ES2730015T3 - Composiciones y métodos para modular expresión de HBV y de TTR - Google Patents
Composiciones y métodos para modular expresión de HBV y de TTR Download PDFInfo
- Publication number
- ES2730015T3 ES2730015T3 ES14791344T ES14791344T ES2730015T3 ES 2730015 T3 ES2730015 T3 ES 2730015T3 ES 14791344 T ES14791344 T ES 14791344T ES 14791344 T ES14791344 T ES 14791344T ES 2730015 T3 ES2730015 T3 ES 2730015T3
- Authority
- ES
- Spain
- Prior art keywords
- certain embodiments
- wing
- segment
- compound
- nucleoside
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 239000000203 mixture Substances 0.000 title claims description 21
- 238000000034 method Methods 0.000 title description 46
- 230000014509 gene expression Effects 0.000 title description 21
- 239000002777 nucleoside Substances 0.000 claims abstract description 431
- 108091034117 Oligonucleotide Proteins 0.000 claims abstract description 403
- 150000001875 compounds Chemical class 0.000 claims abstract description 394
- 125000003835 nucleoside group Chemical group 0.000 claims abstract description 202
- 230000000295 complement effect Effects 0.000 claims abstract description 57
- 150000003833 nucleoside derivatives Chemical class 0.000 claims description 158
- 235000000346 sugar Nutrition 0.000 claims description 134
- 150000004713 phosphodiesters Chemical class 0.000 claims description 44
- 210000004185 liver Anatomy 0.000 claims description 42
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims description 30
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims description 26
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 26
- 125000002619 bicyclic group Chemical group 0.000 claims description 20
- 201000010099 disease Diseases 0.000 claims description 17
- 208000002672 hepatitis B Diseases 0.000 claims description 17
- LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical compound CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 claims description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
- 239000000427 antigen Substances 0.000 claims description 14
- 102000036639 antigens Human genes 0.000 claims description 14
- 108091007433 antigens Proteins 0.000 claims description 14
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 9
- 229940104302 cytosine Drugs 0.000 claims description 9
- 208000035475 disorder Diseases 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 7
- 238000000926 separation method Methods 0.000 claims description 7
- 206010061218 Inflammation Diseases 0.000 claims description 6
- 230000004054 inflammatory process Effects 0.000 claims description 6
- 201000007270 liver cancer Diseases 0.000 claims description 6
- 208000014018 liver neoplasm Diseases 0.000 claims description 6
- 206010023126 Jaundice Diseases 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 208000019423 liver disease Diseases 0.000 claims description 5
- 208000036066 Hemophagocytic Lymphohistiocytosis Diseases 0.000 claims description 4
- 206010019663 Hepatic failure Diseases 0.000 claims description 4
- 208000032672 Histiocytosis haematophagic Diseases 0.000 claims description 4
- 206010058874 Viraemia Diseases 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 208000014752 hemophagocytic syndrome Diseases 0.000 claims description 4
- 208000027866 inflammatory disease Diseases 0.000 claims description 4
- 208000007903 liver failure Diseases 0.000 claims description 4
- 231100000835 liver failure Toxicity 0.000 claims description 4
- 230000004962 physiological condition Effects 0.000 claims description 4
- 241000700605 Viruses Species 0.000 claims description 3
- 238000002054 transplantation Methods 0.000 claims description 2
- 150000008266 deoxy sugars Chemical class 0.000 claims 2
- 241000700721 Hepatitis B virus Species 0.000 abstract description 57
- 230000000692 anti-sense effect Effects 0.000 description 242
- 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 139
- -1 bicyclic sugars Chemical class 0.000 description 128
- 102000039446 nucleic acids Human genes 0.000 description 110
- 108020004707 nucleic acids Proteins 0.000 description 110
- 150000007523 nucleic acids Chemical class 0.000 description 107
- 238000012230 antisense oligonucleotides Methods 0.000 description 84
- 239000000074 antisense oligonucleotide Substances 0.000 description 77
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 69
- OVRNDRQMDRJTHS-KEWYIRBNSA-N N-acetyl-D-galactosamine Chemical compound CC(=O)N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-KEWYIRBNSA-N 0.000 description 67
- ABEXEQSGABRUHS-UHFFFAOYSA-N 16-methylheptadecyl 16-methylheptadecanoate Chemical compound CC(C)CCCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCCCC(C)C ABEXEQSGABRUHS-UHFFFAOYSA-N 0.000 description 66
- 241000764238 Isis Species 0.000 description 66
- 238000005417 image-selected in vivo spectroscopy Methods 0.000 description 65
- 238000012739 integrated shape imaging system Methods 0.000 description 65
- 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 description 61
- 230000004048 modification Effects 0.000 description 59
- 238000012986 modification Methods 0.000 description 59
- 125000006850 spacer group Chemical group 0.000 description 55
- 210000004027 cell Anatomy 0.000 description 54
- 125000001424 substituent group Chemical group 0.000 description 51
- 108020004999 messenger RNA Proteins 0.000 description 50
- 230000000694 effects Effects 0.000 description 48
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 41
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
- 241000699670 Mus sp. Species 0.000 description 39
- 230000027455 binding Effects 0.000 description 36
- 230000005764 inhibitory process Effects 0.000 description 35
- 125000005647 linker group Chemical group 0.000 description 34
- 101100150273 Caenorhabditis elegans srb-1 gene Proteins 0.000 description 33
- 241001465754 Metazoa Species 0.000 description 33
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 33
- 239000008194 pharmaceutical composition Substances 0.000 description 32
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 30
- 108020004414 DNA Proteins 0.000 description 30
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- 125000004429 atom Chemical group 0.000 description 30
- 230000003389 potentiating effect Effects 0.000 description 30
- 230000008685 targeting Effects 0.000 description 30
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 29
- 239000003446 ligand Substances 0.000 description 29
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 27
- 239000002953 phosphate buffered saline Substances 0.000 description 27
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 27
- 238000001727 in vivo Methods 0.000 description 26
- 239000000243 solution Substances 0.000 description 24
- 230000007246 mechanism Effects 0.000 description 23
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 22
- 101710115418 Apolipoprotein(a) Proteins 0.000 description 21
- 102100040214 Apolipoprotein(a) Human genes 0.000 description 21
- 239000003814 drug Substances 0.000 description 21
- 238000009396 hybridization Methods 0.000 description 21
- 125000004432 carbon atom Chemical group C* 0.000 description 20
- 238000007385 chemical modification Methods 0.000 description 20
- 238000006243 chemical reaction Methods 0.000 description 20
- 231100000673 dose–response relationship Toxicity 0.000 description 20
- 239000011541 reaction mixture Substances 0.000 description 20
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
- 230000002829 reductive effect Effects 0.000 description 18
- 239000000126 substance Substances 0.000 description 18
- 125000003118 aryl group Chemical group 0.000 description 17
- 229910052698 phosphorus Inorganic materials 0.000 description 17
- 238000002360 preparation method Methods 0.000 description 17
- 229930024421 Adenine Natural products 0.000 description 16
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 16
- 229960000643 adenine Drugs 0.000 description 16
- 230000037396 body weight Effects 0.000 description 16
- 230000008859 change Effects 0.000 description 16
- 210000003494 hepatocyte Anatomy 0.000 description 16
