JPWO2021202511A5 - - Google Patents
Download PDFInfo
- Publication number
- JPWO2021202511A5 JPWO2021202511A5 JP2022559557A JP2022559557A JPWO2021202511A5 JP WO2021202511 A5 JPWO2021202511 A5 JP WO2021202511A5 JP 2022559557 A JP2022559557 A JP 2022559557A JP 2022559557 A JP2022559557 A JP 2022559557A JP WO2021202511 A5 JPWO2021202511 A5 JP WO2021202511A5
- Authority
- JP
- Japan
- Prior art keywords
- nucleotides
- dsrna agent
- antisense strand
- mapt
- optionally
- Prior art date
- 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
- 125000003729 nucleotide group Chemical group 0.000 claims 64
- 239000002773 nucleotide Substances 0.000 claims 55
- 239000003795 chemical substances by application Substances 0.000 claims 45
- 230000000692 anti-sense effect Effects 0.000 claims 43
- 108091081021 Sense strand Proteins 0.000 claims 28
- 201000011240 Frontotemporal dementia Diseases 0.000 claims 24
- 101000891579 Homo sapiens Microtubule-associated protein tau Proteins 0.000 claims 22
- 102100040243 Microtubule-associated protein tau Human genes 0.000 claims 22
- 230000004048 modification Effects 0.000 claims 18
- 238000012986 modification Methods 0.000 claims 18
- 125000004437 phosphorous atom Chemical group 0.000 claims 16
- 229910052698 phosphorus Inorganic materials 0.000 claims 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 15
- 239000008194 pharmaceutical composition Substances 0.000 claims 14
- 101150070547 MAPT gene Proteins 0.000 claims 13
- 210000004027 cell Anatomy 0.000 claims 13
- 208000011990 Corticobasal Degeneration Diseases 0.000 claims 12
- 208000035475 disorder Diseases 0.000 claims 12
- 230000014509 gene expression Effects 0.000 claims 12
- 230000002401 inhibitory effect Effects 0.000 claims 10
- 238000000034 method Methods 0.000 claims 9
- 108010026424 tau Proteins Proteins 0.000 claims 9
- 102000013498 tau Proteins Human genes 0.000 claims 9
- 229910019142 PO4 Inorganic materials 0.000 claims 8
- 208000034799 Tauopathies Diseases 0.000 claims 8
- 239000010452 phosphate Substances 0.000 claims 8
- -1 thymidine-glycol nucleic acid Chemical class 0.000 claims 8
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims 7
- 102100027831 14-3-3 protein theta Human genes 0.000 claims 6
- 208000024827 Alzheimer disease Diseases 0.000 claims 6
- 208000016270 Corticobasal syndrome Diseases 0.000 claims 6
- 201000010374 Down Syndrome Diseases 0.000 claims 6
- 208000002339 Frontotemporal Lobar Degeneration Diseases 0.000 claims 6
- 208000000609 Pick Disease of the Brain Diseases 0.000 claims 6
- 206010044688 Trisomy 21 Diseases 0.000 claims 6
- 230000005856 abnormality Effects 0.000 claims 6
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims 6
- 208000015122 neurodegenerative disease Diseases 0.000 claims 6
- 210000002682 neurofibrillary tangle Anatomy 0.000 claims 6
- 208000001282 primary progressive aphasia Diseases 0.000 claims 6
- 201000002212 progressive supranuclear palsy Diseases 0.000 claims 6
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 5
- 206010012289 Dementia Diseases 0.000 claims 4
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical group O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 claims 4
- 230000002776 aggregation Effects 0.000 claims 4
- 238000004220 aggregation Methods 0.000 claims 4
