RU2697152C2 - Сопряженные антисмысловые соединения и их применение - Google Patents
Сопряженные антисмысловые соединения и их применение Download PDFInfo
- Publication number
- RU2697152C2 RU2697152C2 RU2015151199A RU2015151199A RU2697152C2 RU 2697152 C2 RU2697152 C2 RU 2697152C2 RU 2015151199 A RU2015151199 A RU 2015151199A RU 2015151199 A RU2015151199 A RU 2015151199A RU 2697152 C2 RU2697152 C2 RU 2697152C2
- Authority
- RU
- Russia
- Prior art keywords
- conjugated
- compound
- oligonucleotide
- antisense compound
- conjugate
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 1480
- 230000000692 anti-sense effect Effects 0.000 title claims description 850
- 239000002777 nucleoside Substances 0.000 claims abstract description 510
- 150000003833 nucleoside derivatives Chemical class 0.000 claims abstract description 303
- 238000000034 method Methods 0.000 claims abstract description 180
- 239000012634 fragment Substances 0.000 claims abstract description 140
- 239000002773 nucleotide Substances 0.000 claims abstract description 52
- 125000003729 nucleotide group Chemical group 0.000 claims abstract description 52
- 150000002148 esters Chemical class 0.000 claims abstract description 18
- 208000024172 Cardiovascular disease Diseases 0.000 claims abstract 2
- 208000030159 metabolic disease Diseases 0.000 claims abstract 2
- 108091034117 Oligonucleotide Proteins 0.000 claims description 1030
- 239000000074 antisense oligonucleotide Substances 0.000 claims description 239
- 238000012230 antisense oligonucleotides Methods 0.000 claims description 239
- 125000003835 nucleoside group Chemical group 0.000 claims description 207
- 102000039446 nucleic acids Human genes 0.000 claims description 113
- 108020004707 nucleic acids Proteins 0.000 claims description 113
- 150000007523 nucleic acids Chemical class 0.000 claims description 113
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims description 99
- -1 bicyclic nucleoside Chemical class 0.000 claims description 89
- 150000004713 phosphodiesters Chemical class 0.000 claims description 86
- 235000000346 sugar Nutrition 0.000 claims description 83
- 230000000295 complement effect Effects 0.000 claims description 48
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 30
- 150000001408 amides Chemical class 0.000 claims description 18
- 108020004999 messenger RNA Proteins 0.000 claims description 16
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 14
- 239000004952 Polyamide Substances 0.000 claims description 12
- 229920002647 polyamide Polymers 0.000 claims description 12
- 150000001412 amines Chemical class 0.000 claims description 11
- 239000002679 microRNA Substances 0.000 claims description 9
- 102100034343 Integrase Human genes 0.000 claims description 8
- 101710203526 Integrase Proteins 0.000 claims description 8
- 108091070501 miRNA Proteins 0.000 claims description 7
- YIMATHOGWXZHFX-WCTZXXKLSA-N (2r,3r,4r,5r)-5-(hydroxymethyl)-3-(2-methoxyethoxy)oxolane-2,4-diol Chemical compound COCCO[C@H]1[C@H](O)O[C@H](CO)[C@H]1O YIMATHOGWXZHFX-WCTZXXKLSA-N 0.000 claims description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
- IHLOTZVBEUFDMD-UUOKFMHZSA-N 7-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-2,2-dioxo-1h-imidazo[4,5-c][1,2,6]thiadiazin-4-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(NS(=O)(=O)NC2=O)=C2N=C1 IHLOTZVBEUFDMD-UUOKFMHZSA-N 0.000 claims description 5
- 230000037361 pathway Effects 0.000 claims description 4
- 101000574648 Homo sapiens Retinoid-inducible serine carboxypeptidase Proteins 0.000 claims 1
- 102100025483 Retinoid-inducible serine carboxypeptidase Human genes 0.000 claims 1
- 108091046869 Telomeric non-coding RNA Proteins 0.000 claims 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 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 abstract description 148
- 239000003446 ligand Substances 0.000 abstract description 123
- 230000000694 effects Effects 0.000 abstract description 37
- 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 abstract description 26
- 210000005229 liver cell Anatomy 0.000 abstract description 15
- 239000000126 substance Substances 0.000 abstract description 8
- 239000003814 drug Substances 0.000 abstract description 7
- 238000001727 in vivo Methods 0.000 abstract description 5
- 239000000178 monomer Substances 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 155
- 125000005647 linker group Chemical group 0.000 description 134
- 210000003041 ligament Anatomy 0.000 description 73
- 229910052760 oxygen Inorganic materials 0.000 description 66
- 125000000623 heterocyclic group Chemical group 0.000 description 57
- 241001465754 Metazoa Species 0.000 description 46
- 229910052717 sulfur Inorganic materials 0.000 description 43
- 229910052739 hydrogen Inorganic materials 0.000 description 36
- 230000027455 binding Effects 0.000 description 34
- 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 description 33
- 108090000623 proteins and genes Proteins 0.000 description 30
- 235000018102 proteins Nutrition 0.000 description 26
- 102000004169 proteins and genes Human genes 0.000 description 26
- 229910052799 carbon Inorganic materials 0.000 description 25
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 24
- 229910052736 halogen Inorganic materials 0.000 description 24
- 150000002367 halogens Chemical class 0.000 description 24
- 229920000728 polyester Polymers 0.000 description 24
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Chemical class OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 23
- 210000003494 hepatocyte Anatomy 0.000 description 22
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 22
- 201000010099 disease Diseases 0.000 description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 21
- 150000004676 glycans Chemical class 0.000 description 21
- 229920001282 polysaccharide Polymers 0.000 description 21
- 239000005017 polysaccharide Substances 0.000 description 21
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 20
- 125000002619 bicyclic group Chemical group 0.000 description 20
- 210000004185 liver Anatomy 0.000 description 20
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical class OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 19
- 229960003082 galactose Drugs 0.000 description 19
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 19
- 239000007787 solid Substances 0.000 description 18
- 235000012000 cholesterol Nutrition 0.000 description 17
- 229940107161 cholesterol Drugs 0.000 description 17
- 239000008194 pharmaceutical composition Substances 0.000 description 17
- WQZGKKKJIJFFOK-SVZMEOIVSA-N (+)-Galactose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-SVZMEOIVSA-N 0.000 description 16
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical class OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 16
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 16
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Chemical class OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 16
- 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 description 16
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 15
- 229910052757 nitrogen Inorganic materials 0.000 description 15
- 125000003342 alkenyl group Chemical group 0.000 description 14
- 125000000217 alkyl group Chemical group 0.000 description 14
- 125000000304 alkynyl group Chemical group 0.000 description 14
- WQZGKKKJIJFFOK-UHFFFAOYSA-N alpha-D-glucopyranose Natural products OCC1OC(O)C(O)C(O)C1O WQZGKKKJIJFFOK-UHFFFAOYSA-N 0.000 description 14
- 235000021092 sugar substitutes Nutrition 0.000 description 14
- 239000003765 sweetening agent Substances 0.000 description 14
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 14
- 229930182830 galactose Chemical class 0.000 description 13
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 12
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 12
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 12
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 12
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 12
- 230000007935 neutral effect Effects 0.000 description 12
- 229910052698 phosphorus Inorganic materials 0.000 description 12
- 239000011574 phosphorus Substances 0.000 description 12
- 108090000765 processed proteins & peptides Proteins 0.000 description 12
- WQZGKKKJIJFFOK-DHVFOXMCSA-N L-galactose Chemical compound OC[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O WQZGKKKJIJFFOK-DHVFOXMCSA-N 0.000 description 11
- 230000035508 accumulation Effects 0.000 description 11
- 238000009825 accumulation Methods 0.000 description 11
- WQZGKKKJIJFFOK-FPRJBGLDSA-N beta-D-galactose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-FPRJBGLDSA-N 0.000 description 11
- 150000001720 carbohydrates Chemical class 0.000 description 11
- 235000014633 carbohydrates Nutrition 0.000 description 11
- 210000003734 kidney Anatomy 0.000 description 11
- 229940002612 prodrug Drugs 0.000 description 11
- 239000000651 prodrug Substances 0.000 description 11
- 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 description 10
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 10
- 241000699666 Mus <mouse, genus> Species 0.000 description 10
- RADKZDMFGJYCBB-UHFFFAOYSA-N Pyridoxal Chemical compound CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 description 10
- 229930003427 Vitamin E Natural products 0.000 description 10
- 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 description 10
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 10
- 230000007423 decrease Effects 0.000 description 10
- 239000003085 diluting agent Substances 0.000 description 10
- 239000003937 drug carrier Substances 0.000 description 10
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 10
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 10
- 238000012986 modification Methods 0.000 description 10
- QTNLALDFXILRQO-UHFFFAOYSA-N nonadecane-1,2,3-triol Chemical compound CCCCCCCCCCCCCCCCC(O)C(O)CO QTNLALDFXILRQO-UHFFFAOYSA-N 0.000 description 10
- 125000002811 oleoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])/C([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])[H] 0.000 description 10
- 229920001223 polyethylene glycol Polymers 0.000 description 10
- 230000003612 virological effect Effects 0.000 description 10
- 235000019165 vitamin E Nutrition 0.000 description 10
- 229940046009 vitamin E Drugs 0.000 description 10
- 239000011709 vitamin E Substances 0.000 description 10
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 9
- 229930024421 Adenine Natural products 0.000 description 9
- 229960000643 adenine Drugs 0.000 description 9
- RFSUNEUAIZKAJO-ZXXMMSQZSA-N alpha-D-fructofuranose Chemical compound OC[C@H]1O[C@@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ZXXMMSQZSA-N 0.000 description 9
- 101150006308 botA gene Proteins 0.000 description 9
- 108010056301 Apolipoprotein C-III Proteins 0.000 description 8
- 102000030169 Apolipoprotein C-III Human genes 0.000 description 8
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 8
- 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 description 8
- WQZGKKKJIJFFOK-ZZWDRFIYSA-N L-glucose Chemical compound OC[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@H]1O WQZGKKKJIJFFOK-ZZWDRFIYSA-N 0.000 description 8
- WQZGKKKJIJFFOK-JFNONXLTSA-N L-mannopyranose Chemical class OC[C@@H]1OC(O)[C@H](O)[C@H](O)[C@H]1O WQZGKKKJIJFFOK-JFNONXLTSA-N 0.000 description 8
- SRBFZHDQGSBBOR-OWMBCFKOSA-N L-ribopyranose Chemical class O[C@H]1COC(O)[C@@H](O)[C@H]1O SRBFZHDQGSBBOR-OWMBCFKOSA-N 0.000 description 8
- SMEROWZSTRWXGI-UHFFFAOYSA-N Lithocholsaeure Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 SMEROWZSTRWXGI-UHFFFAOYSA-N 0.000 description 8
- OSTPHDDSCGGHJD-PPRREVKSSA-N N-[(2R,3R,4S,5S)-6-hydroxy-4,5-dimethoxy-2-methyloxan-3-yl]formamide Chemical compound CO[C@@H]1C(O)O[C@H](C)[C@@H](NC=O)[C@@H]1OC OSTPHDDSCGGHJD-PPRREVKSSA-N 0.000 description 8
- 102000000574 RNA-Induced Silencing Complex Human genes 0.000 description 8
- 108010016790 RNA-Induced Silencing Complex Proteins 0.000 description 8
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 8
- AVVWPBAENSWJCB-TVIMKVIFSA-N alpha-D-galactofuranose Chemical compound OC[C@@H](O)[C@@H]1O[C@H](O)[C@H](O)[C@H]1O AVVWPBAENSWJCB-TVIMKVIFSA-N 0.000 description 8
- MSWZFWKMSRAUBD-DVKNGEFBSA-N alpha-D-galactosamine Chemical compound N[C@H]1[C@@H](O)O[C@H](CO)[C@H](O)[C@@H]1O MSWZFWKMSRAUBD-DVKNGEFBSA-N 0.000 description 8
- AVVWPBAENSWJCB-UKFBFLRUSA-N alpha-D-glucofuranose Chemical compound OC[C@@H](O)[C@H]1O[C@H](O)[C@H](O)[C@H]1O AVVWPBAENSWJCB-UKFBFLRUSA-N 0.000 description 8
- WQZGKKKJIJFFOK-DVKNGEFBSA-N alpha-D-glucose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-DVKNGEFBSA-N 0.000 description 8
- AVVWPBAENSWJCB-DVKNGEFBSA-N alpha-D-mannofuranose Chemical compound OC[C@@H](O)[C@H]1O[C@H](O)[C@@H](O)[C@H]1O AVVWPBAENSWJCB-DVKNGEFBSA-N 0.000 description 8
- WQZGKKKJIJFFOK-PQMKYFCFSA-N alpha-D-mannose Chemical compound OC[C@H]1O[C@H](O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-PQMKYFCFSA-N 0.000 description 8
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 8
- AVVWPBAENSWJCB-DGPNFKTASA-N beta-D-galactofuranose Chemical compound OC[C@@H](O)[C@@H]1O[C@@H](O)[C@H](O)[C@H]1O AVVWPBAENSWJCB-DGPNFKTASA-N 0.000 description 8
- AVVWPBAENSWJCB-VFUOTHLCSA-N beta-D-mannofuranose Chemical compound OC[C@@H](O)[C@H]1O[C@@H](O)[C@@H](O)[C@H]1O AVVWPBAENSWJCB-VFUOTHLCSA-N 0.000 description 8
- WQZGKKKJIJFFOK-RWOPYEJCSA-N beta-D-mannose Chemical compound OC[C@H]1O[C@@H](O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-RWOPYEJCSA-N 0.000 description 8
- SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 description 8
- 229960002246 beta-d-glucopyranose Drugs 0.000 description 8
- 150000002256 galaktoses Chemical class 0.000 description 8
- 229960001031 glucose Drugs 0.000 description 8
- 238000000338 in vitro Methods 0.000 description 8
- 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 description 8
- 150000002703 mannose derivatives Chemical class 0.000 description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
- SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 description 8
- KGSURTOFVLAWDC-DGPNFKTASA-N (2R,3R,4R,5R,6R)-6-(hydroxymethyl)-5-sulfanyloxane-2,3,4-triol Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@H]1S KGSURTOFVLAWDC-DGPNFKTASA-N 0.000 description 7
- KNWYARBAEIMVMZ-VFUOTHLCSA-N (2r,3r,4s,5s,6r)-6-(hydroxymethyl)thiane-2,3,4,5-tetrol Chemical compound OC[C@H]1S[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O KNWYARBAEIMVMZ-VFUOTHLCSA-N 0.000 description 7
- 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 description 7
- 101710095342 Apolipoprotein B Proteins 0.000 description 7
- 102100040202 Apolipoprotein B-100 Human genes 0.000 description 7
- 239000004380 Cholic acid Substances 0.000 description 7
- HMFHBZSHGGEWLO-IOVATXLUSA-N D-xylofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@H]1O HMFHBZSHGGEWLO-IOVATXLUSA-N 0.000 description 7
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 7
- HMFHBZSHGGEWLO-CZBDKTQLSA-N L-xylofuranose Chemical compound OC[C@@H]1OC(O)[C@@H](O)[C@@H]1O HMFHBZSHGGEWLO-CZBDKTQLSA-N 0.000 description 7
- FDJKUWYYUZCUJX-VTERZIIISA-N N-glycoloyl-alpha-neuraminic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@@H]1O[C@@](O)(C(O)=O)C[C@H](O)[C@H]1NC(=O)CO FDJKUWYYUZCUJX-VTERZIIISA-N 0.000 description 7
- PRDZVHCOEWJPOB-IVMDWMLBSA-N N-sulfo-D-glucosamine Chemical compound OC[C@H]1OC(O)[C@H](NS(O)(=O)=O)[C@@H](O)[C@@H]1O PRDZVHCOEWJPOB-IVMDWMLBSA-N 0.000 description 7
- PYMYPHUHKUWMLA-MROZADKFSA-N aldehydo-L-ribose Chemical compound OC[C@H](O)[C@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-MROZADKFSA-N 0.000 description 7
- AVVWPBAENSWJCB-QZABAPFNSA-N beta-D-glucofuranose Chemical compound OC[C@@H](O)[C@H]1O[C@@H](O)[C@H](O)[C@H]1O AVVWPBAENSWJCB-QZABAPFNSA-N 0.000 description 7
- MSFSPUZXLOGKHJ-KTZFPWNASA-N beta-muramic acid Chemical compound OC(=O)[C@@H](C)O[C@@H]1[C@@H](N)[C@H](O)O[C@H](CO)[C@H]1O MSFSPUZXLOGKHJ-KTZFPWNASA-N 0.000 description 7
- 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 description 7
- 229960002471 cholic acid Drugs 0.000 description 7
- 235000019416 cholic acid Nutrition 0.000 description 7
- 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 description 7
- 230000004048 modification Effects 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 229940113082 thymine Drugs 0.000 description 7
- 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 description 6
- 108010010234 HDL Lipoproteins Proteins 0.000 description 6
- 108010007622 LDL Lipoproteins Proteins 0.000 description 6
- 102000007330 LDL Lipoproteins Human genes 0.000 description 6
- GMBQZIIUCVWOCD-WWASVFFGSA-N Sarsapogenine Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)CC[C@H](O)C[C@H]4CC[C@H]3[C@@H]2C1)C)[C@@H]1C)[C@]11CC[C@H](C)CO1 GMBQZIIUCVWOCD-WWASVFFGSA-N 0.000 description 6
- 108020004459 Small interfering RNA Proteins 0.000 description 6
- XCNAXXASMDOJER-DMRKSPOLSA-N [(2R)-2-acetyloxy-2-[(2R,3R,4S,6S)-3,4-diacetyloxy-6-ethylsulfanylthian-2-yl]ethyl] acetate Chemical compound CCS[C@@H]1C[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@H](S1)[C@@H](COC(C)=O)OC(C)=O XCNAXXASMDOJER-DMRKSPOLSA-N 0.000 description 6
- GZCGUPFRVQAUEE-UHFFFAOYSA-N alpha-D-galactose Natural products OCC(O)C(O)C(O)C(O)C=O GZCGUPFRVQAUEE-UHFFFAOYSA-N 0.000 description 6
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 229940104302 cytosine Drugs 0.000 description 6
- 229960002442 glucosamine Drugs 0.000 description 6
- 230000001965 increasing effect Effects 0.000 description 6
- 150000002632 lipids Chemical class 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 125000006239 protecting group Chemical group 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 150000003573 thiols Chemical class 0.000 description 6
- 150000003626 triacylglycerols Chemical class 0.000 description 6
- 229940035893 uracil Drugs 0.000 description 6
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical group CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 5
- DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical group C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 description 5
- DNIAPMSPPWPWGF-VKHMYHEASA-N (+)-propylene glycol Chemical group C[C@H](O)CO DNIAPMSPPWPWGF-VKHMYHEASA-N 0.000 description 5
- REPVLJRCJUVQFA-UHFFFAOYSA-N (-)-isopinocampheol Chemical group C1C(O)C(C)C2C(C)(C)C1C2 REPVLJRCJUVQFA-UHFFFAOYSA-N 0.000 description 5
- YXYPSYDCUBSOOB-LUAWRHEFSA-N (Z)-N-hydroxy-11-methyldodec-2-enamide Chemical compound CC(C)CCCCCCC\C=C/C(=O)NO YXYPSYDCUBSOOB-LUAWRHEFSA-N 0.000 description 5
- YPFDHNVEDLHUCE-UHFFFAOYSA-N 1,3-propanediol Chemical group OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 description 5
- 229940035437 1,3-propanediol Drugs 0.000 description 5
- 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 description 5
- TZMSYXZUNZXBOL-UHFFFAOYSA-N 10H-phenoxazine Chemical compound C1=CC=C2NC3=CC=CC=C3OC2=C1 TZMSYXZUNZXBOL-UHFFFAOYSA-N 0.000 description 5
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 5
- 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 description 5
- AOTQGWFNFTVXNQ-UHFFFAOYSA-N 2-(1-adamantyl)acetic acid Chemical compound C1C(C2)CC3CC2CC1(CC(=O)O)C3 AOTQGWFNFTVXNQ-UHFFFAOYSA-N 0.000 description 5
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 5
- 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 description 5
- 102100032187 Androgen receptor Human genes 0.000 description 5
- 102100040214 Apolipoprotein(a) Human genes 0.000 description 5
- 108010012927 Apoprotein(a) Proteins 0.000 description 5
- 108010074051 C-Reactive Protein Proteins 0.000 description 5
- 102100032752 C-reactive protein Human genes 0.000 description 5
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 5
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 5
- 206010007559 Cardiac failure congestive Diseases 0.000 description 5
- 102100023804 Coagulation factor VII Human genes 0.000 description 5
- NBSCHQHZLSJFNQ-QTVWNMPRSA-N D-Mannose-6-phosphate Chemical compound OC1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H](O)[C@@H]1O NBSCHQHZLSJFNQ-QTVWNMPRSA-N 0.000 description 5
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Chemical group CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 5
- 108010023321 Factor VII Proteins 0.000 description 5
- 108010074864 Factor XI Proteins 0.000 description 5
- 108010063919 Glucagon Receptors Proteins 0.000 description 5
- 102100040890 Glucagon receptor Human genes 0.000 description 5
- 108090000079 Glucocorticoid Receptors Proteins 0.000 description 5
- 102100033417 Glucocorticoid receptor Human genes 0.000 description 5
- 241000700721 Hepatitis B virus Species 0.000 description 5
- 235000021314 Palmitic acid Nutrition 0.000 description 5
- 108010071690 Prealbumin Proteins 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 102000009190 Transthyretin Human genes 0.000 description 5
- DWCSNWXARWMZTG-UHFFFAOYSA-N Trigonegenin A Natural products CC1C(C2(CCC3C4(C)CCC(O)C=C4CCC3C2C2)C)C2OC11CCC(C)CO1 DWCSNWXARWMZTG-UHFFFAOYSA-N 0.000 description 5
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 5
- 125000003545 alkoxy group Chemical group 0.000 description 5
- 125000002877 alkyl aryl group Chemical group 0.000 description 5
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 5
- LKDRXBCSQODPBY-ZXXMMSQZSA-N alpha-D-fructopyranose Chemical class OC[C@]1(O)OC[C@@H](O)[C@@H](O)[C@@H]1O LKDRXBCSQODPBY-ZXXMMSQZSA-N 0.000 description 5
- 108010080146 androgen receptors Proteins 0.000 description 5
- 229960003473 androstanolone Drugs 0.000 description 5
- 125000003710 aryl alkyl group Chemical group 0.000 description 5
- 125000003118 aryl group Chemical group 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 229960002685 biotin Drugs 0.000 description 5
- 235000020958 biotin Nutrition 0.000 description 5
- 239000011616 biotin Substances 0.000 description 5