- 229940002612 prodrug Drugs 0.000 description 16
- 239000000651 prodrug Substances 0.000 description 16
- 108090000623 proteins and genes Proteins 0.000 description 16
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 15
- 102000005427 Asialoglycoprotein Receptor Human genes 0.000 description 15
- 108010071690 Prealbumin Proteins 0.000 description 15
- 102000009190 Transthyretin Human genes 0.000 description 15
- 125000000217 alkyl group Chemical group 0.000 description 15
- 108010006523 asialoglycoprotein receptor Proteins 0.000 description 15
- 230000007935 neutral effect Effects 0.000 description 15
- 239000011780 sodium chloride Substances 0.000 description 15
- 235000021092 sugar substitutes Nutrition 0.000 description 15
- 229910052717 sulfur Inorganic materials 0.000 description 15
- 239000003765 sweetening agent Substances 0.000 description 15
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
- 230000009471 action Effects 0.000 description 14
- 150000001720 carbohydrates Chemical class 0.000 description 14
- 229940079593 drug Drugs 0.000 description 14
- 229910052757 nitrogen Inorganic materials 0.000 description 14
- 229910052760 oxygen Inorganic materials 0.000 description 14
- 239000011574 phosphorus Substances 0.000 description 14
- 102000004506 Blood Proteins Human genes 0.000 description 13
- 108010017384 Blood Proteins Proteins 0.000 description 13
- 235000014633 carbohydrates Nutrition 0.000 description 13
- 239000003153 chemical reaction reagent Substances 0.000 description 13
- 125000001072 heteroaryl group Chemical group 0.000 description 13
- 210000003734 kidney Anatomy 0.000 description 13
- 125000003729 nucleotide group Chemical group 0.000 description 13
- 238000003753 real-time PCR Methods 0.000 description 13
- 229940113082 thymine Drugs 0.000 description 13
- 102100034343 Integrase Human genes 0.000 description 12
- 101710203526 Integrase Proteins 0.000 description 12
- 108700011259 MicroRNAs Proteins 0.000 description 12
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 12
- 125000001931 aliphatic group Chemical group 0.000 description 12
- 210000004369 blood Anatomy 0.000 description 12
- 239000008280 blood Substances 0.000 description 12
- 230000000875 corresponding effect Effects 0.000 description 12
- 235000019439 ethyl acetate Nutrition 0.000 description 12
- 125000003843 furanosyl group Chemical group 0.000 description 12
- 125000000623 heterocyclic group Chemical group 0.000 description 12
- 239000001257 hydrogen Substances 0.000 description 12
- 229910052739 hydrogen Inorganic materials 0.000 description 12
- 239000002679 microRNA Substances 0.000 description 12
- 125000006239 protecting group Chemical group 0.000 description 12
- 238000002560 therapeutic procedure Methods 0.000 description 12
- 101710163270 Nuclease Proteins 0.000 description 11
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 11
- 108020004459 Small interfering RNA Proteins 0.000 description 11
- 108090000340 Transaminases Proteins 0.000 description 11
- 102000003929 Transaminases Human genes 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 11
- 238000003786 synthesis reaction Methods 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 10
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- 125000000304 alkynyl group Chemical group 0.000 description 10
- 108010050122 alpha 1-Antitrypsin Proteins 0.000 description 10
- 102000015395 alpha 1-Antitrypsin Human genes 0.000 description 10
- 125000003710 aryl alkyl group Chemical group 0.000 description 10
- 230000015556 catabolic process Effects 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 230000000770 proinflammatory effect Effects 0.000 description 10
- 230000009467 reduction Effects 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 9
- 241000699660 Mus musculus Species 0.000 description 9
- 238000013381 RNA quantification Methods 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- 239000012267 brine Substances 0.000 description 9
- 238000006731 degradation reaction Methods 0.000 description 9
- 150000002148 esters Chemical class 0.000 description 9
- 239000003068 molecular probe Substances 0.000 description 9
- 239000002773 nucleotide Substances 0.000 description 9
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 9
- 102000004169 proteins and genes Human genes 0.000 description 9
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 9
- 238000011830 transgenic mouse model Methods 0.000 description 9
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
- 238000002965 ELISA Methods 0.000 description 8
- 238000005481 NMR spectroscopy Methods 0.000 description 8
- 125000002252 acyl group Chemical group 0.000 description 8
- 230000008901 benefit Effects 0.000 description 8
- 125000000837 carbohydrate group Chemical group 0.000 description 8
- 125000004122 cyclic group Chemical group 0.000 description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 8
- 210000000056 organ Anatomy 0.000 description 8
- 125000004430 oxygen atom Chemical group O* 0.000 description 8
- 235000018102 proteins Nutrition 0.000 description 8
- 150000003254 radicals Chemical class 0.000 description 8
- 238000011160 research Methods 0.000 description 8
- 239000000523 sample Substances 0.000 description 8
- 230000003612 virological effect Effects 0.000 description 8
- 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 description 7
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 description 7
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 7
- 108010082126 Alanine transaminase Proteins 0.000 description 7
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 7
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 7
- 108010074864 Factor XI Proteins 0.000 description 7
- 241000699666 Mus <mouse, genus> Species 0.000 description 7
- 102100021947 Survival motor neuron protein Human genes 0.000 description 7
- 125000002723 alicyclic group Chemical group 0.000 description 7
- 125000003342 alkenyl group Chemical group 0.000 description 7
- 125000003545 alkoxy group Chemical group 0.000 description 7
- 229940024142 alpha 1-antitrypsin Drugs 0.000 description 7
- 238000003776 cleavage reaction Methods 0.000 description 7
- 239000006184 cosolvent Substances 0.000 description 7
- 230000003247 decreasing effect Effects 0.000 description 7
- 239000005549 deoxyribonucleoside Substances 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 150000002632 lipids Chemical group 0.000 description 7
- 238000005259 measurement Methods 0.000 description 7
- 230000007017 scission Effects 0.000 description 7
- 235000017557 sodium bicarbonate Nutrition 0.000 description 7
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- 229940035893 uracil Drugs 0.000 description 7
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- 206010016654 Fibrosis Diseases 0.000 description 6
- 229910019142 PO4 Inorganic materials 0.000 description 6
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 6
- 102000000574 RNA-Induced Silencing Complex Human genes 0.000 description 6
- 108010016790 RNA-Induced Silencing Complex Proteins 0.000 description 6
- 238000008050 Total Bilirubin Reagent Methods 0.000 description 6
- 238000010521 absorption reaction Methods 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 238000009826 distribution Methods 0.000 description 6
- 238000005516 engineering process Methods 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 229910052731 fluorine Inorganic materials 0.000 description 6
- 230000009368 gene silencing by RNA Effects 0.000 description 6
- 230000002440 hepatic effect Effects 0.000 description 6
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 6
- 230000006872 improvement Effects 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 125000002950 monocyclic group Chemical group 0.000 description 6
- 108091027963 non-coding RNA Proteins 0.000 description 6
- 102000042567 non-coding RNA Human genes 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- 235000021317 phosphate Nutrition 0.000 description 6
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 6
- 125000006413 ring segment Chemical group 0.000 description 6