- 210000004556 brain Anatomy 0.000 claims 4
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 4
- 229920006395 saturated elastomer Polymers 0.000 claims 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical group OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims 3
- 208000023105 Huntington disease Diseases 0.000 claims 3
- 208000026072 Motor neurone disease Diseases 0.000 claims 3
- 208000014060 Niemann-Pick disease Diseases 0.000 claims 3
- 208000018737 Parkinson disease Diseases 0.000 claims 3
- 208000036757 Postencephalitic parkinsonism Diseases 0.000 claims 3
- 206010036631 Presenile dementia Diseases 0.000 claims 3
- 208000037140 Steinert myotonic dystrophy Diseases 0.000 claims 3
- 150000001412 amines Chemical class 0.000 claims 3
- 230000003542 behavioural effect Effects 0.000 claims 3
- 239000007853 buffer solution Substances 0.000 claims 3
- 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 3
- 210000000349 chromosome Anatomy 0.000 claims 3
- 238000003776 cleavage reaction Methods 0.000 claims 3
- 125000004122 cyclic group Chemical group 0.000 claims 3
- 201000010099 disease Diseases 0.000 claims 3
- 230000002518 glial effect Effects 0.000 claims 3
- 238000000338 in vitro Methods 0.000 claims 3
- 239000003446 ligand Substances 0.000 claims 3
- 125000001921 locked nucleotide group Chemical group 0.000 claims 3
- 208000005264 motor neuron disease Diseases 0.000 claims 3
- 230000035772 mutation Effects 0.000 claims 3
- 201000009340 myotonic dystrophy type 1 Diseases 0.000 claims 3
- 208000000170 postencephalitic Parkinson disease Diseases 0.000 claims 3
- 230000007017 scission Effects 0.000 claims 3
- 230000008685 targeting Effects 0.000 claims 3
- 208000035657 Abasia Diseases 0.000 claims 2
- 102000004506 Blood Proteins Human genes 0.000 claims 2
- 108010017384 Blood Proteins Proteins 0.000 claims 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims 2
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims 2
- 108091030071 RNAI Proteins 0.000 claims 2
- 208000018642 Semantic dementia Diseases 0.000 claims 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims 2
- 150000001408 amides Chemical class 0.000 claims 2
- 230000009286 beneficial effect Effects 0.000 claims 2
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 claims 2
- 125000004855 decalinyl group Chemical group C1(CCCC2CCCCC12)* 0.000 claims 2
- 230000000593 degrading effect Effects 0.000 claims 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 claims 2
- 230000009368 gene silencing by RNA Effects 0.000 claims 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 claims 2
- 125000002632 imidazolidinyl group Chemical group 0.000 claims 2
- 125000002636 imidazolinyl group Chemical group 0.000 claims 2
- 238000007913 intrathecal administration Methods 0.000 claims 2
- 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 claims 2
- 125000003965 isoxazolidinyl group Chemical group 0.000 claims 2
- 150000002632 lipids Chemical class 0.000 claims 2
- 108020004999 messenger RNA Proteins 0.000 claims 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 2
- 125000002757 morpholinyl group Chemical group 0.000 claims 2
- 108020004707 nucleic acids Proteins 0.000 claims 2
- 102000039446 nucleic acids Human genes 0.000 claims 2
- 125000000160 oxazolidinyl group Chemical group 0.000 claims 2
