JP2012513953A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2012513953A5 JP2012513953A5 JP2011529188A JP2011529188A JP2012513953A5 JP 2012513953 A5 JP2012513953 A5 JP 2012513953A5 JP 2011529188 A JP2011529188 A JP 2011529188A JP 2011529188 A JP2011529188 A JP 2011529188A JP 2012513953 A5 JP2012513953 A5 JP 2012513953A5
- Authority
- JP
- Japan
- Prior art keywords
- linker
- substituted
- unsubstituted
- oligonucleotide
- oligonucleotides
- 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
- 108091034117 Oligonucleotide Proteins 0.000 claims description 62
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 claims description 35
- 150000001875 compounds Chemical class 0.000 claims description 18
- 239000003446 ligand Substances 0.000 claims description 16
- 239000000816 peptidomimetic Substances 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 6
- 108020004459 Small interfering RNA Proteins 0.000 claims description 5
- 230000000694 effects Effects 0.000 claims description 2
- 108090000623 proteins and genes Proteins 0.000 claims description 2
- 102000004169 proteins and genes Human genes 0.000 claims description 2
- 239000002777 nucleoside Substances 0.000 claims 50
- 125000000217 alkyl group Chemical group 0.000 claims 20
- 229910052760 oxygen Inorganic materials 0.000 claims 15
- 125000003118 aryl group Chemical group 0.000 claims 11
- 125000001072 heteroaryl group Chemical group 0.000 claims 11
- 229910019142 PO4 Inorganic materials 0.000 claims 10
- 239000002202 Polyethylene glycol Substances 0.000 claims 10
- 239000010452 phosphate Substances 0.000 claims 10
- 229920001223 polyethylene glycol Polymers 0.000 claims 10
- 229910052717 sulfur Inorganic materials 0.000 claims 10
- 125000003342 alkenyl group Chemical group 0.000 claims 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims 9
- 229910052799 carbon Inorganic materials 0.000 claims 8
- 229910052739 hydrogen Inorganic materials 0.000 claims 8
- 239000001257 hydrogen Substances 0.000 claims 8
- 239000000651 prodrug Substances 0.000 claims 8
- 229940002612 prodrug Drugs 0.000 claims 8
- 150000003839 salts Chemical class 0.000 claims 8
- 125000003710 aryl alkyl group Chemical group 0.000 claims 7
- 150000002431 hydrogen Chemical group 0.000 claims 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 6
- 229910052757 nitrogen Inorganic materials 0.000 claims 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims 6
- -1 phospho Chemical class 0.000 claims 6
- 125000000304 alkynyl group Chemical group 0.000 claims 5
- NAGJZTKCGNOGPW-UHFFFAOYSA-K dioxido-sulfanylidene-sulfido-$l^{5}-phosphane Chemical compound [O-]P([O-])([S-])=S NAGJZTKCGNOGPW-UHFFFAOYSA-K 0.000 claims 5
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 claims 5
- FUWGSUOSJRCEIV-UHFFFAOYSA-N phosphonothioic O,O-acid Chemical compound OP(O)=S FUWGSUOSJRCEIV-UHFFFAOYSA-N 0.000 claims 5
- 150000008300 phosphoramidites Chemical class 0.000 claims 5
- 239000007787 solid Substances 0.000 claims 5
- 239000001226 triphosphate Substances 0.000 claims 5
- 235000011178 triphosphate Nutrition 0.000 claims 5
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 claims 5
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 claims 4
- OZQGKWOGOZMTOM-UHFFFAOYSA-N [hydroxy(sulfanyl)phosphinothioyl] dihydrogen phosphate Chemical compound OP(O)(=O)OP(O)(S)=S OZQGKWOGOZMTOM-UHFFFAOYSA-N 0.000 claims 4
- 239000001177 diphosphate Substances 0.000 claims 4
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 claims 4
- 235000011180 diphosphates Nutrition 0.000 claims 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 4
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims 4
- 235000021317 phosphate Nutrition 0.000 claims 4
- 125000006239 protecting group Chemical group 0.000 claims 4
- 150000003536 tetrazoles Chemical class 0.000 claims 4
- 150000003852 triazoles Chemical class 0.000 claims 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical group OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims 3
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 claims 3
- 150000005690 diesters Chemical class 0.000 claims 3
- 201000010099 disease Diseases 0.000 claims 3
- 208000035475 disorder Diseases 0.000 claims 3
- 230000009368 gene silencing by RNA Effects 0.000 claims 3
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical group OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 claims 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 3
- 150000005691 triesters Chemical class 0.000 claims 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 claims 2
- IYMAXBFPHPZYIK-BQBZGAKWSA-N Arg-Gly-Asp Chemical compound NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O IYMAXBFPHPZYIK-BQBZGAKWSA-N 0.000 claims 2
- 208000023275 Autoimmune disease Diseases 0.000 claims 2
- 208000035143 Bacterial infection Diseases 0.000 claims 2
- 206010020751 Hypersensitivity Diseases 0.000 claims 2
- 206010061598 Immunodeficiency Diseases 0.000 claims 2
- 208000029462 Immunodeficiency disease Diseases 0.000 claims 2
- 206010062016 Immunosuppression Diseases 0.000 claims 2
- 206010028980 Neoplasm Diseases 0.000 claims 2
- 208000030852 Parasitic disease Diseases 0.000 claims 2
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical group OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims 2
- 208000036142 Viral infection Diseases 0.000 claims 2
- 125000002015 acyclic group Chemical group 0.000 claims 2
- 125000001931 aliphatic group Chemical group 0.000 claims 2
- 230000007815 allergy Effects 0.000 claims 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 2
- 208000022362 bacterial infectious disease Diseases 0.000 claims 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound 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 2
- 125000004122 cyclic group Chemical group 0.000 claims 2
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 claims 2
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 claims 2
- 229930182830 galactose Natural products 0.000 claims 2
- 229910052736 halogen Inorganic materials 0.000 claims 2
- 150000002367 halogens Chemical class 0.000 claims 2
- 230000007813 immunodeficiency Effects 0.000 claims 2
- 230000001506 immunosuppresive effect Effects 0.000 claims 2
- 108020004999 messenger RNA Proteins 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 claims 2
- 125000002098 pyridazinyl group Chemical group 0.000 claims 2
- 230000009385 viral infection Effects 0.000 claims 2
- 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 1
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims 1
- KJJPLEZQSCZCKE-UHFFFAOYSA-N 2-aminopropane-1,3-diol Chemical class OCC(N)CO KJJPLEZQSCZCKE-UHFFFAOYSA-N 0.000 claims 1
- 108091023037 Aptamer Proteins 0.000 claims 1
- 108020004513 Bacterial RNA Proteins 0.000 claims 1
- 229940122361 Bisphosphonate Drugs 0.000 claims 1
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 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
- PNNNRSAQSRJVSB-SLPGGIOYSA-N Fucose Natural products C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C=O PNNNRSAQSRJVSB-SLPGGIOYSA-N 0.000 claims 1