- 238000010898 silica gel chromatography Methods 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 150000008163 sugars Chemical class 0.000 description 6
- 238000013519 translation Methods 0.000 description 6
- 230000014616 translation Effects 0.000 description 6
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 5
- 230000001413 cellular effect Effects 0.000 description 5
- 238000013461 design Methods 0.000 description 5
- 239000012091 fetal bovine serum Substances 0.000 description 5
- 239000011737 fluorine Substances 0.000 description 5
- 229910052736 halogen Inorganic materials 0.000 description 5
- 150000002367 halogens Chemical class 0.000 description 5
- 125000005842 heteroatom Chemical group 0.000 description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 5
- 239000002502 liposome Substances 0.000 description 5
- 210000005229 liver cell Anatomy 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- 230000001404 mediated effect Effects 0.000 description 5
- 230000004060 metabolic process Effects 0.000 description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 5
- 239000002342 ribonucleoside Substances 0.000 description 5
- 238000006467 substitution reaction Methods 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 238000013518 transcription Methods 0.000 description 5
- 230000035897 transcription Effects 0.000 description 5
- 125000006710 (C2-C12) alkenyl group Chemical group 0.000 description 4
- 125000006711 (C2-C12) alkynyl group Chemical group 0.000 description 4
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 4
- OLXZPDWKRNYJJZ-UHFFFAOYSA-N 5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-ol Chemical group C1=NC=2C(N)=NC=NC=2N1C1CC(O)C(CO)O1 OLXZPDWKRNYJJZ-UHFFFAOYSA-N 0.000 description 4
- UHNRLQRZRNKOKU-UHFFFAOYSA-N CCN(CC1=NC2=C(N1)C1=CC=C(C=C1N=C2N)C1=NNC=C1)C(C)=O Chemical compound CCN(CC1=NC2=C(N1)C1=CC=C(C=C1N=C2N)C1=NNC=C1)C(C)=O UHNRLQRZRNKOKU-UHFFFAOYSA-N 0.000 description 4
- 102000004533 Endonucleases Human genes 0.000 description 4
- 108010042407 Endonucleases Proteins 0.000 description 4
- 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 4
- 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 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 150000001408 amides Chemical class 0.000 description 4
- 229910052786 argon Inorganic materials 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 230000005587 bubbling Effects 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 4
- 230000021615 conjugation Effects 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 125000000524 functional group Chemical group 0.000 description 4
- 150000008195 galaktosides Chemical class 0.000 description 4
- 230000002209 hydrophobic effect Effects 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 230000000670 limiting effect Effects 0.000 description 4
- 230000009871 nonspecific binding Effects 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 239000010452 phosphate Substances 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 238000002390 rotary evaporation Methods 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- 239000011593 sulfur Substances 0.000 description 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 4
- 210000002700 urine Anatomy 0.000 description 4
- 108010056301 Apolipoprotein C-III Proteins 0.000 description 3
- 102000001493 Cyclophilins Human genes 0.000 description 3
- 108010068682 Cyclophilins Proteins 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 239000007832 Na2SO4 Substances 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000007882 cirrhosis Effects 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical class [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 3
- 125000001033 ether group Chemical group 0.000 description 3
- 230000004761 fibrosis Effects 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 231100000417 nephrotoxicity Toxicity 0.000 description 3
- 238000002515 oligonucleotide synthesis Methods 0.000 description 3
- 239000008177 pharmaceutical agent Substances 0.000 description 3
- 125000004437 phosphorous atom Chemical group 0.000 description 3
- 125000003367 polycyclic group Chemical group 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 2
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 description 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 2
- KLEGMTRDCCDFJK-XDQSQZFTSA-N 1-[(2R,4S,5R)-4-[[(2R,3S,5R)-3-[[(2R,3S,5R)-5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-3-[[(2R,3S,5R)-3-[[(2R,3S,5R)-3-[[(2R,3S,5R)-3-[[(2R,3S,5R)-3-[[(2R,3S,5R)-3-[[(2R,3R,4R,5R)-3-[[(2R,3R,4R,5R)-3-[[(2R,3R,4R,5R)-5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-3-[[(2R,3R,4R,5R)-5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-3-[[(2R,3R,4R,5R)-5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-3-hydroxy-4-(2-methoxyethoxy)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-4-(2-methoxyethoxy)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-4-(2-methoxyethoxy)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-4-(2-methoxyethoxy)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-5-(6-aminopurin-9-yl)-4-(2-methoxyethoxy)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-5-(2-amino-6-oxo-1H-purin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxyoxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-5-[[[(2R,3S,5R)-2-[[[(2R,3S,5R)-2-[[[(2R,3R,4R,5R)-2-[[[(2R,3R,4R,5R)-2-[[[(2R,3R,4R,5R)-2-[[[(2R,3R,4R,5R)-5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-2-[[hydroxy-[(2R,3R,4R,5R)-2-(hydroxymethyl)-4-(2-methoxyethoxy)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxyphosphinothioyl]oxymethyl]-4-(2-methoxyethoxy)oxolan-3-yl]oxy-sulfanylphosphoryl]oxymethyl]-4-(2-methoxyethoxy)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-4-(2-methoxyethoxy)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(2-amino-6-oxo-1H-purin-9-yl)-4-(2-methoxyethoxy)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(2-amino-6-oxo-1H-purin-9-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound COCCO[C@@H]1[C@H](O)[C@@H](COP(O)(=S)O[C@@H]2[C@@H](COP(O)(=S)O[C@@H]3[C@@H](COP(O)(=S)O[C@@H]4[C@@H](COP(O)(=S)O[C@@H]5[C@@H](COP(O)(=S)O[C@H]6C[C@@H](O[C@@H]6COP(O)(=S)O[C@H]6C[C@@H](O[C@@H]6COP(O)(=S)O[C@H]6C[C@@H](O[C@@H]6COP(O)(=S)O[C@H]6C[C@@H](O[C@@H]6COP(O)(=S)O[C@H]6C[C@@H](O[C@@H]6COP(O)(=S)O[C@H]6C[C@@H](O[C@@H]6COP(O)(=S)O[C@H]6C[C@@H](O[C@@H]6COP(O)(=S)O[C@H]6C[C@@H](O[C@@H]6COP(O)(=S)O[C@H]6C[C@@H](O[C@@H]6COP(O)(=S)O[C@H]6C[C@@H](O[C@@H]6COP(O)(=S)O[C@@H]6[C@@H](COP(O)(=S)O[C@@H]7[C@@H](COP(O)(=S)O[C@@H]8[C@@H](COP(S)(=O)O[C@@H]9[C@@H](COP(O)(=S)O[C@@H]%10[C@@H](CO)O[C@H]([C@@H]%10OCCOC)n%10cc(C)c(=O)[nH]c%10=O)O[C@H]([C@@H]9OCCOC)n9cc(C)c(N)nc9=O)O[C@H]([C@@H]8OCCOC)n8cc(C)c(=O)[nH]c8=O)O[C@H]([C@@H]7OCCOC)n7cc(C)c(=O)[nH]c7=O)O[C@H]([C@@H]6OCCOC)n6cnc7c6nc(N)[nH]c7=O)n6cnc7c6nc(N)[nH]c7=O)n6cc(C)c(=O)[nH]c6=O)n6cc(C)c(=O)[nH]c6=O)n6cnc7c(N)ncnc67)n6cc(C)c(N)nc6=O)n6cnc7c(N)ncnc67)n6cc(C)c(=O)[nH]c6=O)n6cnc7c6nc(N)[nH]c7=O)n6cnc7c(N)ncnc67)n6cnc7c(N)ncnc67)O[C@H]([C@@H]5OCCOC)n5cnc6c(N)ncnc56)O[C@H]([C@@H]4OCCOC)n4cc(C)c(=O)[nH]c4=O)O[C@H]([C@@H]3OCCOC)n3cc(C)c(N)nc3=O)O[C@H]([C@@H]2OCCOC)n2cc(C)c(N)nc2=O)O[C@H]1n1cc(C)c(N)nc1=O KLEGMTRDCCDFJK-XDQSQZFTSA-N 0.000 description 2
- 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
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- FZWGECJQACGGTI-UHFFFAOYSA-N 2-amino-7-methyl-1,7-dihydro-6H-purin-6-one Chemical compound NC1=NC(O)=C2N(C)C=NC2=N1 FZWGECJQACGGTI-UHFFFAOYSA-N 0.000 description 2
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- ASFAFOSQXBRFMV-LJQANCHMSA-N 3-n-(2-benzyl-1,3-dihydroxypropan-2-yl)-1-n-[(1r)-1-(4-fluorophenyl)ethyl]-5-[methyl(methylsulfonyl)amino]benzene-1,3-dicarboxamide Chemical compound N([C@H](C)C=1C=CC(F)=CC=1)C(=O)C(C=1)=CC(N(C)S(C)(=O)=O)=CC=1C(=O)NC(CO)(CO)CC1=CC=CC=C1 ASFAFOSQXBRFMV-LJQANCHMSA-N 0.000 description 2
- OVONXEQGWXGFJD-UHFFFAOYSA-N 4-sulfanylidene-1h-pyrimidin-2-one Chemical compound SC=1C=CNC(=O)N=1 OVONXEQGWXGFJD-UHFFFAOYSA-N 0.000 description 2
- RYVNIFSIEDRLSJ-UHFFFAOYSA-N 5-(hydroxymethyl)cytosine Chemical compound NC=1NC(=O)N=CC=1CO RYVNIFSIEDRLSJ-UHFFFAOYSA-N 0.000 description 2