- 239000002953 phosphate buffered saline Substances 0.000 claims 2
- 125000004193 piperazinyl group Chemical group 0.000 claims 2
- 125000003386 piperidinyl group Chemical group 0.000 claims 2
- 238000000159 protein binding assay Methods 0.000 claims 2
- 125000003072 pyrazolidinyl group Chemical group 0.000 claims 2
- 125000002755 pyrazolinyl group Chemical group 0.000 claims 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims 2
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims 2
- 229920002477 rna polymer Polymers 0.000 claims 2
- 210000002966 serum Anatomy 0.000 claims 2
- 239000000243 solution Substances 0.000 claims 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims 2
- 125000001984 thiazolidinyl group Chemical group 0.000 claims 2
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims 2
- 210000004885 white matter Anatomy 0.000 claims 2
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical group CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 claims 1
- DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical group C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 claims 1
- DNIAPMSPPWPWGF-VKHMYHEASA-N (+)-propylene glycol Chemical group C[C@H](O)CO DNIAPMSPPWPWGF-VKHMYHEASA-N 0.000 claims 1
- REPVLJRCJUVQFA-UHFFFAOYSA-N (-)-isopinocampheol Chemical group C1C(O)C(C)C2C(C)(C)C1C2 REPVLJRCJUVQFA-UHFFFAOYSA-N 0.000 claims 1
- BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 claims 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims 1
- YPFDHNVEDLHUCE-UHFFFAOYSA-N 1,3-propanediol Chemical group OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 claims 1
- 229940035437 1,3-propanediol Drugs 0.000 claims 1
- MPCAJMNYNOGXPB-UHFFFAOYSA-N 1,5-Anhydro-mannit Natural products OCC1OCC(O)C(O)C1O MPCAJMNYNOGXPB-UHFFFAOYSA-N 0.000 claims 1
- MZMNEDXVUJLQAF-UHFFFAOYSA-N 1-o-tert-butyl 2-o-methyl 4-hydroxypyrrolidine-1,2-dicarboxylate Chemical compound COC(=O)C1CC(O)CN1C(=O)OC(C)(C)C MZMNEDXVUJLQAF-UHFFFAOYSA-N 0.000 claims 1
- TZMSYXZUNZXBOL-UHFFFAOYSA-N 10H-phenoxazine Chemical compound C1=CC=C2NC3=CC=CC=C3OC2=C1 TZMSYXZUNZXBOL-UHFFFAOYSA-N 0.000 claims 1
- NVKAWKQGWWIWPM-ABEVXSGRSA-N 17-β-hydroxy-5-α-Androstan-3-one Chemical compound C1C(=O)CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CC[C@H]21 NVKAWKQGWWIWPM-ABEVXSGRSA-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
- 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 1
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 claims 1
- KJJPLEZQSCZCKE-UHFFFAOYSA-N 2-aminopropane-1,3-diol Chemical compound OCC(N)CO KJJPLEZQSCZCKE-UHFFFAOYSA-N 0.000 claims 1
- HIAJCGFYHIANNA-QIZZZRFXSA-N 3b-Hydroxy-5-cholenoic acid Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@@H](CCC(O)=O)C)[C@@]1(C)CC2 HIAJCGFYHIANNA-QIZZZRFXSA-N 0.000 claims 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims 1
- 239000004380 Cholic acid Substances 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
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 claims 1
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Chemical group CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 claims 1
- 108020004414 DNA Proteins 0.000 claims 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 claims 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims 1