- 102000003886 Glycoproteins Human genes 0.000 claims 1
- 108090000288 Glycoproteins Proteins 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- SHZGCJCMOBCMKK-DHVFOXMCSA-N L-fucopyranose Chemical compound C[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-DHVFOXMCSA-N 0.000 claims 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims 1
- 108090001090 Lectins Proteins 0.000 claims 1
- 102000004856 Lectins Human genes 0.000 claims 1
- 239000000637 Melanocyte-Stimulating Hormone Substances 0.000 claims 1
- 108010007013 Melanocyte-Stimulating Hormones Proteins 0.000 claims 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims 1
- 108700011259 MicroRNAs Proteins 0.000 claims 1
- 102000015728 Mucins Human genes 0.000 claims 1
- 108010063954 Mucins Proteins 0.000 claims 1
- 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 1
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 claims 1
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-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
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 claims 1
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 claims 1
- 108010020346 Polyglutamic Acid Proteins 0.000 claims 1
- 102000007615 Pulmonary Surfactant-Associated Protein A Human genes 0.000 claims 1
- 108010007100 Pulmonary Surfactant-Associated Protein A Proteins 0.000 claims 1
- 108010061174 Thyrotropin Proteins 0.000 claims 1
- 102000011923 Thyrotropin Human genes 0.000 claims 1
- 102000004338 Transferrin Human genes 0.000 claims 1
- 108090000901 Transferrin Proteins 0.000 claims 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 claims 1
- 241000700605 Viruses Species 0.000 claims 1
- 229930003779 Vitamin B12 Natural products 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 230000003213 activating effect Effects 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
- 108010072041 arginyl-glycyl-aspartic acid Proteins 0.000 claims 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- 239000003613 bile acid Substances 0.000 claims 1
- 235000020958 biotin Nutrition 0.000 claims 1
- 239000011616 biotin Substances 0.000 claims 1
- 229960002685 biotin Drugs 0.000 claims 1
- 150000004663 bisphosphonates Chemical class 0.000 claims 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 230000015556 catabolic process Effects 0.000 claims 1
- 235000012000 cholesterol Nutrition 0.000 claims 1
- AGVAZMGAQJOSFJ-WZHZPDAFSA-M cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].N#[C-].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP(O)(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O AGVAZMGAQJOSFJ-WZHZPDAFSA-M 0.000 claims 1
- 238000006731 degradation reaction Methods 0.000 claims 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 229960000304 folic acid Drugs 0.000 claims 1
- 235000019152 folic acid Nutrition 0.000 claims 1
- 239000011724 folic acid Substances 0.000 claims 1
- 229920000370 gamma-poly(glutamate) polymer Polymers 0.000 claims 1
- FLQUDUCNBDGCRI-UHFFFAOYSA-N hydroxy-sulfanyl-sulfidophosphanium Chemical compound SP(S)=O FLQUDUCNBDGCRI-UHFFFAOYSA-N 0.000 claims 1
- 125000002632 imidazolidinyl group Chemical group 0.000 claims 1
- 125000002636 imidazolinyl group Chemical group 0.000 claims 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 claims 1
- 125000003965 isoxazolidinyl group Chemical group 0.000 claims 1
- 239000008101 lactose Substances 0.000 claims 1
- 239000002523 lectin Substances 0.000 claims 1
- 150000002632 lipids Chemical class 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 239000002679 microRNA Substances 0.000 claims 1
- 125000002757 morpholinyl group Chemical group 0.000 claims 1
- 201000006417 multiple sclerosis Diseases 0.000 claims 1
- 229950006780 n-acetylglucosamine Drugs 0.000 claims 1
- 239000002773 nucleotide Substances 0.000 claims 1
- 125000003729 nucleotide group Chemical group 0.000 claims 1
- 125000000160 oxazolidinyl group Chemical group 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 125000004193 piperazinyl group Chemical group 0.000 claims 1
- 125000003386 piperidinyl group Chemical group 0.000 claims 1
- 108010064470 polyaspartate Proteins 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 claims 1
- 125000002755 pyrazolinyl group Chemical group 0.000 claims 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims 1
- 150000003431 steroids Chemical class 0.000 claims 1
- 125000001984 thiazolidinyl group Chemical group 0.000 claims 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims 1
- 239000012581 transferrin Substances 0.000 claims 1
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 claims 1
- 239000011715 vitamin B12 Substances 0.000 claims 1
- 235000019163 vitamin B12 Nutrition 0.000 claims 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 33
- 230000002101 lytic effect Effects 0.000 description 9
- 102000004196 processed proteins & peptides Human genes 0.000 description 8
- 150000001413 amino acids Chemical class 0.000 description 7
- 235000001014 amino acid Nutrition 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 4
- 230000002209 hydrophobic effect Effects 0.000 description 4
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 3
- 0 O=C(C*1)*C1=O Chemical compound O=C(C*1)*C1=O 0.000 description 2
- 102000043276 Oncogene Human genes 0.000 description 2
- 108700020796 Oncogene Proteins 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000009089 cytolysis Effects 0.000 description 2
- 210000000805 cytoplasm Anatomy 0.000 description 2
- 210000001163 endosome Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- 108010062307 AAVALLPAVLLALLAP Proteins 0.000 description 1
- 108010051109 Cell-Penetrating Peptides Proteins 0.000 description 1
- 102000020313 Cell-Penetrating Peptides Human genes 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 108700006830 Drosophila Antp Proteins 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 108010087294 GALA peptide Proteins 0.000 description 1
- 108010070875 Human Immunodeficiency Virus tat Gene Products Proteins 0.000 description 1
- 239000012097 Lipofectamine 2000 Substances 0.000 description 1
- 239000012124 Opti-MEM Substances 0.000 description 1
- BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
- 108010069381 Platelet Endothelial Cell Adhesion Molecule-1 Proteins 0.000 description 1
- 102100024616 Platelet endothelial cell adhesion molecule Human genes 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000001345 alkine derivatives Chemical group 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 108010062796 arginyllysine Proteins 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- IVRMZWNICZWHMI-UHFFFAOYSA-N azide group Chemical group [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000005859 cell recognition Effects 0.000 description 1
- BHONFOAYRQZPKZ-LCLOTLQISA-N chembl269478 Chemical compound C([C@H](NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CCCNC(N)=N)[C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(O)=O)C1=CC=CC=C1 BHONFOAYRQZPKZ-LCLOTLQISA-N 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 239000000412 dendrimer Substances 0.000 description 1