- PEHVGBZKEYRQSX-UHFFFAOYSA-N 7-deaza-adenine Chemical compound NC1=NC=NC2=C1C=CN2 PEHVGBZKEYRQSX-UHFFFAOYSA-N 0.000 description 2
- HCGHYQLFMPXSDU-UHFFFAOYSA-N 7-methyladenine Chemical compound C1=NC(N)=C2N(C)C=NC2=N1 HCGHYQLFMPXSDU-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
- UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 2
- MSSXOMSJDRHRMC-UHFFFAOYSA-N 9H-purine-2,6-diamine Chemical compound NC1=NC(N)=C2NC=NC2=N1 MSSXOMSJDRHRMC-UHFFFAOYSA-N 0.000 description 2
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- 102000030169 Apolipoprotein C-III Human genes 0.000 description 2
- 108010083590 Apoproteins Proteins 0.000 description 2
- 102000006410 Apoproteins Human genes 0.000 description 2
- IYHHRZBKXXKDDY-UHFFFAOYSA-N BI-605906 Chemical compound N=1C=2SC(C(N)=O)=C(N)C=2C(C(F)(F)CC)=CC=1N1CCC(S(C)(=O)=O)CC1 IYHHRZBKXXKDDY-UHFFFAOYSA-N 0.000 description 2
- BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 description 2
- KAKZBPTYRLMSJV-UHFFFAOYSA-N Butadiene Chemical compound C=CC=C KAKZBPTYRLMSJV-UHFFFAOYSA-N 0.000 description 2
- BGGALFIXXQOTPY-NRFANRHFSA-N C1(=C(C2=C(C=C1)N(C(C#N)=C2)C[C@@H](N1CCN(CC1)S(=O)(=O)C)C)C)CN1CCC(CC1)NC1=NC(=NC2=C1C=C(S2)CC(F)(F)F)NC Chemical compound C1(=C(C2=C(C=C1)N(C(C#N)=C2)C[C@@H](N1CCN(CC1)S(=O)(=O)C)C)C)CN1CCC(CC1)NC1=NC(=NC2=C1C=C(S2)CC(F)(F)F)NC BGGALFIXXQOTPY-NRFANRHFSA-N 0.000 description 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 2
- 239000004215 Carbon black (E152) Substances 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
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 229930186217 Glycolipid Natural products 0.000 description 2
- 208000032843 Hemorrhage Diseases 0.000 description 2
- 101000889990 Homo sapiens Apolipoprotein(a) Proteins 0.000 description 2
- 101100154772 Homo sapiens TTR gene Proteins 0.000 description 2
- 101000772194 Homo sapiens Transthyretin Proteins 0.000 description 2
- 108010047761 Interferon-alpha Proteins 0.000 description 2
- 102000006992 Interferon-alpha Human genes 0.000 description 2
- QZRGKCOWNLSUDK-UHFFFAOYSA-N Iodochlorine Chemical compound ICl QZRGKCOWNLSUDK-UHFFFAOYSA-N 0.000 description 2
- 108090001030 Lipoproteins Proteins 0.000 description 2
- 102000004895 Lipoproteins Human genes 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 101000793216 Mus musculus Apolipoprotein C-III Proteins 0.000 description 2
- LIMFPAAAIVQRRD-BCGVJQADSA-N N-[2-[(3S,4R)-3-fluoro-4-methoxypiperidin-1-yl]pyrimidin-4-yl]-8-[(2R,3S)-2-methyl-3-(methylsulfonylmethyl)azetidin-1-yl]-5-propan-2-ylisoquinolin-3-amine Chemical compound F[C@H]1CN(CC[C@H]1OC)C1=NC=CC(=N1)NC=1N=CC2=C(C=CC(=C2C=1)C(C)C)N1[C@@H]([C@H](C1)CS(=O)(=O)C)C LIMFPAAAIVQRRD-BCGVJQADSA-N 0.000 description 2
- POFVJRKJJBFPII-UHFFFAOYSA-N N-cyclopentyl-5-[2-[[5-[(4-ethylpiperazin-1-yl)methyl]pyridin-2-yl]amino]-5-fluoropyrimidin-4-yl]-4-methyl-1,3-thiazol-2-amine Chemical compound C1(CCCC1)NC=1SC(=C(N=1)C)C1=NC(=NC=C1F)NC1=NC=C(C=C1)CN1CCN(CC1)CC POFVJRKJJBFPII-UHFFFAOYSA-N 0.000 description 2
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- 108091093037 Peptide nucleic acid Proteins 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 2
- 239000004809 Teflon Substances 0.000 description 2
- 229920006362 Teflon® Polymers 0.000 description 2
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 2
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 2
- LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 2
- 125000004103 aminoalkyl group Chemical group 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000000740 bleeding effect Effects 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 150000001719 carbohydrate derivatives Chemical class 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 150000003857 carboxamides Chemical class 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 229940125898 compound 5 Drugs 0.000 description 2
- 239000013058 crude material Substances 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
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 229960000980 entecavir Drugs 0.000 description 2
- YXPVEXCTPGULBZ-WQYNNSOESA-N entecavir hydrate Chemical compound O.C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)C1=C YXPVEXCTPGULBZ-WQYNNSOESA-N 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 238000007429 general method Methods 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 125000001475 halogen functional group Chemical group 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 208000006454 hepatitis Diseases 0.000 description 2
- 102000056556 human TTR Human genes 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 230000002163 immunogen Effects 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 229950000038 interferon alfa Drugs 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000007913 intrathecal administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 208000018191 liver inflammation Diseases 0.000 description 2
- 210000005228 liver tissue Anatomy 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical class CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 2
- 230000003278 mimic effect Effects 0.000 description 2
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 230000008520 organization Effects 0.000 description 2
- 230000036407 pain Effects 0.000 description 2
- 108010092853 peginterferon alfa-2a Proteins 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000003285 pharmacodynamic effect Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 description 2
- 230000036470 plasma concentration Effects 0.000 description 2
- 230000008488 polyadenylation Effects 0.000 description 2
- 229920000136 polysorbate Polymers 0.000 description 2
- 229950008882 polysorbate Drugs 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 230000007112 pro inflammatory response Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 150000003212 purines Chemical class 0.000 description 2
- 150000003230 pyrimidines Chemical class 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 238000001542 size-exclusion chromatography Methods 0.000 description 2
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 239000008223 sterile water Substances 0.000 description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- IQFYYKKMVGJFEH-CSMHCCOUSA-N telbivudine Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1O[C@@H](CO)[C@H](O)C1 IQFYYKKMVGJFEH-CSMHCCOUSA-N 0.000 description 2
- 229960004556 tenofovir Drugs 0.000 description 2
- VCMJCVGFSROFHV-WZGZYPNHSA-N tenofovir disoproxil fumarate Chemical compound OC(=O)\C=C\C(O)=O.N1=CN=C2N(C[C@@H](C)OCP(=O)(OCOC(=O)OC(C)C)OCOC(=O)OC(C)C)C=NC2=C1N VCMJCVGFSROFHV-WZGZYPNHSA-N 0.000 description 2
- 150000003573 thiols Chemical class 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 230000002110 toxicologic effect Effects 0.000 description 2
- 150000003626 triacylglycerols Chemical class 0.000 description 2
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 2
- 238000000108 ultra-filtration Methods 0.000 description 2
- 230000029812 viral genome replication Effects 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 1
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
- VCQURUZYYSOUHP-UHFFFAOYSA-N (2,3,4,5,6-pentafluorophenyl) 2,2,2-trifluoroacetate Chemical compound FC1=C(F)C(F)=C(OC(=O)C(F)(F)F)C(F)=C1F VCQURUZYYSOUHP-UHFFFAOYSA-N 0.000 description 1
- FYADHXFMURLYQI-UHFFFAOYSA-N 1,2,4-triazine Chemical class C1=CN=NC=N1 FYADHXFMURLYQI-UHFFFAOYSA-N 0.000 description 1
- DIIIISSCIXVANO-UHFFFAOYSA-N 1,2-Dimethylhydrazine Chemical compound CNNC DIIIISSCIXVANO-UHFFFAOYSA-N 0.000 description 1
- PISWNSOQFZRVJK-XLPZGREQSA-N 1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-2-sulfanylidenepyrimidin-4-one Chemical compound S=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 PISWNSOQFZRVJK-XLPZGREQSA-N 0.000 description 1
- 125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 description 1
- BMVXCPBXGZKUPN-UHFFFAOYSA-N 1-hexanamine Chemical compound CCCCCCN BMVXCPBXGZKUPN-UHFFFAOYSA-N 0.000 description 1
- WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 1