- 102000008100 Human Serum Albumin Human genes 0.000 claims 1
- 108091006905 Human Serum Albumin Proteins 0.000 claims 1
- SMEROWZSTRWXGI-UHFFFAOYSA-N Lithocholsaeure Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 SMEROWZSTRWXGI-UHFFFAOYSA-N 0.000 claims 1
- 208000025380 Logopenic progressive aphasia Diseases 0.000 claims 1
- OVRNDRQMDRJTHS-KEWYIRBNSA-N N-acetyl-D-galactosamine Chemical compound 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
- 235000021314 Palmitic acid Nutrition 0.000 claims 1
- 208000027089 Parkinsonian disease Diseases 0.000 claims 1
- 206010034010 Parkinsonism Diseases 0.000 claims 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims 1
- XVIYCJDWYLJQBG-UHFFFAOYSA-N acetic acid;adamantane Chemical compound CC(O)=O.C1C(C2)CC3CC1CC2C3 XVIYCJDWYLJQBG-UHFFFAOYSA-N 0.000 claims 1
- 125000002015 acyclic group Chemical group 0.000 claims 1
- 125000002723 alicyclic group Chemical group 0.000 claims 1
- 125000001931 aliphatic group Chemical group 0.000 claims 1
- 150000001345 alkine derivatives Chemical class 0.000 claims 1
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 claims 1
- 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 1
- 229960003473 androstanolone Drugs 0.000 claims 1
- 150000001540 azides Chemical class 0.000 claims 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims 1
- CKDOCTFBFTVPSN-UHFFFAOYSA-N borneol Chemical group C1CC2(C)C(C)CC1C2(C)C CKDOCTFBFTVPSN-UHFFFAOYSA-N 0.000 claims 1
- 229940116229 borneol Drugs 0.000 claims 1
- 239000004202 carbamide Substances 0.000 claims 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 claims 1
- 235000012000 cholesterol Nutrition 0.000 claims 1
- 229940107161 cholesterol Drugs 0.000 claims 1
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 claims 1
- 229960002471 cholic acid Drugs 0.000 claims 1
- 235000019416 cholic acid Nutrition 0.000 claims 1
- 238000012650 click reaction Methods 0.000 claims 1
- 230000000295 complement effect Effects 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 claims 1
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 claims 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical group OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 claims 1
- 150000002019 disulfides Chemical class 0.000 claims 1
- DTGKSKDOIYIVQL-UHFFFAOYSA-N dl-isoborneol Chemical group C1CC2(C)C(O)CC1C2(C)C DTGKSKDOIYIVQL-UHFFFAOYSA-N 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 238000002337 electrophoretic mobility shift assay Methods 0.000 claims 1
- ZTWTYVWXUKTLCP-UHFFFAOYSA-L ethenyl-dioxido-oxo-$l^{5}-phosphane Chemical compound [O-]P([O-])(=O)C=C ZTWTYVWXUKTLCP-UHFFFAOYSA-L 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
- 238000009472 formulation Methods 0.000 claims 1
- 125000000524 functional group Chemical group 0.000 claims 1
- 229930182830 galactose Natural products 0.000 claims 1
- 229960002442 glucosamine Drugs 0.000 claims 1
- 239000008103 glucose Substances 0.000 claims 1
- 210000003494 hepatocyte Anatomy 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- SMEROWZSTRWXGI-HVATVPOCSA-N lithocholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 SMEROWZSTRWXGI-HVATVPOCSA-N 0.000 claims 1
- 125000002960 margaryl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 229940041616 menthol Drugs 0.000 claims 1