- CKDOCTFBFTVPSN-UHFFFAOYSA-N borneol Chemical group C1CC2(C)C(C)CC1C2(C)C CKDOCTFBFTVPSN-UHFFFAOYSA-N 0.000 description 5
- 229940116229 borneol Drugs 0.000 description 5
- WQLVFSAGQJTQCK-VKROHFNGSA-N diosgenin Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)CC[C@H](O)CC4=CC[C@H]3[C@@H]2C1)C)[C@@H]1C)[C@]11CC[C@@H](C)CO1 WQLVFSAGQJTQCK-VKROHFNGSA-N 0.000 description 5
- WQLVFSAGQJTQCK-UHFFFAOYSA-N diosgenin Natural products CC1C(C2(CCC3C4(C)CCC(O)CC4=CCC3C2C2)C)C2OC11CCC(C)CO1 WQLVFSAGQJTQCK-UHFFFAOYSA-N 0.000 description 5
- 150000002016 disaccharides Chemical class 0.000 description 5
- DTGKSKDOIYIVQL-UHFFFAOYSA-N dl-isoborneol Chemical group C1CC2(C)C(O)CC1C2(C)C DTGKSKDOIYIVQL-UHFFFAOYSA-N 0.000 description 5
- 230000000021 endosomolytic effect Effects 0.000 description 5
- 229940012413 factor vii Drugs 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 230000014509 gene expression Effects 0.000 description 5
- 238000010255 intramuscular injection Methods 0.000 description 5
- 239000007927 intramuscular injection Substances 0.000 description 5
- 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 description 5
- 229940041616 menthol Drugs 0.000 description 5
- 150000002772 monosaccharides Chemical class 0.000 description 5
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 5
- 229920001542 oligosaccharide Polymers 0.000 description 5
- 150000002482 oligosaccharides Chemical class 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- 125000002743 phosphorus functional group Chemical group 0.000 description 5
- 229920000166 polytrimethylene carbonate Chemical group 0.000 description 5
- 229960003581 pyridoxal Drugs 0.000 description 5
- 235000008164 pyridoxal Nutrition 0.000 description 5
- 239000011674 pyridoxal Substances 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 150000004671 saturated fatty acids Chemical group 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 239000008223 sterile water Substances 0.000 description 5
- 150000003431 steroids Chemical class 0.000 description 5
- 238000010254 subcutaneous injection Methods 0.000 description 5
- 239000007929 subcutaneous injection Substances 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- 125000004426 substituted alkynyl group Chemical group 0.000 description 5
- TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 description 5
- 150000004044 tetrasaccharides Chemical class 0.000 description 5
- 125000005309 thioalkoxy group Chemical group 0.000 description 5
- 150000004043 trisaccharides Chemical class 0.000 description 5
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 5
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 5
- 235000019155 vitamin A Nutrition 0.000 description 5
- 239000011719 vitamin A Substances 0.000 description 5
- 229940045997 vitamin a Drugs 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical group O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 4
- LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical compound CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 description 4
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 4
- 102000000844 Cell Surface Receptors Human genes 0.000 description 4
- 108010001857 Cell Surface Receptors Proteins 0.000 description 4
- 108700011259 MicroRNAs Proteins 0.000 description 4
- 108091081021 Sense strand Proteins 0.000 description 4
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 125000002252 acyl group Chemical group 0.000 description 4
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 4
- 238000010253 intravenous injection Methods 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 150000003212 purines Chemical class 0.000 description 4
- 150000003230 pyrimidines Chemical class 0.000 description 4
- 229940104230 thymidine Drugs 0.000 description 4
- 229940088594 vitamin Drugs 0.000 description 4
- 229930003231 vitamin Natural products 0.000 description 4
- 235000013343 vitamin Nutrition 0.000 description 4
- 239000011782 vitamin Substances 0.000 description 4
- 150000003722 vitamin derivatives Chemical class 0.000 description 4
- 101001082110 Acanthamoeba polyphaga mimivirus Eukaryotic translation initiation factor 4E homolog Proteins 0.000 description 3
- 102000007592 Apolipoproteins Human genes 0.000 description 3
- 108010071619 Apolipoproteins Proteins 0.000 description 3
- 102000005427 Asialoglycoprotein Receptor Human genes 0.000 description 3
- 239000004472 Lysine Substances 0.000 description 3
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
- 102000002727 Protein Tyrosine Phosphatase Human genes 0.000 description 3
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 3
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 3
- RTMWIZOXNKJHRE-UHFFFAOYSA-N Tigogenin Natural products CC1COC2CC(C)(OC12)C3CCC4C5CCC6CC(O)CCC6(C)C5CCC34C RTMWIZOXNKJHRE-UHFFFAOYSA-N 0.000 description 3
- 108010006523 asialoglycoprotein receptor Proteins 0.000 description 3
- 238000007385 chemical modification Methods 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 230000021615 conjugation Effects 0.000 description 3
- 239000005549 deoxyribonucleoside Substances 0.000 description 3
- 229940014144 folate Drugs 0.000 description 3
- 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 description 3
- 235000019152 folic acid Nutrition 0.000 description 3
- 239000011724 folic acid Substances 0.000 description 3
- 230000009368 gene silencing by RNA Effects 0.000 description 3
- 238000009396 hybridization Methods 0.000 description 3
- 108020000494 protein-tyrosine phosphatase Proteins 0.000 description 3
- 239000002342 ribonucleoside Substances 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 235000007586 terpenes Nutrition 0.000 description 3
- 150000003527 tetrahydropyrans Chemical group 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 150000003648 triterpenes Chemical class 0.000 description 3
- UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 description 2
- YKBGVTZYEHREMT-KVQBGUIXSA-N 2'-deoxyguanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 YKBGVTZYEHREMT-KVQBGUIXSA-N 0.000 description 2
- VGONTNSXDCQUGY-RRKCRQDMSA-N 2'-deoxyinosine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC2=O)=C2N=C1 VGONTNSXDCQUGY-RRKCRQDMSA-N 0.000 description 2
- MXHRCPNRJAMMIM-SHYZEUOFSA-N 2'-deoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 MXHRCPNRJAMMIM-SHYZEUOFSA-N 0.000 description 2
- CKTSBUTUHBMZGZ-SHYZEUOFSA-N 2'‐deoxycytidine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 CKTSBUTUHBMZGZ-SHYZEUOFSA-N 0.000 description 2
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 2
- MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 2
- UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 description 2
- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 2
- CKTSBUTUHBMZGZ-UHFFFAOYSA-N Deoxycytidine Natural products O=C1N=C(N)C=CN1C1OC(CO)C(O)C1 CKTSBUTUHBMZGZ-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 208000030673 Homozygous familial hypercholesterolemia Diseases 0.000 description 2
- 238000008214 LDL Cholesterol Methods 0.000 description 2
- 108010015847 Non-Receptor Type 1 Protein Tyrosine Phosphatase Proteins 0.000 description 2
- 101710163270 Nuclease Proteins 0.000 description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical class C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 2
- 206010045261 Type IIa hyperlipidaemia Diseases 0.000 description 2
- 102100033001 Tyrosine-protein phosphatase non-receptor type 1 Human genes 0.000 description 2
- 101000647994 Xenopus laevis Signal transducer and activator of transcription 3.1 Proteins 0.000 description 2
- 229960005305 adenosine Drugs 0.000 description 2
- GZCGUPFRVQAUEE-DPYQTVNSSA-N aldehydo-L-galactose Chemical class OC[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C=O GZCGUPFRVQAUEE-DPYQTVNSSA-N 0.000 description 2
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- VGONTNSXDCQUGY-UHFFFAOYSA-N desoxyinosine Natural products C1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 VGONTNSXDCQUGY-UHFFFAOYSA-N 0.000 description 2
- MXHRCPNRJAMMIM-UHFFFAOYSA-N desoxyuridine Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 MXHRCPNRJAMMIM-UHFFFAOYSA-N 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000008103 glucose Chemical class 0.000 description 2
- 229940029575 guanosine Drugs 0.000 description 2
- 230000002163 immunogen Effects 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 238000011282 treatment Methods 0.000 description 2
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 2
- 229940045145 uridine Drugs 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 1
- 101710081722 Antitrypsin Proteins 0.000 description 1
- 101000663378 Caenorhabditis elegans Serpentine receptor class beta-1 Proteins 0.000 description 1
- 101100150273 Caenorhabditis elegans srb-1 gene Proteins 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- AVVWPBAENSWJCB-IVMDWMLBSA-N D-glucofuranose Chemical compound OC[C@@H](O)[C@H]1OC(O)[C@H](O)[C@H]1O AVVWPBAENSWJCB-IVMDWMLBSA-N 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 108010016626 Dipeptides Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 108010023302 HDL Cholesterol Proteins 0.000 description 1
- 241000764238 Isis Species 0.000 description 1
- 150000001102 L-riboses Chemical class 0.000 description 1
- 108010028554 LDL Cholesterol Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010038910 Retinitis Diseases 0.000 description 1
- 102000006382 Ribonucleases Human genes 0.000 description 1
- 108010083644 Ribonucleases Proteins 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000001475 anti-trypsic effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 150000001841 cholesterols Chemical class 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- XCWFZHPEARLXJI-UHFFFAOYSA-N fomivirsen Chemical compound C1C(N2C3=C(C(NC(N)=N3)=O)N=C2)OC(CO)C1OP(O)(=S)OCC1OC(N(C)C(=O)\N=C(\N)C=C)CC1OP(O)(=S)OCC1OC(N2C3=C(C(NC(N)=N3)=O)N=C2)CC1OP(O)(=S)OCC1OC(N2C(NC(=O)C(C)=C2)=O)CC1OP(O)(=S)OCC1OC(N2C(NC(=O)C(C)=C2)=O)CC1OP(O)(=S)OCC1OC(N2C(NC(=O)C(C)=C2)=O)CC1OP(O)(=S)OCC1OC(N2C3=C(C(NC(N)=N3)=O)N=C2)CC1OP(O)(=S)OCC1OC(N2C(N=C(N)C=C2)=O)CC1OP(O)(=S)OCC(C(C1)OP(S)(=O)OCC2C(CC(O2)N2C(N=C(N)C=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C(NC(=O)C(C)=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C(NC(=O)C(C)=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C(N=C(N)C=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C(NC(=O)C(C)=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C(NC(=O)C(C)=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C(N=C(N)C=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C(NC(=O)C(C)=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C(NC(=O)C(C)=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=S)OCC2C(CC(O2)N2C(N=C(N)C=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C3=C(C(NC(N)=N3)=O)N=C2)O)OC1N1C=C(C)C(=O)NC1=O XCWFZHPEARLXJI-UHFFFAOYSA-N 0.000 description 1
- 229960001447 fomivirsen Drugs 0.000 description 1
- DLKYYJFLRUUGHJ-SSJCJZGYSA-A fomivirsen sodium Chemical compound [Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP([O-])(=S)O[C@@H]2[C@H](O[C@H](C2)N2C(NC(=O)C(C)=C2)=O)COP([O-])(=S)O[C@@H]2[C@H](O[C@H](C2)N2C(N=C(N)C=C2)=O)COP([O-])(=S)O[C@@H]2[C@H](O[C@H](C2)N2C(NC(=O)C(C)=C2)=O)COP([O-])(=S)O[C@@H]2[C@H](O[C@H](C2)N2C(NC(=O)C(C)=C2)=O)COP([O-])(=S)O[C@@H]2[C@H](O[C@H](C2)N2C(N=C(N)C=C2)=O)COP([O-])(=S)O[C@@H]2[C@H](O[C@H](C2)N2C(NC(=O)C(C)=C2)=O)COP([O-])(=S)O[C@@H]2[C@H](O[C@H](C2)N2C(NC(=O)C(C)=C2)=O)COP([O-])(=S)O[C@@H]2[C@H](O[C@H](C2)N2C(N=C(N)C=C2)=O)COP([O-])(=S)O[C@@H]2[C@H](O[C@H](C2)N2C(NC(=O)C(C)=C2)=O)COP([O-])(=S)O[C@@H]2[C@H](O[C@H](C2)N2C(N=C(N)C=C2)=O)COP([O-])(=S)O[C@@H]2[C@H](O[C@H](C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP([O-])(=S)O[C@@H]2[C@H](O[C@H](C2)N2C(NC(=O)C(C)=C2)=O)COP([O-])(=S)O[C@@H]2[C@H](O[C@H](C2)N2C(NC(=O)C(C)=C2)=O)COP([O-])(=S)O[C@@H]2[C@H](O[C@H](C2)N2C(NC(=O)C(C)=C2)=O)COP([O-])(=S)O[C@@H]2[C@H](O[C@H](C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP([S-])(=O)O[C@@H]2[C@H](O[C@H](C2)N2C(N=C(N)C=C2)=O)COP([O-])(=S)O[C@@H]2[C@H](O[C@H](C2)N2C3=C(C(NC(N)=N3)=O)N=C2)CO)[C@@H](OP([O-])(=S)OC[C@@H]2[C@H](C[C@@H](O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP([O-])(=S)OC[C@@H]2[C@H](C[C@@H](O2)N2C(N=C(N)C=C2)=O)OP([O-])(=S)OC[C@@H]2[C@H](C[C@@H](O2)N2C3=C(C(NC(N)=N3)=O)N=C2)O)C1 DLKYYJFLRUUGHJ-SSJCJZGYSA-A 0.000 description 1
- OFMXGFHWLZPCFL-SVRPQWSVSA-N friedelin Chemical compound C([C@H]1[C@]2(C)CC[C@@]34C)C(C)(C)CC[C@]1(C)CC[C@]2(C)[C@H]4CC[C@@]1(C)[C@H]3CCC(=O)[C@@H]1C OFMXGFHWLZPCFL-SVRPQWSVSA-N 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 230000030279 gene silencing Effects 0.000 description 1
- 238000012226 gene silencing method Methods 0.000 description 1
- 125000001841 imino group Chemical group [H]N=* 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 229940098262 kynamro Drugs 0.000 description 1
- 210000005228 liver tissue Anatomy 0.000 description 1
- 150000002668 lysine derivatives Chemical class 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 108091060283 mipomersen Proteins 0.000 description 1
- OSGPYAHSKOGBFY-KMHHXCEHSA-A mipomersen sodium Chemical compound [Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].N1([C@H]2C[C@@H]([C@H](O2)COP([O-])(=O)S[C@@H]2[C@H](O[C@H](C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP([O-])(=O)S[C@@H]2[C@H](O[C@H](C2)N2C(NC(=O)C(C)=C2)=O)COP([O-])(=O)S[C@@H]2[C@H](O[C@H](C2)N2C(N=C(N)C(C)=C2)=O)COP([O-])(=O)S[C@@H]2[C@H](O[C@H](C2)N2C(NC(=O)C(C)=C2)=O)COP([O-])(=O)S[C@@H]2[C@H](O[C@H](C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP([O-])(=O)S[C@@H]2[C@H](O[C@H](C2)N2C3=NC=NC(N)=C3N=C2)COP([O-])(=O)S[C@H]2[C@H]([C@@H](O[C@@H]2COP([O-])(=O)S[C@H]2[C@H]([C@@H](O[C@@H]2COP([O-])(=O)S[C@H]2[C@H]([C@@H](O[C@@H]2COP([O-])(=O)S[C@H]2[C@H]([C@@H](O[C@@H]2COP([O-])(=O)S[C@H]2[C@H]([C@@H](O[C@@H]2CO)N2C3=C(C(NC(N)=N3)=O)N=C2)OCCOC)N2C(N=C(N)C(C)=C2)=O)OCCOC)N2C(N=C(N)C(C)=C2)=O)OCCOC)N2C(NC(=O)C(C)=C2)=O)OCCOC)N2C(N=C(N)C(C)=C2)=O)OCCOC)SP([O-])(=O)OC[C@H]2O[C@H](C[C@@H]2SP([O-])(=O)OC[C@H]2O[C@H](C[C@@H]2SP([O-])(=O)OC[C@H]2O[C@H](C[C@@H]2SP([O-])(=O)OC[C@@H]2[C@H]([C@H]([C@@H](O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OCCOC)SP([O-])(=O)OC[C@H]2[C@@H]([C@@H]([C@H](O2)N2C(N=C(N)C(C)=C2)=O)OCCOC)SP([O-])(=O)OC[C@H]2[C@@H]([C@@H]([C@H](O2)N2C3=NC=NC(N)=C3N=C2)OCCOC)SP([O-])(=O)OC[C@H]2[C@@H]([C@@H]([C@H](O2)N2C(N=C(N)C(C)=C2)=O)OCCOC)SP([O-])(=O)OC[C@H]2[C@H](O)[C@@H]([C@H](O2)N2C(N=C(N)C(C)=C2)=O)OCCOC)N2C(N=C(N)C(C)=C2)=O)N2C(NC(=O)C(C)=C2)=O)N2C(NC(=O)C(C)=C2)=O)C=C(C)C(N)=NC1=O OSGPYAHSKOGBFY-KMHHXCEHSA-A 0.000 description 1
- 108091027963 non-coding RNA Proteins 0.000 description 1
- 102000042567 non-coding RNA Human genes 0.000 description 1
- 210000004738 parenchymal cell Anatomy 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/7105—Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/7125—Nucleic acids or oligonucleotides having modified internucleoside linkage, i.e. other than 3'-5' phosphodiesters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/713—Double-stranded nucleic acids or oligonucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
- A61K47/549—Sugars, nucleosides, nucleotides or nucleic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
- C07H21/04—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/111—General methods applicable to biologically active non-coding nucleic acids
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
- C12N15/1137—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against enzymes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y301/00—Hydrolases acting on ester bonds (3.1)
- C12Y301/03—Phosphoric monoester hydrolases (3.1.3)
- C12Y301/03048—Protein-tyrosine-phosphatase (3.1.3.48)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/11—Antisense
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/11—Antisense
- C12N2310/113—Antisense targeting other non-coding nucleic acids, e.g. antagomirs
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/14—Type of nucleic acid interfering nucleic acids [NA]
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/17—Immunomodulatory nucleic acids
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/31—Chemical structure of the backbone
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/31—Chemical structure of the backbone
- C12N2310/315—Phosphorothioates
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/32—Chemical structure of the sugar
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/32—Chemical structure of the sugar
- C12N2310/321—2'-O-R Modification
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/32—Chemical structure of the sugar
- C12N2310/322—2'-R Modification
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/32—Chemical structure of the sugar
- C12N2310/323—Chemical structure of the sugar modified ring structure
- C12N2310/3231—Chemical structure of the sugar modified ring structure having an additional ring, e.g. LNA, ENA
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/33—Chemical structure of the base
- C12N2310/334—Modified C
- C12N2310/3341—5-Methylcytosine
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/34—Spatial arrangement of the modifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/34—Spatial arrangement of the modifications
- C12N2310/341—Gapmers, i.e. of the type ===---===
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/34—Spatial arrangement of the modifications
- C12N2310/346—Spatial arrangement of the modifications having a combination of backbone and sugar modifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/35—Nature of the modification
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/35—Nature of the modification
- C12N2310/351—Conjugate
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/35—Nature of the modification
- C12N2310/351—Conjugate
- C12N2310/3511—Conjugate intercalating or cleaving agent
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/35—Nature of the modification
- C12N2310/351—Conjugate
- C12N2310/3513—Protein; Peptide
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/35—Nature of the modification
- C12N2310/351—Conjugate
- C12N2310/3515—Lipophilic moiety, e.g. cholesterol
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/35—Nature of the modification
- C12N2310/352—Nature of the modification linked to the nucleic acid via a carbon atom
- C12N2310/3525—MOE, methoxyethoxy
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/35—Nature of the modification
- C12N2310/353—Nature of the modification linked to the nucleic acid via an atom other than carbon
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2320/00—Applications; Uses
- C12N2320/30—Special therapeutic applications
- C12N2320/32—Special delivery means, e.g. tissue-specific
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Virology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Steroid Compounds (AREA)
- Liquid Crystal Substances (AREA)
Applications Claiming Priority (15)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361818442P | 2013-05-01 | 2013-05-01 | |
| US61/818,442 | 2013-05-01 | ||
| US201361823826P | 2013-05-15 | 2013-05-15 | |
| US61/823,826 | 2013-05-15 | ||
| US201361843887P | 2013-07-08 | 2013-07-08 | |
| US61/843,887 | 2013-07-08 | ||
| US201361871673P | 2013-08-29 | 2013-08-29 | |
| US61/871,673 | 2013-08-29 | ||
| US201361880790P | 2013-09-20 | 2013-09-20 | |
| US61/880,790 | 2013-09-20 | ||
| US201461976991P | 2014-04-08 | 2014-04-08 | |
| US61/976,991 | 2014-04-08 | ||
| US201461986867P | 2014-04-30 | 2014-04-30 | |
| US61/986,867 | 2014-04-30 | ||
| PCT/US2014/036452 WO2014179620A1 (en) | 2013-05-01 | 2014-05-01 | Conjugated antisense compounds and their use |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2019124314A Division RU2019124314A (ru) | 2013-05-01 | 2014-05-01 | Сопряженные антисмысловые соединения и их применение |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| RU2015151199A RU2015151199A (ru) | 2017-06-05 |
| RU2015151199A3 RU2015151199A3 (cg-RX-API-DMAC7.html) | 2018-03-27 |
| RU2697152C2 true RU2697152C2 (ru) | 2019-08-12 |
Family
ID=51843959
Family Applications (8)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2015151199A RU2697152C2 (ru) | 2013-05-01 | 2014-05-01 | Сопряженные антисмысловые соединения и их применение |
| RU2019124314A RU2019124314A (ru) | 2013-05-01 | 2014-05-01 | Сопряженные антисмысловые соединения и их применение |
| RU2015151204A RU2686080C2 (ru) | 2013-05-01 | 2014-05-01 | Композиции и способы |
| RU2015151203A RU2650510C2 (ru) | 2013-05-01 | 2014-05-01 | Композиции и способы модулирования экспрессии аполипопротеина c-iii |
| RU2018112167A RU2018112167A (ru) | 2013-05-01 | 2014-05-01 | Композиции и способы модулирования экспрессии аполипопротеина c-iii |
| RU2015151202A RU2670614C9 (ru) | 2013-05-01 | 2014-05-01 | Композиции и способы модулирования экспрессии hbv и ttr |
| RU2019110030A RU2019110030A (ru) | 2013-05-01 | 2014-05-01 | Композиции и способы |
| RU2015151200A RU2699985C2 (ru) | 2013-05-01 | 2014-05-01 | Композиции и способы модулирования экспрессии аполипопротеина (а) |
Family Applications After (7)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2019124314A RU2019124314A (ru) | 2013-05-01 | 2014-05-01 | Сопряженные антисмысловые соединения и их применение |
| RU2015151204A RU2686080C2 (ru) | 2013-05-01 | 2014-05-01 | Композиции и способы |
| RU2015151203A RU2650510C2 (ru) | 2013-05-01 | 2014-05-01 | Композиции и способы модулирования экспрессии аполипопротеина c-iii |
| RU2018112167A RU2018112167A (ru) | 2013-05-01 | 2014-05-01 | Композиции и способы модулирования экспрессии аполипопротеина c-iii |
| RU2015151202A RU2670614C9 (ru) | 2013-05-01 | 2014-05-01 | Композиции и способы модулирования экспрессии hbv и ttr |
| RU2019110030A RU2019110030A (ru) | 2013-05-01 | 2014-05-01 | Композиции и способы |
| RU2015151200A RU2699985C2 (ru) | 2013-05-01 | 2014-05-01 | Композиции и способы модулирования экспрессии аполипопротеина (а) |