- TZMSYXZUNZXBOL-UHFFFAOYSA-N 10H-phenoxazine Chemical compound C1=CC=C2NC3=CC=CC=C3OC2=C1 TZMSYXZUNZXBOL-UHFFFAOYSA-N 0.000 description 1
- 238000004293 19F NMR spectroscopy Methods 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- QSHACTSJHMKXTE-UHFFFAOYSA-N 2-(2-aminopropyl)-7h-purin-6-amine Chemical compound CC(N)CC1=NC(N)=C2NC=NC2=N1 QSHACTSJHMKXTE-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- MSWZFWKMSRAUBD-GASJEMHNSA-N 2-amino-2-deoxy-D-galactopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O MSWZFWKMSRAUBD-GASJEMHNSA-N 0.000 description 1
- JRYMOPZHXMVHTA-DAGMQNCNSA-N 2-amino-7-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1h-pyrrolo[2,3-d]pyrimidin-4-one Chemical compound C1=CC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O JRYMOPZHXMVHTA-DAGMQNCNSA-N 0.000 description 1
- WKMPTBDYDNUJLF-UHFFFAOYSA-N 2-fluoroadenine Chemical compound NC1=NC(F)=NC2=C1N=CN2 WKMPTBDYDNUJLF-UHFFFAOYSA-N 0.000 description 1
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- CFIBTBBTJWHPQV-UHFFFAOYSA-N 2-methyl-n-(6-oxo-3,7-dihydropurin-2-yl)propanamide Chemical compound N1C(NC(=O)C(C)C)=NC(=O)C2=C1N=CN2 CFIBTBBTJWHPQV-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 108020003589 5' Untranslated Regions Proteins 0.000 description 1
- ACEMKCOYIINOHN-UHFFFAOYSA-N 5-methyl-1h-pyrimidine-2,4-dione;pyrimidine Chemical compound C1=CN=CN=C1.CC1=CNC(=O)NC1=O ACEMKCOYIINOHN-UHFFFAOYSA-N 0.000 description 1
- UJBCLAXPPIDQEE-UHFFFAOYSA-N 5-prop-1-ynyl-1h-pyrimidine-2,4-dione Chemical compound CC#CC1=CNC(=O)NC1=O UJBCLAXPPIDQEE-UHFFFAOYSA-N 0.000 description 1
- QQJXZVKXNSFHRI-UHFFFAOYSA-N 6-Benzamidopurine Chemical compound N=1C=NC=2N=CNC=2C=1NC(=O)C1=CC=CC=C1 QQJXZVKXNSFHRI-UHFFFAOYSA-N 0.000 description 1
- KXBCLNRMQPRVTP-UHFFFAOYSA-N 6-amino-1,5-dihydroimidazo[4,5-c]pyridin-4-one Chemical compound O=C1NC(N)=CC2=C1N=CN2 KXBCLNRMQPRVTP-UHFFFAOYSA-N 0.000 description 1
- DCPSTSVLRXOYGS-UHFFFAOYSA-N 6-amino-1h-pyrimidine-2-thione Chemical compound NC1=CC=NC(S)=N1 DCPSTSVLRXOYGS-UHFFFAOYSA-N 0.000 description 1
- QNNARSZPGNJZIX-UHFFFAOYSA-N 6-amino-5-prop-1-ynyl-1h-pyrimidin-2-one Chemical compound CC#CC1=CNC(=O)N=C1N QNNARSZPGNJZIX-UHFFFAOYSA-N 0.000 description 1
- NJBMMMJOXRZENQ-UHFFFAOYSA-N 6H-pyrrolo[2,3-f]quinoline Chemical compound c1cc2ccc3[nH]cccc3c2n1 NJBMMMJOXRZENQ-UHFFFAOYSA-N 0.000 description 1
- LOSIULRWFAEMFL-UHFFFAOYSA-N 7-deazaguanine Chemical compound O=C1NC(N)=NC2=C1CC=N2 LOSIULRWFAEMFL-UHFFFAOYSA-N 0.000 description 1
- HRYKDUPGBWLLHO-UHFFFAOYSA-N 8-azaadenine Chemical compound NC1=NC=NC2=NNN=C12 HRYKDUPGBWLLHO-UHFFFAOYSA-N 0.000 description 1
- LPXQRXLUHJKZIE-UHFFFAOYSA-N 8-azaguanine Chemical compound NC1=NC(O)=C2NN=NC2=N1 LPXQRXLUHJKZIE-UHFFFAOYSA-N 0.000 description 1
- 229960005508 8-azaguanine Drugs 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 239000004382 Amylase Substances 0.000 description 1
- 102000013142 Amylases Human genes 0.000 description 1
- 108010065511 Amylases Proteins 0.000 description 1
- 101710081722 Antitrypsin Proteins 0.000 description 1
- 102100030970 Apolipoprotein C-III Human genes 0.000 description 1
- 108010071619 Apolipoproteins Proteins 0.000 description 1
- 102000007592 Apolipoproteins Human genes 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 1
- QCMYYKRYFNMIEC-UHFFFAOYSA-N COP(O)=O Chemical class COP(O)=O QCMYYKRYFNMIEC-UHFFFAOYSA-N 0.000 description 1
- 101100172874 Caenorhabditis elegans sec-3 gene Proteins 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 229940126657 Compound 17 Drugs 0.000 description 1
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
- 125000000824 D-ribofuranosyl group Chemical group [H]OC([H])([H])[C@@]1([H])OC([H])(*)[C@]([H])(O[H])[C@]1([H])O[H] 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical group C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 239000012981 Hank's balanced salt solution Substances 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 208000031220 Hemophilia Diseases 0.000 description 1
- 208000009292 Hemophilia A Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000793223 Homo sapiens Apolipoprotein C-III Proteins 0.000 description 1
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010022004 Influenza like illness Diseases 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 241000282567 Macaca fascicularis Species 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 229910003849 O-Si Inorganic materials 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- 229910003872 O—Si Inorganic materials 0.000 description 1
- 108010011536 PTEN Phosphohydrolase Proteins 0.000 description 1
- 102000014160 PTEN Phosphohydrolase Human genes 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 229920000297 Rayon Polymers 0.000 description 1
- 206010038910 Retinitis Diseases 0.000 description 1
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 101000874347 Streptococcus agalactiae IgA FC receptor Proteins 0.000 description 1
- 108091036066 Three prime untranslated region Proteins 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 229960001997 adefovir Drugs 0.000 description 1
- WOZSCQDILHKSGG-UHFFFAOYSA-N adefovir depivoxil Chemical compound N1=CN=C2N(CCOCP(=O)(OCOC(=O)C(C)(C)C)OCOC(=O)C(C)(C)C)C=NC2=C1N WOZSCQDILHKSGG-UHFFFAOYSA-N 0.000 description 1
- QBYJBZPUGVGKQQ-SJJAEHHWSA-N aldrin Chemical compound C1[C@H]2C=C[C@@H]1[C@H]1[C@@](C3(Cl)Cl)(Cl)C(Cl)=C(Cl)[C@@]3(Cl)[C@H]12 QBYJBZPUGVGKQQ-SJJAEHHWSA-N 0.000 description 1
- 125000002877 alkyl aryl group Chemical group 0.000 description 1
- 125000005600 alkyl phosphonate group Chemical group 0.000 description 1
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 125000002344 aminooxy group Chemical group [H]N([H])O[*] 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 235000019418 amylase Nutrition 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 230000001475 anti-trypsic effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000003529 anticholesteremic agent Substances 0.000 description 1
- 229940127226 anticholesterol agent Drugs 0.000 description 1
- 230000004596 appetite loss Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000005872 benzooxazolyl group Chemical group 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 229920000249 biocompatible polymer Polymers 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 239000010836 blood and blood product Substances 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000004700 cellular uptake Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000013626 chemical specie Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 150000001841 cholesterols Chemical class 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 235000021310 complex sugar Nutrition 0.000 description 1
- 229940126543 compound 14 Drugs 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 125000001651 cyanato group Chemical group [*]OC#N 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 125000002704 decyl group Chemical group [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])* 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 150000001993 dienes Chemical class 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- RJBIAAZJODIFHR-UHFFFAOYSA-N dihydroxy-imino-sulfanyl-$l^{5}-phosphane Chemical compound NP(O)(O)=S RJBIAAZJODIFHR-UHFFFAOYSA-N 0.000 description 1
- NAGJZTKCGNOGPW-UHFFFAOYSA-K dioxido-sulfanylidene-sulfido-$l^{5}-phosphane Chemical compound [O-]P([O-])([S-])=S NAGJZTKCGNOGPW-UHFFFAOYSA-K 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 125000003438 dodecyl group Chemical group [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])* 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethyl mercaptane Natural products CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000010685 fatty oil Substances 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
- 235000013305 food Nutrition 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 229960003082 galactose Drugs 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000030279 gene silencing Effects 0.000 description 1