- 229920000736 dendritic polymer Polymers 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 238000003670 luciferase enzyme activity assay Methods 0.000 description 1
- 230000034217 membrane fusion Effects 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 230000005588 protonation Effects 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US9949708P | 2008-09-23 | 2008-09-23 | |
| US61/099,497 | 2008-09-23 | ||
| PCT/US2009/058084 WO2010039548A2 (en) | 2008-09-23 | 2009-09-23 | Chemical modifications of monomers and oligonucleotides with cycloaddition |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014185220A Division JP6053735B2 (ja) | 2008-09-23 | 2014-09-11 | 付加環化を用いたモノマーおよびオリゴヌクレオチドの化学修飾 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2012513953A JP2012513953A (ja) | 2012-06-21 |
| JP2012513953A5 true JP2012513953A5 (enExample) | 2012-11-08 |
Family
ID=42038746
Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2011529188A Pending JP2012513953A (ja) | 2008-09-23 | 2009-09-23 | 付加環化を用いたモノマーおよびオリゴヌクレオチドの化学修飾 |
| JP2014185220A Active JP6053735B2 (ja) | 2008-09-23 | 2014-09-11 | 付加環化を用いたモノマーおよびオリゴヌクレオチドの化学修飾 |
| JP2016231739A Active JP6484602B2 (ja) | 2008-09-23 | 2016-11-29 | 付加環化を用いたモノマーおよびオリゴヌクレオチドの化学修飾 |
| JP2019026194A Active JP6885976B2 (ja) | 2008-09-23 | 2019-02-18 | 付加環化を用いたモノマーおよびオリゴヌクレオチドの化学修飾 |
Family Applications After (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014185220A Active JP6053735B2 (ja) | 2008-09-23 | 2014-09-11 | 付加環化を用いたモノマーおよびオリゴヌクレオチドの化学修飾 |
| JP2016231739A Active JP6484602B2 (ja) | 2008-09-23 | 2016-11-29 | 付加環化を用いたモノマーおよびオリゴヌクレオチドの化学修飾 |
| JP2019026194A Active JP6885976B2 (ja) | 2008-09-23 | 2019-02-18 | 付加環化を用いたモノマーおよびオリゴヌクレオチドの化学修飾 |
Country Status (6)
| Country | Link |
|---|---|
| US (3) | US8962580B2 (enExample) |
| EP (2) | EP3587434A1 (enExample) |
| JP (4) | JP2012513953A (enExample) |
| AU (2) | AU2009298802A1 (enExample) |
| CA (1) | CA2737661C (enExample) |
| WO (1) | WO2010039548A2 (enExample) |
Families Citing this family (142)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012513953A (ja) * | 2008-09-23 | 2012-06-21 | アルニラム ファーマスーティカルズ インコーポレイテッド | 付加環化を用いたモノマーおよびオリゴヌクレオチドの化学修飾 |
| CN102459298A (zh) * | 2009-05-05 | 2012-05-16 | 阿尔特姆恩科技责任有限公司 | 化学可编程免疫 |
| FR2952372B1 (fr) * | 2009-11-10 | 2012-03-23 | Centre Nat Rech Scient | Nouveaux derives de mannopyranoside ayant une activite anticancereuse |
| WO2011079188A2 (en) * | 2009-12-23 | 2011-06-30 | Life Technologies Corporation | Protein modification from the oxidation of clickable polyunsaturated fatty acid analogs |
| EP2525781A1 (en) | 2010-01-22 | 2012-11-28 | Schering Corporation | Novel cationic lipids for oligonucleotide delivery |
| US9198972B2 (en) | 2010-01-28 | 2015-12-01 | Alnylam Pharmaceuticals, Inc. | Monomers and oligonucleotides comprising cycloaddition adduct(s) |
| EP3406730B1 (en) | 2010-08-31 | 2022-02-23 | Sirna Therapeutics, Inc. | Novel single chemical entities and methods for delivery of oligonucleotides |
| EP2630196B1 (en) | 2010-10-20 | 2017-09-06 | Li-Cor, Inc. | Cyanine dyes and their conjugates |
| WO2013033230A1 (en) | 2011-08-29 | 2013-03-07 | Isis Pharmaceuticals, Inc. | Oligomer-conjugate complexes and their use |
| AR088441A1 (es) | 2011-09-12 | 2014-06-11 | Idenix Pharmaceuticals Inc | Compuestos de carboniloximetilfosforamidato sustituido y composiciones farmaceuticas para el tratamiento de infecciones virales |
| IN2014CN03043A (enExample) | 2011-09-30 | 2015-07-03 | Univ Tufts | |
| PE20142362A1 (es) * | 2011-11-18 | 2015-01-30 | Alnylam Pharmaceuticals Inc | Agentes de iarn, composiciones y metodos de uso de los mismos para tratar enfermedades asociadas con transtiretina (ttr) |
| EP2794627B1 (en) | 2011-12-22 | 2018-09-26 | Alios Biopharma, Inc. | Substituted nucleosides, nucleotides and analogs thereof |
| AU2013221448B2 (en) * | 2012-02-16 | 2017-02-23 | The University Of Toledo | Xenoantigen-displaying anti-cancer vaccines and method of making |
| USRE48171E1 (en) | 2012-03-21 | 2020-08-25 | Janssen Biopharma, Inc. | Substituted nucleosides, nucleotides and analogs thereof |
| US9441007B2 (en) | 2012-03-21 | 2016-09-13 | Alios Biopharma, Inc. | Substituted nucleosides, nucleotides and analogs thereof |
| US9254311B2 (en) | 2012-04-02 | 2016-02-09 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of proteins |
| AU2013243954A1 (en) | 2012-04-02 | 2014-10-30 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of cosmetic proteins and peptides |
| US9283287B2 (en) | 2012-04-02 | 2016-03-15 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of nuclear proteins |
| US10501513B2 (en) | 2012-04-02 | 2019-12-10 | Modernatx, Inc. | Modified polynucleotides for the production of oncology-related proteins and peptides |
| CN102675626B (zh) * | 2012-04-28 | 2014-05-28 | 南京威尔化工有限公司 | 含三氮唑的聚乙二醇蛋白质修饰剂及其制备方法和应用 |
| TW201808342A (zh) * | 2012-05-02 | 2018-03-16 | 喜納製藥公司 | 包含四ｇａｌｎａｃ之新穎結合物及傳送寡核苷酸之方法 |
| AR090905A1 (es) * | 2012-05-02 | 2014-12-17 | Merck Sharp & Dohme | Conjugados que contienen tetragalnac y peptidos y procedimientos para la administracion de oligonucleotidos, composicion farmaceutica |
| US9296778B2 (en) | 2012-05-22 | 2016-03-29 | Idenix Pharmaceuticals, Inc. | 3′,5′-cyclic phosphate prodrugs for HCV infection |
| WO2013177188A1 (en) | 2012-05-22 | 2013-11-28 | Idenix Pharmaceuticals, Inc. | 3',5'-cyclic phosphoramidate prodrugs for hcv infection |
| JP6165848B2 (ja) | 2012-05-22 | 2017-07-19 | イデニク ファーマシューティカルズ エルエルシー | 肝疾患のためのｄ−アミノ酸化合物 |
| HUE029038T2 (en) | 2012-05-25 | 2017-01-30 | Janssen Sciences Ireland Uc | Uracil spirooxetan nucleosides |
| EP2900682A1 (en) | 2012-09-27 | 2015-08-05 | IDENIX Pharmaceuticals, Inc. | Esters and malonates of sate prodrugs |
| JP6523958B2 (ja) * | 2012-09-28 | 2019-06-05 | タフツ・ユニバーシティ | ウリジン二リン酸誘導体、プロドラッグ、組成物およびそれらの使用 |
| NZ706985A (en) | 2012-10-08 | 2018-08-31 | Centre Nat Rech Scient | 2’-chloro nucleoside analogs for hcv infection |
| EP2935304A1 (en) | 2012-12-19 | 2015-10-28 | IDENIX Pharmaceuticals, Inc. | 4'-fluoro nucleosides for the treatment of hcv |
| US10550385B2 (en) * | 2012-12-20 | 2020-02-04 | Sirna Therapeutics, Inc. | Post-synthetic orthogonal amidation plus metal catalyzed azide-alkyne cycloaddition click chemistry on siRNA |
| WO2014137930A1 (en) | 2013-03-04 | 2014-09-12 | Idenix Pharmaceuticals, Inc. | Thiophosphate nucleosides for the treatment of hcv |
| EP2970358B1 (en) | 2013-03-04 | 2021-06-30 | Idenix Pharmaceuticals LLC | 3'-deoxy nucleosides for the treatment of hcv |
| US20140271547A1 (en) | 2013-03-13 | 2014-09-18 | Idenix Pharmaceuticals, Inc. | Amino acid phosphoramidate pronucleotides of 2'-cyano, azido and amino nucleosides for the treatment of hcv |
| AR095442A1 (es) | 2013-03-13 | 2015-10-14 | Univ Tufts | Derivados de nucleósido de uridina, composiciones y métodos de uso |