Country Status (40)
Families Citing this family (508)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2740785C (en) | 2008-10-15 | 2017-06-20 | Isis Pharmaceuticals, Inc. | Modulation of factor 11 expression |
| CN102282155B (zh) | 2008-12-02 | 2017-06-09 | 日本波涛生命科学公司 | 磷原子修饰的核酸的合成方法 |
| BR112012000828A8 (pt) | 2009-07-06 | 2017-10-10 | Ontorii Inc | Novas pró-drogas de ácido nucleico e métodos de uso das mesmas |
| EP2620428B1 (en) | 2010-09-24 | 2019-05-22 | Wave Life Sciences Ltd. | Asymmetric auxiliary group |
| CA3077910A1 (en) | 2010-11-17 | 2012-05-24 | Ionis Pharmaceuticals, Inc. | Modulation of alpha synuclein expression |
| ES2626488T3 (es) | 2011-07-19 | 2017-07-25 | Wave Life Sciences Pte. Ltd. | Procedimientos para la síntesis de ácidos nucleicos funcionalizados |
| EP3640332A1 (en) * | 2011-08-29 | 2020-04-22 | Ionis Pharmaceuticals, Inc. | Oligomer-conjugate complexes and their use |
| EP2831231A1 (en) | 2012-03-30 | 2015-02-04 | Isis Pharmaceuticals, Inc. | Compositions and methods for modulating tau expression for reducing seizure and modifying a neurodegenerative syndrome |
| EP3336189A1 (en) * | 2012-04-20 | 2018-06-20 | Ionis Pharmaceuticals, Inc. | Oligomeric compounds comprising bicyclic nucleotides and uses thereof |
| US9574193B2 (en) | 2012-05-17 | 2017-02-21 | Ionis Pharmaceuticals, Inc. | Methods and compositions for modulating apolipoprotein (a) expression |
| WO2013173789A2 (en) | 2012-05-17 | 2013-11-21 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotide compositions |
| RU2624028C2 (ru) * | 2012-05-24 | 2017-06-30 | Ионис Фармасьютикалз, Инк. | Способы и композиции для модулирования экспрессии аполипопротеина (а) |
| ES2862073T3 (es) | 2012-07-13 | 2021-10-06 | Wave Life Sciences Ltd | Grupo auxiliar asimétrico |
| BR112015000723A2 (pt) | 2012-07-13 | 2017-06-27 | Shin Nippon Biomedical Laboratories Ltd | adjuvante de ácido nucléico quiral |
| ES2940887T3 (es) | 2012-07-13 | 2023-05-12 | Wave Life Sciences Ltd | Método de preparación de oligonucleótidos quirales |
| WO2014076196A1 (en) | 2012-11-15 | 2014-05-22 | Santaris Pharma A/S | Anti apob antisense conjugate compounds |
| JP6580993B2 (ja) * | 2013-01-30 | 2019-09-25 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | Lnaオリゴヌクレオチド糖質コンジュゲート |
| AU2014216137B2 (en) * | 2013-02-14 | 2018-05-10 | Ionis Pharmaceuticals, Inc. | Modulation of Apolipoprotein C-III (ApoCIII) expression in lipoprotein lipase deficient (LPLD) populations |
| CN105378080A (zh) | 2013-05-01 | 2016-03-02 | 莱古路斯治疗法股份有限公司 | 用于调节mir-122的微小rna化合物和方法 |
| HUE050394T2 (hu) | 2013-05-01 | 2020-11-30 | Ionis Pharmaceuticals Inc | Apolipoprotein(a) expressziójának módosítására szolgáló eljárások és készítmények |
| US9506030B2 (en) | 2013-05-01 | 2016-11-29 | Regulus Therapeutics Inc. | Compounds and methods for enhanced cellular uptake |
| HRP20200163T1 (hr) | 2013-06-27 | 2020-08-07 | Roche Innovation Center Copenhagen A/S | Antisens oligomeri i konjugati koji ciljno djeluju na pcsk9 |
| DK3019200T3 (da) * | 2013-07-11 | 2022-06-20 | Alnylam Pharmaceuticals Inc | Oligonukleotid-ligand-konjugater og fremgangsmåde til fremstiling deraf |
| JP6617702B2 (ja) | 2013-07-15 | 2019-12-11 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | Fty720のアザサイクリック拘束アナログ |
| TWI657819B (zh) | 2013-07-19 | 2019-05-01 | 美商Ionis製藥公司 | 用於調節τ蛋白表現之組合物 |
| WO2015042447A1 (en) | 2013-09-20 | 2015-03-26 | Isis Pharmaceuticals, Inc. | Targeted therapeutic nucleosides and their use |
| TWI669393B (zh) * | 2013-10-02 | 2019-08-21 | 艾爾妮蘭製藥公司 | 抑制lect2基因表現之組合物及方法 |
| US11162096B2 (en) | 2013-10-14 | 2021-11-02 | Ionis Pharmaceuticals, Inc | Methods for modulating expression of C9ORF72 antisense transcript |
| WO2015061536A1 (en) * | 2013-10-25 | 2015-04-30 | Regulus Therapeutics Inc. | Microrna compounds and methods for modulating mir-21 activity |
| RU2016122168A (ru) * | 2013-11-14 | 2017-12-19 | Рош Инновейшен Сентер Копенгаген А/С | Антисмысловые конъюгаты, направленные на аполипопротеин b |
| JP6482475B2 (ja) * | 2014-01-07 | 2019-03-13 | レナセラピューティクス株式会社 | アンチセンスオリゴヌクレオチド及び糖誘導体を含む二本鎖オリゴヌクレオチド |
| US10322173B2 (en) | 2014-01-15 | 2019-06-18 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant having anti-allergic activity, and anti-allergic agent |
| JPWO2015108048A1 (ja) | 2014-01-15 | 2017-03-23 | 株式会社新日本科学 | 抗腫瘍作用を有するキラル核酸アジュバンド及び抗腫瘍剤 |
| WO2015108047A1 (ja) | 2014-01-15 | 2015-07-23 | 株式会社新日本科学 | 免疫誘導活性を有するキラル核酸アジュバンド及び免疫誘導活性剤 |
| CN113278617A (zh) | 2014-01-16 | 2021-08-20 | 波涛生命科学有限公司 | 手性设计 |
| EP3105331B1 (en) | 2014-02-11 | 2021-06-23 | Alnylam Pharmaceuticals, Inc. | Ketohexokinase (khk) irna compositions and methods of use thereof |
| RU2702838C2 (ru) | 2014-03-19 | 2019-10-11 | Ионис Фармасьютикалз, Инк. | Композиции для модуляции экспрессии атаксина 2 |
| US10006027B2 (en) | 2014-03-19 | 2018-06-26 | Ionis Pharmaceuticals, Inc. | Methods for modulating Ataxin 2 expression |
| SG11201608109TA (en) | 2014-04-01 | 2016-10-28 | Ionis Pharmaceuticals Inc | Compositions for modulating sod-1 expression |
| EP3137115B1 (en) * | 2014-05-01 | 2020-10-14 | Ionis Pharmaceuticals, Inc. | Method for synthesis of reactive conjugate clusters |
| AU2015252895B2 (en) | 2014-05-01 | 2021-07-15 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating angiopoietin-like 3 expression |
| CN106232804B (zh) | 2014-05-01 | 2019-10-25 | Ionis制药公司 | 用于调节补体因子b表达的组合物和方法 |
| KR20200102553A (ko) | 2014-05-01 | 2020-08-31 | 아이오니스 파마수티컬즈, 인코포레이티드 | 성장 호르몬 수용체 발현을 조절하기 위한 조성물 및 방법 |
| EP4534092A3 (en) | 2014-05-01 | 2025-07-02 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating pkk expression |
| GB201408623D0 (en) * | 2014-05-15 | 2014-07-02 | Santaris Pharma As | Oligomers and oligomer conjugates |
| CA3215908A1 (en) | 2014-05-22 | 2015-11-26 | Alnylam Pharmaceuticals, Inc. | Angiotensinogen (agt) irna compositions and methods of use thereof |
| GB201410693D0 (en) | 2014-06-16 | 2014-07-30 | Univ Southampton | Splicing modulation |
| US9487783B2 (en) | 2014-08-07 | 2016-11-08 | Regulus Therapeutics Inc. | Targeting microRNAs for metabolic disorders |
| US10436802B2 (en) | 2014-09-12 | 2019-10-08 | Biogen Ma Inc. | Methods for treating spinal muscular atrophy |
| CN107109411B (zh) | 2014-10-03 | 2022-07-01 | 冷泉港实验室 | 核基因输出的定向增加 |
| US20170327524A1 (en) | 2014-10-10 | 2017-11-16 | Hoffmann-La Roche, Inc. | Galnac phosphoramidites, nucleic acid conjugates thereof and their use |
| EP3207138B1 (en) * | 2014-10-17 | 2020-07-15 | Alnylam Pharmaceuticals, Inc. | Polynucleotide agents targeting aminolevulinic acid synthase-1 (alas1) and uses thereof |
| JOP20200092A1 (ar) | 2014-11-10 | 2017-06-16 | Alnylam Pharmaceuticals Inc | تركيبات iRNA لفيروس الكبد B (HBV) وطرق لاستخدامها |
| CN107250362B (zh) * | 2014-11-17 | 2021-10-22 | 阿尔尼拉姆医药品有限公司 | 载脂蛋白C3(APOC3)iRNA组合物及其使用方法 |
| US20170369872A1 (en) | 2014-12-18 | 2017-12-28 | Alnylam Pharmaceuticals, Inc. | Reversir tm compounds |
| US10793855B2 (en) | 2015-01-06 | 2020-10-06 | Ionis Pharmaceuticals, Inc. | Compositions for modulating expression of C9ORF72 antisense transcript |
| US10538763B2 (en) | 2015-01-16 | 2020-01-21 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulation of DUX4 |
| CA2976445A1 (en) | 2015-02-13 | 2016-08-18 | Alnylam Pharmaceuticals, Inc. | Patatin-like phospholipase domain containing 3 (pnpla3) irna compositions and methods of use thereof |
| JP6826984B2 (ja) * | 2015-02-15 | 2021-02-10 | アークトゥラス・セラピューティクス・インコーポレイテッドArcturus Therapeutics,Inc. | アシル−アミノ−lnaオリゴヌクレオチドおよび/またはヒドロカルビル−アミノ−lnaオリゴヌクレオチド |
| US11129844B2 (en) | 2015-03-03 | 2021-09-28 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating MECP2 expression |
| EP3277811B1 (en) | 2015-04-03 | 2020-12-23 | University of Massachusetts | Fully stabilized asymmetric sirna |
| EP3277817A4 (en) | 2015-04-03 | 2018-12-05 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulating tmprss6 expression |
| MX2017012610A (es) | 2015-04-08 | 2018-03-16 | Alnylam Pharmaceuticals Inc | Composiciones y metodos para inhibir la expresion del gen lect2. |
| WO2016167780A1 (en) | 2015-04-16 | 2016-10-20 | Ionis Pharmaceuticals, Inc. | Compositions for modulating expression of c9orf72 antisense transcript |
| WO2016172734A1 (en) | 2015-04-24 | 2016-10-27 | California Institute Of Technology | Reactivation of x chromosome genes |
| EP3310918B1 (en) | 2015-06-18 | 2020-08-05 | Alnylam Pharmaceuticals, Inc. | Polynucleotide agents targeting hydroxyacid oxidase (glycolate oxidase, hao1) and methods of use thereof |
| WO2016209862A1 (en) | 2015-06-23 | 2016-12-29 | Alnylam Pharmaceuticals, Inc. | Glucokinase (gck) irna compositions and methods of use thereof |
| EP3313989B1 (en) | 2015-06-29 | 2024-12-25 | Ionis Pharmaceuticals, Inc. | Modified crispr rna and modified single crispr rna and uses thereof |
| AU2016294347B2 (en) | 2015-07-10 | 2022-07-28 | Ionis Pharmaceuticals, Inc. | Modulators of diacyglycerol acyltransferase 2 (DGAT2) |
| WO2017011286A1 (en) | 2015-07-10 | 2017-01-19 | Alnylam Pharmaceuticals, Inc. | Insulin-like growth factor binding protein, acid labile subunit (igfals) and insulin-like growth factor 1 (igf-1) irna compositions and methods of use thereof |
| US20180193471A1 (en) * | 2015-07-16 | 2018-07-12 | Kyowa Hakko Kirin Co., Ltd. | ß2GPI GENE EXPRESSION-SUPPRESSING NUCLEIC ACID CONJUGATE |
| MA43072A (fr) * | 2015-07-22 | 2018-05-30 | Wave Life Sciences Ltd | Compositions d'oligonucléotides et procédés associés |
| EP3331892B1 (en) | 2015-08-06 | 2019-07-03 | F.Hoffmann-La Roche Ag | Processes for the preparation of galnac acid derivatives |
| CN105111119B (zh) * | 2015-08-14 | 2017-04-12 | 天津小新医药科技有限公司 | 一类卤代苯l‑薄荷醇类p2y12受体拮抗剂及其用途 |
| EP3334499A4 (en) | 2015-08-14 | 2019-04-17 | University of Massachusetts | BIOACTIVE CONJUGATES FOR THE RELEASE OF OLIGONUCLEOTIDES |
| CN105111118B (zh) * | 2015-08-14 | 2017-04-12 | 天津小新医药科技有限公司 | L‑薄荷醇类p2y12受体拮抗剂、制备方法及其用途 |
| KR20180043819A (ko) | 2015-08-24 | 2018-04-30 | 로슈 이노베이션 센터 코펜하겐 에이/에스 | Lna-g 방법 |
| CN114525280A (zh) | 2015-09-02 | 2022-05-24 | 阿尔尼拉姆医药品有限公司 | 程序性细胞死亡1配体1(PD-L1)的iRNA组合物及其使用方法 |
| US10995068B2 (en) | 2015-09-24 | 2021-05-04 | The Regents Of The University Of California | Synthetic sphingolipid-like molecules, drugs, methods of their synthesis and methods of treatment |
| RU2018113709A (ru) | 2015-09-24 | 2019-10-30 | Айонис Фармасьютикалз, Инк. | Модуляторы экспрессии kras |
| WO2017053720A1 (en) * | 2015-09-25 | 2017-03-30 | Tarveda Therapeutics, Inc. | RNAi CONJUGATES, PARTICLES AND FORMULATIONS THEREOF |
| EP3353306A4 (en) | 2015-09-25 | 2019-06-05 | Ionis Pharmaceuticals, Inc. | Conjugated antisense compounds and their use |
| WO2017053995A1 (en) * | 2015-09-25 | 2017-03-30 | Ionis Pharmaceuticals, Inc. | Conjugated antisense compounds and their use |
| WO2017053781A1 (en) | 2015-09-25 | 2017-03-30 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating ataxin 3 expression |
| JOP20210043A1 (ar) * | 2015-10-01 | 2017-06-16 | Arrowhead Pharmaceuticals Inc | تراكيب وأساليب لتثبيط تعبير جيني للـ lpa |
| CN108136041B (zh) | 2015-10-02 | 2022-12-30 | 罗氏创新中心哥本哈根有限公司 | 寡核苷酸缀合方法 |
| BR122020023854B1 (pt) | 2015-10-08 | 2022-11-29 | Ionis Pharmaceuticals, Inc | Composto compreendendo oligonucleotídeo modificado e seu uso, uso do oligonucleotídeo modificado, composição e seu uso |
| KR102422625B1 (ko) | 2015-10-09 | 2022-07-20 | 유니버시티 오브 사우스앰톤 | 유전자 발현의 조절 및 탈조절된 단백질 발현의 스크리닝 |
| EP3394258B1 (en) | 2015-10-22 | 2021-09-22 | Roche Innovation Center Copenhagen A/S | In vitro toxicity screening assay |
| WO2017068087A1 (en) | 2015-10-22 | 2017-04-27 | Roche Innovation Center Copenhagen A/S | Oligonucleotide detection method |
| EP3370708A4 (en) | 2015-11-06 | 2019-06-26 | Ionis Pharmaceuticals, Inc. | MODULATION OF APOLIPOPROTEIN (A) EXPRESSION |
| FI4119569T3 (fi) | 2015-11-06 | 2024-08-30 | Ionis Pharmaceuticals Inc | Konjugoituja antisense-yhdisteitä käytettäviksi hoidossa |
| JP6649482B2 (ja) * | 2015-11-16 | 2020-02-19 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | GalNAcクラスターホスホロアミダイト |
| WO2017096395A1 (en) | 2015-12-04 | 2017-06-08 | Ionis Pharmaceuticals, Inc. | Methods of treating breast cancer |
| US11096956B2 (en) | 2015-12-14 | 2021-08-24 | Stoke Therapeutics, Inc. | Antisense oligomers and uses thereof |
| KR102604132B1 (ko) | 2015-12-14 | 2023-11-17 | 콜드스프링하버러보러토리 | 상염색체 우성 정신 지체 5 및 드라베 증후군의 치료를 위한 안티센스 올리고머 |
| AU2016381174A1 (en) | 2015-12-31 | 2018-05-31 | Ionis Pharmaceuticals, Inc. | Methods for reducing Ataxin-2 expression |
| AU2017205462A1 (en) | 2016-01-05 | 2018-06-07 | Ionis Pharmaceuticals, Inc. | Methods for reducing LRRK2 expression |
| AU2017207341A1 (en) | 2016-01-12 | 2018-08-02 | Interleukin Genetics, Inc. | Methods for predicting response to treatment |
| CN116064544A (zh) | 2016-01-26 | 2023-05-05 | 日产化学株式会社 | 单链寡核苷酸 |
| ES2858090T3 (es) | 2016-01-29 | 2021-09-29 | Kyowa Kirin Co Ltd | Complejo de ácidos nucleicos |
| US10478503B2 (en) * | 2016-01-31 | 2019-11-19 | University Of Massachusetts | Branched oligonucleotides |
| US10246709B2 (en) | 2016-03-07 | 2019-04-02 | Arrowhead Pharmaceuticals, Inc. | Targeting ligands for therapeutic compounds |
| AU2017229778A1 (en) | 2016-03-09 | 2018-08-16 | Ionis Pharmaceuticals, Inc. | Methods and compositions for inhibiting PMP22 expression |
| MX2018010830A (es) | 2016-03-14 | 2019-02-07 | Hoffmann La Roche | Oligonucleotidos para reducir la expresion de pd-l1. |
| AU2017234678A1 (en) | 2016-03-16 | 2018-08-16 | Ionis Pharmaceuticals, Inc. | Methods of modulating KEAP1 |
| WO2017161168A1 (en) | 2016-03-16 | 2017-09-21 | Ionis Pharmaceuticals, Inc. | Modulation of dyrk1b expression |
| EP3228326A1 (en) * | 2016-04-05 | 2017-10-11 | Silence Therapeutics GmbH | Nucleic acid linked to a trivalent glycoconjugate |
| MA45478A (fr) * | 2016-04-11 | 2019-02-20 | Arbutus Biopharma Corp | Compositions de conjugués d'acides nucléiques ciblés |
| US20190142856A1 (en) | 2016-04-13 | 2019-05-16 | Ionis Pharmaceuticals, Inc. | Methods for reducing c9orf72 expression |
| JP6985288B2 (ja) | 2016-04-14 | 2021-12-22 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | トリチル−モノ−GalNAc化合物とその利用 |
| MA45295A (fr) | 2016-04-19 | 2019-02-27 | Alnylam Pharmaceuticals Inc | Composition d'arni de protéine de liaison de lipoprotéines haute densité (hdlbp/vigiline) et procédés pour les utiliser |
| US11390867B2 (en) | 2016-04-29 | 2022-07-19 | Nanyang Technological University | G-quadruplex-containing antisense oligonucleotides |
| MA45270A (fr) | 2016-05-04 | 2017-11-09 | Wave Life Sciences Ltd | Compositions d'oligonucléotides et procédés associés |
| KR102608220B1 (ko) | 2016-05-06 | 2023-11-29 | 아이오니스 파마수티컬즈, 인코포레이티드 | Glp-1 수용체 리간드 모이어티 컨쥬게이트된 올리고뉴클레오티드 및 이의 용도 |
| JP7012033B2 (ja) | 2016-06-17 | 2022-02-10 | エフ.ホフマン-ラ ロシュ アーゲー | インビトロ腎毒性スクリーニングアッセイ |
| MA45496A (fr) | 2016-06-17 | 2019-04-24 | Hoffmann La Roche | Molécules d'acide nucléique pour la réduction de l'arnm de padd5 ou pad7 pour le traitement d'une infection par l'hépatite b |
| US11105794B2 (en) | 2016-06-17 | 2021-08-31 | Hoffmann-La Roche Inc. | In vitro nephrotoxicity screening assay |
| CA3023514A1 (en) | 2016-06-17 | 2017-12-21 | Ionis Pharmaceuticals, Inc. | Modulation of gys1 expression |
| WO2017220751A1 (en) | 2016-06-22 | 2017-12-28 | Proqr Therapeutics Ii B.V. | Single-stranded rna-editing oligonucleotides |
| ES2952757T3 (es) * | 2016-06-30 | 2023-11-03 | Kyowa Kirin Co Ltd | Complejo de ácidos nucleicos |
| WO2018013525A1 (en) | 2016-07-11 | 2018-01-18 | Translate Bio Ma, Inc. | Nucleic acid conjugates and uses thereof |
| EP3484908A4 (en) | 2016-07-15 | 2020-04-08 | AM Chemicals Llc | NON-NUCLEOSIDIC SOLID CARRIERS AND PHOSPHORAMIDITE BUILDING BLOCKS FOR OLIGONUCLEOTID SYNTHESIS |
| MX2019000619A (es) | 2016-07-15 | 2019-08-01 | Ionis Pharmaceuticals Inc | Compuestos y metodos para la modulacion de smn2. |
| US11753638B2 (en) | 2016-08-12 | 2023-09-12 | University Of Massachusetts | Conjugated oligonucleotides |
| CA3033867A1 (en) * | 2016-08-17 | 2018-02-22 | Solstice Biologics, Ltd. | Polynucleotide constructs |
| DK3507366T3 (da) | 2016-09-01 | 2020-11-02 | Proqr Therapeutics Ii Bv | Kemisk modificeret, enkeltstrengede rna-modificerende oligonukleotider |
| CN116942841A (zh) | 2016-09-02 | 2023-10-27 | 箭头药业股份有限公司 | 靶向配体 |
| WO2018057837A1 (en) * | 2016-09-23 | 2018-03-29 | Ionis Pharmaceuticals, Inc. | Gene therapy and targeted delivery of conjugated compounds |
| JOP20190065A1 (ar) | 2016-09-29 | 2019-03-28 | Ionis Pharmaceuticals Inc | مركبات وطرق لتقليل التعبير عن tau |
| WO2018067900A1 (en) * | 2016-10-06 | 2018-04-12 | Ionis Pharmaceuticals, Inc. | Method of conjugating oligomeric compounds |
| WO2018081661A1 (en) | 2016-10-27 | 2018-05-03 | California Institute Of Technology | Hdac inhibitor compositions for reactivation of the x chromosome |
| JOP20190104A1 (ar) | 2016-11-10 | 2019-05-07 | Ionis Pharmaceuticals Inc | مركبات وطرق لتقليل التعبير عن atxn3 |
| WO2018089914A1 (en) * | 2016-11-11 | 2018-05-17 | Alios Biopharma, Inc. | Oligonucleotide targeting strategy for hbv cccdna |
| TWI788312B (zh) | 2016-11-23 | 2023-01-01 | 美商阿尼拉製藥公司 | 絲胺酸蛋白酶抑制因子A1 iRNA組成物及其使用方法 |
| EP3548005A4 (en) | 2016-11-29 | 2020-06-17 | Puretech Health LLC | Exosomes for delivery of therapeutic agents |
| EP3548620A4 (en) | 2016-12-02 | 2020-07-22 | Cold Spring Harbor Laboratory | MODULATION OF THE EXPRESSION OF LNC05 |
| US11033571B2 (en) * | 2016-12-13 | 2021-06-15 | Am Sciences Inc | Pharmaceutical composition for preventing or treating hepatitis B |
| TWI865997B (zh) | 2016-12-16 | 2024-12-11 | 美商阿尼拉製藥公司 | 使用甲狀腺素運載蛋白(TTR)iRNA組成物於治療或預防TTR相關疾病之方法 |
| CN108239644B (zh) * | 2016-12-23 | 2021-05-28 | 苏州瑞博生物技术股份有限公司 | 一种小干扰核酸和药物组合物及其用途 |
| US10337070B2 (en) | 2017-01-12 | 2019-07-02 | Cardioforecast Ltd. | Methods and kits for treating cardiovascular disease |
| EP3568479A1 (en) | 2017-01-13 | 2019-11-20 | Roche Innovation Center Copenhagen A/S | Antisense oligonucleotides for modulating nfkb1 expression |
| US20190338286A1 (en) | 2017-01-13 | 2019-11-07 | Roche Innovation Center Copenhagen A/S | Antisense oligonucleotides for modulating rel expression |
| WO2018130581A1 (en) | 2017-01-13 | 2018-07-19 | Roche Innovation Center Copenhagen A/S | Antisense oligonucleotides for modulating rela expression |
| US20190345495A1 (en) | 2017-01-13 | 2019-11-14 | Roche Innovation Center Copenhagen A/S | Antisense oligonucleotides for modulating nfkb2 expression |
| EP3568481A1 (en) | 2017-01-13 | 2019-11-20 | Roche Innovation Center Copenhagen A/S | Antisense oligonucleotides for modulating relb expression |
| MX2019009305A (es) | 2017-02-06 | 2019-09-19 | Nissan Chemical Corp | Oligonucleotido de cadena simple. |
| WO2018165564A1 (en) * | 2017-03-09 | 2018-09-13 | Ionis Pharmaceuticals, Inc. | Morpholino modified oligomeric compounds |
| EP3594346A4 (en) | 2017-03-10 | 2020-12-16 | National Center For Child Health And Development | ANTISENS OLIGONUCLEOTIDE AND COMPOSITION FOR THE PREVENTION OR TREATMENT OF TYPE IA GLYCOGEN STORAGE DISEASE |
| JOP20190215A1 (ar) | 2017-03-24 | 2019-09-19 | Ionis Pharmaceuticals Inc | مُعدّلات التعبير الوراثي عن pcsk9 |
| EP3385272A1 (en) | 2017-04-05 | 2018-10-10 | Silence Therapeutics GmbH | Further novel oligonucleotide-ligand conjugates |
| US11015198B2 (en) | 2017-04-05 | 2021-05-25 | Silence Therapeutics Gmbh | Products and compositions |
| EP3950004A1 (en) | 2017-04-11 | 2022-02-09 | Arbutus Biopharma Corporation | Targeted compositions |
| CN118384268A (zh) | 2017-04-18 | 2024-07-26 | 阿尔尼拉姆医药品有限公司 | 具有乙肝病毒(hbv)感染的受试者的治疗方法 |
| WO2018215049A1 (en) | 2017-05-23 | 2018-11-29 | F. Hoffmann-La Roche Ag | Process for galnac oligonucleotide conjugates |
| JP6952366B2 (ja) * | 2017-05-26 | 2021-10-20 | 国立研究開発法人国立循環器病研究センター | Pcsk9を標的としたアンチセンス核酸 |
| JP2020522510A (ja) | 2017-06-02 | 2020-07-30 | ウェイブ ライフ サイエンシズ リミテッドWave Life Sciences Ltd. | オリゴヌクレオチド組成物及びその使用方法 |
| JP2020522265A (ja) * | 2017-06-02 | 2020-07-30 | ウェイブ ライフ サイエンシズ リミテッドWave Life Sciences Ltd. | オリゴヌクレオチド組成物及びその使用方法 |
| US11401519B2 (en) | 2017-06-07 | 2022-08-02 | University Of Massachusetts | Anti-ADAM33 oligonucleotides and related methods |
| EP3642341A4 (en) | 2017-06-23 | 2021-06-16 | University Of Massachusetts | TWO-DAY SELF-RELEASING SIRNA AND RELATED PROCEDURES |
| US11597744B2 (en) | 2017-06-30 | 2023-03-07 | Sirius Therapeutics, Inc. | Chiral phosphoramidite auxiliaries and methods of their use |
| EP3652317A1 (en) | 2017-07-13 | 2020-05-20 | Alnylam Pharmaceuticals, Inc. | Lactate dehydrogenase a (ldha) irna compositions and methods of use thereof |
| US11555188B2 (en) | 2017-07-26 | 2023-01-17 | Nissan Chemical Corporation | Single-stranded oligonucleotide |
| TW201909925A (zh) * | 2017-08-02 | 2019-03-16 | 日商協和醱酵麒麟有限公司 | 核酸複合體 |
| WO2019027009A1 (ja) * | 2017-08-02 | 2019-02-07 | 協和発酵キリン株式会社 | 核酸複合体 |
| WO2019030313A2 (en) | 2017-08-11 | 2019-02-14 | Roche Innovation Center Copenhagen A/S | OLIGONUCLEOTIDES FOR MODULATION OF UBE3C EXPRESSION |
| CA3073213A1 (en) | 2017-08-17 | 2019-02-21 | Alnylam Pharmaceuticals, Inc. | Tunable reversir tm compounds |
| AU2018318231A1 (en) | 2017-08-18 | 2020-02-13 | Ionis Pharmaceuticals, Inc. | Modulation of the notch signaling pathway for treatment of respiratory disorders |
| WO2019038228A1 (en) | 2017-08-22 | 2019-02-28 | Roche Innovation Center Copenhagen A/S | OLIGONUCLEOTIDES FOR MODULATION OF TOM1 EXPRESSION |
| CN111278991B (zh) | 2017-08-25 | 2022-04-01 | 斯托克制药公司 | 用于治疗病况和疾病的反义寡聚体 |
| WO2019051173A1 (en) | 2017-09-08 | 2019-03-14 | Ionis Pharmaceuticals, Inc. | MODULATORS OF SMAD7 EXPRESSION |
| KR20200100601A (ko) * | 2017-09-14 | 2020-08-26 | 얀센 바이오파마, 인크. | GalNAc 유도체 |
| WO2019067875A1 (en) | 2017-09-29 | 2019-04-04 | Regeneron Pharmaceuticals, Inc. | NON-HUMAN ANIMALS COMPRISING A HUMANIZED TTR LOCUS AND METHODS OF USE |
| IL311170A (en) | 2017-09-29 | 2024-04-01 | Intellia Therapeutics Inc | Compositions and methods for ttr gene editing and treating attr amyloidosis |
| JP2021502059A (ja) | 2017-10-13 | 2021-01-28 | ロシュ イノベーション センター コペンハーゲン エーエス | 部分的に立体定義されたオリゴヌクレオチドのサブライブラリーを使用することによる、アンチセンスオリゴヌクレオチドの、改良された立体定義されたホスホロチオエートオリゴヌクレオチド変異体を同定するための方法 |