- 230000003278 mimic effect Effects 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 150000002772 monosaccharides Chemical class 0.000 claims 1
- ONKSSDKXDIVIHK-UHFFFAOYSA-N n,n-didecyldodecanamide Chemical group CCCCCCCCCCCC(=O)N(CCCCCCCCCC)CCCCCCCCCC ONKSSDKXDIVIHK-UHFFFAOYSA-N 0.000 claims 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 claims 1
- 230000001537 neural effect Effects 0.000 claims 1
- 210000002569 neuron Anatomy 0.000 claims 1
- QTNLALDFXILRQO-UHFFFAOYSA-N nonadecane-1,2,3-triol Chemical group CCCCCCCCCCCCCCCCC(O)C(O)CO QTNLALDFXILRQO-UHFFFAOYSA-N 0.000 claims 1
- 229920001542 oligosaccharide Polymers 0.000 claims 1
- 150000002482 oligosaccharides Chemical class 0.000 claims 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 claims 1
- 150000004713 phosphodiesters Chemical class 0.000 claims 1
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 claims 1
- 150000008298 phosphoramidates Chemical class 0.000 claims 1
- 229920000166 polytrimethylene carbonate Chemical group 0.000 claims 1
- 229930002330 retinoic acid Natural products 0.000 claims 1
- 239000011780 sodium chloride Substances 0.000 claims 1
- 229940124530 sulfonamide Drugs 0.000 claims 1
- 150000003456 sulfonamides Chemical class 0.000 claims 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims 1
- 208000024891 symptom Diseases 0.000 claims 1
- TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 claims 1
- 229940124597 therapeutic agent Drugs 0.000 claims 1
- 150000003568 thioethers Chemical class 0.000 claims 1
- 150000003573 thiols Chemical class 0.000 claims 1
- 229960001727 tretinoin Drugs 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 1
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US202063002030P | 2020-03-30 | 2020-03-30 | |
| US63/002,030 | 2020-03-30 | ||
| US202163164467P | 2021-03-22 | 2021-03-22 | |
| US63/164,467 | 2021-03-22 | ||
| PCT/US2021/024858 WO2021202511A2 (en) | 2020-03-30 | 2021-03-30 | MICROTUBULE ASSOCIATED PROTEIN TAU (MAPT) iRNA AGENT COMPOSITIONS AND METHODS OF USE THEREOF |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2023521604A JP2023521604A (ja) | 2023-05-25 |
| JP2023521604A5 JP2023521604A5 (https=) | 2024-04-10 |
| JPWO2021202511A5 true JPWO2021202511A5 (https=) | 2024-04-10 |
Family
ID=77929772
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2022559557A Pending JP2023521604A (ja) | 2020-03-30 | 2021-03-30 | 微小管関連タンパク質タウ（ＭＡＰＴ）ｉＲＮＡ剤組成物およびその使用方法 |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US20230203486A1 (https=) |
| EP (1) | EP4126230A4 (https=) |
| JP (1) | JP2023521604A (https=) |
| KR (1) | KR20230005194A (https=) |
| CN (1) | CN116234585A (https=) |
| AU (1) | AU2021246024A1 (https=) |
| BR (1) | BR112022019606A2 (https=) |
| CA (1) | CA3178304A1 (https=) |
| IL (1) | IL296851A (https=) |
| MX (1) | MX2022012293A (https=) |
| TW (1) | TW202143984A (https=) |
| WO (1) | WO2021202511A2 (https=) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20240067943A (ko) * | 2021-09-24 | 2024-05-17 | 알닐람 파마슈티칼스 인코포레이티드 | 미소관 연관 단백질 타우(MAPT) iRNA 제제 조성물 및 이의 사용 방법 |
| US20250340872A1 (en) * | 2021-10-07 | 2025-11-06 | Ionis Pharmaceuticals, Inc. | Compounds and methods for reducing tau expression |
| EP4448765A1 (en) * | 2021-12-13 | 2024-10-23 | Eli Lilly and Company | Mapt rna interference agents |