| PT2968385T (pt) | 2013-03-13 | 2018-10-09 | Univ Tufts | Derivados nucleósidos de uridina, composições e métodos de uso |
| WO2014165542A1 (en) | 2013-04-01 | 2014-10-09 | Idenix Pharmaceuticals, Inc. | 2',4'-fluoro nucleosides for the treatment of hcv |
| PL2992098T3 (pl) | 2013-05-01 | 2019-09-30 | Ionis Pharmaceuticals, Inc. | Kompozycje i sposoby modulowania ekspresji hbv i ttr |
| WO2014197578A1 (en) | 2013-06-05 | 2014-12-11 | Idenix Pharmaceuticals, Inc. | 1',4'-thio nucleosides for the treatment of hcv |
| CN105492429A (zh) | 2013-07-02 | 2016-04-13 | 米伦纽姆医药公司 | Sumo活化酶的杂芳基抑制剂 |
| EP3027636B1 (en) | 2013-08-01 | 2022-01-05 | Idenix Pharmaceuticals LLC | D-amino acid phosphoramidate pronucleotides of halogeno pyrimidine compounds for liver disease |
| EP2913064A1 (en) * | 2014-02-26 | 2015-09-02 | celares GmbH | Branched drug-linker conjugates for the coupling to biological targeting molecules |
| EP3131914B1 (en) | 2014-04-16 | 2023-05-10 | Idenix Pharmaceuticals LLC | 3'-substituted methyl or alkynyl nucleosides for the treatment of hcv |
| DK3137476T3 (da) | 2014-04-28 | 2019-11-18 | Ionis Pharmaceuticals Inc | Linker-modificerede oligomerforbindelser |
| MX373283B (es) | 2014-05-01 | 2020-05-20 | Ionis Pharmaceuticals Inc | Composiciones y metodos para modular la expresion del receptor de la hormona del crecimiento. |
| EP3137605B1 (en) | 2014-05-01 | 2020-10-28 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating angiopoietin-like 3 expression |
| PH12016502062B1 (en) | 2014-05-01 | 2023-01-27 | Ionis Pharmaceuticals Inc | Compositions and methods for modulating complement factor b expression |
| EP4534092A3 (en) | 2014-05-01 | 2025-07-02 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating pkk expression |
| US10570169B2 (en) | 2014-05-22 | 2020-02-25 | Ionis Pharmaceuticals, Inc. | Conjugated antisense compounds and their use |
| WO2015179790A1 (en) | 2014-05-23 | 2015-11-26 | Centrillion Technology Holding Corporation | Oligonucleotide probe inversion process for in situ synthesized probe arrays |
| PL3164130T3 (pl) | 2014-07-01 | 2020-02-28 | Millennium Pharmaceuticals, Inc. | Związki heteroarylowe użyteczne jako inhibitory enzymu aktywującego sumo |
| WO2016030863A1 (en) * | 2014-08-29 | 2016-03-03 | Glaxosmithkline Intellectual Property Development Limited | Compounds and methods for treating viral infections |
| WO2016040748A1 (en) | 2014-09-12 | 2016-03-17 | Ionis Pharmaceuticals, Inc. | Compositions and methods for detection of smn protein in a subject and treatment of a subject |
| JP7105065B2 (ja) * | 2014-12-15 | 2022-07-22 | ダイセルナ ファーマシューティカルズ， インコーポレイテッド | リガンド修飾二本鎖核酸 |
| JP6667179B2 (ja) * | 2015-03-24 | 2020-03-18 | 国立大学法人岐阜大学 | オリゴヌクレオチド誘導体及びそれを用いたオリゴヌクレオチド構築物並びにそれらの製造方法 |
| BR112017028194B1 (pt) | 2015-07-10 | 2023-03-14 | Ionis Pharmaceuticals, Inc | Composto oligomérico modulador de diaciglicerol aciltransferase 2 (dgat2), composição, e seus usos |
| US10695735B2 (en) * | 2015-08-18 | 2020-06-30 | Centrillion Technology Holdings Corporation | Probe inversion process for in situ synthesized probe arrays |
| WO2017031278A1 (en) * | 2015-08-18 | 2017-02-23 | Centrillion Technology Holdings Corporation | Probe inversion process for in situ synthesized probe arrays |
| TWI791251B (zh) | 2015-08-26 | 2023-02-01 | 比利時商健生藥品公司 | 使用作為ｐｒｍｔ５抑制劑之新穎經６-６雙環芳香環取代之核苷類似物 |
| AR106135A1 (es) | 2015-09-24 | 2017-12-13 | Ionis Pharmaceuticals Inc | Moduladores de la expresión del sarcoma de la rata de kirsten (kras) |
| KR20250078597A (ko) | 2015-11-06 | 2025-06-02 | 아이오니스 파마수티컬즈, 인코포레이티드 | 아포리포프로테인 (a) 발현 조정 |
| SMT202400375T1 (it) | 2015-11-06 | 2024-11-15 | Ionis Pharmaceuticals Inc | Composti antisenso coniugati per uso in terapia |
| NZ744357A (en) | 2016-03-07 | 2025-09-26 | Arrowhead Pharmaceuticals Inc | Targeting ligands for therapeutic compounds |
| TN2018000310A1 (en) | 2016-03-10 | 2020-01-16 | Janssen Pharmaceutica Nv | Substituted nucleoside analogues for use as prmt5 inhibitors |
| CN109153697A (zh) | 2016-04-14 | 2019-01-04 | 豪夫迈·罗氏有限公司 | 三苯甲基-单-GalNAc化合物及其用途 |
| AU2017296195A1 (en) | 2016-07-11 | 2019-01-24 | Translate Bio Ma, Inc. | Nucleic acid conjugates and uses thereof |
| EP4206213A1 (en) | 2016-07-15 | 2023-07-05 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulation of smn2 |
| US10781175B2 (en) | 2016-07-15 | 2020-09-22 | Am Chemicals Llc | Solid supports and phosphoramidite building blocks for oligonucleotide conjugates |
| WO2018035380A1 (en) | 2016-08-17 | 2018-02-22 | Solstice Biologics, Ltd. | Polynucleotide constructs |
| KR102856522B1 (ko) | 2016-09-02 | 2025-09-08 | 애로우헤드 파마슈티컬스 인코포레이티드 | 표적화 리간드 |
| JP7101171B2 (ja) | 2016-10-03 | 2022-07-14 | ヤンセン ファーマシューティカ エヌ．ベー． | Ｐｒｍｔ５阻害剤として使用するための新規な単環式および二環式環系置換カルバヌクレオシド類似体 |
| CN109661233A (zh) | 2016-10-06 | 2019-04-19 | Ionis 制药公司 | 缀合低聚化合物的方法 |
| KR20220147720A (ko) | 2016-11-14 | 2022-11-03 | 항저우 디에이씨 바이오테크 씨오, 엘티디 | 결합 링커, 그러한 결합 링커를 함유하는 세포 결합 분자-약물 결합체, 링커를 갖는 그러한 결합체의 제조 및 사용 |
| ES2971035T3 (es) | 2017-02-27 | 2024-06-03 | Janssen Pharmaceutica Nv | Uso de biomarcadores en la identificación de pacientes con cáncer que mostrarán respuesta al tratamiento con un inhibidor de prmt5 |
| JOP20190215A1 (ar) | 2017-03-24 | 2019-09-19 | Ionis Pharmaceuticals Inc | مُعدّلات التعبير الوراثي عن pcsk9 |
| CN110520531A (zh) | 2017-04-05 | 2019-11-29 | 赛伦斯治疗有限责任公司 | 产品和组合物 |
| CN108728397B (zh) * | 2017-04-17 | 2022-05-20 | 中国科学院微生物研究所 | 对昆虫蛋白或昆虫表达系统表达的外源蛋白进行标记的方法 |
| KR20190141747A (ko) | 2017-05-01 | 2019-12-24 | 길리애드 사이언시즈, 인코포레이티드 | (S)-2-에틸부틸 2-(((S)-(((2R,3S,4R,5R)-5-(4-아미노피롤로[2,1-f] [1,2,4]트리아진-7-일)-5-시아노-3,4-디히드록시테트라히드로푸란-2-일)메톡시)(페녹시) 포스포릴)아미노)프로파노에이트의 결정질 형태 |
| US11597744B2 (en) | 2017-06-30 | 2023-03-07 | Sirius Therapeutics, Inc. | Chiral phosphoramidite auxiliaries and methods of their use |
| US10675296B2 (en) | 2017-07-11 | 2020-06-09 | Gilead Sciences, Inc. | Compositions comprising an RNA polymerase inhibitor and cyclodextrin for treating viral infections |
| CA3084449A1 (en) | 2017-12-08 | 2019-06-13 | Janssen Pharmaceutica Nv | Novel spirobicyclic analogues |
| EP3737424A4 (en) | 2018-01-10 | 2021-10-27 | Translate Bio MA, Inc. | COMPOSITIONS AND METHODS TO FACILITATE THE DELIVERY OF SYNTHETIC NUCLEIC ACIDS INTO CELLS |
| CA3088522A1 (en) | 2018-01-15 | 2019-07-18 | Ionis Pharmaceuticals, Inc. | Modulators of dnm2 expression |
| US11332733B2 (en) | 2018-02-12 | 2022-05-17 | lonis Pharmaceuticals, Inc. | Modified compounds and uses thereof |
| WO2019173602A1 (en) * | 2018-03-07 | 2019-09-12 | Emory University | 4'-halogen containing nucleotide and nucleoside therapeutic compositions and uses related thereto |
| SG11202010910QA (en) * | 2018-05-07 | 2020-12-30 | Alnylam Pharmaceuticals Inc | Extrahepatic delivery |
| CU20200082A7 (es) | 2018-05-09 | 2021-06-08 | Ionis Pharmaceuticals Inc | Compuestos y métodos para la reducción de la expresión de fxi |
| US12496311B2 (en) | 2018-07-17 | 2025-12-16 | Aronora, Inc. | Methods for safely reducing thrombopoietin |
| EP3833397A4 (en) | 2018-08-08 | 2023-06-14 | Arcturus Therapeutics, Inc. | COMPOSITIONS AND AGENTS AGAINST NON-ALCOHOLIC STEATOHEPATITIS |