| RU2766360C2 (ru) | 2017-10-16 | 2022-03-15 | Ф. Хоффманн-Ля Рош Аг | МОЛЕКУЛЫ НУКЛЕИНОВЫХ КИСЛОТ ДЛЯ УМЕНЬШЕНИЯ УРОВНЯ мРНК PAPD5 ИЛИ PAPD7 ДЛЯ ЛЕЧЕНИЯ ИНФЕКЦИОННОГО ГЕПАТИТА В |
| EP3704252A1 (en) | 2017-11-01 | 2020-09-09 | Alnylam Pharmaceuticals, Inc. | Complement component c3 irna compositions and methods of use thereof |
| TWI809004B (zh) | 2017-11-09 | 2023-07-21 | 美商Ionis製藥公司 | 用於降低snca表現之化合物及方法 |
| EP3710587A1 (en) | 2017-11-16 | 2020-09-23 | Alnylam Pharmaceuticals, Inc. | Kisspeptin 1 (kiss1) irna compositions and methods of use thereof |
| WO2019100039A1 (en) | 2017-11-20 | 2019-05-23 | Alnylam Pharmaceuticals, Inc. | Serum amyloid p component (apcs) irna compositions and methods of use thereof |
| CN110997917B (zh) * | 2017-12-01 | 2024-04-09 | 苏州瑞博生物技术股份有限公司 | 一种核酸、含有该核酸的组合物与缀合物及制备方法和用途 |
| CN118291457A (zh) | 2017-12-01 | 2024-07-05 | 苏州瑞博生物技术股份有限公司 | 一种核酸、含有该核酸的组合物与缀合物及制备方法和用途 |
| CN110945131B (zh) * | 2017-12-01 | 2024-05-28 | 苏州瑞博生物技术股份有限公司 | 一种核酸、含有该核酸的组合物与缀合物及制备方法和用途 |
| EP3718572B1 (en) | 2017-12-01 | 2024-07-31 | Suzhou Ribo Life Science Co., Ltd. | Nucleic acid, composition and conjugate containing nucleic acid, preparation method and use |
| EP4455285A3 (en) | 2017-12-01 | 2025-02-26 | Suzhou Ribo Life Science Co., Ltd. | Nucleic acid, composition and conjugate comprising the same, and preparation method and use thereof |
| CN111050807B (zh) * | 2017-12-01 | 2024-05-28 | 苏州瑞博生物技术股份有限公司 | 一种核酸、含有该核酸的组合物与缀合物及制备方法和用途 |
| AU2018374219C1 (en) | 2017-12-01 | 2023-05-11 | Suzhou Ribo Life Science Co., Ltd. | Double-stranded oligonucleotide, composition and conjugate comprising double-stranded oligonucleotide, preparation method therefor and use thereof |
| CN111344408A (zh) | 2017-12-11 | 2020-06-26 | 哥本哈根罗氏创新中心 | 用于调控fndc3b表达的寡核苷酸 |
| WO2019115417A2 (en) | 2017-12-12 | 2019-06-20 | Roche Innovation Center Copenhagen A/S | Oligonucleotides for modulating rb1 expression |
| EP4257691A3 (en) | 2017-12-14 | 2024-01-10 | Ionis Pharmaceuticals, Inc. | Conjugated antisense compounds and their use |
| EA202091520A1 (ru) | 2017-12-18 | 2020-10-05 | Элнилэм Фармасьютикалз, Инк. | Композиции на основе irna против бокса-1 высокомобильной группы (hmgb1) и способы их применения |
| US20200378970A1 (en) | 2017-12-21 | 2020-12-03 | Hoffmann-La Roche Inc. | Companion diagnostic for htra1 rna antagonists |
| WO2019126641A2 (en) | 2017-12-21 | 2019-06-27 | Ionis Pharmaceuticals, Inc. | Modulation of frataxin expression |
| JP2021508327A (ja) | 2017-12-22 | 2021-03-04 | ロシュ イノベーション センター コペンハーゲン エーエス | 新規のチオホスホラミダイト |
| EP3728591B1 (en) | 2017-12-22 | 2025-07-23 | Roche Innovation Center Copenhagen A/S | Gapmer oligonucleotides comprising a phosphorodithioate internucleoside linkage |
| KR20200104345A (ko) | 2017-12-22 | 2020-09-03 | 로슈 이노베이션 센터 코펜하겐 에이/에스 | 포스포로디티오에이트 뉴클레오시드간 연결을 포함하는 올리고뉴클레오티드 |
| EP3677588A4 (en) * | 2017-12-26 | 2020-11-25 | Guangzhou Ribobio Co., Ltd. | MODIFIED OLIGONUCLEOTIDES AND COMPOUND WHICH CAN BE USED FOR THE SYNTHESIS OF THEM |
| CN109957566B (zh) * | 2017-12-26 | 2023-08-25 | 广州市锐博生物科技有限公司 | 修饰的寡核苷酸和可用于合成修饰的寡核苷酸的化合物 |
| KR102617947B1 (ko) | 2017-12-29 | 2023-12-27 | 쑤저우 리보 라이프 사이언스 컴퍼니, 리미티드 | 접합체와 제조 및 그 용도 |
| WO2019140102A1 (en) | 2018-01-10 | 2019-07-18 | Translate Bio Ma, Inc. | Compositions and methods for facilitating delivery of synthetic nucleic acids to cells |
| US20210095274A1 (en) | 2018-01-10 | 2021-04-01 | Roche Innovation Center Copenhagen A/S | Oligonucleotides for modulating pias4 expression |
| MX2020007439A (es) | 2018-01-12 | 2020-09-14 | Bristol Myers Squibb Co | Oligonucleotidos antisentido que actuan sobre alfa-sinucleina y usos de estos. |
| JP2021510295A (ja) | 2018-01-12 | 2021-04-22 | ロシュ イノベーション センター コペンハーゲン エーエス | Gsk3b発現を調節するためのオリゴヌクレオチド |
| KR20200109338A (ko) | 2018-01-12 | 2020-09-22 | 로슈 이노베이션 센터 코펜하겐 에이/에스 | 알파-시누클레인 안티센스 올리고뉴클레오티드 및 이의 용도 |
| US11447775B2 (en) | 2018-01-12 | 2022-09-20 | Bristol-Myers Squibb Company | Antisense oligonucleotides targeting alpha-synuclein and uses thereof |
| BR112020014425A2 (pt) | 2018-01-15 | 2020-12-29 | Ionis Pharmaceuticals, Inc. | Moduladores de expressão de dnm2 |
| JP2021510525A (ja) | 2018-01-17 | 2021-04-30 | ロシュ イノベーション センター コペンハーゲン エーエス | Erc1発現を調節するためのオリゴヌクレオチド |
| EP3740573A1 (en) | 2018-01-18 | 2020-11-25 | Roche Innovation Center Copenhagen A/S | Antisense oligonucleotides targeting srebp1 |
| WO2019145386A1 (en) | 2018-01-26 | 2019-08-01 | Roche Innovation Center Copenhagen A/S | Oligonucleotides for modulating csnk1d expression |
| WO2019157531A1 (en) | 2018-02-12 | 2019-08-15 | Ionis Pharmaceuticals, Inc. | Modified compounds and uses thereof |
| WO2019161105A1 (en) | 2018-02-14 | 2019-08-22 | Deep Genomics Incorporated | Oligonucleotide therapy for wilson disease |
| CN112020559A (zh) | 2018-02-21 | 2020-12-01 | 百时美施贵宝公司 | Camk2d反义寡核苷酸及其用途 |
| EP3759127A4 (en) | 2018-03-02 | 2022-03-30 | Ionis Pharmaceuticals, Inc. | COMPOUNDS AND METHODS FOR MODULATING AMYLOID BETA PRECURSOR PROTEIN |
| TWI840345B (zh) | 2018-03-02 | 2024-05-01 | 美商Ionis製藥公司 | Irf4表現之調節劑 |
| KR20210130854A (ko) | 2018-03-09 | 2021-11-01 | 다이이찌 산쿄 가부시키가이샤 | 당원병 Ia형 치료약 |
| WO2019183440A1 (en) | 2018-03-22 | 2019-09-26 | Ionis Pharmaceuticals, Inc. | Methods for modulating fmr1 expression |
| BR112020020220A8 (pt) | 2018-04-05 | 2021-02-17 | Centre Leon Berard | uso de inibidores da fubp1 para o tratamento de infecção pelo vírus da hepatite b |
| MX2020010721A (es) | 2018-04-11 | 2020-11-06 | Ionis Pharmaceuticals Inc | Moduladores de la expresion de ezh2. |
| EP3788065B1 (en) | 2018-04-30 | 2025-08-27 | The Children's Hospital Of Philadelphia | Improving anemias by combining agents |
| US12060558B2 (en) | 2018-05-04 | 2024-08-13 | Stoke Therapeutics, Inc. | Methods and compositions for treatment of cholesteryl ester storage disease |
| EP3790990A1 (en) | 2018-05-07 | 2021-03-17 | Roche Innovation Center Copenhagen A/S | Quality control of lna oligonucleotide therapeutics using massively parallel sequencing |
| WO2019217369A1 (en) | 2018-05-08 | 2019-11-14 | Regulus Therapeutics Inc. | Galnac conjugated modified oligonucleotide as mir-122 inhibitor having hcv antiviral activity with reduced hyperbilirubinemia side-effect |
| CR20200605A (es) * | 2018-05-09 | 2021-01-29 | Ionis Pharmaceuticals Inc | Compuestos y métodos para la reducción de la expresión de fxi |
| CR20200604A (es) | 2018-05-09 | 2021-02-09 | Ionis Pharmaceuticals Inc | Compuestos y métodos para reducir de la expresión de atxn3 |
| US12391942B2 (en) | 2018-05-11 | 2025-08-19 | Wave Life Sciences Ltd. | Oligonucleotide compositions and methods of use thereof |
| TWI851574B (zh) | 2018-05-14 | 2024-08-11 | 美商阿尼拉製藥公司 | 血管收縮素原(AGT)iRNA組成物及其使用方法 |
| GB201808146D0 (en) | 2018-05-18 | 2018-07-11 | Proqr Therapeutics Ii Bv | Stereospecific Linkages in RNA Editing Oligonucleotides |
| AU2019287635A1 (en) | 2018-06-14 | 2020-12-17 | Ionis Pharmaceuticals, Inc. | Compounds and methods for increasing STMN2 expression |
| TWI833770B (zh) | 2018-06-27 | 2024-03-01 | 美商Ionis製藥公司 | 用於減少 lrrk2 表現之化合物及方法 |
| CA3103054A1 (en) | 2018-07-03 | 2020-01-09 | F. Hoffmann-La Roche Ag | Oligonucleotides for modulating tau expression |
| WO2020007826A1 (en) | 2018-07-05 | 2020-01-09 | Roche Innovation Center Copenhagen A/S | Antisense oligonucleotides targeting mbtps1 |
| WO2020011744A2 (en) | 2018-07-11 | 2020-01-16 | Roche Innovation Center Copenhagen A/S | Antisense oligonucleotides targeting cers5 |
| WO2020011745A2 (en) | 2018-07-11 | 2020-01-16 | Roche Innovation Center Copenhagen A/S | Antisense oligonucleotides targeting cers6 |
| JP7616987B2 (ja) | 2018-07-13 | 2025-01-17 | エフ. ホフマン-ラ ロシュ アーゲー | Rtel1発現の調節用のオリゴヌクレオチド |
| WO2020018558A1 (en) | 2018-07-17 | 2020-01-23 | Aronora, Inc. | Methods for safely reducing thrombopoietin |
| MX2021000922A (es) | 2018-07-25 | 2021-03-31 | Ionis Pharmaceuticals Inc | Compuestos y metodos para reducir la expresion de la atxn2. |
| EP4122943B1 (en) | 2018-07-31 | 2024-05-29 | Roche Innovation Center Copenhagen A/S | Oligonucleotides comprising a phosphorotrithioate internucleoside linkage |
| CN119912512A (zh) | 2018-07-31 | 2025-05-02 | 罗氏创新中心哥本哈根有限公司 | 包含三硫代磷酸酯核苷间键的寡核苷酸 |
| WO2020033748A1 (en) | 2018-08-08 | 2020-02-13 | Arcturus Therapeutics, Inc. | Compositions and agents against nonalcoholic steatohepatitis |
| BR112021002440A2 (pt) | 2018-08-10 | 2021-05-04 | University Of Massachusetts | oligonucleotídeos modificados visando snps |
| JP7625512B2 (ja) | 2018-08-13 | 2025-02-03 | 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 | B型肝炎ウイルス(HBV)dsRNA物質組成物およびその使用方法 |
| WO2020038377A1 (zh) | 2018-08-21 | 2020-02-27 | 苏州瑞博生物技术有限公司 | 一种核酸、含有该核酸的药物组合物和缀合物及其用途 |
| US11279930B2 (en) | 2018-08-23 | 2022-03-22 | University Of Massachusetts | O-methyl rich fully stabilized oligonucleotides |
| US20220160870A1 (en) | 2018-08-28 | 2022-05-26 | Roche Innovation Center Copenhagen A/S | Neoantigen engineering using splice modulating compounds |
| CA3105385A1 (en) | 2018-09-18 | 2020-03-26 | Alnylam Pharmaceuticals, Inc. | Ketohexokinase (khk) irna compositions and methods of use thereof |
| TWI869213B (zh) | 2018-09-19 | 2025-01-01 | 美商Ionis製藥公司 | Pnpla3表現之調節劑 |
| CN111655297A (zh) * | 2018-09-30 | 2020-09-11 | 苏州瑞博生物技术有限公司 | 一种siRNA缀合物及其制备方法和用途 |
| WO2020077390A1 (en) * | 2018-10-18 | 2020-04-23 | Murdoch University | Antisense therapy for ptp1b related conditions |
| US10913951B2 (en) | 2018-10-31 | 2021-02-09 | University of Pittsburgh—of the Commonwealth System of Higher Education | Silencing of HNF4A-P2 isoforms with siRNA to improve hepatocyte function in liver failure |
| CN113286885A (zh) | 2018-11-09 | 2021-08-20 | 诺华股份有限公司 | 用靶向apo(a)的经缀合的反义化合物降低心血管事件的风险的方法 |
| TW202028222A (zh) | 2018-11-14 | 2020-08-01 | 美商Ionis製藥公司 | Foxp3表現之調節劑 |
| BR112021008967A2 (pt) | 2018-11-15 | 2021-08-17 | Ionis Pharmaceuticals, Inc. | moduladores da expressão de irf5 |
| AU2019384181B2 (en) | 2018-11-21 | 2025-04-10 | Ionis Pharmaceuticals, Inc. | Compounds and methods for reducing prion expression |
| US12416004B2 (en) | 2018-11-23 | 2025-09-16 | Sanofi | RNA compositions and methods for inhibiting ANGPTL8 |
| CN113286600A (zh) | 2018-11-30 | 2021-08-20 | 协和麒麟株式会社 | 核酸复合物 |
| WO2020117706A1 (en) | 2018-12-03 | 2020-06-11 | Triplet Therapeutics, Inc. | Methods for the treatment of trinucleotide repeat expansion disorders associated with mlh3 activity |
| AU2019406186A1 (en) | 2018-12-20 | 2021-07-15 | Praxis Precision Medicines, Inc. | Compositions and methods for the treatment of KCNT1 related disorders |
| AU2019403447B2 (en) | 2018-12-21 | 2023-07-27 | Ionis Pharmaceuticals, Inc. | Modulators of HSD17B13 expression |
| GB201821269D0 (en) | 2018-12-28 | 2019-02-13 | Nippon Shinyaku Co Ltd | Myostatin signal inhibitor |
| EP3903830A4 (en) * | 2018-12-28 | 2023-04-26 | Suzhou Ribo Life Science Co., Ltd. | NUCLEIC ACID, COMPOSITION AND CONJUGATE WITH NUCLEIC ACID, PROCESS FOR THEIR PREPARATION AND ITS USE |
| CN111377985B (zh) * | 2018-12-29 | 2023-11-10 | 苏州瑞博生物技术股份有限公司 | 化合物和缀合物及其制备方法和用途 |
| CN113330117B (zh) * | 2019-01-18 | 2024-05-28 | 苏州瑞博生物技术股份有限公司 | 一种核酸、含有该核酸的组合物与缀合物及制备方法和用途 |
| JP2022523467A (ja) | 2019-01-18 | 2022-04-25 | ユニバーシティ・オブ・マサチューセッツ | 動的な薬物動態を修飾するアンカー |
| WO2020160453A1 (en) | 2019-01-31 | 2020-08-06 | Ionis Pharmaceuticals, Inc. | Modulators of yap1 expression |
| TW202102516A (zh) | 2019-02-20 | 2021-01-16 | 丹麥商羅氏創新中心哥本哈根有限公司 | 膦醯基乙酸酯間隙子寡核苷酸 |
| CN113474352A (zh) | 2019-02-20 | 2021-10-01 | 罗氏创新中心哥本哈根有限公司 | 新型亚磷酰胺 |
| CN109799330B (zh) * | 2019-02-22 | 2021-03-02 | 华中科技大学同济医学院附属同济医院 | 神经氨酸及神经氨酸酶抑制剂在慢性心力衰竭中的应用 |
| WO2020173845A1 (en) | 2019-02-26 | 2020-09-03 | Roche Innovation Center Copenhagen A/S | Oligonucleotide formulation method |
| US11279932B2 (en) | 2019-02-27 | 2022-03-22 | Ionis Pharmaceuticals, Inc. | Modulators of MALAT1 expression |
| US20220145292A1 (en) * | 2019-02-28 | 2022-05-12 | Deep Genomics Incorporated | Ligand clusters and methods of their use and preparation |
| CA3133629A1 (en) * | 2019-03-21 | 2020-09-24 | Mitotherapeutix Llc | Multivalent ligand clusters for targeted delivery of therapeutic agents |
| MX2021011916A (es) | 2019-03-29 | 2021-10-26 | Ionis Pharmaceuticals Inc | Compuestos y metodos para modular ube3a-ats. |
| WO2020201144A1 (en) | 2019-04-02 | 2020-10-08 | Proqr Therapeutics Ii B.V. | Antisense oligonucleotides for immunotherapy |
| BR112021019182A2 (pt) | 2019-04-03 | 2022-05-31 | Bristol Myers Squibb Co | Oligonucleotídeos angptl2 antissenso e seus usos |
| EP3972983A4 (en) * | 2019-05-17 | 2023-05-24 | Ionis Pharmaceuticals, Inc. | SYNTHESIS OF OLIGOMERIC COMPOUNDS COMPRISING PHOSPHOROTHIOATE DIESTER AND PHOSPHATE DIESTER BONDS |
| JP7610268B2 (ja) | 2019-05-22 | 2025-01-08 | スーチョウ リボ ライフ サイエンス カンパニー、リミテッド | 核酸、薬物組成物及び複合体ならびに調製方法と使用 |
| CN113227376B (zh) * | 2019-05-22 | 2024-04-09 | 苏州瑞博生物技术股份有限公司 | 核酸、药物组合物与缀合物及制备方法和用途 |
| US20240200060A1 (en) | 2019-05-22 | 2024-06-20 | Suzhou Ribo Life Science Co., Ltd. | Nucleic acid, pharmaceutical composition, conjugate, preparation method, and use |
| WO2020233651A1 (zh) | 2019-05-22 | 2020-11-26 | 苏州瑞博生物技术股份有限公司 | 核酸、药物组合物与缀合物及制备方法和用途 |
| EP3992290A4 (en) | 2019-05-24 | 2023-11-15 | Suzhou Ribo Life Science Co., Ltd. | NUCLEIC ACID, PHARMACEUTICAL COMPOSITION AND CONJUGATE, METHOD FOR THE PRODUCTION THEREOF AND USE THEREOF |
| US20220186221A1 (en) | 2019-05-24 | 2022-06-16 | Suzhou Ribo Life Science Co., Ltd. | Nucleic acid, pharmaceutical composition and conjugate, preparation method and use |
| JP7610849B2 (ja) | 2019-05-24 | 2025-01-09 | スーチョウ リボ ライフ サイエンス カンパニー、リミテッド | 核酸、薬物組成物及び複合体ならびに調製方法と使用 |
| PT3976791T (pt) | 2019-05-28 | 2025-06-26 | Ionis Pharmaceuticals Inc | Compostos e métodos para reduzir a expressão da fus |
| BR112021023488A2 (pt) | 2019-05-31 | 2022-01-18 | Aligos Therapeutics Inc | Oligonucleotídeos de gapmer modificados e métodos de uso |
| WO2020247452A1 (en) | 2019-06-04 | 2020-12-10 | Regeneron Pharmaceuticals, Inc. | Non-human animals comprising a humanized ttr locus with a beta-slip mutation and methods of use |
| AU2020301419A1 (en) | 2019-06-25 | 2022-01-20 | Amgen Inc. | Purification methods for carbohydrate-linked oligonucleotides |
| ES3048358T3 (en) | 2019-07-26 | 2025-12-10 | Ionis Pharmaceuticals Inc | Compounds and methods for modulating gfap |
| WO2021022108A2 (en) | 2019-08-01 | 2021-02-04 | Alnylam Pharmaceuticals, Inc. | CARBOXYPEPTIDASE B2 (CPB2) iRNA COMPOSITIONS AND METHODS OF USE THEREOF |
| WO2021022109A1 (en) | 2019-08-01 | 2021-02-04 | Alnylam Pharmaceuticals, Inc. | SERPIN FAMILY F MEMBER 2 (SERPINF2) iRNA COMPOSITIONS AND METHODS OF USE THEREOF |
| WO2021030213A1 (en) | 2019-08-09 | 2021-02-18 | University Of Massachusetts | Chemically modified oligonucleotides targeting snps |
| WO2021030522A1 (en) | 2019-08-13 | 2021-02-18 | Alnylam Pharmaceuticals, Inc. | SMALL RIBOSOMAL PROTEIN SUBUNIT 25 (RPS25) iRNA AGENT COMPOSITIONS AND METHODS OF USE THEREOF |
| CN114555621B (zh) * | 2019-08-15 | 2025-10-28 | Ionis制药公司 | 键修饰的寡聚化合物及其用途 |
| US20220290156A1 (en) | 2019-08-27 | 2022-09-15 | Sanofi | Compositions and methods for inhibiting pcsk9 |
| CN113891892B (zh) | 2019-08-29 | 2024-01-30 | 苏州瑞博生物技术股份有限公司 | 化合物和药物缀合物及其制备方法和用途 |
| EP4022062A1 (en) | 2019-08-30 | 2022-07-06 | Alnylam Pharmaceuticals, Inc. | Neurofilament light chain (nfl) as a biomarker for transthyretin amyloidosis polyneuropathy |
| US12290567B2 (en) | 2019-09-03 | 2025-05-06 | Arcturus Therapeutics, Inc. | Asialoglycoprotein Receptor mediated delivery of therapeutically active conjugates |
| CN119326905A (zh) | 2019-09-10 | 2025-01-21 | 第一三共株式会社 | 用于递送至肝脏的GalNAc-寡核苷酸偶联物及其制备方法 |
| US12365894B2 (en) | 2019-09-16 | 2025-07-22 | University Of Massachusetts | Branched lipid conjugates of siRNA for specific tissue delivery |
| TW202126304A (zh) | 2019-09-20 | 2021-07-16 | 瑞士商赫孚孟拉羅股份公司 | 使用核心蛋白異位調節劑治療hbv感染之方法 |
| WO2021067747A1 (en) | 2019-10-04 | 2021-04-08 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for silencing ugt1a1 gene expression |
| CN114728017B (zh) | 2019-10-14 | 2025-10-28 | 阿斯利康(瑞典)有限公司 | Pnpla3表达的调节剂 |
| US12486512B2 (en) | 2019-10-18 | 2025-12-02 | Alnylam Pharmaceuticals, Inc. | Solute carrier family member iRNA compositions and methods of use thereof |
| JP7676377B2 (ja) | 2019-10-22 | 2025-05-14 | 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 | 補体成分C3 iRNA組成物およびその使用方法 |
| MX2022004388A (es) | 2019-11-01 | 2022-05-06 | Alnylam Pharmaceuticals Inc | Composiciones de agentes de arni de huntingtina (htt) y metodos de uso de las mismas. |
| JP7707164B2 (ja) | 2019-11-13 | 2025-07-14 | 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 | アンギオテンシノーゲン(agt)関連障害を処置するための方法および組成物 |
| US20230056569A1 (en) | 2019-11-22 | 2023-02-23 | Alnylam Pharmaceuticals, Inc. | Ataxin3 (atxn3) rnai agent compositions and methods of use thereof |
| CN112876534B (zh) * | 2019-11-29 | 2024-02-09 | 苏州瑞博生物技术股份有限公司 | 肝靶向化合物及缀合物 |
| MX2022006433A (es) | 2019-12-13 | 2022-06-23 | Alnylam Pharmaceuticals Inc | Composiciones de agentes de acido ribonucleico de interferencia (arni) del marco de lectura abierto 72 del cromosoma 9 humano (c9orf72) y metodos de uso de los mismos. |
| WO2021126734A1 (en) | 2019-12-16 | 2021-06-24 | Alnylam Pharmaceuticals, Inc. | Patatin-like phospholipase domain containing 3 (pnpla3) irna compositions and methods of use thereof |
| CN111041025B (zh) * | 2019-12-17 | 2021-06-18 | 深圳市瑞吉生物科技有限公司 | 基于结合N-乙酰半乳糖胺多肽的mRNA靶向分子及其制备方法 |
| CN114867856A (zh) | 2019-12-19 | 2022-08-05 | 豪夫迈·罗氏有限公司 | Saraf抑制剂用于治疗乙型肝炎病毒感染的用途 |
| JP2023506550A (ja) | 2019-12-19 | 2023-02-16 | エフ. ホフマン-ラ ロシュ エージー. | B型肝炎ウイルス感染症を処置するためのsbds阻害剤の使用 |
| EP4077670A1 (en) | 2019-12-19 | 2022-10-26 | F. Hoffmann-La Roche AG | Use of cops3 inhibitors for treating hepatitis b virus infection |
| EP4077667A1 (en) | 2019-12-19 | 2022-10-26 | F. Hoffmann-La Roche AG | Use of sept9 inhibitors for treating hepatitis b virus infection |
| CN114829599A (zh) | 2019-12-19 | 2022-07-29 | 豪夫迈·罗氏有限公司 | Scamp3抑制剂用于治疗乙型肝炎病毒感染的用途 |
| CA3163646A1 (en) | 2019-12-24 | 2021-07-01 | F. Hoffman-La Roche Ag | Pharmaceutical combination of antiviral agents targeting hbv and/or an immune modulator for treatment of hbv |
| CN115103674A (zh) | 2019-12-24 | 2022-09-23 | 豪夫迈·罗氏有限公司 | 使用tlr7激动剂治疗病毒感染的方法 |
| JP2023509870A (ja) | 2019-12-24 | 2023-03-10 | エフ. ホフマン-ラ ロシュ アーゲー | Hbvの処置のためのhbvを標的とする治療用オリゴヌクレオチドとtlr7アゴニストとの医薬組合せ |
| EP4071163A4 (en) * | 2020-01-30 | 2024-03-20 | Eisai R&D Management Co., Ltd. | NUCLEIC ACID COMPLEX AND PHARMACEUTICAL COMPOSITION CONTAINING SAME |
| KR20220140593A (ko) | 2020-02-10 | 2022-10-18 | 알닐람 파마슈티칼스 인코포레이티드 | Vegf-a 발현을 사일런싱하기 위한 조성물 및 방법 |
| KR20220143106A (ko) | 2020-02-18 | 2022-10-24 | 알닐람 파마슈티칼스 인코포레이티드 | 아포지질단백질 C3 (APOC3) iRNA 조성물 및 이의 사용 방법 |
| BR112022016238A2 (pt) | 2020-02-28 | 2022-10-11 | Ionis Pharmaceuticals Inc | Compostos e métodos para modular smn2 |
| GB2627637B (en) | 2020-03-04 | 2024-11-20 | Verve Therapeutics Inc | A method for reducing the risk of coronary disease |
| EP4114947A1 (en) | 2020-03-05 | 2023-01-11 | Alnylam Pharmaceuticals, Inc. | Complement component c3 irna compositions and methods of use thereof for treating or preventing complement component c3-associated diseases |
| IL296106A (en) | 2020-03-06 | 2022-11-01 | Alnylam Pharmaceuticals Inc | Compositions and methods for inhibiting expression of transthyretin (ttr) |
| JP2023516095A (ja) | 2020-03-06 | 2023-04-17 | 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 | ケトヘキソキナーゼ(KHK)iRNA組成物およびその使用方法 |
| EP4121534A1 (en) | 2020-03-18 | 2023-01-25 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for treating subjects having a heterozygous alanine-glyoxylate aminotransferase gene (agxt) variant |
| CA3175278A1 (en) | 2020-03-23 | 2021-09-30 | Amgen Inc. | Monoclonal antibodies to chemically-modified nucleic acids and uses thereof |
| JP7760130B2 (ja) * | 2020-03-26 | 2025-10-27 | 国立研究開発法人国立循環器病研究センター | Apoc3を標的としたアンチセンス核酸 |
| JP2023519274A (ja) | 2020-03-26 | 2023-05-10 | 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 | コロナウイルスiRNA組成物およびその使用方法 |
| CN117377763A (zh) | 2020-04-06 | 2024-01-09 | 阿尔尼拉姆医药品有限公司 | 用于沉默myoc表达的组合物和方法 |
| EP4133079A1 (en) | 2020-04-07 | 2023-02-15 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for silencing scn9a expression |
| WO2021206917A1 (en) | 2020-04-07 | 2021-10-14 | Alnylam Pharmaceuticals, Inc. | ANGIOTENSIN-CONVERTING ENZYME 2 (ACE2) iRNA COMPOSITIONS AND METHODS OF USE THEREOF |
| EP4133077A1 (en) | 2020-04-07 | 2023-02-15 | Alnylam Pharmaceuticals, Inc. | Transmembrane serine protease 2 (tmprss2) irna compositions and methods of use thereof |
| IL297482A (en) | 2020-04-21 | 2022-12-01 | Flagship Pioneering Inc | Bifunctional molecules and methods of using thereof |
| CN111575279A (zh) * | 2020-04-27 | 2020-08-25 | 江苏为真生物医药技术股份有限公司 | 利用asgpr小分子配体特异性捕获肝细胞外囊泡或循环肿瘤细胞的方法 |
| IL297702A (en) | 2020-04-27 | 2022-12-01 | Alnylam Pharmaceuticals Inc | Apolipoprotein e (apoe) irna agent compositions and methods of use thereof |
| WO2021222549A1 (en) | 2020-04-30 | 2021-11-04 | Alnylam Pharmaceuticals, Inc. | Complement factor b (cfb) irna compositions and methods of use thereof |
| IL297435A (en) | 2020-05-01 | 2022-12-01 | Ionis Pharmaceuticals Inc | Compounds and methods for modulating atxn1 |
| CN115867657A (zh) | 2020-05-11 | 2023-03-28 | 斯托克制药公司 | 用于治疗疾患和疾病的opa1反义寡聚物 |
| CA3162416C (en) | 2020-05-15 | 2023-07-04 | Korro Bio, Inc. | Methods and compositions for the adar-mediated editing of argininosuccinate synthetase (ass1) |
| WO2021231685A1 (en) | 2020-05-15 | 2021-11-18 | Korro Bio, Inc. | Methods and compositions for the adar-mediated editing of transmembrane channel-like protein 1 (tmc1) |
| WO2021231692A1 (en) | 2020-05-15 | 2021-11-18 | Korro Bio, Inc. | Methods and compositions for the adar-mediated editing of otoferlin (otof) |
| EP4150089A1 (en) | 2020-05-15 | 2023-03-22 | Korro Bio, Inc. | Methods and compositions for the adar-mediated editing of retinoschisin 1 (rs1) |
