@H](O1)CO)* 0.000 claims description 4
• 101710163270 Nuclease Proteins 0.000 claims description 3
• 238000006467 substitution reaction Methods 0.000 claims description 3
• UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 claims description 2
• 108020003589 5' Untranslated Regions Proteins 0.000 claims description 2
• 102000012605 Cystic Fibrosis Transmembrane Conductance Regulator Human genes 0.000 claims description 2
• 108010079245 Cystic Fibrosis Transmembrane Conductance Regulator Proteins 0.000 claims description 2
• UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 claims description 2
• 102000052510 DNA-Binding Proteins Human genes 0.000 claims description 2
• 101710096438 DNA-binding protein Proteins 0.000 claims description 2
• 102000004190 Enzymes Human genes 0.000 claims description 2
• 108090000790 Enzymes Proteins 0.000 claims description 2
• 108091026898 Leader sequence (mRNA) Proteins 0.000 claims description 2
• 102000007981 Ornithine carbamoyltransferase Human genes 0.000 claims description 2
• 101710198224 Ornithine carbamoyltransferase, mitochondrial Proteins 0.000 claims description 2
• 108010069013 Phenylalanine Hydroxylase Proteins 0.000 claims description 2
• 102100038223 Phenylalanine-4-hydroxylase Human genes 0.000 claims description 2
• 108091036066 Three prime untranslated region Proteins 0.000 claims description 2
• 241000700605 Viruses Species 0.000 claims description 2
• 150000003838 adenosines Chemical class 0.000 claims description 2
• DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 claims description 2
• 230000027455 binding Effects 0.000 claims description 2
• 239000003795 chemical substances by application Substances 0.000 claims description 2
• 239000002872 contrast media Substances 0.000 claims description 2
• UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 claims description 2
• 239000000499 gel Substances 0.000 claims description 2
• 238000001727 in vivo Methods 0.000 claims description 2
• 238000007918 intramuscular administration Methods 0.000 claims description 2
• 238000007913 intrathecal administration Methods 0.000 claims description 2
• 239000003446 ligand Substances 0.000 claims description 2
• 150000002632 lipids Chemical class 0.000 claims description 2
• 239000002502 liposome Substances 0.000 claims description 2
• 239000002105 nanoparticle Substances 0.000 claims description 2
• 229920000642 polymer Polymers 0.000 claims description 2
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 2
• 230000002685 pulmonary effect Effects 0.000 claims description 2
• 150000003384 small molecules Chemical class 0.000 claims description 2
• 239000002047 solid lipid nanoparticle Substances 0.000 claims description 2
• 238000007920 subcutaneous administration Methods 0.000 claims description 2
• 230000008685 targeting Effects 0.000 claims description 2
• 230000001225 therapeutic effect Effects 0.000 claims description 2
• DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 claims description 2
• 229940045145 uridine Drugs 0.000 claims description 2
• 238000002347 injection Methods 0.000 claims 1
• 239000007924 injection Substances 0.000 claims 1
• 210000003462 vein Anatomy 0.000 claims 1
• 238000000034 method Methods 0.000 description 5
• 238000001990 intravenous administration Methods 0.000 description 1
• 230000008488 polyadenylation Effects 0.000 description 1