- 238000012226 gene silencing method Methods 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 230000001553 hepatotropic effect Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 125000001183 hydrocarbyl group Chemical group 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 239000002117 illicit drug Substances 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 125000001841 imino group Chemical group [H]N=* 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000000185 intracerebroventricular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 230000002601 intratumoral effect Effects 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 230000007803 itching Effects 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229960001627 lamivudine Drugs 0.000 description 1
- JTEGQNOMFQHVDC-NKWVEPMBSA-N lamivudine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 208000019017 loss of appetite Diseases 0.000 description 1
- 235000021266 loss of appetite Nutrition 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 210000003712 lysosome Anatomy 0.000 description 1
- 230000001868 lysosomic effect Effects 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 230000010120 metabolic dysregulation Effects 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- 210000002161 motor neuron Anatomy 0.000 description 1
- XBDUZBHKKUFFRH-UHFFFAOYSA-N n-(2-oxo-1h-pyrimidin-6-yl)benzamide Chemical compound OC1=NC=CC(NC(=O)C=2C=CC=CC=2)=N1 XBDUZBHKKUFFRH-UHFFFAOYSA-N 0.000 description 1
- FMKLITBCOZWOEX-UHFFFAOYSA-N n-(5-methyl-2-oxo-1h-pyrimidin-6-yl)benzamide Chemical compound CC1=CNC(=O)N=C1NC(=O)C1=CC=CC=C1 FMKLITBCOZWOEX-UHFFFAOYSA-N 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 230000032405 negative regulation of neuron apoptotic process Effects 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 125000002347 octyl 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])[H] 0.000 description 1
- 229940046166 oligodeoxynucleotide Drugs 0.000 description 1
- 238000006384 oligomerization reaction Methods 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 229920000620 organic polymer Polymers 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 210000004738 parenchymal cell Anatomy 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 239000012466 permeate Substances 0.000 description 1
- 229950000688 phenothiazine Drugs 0.000 description 1
- 150000002991 phenoxazines Chemical class 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- ACVYVLVWPXVTIT-UHFFFAOYSA-M phosphinate Chemical compound [O-][PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-M 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
- 150000008300 phosphoramidites Chemical class 0.000 description 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 229940068886 polyethylene glycol 300 Drugs 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000001124 posttranscriptional effect Effects 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- IGFXRKMLLMBKSA-UHFFFAOYSA-N purine Chemical compound N1=C[N]C2=NC=NC2=C1 IGFXRKMLLMBKSA-UHFFFAOYSA-N 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- RXTQGIIIYVEHBN-UHFFFAOYSA-N pyrimido[4,5-b]indol-2-one Chemical compound C1=CC=CC2=NC3=NC(=O)N=CC3=C21 RXTQGIIIYVEHBN-UHFFFAOYSA-N 0.000 description 1
- SRBUGYKMBLUTIS-UHFFFAOYSA-N pyrrolo[2,3-d]pyrimidin-2-one Chemical compound O=C1N=CC2=CC=NC2=N1 SRBUGYKMBLUTIS-UHFFFAOYSA-N 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 238000001525 receptor binding assay Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 125000000548 ribosyl group Chemical group C1([C@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 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 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 238000003307 slaughter Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000007974 sodium acetate buffer Substances 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- 125000005864 sulfonamidyl group Chemical group 0.000 description 1
- 125000004962 sulfoxyl group Chemical group 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229960005311 telbivudine Drugs 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 150000003527 tetrahydropyrans Chemical class 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000005309 thioalkoxy group Chemical group 0.000 description 1
- 125000004001 thioalkyl group Chemical group 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000723 toxicological property Toxicity 0.000 description 1
- 230000014621 translational initiation Effects 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000002747 voluntary effect Effects 0.000 description 1
- 229940075420 xanthine Drugs 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
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)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Microbiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (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 (8)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361818442P | 2013-05-01 | 2013-05-01 | |
| US201361823826P | 2013-05-15 | 2013-05-15 | |
| US201361843887P | 2013-07-08 | 2013-07-08 | |
| US201361871673P | 2013-08-29 | 2013-08-29 | |
| US201361880790P | 2013-09-20 | 2013-09-20 | |
| US201461976991P | 2014-04-08 | 2014-04-08 | |
| US201461986867P | 2014-04-30 | 2014-04-30 | |
| PCT/US2014/036463 WO2014179627A2 (en) | 2013-05-01 | 2014-05-01 | Compositions and methods for modulating hbv and ttr expression |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2730015T3 true ES2730015T3 (es) | 2019-11-07 |
Family
ID=51843959
Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES14791187T Active ES2819213T3 (es) | 2013-05-01 | 2014-05-01 | Composiciones y métodos para modular la expresión de apolipoproteína (a) |
| ES19164959T Active ES2885174T3 (es) | 2013-05-01 | 2014-05-01 | Composiciones y métodos para modular expresión de TTR |
| ES14791557T Active ES2778442T3 (es) | 2013-05-01 | 2014-05-01 | Composiciones y procedimientos de modulación de la expresión de la apolipoproteína C-III |
| ES14791344T Active ES2730015T3 (es) | 2013-05-01 | 2014-05-01 | Composiciones y métodos para modular expresión de HBV y de TTR |
Family Applications Before (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES14791187T Active ES2819213T3 (es) | 2013-05-01 | 2014-05-01 | Composiciones y métodos para modular la expresión de apolipoproteína (a) |
| ES19164959T Active ES2885174T3 (es) | 2013-05-01 | 2014-05-01 | Composiciones y métodos para modular expresión de TTR |
| ES14791557T Active ES2778442T3 (es) | 2013-05-01 | 2014-05-01 | Composiciones y procedimientos de modulación de la expresión de la apolipoproteína C-III |
Country Status (40)
Families Citing this family (507)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2009305636A1 (en) | 2008-10-15 | 2010-04-22 | Ionis Pharmaceuticals, Inc. | Modulation of Factor 11 expression |
| SG171914A1 (en) | 2008-12-02 | 2011-07-28 | Chiralgen Ltd | Method for the synthesis of phosphorus atom modified nucleic acids |
| IN2012DN00720A (OSRAM) | 2009-07-06 | 2015-06-19 | Ontorii Inc | |
| WO2012039448A1 (ja) | 2010-09-24 | 2012-03-29 | 株式会社キラルジェン | 不斉補助基 |
| EP3521451A1 (en) | 2010-11-17 | 2019-08-07 | Ionis Pharmaceuticals, Inc. | Modulation of alpha synuclein expression |
| MX347361B (es) | 2011-07-19 | 2017-04-12 | Wave Life Sciences Ltd | Metodos para la sintesis de acidos nucleicos funcionalizados. |
| WO2013033230A1 (en) * | 2011-08-29 | 2013-03-07 | Isis Pharmaceuticals, Inc. | Oligomer-conjugate complexes and their use |
| WO2013148260A1 (en) | 2012-03-30 | 2013-10-03 | Washington University | Methods for modulating tau expression for reducing seizure and modifying a neurodegenerative syndrome |
| EP2839006B1 (en) * | 2012-04-20 | 2018-01-03 | Ionis Pharmaceuticals, Inc. | Oligomeric compounds comprising bicyclic nucleotides and uses thereof |
| 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) |
| AU2013287630B2 (en) | 2012-07-13 | 2017-05-25 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant |
| EP2872485B1 (en) | 2012-07-13 | 2020-12-16 | Wave Life Sciences Ltd. | Asymmetric auxiliary group |
| EP2872147B1 (en) | 2012-07-13 | 2022-12-21 | Wave Life Sciences Ltd. | Method for making chiral oligonucleotides |