| EP4150086A1 (en) | 2020-05-15 | 2023-03-22 | Korro Bio, Inc. | Methods and compositions for the adar-mediated editing of leucine rich repeat kinase 2 (lrrk2) |
| WO2021231698A1 (en) | 2020-05-15 | 2021-11-18 | Korro Bio, Inc. | Methods and compositions for the adar-mediated editing of argininosuccinate lyase (asl) |
| WO2021231679A1 (en) | 2020-05-15 | 2021-11-18 | Korro Bio, Inc. | Methods and compositions for the adar-mediated editing of gap junction protein beta 2 (gjb2) |
| EP4150076A1 (en) | 2020-05-15 | 2023-03-22 | Korro Bio, Inc. | Methods and compositions for the adar-mediated editing of methyl-cpg binding protein 2 (mecp2) |
| CN113683651A (zh) * | 2020-05-19 | 2021-11-23 | 上海京新生物医药有限公司 | 一种GalNAc中间体的制备方法 |
| AR122534A1 (es) | 2020-06-03 | 2022-09-21 | Triplet Therapeutics Inc | Métodos para el tratamiento de los trastornos de expansión por repetición de nucleótidos asociados con la actividad de msh3 |
| WO2021252557A1 (en) | 2020-06-09 | 2021-12-16 | Alnylam Pharmaceuticals, Inc. | Rnai compositions and methods of use thereof for delivery by inhalation |
| EP4649951A2 (en) | 2020-06-09 | 2025-11-19 | Alnylam Pharmaceuticals, Inc. | Sirna compositions and methods for silencing gpam (glycerol-3-phosphate acyltransferase 1, mitochondrial) expression |
| US20240033278A9 (en) * | 2020-06-10 | 2024-02-01 | Medshine Discovery Inc. | Conjugate group and conjugate |
| BR112022024420A2 (pt) | 2020-06-18 | 2023-01-17 | Alnylam Pharmaceuticals Inc | Composições de irna de xantina desidrogenase (xdh) e métodos de uso das mesmas |
| JP2023532040A (ja) * | 2020-06-24 | 2023-07-26 | サプリーム テクノロジーズ,ベー.フェー. | GalNAc及びサポニンのコンジュゲート、前記コンジュゲート及びGalNAc-オリゴヌクレオチドコンジュゲートを含む治療組成物 |
| AR122731A1 (es) | 2020-06-26 | 2022-10-05 | Hoffmann La Roche | Oligonucleótidos mejorados para modular la expresión de fubp1 |
| EP4172338A4 (en) | 2020-06-29 | 2025-06-11 | Ionis Pharmaceuticals, Inc. | COMPOUNDS AND METHODS FOR MODULATING PLP1 |
| CN111744019B (zh) | 2020-07-01 | 2023-08-04 | 深圳瑞吉生物科技有限公司 | 基于甘露糖的mRNA靶向递送系统及其应用 |
| CA3177613A1 (en) | 2020-07-10 | 2022-04-13 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Methods and compositions for treating epilepsy |
| WO2022026589A1 (en) | 2020-07-28 | 2022-02-03 | Ionis Pharmaceuticals, Inc. | Compounds and methods for reducing app expression |
| EP4192476A4 (en) | 2020-08-07 | 2024-09-18 | Ionis Pharmaceuticals, Inc. | COMPOUNDS AND METHODS FOR MODULATING SCN2A |
| PE20230993A1 (es) * | 2020-08-13 | 2023-06-23 | Amgen Inc | Construcciones de iarn y metodos para inhibir la expresion de marc1 |
| JP2023538630A (ja) | 2020-08-21 | 2023-09-08 | エフ. ホフマン-ラ ロシュ アーゲー | B型肝炎ウイルス感染症を処置するためのa1cf阻害剤の使用 |
| WO2022066847A1 (en) | 2020-09-24 | 2022-03-31 | Alnylam Pharmaceuticals, Inc. | Dipeptidyl peptidase 4 (dpp4) irna compositions and methods of use thereof |
| TW202229552A (zh) | 2020-10-05 | 2022-08-01 | 美商艾拉倫製藥股份有限公司 | G蛋白-偶合受體75(GPR75)iRNA組成物及其使用方法 |
| EP4229200A1 (en) | 2020-10-16 | 2023-08-23 | Sanofi | Novel rna compositions and methods for inhibiting angptl3 |
| US20240035029A1 (en) | 2020-10-16 | 2024-02-01 | Sanofi | Rna compositions and methods for inhibiting lipoprotein(a) |
| WO2022087329A1 (en) | 2020-10-23 | 2022-04-28 | Alnylam Pharmaceuticals, Inc. | Mucin 5b (muc5b) irna compositions and methods of use thereof |
| AU2021380809A1 (en) | 2020-11-13 | 2023-06-22 | Alnylam Pharmaceuticals, Inc. | COAGULATION FACTOR V (F5) iRNA COMPOSITIONS AND METHODS OF USE THEREOF |
| ES2990026T3 (es) | 2020-11-18 | 2024-11-28 | Ionis Pharmaceuticals Inc | Compuestos y métodos para modular la expresión del angiotensinógeno |
| US20240002853A1 (en) | 2020-11-23 | 2024-01-04 | Alpha Anomeric Sas | Nucleic acid duplexes |
| WO2022125490A1 (en) | 2020-12-08 | 2022-06-16 | Alnylam Pharmaceuticals, Inc. | Coagulation factor x (f10) irna compositions and methods of use thereof |
| GB2603454A (en) | 2020-12-09 | 2022-08-10 | Ucl Business Ltd | Novel therapeutics for the treatment of neurodegenerative disorders |
| TW202242111A (zh) | 2020-12-18 | 2022-11-01 | 美商Ionis製藥公司 | 用於調節因子xii之化合物及方法 |
| US20250304966A1 (en) | 2020-12-23 | 2025-10-02 | Argonaute RNA Limited | Treatment of cardiovascular disease |
| US20250320500A1 (en) | 2020-12-29 | 2025-10-16 | Suzhou Ribo Life Science Co., Ltd. | Nucleic acid, pharmaceutical composition and sirna conjugate containing the nucleic acid, preparation method therefor, and use thereof |
| EP4274896A1 (en) | 2021-01-05 | 2023-11-15 | Alnylam Pharmaceuticals, Inc. | Complement component 9 (c9) irna compositions and methods of use thereof |
| WO2022162161A1 (en) * | 2021-01-30 | 2022-08-04 | E-Therapeutics Plc | Conjugated oligonucleotide compounds, methods of making and uses thereof |
| CN116848127A (zh) * | 2021-01-30 | 2023-10-03 | e-生物有限公司 | 缀合寡核苷酸化合物、其制备方法和用途 |
| CA3204317A1 (en) * | 2021-01-30 | 2022-08-04 | Ahmad Ali MORTAZAVI | Conjugated oligonucleotide compounds, methods of making and uses thereof |
| WO2022162157A1 (en) * | 2021-01-30 | 2022-08-04 | E-Therapeutics Plc | Conjugated oligonucleotide compounds, methods of making and uses thereof |
| AU2022214281A1 (en) | 2021-01-30 | 2023-07-27 | E-Therapeutics Plc | Conjugated oligonucleotide compounds, methods of making and uses thereof |
| CN117355534A (zh) * | 2021-01-30 | 2024-01-05 | e-生物有限公司 | 缀合寡核苷酸化合物、其制备方法和用途 |
| TW202246500A (zh) | 2021-02-02 | 2022-12-01 | 瑞士商赫孚孟拉羅股份公司 | 用於抑制 rtel1 表現之增強型寡核苷酸 |
| IL304880A (en) | 2021-02-12 | 2023-10-01 | Alnylam Pharmaceuticals Inc | Superoxide dismutase 1 (sod1) irna compositions and methods of use thereof for treating or preventing superoxide dismutase 1- (sod1-) associated neurodegenerative diseases |
| WO2022175749A1 (en) * | 2021-02-18 | 2022-08-25 | Oneglobe Holdings Limited | Compositions for conjugating oligonucleotides and carbohydrates |
| JP2024509783A (ja) | 2021-02-25 | 2024-03-05 | 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 | プリオンタンパク質(prnp)irna組成物およびその使用方法 |
| KR20230150844A (ko) | 2021-02-26 | 2023-10-31 | 알닐람 파마슈티칼스 인코포레이티드 | 케토헥소키나아제(KHK) iRNA 조성물 및 이의 사용 방법 |
| AU2022231003A1 (en) | 2021-03-04 | 2023-09-14 | Alnylam Pharmaceuticals, Inc. | Angiopoietin-like 3 (angptl3) irna compositions and methods of use thereof |
| WO2022189861A1 (en) | 2021-03-08 | 2022-09-15 | Tollys | Carbohydrate conjugates of tlr3 ligands and uses thereof |
| IL305668A (en) | 2021-03-08 | 2023-11-01 | Servier Lab | Antisense oligonucleotides to inhibit alpha-synuclein expression |
| EP4305169A1 (en) | 2021-03-12 | 2024-01-17 | Alnylam Pharmaceuticals, Inc. | Glycogen synthase kinase 3 alpha (gsk3a) irna compositions and methods of use thereof |
| KR20230162024A (ko) | 2021-03-29 | 2023-11-28 | 알닐람 파마슈티칼스 인코포레이티드 | 헌팅틴(HTT) iRNA 제제 조성물 및 이의 사용 방법 |
| EP4314293A1 (en) | 2021-04-01 | 2024-02-07 | Alnylam Pharmaceuticals, Inc. | Proline dehydrogenase 2 (prodh2) irna compositions and methods of use thereof |
| MX2023012216A (es) | 2021-04-14 | 2023-10-26 | Dicerna Pharmaceuticals Inc | Composiciones y metodos para modular la expresion de pnpla3. |
| CA3216106A1 (en) | 2021-04-26 | 2022-11-03 | Alnylam Pharmaceuticals, Inc. | Transmembrane protease, serine 6 (tmprss6) irna compositions and methods of use thereof |
| WO2022232343A1 (en) | 2021-04-29 | 2022-11-03 | Alnylam Pharmaceuticals, Inc. | Signal transducer and activator of transcription factor 6 (stat6) irna compositions and methods of use thereof |
| WO2022232650A1 (en) * | 2021-04-30 | 2022-11-03 | Ionis Pharmaceuticals, Inc. | Methods for reducing agt expression |
| EP4341401A1 (en) | 2021-05-18 | 2024-03-27 | Alnylam Pharmaceuticals, Inc. | Sodium-glucose cotransporter-2 (sglt2) irna compositions and methods of use thereof |
| WO2022246023A1 (en) | 2021-05-20 | 2022-11-24 | Korro Bio, Inc. | Methods and compositions for adar-mediated editing |
| WO2022256283A2 (en) | 2021-06-01 | 2022-12-08 | Korro Bio, Inc. | Methods for restoring protein function using adar |
| JP2024522996A (ja) | 2021-06-02 | 2024-06-25 | 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 | パタチン様ホスホリパーゼドメイン含有3(PNPLA3)iRNA組成物およびその使用方法 |
| AU2022283796A1 (en) | 2021-06-04 | 2023-11-09 | Alnylam Pharmaceuticals, Inc. | HUMAN CHROMOSOME 9 OPEN READING FRAME 72 (C9ORF72) iRNA AGENT COMPOSITIONS AND METHODS OF USE THEREOF |
| JP2024523000A (ja) | 2021-06-08 | 2024-06-25 | 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 | シュタルガルト病及び/又は網膜結合タンパク質4(rbp4)関連障害を治療又は予防するための組成物及び方法 |
| BR112023026050A2 (pt) | 2021-06-18 | 2024-03-05 | Ionis Pharmaceuticals Inc | Compostos e métodos para reduzir expressão de ifnar1 |
| IL309334A (en) | 2021-06-23 | 2024-02-01 | Univ Massachusetts | Anti-FLT1 optimized oligonucleotide compounds for the treatment of preeclampsia and other angiogenic disorders |
| MX2024000208A (es) * | 2021-06-24 | 2024-01-29 | Lilly Co Eli | Restos de administracion terapeutica novedosos y usos de estos. |
| PE20250353A1 (es) * | 2021-06-24 | 2025-02-06 | Lilly Co Eli | Terapeutica con arn novedosos y usos de estos |
| US20230194709A9 (en) | 2021-06-29 | 2023-06-22 | Seagate Technology Llc | Range information detection using coherent pulse sets with selected waveform characteristics |
| US20250034564A1 (en) | 2021-06-29 | 2025-01-30 | Korro Bio, Inc. | Methods and Compositions for ADAR-Mediated Editing |
| KR20240026203A (ko) | 2021-06-30 | 2024-02-27 | 알닐람 파마슈티칼스 인코포레이티드 | 안지오텐시노겐(agt)-관련 장애를 치료하는 방법 및 조성물 |
| JP2024524330A (ja) * | 2021-07-02 | 2024-07-05 | 上海拓界生物医薬科技有限公司 | 核酸リガンド及びその複合体、その調製方法と用途 |
| US20240316093A1 (en) | 2021-07-08 | 2024-09-26 | Nippon Shinyaku Co., Ltd. | Nephrotoxicity reducing agent |
| IL310001A (en) | 2021-07-08 | 2024-03-01 | Nippon Shinyaku Co Ltd | Precipitation suppressing agent |
| TW202308664A (zh) | 2021-07-08 | 2023-03-01 | 日商日本新藥股份有限公司 | 腎毒性減輕劑 |
| JP2024528659A (ja) | 2021-07-19 | 2024-07-30 | 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 | 非原発性高シュウ酸尿症疾患または障害を有するまたは発症するリスクがある対象を治療するための方法および組成物 |
| WO2023003995A1 (en) | 2021-07-23 | 2023-01-26 | Alnylam Pharmaceuticals, Inc. | Beta-catenin (ctnnb1) irna compositions and methods of use thereof |
| JP2024529437A (ja) | 2021-07-29 | 2024-08-06 | 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 | 3-ヒドロキシ-3-メチルグリタル-COAレダクターゼ(HMGCR)iRNA組成物およびその使用方法 |
| AR126675A1 (es) | 2021-08-03 | 2023-11-01 | Alnylam Pharmaceuticals Inc | COMPOSICIONES DE ARNi CONTRA LA TRANSTIRRETINA (TTR) Y SUS MÉTODOS DE USO |
| CA3226651A1 (en) * | 2021-08-03 | 2023-02-09 | Kallanthottathil G. Rajeev | Compositions and methods for targeted rna delivery |
| PE20241132A1 (es) | 2021-08-04 | 2024-05-24 | Alnylam Pharmaceuticals Inc | Composiciones de arni y metodos para silenciar el angiotensinogeno (agt) |
| CA3228733A1 (en) | 2021-08-13 | 2023-02-16 | Alnylam Pharmaceuticals, Inc. | Factor xii (f12) irna compositions and methods of use thereof |
| AU2022339821A1 (en) | 2021-08-31 | 2024-03-07 | Alnylam Pharmaceuticals, Inc. | Cell death-inducing dffa-like effector b (cideb) irna compositions and methods of use thereof |
| JP2024531728A (ja) | 2021-09-14 | 2024-08-29 | アルゴノート アールエヌエー リミテッド | 心血管疾患の処置 |
| WO2023044370A2 (en) | 2021-09-17 | 2023-03-23 | Alnylam Pharmaceuticals, Inc. | Irna compositions and methods for silencing complement component 3 (c3) |
| CA3232191A1 (en) * | 2021-09-18 | 2023-03-23 | Chong Li | Lpa inhibitor and use thereof |
| AU2022345881A1 (en) | 2021-09-20 | 2024-03-21 | Alnylam Pharmaceuticals, Inc. | Inhibin subunit beta e (inhbe) modulator compositions and methods of use thereof |
| MX2024003477A (es) * | 2021-09-23 | 2024-04-05 | Shanghai Argo Biopharmaceutical Co Ltd | Cluster de ligandos multivalentes con andamio de diamina para el suministro dirigido de agentes terapeuticos. |
| US20250115915A1 (en) | 2021-10-01 | 2025-04-10 | Adarx Pharmaceuticals, Inc. | Prekallikrein-modulating compositions and methods of use thereof |
| US20250352667A1 (en) | 2021-10-22 | 2025-11-20 | Korro Bio, Inc. | Methods and compositions for disrupting nrf2-keap1 protein interaction by adar mediated rna editing |
| KR20240095325A (ko) | 2021-10-29 | 2024-06-25 | 알닐람 파마슈티칼스 인코포레이티드 | 보체 인자 b (cfb) irna 조성물 및 이의 사용 방법 |
| TW202334418A (zh) | 2021-10-29 | 2023-09-01 | 美商艾拉倫製藥股份有限公司 | 杭丁頓(HTT)iRNA劑組成物及其使用方法 |
| CN118284695A (zh) | 2021-11-11 | 2024-07-02 | 豪夫迈·罗氏有限公司 | 用于治疗hbv的药物组合 |
| WO2023102188A1 (en) | 2021-12-03 | 2023-06-08 | Quralis Corporation | Gapmer antisense oligonucleotides with modified backbone chemistries |
| GB202117758D0 (en) | 2021-12-09 | 2022-01-26 | Ucl Business Ltd | Therapeutics for the treatment of neurodegenerative disorders |
| TW202340466A (zh) * | 2021-12-16 | 2023-10-16 | 大陸商上海拓界生物醫藥科技有限公司 | 一種dsrna、其製備方法及應用 |
| KR20240116539A (ko) * | 2021-12-16 | 2024-07-29 | 투오지에 바이오텍 (상하이) 컴퍼니 리미티드 | LPA를 표적으로 하는 siRNA 및 접합체 |
| CN119095603A (zh) | 2021-12-17 | 2024-12-06 | 豪夫迈·罗氏有限公司 | 用于调节rtel1和fubp1的寡核苷酸的组合 |
| CA3243093A1 (en) * | 2022-01-20 | 2025-04-08 | Tuojie Biotech (Shanghai) Co., Ltd. | DOUBLE-STRANDED RNA, ITS USES AND PREPARATION PROCESS |
| TW202345865A (zh) * | 2022-01-24 | 2023-12-01 | 大陸商上海舶望製藥有限公司 | 抑制LPA(Apo(a))蛋白表達的組合物和方法 |
| WO2023141314A2 (en) | 2022-01-24 | 2023-07-27 | Alnylam Pharmaceuticals, Inc. | Heparin sulfate biosynthesis pathway enzyme irna agent compositions and methods of use thereof |
| CN117756866A (zh) * | 2022-01-30 | 2024-03-26 | 大睿生物医药科技(上海)有限公司 | 含有n-乙酰半乳糖胺的靶向配体 |
| AR128558A1 (es) | 2022-02-21 | 2024-05-22 | Hoffmann La Roche | Oligonucleótido antisentido |
| US20250188469A1 (en) | 2022-03-10 | 2025-06-12 | Nippon Shinyaku Co., Ltd. | Antiviral antisense oligomer |
| CN114703184B (zh) * | 2022-03-11 | 2024-06-18 | 厦门甘宝利生物医药有限公司 | Lpa抑制剂及其用途 |
| TW202345867A (zh) | 2022-03-16 | 2023-12-01 | 日商第一三共股份有限公司 | 抑制運鐵蛋白受體2表現的siRNA |
| CN119213005A (zh) | 2022-03-16 | 2024-12-27 | 艾姆皮瑞克公司 | 用于提高siRNA生物利用度的GALNAC组合物 |
| WO2023176863A1 (ja) | 2022-03-16 | 2023-09-21 | 第一三共株式会社 | RNAi活性を有する化学修飾オリゴヌクレオチド |
| TW202403044A (zh) | 2022-03-28 | 2024-01-16 | 美商安彼瑞可股份有限公司 | 經修飾之寡核苷酸 |
| CN115028670B (zh) * | 2022-06-24 | 2023-07-28 | 四川大学华西医院 | 一种n-乙酰基-d-半乳糖胺三聚体前体的制备方法 |
| CN119654412A (zh) * | 2022-06-27 | 2025-03-18 | 中美瑞康核酸技术(南通)研究院有限公司 | 激活补体因子h表达的寡核苷酸调节剂 |
| JP2025524566A (ja) | 2022-07-15 | 2025-07-30 | プロキューアール セラピューティクス ツー ベスローテン フェンノートシャップ | Adar媒介rna編集のためのオリゴヌクレオチドおよびその使用 |
| EP4555085A1 (en) | 2022-07-15 | 2025-05-21 | ProQR Therapeutics II B.V. | Chemically modified oligonucleotides for adar-mediated rna editing |
| CN116814621B (zh) * | 2022-08-05 | 2025-09-09 | 厦门甘宝利生物医药有限公司 | 一种抑制apoc3基因表达的rna抑制剂及其应用 |
| CN120077130A (zh) | 2022-08-18 | 2025-05-30 | 阿尔尼拉姆医药品有限公司 | 通用非靶向sirna组合物及其使用方法 |
| JP2025532593A (ja) | 2022-09-15 | 2025-10-01 | リジェネロン・ファーマシューティカルズ・インコーポレイテッド | 17b-ヒドロキシステロイドデヒドロゲナーゼ13型(hsd17b13)irna組成物およびその使用方法 |
| CA3268249A1 (en) | 2022-09-23 | 2024-03-28 | Ionis Pharmaceuticals, Inc. | COMPOUNDS AND METHODS FOR REDUCING MECP2 EXPRESSION |
| WO2024098061A2 (en) | 2022-11-04 | 2024-05-10 | Genkardia Inc. | Oligonucleotide-based therapeutics targeting cyclin d2 for the treatment of heart failure |
| WO2024106539A1 (ja) * | 2022-11-18 | 2024-05-23 | 株式会社ボナック | リガンドコンジュゲート物質及びそれを含む核酸並びにその用途 |
| AU2023383571A1 (en) | 2022-11-18 | 2025-07-03 | Genkardia Inc. | Methods and compositions for preventing, treating, or reversing cardiac diastolic dysfunction |
| WO2024112937A2 (en) * | 2022-11-23 | 2024-05-30 | Pretzel Therapeutics, Inc. | Compositions and methods for treatment of cancer and metabolic disease |
| KR20250116697A (ko) | 2022-12-02 | 2025-08-01 | 상하이 아르고 바이오파마슈티칼 씨오., 엘티디. | 비시클릭 무염기 핵산 유사체 및 이들로부터 제조된 올리고머 화합물 |
| EP4592432A3 (en) | 2022-12-19 | 2025-10-29 | Arnatar Therapeutics | Arnatar compounds and methods for enhanced cellular uptake |
| WO2024137543A1 (en) | 2022-12-19 | 2024-06-27 | Arnatar Therapeutics, Inc | Advanced rna targeting (arnatar) |
| AR131419A1 (es) * | 2022-12-21 | 2025-03-19 | Lilly Co Eli | TERAPÉUTICOS NOVEDOSOS DE iARN DE FAS Y USOS DE ESTOS |
| EP4649153A1 (en) * | 2023-01-10 | 2025-11-19 | Ausperbio Therapeutics Inc. | Modified multi-segmented antisense oligonucleotides for use |
| AU2024217843A1 (en) | 2023-02-09 | 2025-07-31 | Alnylam Pharmaceuticals, Inc. | Reversir molecules and methods of use thereof |
| WO2024175113A1 (zh) * | 2023-02-24 | 2024-08-29 | 南京明德新药研发有限公司 | 包含R和E的双链siRNA类似物及其缀合物 |
| AU2024258561A1 (en) | 2023-04-20 | 2025-10-30 | Adarx Pharmaceuticals, Inc. | Mapt-modulating compositions and methods of use thereof |
| WO2024220746A2 (en) | 2023-04-21 | 2024-10-24 | Flagship Pioneering Innovations Vii, Llc | Rnai agents targeting fatty acid synthase and related methods |
| WO2024221135A1 (en) * | 2023-04-23 | 2024-10-31 | Ausper Biopharma Co., Ltd. | Oligonucleotides for use in modulating immune responses against hepatitis b viral infection |
| US20240374741A1 (en) * | 2023-05-11 | 2024-11-14 | Synerk Biotech Limited | Compound, a conjugate and uses thereof |
| WO2024238396A1 (en) | 2023-05-12 | 2024-11-21 | Adarx Pharmaceuticals, Inc. | Nmda ligand conjugated compounds and uses thereof |
| UY40743A (es) * | 2023-05-19 | 2024-12-13 | Shanghai Argo Biopharmaceutical Co Ltd | COMPOSICIONES Y MÉTODOS PARA INHIBIR LA EXPRESIÓN DEL factor de coagulación XI (FXI) |
| AU2024279767A1 (en) | 2023-05-26 | 2025-12-04 | Adarx Pharmaceuticals, Inc. | Sod1-modulating compositions and methods of use thereof |
| CN121079106A (zh) * | 2023-05-31 | 2025-12-05 | 上海拓界生物医药科技有限公司 | 一种靶向LPA的dsRNA及其应用 |
| WO2024255761A1 (zh) * | 2023-06-12 | 2024-12-19 | 大睿生物 | 包含糖的寡核苷酸递送配体 |
| AU2024302527A1 (en) | 2023-06-13 | 2025-11-13 | Arnatar Therapeutics, Inc | Advanced rna targeting (arnatar) for angiotensinogen |
| WO2024263694A1 (en) | 2023-06-20 | 2024-12-26 | Adarx Pharmaceuticals, Inc. | Lrrk2-modulating compositions and methods of use thereof |
| CN119219716A (zh) * | 2023-06-30 | 2024-12-31 | 上海维申医药有限公司 | 新型GalNAc的靶向递送片段及其制备和应用 |
| WO2025015338A1 (en) | 2023-07-13 | 2025-01-16 | Korro Bio, Inc. | Rna-editing oligonucleotides and uses thereof |
| AU2024287308A1 (en) | 2023-07-13 | 2025-12-18 | Korro Bio, Inc. | Rna-editing oligonucleotides and uses thereof |
| WO2025021831A1 (en) * | 2023-07-24 | 2025-01-30 | Astrazeneca Ab | Multivalent cargo-carrying complexes and uses thereof |
| GB202311324D0 (en) | 2023-07-24 | 2023-09-06 | Astrazeneca Ab | Multivalent cargo-carrying complexes and uses thereof |
| GB202311334D0 (en) | 2023-07-24 | 2023-09-06 | Astrazeneca Ab | Multivalent cargo-carrying complexes and uses thereof |
| WO2025034422A1 (en) | 2023-08-04 | 2025-02-13 | Alnylam Pharmaceuticals, Inc. | Methods and compositions for treating ctnnb1-associated disorders |
| WO2025036916A1 (en) | 2023-08-16 | 2025-02-20 | Les Laboratoires Servier | Oligonucleotides for modulating kcnt1 expression |
| WO2025045194A1 (zh) * | 2023-08-31 | 2025-03-06 | 正大天晴药业集团股份有限公司 | 靶向凝血因子xi的双链核糖核酸 |
| TW202526017A (zh) * | 2023-09-14 | 2025-07-01 | 美商Ionis製藥公司 | 用於減少apociii表現的化合物及方法 |
| CN116925160B (zh) * | 2023-09-15 | 2023-12-08 | 天津全和诚科技有限责任公司 | 一种GalNAc含糖环中间体及其制备方法 |
| WO2025064819A1 (en) * | 2023-09-21 | 2025-03-27 | Ionis Pharmaceuticals, Inc. | Compounds and methods for inhibiting lpa |
| US20250215044A1 (en) * | 2023-09-21 | 2025-07-03 | Ionis Pharmaceuticals, Inc. | Compounds and Methods for Inhibiting LPA |
| GB202314724D0 (en) | 2023-09-26 | 2023-11-08 | Astrazeneca Ab | compounds and methods for reducing psd3 expression |
| WO2025072748A2 (en) * | 2023-09-29 | 2025-04-03 | Insitro, Inc. | Compositions and methods for treating nonalcoholic fatty liver disease |
| CN118680948B (zh) * | 2023-10-20 | 2025-08-22 | 思合基因(北京)生物科技有限公司 | 寡核苷酸及其在抗乙型肝炎病毒中的应用 |
| AU2024369609A1 (en) | 2023-10-31 | 2025-12-11 | Korro Bio, Inc. | Oligonucleotides comprising phosphoramidate internucleotide linkages |
| TW202521133A (zh) * | 2023-11-27 | 2025-06-01 | 大陸商上海舶望製藥有限公司 | 抑制甲狀腺素運載蛋白(ttr)表達的組合物和方法 |
| WO2025119212A1 (zh) * | 2023-12-05 | 2025-06-12 | 广东东阳光药业股份有限公司 | 一种新型的双链siRNA、其缀合物及其用途 |
| CN120309684A (zh) * | 2024-01-15 | 2025-07-15 | 武汉人福创新药物研发中心有限公司 | 靶向化合物及其用途 |
| CN117568313B (zh) * | 2024-01-15 | 2024-04-26 | 上海贝斯昂科生物科技有限公司 | 基因编辑组合物及其用途 |
| WO2025155911A1 (en) | 2024-01-18 | 2025-07-24 | Proqr Therapeutics Ii B.V. | Antisense oligonucleotides for the treatment of hurler syndrome |
| EP4671372A2 (en) | 2024-01-29 | 2025-12-31 | Arnatar Therapeutics, Inc | Translation-enhancing nucleic acid compounds: Upward regulation 1 coupled with ASO (ACT-UP1) and their uses |
| WO2025165891A1 (en) | 2024-01-29 | 2025-08-07 | Arnatar Therapeutics, Inc | Translation enhancing nucleic acid compounds: aso coupled translation - upregulation 1 (act-up1) and uses thereof |
| WO2025196505A2 (en) | 2024-03-22 | 2025-09-25 | Takeda Pharmaceutical Company Limited | Compositions and methods for inhibiting cytochrome p450 family 7 subfamily a member 1 (cyp7a1) expression |
| GB202404661D0 (en) | 2024-04-02 | 2024-05-15 | Proqr Therapeutics Ii Bv | Antisense oligoncleotides for the treatment of liver disease |
| WO2025224230A1 (en) | 2024-04-25 | 2025-10-30 | Proqr Therapeutics Ii B.V. | Antisense oligonucleotides for the treatment of fatty liver disease |
| CN118146284B (zh) * | 2024-05-08 | 2024-07-26 | 北京悦康科创医药科技股份有限公司 | 一种GalNAc化合物、其与寡核苷酸缀合物及制备方法 |
| WO2025242702A1 (en) * | 2024-05-23 | 2025-11-27 | Glaxosmithkline Intellectual Property Development Limited | Enzymatic process for producing n-acetyl galactosamine clusters |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2249463C2 (ru) * | 1998-08-19 | 2005-04-10 | Бакстер Хелфкэа С.А. | Иммуногенный конъюгат бета-пропионамид-связанного полисахарида с белком, использующийся в качестве вакцины |
| WO2009073809A2 (en) * | 2007-12-04 | 2009-06-11 | Alnylam Pharmaceuticals, Inc. | Carbohydrate conjugates as delivery agents for oligonucleotides |
| WO2009126933A2 (en) * | 2008-04-11 | 2009-10-15 | Alnylam Pharmaceuticals, Inc. | Site-specific delivery of nucleic acids by combining targeting ligands with endosomolytic components |
| WO2013033230A1 (en) * | 2011-08-29 | 2013-03-07 | Isis Pharmaceuticals, Inc. | Oligomer-conjugate complexes and their use |