| TWI869213B (zh) | 2018-09-19 | 2025-01-01 | 美商Ionis製藥公司 | Pnpla3表現之調節劑 |
| IL283967B2 (en) | 2018-12-21 | 2025-03-01 | Ionis Pharmaceuticals Inc | Modulators of hsd17b13 expression |
| EP3902813A4 (en) * | 2018-12-28 | 2022-05-04 | Sirnaomics, Inc. | TARGETED DELIVERY OF THERAPEUTIC MOLECULES |
| TW202112375A (zh) | 2019-06-06 | 2021-04-01 | 比利時商健生藥品公司 | 使用ｐｒｍｔ５抑制劑治療癌症之方法 |
| EP4045062A1 (en) | 2019-10-14 | 2022-08-24 | Astrazeneca AB | Modulators of pnpla3 expression |
| CN119607006A (zh) | 2019-12-09 | 2025-03-14 | 艾姆皮瑞克公司 | 用于治疗血管生成素样4(angptl4)相关疾病的寡核苷酸 |
| CN118766947A (zh) | 2020-01-27 | 2024-10-15 | 吉利德科学公司 | 用于治疗SARS CoV-2感染的方法 |
| TWI883391B (zh) | 2020-02-18 | 2025-05-11 | 美商基利科學股份有限公司 | 抗病毒化合物 |
| CA3171648A1 (en) | 2020-02-18 | 2021-08-26 | Gilead Sciences, Inc. | Antiviral compounds |
| TWI775313B (zh) | 2020-02-18 | 2022-08-21 | 美商基利科學股份有限公司 | 抗病毒化合物 |
| BR112022016238A2 (pt) | 2020-02-28 | 2022-10-11 | Ionis Pharmaceuticals Inc | Compostos e métodos para modular smn2 |
| CA3169340A1 (en) | 2020-03-12 | 2021-09-16 | Pavel R. Badalov | Methods of preparing 1'-cyano nucleosides |
| CN111303235B (zh) * | 2020-03-12 | 2021-08-13 | 中国科学院微生物研究所 | 一种抗流感病毒化合物及其制备方法与应用 |
| US20230140044A1 (en) * | 2020-03-20 | 2023-05-04 | University Of Massachusetts | Micrornas for the prevention of clinical venous thromboembolic disease |
| JP7482250B2 (ja) | 2020-04-06 | 2024-05-13 | ギリアード サイエンシーズ， インコーポレイテッド | １’－シアノ置換カルバヌクレオシド類似体の吸入製剤 |
| WO2021206922A1 (en) * | 2020-04-07 | 2021-10-14 | Alnylam Pharmaceuticals, Inc. | Transmembrane serine protease 2 (tmprss2) irna compositions and methods of use thereof |
| WO2021206917A1 (en) * | 2020-04-07 | 2021-10-14 | Alnylam Pharmaceuticals, Inc. | ANGIOTENSIN-CONVERTING ENZYME 2 (ACE2) iRNA COMPOSITIONS AND METHODS OF USE THEREOF |
| CA3176196A1 (en) | 2020-04-21 | 2021-10-28 | Flagship Pioneering, Inc. | Bifunctional molecules and methods of using thereof |
| PL4157272T3 (pl) | 2020-05-29 | 2025-10-20 | Gilead Sciences, Inc. | Remdesiwir do leczenia zakażeń wirusowych |
| JP2023531524A (ja) | 2020-06-24 | 2023-07-24 | ギリアード サイエンシーズ， インコーポレイテッド | １’－シアノヌクレオシド類似体及びその使用 |
| CR20230100A (es) | 2020-08-24 | 2023-04-28 | Gilead Sciences Inc | Compuestos fosfolípidos y usos de los mismos |
| LT4204421T (lt) | 2020-08-27 | 2024-06-25 | Gilead Sciences, Inc. | Virusinių infekcijų gydymui skirti junginiai ir būdai |
| TW202344257A (zh) | 2020-10-16 | 2023-11-16 | 美商基利科學股份有限公司 | 磷脂化合物及其用途 |
| WO2022109139A1 (en) | 2020-11-18 | 2022-05-27 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulating angiotensinogen expression |
| EP4175964A1 (en) * | 2021-01-30 | 2023-05-10 | E-Therapeutics plc | Conjugated oligonucleotide compounds, methods of making and uses thereof |
| EP4357334A3 (en) * | 2021-01-30 | 2024-08-07 | E-Therapeutics plc | Conjugated oligonucleotide compounds, methods of making and uses thereof |
| PL4323362T3 (pl) | 2021-04-16 | 2025-08-18 | Gilead Sciences, Inc. | Sposoby wytwarzania karbanukleozydów z zastosowaniem amidów |
| JP2024523237A (ja) | 2021-06-18 | 2024-06-28 | ホンジーン バイオテック コーポレイション | 官能化されたｎ－アセチルガラクトサミンヌクレオシド |
| JP2024528697A (ja) | 2021-07-20 | 2024-07-30 | エイジーエス・セラピューティクス・ソシエテ・パール・アクシオン・サンプリフィエ | 微細藻類由来の細胞外小胞、その調製および使用 |
| AU2022328698B2 (en) | 2021-08-18 | 2025-02-20 | Gilead Sciences, Inc. | Phospholipid compounds and methods of making and using the same |
| WO2023034719A1 (en) | 2021-08-30 | 2023-03-09 | Hongene Biotech Corporation | Functionalized n-acetylgalactosamine analogs |
| MX2024004011A (es) | 2021-10-01 | 2024-07-01 | Adarx Pharmaceuticals Inc | Composiciones moduladoras de precalicreína y métodos de uso de estas. |
| EP4448540A1 (en) | 2021-12-15 | 2024-10-23 | Hongene Biotech Corporation | Functionalized n-acetylgalactosamine analogs |
| US20230210998A1 (en) * | 2021-12-30 | 2023-07-06 | Navidea Biopharmaceuticals, Inc. | Methods for the conjugation of anthracyclines to carbohydrate polymeric carriers |
| WO2023144127A1 (en) | 2022-01-31 | 2023-08-03 | Ags Therapeutics Sas | Extracellular vesicles from microalgae, their biodistribution upon administration, and uses |
| US20230295172A1 (en) | 2022-03-02 | 2023-09-21 | Gilead Sciences, Inc. | Compounds and methods for treatment of viral infections |
| IL315546A (en) | 2022-03-16 | 2024-11-01 | Empirico Inc | GALNAC compositions to improve siRNA bioavailability |
| AU2023245603A1 (en) | 2022-03-28 | 2024-11-07 | Empirico Inc. | Modified oligonucleotides |
| WO2023232976A1 (en) | 2022-06-03 | 2023-12-07 | Ags Therapeutics Sas | Extracellular vesicles from genetically-modified microalgae containing endogenously-loaded cargo, their preparation, and uses |
| JP2025535944A (ja) | 2022-10-24 | 2025-10-30 | エイジーエス・セラピューティクス・ソシエテ・パール・アクシオン・サンプリフィエ | 微細藻類由来の細胞外小胞、鼻腔内投与時のそれらの生体内分布、及びそれらの使用 |
| KR20250099265A (ko) * | 2022-11-23 | 2025-07-01 | 일라이 릴리 앤드 캄파니 | 표적화 리간드-접합된 뉴클레오티드 포스포르아미다이트의 합성 방법 |
| WO2024118503A1 (en) | 2022-11-28 | 2024-06-06 | Hongene Biotech Corporation | Functionalized n-acetylgalactosamine analogs |
| WO2024220930A2 (en) | 2023-04-20 | 2024-10-24 | Adarx Pharmaceuticals, Inc. | Mapt-modulating compositions and methods of use thereof |
| WO2024238396A1 (en) | 2023-05-12 | 2024-11-21 | Adarx Pharmaceuticals, Inc. | Nmda ligand conjugated compounds and uses thereof |
| AU2024279767A1 (en) | 2023-05-26 | 2025-12-04 | Adarx Pharmaceuticals, Inc. | Sod1-modulating compositions and methods of use thereof |
| WO2024263694A1 (en) | 2023-06-20 | 2024-12-26 | Adarx Pharmaceuticals, Inc. | Lrrk2-modulating compositions and methods of use thereof |
| WO2025038963A1 (en) * | 2023-08-17 | 2025-02-20 | Adarx Pharmaceuticals, Inc. | Oligonucleotides containing multiple ligands and/or lipids |
| WO2025038960A1 (en) * | 2023-08-17 | 2025-02-20 | Adarx Pharmaceuticals, Inc. | Oligonucleotides containing a ligand at an internal position |
| WO2025038970A1 (en) * | 2023-08-17 | 2025-02-20 | Adarx Pharmaceuticals, Inc. | Modified oligonucleotides containing multiple oligonucleotides |
| CN117417400B (zh) * | 2023-12-18 | 2024-02-20 | 苏州诺维康生物科技有限公司 | 2'-o-丙炔基-5'-二甲氧三苯甲基-n4-乙酰基-胞苷的合成方法 |
| US12357577B1 (en) | 2024-02-02 | 2025-07-15 | Gilead Sciences, Inc. | Pharmaceutical formulations and uses thereof |
| WO2025176847A1 (en) | 2024-02-21 | 2025-08-28 | Ags Therapeutics Sas | Ocular delivery of active agents via microalgae extracellular vesicles |
Family Cites Families (143)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5218A (en) | 1847-08-07 | Improvement in plows | ||
| US105A (en) | 1836-12-15 | knight | ||
| US1861608A (en) | 1929-12-21 | 1932-06-07 | Emerson Electric Mfg Co | Fan and means for directing the air current therethrough |
| US1861108A (en) | 1930-01-24 | 1932-05-31 | Eugene O Brace | Integral clutch and transmission control |
| US3687808A (en) | 1969-08-14 | 1972-08-29 | Univ Leland Stanford Junior | Synthetic polynucleotides |
| US3974808A (en) | 1975-07-02 | 1976-08-17 | Ford Motor Company | Air intake duct assembly |