| JP2025507372A (ja) * | 2022-02-11 | 2025-03-18 | アルナイラム ファーマシューティカルズ， インコーポレイテッド | 微小管関連タンパク質タウ（ＭＡＰＴ）ｉＲＮＡ剤組成物およびその使用方法 |
| EP4493691A2 (en) * | 2022-03-16 | 2025-01-22 | JANSSEN Pharmaceutica NV | Mapt sirna and uses thereof |
| KR20250129743A (ko) * | 2022-12-29 | 2025-08-29 | 보이저 테라퓨틱스, 인크. | Mapt를 조절하기 위한 조성물 및 방법 |
| WO2024201423A2 (en) * | 2023-03-30 | 2024-10-03 | Biorchestra Co., Ltd. | Microtubule-associated protein tau targeting sirnas and uses thereof |
| WO2024220930A2 (en) * | 2023-04-20 | 2024-10-24 | Adarx Pharmaceuticals, Inc. | Mapt-modulating compositions and methods of use thereof |
| AU2024315297A1 (en) * | 2023-08-01 | 2026-02-12 | Tuojie Biotech (Shanghai) Co., Ltd. | Dsrna targeting mapt and pharmaceutical use thereof |
| WO2025027577A1 (en) * | 2023-08-02 | 2025-02-06 | Consejo Nacional De Investigaciones Científicas Y Técnicas (Conicet) | Micrornas designed against the microtubule-associated protein tau for the treatment of tauopathies |
| TW202515584A (zh) * | 2023-10-11 | 2025-04-16 | 大陸商上海舶望製藥有限公司 | 用於抑制微管相關蛋白ｔａｕ（ｍａｐｔ）表達的組合物和方法 |
| US12551569B2 (en) | 2024-03-31 | 2026-02-17 | Arrowhead Pharmaceuticals, Inc. | RNAi agents for inhibiting expression of microtubule associated protein tau (MAPT), compositions thereof, and methods of use |
| WO2025233849A2 (en) * | 2024-05-07 | 2025-11-13 | Janssen Pharmaceutica Nv | MAPT siRNA AND USES THEREOF |
| WO2026010722A1 (en) * | 2024-07-03 | 2026-01-08 | Voyager Therapeutics, Inc. | Compositions and methods for regulating mapt |
| WO2026017176A1 (zh) * | 2024-07-19 | 2026-01-22 | 北京安龙生物医药有限公司 | 靶向微管相关蛋白Tau基因的寡核苷酸及其用途 |
| CN121780524A (zh) * | 2024-08-02 | 2026-04-03 | 北京尧景基因技术有限公司 | 抑制MAPT基因表达的siRNA及其缀合物和应用 |
| WO2026067655A1 (zh) * | 2024-09-26 | 2026-04-02 | 大睿生物医药科技(上海)有限公司 | 调控TAU表达的dsRNA分子 |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8101741B2 (en) * | 2005-11-02 | 2012-01-24 | Protiva Biotherapeutics, Inc. | Modified siRNA molecules and uses thereof |
| GB0605337D0 (en) * | 2006-03-17 | 2006-04-26 | Genomica Sau | Treatment of CNS conditions |
| AU2013203395A1 (en) * | 2012-03-30 | 2013-10-17 | Isis Pharmaceuticals, Inc. | Compositions and methods for modulating TAU expression for reducing seizure and modifying a neurodegenerative syndrome |
| US9133461B2 (en) * | 2012-04-10 | 2015-09-15 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of the ALAS1 gene |
| ES2807379T3 (es) * | 2013-03-14 | 2021-02-22 | Ionis Pharmaceuticals Inc | Composiciones y métodos para regular la expresión de Tau |
| JP2016523980A (ja) * | 2013-07-11 | 2016-08-12 | ザ トラスティーズ オブ コロンビア ユニバーシティ イン ザ シティ オブ ニューヨーク | タウ発現を抑制するマイクロｒｎａ |
| TWI772856B (zh) * | 2013-07-19 | 2022-08-01 | 美商百健Ｍａ公司 | 用於調節τ蛋白表現之組合物 |
| EP3043826A4 (en) * | 2013-09-13 | 2017-05-24 | Moderna Therapeutics, Inc. | Polynucleotide compositions containing amino acids |
| IL316808A (en) * | 2014-08-20 | 2025-01-01 | Alnylam Pharmaceuticals Inc | Modified double-stranded RNA materials and their uses |
| AU2016215155A1 (en) * | 2015-02-04 | 2017-08-17 | F. Hoffmann-La Roche Ag | Tau antisense oligomers and uses thereof |
| EP3274456B1 (en) * | 2015-03-25 | 2020-06-24 | Università Degli Studi Di Trento | Rna interference mediated therapy for neurodegenerative diseases |