| RU2015119411A (ru) * | 2012-11-15 | 2017-01-10 | Рош Инновейшен Сентер Копенгаген А/С | Конъюгаты антисмысловых соединений, направленные на аполипопротеин в |
| WO2014118267A1 (en) * | 2013-01-30 | 2014-08-07 | Santaris Pharma A/S | Lna oligonucleotide carbohydrate conjugates |
| ES2680599T3 (es) | 2013-02-14 | 2018-09-10 | Ionis Pharmaceuticals, Inc. | Modulación de la expresión de apolipoproteína C-III (ApoCIII) en poblaciones deficientes en lipoproteína lipasa (LPLD) |
| NZ630890A (en) | 2013-05-01 | 2017-09-29 | Regulus Therapeutics Inc | Microrna compounds and methods for modulating mir-122 |
| US9506030B2 (en) | 2013-05-01 | 2016-11-29 | Regulus Therapeutics Inc. | Compounds and methods for enhanced cellular uptake |
| PL2992098T3 (pl) | 2013-05-01 | 2019-09-30 | Ionis Pharmaceuticals, Inc. | Kompozycje i sposoby modulowania ekspresji hbv i ttr |
| SG10201908122XA (en) | 2013-06-27 | 2019-10-30 | Roche Innovation Ct Copenhagen As | Antisense oligomers and conjugates targeting pcsk9 |
| EP3019200B1 (en) * | 2013-07-11 | 2022-03-23 | Alnylam Pharmaceuticals, Inc. | Oligonucleotide-ligand conjugates and process for their preparation |
| 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 |
| TW202246503A (zh) | 2013-07-19 | 2022-12-01 | 美商百健Ma公司 | 用於調節τ蛋白表現之組合物 |
| US9943604B2 (en) | 2013-09-20 | 2018-04-17 | Ionis Pharmaceuticals, Inc. | Targeted therapeutic nucleosides and their use |
| US10077444B2 (en) * | 2013-10-02 | 2018-09-18 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of the LECT2 gene |
| US11162096B2 (en) | 2013-10-14 | 2021-11-02 | Ionis Pharmaceuticals, Inc | Methods for modulating expression of C9ORF72 antisense transcript |
| EP3060664B1 (en) | 2013-10-25 | 2021-07-07 | Sanofi | Microrna compounds and methods for modulating mir-21 activity |
| KR20160083876A (ko) * | 2013-11-14 | 2016-07-12 | 로슈 이노베이션 센터 코펜하겐 에이/에스 | ApoB 안티센스 접합체 화합물 |
| 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 |
| EP3095460A4 (en) | 2014-01-15 | 2017-08-23 | 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 |
| US10144933B2 (en) | 2014-01-15 | 2018-12-04 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant having immunity induction activity, and immunity induction activator |
| CN106068325B (zh) | 2014-01-16 | 2021-07-09 | 波涛生命科学有限公司 | 手性设计 |
| EA201691587A1 (ru) | 2014-02-11 | 2017-01-30 | Элнилэм Фармасьютикалз, Инк. | КОМПОЗИЦИИ НА ОСНОВЕ iRNA ДЛЯ КЕТОГЕКСОКИНАЗЫ (KHK) И СПОСОБЫ ИХ ПРИМЕНЕНИЯ |
| PL3119888T3 (pl) | 2014-03-19 | 2021-12-20 | Ionis Pharmaceuticals, Inc. | Kompozycje do modulacji ekspresji ataksyny 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 |
| EP4223315A3 (en) * | 2014-05-01 | 2023-08-23 | Ionis Pharmaceuticals, Inc. | Method for synthesis of reactive conjugate clusters |
| MX373283B (es) | 2014-05-01 | 2020-05-20 | Ionis Pharmaceuticals Inc | Composiciones y metodos para modular la expresion del receptor de la hormona del crecimiento. |
| EP4534092A3 (en) | 2014-05-01 | 2025-07-02 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating pkk expression |
| PH12016502062B1 (en) * | 2014-05-01 | 2023-01-27 | Ionis Pharmaceuticals Inc | Compositions and methods for modulating complement factor b expression |
| EP3137605B1 (en) | 2014-05-01 | 2020-10-28 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating angiopoietin-like 3 expression |
| GB201408623D0 (en) | 2014-05-15 | 2014-07-02 | Santaris Pharma As | Oligomers and oligomer conjugates |
| EA201692370A1 (ru) | 2014-05-22 | 2017-03-31 | Элнилэм Фармасьютикалз, Инк. | КОМПОЗИЦИИ иРНК АНГИОТЕНЗИНОГЕНА (AGT) И СПОСОБЫ ИХ ИСПОЛЬЗОВАНИЯ |
| GB201410693D0 (en) | 2014-06-16 | 2014-07-30 | Univ Southampton | Splicing modulation |
| JP2017523790A (ja) | 2014-08-07 | 2017-08-24 | レグルス セラピューティクス インコーポレイテッド | 代謝障害のためのマイクロrnaの標的化 |
| WO2016040748A1 (en) | 2014-09-12 | 2016-03-17 | Ionis Pharmaceuticals, Inc. | Compositions and methods for detection of smn protein in a subject and treatment of a subject |
| EP3201339A4 (en) | 2014-10-03 | 2018-09-19 | Cold Spring Harbor Laboratory | Targeted augmentation of nuclear gene output |
| SG11201702877TA (en) * | 2014-10-10 | 2017-05-30 | Hoffmann La Roche | 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 |
| AU2015350120B2 (en) | 2014-11-17 | 2021-05-27 | Alnylam Pharmaceuticals, Inc. | Apolipoprotein C3 (APOC3) iRNA compositions and methods of use thereof |
| EP3234141A4 (en) | 2014-12-18 | 2018-06-20 | Alnylam Pharmaceuticals, Inc. | Reversir tm compounds |
| WO2016112132A1 (en) | 2015-01-06 | 2016-07-14 | 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 |
| US10731154B2 (en) | 2015-02-15 | 2020-08-04 | Arcturus Therapeutics, Inc. | Acyl-amino-LNA and/or hydrocarbyl-amino-LNA oligonucleotides |
| US11129844B2 (en) | 2015-03-03 | 2021-09-28 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating MECP2 expression |
| JP6892433B2 (ja) | 2015-04-03 | 2021-06-23 | ユニバーシティ・オブ・マサチューセッツUniversity Of Massachusetts | 十分に安定化された非対称sirna |
| JP6833705B2 (ja) * | 2015-04-03 | 2021-02-24 | アイオーニス ファーマシューティカルズ, インコーポレーテッドIonis Pharmaceuticals,Inc. | Tmprss6発現を調節するための化合物及び方法 |
| 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 |
| EP3286310A4 (en) | 2015-04-24 | 2019-01-09 | California Institute of Technology | REACTIVATION OF X-CHROMOSOME GENES |
| WO2016205323A1 (en) | 2015-06-18 | 2016-12-22 | Alnylam Pharmaceuticals, Inc. | Polynucleotde 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 |
| EP4545544A3 (en) | 2015-06-29 | 2025-10-08 | Ionis Pharmaceuticals, Inc. | Modified crispr rna and modified single crispr rna and uses thereof |
| BR112017028194B1 (pt) | 2015-07-10 | 2023-03-14 | Ionis Pharmaceuticals, Inc | Composto oligomérico modulador de diaciglicerol aciltransferase 2 (dgat2), composição, e seus usos |
| 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 |
| EP3323893A4 (en) * | 2015-07-16 | 2019-03-27 | Kyowa Hakko Kirin Co., Ltd. | BETA2GPI GENE EXPRESSION-INHIBITING NUCLEIC ACID COMPLEX |
| MA43072A (fr) | 2015-07-22 | 2018-05-30 | Wave Life Sciences Ltd | Compositions d'oligonucléotides et procédés associés |
| PL3331892T3 (pl) | 2015-08-06 | 2019-11-29 | Hoffmann La Roche | Sposób wytwarzania pochodnych kwasu GalNAc |
| 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 |
| 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 |
| US10633653B2 (en) | 2015-08-14 | 2020-04-28 | University Of Massachusetts | Bioactive conjugates for oligonucleotide delivery |
| KR20180043819A (ko) | 2015-08-24 | 2018-04-30 | 로슈 이노베이션 센터 코펜하겐 에이/에스 | Lna-g 방법 |
| EA201890619A1 (ru) | 2015-09-02 | 2018-09-28 | Элнилэм Фармасьютикалз, Инк. | КОМПОЗИЦИИ iRNA ЛИГАНДА 1 БЕЛКА ЗАПРОГРАММИРОВАННОЙ ГИБЕЛИ КЛЕТОК 1 (PD-L1) И СПОСОБЫ ИХ ПРИМЕНЕНИЯ |
| AR106135A1 (es) | 2015-09-24 | 2017-12-13 | Ionis Pharmaceuticals Inc | Moduladores de la expresión del sarcoma de la rata de kirsten (kras) |
| JP6853539B2 (ja) | 2015-09-24 | 2021-03-31 | 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The Regents Of The University Of California | 合成スフィンゴ脂質様分子、薬物、これらの合成方法、および処置方法 |
| US20180273948A1 (en) * | 2015-09-25 | 2018-09-27 | Tarveda Therapeutics, Inc. | RNAi CONJUGATES, PARTICLES AND FORMULATIONS THEREOF |
| US20210052631A1 (en) * | 2015-09-25 | 2021-02-25 | Ionis Pharmaceuticals, Inc. | Conjugated antisense compounds and their use |
| JP2018528783A (ja) | 2015-09-25 | 2018-10-04 | アイオーニス ファーマシューティカルズ, インコーポレーテッドIonis Pharmaceuticals,Inc. | コンジュゲートアンチセンス化合物及びその使用 |
| EP3353303B1 (en) | 2015-09-25 | 2023-08-02 | 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 |
| WO2017055423A1 (en) | 2015-10-02 | 2017-04-06 | Roche Innovation Center Copenhagen A/S | Oligonucleotide conjugation process |
| MY200263A (en) | 2015-10-08 | 2023-12-18 | Ionis Pharmaceuticals Inc | Compounds and methods for modulating angiotensinogen expression |
| KR102422625B1 (ko) | 2015-10-09 | 2022-07-20 | 유니버시티 오브 사우스앰톤 | 유전자 발현의 조절 및 탈조절된 단백질 발현의 스크리닝 |
| WO2017068087A1 (en) | 2015-10-22 | 2017-04-27 | Roche Innovation Center Copenhagen A/S | Oligonucleotide detection method |
| WO2017067970A1 (en) | 2015-10-22 | 2017-04-27 | Roche Innovation Center Copenhagen A/S | In vitro toxicity screening assay |