| DE3023787A1 (de) | 1980-06-25 | 1982-01-21 | Studiengesellschaft Kohle mbH, 4330 Mülheim | Verfahren zur erhoehung der inkorporation und der expression von genetischem material in die kerne von intakten zellen mit hilfe von liposomen |
| US4469863A (en) | 1980-11-12 | 1984-09-04 | Ts O Paul O P | Nonionic nucleic acid alkyl and aryl phosphonates and processes for manufacture and use thereof |
| US5023243A (en) | 1981-10-23 | 1991-06-11 | Molecular Biosystems, Inc. | Oligonucleotide therapeutic agent and method of making same |
| US4522811A (en) | 1982-07-08 | 1985-06-11 | Syntex (U.S.A.) Inc. | Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides |
| JPS5927900A (ja) | 1982-08-09 | 1984-02-14 | Wakunaga Seiyaku Kk | 固定化オリゴヌクレオチド |
| US4708708A (en) | 1982-12-06 | 1987-11-24 | International Paper Company | Method and apparatus for skiving and hemming |
| FR2540122B1 (fr) | 1983-01-27 | 1985-11-29 | Centre Nat Rech Scient | Nouveaux composes comportant une sequence d'oligonucleotide liee a un agent d'intercalation, leur procede de synthese et leur application |
| US4605735A (en) | 1983-02-14 | 1986-08-12 | Wakunaga Seiyaku Kabushiki Kaisha | Oligonucleotide derivatives |
| US4948882A (en) | 1983-02-22 | 1990-08-14 | Syngene, Inc. | Single-stranded labelled oligonucleotides, reactive monomers and methods of synthesis |
| US4824941A (en) | 1983-03-10 | 1989-04-25 | Julian Gordon | Specific antibody to the native form of 2'5'-oligonucleotides, the method of preparation and the use as reagents in immunoassays or for binding 2'5'-oligonucleotides in biological systems |
| US4587044A (en) | 1983-09-01 | 1986-05-06 | The Johns Hopkins University | Linkage of proteins to nucleic acids |
| US5118802A (en) | 1983-12-20 | 1992-06-02 | California Institute Of Technology | DNA-reporter conjugates linked via the 2' or 5'-primary amino group of the 5'-terminal nucleoside |
| US4828991A (en) | 1984-01-31 | 1989-05-09 | Akzo N.V. | Tumor specific monoclonal antibodies |
| US5258506A (en) | 1984-10-16 | 1993-11-02 | Chiron Corporation | Photolabile reagents for incorporation into oligonucleotide chains |
| US5430136A (en) | 1984-10-16 | 1995-07-04 | Chiron Corporation | Oligonucleotides having selectably cleavable and/or abasic sites |
| US4828979A (en) | 1984-11-08 | 1989-05-09 | Life Technologies, Inc. | Nucleotide analogs for nucleic acid labeling and detection |
| US5235033A (en) | 1985-03-15 | 1993-08-10 | Anti-Gene Development Group | Alpha-morpholino ribonucleoside derivatives and polymers thereof |
| EP0215942B1 (en) | 1985-03-15 | 1995-07-12 | Antivirals Inc. | Polynucleotide assay reagent and method |
| US4762779A (en) | 1985-06-13 | 1988-08-09 | Amgen Inc. | Compositions and methods for functionalizing nucleic acids |
| US5317098A (en) | 1986-03-17 | 1994-05-31 | Hiroaki Shizuya | Non-radioisotope tagging of fragments |
| JPS638396A (ja) | 1986-06-30 | 1988-01-14 | Wakunaga Pharmaceut Co Ltd | ポリ標識化オリゴヌクレオチド誘導体 |
| US4904582A (en) | 1987-06-11 | 1990-02-27 | Synthetic Genetics | Novel amphiphilic nucleic acid conjugates |
| US5585481A (en) | 1987-09-21 | 1996-12-17 | Gen-Probe Incorporated | Linking reagents for nucleotide probes |
| US5525465A (en) | 1987-10-28 | 1996-06-11 | Howard Florey Institute Of Experimental Physiology And Medicine | Oligonucleotide-polyamide conjugates and methods of production and applications of the same |
| DE3738460A1 (de) | 1987-11-12 | 1989-05-24 | Max Planck Gesellschaft | Modifizierte oligonukleotide |
| US5082830A (en) | 1988-02-26 | 1992-01-21 | Enzo Biochem, Inc. | End labeled nucleotide probe |
| US5109124A (en) | 1988-06-01 | 1992-04-28 | Biogen, Inc. | Nucleic acid probe linked to a label having a terminal cysteine |
| US5149782A (en) | 1988-08-19 | 1992-09-22 | Tanox Biosystems, Inc. | Molecular conjugates containing cell membrane-blending agents |
| US5262536A (en) | 1988-09-15 | 1993-11-16 | E. I. Du Pont De Nemours And Company | Reagents for the preparation of 5'-tagged oligonucleotides |
| US5512439A (en) | 1988-11-21 | 1996-04-30 | Dynal As | Oligonucleotide-linked magnetic particles and uses thereof |
| CA2006008C (en) | 1988-12-20 | 2000-02-15 | Donald J. Kessler | Method for making synthetic oligonucleotides which bind specifically to target sites on duplex dna molecules, by forming a colinear triplex, the synthetic oligonucleotides and methods of use |
| US5599923A (en) | 1989-03-06 | 1997-02-04 | Board Of Regents, University Of Tx | Texaphyrin metal complexes having improved functionalization |
| US5457183A (en) | 1989-03-06 | 1995-10-10 | Board Of Regents, The University Of Texas System | Hydroxylated texaphyrins |
| US5391723A (en) | 1989-05-31 | 1995-02-21 | Neorx Corporation | Oligonucleotide conjugates |
| US5256775A (en) | 1989-06-05 | 1993-10-26 | Gilead Sciences, Inc. | Exonuclease-resistant oligonucleotides |
| US4958013A (en) | 1989-06-06 | 1990-09-18 | Northwestern University | Cholesteryl modified oligonucleotides |
| NL8901881A (nl) | 1989-07-20 | 1991-02-18 | Rockwool Grodan Bv | Drainagekoppelelement. |
| US5451463A (en) | 1989-08-28 | 1995-09-19 | Clontech Laboratories, Inc. | Non-nucleoside 1,3-diol reagents for labeling synthetic oligonucleotides |
| US5254469A (en) | 1989-09-12 | 1993-10-19 | Eastman Kodak Company | Oligonucleotide-enzyme conjugate that can be used as a probe in hybridization assays and polymerase chain reaction procedures |
| US5264562A (en) | 1989-10-24 | 1993-11-23 | Gilead Sciences, Inc. | Oligonucleotide analogs with novel linkages |
| US5264564A (en) | 1989-10-24 | 1993-11-23 | Gilead Sciences | Oligonucleotide analogs with novel linkages |
| WO1991006309A1 (en) | 1989-11-03 | 1991-05-16 | Vanderbilt University | Method of in vivo delivery of functioning foreign genes |
| US5292873A (en) | 1989-11-29 | 1994-03-08 | The Research Foundation Of State University Of New York | Nucleic acids labeled with naphthoquinone probe |
| US5177198A (en) | 1989-11-30 | 1993-01-05 | University Of N.C. At Chapel Hill | Process for preparing oligoribonucleoside and oligodeoxyribonucleoside boranophosphates |
| US5223168A (en) | 1989-12-12 | 1993-06-29 | Gary Holt | Surface cleaner and treatment |
| US5130302A (en) | 1989-12-20 | 1992-07-14 | Boron Bilogicals, Inc. | Boronated nucleoside, nucleotide and oligonucleotide compounds, compositions and methods for using same |
| US5486603A (en) | 1990-01-08 | 1996-01-23 | Gilead Sciences, Inc. | Oligonucleotide having enhanced binding affinity |
| US6153737A (en) | 1990-01-11 | 2000-11-28 | Isis Pharmaceuticals, Inc. | Derivatized oligonucleotides having improved uptake and other properties |
| US5459255A (en) | 1990-01-11 | 1995-10-17 | Isis Pharmaceuticals, Inc. | N-2 substituted purines |
| US5587361A (en) | 1991-10-15 | 1996-12-24 | Isis Pharmaceuticals, Inc. | Oligonucleotides having phosphorothioate linkages of high chiral purity |
| US5587470A (en) | 1990-01-11 | 1996-12-24 | Isis Pharmaceuticals, Inc. | 3-deazapurines |
| US5506351A (en) | 1992-07-23 | 1996-04-09 | Isis Pharmaceuticals | Process for the preparation of 2'-O-alkyl guanosine and related compounds |