Family Cites Families (375)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3687808A (en) | 1969-08-14 | 1972-08-29 | Univ Leland Stanford Junior | Synthetic polynucleotides |
| US4458066A (en) | 1980-02-29 | 1984-07-03 | University Patents, Inc. | Process for preparing polynucleotides |
| US5132418A (en) | 1980-02-29 | 1992-07-21 | University Patents, Inc. | Process for preparing polynucleotides |
| US4500707A (en) | 1980-02-29 | 1985-02-19 | University Patents, Inc. | Nucleosides useful in the preparation of polynucleotides |
| 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 |
| US4668777A (en) | 1981-03-27 | 1987-05-26 | University Patents, Inc. | Phosphoramidite nucleoside compounds |
| US4415732A (en) | 1981-03-27 | 1983-11-15 | University Patents, Inc. | Phosphoramidite compounds and processes |
| US4973679A (en) | 1981-03-27 | 1990-11-27 | University Patents, Inc. | Process for oligonucleo tide synthesis using phosphormidite intermediates |
| US5023243A (en) | 1981-10-23 | 1991-06-11 | Molecular Biosystems, Inc. | Oligonucleotide therapeutic agent and method of making same |
| US4476301A (en) | 1982-04-29 | 1984-10-09 | Centre National De La Recherche Scientifique | Oligonucleotides, a process for preparing the same and their application as mediators of the action of interferon |
| DE3329892A1 (de) | 1983-08-18 | 1985-03-07 | Köster, Hubert, Prof. Dr., 2000 Hamburg | Verfahren zur herstellung von oligonucleotiden |
| US5118800A (en) | 1983-12-20 | 1992-06-02 | California Institute Of Technology | Oligonucleotides possessing a primary amino group in the terminal nucleotide |
| USRE34036E (en) | 1984-06-06 | 1992-08-18 | National Research Development Corporation | Data transmission using a transparent tone-in band system |
| US5550111A (en) | 1984-07-11 | 1996-08-27 | Temple University-Of The Commonwealth System Of Higher Education | Dual action 2',5'-oligoadenylate antiviral derivatives and uses thereof |
| FR2567892B1 (fr) | 1984-07-19 | 1989-02-17 | Centre Nat Rech Scient | Nouveaux oligonucleotides, leur procede de preparation et leurs applications comme mediateurs dans le developpement des effets des interferons |
| US5367066A (en) | 1984-10-16 | 1994-11-22 | Chiron Corporation | Oligonucleotides with selectably cleavable and/or abasic sites |
| FR2575751B1 (fr) | 1985-01-08 | 1987-04-03 | Pasteur Institut | Nouveaux nucleosides de derives de l'adenosine, leur preparation et leurs applications biologiques |
| US4751219A (en) | 1985-02-05 | 1988-06-14 | Nederlandse Centrale Organisatie Voor Toegepast-Natuur-Wetenschappelijk Onderzoek | Synthetic glycolipides, a process for the preparation thereof and several uses for these synthetic glycolipides |
| US5235033A (en) | 1985-03-15 | 1993-08-10 | Anti-Gene Development Group | Alpha-morpholino ribonucleoside derivatives and polymers thereof |
| US5506337A (en) | 1985-03-15 | 1996-04-09 | Antivirals Inc. | Morpholino-subunit combinatorial library and method |
| US5166315A (en) | 1989-12-20 | 1992-11-24 | Anti-Gene Development Group | Sequence-specific binding polymers for duplex nucleic acids |
| US5034506A (en) | 1985-03-15 | 1991-07-23 | Anti-Gene Development Group | Uncharged morpholino-based polymers having achiral intersubunit linkages |
| US5185444A (en) | 1985-03-15 | 1993-02-09 | Anti-Gene Deveopment Group | Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages |
| US5405938A (en) | 1989-12-20 | 1995-04-11 | Anti-Gene Development Group | Sequence-specific binding polymers for duplex nucleic acids |
| DE3788914T2 (de) | 1986-09-08 | 1994-08-25 | Ajinomoto Kk | Verbindungen zur Spaltung von RNS an eine spezifische Position, Oligomere, verwendet bei der Herstellung dieser Verbindungen und Ausgangsprodukte für die Synthese dieser Oligomere. |
| US5276019A (en) | 1987-03-25 | 1994-01-04 | The United States Of America As Represented By The Department Of Health And Human Services | Inhibitors for replication of retroviruses and for the expression of oncogene products |
| US5264423A (en) | 1987-03-25 | 1993-11-23 | The United States Of America As Represented By The Department Of Health And Human Services | Inhibitors for replication of retroviruses and for the expression of oncogene products |
| GB8712540D0 (en) * | 1987-05-28 | 1987-07-01 | Ucb Sa | Expression of human proapolipoprotein a-i |
| CA1340032C (en) | 1987-06-24 | 1998-09-08 | Jim Haralambidis | Lucleoside derivatives |
| US5188897A (en) | 1987-10-22 | 1993-02-23 | Temple University Of The Commonwealth System Of Higher Education | Encapsulated 2',5'-phosphorothioate oligoadenylates |
| US4924624A (en) | 1987-10-22 | 1990-05-15 | Temple University-Of The Commonwealth System Of Higher Education | 2,',5'-phosphorothioate oligoadenylates and plant antiviral uses thereof |
| EP0348458B1 (en) | 1987-11-30 | 1997-04-09 | University Of Iowa Research Foundation | Dna molecules stabilized by modifications of the 3'-terminal phosphodiester linkage and their use as nucleic acid probes and as therapeutic agents to block the expression of specifically targeted genes |
| US5403711A (en) | 1987-11-30 | 1995-04-04 | University Of Iowa Research Foundation | Nucleic acid hybridization and amplification method for detection of specific sequences in which a complementary labeled nucleic acid probe is cleaved |
| EP0406309A4 (en) | 1988-03-25 | 1992-08-19 | The University Of Virginia Alumni Patents Foundation | Oligonucleotide n-alkylphosphoramidates |
| US5278302A (en) | 1988-05-26 | 1994-01-11 | University Patents, Inc. | Polynucleotide phosphorodithioates |
| US5216141A (en) | 1988-06-06 | 1993-06-01 | Benner Steven A | Oligonucleotide analogs containing sulfur linkages |
| US5175273A (en) | 1988-07-01 | 1992-12-29 | Genentech, Inc. | Nucleic acid intercalating agents |
| US5194599A (en) | 1988-09-23 | 1993-03-16 | Gilead Sciences, Inc. | Hydrogen phosphonodithioate compositions |
| US5256775A (en) | 1989-06-05 | 1993-10-26 | Gilead Sciences, Inc. | Exonuclease-resistant oligonucleotides |
| US5134066A (en) | 1989-08-29 | 1992-07-28 | Monsanto Company | Improved probes using nucleosides containing 3-dezauracil analogs |
| US5591722A (en) | 1989-09-15 | 1997-01-07 | Southern Research Institute | 2'-deoxy-4'-thioribonucleosides and their antiviral activity |
| US5721218A (en) | 1989-10-23 | 1998-02-24 | Gilead Sciences, Inc. | Oligonucleotides with inverted polarity |
| US5399676A (en) | 1989-10-23 | 1995-03-21 | Gilead Sciences | Oligonucleotides with inverted polarity |
| 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 |
| JPH05504552A (ja) | 1989-10-24 | 1993-07-15 | ギリアド サイエンシズ,インコーポレイテッド | 2’位が改変されたオリゴヌクレオチド |
| US5177198A (en) | 1989-11-30 | 1993-01-05 | University Of N.C. At Chapel Hill | Process for preparing oligoribonucleoside and oligodeoxyribonucleoside boranophosphates |
| US5130302A (en) | 1989-12-20 | 1992-07-14 | Boron Bilogicals, Inc. | Boronated nucleoside, nucleotide and oligonucleotide compounds, compositions and methods for using same |
| US5587470A (en) | 1990-01-11 | 1996-12-24 | Isis Pharmaceuticals, Inc. | 3-deazapurines |
| US5587361A (en) | 1991-10-15 | 1996-12-24 | Isis Pharmaceuticals, Inc. | Oligonucleotides having phosphorothioate linkages of high chiral purity |
| US5623065A (en) | 1990-08-13 | 1997-04-22 | Isis Pharmaceuticals, Inc. | Gapped 2' modified oligonucleotides |
| US5859221A (en) | 1990-01-11 | 1999-01-12 | Isis Pharmaceuticals, Inc. | 2'-modified oligonucleotides |
| US5459255A (en) | 1990-01-11 | 1995-10-17 | Isis Pharmaceuticals, Inc. | N-2 substituted purines |
| US5457191A (en) | 1990-01-11 | 1995-10-10 | Isis Pharmaceuticals, Inc. | 3-deazapurines |
| US5670633A (en) | 1990-01-11 | 1997-09-23 | Isis Pharmaceuticals, Inc. | Sugar modified oligonucleotides that detect and modulate gene expression |
| US7101993B1 (en) | 1990-01-11 | 2006-09-05 | Isis Pharmaceuticals, Inc. | Oligonucleotides containing 2′-O-modified purines |
| US5681941A (en) | 1990-01-11 | 1997-10-28 | Isis Pharmaceuticals, Inc. | Substituted purines and oligonucleotide cross-linking |
| US5646265A (en) | 1990-01-11 | 1997-07-08 | Isis Pharmceuticals, Inc. | Process for the preparation of 2'-O-alkyl purine phosphoramidites |
| US6005087A (en) | 1995-06-06 | 1999-12-21 | Isis Pharmaceuticals, Inc. | 2'-modified oligonucleotides |
| US5220007A (en) | 1990-02-15 | 1993-06-15 | The Worcester Foundation For Experimental Biology | Method of site-specific alteration of RNA and production of encoded polypeptides |
| 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 |
| US5321131A (en) | 1990-03-08 | 1994-06-14 | Hybridon, Inc. | Site-specific functionalization of oligodeoxynucleotides for non-radioactive labelling |
| US5470967A (en) | 1990-04-10 | 1995-11-28 | The Dupont Merck Pharmaceutical Company | Oligonucleotide analogs with sulfamate linkages |
| GB9009980D0 (en) | 1990-05-03 | 1990-06-27 | Amersham Int Plc | Phosphoramidite derivatives,their preparation and the use thereof in the incorporation of reporter groups on synthetic oligonucleotides |
| EP0745689A3 (en) | 1990-05-11 | 1996-12-11 | Microprobe Corporation | A dipstick for a nucleic acid hybridization assay |
| US5610289A (en) | 1990-07-27 | 1997-03-11 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogues |
| US5602240A (en) | 1990-07-27 | 1997-02-11 | Ciba Geigy Ag. | Backbone modified oligonucleotide analogs |
| US5541307A (en) | 1990-07-27 | 1996-07-30 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogs and solid phase synthesis thereof |
| US5378825A (en) | 1990-07-27 | 1995-01-03 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogs |
| US5489677A (en) | 1990-07-27 | 1996-02-06 | Isis Pharmaceuticals, Inc. | Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms |
| US5618704A (en) | 1990-07-27 | 1997-04-08 | Isis Pharmacueticals, Inc. | Backbone-modified oligonucleotide analogs and preparation thereof through radical coupling |
| US5608046A (en) | 1990-07-27 | 1997-03-04 | Isis Pharmaceuticals, Inc. | Conjugated 4'-desmethyl nucleoside analog compounds |
| US5623070A (en) | 1990-07-27 | 1997-04-22 | Isis Pharmaceuticals, Inc. | Heteroatomic oligonucleoside linkages |
| US5677437A (en) | 1990-07-27 | 1997-10-14 | Isis Pharmaceuticals, Inc. | Heteroatomic oligonucleoside linkages |
| ATE154246T1 (de) | 1990-07-27 | 1997-06-15 | Isis Pharmaceuticals Inc | Nuklease resistente, pyrimidin modifizierte oligonukleotide, die die gen-expression detektieren und modulieren |
| US5223618A (en) | 1990-08-13 | 1993-06-29 | Isis Pharmaceuticals, Inc. | 4'-desmethyl nucleoside analog compounds |
| US5386023A (en) | 1990-07-27 | 1995-01-31 | Isis Pharmaceuticals | Backbone modified oligonucleotide analogs and preparation thereof through reductive coupling |
| FI930455A7 (fi) | 1990-08-03 | 1993-03-24 | Sanofi Sa | Yhdisteitä ja menetelmiä geeniekspression inhiboimiseksi |
| US5177196A (en) | 1990-08-16 | 1993-01-05 | Microprobe Corporation | Oligo (α-arabinofuranosyl nucleotides) and α-arabinofuranosyl precursors thereof |
| US5214134A (en) | 1990-09-12 | 1993-05-25 | Sterling Winthrop Inc. | Process of linking nucleosides with a siloxane bridge |
| US5561225A (en) | 1990-09-19 | 1996-10-01 | Southern Research Institute | Polynucleotide analogs containing sulfonate and sulfonamide internucleoside linkages |
| EP0549686A4 (en) | 1990-09-20 | 1995-01-18 | Gilead Sciences Inc | Modified internucleoside linkages |
| US5432272A (en) | 1990-10-09 | 1995-07-11 | Benner; Steven A. | Method for incorporating into a DNA or RNA oligonucleotide using nucleotides bearing heterocyclic bases |
| US6582908B2 (en) | 1990-12-06 | 2003-06-24 | Affymetrix, Inc. | Oligonucleotides |
| US5948903A (en) | 1991-01-11 | 1999-09-07 | Isis Pharmaceuticals, Inc. | Synthesis of 3-deazapurines |
| US5672697A (en) | 1991-02-08 | 1997-09-30 | Gilead Sciences, Inc. | Nucleoside 5'-methylene phosphonates |
| US7015315B1 (en) | 1991-12-24 | 2006-03-21 | Isis Pharmaceuticals, Inc. | Gapped oligonucleotides |
| US5571799A (en) | 1991-08-12 | 1996-11-05 | Basco, Ltd. | (2'-5') oligoadenylate analogues useful as inhibitors of host-v5.-graft response |
| EP0538194B1 (de) | 1991-10-17 | 1997-06-04 | Novartis AG | Bicyclische Nukleoside, Oligonukleotide, Verfahren zu deren Herstellung und Zwischenprodukte |
| US5594121A (en) | 1991-11-07 | 1997-01-14 | Gilead Sciences, Inc. | Enhanced triple-helix and double-helix formation with oligomers containing modified purines |
| EP0637965B1 (en) | 1991-11-26 | 2002-10-16 | Isis Pharmaceuticals, Inc. | Enhanced triple-helix and double-helix formation with oligomers containing modified pyrimidines |
| US5484908A (en) | 1991-11-26 | 1996-01-16 | Gilead Sciences, Inc. | Oligonucleotides containing 5-propynyl pyrimidines |
| TW393513B (en) | 1991-11-26 | 2000-06-11 | Isis Pharmaceuticals Inc | Enhanced triple-helix and double-helix formation with oligomers containing modified pyrimidines |
| US5792608A (en) | 1991-12-12 | 1998-08-11 | Gilead Sciences, Inc. | Nuclease stable and binding competent oligomers and methods for their use |
| US5359044A (en) | 1991-12-13 | 1994-10-25 | Isis Pharmaceuticals | Cyclobutyl oligonucleotide surrogates |
| ATE515510T1 (de) * | 1991-12-24 | 2011-07-15 | Isis Pharmaceuticals Inc | Durch dna-abschnitte unterbrochene modifizierte oligonukleotide |
| US5700922A (en) | 1991-12-24 | 1997-12-23 | Isis Pharmaceuticals, Inc. | PNA-DNA-PNA chimeric macromolecules |
| FR2687679B1 (fr) | 1992-02-05 | 1994-10-28 | Centre Nat Rech Scient | Oligothionucleotides. |
| US5633360A (en) | 1992-04-14 | 1997-05-27 | Gilead Sciences, Inc. | Oligonucleotide analogs capable of passive cell membrane permeation |
| US5434257A (en) | 1992-06-01 | 1995-07-18 | Gilead Sciences, Inc. | Binding compentent oligomers containing unsaturated 3',5' and 2',5' linkages |
| EP0577558A2 (de) | 1992-07-01 | 1994-01-05 | Ciba-Geigy Ag | Carbocyclische Nukleoside mit bicyclischen Ringen, Oligonukleotide daraus, Verfahren zu deren Herstellung, deren Verwendung und Zwischenproduckte |
| US5652355A (en) | 1992-07-23 | 1997-07-29 | Worcester Foundation For Experimental Biology | Hybrid oligonucleotide phosphorothioates |
| JPH08502723A (ja) | 1992-07-27 | 1996-03-26 | ハイブライドン インコーポレイテッド | オリゴヌクレオチド・アルキルホスホノチオエート |
| WO1994014226A1 (en) | 1992-12-14 | 1994-06-23 | Honeywell Inc. | Motor system with individually controlled redundant windings |
| AU6165494A (en) | 1993-01-25 | 1994-08-15 | Hybridon, Inc. | Oligonucleotide alkylphosphonates and alkylphosphonothioates |
| US5476925A (en) | 1993-02-01 | 1995-12-19 | Northwestern University | Oligodeoxyribonucleotides including 3'-aminonucleoside-phosphoramidate linkages and terminal 3'-amino groups |
| GB9304618D0 (en) | 1993-03-06 | 1993-04-21 | Ciba Geigy Ag | Chemical compounds |
| GB9304620D0 (en) | 1993-03-06 | 1993-04-21 | Ciba Geigy Ag | Compounds |
| EP0691968B1 (en) | 1993-03-30 | 1997-07-16 | Sanofi | Acyclic nucleoside analogs and oligonucleotide sequences containing them |
| EP0691977B1 (en) | 1993-03-31 | 1997-11-26 | Sanofi | Oligonucleotides with amide linkages replacing phosphodiester linkages |
| US5502177A (en) | 1993-09-17 | 1996-03-26 | Gilead Sciences, Inc. | Pyrimidine derivatives for labeled binding partners |
| US5801154A (en) | 1993-10-18 | 1998-09-01 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotide modulation of multidrug resistance-associated protein |
| US5457187A (en) | 1993-12-08 | 1995-10-10 | Board Of Regents University Of Nebraska | Oligonucleotides containing 5-fluorouracil |
| US5446137B1 (en) | 1993-12-09 | 1998-10-06 | Behringwerke Ag | Oligonucleotides containing 4'-substituted nucleotides |
| ES2149962T3 (es) | 1993-12-09 | 2000-11-16 | Univ Jefferson | Compuestos y metodos para mutaciones dirigidas al sitio en celulas eucarioticas. |
| US5519134A (en) | 1994-01-11 | 1996-05-21 | Isis Pharmaceuticals, Inc. | Pyrrolidine-containing monomers and oligomers |
| US5728518A (en) | 1994-01-12 | 1998-03-17 | The Immune Response Corporation | Antiviral poly-and oligonucleotides |
| US5596091A (en) | 1994-03-18 | 1997-01-21 | The Regents Of The University Of California | Antisense oligonucleotides comprising 5-aminoalkyl pyrimidine nucleotides |
| US5627053A (en) | 1994-03-29 | 1997-05-06 | Ribozyme Pharmaceuticals, Inc. | 2'deoxy-2'-alkylnucleotide containing nucleic acid |
| US5625050A (en) | 1994-03-31 | 1997-04-29 | Amgen Inc. | Modified oligonucleotides and intermediates useful in nucleic acid therapeutics |
| US5646269A (en) | 1994-04-28 | 1997-07-08 | Gilead Sciences, Inc. | Method for oligonucleotide analog synthesis |
| US5525711A (en) | 1994-05-18 | 1996-06-11 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Pteridine nucleotide analogs as fluorescent DNA probes |
| US5597909A (en) | 1994-08-25 | 1997-01-28 | Chiron Corporation | Polynucleotide reagents containing modified deoxyribose moieties, and associated methods of synthesis and use |
| US5599706A (en) | 1994-09-23 | 1997-02-04 | Stinchcomb; Dan T. | Ribozymes targeted to apo(a) mRNA |
| US5681940A (en) * | 1994-11-02 | 1997-10-28 | Icn Pharmaceuticals | Sugar modified nucleosides and oligonucleotides |
| US6172045B1 (en) | 1994-12-07 | 2001-01-09 | Neorx Corporation | Cluster clearing agents |
| US6908903B1 (en) | 1994-12-07 | 2005-06-21 | Aletheon Pharmaceuticals, Inc. | Cluster clearing agents |
| US5652356A (en) | 1995-08-17 | 1997-07-29 | Hybridon, Inc. | Inverted chimeric and hybrid oligonucleotides |
| US20030119724A1 (en) | 1995-11-22 | 2003-06-26 | Ts`O Paul O.P. | Ligands to enhance cellular uptake of biomolecules |
| JP2000501414A (ja) | 1995-11-22 | 2000-02-08 | ザ・ジョンズ・ホプキンス・ユニバーシティー | 生体分子の細胞取り込みを高めるリガンド |
| US5998203A (en) | 1996-04-16 | 1999-12-07 | Ribozyme Pharmaceuticals, Inc. | Enzymatic nucleic acids containing 5'-and/or 3'-cap structures |
| US6620916B1 (en) | 1996-09-26 | 2003-09-16 | Ajinomoto Co., Inc. | Modified physiologically active proteins and medicinal compositions containing the same |
| US6770748B2 (en) | 1997-03-07 | 2004-08-03 | Takeshi Imanishi | Bicyclonucleoside and oligonucleotide analogue |
| JP3756313B2 (ja) | 1997-03-07 | 2006-03-15 | 武 今西 | 新規ビシクロヌクレオシド及びオリゴヌクレオチド類縁体 |
| USRE44779E1 (en) | 1997-03-07 | 2014-02-25 | Santaris Pharma A/S | Bicyclonucleoside and oligonucleotide analogues |
| US6794499B2 (en) | 1997-09-12 | 2004-09-21 | Exiqon A/S | Oligonucleotide analogues |
| US7572582B2 (en) | 1997-09-12 | 2009-08-11 | Exiqon A/S | Oligonucleotide analogues |
| EP2253639A1 (en) | 1997-09-12 | 2010-11-24 | Exiqon A/S | Bi- and tri-cyclic nucleoside, nucleotide and oligonucleoide analogues |
| US20040171564A1 (en) | 1997-11-20 | 2004-09-02 | Honkanen Richard E. | Antisense oligonucleotide modulation of human serine/threonine protein phosphatase gene expression |
| US20030228597A1 (en) | 1998-04-13 | 2003-12-11 | Cowsert Lex M. | Identification of genetic targets for modulation by oligonucleotides and generation of oligonucleotides for gene modulation |
| US6300319B1 (en) | 1998-06-16 | 2001-10-09 | Isis Pharmaceuticals, Inc. | Targeted oligonucleotide conjugates |
| US6043352A (en) | 1998-08-07 | 2000-03-28 | Isis Pharmaceuticals, Inc. | 2'-O-Dimethylaminoethyloxyethyl-modified oligonucleotides |
| WO2000010599A2 (en) | 1998-08-19 | 2000-03-02 | North American Vaccine, Inc. | IMMUNOGENIC β-PROPIONAMIDO-LINKED POLYSACCHARIDE PROTEIN CONJUGATE USEFUL AS A VACCINE PRODUCED USING AN N-ACRYLOYLATED POLYSACCHARIDE |
| US6166239A (en) | 1998-09-04 | 2000-12-26 | Isis Pharmaceuticals, Inc. | Oligonucleotide protecting groups |
| EP1152009B2 (en) | 1999-02-12 | 2017-09-06 | Daiichi Sankyo Company, Limited | Novel nucleosides and oligonucleotide analogues |
| US20030170249A1 (en) | 1999-02-19 | 2003-09-11 | Hakomori Sen-Itiroh | Vaccines directed to cancer-associated carbohydrate antigens |
| US7084125B2 (en) | 1999-03-18 | 2006-08-01 | Exiqon A/S | Xylo-LNA analogues |
| US7098192B2 (en) | 1999-04-08 | 2006-08-29 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotide modulation of STAT3 expression |
| US6159694A (en) | 1999-04-08 | 2000-12-12 | Isis Pharmaceuticals Inc. | Antisense modulation of stat3 expression |
| IL145778A0 (en) | 1999-04-21 | 2002-07-25 | American Home Prod | Methods and compositions for inhibiting the function of polynucleotide sequences |
| CN102180924A (zh) | 1999-05-04 | 2011-09-14 | 桑塔里斯制药公司 | L-核糖-lna类似物 |
| US6525191B1 (en) | 1999-05-11 | 2003-02-25 | Kanda S. Ramasamy | Conformationally constrained L-nucleosides |
| US6383812B1 (en) | 1999-05-28 | 2002-05-07 | Academia Sinica | Anti liver disease drug R-YEEE and method of synthesizing branched galactose-terminal glycoproteins |
| US8541548B2 (en) | 1999-06-07 | 2013-09-24 | Arrowhead Madison Inc. | Compounds and methods for reversible modification of biologically active molecules |
| US20080281041A1 (en) | 1999-06-07 | 2008-11-13 | Rozema David B | Reversibly Masked Polymers |
| US6656730B1 (en) | 1999-06-15 | 2003-12-02 | Isis Pharmaceuticals, Inc. | Oligonucleotides conjugated to protein-binding drugs |
| CA2379152A1 (en) | 1999-07-16 | 2001-01-25 | Hyseq, Inc. | Novel angiopoietin materials and methods |
| JP4151751B2 (ja) | 1999-07-22 | 2008-09-17 | 第一三共株式会社 | 新規ビシクロヌクレオシド類縁体 |
| DE19935303A1 (de) | 1999-07-28 | 2001-02-08 | Aventis Pharma Gmbh | Oligonukleotide zur Inhibierung der Expression von humanem eg5 |
| US20020082227A1 (en) | 1999-09-30 | 2002-06-27 | Scott Henry | Use of oligonucleotides for inhibition of complement activation |
| US20050112118A1 (en) | 1999-12-02 | 2005-05-26 | Myriad Genetics, Incorporated | Compositions and methods for treating inflammatory disorders |
| EP1239050A4 (en) | 1999-12-09 | 2004-07-21 | Sankyo Co | METHOD FOR TESTING CURATIVE OR PREVENTIVE AGENT OF HYPERLIPEMIA |
| DE60027203T2 (de) | 1999-12-30 | 2007-01-04 | K.U. Leuven Research & Development | Cyclohexennukleinsäuren |
| US20020055479A1 (en) | 2000-01-18 | 2002-05-09 | Cowsert Lex M. | Antisense modulation of PTP1B expression |
| US6261840B1 (en) | 2000-01-18 | 2001-07-17 | Isis Pharmaceuticals, Inc. | Antisense modulation of PTP1B expression |