| CN108135921B (zh) * | 2015-07-22 | 2023-10-17 | 波涛生命科学有限公司 | 寡核苷酸组合物及其方法 |
| PH12018501207B1 (en) * | 2015-12-21 | 2024-02-23 | Novartis Ag | Compositions and methods for decreasing tau expression |
| CA3086485A1 (en) * | 2017-12-21 | 2019-06-27 | Alnylam Pharmaceuticals, Inc. | Chirally-enriched double-stranded rna agents |
| SG11202012759XA (en) * | 2018-07-03 | 2021-01-28 | Hoffmann La Roche | Oligonucleotides for modulating tau expression |
| WO2021156833A1 (en) * | 2020-02-07 | 2021-08-12 | Biorchestra Co., Ltd. | Use of mirna-485 inhibitors for treating tauopathy |
| AU2021238319A1 (en) * | 2020-03-18 | 2022-10-06 | University Of Massachusetts | Oligonucleotides for MAPT modulation |
-
2021
- 2021-03-30 AU AU2021246024A patent/AU2021246024A1/en active Pending
- 2021-03-30 TW TW110111671A patent/TW202143984A/zh unknown
- 2021-03-30 WO PCT/US2021/024858 patent/WO2021202511A2/en not_active Ceased
- 2021-03-30 IL IL296851A patent/IL296851A/en unknown
- 2021-03-30 EP EP21779121.9A patent/EP4126230A4/en active Pending
- 2021-03-30 KR KR1020227037984A patent/KR20230005194A/ko active Pending
- 2021-03-30 JP JP2022559557A patent/JP2023521604A/ja active Pending
- 2021-03-30 MX MX2022012293A patent/MX2022012293A/es unknown
- 2021-03-30 US US17/995,035 patent/US20230203486A1/en active Pending
- 2021-03-30 CA CA3178304A patent/CA3178304A1/en active Pending
- 2021-03-30 BR BR112022019606A patent/BR112022019606A2/pt unknown
- 2021-03-30 CN CN202180039190.6A patent/CN116234585A/zh active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7805386B2 (ja) | Ｌｐａ発現を阻害するための組成物及び方法 | |
| JPWO2021202511A5 (https=) | ||
| US20230118177A1 (en) | Compositions and methods for modulating growth hormone receptor expression | |
| JP2020058368A (ja) | 補体ｂ因子発現を調節するための組成物及び方法 | |
| JP2020096629A (ja) | Ｐｋｋ発現を調節するための組成物及び方法 | |
| CN115397436B (zh) | 用于抑制PNPLA3表达的RNAi剂、其药物组合物和使用方法 | |
| TR201816256T4 (tr) | Bir süjede smn2 uç birleştirmesinin modülasyonu için bileşimler ve yöntemler. | |
| TW202540423A (zh) | 用於抑制17β-HSD第13型(HSD17B13)表現之RNAi藥劑、其組合物及使用方法 | |
| AU2006243218B2 (en) | Use of low doses of oligonucleotides antisense to TGF-beta, VEGF, interleukin-10, c-jun, c-fos or prostaglandin E2 genes in the treatment of tumors | |
| US10933081B2 (en) | Myostatin iRNA compositions and methods of use thereof | |
| US20240240187A1 (en) | Sirna targeting tmprss6 for the treatment of myeloproliferative disorders | |
| IL294728A (en) | lrrk2 RNA material preparations and methods of using them | |
| JPWO2023049871A5 (https=) | ||
| CN110832078A (zh) | 抑制apcs表达的核酸 | |
| US11634715B2 (en) | Methods and compositions for treating bile duct paucity-associated conditions | |
| WO2025098117A1 (zh) | 一种抑制甲状腺素转运蛋白(TTR)表达的RNAi试剂、组合物及应用 | |
| WO2025040002A1 (zh) | 靶向inhbe基因的双链寡核苷酸、缀合物、组合物及其用途 | |
| JPWO2021222065A5 (https=) | ||
| JPWO2023154900A5 (https=) | ||
| RU2024111073A (ru) | КОМПОЗИЦИИ АГЕНТА иРНК ПРОТИВ АССОЦИИРОВАННОГО С МИКРОТРУБОЧКАМИ ТАУ-БЕЛКА (MAPT) И СПОСОБЫ ИХ ПРИМЕНЕНИЯ | |
| WO2022184852A1 (en) | Conjugated nucleic acids comprising a phosphorodithioate for inhibiting gene expression in a cell | |
| JPWO2021150969A5 (https=) | ||
| JPWO2023278607A5 (https=) | ||
| WO2026056905A1 (en) | Method for the treatment of amyotrophic lateral sclerosis by oligonucleotide agent | |
| JPWO2022271972A5 (https=) |