| US5457191A (en) | 1990-01-11 | 1995-10-10 | Isis Pharmaceuticals, Inc. | 3-deazapurines |
| US5212295A (en) | 1990-01-11 | 1993-05-18 | Isis Pharmaceuticals | Monomers for preparation of oligonucleotides having chiral phosphorus linkages |
| US5578718A (en) | 1990-01-11 | 1996-11-26 | Isis Pharmaceuticals, Inc. | Thiol-derivatized nucleosides |
| US5149797A (en) | 1990-02-15 | 1992-09-22 | The Worcester Foundation For Experimental Biology | Method of site-specific alteration of rna and production of encoded polypeptides |
| AU7579991A (en) | 1990-02-20 | 1991-09-18 | Gilead Sciences, Inc. | Pseudonucleosides and pseudonucleotides and their polymers |
| US5214136A (en) | 1990-02-20 | 1993-05-25 | Gilead Sciences, Inc. | Anthraquinone-derivatives oligonucleotides |
| DE69032425T2 (de) | 1990-05-11 | 1998-11-26 | Microprobe Corp., Bothell, Wash. | Teststreifen zum Eintauchen für Nukleinsäure-Hybridisierungsassays und Verfahren zur kovalenten Immobilisierung von Oligonucleotiden |
| US5688941A (en) | 1990-07-27 | 1997-11-18 | Isis Pharmaceuticals, Inc. | Methods of making conjugated 4' desmethyl nucleoside analog compounds |
| US5138045A (en) | 1990-07-27 | 1992-08-11 | Isis Pharmaceuticals | Polyamine conjugated oligonucleotides |
| US5608046A (en) | 1990-07-27 | 1997-03-04 | Isis Pharmaceuticals, Inc. | Conjugated 4'-desmethyl nucleoside analog compounds |
| US5610289A (en) | 1990-07-27 | 1997-03-11 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogues |
| US5489677A (en) | 1990-07-27 | 1996-02-06 | Isis Pharmaceuticals, Inc. | Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms |
| US5223618A (en) | 1990-08-13 | 1993-06-29 | Isis Pharmaceuticals, Inc. | 4'-desmethyl nucleoside analog compounds |
| US5378825A (en) | 1990-07-27 | 1995-01-03 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogs |
| US5614617A (en) | 1990-07-27 | 1997-03-25 | Isis Pharmaceuticals, Inc. | Nuclease resistant, pyrimidine modified oligonucleotides that detect and modulate gene expression |
| US5386023A (en) | 1990-07-27 | 1995-01-31 | Isis Pharmaceuticals | Backbone modified oligonucleotide analogs and preparation thereof through reductive coupling |
| US5541307A (en) | 1990-07-27 | 1996-07-30 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogs and solid phase synthesis thereof |
| US5218105A (en) | 1990-07-27 | 1993-06-08 | Isis Pharmaceuticals | Polyamine conjugated oligonucleotides |
| US5602240A (en) | 1990-07-27 | 1997-02-11 | Ciba Geigy Ag. | Backbone modified oligonucleotide analogs |
| US5245022A (en) | 1990-08-03 | 1993-09-14 | Sterling Drug, Inc. | Exonuclease resistant terminally substituted oligonucleotides |
| US6262241B1 (en) | 1990-08-13 | 2001-07-17 | Isis Pharmaceuticals, Inc. | Compound for detecting and modulating RNA activity and gene expression |
| US5512667A (en) | 1990-08-28 | 1996-04-30 | Reed; Michael W. | Trifunctional intermediates for preparing 3'-tailed oligonucleotides |
| EP0556301B1 (en) | 1990-11-08 | 2001-01-10 | Hybridon, Inc. | Incorporation of multiple reporter groups on synthetic oligonucleotides |
| US20020123476A1 (en) | 1991-03-19 | 2002-09-05 | Emanuele R. Martin | Therapeutic delivery compositions and methods of use thereof |
| US6933286B2 (en) | 1991-03-19 | 2005-08-23 | R. Martin Emanuele | Therapeutic delivery compositions and methods of use thereof |
| US5539082A (en) | 1993-04-26 | 1996-07-23 | Nielsen; Peter E. | Peptide nucleic acids |
| US5371241A (en) | 1991-07-19 | 1994-12-06 | Pharmacia P-L Biochemicals Inc. | Fluorescein labelled phosphoramidites |
| US5599797A (en) | 1991-10-15 | 1997-02-04 | Isis Pharmaceuticals, Inc. | Oligonucleotides having phosphorothioate linkages of high chiral purity |
| US6335434B1 (en) | 1998-06-16 | 2002-01-01 | Isis Pharmaceuticals, Inc., | Nucleosidic and non-nucleosidic folate conjugates |
| US6235887B1 (en) | 1991-11-26 | 2001-05-22 | Isis Pharmaceuticals, Inc. | Enhanced triple-helix and double-helix formation directed by oligonucleotides containing modified pyrimidines |
| US5484908A (en) | 1991-11-26 | 1996-01-16 | Gilead Sciences, Inc. | Oligonucleotides containing 5-propynyl pyrimidines |
| US5359044A (en) | 1991-12-13 | 1994-10-25 | Isis Pharmaceuticals | Cyclobutyl oligonucleotide surrogates |
| US5595726A (en) | 1992-01-21 | 1997-01-21 | Pharmacyclics, Inc. | Chromophore probe for detection of nucleic acid |
| US5565552A (en) | 1992-01-21 | 1996-10-15 | Pharmacyclics, Inc. | Method of expanded porphyrin-oligonucleotide conjugate synthesis |
| EP0642589A4 (en) | 1992-05-11 | 1997-05-21 | Ribozyme Pharm Inc | METHOD AND REAGENT TO INHIBIT VIRAL REPLICATION. |
| FR2692265B1 (fr) | 1992-05-25 | 1996-11-08 | Centre Nat Rech Scient | Composes biologiquement actifs de type phosphotriesters. |
| US6172208B1 (en) | 1992-07-06 | 2001-01-09 | Genzyme Corporation | Oligonucleotides modified with conjugate groups |
| US5272250A (en) | 1992-07-10 | 1993-12-21 | Spielvogel Bernard F | Boronated phosphoramidate compounds |
| CA2140343A1 (en) | 1992-07-17 | 1994-02-03 | Sean M. Sullivan | Method and reagent for treatment of animal diseases |
| US5721138A (en) | 1992-12-15 | 1998-02-24 | Sandford University | Apolipoprotein(A) promoter and regulatory sequence constructs and methods of use |
| US5574142A (en) | 1992-12-15 | 1996-11-12 | Microprobe Corporation | Peptide linkers for improved oligonucleotide delivery |
| US5476925A (en) | 1993-02-01 | 1995-12-19 | Northwestern University | Oligodeoxyribonucleotides including 3'-aminonucleoside-phosphoramidate linkages and terminal 3'-amino groups |
| GB9304620D0 (en) | 1993-03-06 | 1993-04-21 | Ciba Geigy Ag | Compounds |
| FR2705099B1 (fr) | 1993-05-12 | 1995-08-04 | Centre Nat Rech Scient | Oligonucléotides phosphorothioates triesters et procédé de préparation. |
| US5571902A (en) | 1993-07-29 | 1996-11-05 | Isis Pharmaceuticals, Inc. | Synthesis of oligonucleotides |
| DE69433036T2 (de) | 1993-09-03 | 2004-05-27 | Isis Pharmaceuticals, Inc., Carlsbad | Aminoderivatisierte nukleoside und oligonukleoside |
| US5519134A (en) | 1994-01-11 | 1996-05-21 | Isis Pharmaceuticals, Inc. | Pyrrolidine-containing monomers and oligomers |
| US5539083A (en) | 1994-02-23 | 1996-07-23 | Isis Pharmaceuticals, Inc. | Peptide nucleic acid combinatorial libraries and improved methods of synthesis |
| IL112920A (en) | 1994-03-07 | 2003-04-10 | Dow Chemical Co | Composition comprising a dendritic polymer complexed with at least one unit of biological response modifier and a process for the preparation thereof |
| US5554746A (en) | 1994-05-16 | 1996-09-10 | Isis Pharmaceuticals, Inc. | Lactam nucleic acids |
| US5597696A (en) | 1994-07-18 | 1997-01-28 | Becton Dickinson And Company | Covalent cyanine dye oligonucleotide conjugates |
| US5580731A (en) | 1994-08-25 | 1996-12-03 | Chiron Corporation | N-4 modified pyrimidine deoxynucleotides and oligonucleotide probes synthesized therewith |
| US5801155A (en) | 1995-04-03 | 1998-09-01 | Epoch Pharmaceuticals, Inc. | Covalently linked oligonucleotide minor grove binder conjugates |