| US7179796B2 (en) | 2000-01-18 | 2007-02-20 | Isis Pharmaceuticals, Inc. | Antisense modulation of PTP1B expression |
| US6602857B1 (en) | 2000-01-18 | 2003-08-05 | Isis Pharmaceuticals, Inc. | Antisense modulation of PTP1B expression |
| US7833992B2 (en) | 2001-05-18 | 2010-11-16 | Merck Sharpe & Dohme | Conjugates and compositions for cellular delivery |
| US7491805B2 (en) | 2001-05-18 | 2009-02-17 | Sirna Therapeutics, Inc. | Conjugates and compositions for cellular delivery |
| US8202979B2 (en) | 2002-02-20 | 2012-06-19 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid |
| WO2001060860A2 (en) | 2000-02-17 | 2001-08-23 | Millennium Predictive Medicine, Inc. | Genes differentially expressed in human prostate cancer and their use |
| EP1314734A1 (en) | 2000-08-29 | 2003-05-28 | Takeshi Imanishi | Novel nucleoside analogs and oligonucleotide derivatives containing these analogs |
| US6426220B1 (en) | 2000-10-30 | 2002-07-30 | Isis Pharmaceuticals, Inc. | Antisense modulation of calreticulin expression |
| CN100406065C (zh) * | 2000-12-01 | 2008-07-30 | 细胞工厂治疗公司 | 糖基化/半乳糖基化肽、双官能接头和核苷酸单体/多聚体的缀合物以及相关的组合物和使用方法 |
| US20030077829A1 (en) | 2001-04-30 | 2003-04-24 | Protiva Biotherapeutics Inc.. | Lipid-based formulations |
| EP1403367A4 (en) | 2001-06-08 | 2005-08-17 | Sankyo Co | A MEDICAMENT TEST METHOD FOR TREATING OR PREVENTING DISEASES SUCH AS HYPERLIPEMIA |
| WO2003004602A2 (en) | 2001-07-03 | 2003-01-16 | Isis Pharmaceuticals, Inc. | Nuclease resistant chimeric oligonucleotides |
| US20030175906A1 (en) | 2001-07-03 | 2003-09-18 | Muthiah Manoharan | Nuclease resistant chimeric oligonucleotides |
| US20030158403A1 (en) | 2001-07-03 | 2003-08-21 | Isis Pharmaceuticals, Inc. | Nuclease resistant chimeric oligonucleotides |
| US7425545B2 (en) * | 2001-07-25 | 2008-09-16 | Isis Pharmaceuticals, Inc. | Modulation of C-reactive protein expression |
| US6964950B2 (en) | 2001-07-25 | 2005-11-15 | Isis Pharmaceuticals, Inc. | Antisense modulation of C-reactive protein expression |
| US7227014B2 (en) | 2001-08-07 | 2007-06-05 | Isis Pharmaceuticals, Inc. | Antisense modulation of apolipoprotein (a) expression |
| US7259150B2 (en) | 2001-08-07 | 2007-08-21 | Isis Pharmaceuticals, Inc. | Modulation of apolipoprotein (a) expression |
| WO2003014397A1 (en) | 2001-08-09 | 2003-02-20 | Biomedlab Corporation | Probe for detection of enteric virus detection kit and method for enteric virus with the same |
| WO2003020739A2 (en) | 2001-09-04 | 2003-03-13 | Exiqon A/S | Novel lna compositions and uses thereof |
| US7439043B2 (en) | 2001-10-10 | 2008-10-21 | Neose Technologies, Inc. | Galactosyl nucleotide sugars |
| EP1451578B1 (en) | 2001-11-16 | 2013-08-21 | Genentech, Inc. | Use of angptl3 antagonists for the treatment of liver diseases |
| US20100240730A1 (en) | 2002-02-20 | 2010-09-23 | Merck Sharp And Dohme Corp. | RNA Interference Mediated Inhibition of Gene Expression Using Chemically Modified Short Interfering Nucleic Acid (siNA) |
| WO2004011624A2 (en) | 2002-07-31 | 2004-02-05 | Nucleonics, Inc. | Double stranded rna structures and constructs, and methods for generating and using the same |
| WO2004014933A1 (en) | 2002-08-07 | 2004-02-19 | University Of Massachusetts | Compositions for rna interference and methods of use thereof |
| EP1543019A2 (en) | 2002-09-11 | 2005-06-22 | Santaris Pharma A/S | Modified pna molecules |
| CA2502649A1 (en) | 2002-10-18 | 2004-04-29 | Nucleonics Inc. | Double-stranded rna structures and constructs, and methods for generating and using the same |
| AU2003291753B2 (en) | 2002-11-05 | 2010-07-08 | Isis Pharmaceuticals, Inc. | Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation |
| WO2004044139A2 (en) | 2002-11-05 | 2004-05-27 | Isis Parmaceuticals, Inc. | Modified oligonucleotides for use in rna interference |
| US20060009410A1 (en) | 2002-11-13 | 2006-01-12 | Crooke Rosanne M | Effects of apolipoprotein B inhibition on gene expression profiles in animals |
| US7511131B2 (en) | 2002-11-13 | 2009-03-31 | Genzyme Corporation | Antisense modulation of apolipoprotein B expression |
| WO2004044181A2 (en) | 2002-11-13 | 2004-05-27 | Isis Pharmaceuticals, Inc. | Antisense modulation of apolipoprotein b expression |
| US8090542B2 (en) | 2002-11-14 | 2012-01-03 | Dharmacon Inc. | Functional and hyperfunctional siRNA |
| EP2474631B1 (en) | 2002-12-20 | 2014-02-12 | Celera Corporation | Genetic polymorphisms associated with myocardial infarction, methods of detection and uses thereof |
| US6673661B1 (en) | 2002-12-20 | 2004-01-06 | Taiwan Semiconductor Manufacturing Co., Ltd. | Self-aligned method for forming dual gate thin film transistor (TFT) device |
| WO2004063208A1 (en) | 2003-01-09 | 2004-07-29 | Postech Foundation | New phosphoramidite compounds |
| WO2004072046A2 (en) | 2003-02-12 | 2004-08-26 | Carex S.A. | Quinoline derivatives and their use for modulation of lxr activity |
| US7803781B2 (en) | 2003-02-28 | 2010-09-28 | Isis Pharmaceuticals, Inc. | Modulation of growth hormone receptor expression and insulin-like growth factor expression |
| ATE479752T1 (de) * | 2003-03-07 | 2010-09-15 | Alnylam Pharmaceuticals Inc | Therapeutische zusammensetzungen |
| JP2006522158A (ja) * | 2003-04-03 | 2006-09-28 | 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 | iRNA複合体 |
| US7598227B2 (en) | 2003-04-16 | 2009-10-06 | Isis Pharmaceuticals Inc. | Modulation of apolipoprotein C-III expression |
| US7851615B2 (en) | 2003-04-17 | 2010-12-14 | Alnylam Pharmaceuticals, Inc. | Lipophilic conjugated iRNA agents |
| US7723509B2 (en) | 2003-04-17 | 2010-05-25 | Alnylam Pharmaceuticals | IRNA agents with biocleavable tethers |
| JP4597976B2 (ja) | 2003-04-17 | 2010-12-15 | 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 | 修飾iRNA剤 |
| US7750142B2 (en) | 2003-04-28 | 2010-07-06 | Isis Pharmaceuticals, Inc. | Modulation of glucagon receptor expression |
| US7399853B2 (en) | 2003-04-28 | 2008-07-15 | Isis Pharmaceuticals | Modulation of glucagon receptor expression |
| WO2004101619A1 (ja) | 2003-05-15 | 2004-11-25 | Shionogi Co., Ltd. | 機能的糖ペプチドの合理的設計および合成 |
| WO2004106356A1 (en) | 2003-05-27 | 2004-12-09 | Syddansk Universitet | Functionalized nucleotide derivatives |
| DK1661905T3 (da) | 2003-08-28 | 2012-07-23 | Takeshi Imanishi | Hidtil ukendte syntetiske nukleinsyrer af N-O-krydsbindingstype |
| WO2005027962A1 (en) | 2003-09-18 | 2005-03-31 | Isis Pharmaceuticals, Inc. | 4’-thionucleosides and oligomeric compounds |
| EA009670B1 (ru) * | 2003-09-18 | 2008-02-28 | Ай Эс Ай Эс ФАРМАСЬЮТИКАЛЗ, ИНК. | МОДУЛИРОВАНИЕ ЭКСПРЕССИИ eIF4E |
| US8258105B2 (en) * | 2003-10-07 | 2012-09-04 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotides optimized for kidney targeting |
| US7959919B2 (en) | 2003-11-19 | 2011-06-14 | Novelmed Therapeutics, Inc. | Method of inhibiting factor B-mediated complement activation |
| WO2005065686A1 (en) | 2004-01-07 | 2005-07-21 | Adipogen Pharmaceuticals Pty Limited | Differentiation modulating agents and uses therefor |
| WO2005071080A2 (en) | 2004-01-20 | 2005-08-04 | Isis Pharmaceuticals, Inc. | Modulation of glucocorticoid receptor expression |
| JP4628960B2 (ja) * | 2004-02-05 | 2011-02-09 | 独立行政法人科学技術振興機構 | リンカー化合物及びリガンド複合体、並びにそれらの製造方法 |
| US20050244869A1 (en) | 2004-04-05 | 2005-11-03 | Brown-Driver Vickie L | Modulation of transthyretin expression |
| WO2005097155A1 (ja) | 2004-04-08 | 2005-10-20 | Takara Bio Inc. | 神経突起伸長誘導剤 |
| CN101052717A (zh) | 2004-05-11 | 2007-10-10 | α基因株式会社 | 诱发rna干扰的多核苷酸以及使用该多核苷酸的基因表达抑制方法 |
| JP2008501694A (ja) | 2004-06-03 | 2008-01-24 | アイシス ファーマシューティカルズ、インク. | 遺伝子調節の使用のために個別に修飾された鎖を有する二本鎖組成物 |
| PT1771474E (pt) | 2004-07-20 | 2010-05-03 | Genentech Inc | Inibidores de proteína 4 do tipo angiopoietina, combinações e sua utilização |
| EP1781698B1 (en) | 2004-07-20 | 2016-07-06 | Genentech, Inc. | Compositions and methods of using angiopoietin-like 4 protein |
| DK1786472T3 (da) | 2004-08-10 | 2013-04-15 | Genzyme Corp | Antisense-modulering af apolipoprotein B-ekspression |
| US7582744B2 (en) | 2004-08-10 | 2009-09-01 | Alnylam Pharmaceuticals, Inc. | Chemically modified oligonucleotides |
| WO2006031461A2 (en) | 2004-09-09 | 2006-03-23 | Isis Pharmaceuticals, Inc. | Pyrrolidinyl groups for attaching conjugates to oligomeric compounds |
| JP4944034B2 (ja) | 2004-10-13 | 2012-05-30 | アイシス ファーマシューティカルズ, インコーポレーテッド | Ptp1b発現のアンチセンス調節 |
| US20080261905A1 (en) | 2004-11-08 | 2008-10-23 | K.U. Leuven Research And Development | Modified Nucleosides for Rna Interference |
| US20060148740A1 (en) | 2005-01-05 | 2006-07-06 | Prosensa B.V. | Mannose-6-phosphate receptor mediated gene transfer into muscle cells |
| JP2008527993A (ja) | 2005-01-24 | 2008-07-31 | アヴァリス・アクチエボラーグ | 特異性及び送達の改善のためのsiRNA分子、shRNA分子又はアンチセンス分子及び機能的実体を含む複合体 |
| EA200800823A1 (ru) * | 2005-09-15 | 2008-10-30 | Сантарис Фарма А/С | Соединения-антагонисты рнк для ингибирования экспрессии аро-в100 |
| US20070087987A1 (en) | 2005-09-19 | 2007-04-19 | Monia Brett P | Modulation of glucagon receptor expression |
| CN101313066A (zh) | 2005-09-19 | 2008-11-26 | 强生医药研究及开发有限责任公司 | 糖皮质激素受体表达的调节 |
| EP2161038B1 (en) | 2006-01-26 | 2013-12-25 | Isis Pharmaceuticals, Inc. | Compositions and their uses directed to Huntingtin |
| US7569686B1 (en) | 2006-01-27 | 2009-08-04 | Isis Pharmaceuticals, Inc. | Compounds and methods for synthesis of bicyclic nucleic acid analogs |
| CN102908630B (zh) | 2006-01-27 | 2014-11-19 | Isis制药公司 | 6-修饰的双环核酸类似物 |
| US20090292006A1 (en) | 2006-05-05 | 2009-11-26 | Sanjay Bhanot | Compounds and methods for modulating expression of dgat2 |
| ES2366973T3 (es) * | 2006-05-05 | 2011-10-27 | Isis Pharmaceuticals, Inc. | Compuestos y procedimiento para modular la expresión génica. |
| US7666854B2 (en) | 2006-05-11 | 2010-02-23 | Isis Pharmaceuticals, Inc. | Bis-modified bicyclic nucleic acid analogs |
| JP5441688B2 (ja) | 2006-05-11 | 2014-03-12 | アイシス ファーマシューティカルズ, インコーポレーテッド | 5’修飾二環式核酸類似体 |
| JP2010500290A (ja) | 2006-08-04 | 2010-01-07 | アイシス ファーマシューティカルズ, インコーポレーテッド | Jnkタンパク質を調節するための組成物および方法 |
| KR101133799B1 (ko) | 2006-08-18 | 2012-04-24 | 에프. 호프만-라 로슈 아게 | 폴리뉴클레오타이드의 생체내 전달을 위한 다가접합체 |
| US8658211B2 (en) | 2006-08-18 | 2014-02-25 | Arrowhead Madison Inc. | Polyconjugates for in vivo delivery of polynucleotides |
| EP2081949B1 (en) | 2006-09-22 | 2014-12-10 | GE Healthcare Dharmacon, Inc. | Tripartite oligonucleotide complexes and methods for gene silencing by rna interference |
| WO2008049085A1 (en) | 2006-10-18 | 2008-04-24 | Isis Pharmaceuticals, Inc. | Antisense compounds |
| US8084437B2 (en) | 2006-11-27 | 2011-12-27 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
| US8093222B2 (en) | 2006-11-27 | 2012-01-10 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
| KR101503937B1 (ko) | 2006-12-08 | 2015-03-18 | 렉시컨 파마슈티컬스 인코퍼레이티드 | Angptl3 에 대한 단일클론 항체 |
| CN101616690B (zh) * | 2006-12-20 | 2015-11-25 | 爱克索马美国有限责任公司 | 用于治疗IL-1β相关疾病的方法 |
| EP2125852B1 (en) | 2007-02-15 | 2016-04-06 | Ionis Pharmaceuticals, Inc. | 5'-substituted-2'-f modified nucleosides and oligomeric compounds prepared therefrom |
| EP2604283A1 (en) | 2007-02-16 | 2013-06-19 | KTB Tumorforschungsgesellschaft mbH | Receptor And Antigen Targeted Prodrug |
| AU2008221287A1 (en) | 2007-03-01 | 2008-09-04 | Wellstat Immunotherapeutics, Llc | Treatment of diseases characterized by inflammation |
| CA2679244A1 (en) | 2007-03-02 | 2009-03-05 | Mdrna, Inc. | Nucleic acid compounds for inhibiting myc gene expression and uses thereof |
| WO2008131419A2 (en) | 2007-04-23 | 2008-10-30 | Alnylam Pharmaceuticals, Inc. | Glycoconjugates of rna interference agents |
| DK2170917T3 (da) | 2007-05-30 | 2012-10-08 | Isis Pharmaceuticals Inc | N-Substituerede bicycliske nukleinsyreanaloge med aminomethylenbro |
| ES2386492T3 (es) | 2007-06-08 | 2012-08-21 | Isis Pharmaceuticals, Inc. | Análogos de ácidos nucleicos bicíclicos carbocíclicos |
| WO2009003009A1 (en) | 2007-06-26 | 2008-12-31 | Enanta Pharmaceuticals, Inc. | Substituted pyrrolidine as anti-infectives |
| ES2376507T5 (es) | 2007-07-05 | 2015-08-31 | Isis Pharmaceuticals, Inc. | Análogos de ácidos nucleicos bicíclicos 6-disustituidos |
| EP2188298B1 (en) | 2007-08-15 | 2013-09-18 | Isis Pharmaceuticals, Inc. | Tetrahydropyran nucleic acid analogs |
| BRPI0815324A2 (pt) * | 2007-08-20 | 2015-07-14 | Protalix Ltd | "conjugado protêico que contém sacarídeos, processo de separação do conjugado protêico que contém sacarídeos, composição farmacêutica do conjugado protêico que contém sacarídeos, uso do conjugado protêico que contém sacarídeos e composto do conjugado protêico que contém sacarídeos" |
| JP5792955B2 (ja) * | 2007-10-01 | 2015-10-14 | アイシス ファーマシューティカルズ, インコーポレーテッド | 線維芽細胞増殖因子受容体4発現のアンチセンスモジュレーション |
| US9029337B2 (en) | 2007-11-09 | 2015-05-12 | Isis Pharmaceuticals, Inc. | Modulation of factor 7 expression |
| WO2009067647A1 (en) | 2007-11-21 | 2009-05-28 | Isis Pharmaceuticals, Inc. | Carbocyclic alpha-l-bicyclic nucleic acid analogs |
| EP3673910B1 (en) | 2007-12-27 | 2023-11-22 | Stelic Institute & Co., Inc. | Sugar chain-related gene and use thereof |
| AU2009241591A1 (en) | 2008-01-31 | 2009-11-05 | Alnylam Pharmaceuticals, Inc. | Optimized methods for delivery of DSRNA targeting the PCSK9 gene |
| US8530640B2 (en) | 2008-02-07 | 2013-09-10 | Isis Pharmaceuticals, Inc. | Bicyclic cyclohexitol nucleic acid analogs |
| WO2009142822A2 (en) | 2008-03-26 | 2009-11-26 | Alnylam Pharmaceuticals, Inc. | 2-f modified rna interference agents |
| WO2009143369A2 (en) | 2008-05-22 | 2009-11-26 | Isis Pharmaceuticals, Inc. | Method of preparing nucleosides and analogs thereof without using chromatography |
| WO2009148605A2 (en) | 2008-06-04 | 2009-12-10 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
| WO2010006215A1 (en) | 2008-07-09 | 2010-01-14 | Celera Corporation | Genetic polymorphisms associated with cardiovascular diseases, methods of detection and uses thereof |
| EP2323667A4 (en) | 2008-08-07 | 2012-07-25 | Isis Pharmaceuticals Inc | MODULATION OF TRANSTHYRETIN EXPRESSION BY TREATMENT OF CNS DISEASES |
| WO2010039548A2 (en) | 2008-09-23 | 2010-04-08 | Alnylam Pharmaceuticals, Inc. | Chemical modifications of monomers and oligonucleotides with cycloaddition |
| WO2010036696A1 (en) | 2008-09-24 | 2010-04-01 | Isis Pharmaceuticals, Inc. | Cyclohexenyl nucleic acid analogs |
| EP2356129B1 (en) | 2008-09-24 | 2013-04-03 | Isis Pharmaceuticals, Inc. | Substituted alpha-l-bicyclic nucleosides |
| CA2740785C (en) | 2008-10-15 | 2017-06-20 | Isis Pharmaceuticals, Inc. | Modulation of factor 11 expression |
| PL2937418T3 (pl) * | 2008-10-20 | 2018-04-30 | Alnylam Pharmaceuticals, Inc. | Kompozycje i sposoby hamowania ekspresji transtyretyny |
| EP2447274B1 (en) | 2008-10-24 | 2017-10-04 | Ionis Pharmaceuticals, Inc. | Oligomeric compounds and methods |
| WO2010048552A2 (en) | 2008-10-24 | 2010-04-29 | Isis Pharmaceuticals, Inc. | Methods of using oligomeric compounds comprising 2'-substituted nucleosides |
| PL2355851T3 (pl) | 2008-11-10 | 2018-08-31 | Arbutus Biopharma Corporation | Nowe lipidy i kompozycje do dostarczania środków terapeutycznych |
| CA2750561C (en) | 2009-01-26 | 2017-10-10 | Protiva Biotherapeutics, Inc. | Compositions and methods for silencing apolipoprotein c-iii expression |
| EP3243504A1 (en) | 2009-01-29 | 2017-11-15 | Arbutus Biopharma Corporation | Improved lipid formulation |
| WO2010101951A1 (en) | 2009-03-02 | 2010-09-10 | Alnylam Pharmaceuticals, Inc. | Nucleic acid chemical modifications |
| FR2943060B1 (fr) | 2009-03-13 | 2013-01-04 | Commissariat Energie Atomique | Agents chelatants d'ions metalliques, leurs procedes de preparation et leurs applications |
| NZ595891A (en) | 2009-04-15 | 2013-06-28 | Isis Pharmaceuticals Inc | Modulation of inflammatory responses by factor xi |
| US8883202B2 (en) | 2009-05-05 | 2014-11-11 | Tekmira Pharmaceuticals Corporation | Lipid compositions |
| CA2764158A1 (en) | 2009-06-01 | 2010-12-09 | Halo-Bio Rnai Therapeutics, Inc. | Polynucleotides for multivalent rna interference, compositions and methods of use thereof |
| LT2440183T (lt) | 2009-06-10 | 2018-08-10 | Arbutus Biopharma Corporation | Patobulinta lipido kompozicija |
| MX2011013421A (es) | 2009-06-15 | 2012-03-16 | Alnylam Pharmaceuticals Inc | Arnds formulado con lipido de direccionamiento del gen pcsk9. |
| CA2767225A1 (en) | 2009-07-06 | 2011-01-13 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for enhancing production of a biological product |
| WO2011005861A1 (en) | 2009-07-07 | 2011-01-13 | Alnylam Pharmaceuticals, Inc. | Oligonucleotide end caps |
| WO2011005860A2 (en) | 2009-07-07 | 2011-01-13 | Alnylam Pharmaceuticals, Inc. | 5' phosphate mimics |
| WO2011008995A1 (en) | 2009-07-16 | 2011-01-20 | Isis Pharmaceuticals, Inc. | Modulation of factor 7 expression |
| US9012421B2 (en) | 2009-08-06 | 2015-04-21 | Isis Pharmaceuticals, Inc. | Bicyclic cyclohexose nucleic acid analogs |
| US8901072B2 (en) * | 2009-08-12 | 2014-12-02 | The Medicines Company | Glycopeptide and lipoglycopeptide antibiotics with improved solubility |
| US8552163B2 (en) | 2009-09-25 | 2013-10-08 | Johns Hopkins University | Liver-targeting agents and their synthesis |
| JP5892938B2 (ja) | 2009-10-16 | 2016-03-30 | グラクソ グループ リミテッドGlaxo Group Limited | Hbvアンチセンス阻害剤 |
| TWI388338B (zh) | 2009-10-26 | 2013-03-11 | Iner Aec Executive Yuan | 對聚合醣鏈進行放射標誌以作為肝受體造影劑之方法 |
| TWI391144B (zh) | 2009-10-26 | 2013-04-01 | Iner Aec Executive Yuan | 一種定量肝殘餘功能的檢驗方法與其新穎肝受體造影檢驗藥劑 |
| WO2011056883A1 (en) * | 2009-11-03 | 2011-05-12 | Alnylam Pharmaceuticals, Inc. | Lipid formulated compositions and methods for inhibiting expression of transthyretin (ttr) |
| WO2011072290A2 (en) | 2009-12-11 | 2011-06-16 | The Regents Of The University Of Michigan | Targeted dendrimer-drug conjugates |
| CA2786071C (en) | 2010-01-08 | 2021-01-12 | Isis Pharmaceuticals, Inc. | Modulation of angiopoietin-like 3 expression |
| US9198972B2 (en) | 2010-01-28 | 2015-12-01 | Alnylam Pharmaceuticals, Inc. | Monomers and oligonucleotides comprising cycloaddition adduct(s) |
| WO2011104169A1 (en) | 2010-02-24 | 2011-09-01 | F. Hoffmann-La Roche Ag | Compositions for targeted delivery of sirna |
| WO2011115818A1 (en) | 2010-03-17 | 2011-09-22 | Isis Pharmaceuticals, Inc. | 5'-substituted bicyclic nucleosides and oligomeric compounds prepared therefrom |
| US20130109817A1 (en) | 2010-03-26 | 2013-05-02 | Mersana Therapeutics, Inc. | Modified Polymers for Delivery of Polynucleotides, Method of Manufacture, and Methods of Use Thereof |
| WO2011120053A1 (en) | 2010-03-26 | 2011-09-29 | Mersana Therapeutics, Inc. | Modified polymers for delivery of polynucleotides, method of manufacture, and methods of use thereof |
| US9102938B2 (en) | 2010-04-01 | 2015-08-11 | Alnylam Pharmaceuticals, Inc. | 2′ and 5′ modified monomers and oligonucleotides |
| US9725479B2 (en) | 2010-04-22 | 2017-08-08 | Ionis Pharmaceuticals, Inc. | 5′-end derivatives |
| WO2011133876A2 (en) | 2010-04-22 | 2011-10-27 | Alnylam Pharmaceuticals, Inc. | Oligonucleotides comprising acyclic and abasic nucleosides and analogs |
| EP2625186B1 (en) | 2010-04-28 | 2016-07-27 | Ionis Pharmaceuticals, Inc. | 5' modified nucleosides and oligomeric compounds prepared therefrom |
| US8993738B2 (en) | 2010-04-28 | 2015-03-31 | Isis Pharmaceuticals, Inc. | Modified nucleosides, analogs thereof and oligomeric compounds prepared therefrom |
| RS56011B1 (sr) | 2010-04-29 | 2017-09-29 | Ionis Pharmaceuticals Inc | Modulacija ekspresije transtiretina |
| WO2011163121A1 (en) | 2010-06-21 | 2011-12-29 | Alnylam Pharmaceuticals, Inc. | Multifunctional copolymers for nucleic acid delivery |
| WO2012037254A1 (en) * | 2010-09-15 | 2012-03-22 | Alnylam Pharmaceuticals, Inc. | MODIFIED iRNA AGENTS |
| WO2012067970A2 (en) | 2010-11-11 | 2012-05-24 | Ted M Dawson | Transcriptional repression leading to parkinson's disease |
| WO2012068187A1 (en) | 2010-11-19 | 2012-05-24 | Merck Sharp & Dohme Corp. | Poly(amide) polymers for the delivery of oligonucleotides |
| CN103492568B (zh) | 2010-12-17 | 2017-04-12 | 箭头研究公司 | 用于siRNA的半乳糖簇‑药代动力学调节剂靶向部分 |
| US8501930B2 (en) | 2010-12-17 | 2013-08-06 | Arrowhead Madison Inc. | Peptide-based in vivo siRNA delivery system |
| KR20130108655A (ko) | 2010-12-29 | 2013-10-04 | 에프. 호프만-라 로슈 아게 | 핵산의 세포내 전달을 위한 소분자 접합체 |
| EP3467109A1 (en) | 2011-02-08 | 2019-04-10 | Ionis Pharmaceuticals, Inc. | Oligomeric compounds comprising bicyclic nucleotides and uses thereof |
| PE20142463A1 (es) | 2011-04-01 | 2015-01-22 | Isis Pharmaceuticals Inc | Modulacion de la expresion del transductor de senales y activador de la transcripcion 3 (stat3) |
| EP2697244B1 (en) * | 2011-04-13 | 2017-05-17 | Ionis Pharmaceuticals, Inc. | Antisense modulation of ptp1b expression |
| KR102055331B1 (ko) | 2011-04-21 | 2019-12-12 | 아이오니스 파마수티컬즈, 인코포레이티드 | B형 간염 바이러스(hbv) 발현 조절 |
| US20120295961A1 (en) | 2011-04-21 | 2012-11-22 | Swayze Eric E | Modulation of hepatitis b virus (hbv) expression |
| SG194671A1 (en) | 2011-04-27 | 2013-12-30 | Isis Pharmaceuticals Inc | Modulation of apolipoprotein ciii (apociii) expression |
| WO2012174154A1 (en) | 2011-06-13 | 2012-12-20 | Isis Pharmaceuticals, Inc. | Modulation of inflammatory responses by factor vii |
| AU2012271357A1 (en) * | 2011-06-16 | 2013-05-02 | Ionis Pharmaceuticals, Inc. | Antisense modulation of fibroblast growth factor receptor 4 expression |
| BR112013032645A2 (pt) | 2011-06-21 | 2016-11-22 | Alnylam Pharmaceuticals | composições e métodos para inibição de expressão de apolipoproteína c-iii (apoc3) |
| EP3444348A1 (en) * | 2011-06-21 | 2019-02-20 | Alnylam Pharmaceuticals, Inc. | Angiopoietin-like 3 (angptl3) irna compositions and methods of use thereof |
| WO2012177639A2 (en) | 2011-06-22 | 2012-12-27 | Alnylam Pharmaceuticals, Inc. | Bioprocessing and bioproduction using avian cell lines |
| US20130017250A1 (en) * | 2011-07-15 | 2013-01-17 | The Trustees Of Columbia University In The City Of New York | Methods For High Density Lipoprotein Cholesterol Regulation |
| HK1199736A1 (en) | 2011-08-26 | 2015-07-17 | 箭头研究公司 | Poly(vinyl ester) polymers for in vivo nucleic acid delivery |