| US5672662A (en) | 1995-07-07 | 1997-09-30 | Shearwater Polymers, Inc. | Poly(ethylene glycol) and related polymers monosubstituted with propionic or butanoic acids and functional derivatives thereof for biotechnical applications |
| US6444806B1 (en) | 1996-04-30 | 2002-09-03 | Hisamitsu Pharmaceutical Co., Inc. | Conjugates and methods of forming conjugates of oligonucleotides and carbohydrates |
| US6300319B1 (en) | 1998-06-16 | 2001-10-09 | Isis Pharmaceuticals, Inc. | Targeted oligonucleotide conjugates |
| US6335437B1 (en) | 1998-09-07 | 2002-01-01 | Isis Pharmaceuticals, Inc. | Methods for the preparation of conjugated oligomers |
| DE19956568A1 (de) | 1999-01-30 | 2000-08-17 | Roland Kreutzer | Verfahren und Medikament zur Hemmung der Expression eines vorgegebenen Gens |
| US20030083273A1 (en) * | 1999-04-20 | 2003-05-01 | Tod M. Woolf | Antisense oligomers |
| US6395437B1 (en) | 1999-10-29 | 2002-05-28 | Advanced Micro Devices, Inc. | Junction profiling using a scanning voltage micrograph |
| GB0001309D0 (en) | 2000-01-20 | 2000-03-08 | Nestle Sa | Valve arrangement |
| US6287860B1 (en) | 2000-01-20 | 2001-09-11 | Isis Pharmaceuticals, Inc. | Antisense inhibition of MEKK2 expression |
| DK2796553T3 (da) | 2000-03-30 | 2019-09-30 | Whitehead Inst Biomedical Res | Rna-sekvensspecifikke formidlere af rna-interferens |
| US6559279B1 (en) | 2000-09-08 | 2003-05-06 | Isis Pharmaceuticals, Inc. | Process for preparing peptide derivatized oligomeric compounds |
| CZ302719B6 (cs) | 2000-12-01 | 2011-09-21 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Izolovaná molekula dvouretezcové RNA, zpusob její výroby a její použití |
| ATE469135T1 (de) * | 2002-05-30 | 2010-06-15 | Scripps Research Inst | Kupferkatalysierte ligierung von aziden und acetylenen |
| US8431558B2 (en) | 2004-11-01 | 2013-04-30 | The Regents Of The University Of California | Compositions and methods for modification of biomolecules |
| US20060147963A1 (en) | 2004-12-30 | 2006-07-06 | Affymetrix, Inc. | Detection of polynucleotides on nucleic acid arrays using azido-modified triphosphate nucleotide analogs |
| JP2008540338A (ja) * | 2005-04-27 | 2008-11-20 | シーメンス メディカル ソリューションズ ユーエスエー インコーポレイテッド | 分子画像化プローブのクリックケミストリー合成法 |
| AU2006243370B2 (en) * | 2005-05-02 | 2012-06-28 | Basf Aktiengesellschaft | New labelling strategies for the sensitive detection of analytes |
| AU2006247520A1 (en) * | 2005-05-18 | 2006-11-23 | Wyeth | 3-cyanoquinoline inhibitors of TPL2 kinase and methods of making and using the same |
| WO2007081031A1 (ja) * | 2006-01-16 | 2007-07-19 | Hokkaido University | 糖転移酵素阻害剤 |
| US20100184209A1 (en) | 2006-02-17 | 2010-07-22 | Dharmacon, Inc. | Compositions and methods for inhibiting gene silencing by rna interference |
| CA2650668A1 (en) * | 2006-04-28 | 2007-11-08 | Centre National De La Recherche Scientifique | Method for the synthesis of triazole-containing oligonucleotide deratives |
| AU2007299705B2 (en) | 2006-09-22 | 2012-09-06 | Dharmacon, Inc. | Duplex oligonucleotide complexes and methods for gene silencing by RNA interference |
| EP2089343B1 (en) | 2006-10-31 | 2011-07-06 | baseclick GmbH | Click chemistry for the production of reporter molecules |
| US20100143980A1 (en) * | 2007-02-22 | 2010-06-10 | Kuberan Balagurunathan | Synthesis of novel xylosides and potential uses thereof |
| CN101925366B (zh) | 2007-11-21 | 2015-02-04 | 乔治亚大学研究基金公司 | 炔烃以及炔烃与1,3-偶极-官能化合物反应的方法 |
| CN101497638B (zh) * | 2008-01-30 | 2012-09-26 | 中国科学院大连化学物理研究所 | 一种nad+类似物及其合成和应用 |
| JP2012513953A (ja) * | 2008-09-23 | 2012-06-21 | アルニラム ファーマスーティカルズ インコーポレイテッド | 付加環化を用いたモノマーおよびオリゴヌクレオチドの化学修飾 |
| DE102009039097B3 (de) | 2009-08-27 | 2010-11-25 | Siemens Aktiengesellschaft | Verfahren zum Übertragen von Daten in einem Sensornetzwerk, Sensorknoten und Zentral-Rechner |
| US8315599B2 (en) | 2010-07-09 | 2012-11-20 | Telecommunication Systems, Inc. | Location privacy selector |
| WO2015059886A1 (ja) | 2013-10-21 | 2015-04-30 | キヤノン株式会社 | 放射線撮影装置およびその制御方法、放射線画像処理装置および方法、並びに、プログラムおよびコンピュータ可読記憶媒体 |
| FI3921593T3 (fi) | 2019-02-04 | 2023-05-29 | Detnet South Africa Pty Ltd | Säiliöpumppu |
| KR102318555B1 (ko) | 2020-03-19 | 2021-10-29 | 한국과학기술연구원 | 광소자용 역나노콘과 그 제조방법 |
-
2009
- 2009-09-23 JP JP2011529188A patent/JP2012513953A/ja active Pending
- 2009-09-23 EP EP19173718.8A patent/EP3587434A1/en not_active Ceased
- 2009-09-23 US US13/120,389 patent/US8962580B2/en active Active
- 2009-09-23 EP EP09737234A patent/EP2342616A2/en not_active Ceased
- 2009-09-23 WO PCT/US2009/058084 patent/WO2010039548A2/en not_active Ceased
- 2009-09-23 CA CA2737661A patent/CA2737661C/en active Active
- 2009-09-23 AU AU2009298802A patent/AU2009298802A1/en not_active Abandoned
-
2014
- 2014-09-11 JP JP2014185220A patent/JP6053735B2/ja active Active
- 2014-12-31 US US14/587,957 patent/US20150203847A1/en not_active Abandoned
-
2016
- 2016-04-14 AU AU2016202354A patent/AU2016202354B2/en active Active
- 2016-11-29 JP JP2016231739A patent/JP6484602B2/ja active Active
-
2018
- 2018-08-16 US US16/104,045 patent/US20190048344A1/en not_active Abandoned
-
2019
- 2019-02-18 JP JP2019026194A patent/JP6885976B2/ja active Active
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2012513953A5 (enExample) | ||
| ES2932831T3 (es) | Productos y composiciones | |
| ES2908978T3 (es) | Nuevas entidades químicas simples y métodos para la administración de oligonucleótidos | |
| US12275938B2 (en) | Modified RNA agents with reduced off-target effect | |
| CN113166759B (zh) | 经化学修饰的RNAi构建体及其用途 | |
| AU2013256341B2 (en) | Novel tetraGalNAc and peptide containing conjugates and methods for delivery of oligonucleotides | |
| EP2555777B1 (en) | Novel single chemical entities and methods for delivery of oligonucleotides | |
| ES2690538T3 (es) | Composiciones y métodos para inhibir la expresión génica del virus de la hepatitis B | |
| ES2800065T3 (es) | Agentes de iARN, composiciones y métodos de uso de los mismos para tratar enfermedades asociadas con transtiretina (TTR) | |
| US20180221494A1 (en) | Site-specific delivery of nucleic acids by combining targeting ligands with endosomolytic components | |
| JP7461886B2 (ja) | 標的遺伝子の発現を抑制するためのジチオリン酸結合を含む核酸 | |
| Nielsen et al. | Peptide nucleic acid (PNA) cell penetrating peptide (CPP) conjugates as carriers for cellular delivery of antisense oligomers | |
| ES2936109T3 (es) | Inhibición de TMPRSS6 mediada por interferencia de ARN | |
| JP2011505425A (ja) | オリゴヌクレオチドの送達剤としての糖質コンジュゲート | |
| JP2022506503A (ja) | 修飾二重鎖オリゴヌクレオチド | |
| CA3056179A1 (en) | Products and compositions | |
| JP2023545406A (ja) | ウイルス性疾患を治療するためのヌクレオシド含有ｓｉＲＮＡ | |
| BR112021001181A2 (pt) | ácidos nucleicos para inibir a expressão de tmprss6 e quelantes de ferro | |
| US20230272385A1 (en) | siRNAs WITH VINYLPHOSPHONATE AT THE 5' END OF THE ANTISENSE STRAND | |
| AU2017206154A1 (en) | Site-specific delivery of nucleic acids by combining targeting ligands with endosomolytic components | |
| HK40038989A (en) | Sirnas with vinylphosphonate at the 5' end of the antisense strand | |
| NZ624471A (en) | Modified rnai agents |