| RU2598709C2 (ru) | 2011-09-20 | 2016-09-27 | Айсис Фармасьютикалс, Инк. | Антисмысловая регуляция экспрессии gcgr |
| WO2013063313A1 (en) | 2011-10-25 | 2013-05-02 | Isis Pharmaceuticals, Inc. | Antisense modulation of gccr expression |
| AU2012340159B2 (en) | 2011-11-18 | 2017-09-07 | Alnylam Pharmaceuticals, Inc. | RNAi agents, compositions and methods of use thereof for treating transthyretin (TTR) associated diseases |
| US20150031747A1 (en) | 2012-02-08 | 2015-01-29 | Isis Pharmaceuticals, Inc. | Methods and compositions for modulating factor vii expression |
| WO2013142514A1 (en) | 2012-03-19 | 2013-09-26 | Isis Pharmaceuticals, Inc. | Methods and compositions for modulating alpha-1-antitrypsin expression |
| WO2013142571A2 (en) | 2012-03-20 | 2013-09-26 | Cornell University | Assays for the identification of compounds that modulate lipid homeostasis |
| US9133461B2 (en) | 2012-04-10 | 2015-09-15 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of the ALAS1 gene |
| EP3336189A1 (en) | 2012-04-20 | 2018-06-20 | Ionis Pharmaceuticals, Inc. | Oligomeric compounds comprising bicyclic nucleotides and uses thereof |
| WO2013159109A1 (en) | 2012-04-20 | 2013-10-24 | Isis Pharmaceuticals, Inc. | Modulation of hepatitis b virus (hbv) expression |
| EP3453762B1 (en) | 2012-05-02 | 2021-04-21 | Sirna Therapeutics, Inc. | Short interfering nucleic acid (sina) compositions |
| 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 |
| WO2013173789A2 (en) | 2012-05-17 | 2013-11-21 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotide compositions |
| US9574193B2 (en) | 2012-05-17 | 2017-02-21 | Ionis Pharmaceuticals, Inc. | Methods and compositions for modulating apolipoprotein (a) expression |
| RU2624028C2 (ru) | 2012-05-24 | 2017-06-30 | Ионис Фармасьютикалз, Инк. | Способы и композиции для модулирования экспрессии аполипопротеина (а) |
| US20150322428A1 (en) | 2012-06-18 | 2015-11-12 | Isis Pharmaceuticals, Inc. | Compounds and methods for improved cellular uptake of antisense compounds |
| DK2879718T3 (da) | 2012-08-06 | 2023-06-19 | Alnylam Pharmaceuticals Inc | Proces til fremstilling af kulhydratkonjugerede RNA-stoffer |
| WO2014059353A2 (en) | 2012-10-11 | 2014-04-17 | Isis Pharmaceuticals, Inc. | Oligomeric compounds comprising bicyclic nucleosides and uses thereof |
| WO2014076196A1 (en) | 2012-11-15 | 2014-05-22 | Santaris Pharma A/S | Anti apob antisense conjugate compounds |
| WO2014118272A1 (en) | 2013-01-30 | 2014-08-07 | Santaris Pharma A/S | Antimir-122 oligonucleotide carbohydrate conjugates |
| JP6580993B2 (ja) | 2013-01-30 | 2019-09-25 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | Lnaオリゴヌクレオチド糖質コンジュゲート |
| HUE050394T2 (hu) * | 2013-05-01 | 2020-11-30 | Ionis Pharmaceuticals Inc | Apolipoprotein(a) expressziójának módosítására szolgáló eljárások és készítmények |
| AU2013389474B2 (en) | 2013-05-16 | 2018-11-15 | Racthera Co., Ltd. | Transplantation adjuvant in cell therapy using neural progenitor cells |
| EP3011028B1 (en) | 2013-06-21 | 2019-06-12 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulation of target nucleic acids |
| HRP20200163T1 (hr) | 2013-06-27 | 2020-08-07 | Roche Innovation Center Copenhagen A/S | Antisens oligomeri i konjugati koji ciljno djeluju na pcsk9 |
| US20170073689A1 (en) | 2013-07-02 | 2017-03-16 | Ionis Pharmaceuticals, Inc. | Modulators of growth hormone receptor |
| DK3019200T3 (da) | 2013-07-11 | 2022-06-20 | Alnylam Pharmaceuticals Inc | Oligonukleotid-ligand-konjugater og fremgangsmåde til fremstiling deraf |
| LT3043827T (lt) | 2013-09-13 | 2019-08-12 | Ionis Pharmaceuticals, Inc. | Komplemento faktoriaus b moduliatoriai |
| WO2015042447A1 (en) | 2013-09-20 | 2015-03-26 | Isis Pharmaceuticals, Inc. | Targeted therapeutic nucleosides and their use |
| RU2016122168A (ru) | 2013-11-14 | 2017-12-19 | Рош Инновейшен Сентер Копенгаген А/С | Антисмысловые конъюгаты, направленные на аполипопротеин b |
| CA2932904A1 (en) | 2013-12-06 | 2015-06-11 | Dicerna Pharmaceuticals, Inc. | Methods and compositions for the specific inhibition of transthyretin (ttr) by double-stranded rna |
| KR20200102553A (ko) | 2014-05-01 | 2020-08-31 | 아이오니스 파마수티컬즈, 인코포레이티드 | 성장 호르몬 수용체 발현을 조절하기 위한 조성물 및 방법 |
| EP4534092A3 (en) | 2014-05-01 | 2025-07-02 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating pkk expression |
| AU2015252895B2 (en) | 2014-05-01 | 2021-07-15 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating angiopoietin-like 3 expression |
| EP3137115B1 (en) | 2014-05-01 | 2020-10-14 | Ionis Pharmaceuticals, Inc. | Method for synthesis of reactive conjugate clusters |
| CN106232804B (zh) | 2014-05-01 | 2019-10-25 | Ionis制药公司 | 用于调节补体因子b表达的组合物和方法 |
| WO2015179693A1 (en) | 2014-05-22 | 2015-11-26 | Isis Pharmaceuticals, Inc. | Conjugated antisense compounds and their use |
| US20170145424A1 (en) | 2014-06-06 | 2017-05-25 | Ionis Pharmaceuticals, Inc. | Compositions and methods for enhanced intestinal absorption of conjugated oligomeric compounds |
| FI4119569T3 (fi) * | 2015-11-06 | 2024-08-30 | Ionis Pharmaceuticals Inc | Konjugoituja antisense-yhdisteitä käytettäviksi hoidossa |
| EP3370708A4 (en) * | 2015-11-06 | 2019-06-26 | Ionis Pharmaceuticals, Inc. | MODULATION OF APOLIPOPROTEIN (A) EXPRESSION |
-
2014
- 2014-05-01 HU HUE14791187A patent/HUE050394T2/hu unknown
- 2014-05-01 NZ NZ631552A patent/NZ631552A/en not_active IP Right Cessation
- 2014-05-01 CA CA2921509A patent/CA2921509C/en active Active
- 2014-05-01 MX MX2015015263A patent/MX373306B/es active IP Right Grant
- 2014-05-01 SI SI201431660T patent/SI2992009T1/sl unknown
- 2014-05-01 DK DK14791557.3T patent/DK2991656T3/da active
- 2014-05-01 JP JP2016512054A patent/JP6995478B2/ja active Active
- 2014-05-01 CN CN201910036892.3A patent/CN110042098B/zh active Active
- 2014-05-01 MX MX2015015264A patent/MX2015015264A/es active IP Right Grant
- 2014-05-01 KR KR1020217003080A patent/KR20210014758A/ko not_active Ceased
- 2014-05-01 IL IL296543A patent/IL296543B2/en unknown
- 2014-05-01 EP EP20205948.1A patent/EP3828275A1/en active Pending
- 2014-05-01 CN CN201480035618.XA patent/CN105378085B/zh active Active
- 2014-05-01 KR KR1020157033027A patent/KR101857707B1/ko active Active
- 2014-05-01 KR KR1020187013079A patent/KR102138781B1/ko active Active
- 2014-05-01 RU RU2015151199A patent/RU2697152C2/ru active
- 2014-05-01 CA CA2921514A patent/CA2921514C/en active Active
- 2014-05-01 JP JP2016512055A patent/JP6456362B2/ja not_active Expired - Fee Related
- 2014-05-01 ME MEP-2019-157A patent/ME03390B/me unknown
- 2014-05-01 PE PE2015002330A patent/PE20152002A1/es unknown
- 2014-05-01 RU RU2019124314A patent/RU2019124314A/ru unknown
- 2014-05-01 RU RU2015151204A patent/RU2686080C2/ru active
- 2014-05-01 IL IL315582A patent/IL315582A/en unknown
- 2014-05-01 MX MX2016012654A patent/MX381034B/es unknown
- 2014-05-01 CR CR20190269A patent/CR20190269A/es unknown
- 2014-05-01 SG SG11201508800WA patent/SG11201508800WA/en unknown
- 2014-05-01 JP JP2016512053A patent/JP6387084B2/ja active Active
- 2014-05-01 EP EP14792010.2A patent/EP2991661B1/en active Active
- 2014-05-01 RU RU2015151203A patent/RU2650510C2/ru active
- 2014-05-01 MX MX2015015239A patent/MX373334B/es active IP Right Grant
- 2014-05-01 EP EP22181753.9A patent/EP4155403A1/en active Pending
- 2014-05-01 AU AU2014259757A patent/AU2014259757B2/en not_active Ceased
- 2014-05-01 CN CN201480035633.4A patent/CN105378082B/zh active Active
- 2014-05-01 RU RU2018112167A patent/RU2018112167A/ru not_active Application Discontinuation
- 2014-05-01 NZ NZ631537A patent/NZ631537A/en unknown
- 2014-05-01 NZ NZ753018A patent/NZ753018A/en unknown
- 2014-05-01 MX MX2015015220A patent/MX384824B/es unknown
- 2014-05-01 PL PL14791187T patent/PL2992009T3/pl unknown
- 2014-05-01 CN CN201910037434.1A patent/CN110079524B/zh active Active
- 2014-05-01 KR KR1020247009422A patent/KR20240042220A/ko active Pending
- 2014-05-01 MY MYPI2015703904A patent/MY178929A/en unknown
- 2014-05-01 JP JP2016512051A patent/JP6769866B2/ja active Active
- 2014-05-01 RU RU2015151202A patent/RU2670614C9/ru active
- 2014-05-01 MY MYPI2018000863A patent/MY198359A/en unknown
- 2014-05-01 AU AU2014259756A patent/AU2014259756B2/en active Active
- 2014-05-01 WO PCT/US2014/036460 patent/WO2014179625A1/en not_active Ceased
- 2014-05-01 KR KR1020217033430A patent/KR102482890B1/ko active Active
- 2014-05-01 NZ NZ631512A patent/NZ631512A/en unknown
- 2014-05-01 PT PT147911879T patent/PT2992009T/pt unknown
- 2014-05-01 AU AU2014259759A patent/AU2014259759B2/en not_active Expired - Fee Related
- 2014-05-01 EA EA201592093A patent/EA031393B1/ru unknown
- 2014-05-01 PL PL14791344T patent/PL2992098T3/pl unknown
- 2014-05-01 US US14/267,842 patent/US9127276B2/en active Active
- 2014-05-01 UA UAA201511840A patent/UA121017C2/uk unknown
- 2014-05-01 KR KR1020157033025A patent/KR102235678B1/ko not_active Expired - Fee Related
- 2014-05-01 BR BR112015027369-6A patent/BR112015027369B1/pt active IP Right Grant
- 2014-05-01 SI SI201431207T patent/SI2992098T1/sl unknown
- 2014-05-01 HR HRP20201378TT patent/HRP20201378T1/hr unknown
- 2014-05-01 ES ES19164959T patent/ES2885174T3/es active Active
- 2014-05-01 CN CN201910037432.2A patent/CN110066795A/zh active Pending
- 2014-05-01 EA EA201891479A patent/EA036584B1/ru unknown
- 2014-05-01 RU RU2019110030A patent/RU2019110030A/ru unknown
- 2014-05-01 EP EP19164959.9A patent/EP3524680B1/en active Active
- 2014-05-01 MX MX2015015234A patent/MX2015015234A/es active IP Right Grant
- 2014-05-01 DK DK14791187.9T patent/DK2992009T3/da active
- 2014-05-01 KR KR1020217039866A patent/KR102558571B1/ko active Active
- 2014-05-01 BR BR122018009831-7A patent/BR122018009831B1/pt active IP Right Grant
- 2014-05-01 PT PT14791344T patent/PT2992098T/pt unknown
- 2014-05-01 PE PE2016001724A patent/PE20161430A1/es unknown
- 2014-05-01 LT LTEP14791344.6T patent/LT2992098T/lt unknown
- 2014-05-01 EP EP24189241.3A patent/EP4438129A3/en active Pending
- 2014-05-01 CN CN201480035625.XA patent/CN105377887B/zh active Active
- 2014-05-01 KR KR1020237024621A patent/KR102712053B1/ko active Active
- 2014-05-01 SG SG10201906382QA patent/SG10201906382QA/en unknown
- 2014-05-01 KR KR1020227025268A patent/KR102651423B1/ko active Active
- 2014-05-01 NZ NZ740338A patent/NZ740338A/en unknown
- 2014-05-01 EP EP19160031.1A patent/EP3546579A1/en active Pending
- 2014-05-01 KR KR1020217009333A patent/KR20210037752A/ko not_active Ceased
- 2014-05-01 RS RS20190682A patent/RS58981B1/sr unknown
- 2014-05-01 BR BR112015027321A patent/BR112015027321A8/pt not_active Application Discontinuation
- 2014-05-01 CA CA2921518A patent/CA2921518A1/en not_active Abandoned
- 2014-05-01 SG SG11201508870VA patent/SG11201508870VA/en unknown
- 2014-05-01 ES ES14791344T patent/ES2730015T3/es active Active
- 2014-05-01 CN CN201480035624.5A patent/CN105392488B/zh active Active
- 2014-05-01 DK DK14791344.6T patent/DK2992098T3/da active
- 2014-05-01 BR BR112015027377-7A patent/BR112015027377B1/pt active IP Right Grant
- 2014-05-01 CN CN201480035635.3A patent/CN108064162B/zh active Active
- 2014-05-01 KR KR1020157033031A patent/KR20160002977A/ko not_active Ceased
- 2014-05-01 CA CA2921162A patent/CA2921162A1/en active Pending
- 2014-05-01 WO PCT/US2014/036466 patent/WO2014179629A2/en not_active Ceased
- 2014-05-01 EP EP14791187.9A patent/EP2992009B1/en active Active
- 2014-05-01 CA CA2921167A patent/CA2921167C/en active Active
- 2014-05-01 EP EP14791344.6A patent/EP2992098B1/en active Active
- 2014-05-01 ES ES14791187T patent/ES2819213T3/es active Active
- 2014-05-01 RS RS20201052A patent/RS60796B1/sr unknown
- 2014-05-01 ES ES14791557T patent/ES2778442T3/es active Active
- 2014-05-01 KR KR1020227045740A patent/KR20230006933A/ko not_active Ceased
- 2014-05-01 LT LTEP14791187.9T patent/LT2992009T/lt unknown
- 2014-05-01 HR HRP20190987TT patent/HRP20190987T1/hr unknown
- 2014-05-01 HU HUE14791344A patent/HUE043697T2/hu unknown
- 2014-05-01 EP EP25155370.7A patent/EP4529927A3/en active Pending
- 2014-05-01 CN CN202111358415.2A patent/CN114058617A/zh active Pending
- 2014-05-01 CN CN202110394825.6A patent/CN113293163A/zh active Pending
- 2014-05-01 KR KR1020247032116A patent/KR20240147701A/ko active Pending
- 2014-05-01 EP EP19217148.6A patent/EP3690049A1/en active Pending
- 2014-05-01 KR KR1020207021245A patent/KR20200090966A/ko not_active Ceased
- 2014-05-01 MA MA60161A patent/MA60161B1/fr unknown
- 2014-05-01 UA UAA201708429A patent/UA120287C2/uk unknown
- 2014-05-01 AU AU2014259750A patent/AU2014259750B2/en active Active
- 2014-05-01 DK DK19164959.9T patent/DK3524680T3/da active
- 2014-05-01 US US14/888,318 patent/US9714421B2/en not_active Expired - Fee Related
- 2014-05-01 WO PCT/US2014/036463 patent/WO2014179627A2/en not_active Ceased
- 2014-05-01 KR KR1020157033028A patent/KR102315836B1/ko active Active
- 2014-05-01 CN CN202011081520.1A patent/CN112921036B/zh active Active
- 2014-05-01 PT PT191649599T patent/PT3524680T/pt unknown
- 2014-05-01 JP JP2016512052A patent/JP6216444B2/ja active Active
- 2014-05-01 EP EP19206748.6A patent/EP3633039A1/en not_active Withdrawn
- 2014-05-01 KR KR1020157033029A patent/KR102424855B1/ko active Active
- 2014-05-01 CN CN202010402246.7A patent/CN111593051A/zh active Pending
- 2014-05-01 BR BR112015027322A patent/BR112015027322A8/pt not_active Application Discontinuation
- 2014-05-01 IL IL284593A patent/IL284593B2/en unknown
- 2014-05-01 CN CN202411684710.0A patent/CN119913147A/zh active Pending
- 2014-05-01 SG SG10201801507RA patent/SG10201801507RA/en unknown
- 2014-05-01 SM SM20190316T patent/SMT201900316T1/it unknown
- 2014-05-01 EP EP14791863.5A patent/EP2992097B1/en active Active
- 2014-05-01 EP EP14791557.3A patent/EP2991656B1/en active Active
- 2014-05-01 SG SG10201801813YA patent/SG10201801813YA/en unknown
- 2014-05-01 KR KR1020197019617A patent/KR102212275B1/ko active Active
- 2014-05-01 RU RU2015151200A patent/RU2699985C2/ru active
- 2014-05-01 BR BR112015027319A patent/BR112015027319A8/pt active Search and Examination
- 2014-05-01 WO PCT/US2014/036462 patent/WO2014179626A2/en not_active Ceased
- 2014-05-01 WO PCT/US2014/036452 patent/WO2014179620A1/en not_active Ceased
- 2014-05-01 AU AU2014259755A patent/AU2014259755B2/en active Active
- 2014-12-30 US US14/586,826 patent/US9163239B2/en active Active
- 2014-12-30 US US14/586,751 patent/US9181549B2/en active Active
- 2014-12-31 US US14/588,061 patent/US9181550B2/en active Active
-
2015
- 2015-02-27 US US14/633,491 patent/US9145558B2/en active Active
- 2015-06-19 US US14/744,539 patent/US20160017323A1/en not_active Abandoned
- 2015-08-10 US US14/822,493 patent/US9932580B2/en active Active
- 2015-08-28 US US14/839,580 patent/US9957504B2/en active Active
- 2015-08-28 US US14/839,521 patent/US9932581B2/en active Active
- 2015-09-29 ZA ZA2015/07218A patent/ZA201507218B/en unknown
- 2015-09-29 ZA ZA2015/07216A patent/ZA201507216B/en unknown
- 2015-10-15 IL IL242124A patent/IL242124B/en active IP Right Grant
- 2015-10-15 IL IL242126A patent/IL242126B/en active IP Right Grant
- 2015-10-15 IL IL242125A patent/IL242125B/en active IP Right Grant
- 2015-10-15 IL IL242132A patent/IL242132B/en active IP Right Grant
- 2015-10-28 DO DO2015000268A patent/DOP2015000268A/es unknown
- 2015-10-29 PH PH12015502493A patent/PH12015502493B1/en unknown
- 2015-10-30 CL CL2015003217A patent/CL2015003217A1/es unknown
- 2015-10-30 MX MX2021008901A patent/MX2021008901A/es unknown
- 2015-10-30 MX MX2019010441A patent/MX2019010441A/es unknown
- 2015-10-30 MX MX2020002184A patent/MX2020002184A/es unknown
- 2015-10-30 MX MX2019010443A patent/MX2019010443A/es unknown
- 2015-10-30 MX MX2020004209A patent/MX2020004209A/es unknown
- 2015-10-30 MX MX2021008899A patent/MX2021008899A/es unknown
- 2015-11-12 CR CR20150612A patent/CR20150612A/es unknown
-
2016
- 2016-09-07 CL CL2016002262A patent/CL2016002262A1/es unknown
- 2016-10-24 DO DO2016000287A patent/DOP2016000287A/es unknown
-
2017
- 2017-01-19 AU AU2017200365A patent/AU2017200365C1/en active Active
- 2017-02-13 AU AU2017200950A patent/AU2017200950B2/en active Active
- 2017-05-23 AU AU2017203436A patent/AU2017203436B2/en active Active
- 2017-06-09 US US15/618,365 patent/US20180002693A1/en not_active Abandoned
- 2017-08-25 US US15/687,306 patent/US10683499B2/en active Active
- 2017-09-22 JP JP2017182019A patent/JP6592486B2/ja active Active
-
2018
- 2018-02-07 US US15/891,156 patent/US10883104B2/en active Active
- 2018-02-07 US US15/891,118 patent/US10927372B2/en active Active
- 2018-02-14 US US15/896,379 patent/US20190055554A1/en not_active Abandoned
- 2018-08-07 JP JP2018148112A patent/JP6652602B2/ja active Active
- 2018-09-12 PH PH12018501963A patent/PH12018501963A1/en unknown
- 2018-09-20 IL IL261901A patent/IL261901B/en active IP Right Grant
- 2018-11-22 AU AU2018267625A patent/AU2018267625B2/en active Active
- 2018-12-18 JP JP2018236205A patent/JP6639629B2/ja not_active Expired - Fee Related
- 2018-12-19 IL IL263843A patent/IL263843B/en active IP Right Grant
- 2018-12-26 US US16/232,733 patent/US10844379B2/en active Active
-
2019
- 2019-01-14 IL IL264241A patent/IL264241B/en active IP Right Grant
- 2019-01-31 IL IL264580A patent/IL264580B/en active IP Right Grant
- 2019-02-07 AU AU2019200820A patent/AU2019200820B2/en active Active
- 2019-04-15 AU AU2019202598A patent/AU2019202598A1/en not_active Abandoned
- 2019-05-25 AU AU2019203674A patent/AU2019203674B2/en active Active
- 2019-05-29 PH PH12019501191A patent/PH12019501191A1/en unknown
- 2019-06-26 CY CY20191100660T patent/CY1121879T1/el unknown
- 2019-07-03 AU AU2019204784A patent/AU2019204784C1/en active Active
- 2019-09-19 JP JP2019170394A patent/JP7429103B2/ja active Active
- 2019-11-06 IL IL270464A patent/IL270464B/en unknown
- 2019-11-22 JP JP2019211074A patent/JP6866459B2/ja active Active
- 2019-11-22 JP JP2019211075A patent/JP2020039355A/ja active Pending
- 2019-12-20 JP JP2019229981A patent/JP2020058370A/ja not_active Ceased
-
2020
- 2020-01-23 JP JP2020008836A patent/JP2020074787A/ja active Pending
- 2020-02-12 IL IL272617A patent/IL272617A/en unknown
- 2020-02-13 US US16/790,557 patent/US20220275365A9/en not_active Abandoned
- 2020-03-02 US US16/806,941 patent/US20200224198A1/en not_active Abandoned
- 2020-03-09 IL IL273184A patent/IL273184B/en unknown
- 2020-03-10 IL IL273205A patent/IL273205A/en unknown
- 2020-03-15 IL IL273312A patent/IL273312A/en unknown
- 2020-04-20 IL IL274064A patent/IL274064B/en active IP Right Grant
- 2020-06-24 US US16/910,727 patent/US20210130823A1/en not_active Abandoned
- 2020-07-22 AU AU2020207820A patent/AU2020207820A1/en not_active Withdrawn
- 2020-08-11 AU AU2020217347A patent/AU2020217347A1/en not_active Abandoned
- 2020-09-14 AU AU2020233603A patent/AU2020233603A1/en not_active Abandoned
- 2020-09-22 CY CY20201100892T patent/CY1123369T1/el unknown
- 2020-09-23 JP JP2020158332A patent/JP7177127B2/ja active Active
- 2020-10-01 US US17/060,440 patent/US11851655B2/en active Active
- 2020-10-14 US US17/070,287 patent/US11299736B1/en active Active
- 2020-12-07 US US17/114,177 patent/US20210395734A1/en not_active Abandoned
-
2021
- 2021-02-17 JP JP2021023118A patent/JP2021074021A/ja not_active Withdrawn
- 2021-04-07 JP JP2021065088A patent/JP7339294B2/ja active Active
- 2021-05-17 DO DO2021000095A patent/DOP2021000095A/es unknown
- 2021-06-02 IL IL283660A patent/IL283660A/en unknown
- 2021-06-14 IL IL284000A patent/IL284000A/en unknown
- 2021-06-23 AU AU2021204244A patent/AU2021204244B2/en active Active
- 2021-11-05 JP JP2021181533A patent/JP2022017514A/ja active Pending
-
2022
- 2022-04-27 AU AU2022202770A patent/AU2022202770B2/en active Active
- 2022-11-10 JP JP2022180094A patent/JP2023012548A/ja active Pending
-
2023
- 2023-06-07 JP JP2023093703A patent/JP7633311B2/ja active Active
- 2023-07-11 US US18/350,195 patent/US20240247260A1/en not_active Abandoned
- 2023-10-23 JP JP2023181938A patent/JP2024010070A/ja active Pending
- 2023-11-03 US US18/501,779 patent/US12291709B2/en active Active
-
2024
- 2024-01-17 AU AU2024200296A patent/AU2024200296A1/en active Pending
- 2024-06-05 JP JP2024091116A patent/JP2024116224A/ja active Pending
- 2024-11-22 AU AU2024266799A patent/AU2024266799A1/en active Pending
- 2024-12-16 US US18/983,163 patent/US20250346899A1/en active Pending
-
2025
- 2025-02-06 JP JP2025018106A patent/JP2025072530A/ja active Pending
- 2025-07-14 JP JP2025118631A patent/JP2025174962A/ja active Pending
- 2025-08-13 NO NO2025037C patent/NO2025037I1/no unknown
- 2025-08-18 FI FIC20250028C patent/FIC20250028I1/fi unknown
- 2025-08-30 FR FR25C1033C patent/FR25C1033I1/fr active Active
- 2025-09-03 NL NL301341C patent/NL301341I2/nl unknown
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2249463C2 (ru) * | 1998-08-19 | 2005-04-10 | Бакстер Хелфкэа С.А. | Иммуногенный конъюгат бета-пропионамид-связанного полисахарида с белком, использующийся в качестве вакцины |
| WO2009073809A2 (en) * | 2007-12-04 | 2009-06-11 | Alnylam Pharmaceuticals, Inc. | Carbohydrate conjugates as delivery agents for oligonucleotides |
| WO2009126933A2 (en) * | 2008-04-11 | 2009-10-15 | Alnylam Pharmaceuticals, Inc. | Site-specific delivery of nucleic acids by combining targeting ligands with endosomolytic components |
| WO2013033230A1 (en) * | 2011-08-29 | 2013-03-07 | Isis Pharmaceuticals, Inc. | Oligomer-conjugate complexes and their use |
Non-Patent Citations (1)
| Title |
|---|
| KHOREV O. et al. "Trivalent, Gal/GalNAc-containing ligands designed for the asialoglycoprotein receptor". Bioorganic & Medicinal Chemistry, 2008, v.16, p.5216-5231. * |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2697152C2 (ru) | Сопряженные антисмысловые соединения и их применение | |
| US10570169B2 (en) | Conjugated antisense compounds and their use | |
| HK40085260A (en) | Conjugated antisense compounds and their use | |
| RU2782034C2 (ru) | Композиции и способы модулирования экспрессии hbv и ttr | |
| RU2824214C1 (ru) | Композиции и способы модулирования экспрессии аполипопротеина (a) | |
| HK1221404B (en) | Conjugated antisense compounds and their use |