| SMT202400375T1 (it) | 2015-11-06 | 2024-11-15 | Ionis Pharmaceuticals Inc | Composti antisenso coniugati per uso in terapia |
| KR20250078597A (ko) * | 2015-11-06 | 2025-06-02 | 아이오니스 파마수티컬즈, 인코포레이티드 | 아포리포프로테인 (a) 발현 조정 |
| CN108738321B (zh) * | 2015-11-16 | 2021-06-11 | 豪夫迈·罗氏有限公司 | GalNAc簇亚磷酰胺 |
| WO2017096395A1 (en) | 2015-12-04 | 2017-06-08 | Ionis Pharmaceuticals, Inc. | Methods of treating breast cancer |
| KR102604132B1 (ko) | 2015-12-14 | 2023-11-17 | 콜드스프링하버러보러토리 | 상염색체 우성 정신 지체 5 및 드라베 증후군의 치료를 위한 안티센스 올리고머 |
| US11096956B2 (en) | 2015-12-14 | 2021-08-24 | Stoke Therapeutics, Inc. | Antisense oligomers and uses thereof |
| AU2016381174A1 (en) | 2015-12-31 | 2018-05-31 | Ionis Pharmaceuticals, Inc. | Methods for reducing Ataxin-2 expression |
| WO2017120365A1 (en) | 2016-01-05 | 2017-07-13 | Ionis Pharmaceuticals, Inc. | Methods for reducing lrrk2 expression |
| WO2017123696A1 (en) | 2016-01-12 | 2017-07-20 | Interleukin Genetics, Inc. | Methods for predicting response to treatment |
| MX2018009090A (es) | 2016-01-26 | 2019-03-28 | Nissan Chemical Corp | Oligonucleótido de cadena simple. |
| AU2017213404A1 (en) * | 2016-01-29 | 2018-09-20 | Kyowa Kirin Co., Ltd. | Nucleic acid conjugate |
| JP7749201B6 (ja) * | 2016-01-31 | 2025-10-21 | ユニバーシティー オブ マサチューセッツ | 分岐オリゴヌクレオチド |
| NZ744357A (en) | 2016-03-07 | 2025-09-26 | Arrowhead Pharmaceuticals Inc | Targeting ligands for therapeutic compounds |
| EP3426349A4 (en) | 2016-03-09 | 2020-01-01 | Ionis Pharmaceuticals, Inc. | Methods and compositions for inhibiting pmp22 expression |
| PL3430141T3 (pl) | 2016-03-14 | 2022-02-28 | F. Hoffmann-La Roche Ag | Oligonukleotydy do obniżenia ekspresji pd-l1 |
| US10577607B2 (en) | 2016-03-16 | 2020-03-03 | Ionis Pharmaceuticals, Inc. | Modulation of DYRK1B expression |
| EP3429690A4 (en) | 2016-03-16 | 2019-10-23 | Ionis Pharmaceuticals, Inc. | METHOD FOR MODULATING KEAP1 |
| 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 |
| CA3017532A1 (en) | 2016-04-13 | 2017-10-19 | Ionis Pharmaceuticals, Inc. | Methods for reducing c9orf72 expression |
| CN109153697A (zh) | 2016-04-14 | 2019-01-04 | 豪夫迈·罗氏有限公司 | 三苯甲基-单-GalNAc化合物及其用途 |
| 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 |
| SG11201809002RA (en) | 2016-04-29 | 2018-11-29 | Univ Nanyang Tech | G-quadruplex-containing antisense oligonucleotides |
| MA45270A (fr) | 2016-05-04 | 2017-11-09 | Wave Life Sciences Ltd | Compositions d'oligonucléotides et procédés associés |
| AU2017260003B2 (en) | 2016-05-06 | 2019-12-05 | Astrazeneca Ab | GLP-1 receptor ligand moiety conjugated oligonucleotides and uses thereof |
| US11236339B2 (en) | 2016-06-17 | 2022-02-01 | Ionis Pharmaceuticals, Inc. | Modulation of GYS1 expression |
| 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 |
| JP7049271B2 (ja) | 2016-06-17 | 2022-04-06 | 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 |
| CN109477103A (zh) | 2016-06-22 | 2019-03-15 | ProQR治疗上市公司Ⅱ | 单链rna-编辑寡核苷酸 |
| EP3498724B1 (en) * | 2016-06-30 | 2023-06-21 | Kyowa Kirin Co., Ltd. | Nucleic acid complex |
| AU2017296195A1 (en) | 2016-07-11 | 2019-01-24 | Translate Bio Ma, Inc. | Nucleic acid conjugates and uses thereof |
| EP4206213A1 (en) | 2016-07-15 | 2023-07-05 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulation of smn2 |
| US10781175B2 (en) | 2016-07-15 | 2020-09-22 | Am Chemicals Llc | Solid supports and phosphoramidite building blocks for oligonucleotide conjugates |
| WO2018031933A2 (en) | 2016-08-12 | 2018-02-15 | University Of Massachusetts | Conjugated oligonucleotides |
| WO2018035380A1 (en) * | 2016-08-17 | 2018-02-22 | Solstice Biologics, Ltd. | Polynucleotide constructs |
| NZ751483A (en) | 2016-09-01 | 2022-07-01 | Proqr Therapeutics Ii Bv | Chemically modified single-stranded rna-editing oligonucleotides |
| KR102856522B1 (ko) * | 2016-09-02 | 2025-09-08 | 애로우헤드 파마슈티컬스 인코포레이티드 | 표적화 리간드 |
| US20190275171A1 (en) * | 2016-09-23 | 2019-09-12 | 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 |
| CN109661233A (zh) * | 2016-10-06 | 2019-04-19 | Ionis 制药公司 | 缀合低聚化合物的方法 |
| JP2019537427A (ja) | 2016-10-27 | 2019-12-26 | カリフォルニア インスティチュート オブ テクノロジー | X染色体の再活性化のためのhdac阻害剤組成物 |
| JOP20190104A1 (ar) | 2016-11-10 | 2019-05-07 | Ionis Pharmaceuticals Inc | مركبات وطرق لتقليل التعبير عن atxn3 |
| JP2019533472A (ja) * | 2016-11-11 | 2019-11-21 | ヤンセン バイオファーマ インク. | Hbv cccdnaのオリゴヌクレオチド標的化戦略 |
| 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 |
| CN110177544A (zh) | 2016-11-29 | 2019-08-27 | 普尔泰克健康有限公司 | 用于递送治疗剂的外泌体 |
| US11033570B2 (en) | 2016-12-02 | 2021-06-15 | Cold Spring Harbor Laboratory | Modulation of Lnc05 expression |
| EP3556402A4 (en) * | 2016-12-13 | 2020-08-05 | AM Sciences Inc | PHARMACEUTICAL COMPOSITION FOR THE PREVENTION OR TREATMENT OF HEPATITIS B |
| EP3555292A1 (en) | 2016-12-16 | 2019-10-23 | Alnylam Pharmaceuticals, Inc. | Methods for treating or preventing ttr-associated diseases using transthyretin (ttr) irna compositions |
| 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 |
| US20190338286A1 (en) | 2017-01-13 | 2019-11-07 | Roche Innovation Center Copenhagen A/S | Antisense oligonucleotides for modulating rel expression |
| US20190367920A1 (en) | 2017-01-13 | 2019-12-05 | Roche Innovation Center Copenhagen A/S | Antisense oligonucleotides for modulating nfkb1 expression |
| EP3568477A1 (en) | 2017-01-13 | 2019-11-20 | Roche Innovation Center Copenhagen A/S | Antisense oligonucleotides for modulating rela expression |
| WO2018130585A1 (en) | 2017-01-13 | 2018-07-19 | Roche Innovation Center Copenhagen A/S | Antisense oligonucleotides for modulating relb expression |
| WO2018130584A1 (en) | 2017-01-13 | 2018-07-19 | Roche Innovation Center Copenhagen A/S | Antisense oligonucleotides for modulating nfkb2 expression |
| EP3584319A4 (en) | 2017-02-06 | 2021-04-14 | Nissan Chemical Corporation | SINGLE-STRAND OLIGONUCLEOTIDE |
| WO2018165564A1 (en) * | 2017-03-09 | 2018-09-13 | Ionis Pharmaceuticals, Inc. | Morpholino modified oligomeric compounds |
| WO2018164275A1 (ja) | 2017-03-10 | 2018-09-13 | 国立研究開発法人国立成育医療研究センター | アンチセンスオリゴヌクレオチドおよび糖原病Ia型予防または治療用組成物 |
| JOP20190215A1 (ar) * | 2017-03-24 | 2019-09-19 | Ionis Pharmaceuticals Inc | مُعدّلات التعبير الوراثي عن pcsk9 |
| CN110520531A (zh) * | 2017-04-05 | 2019-11-29 | 赛伦斯治疗有限责任公司 | 产品和组合物 |
| EP3385272A1 (en) * | 2017-04-05 | 2018-10-10 | Silence Therapeutics GmbH | Further novel oligonucleotide-ligand conjugates |
| JP2020516296A (ja) | 2017-04-11 | 2020-06-11 | アルブータス・バイオファーマー・コーポレイション | 標的化組成物 |
| CA3059446A1 (en) | 2017-04-18 | 2018-10-25 | Alnylam Pharmaceuticals, Inc. | Methods for the treatment of subjects having a hepatitis b virus (hbv) infection |
| 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 |
| US11603532B2 (en) | 2017-06-02 | 2023-03-14 | Wave Life Sciences Ltd. | Oligonucleotide compositions and methods of use thereof |
| CN120330183A (zh) * | 2017-06-02 | 2025-07-18 | 波涛生命科学有限公司 | 寡核苷酸组合物及其使用方法 |
| WO2018226788A1 (en) | 2017-06-07 | 2018-12-13 | University Of Massachusetts | Anti-adam33 oligonucleotides and related methods |
| US10844377B2 (en) | 2017-06-23 | 2020-11-24 | University Of Massachusetts | Two-tailed self-delivering siRNA |
| US11597744B2 (en) | 2017-06-30 | 2023-03-07 | Sirius Therapeutics, Inc. | Chiral phosphoramidite auxiliaries and methods of their use |
| CA3069868A1 (en) | 2017-07-13 | 2019-01-17 | Alnylam Pharmaceuticals Inc. | Lactate dehydrogenase a (ldha) irna compositions and methods of use thereof |
| JP7384033B2 (ja) | 2017-07-26 | 2023-11-21 | 日産化学株式会社 | 一本鎖オリゴヌクレオチド |
| TW201920668A (zh) * | 2017-08-02 | 2019-06-01 | 日商協和醱酵麒麟有限公司 | 核酸複合體 |
| WO2019027015A1 (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 |
| WO2019036612A1 (en) | 2017-08-17 | 2019-02-21 | Alnylam Pharmaceuticals, Inc. | ADJUSTABLE REVERSIR TM COMPOUNDS |
| WO2019036613A1 (en) | 2017-08-18 | 2019-02-21 | Ionis Pharmaceuticals, Inc. | MODULATION OF THE NOTCH SIGNALING PATHWAY FOR THE TREATMENT OF RESPIRATORY DISORDERS |
| WO2019038228A1 (en) | 2017-08-22 | 2019-02-28 | Roche Innovation Center Copenhagen A/S | OLIGONUCLEOTIDES FOR MODULATION OF TOM1 EXPRESSION |
| SG11202001590RA (en) | 2017-08-25 | 2020-03-30 | Stoke Therapeutics Inc | Antisense oligomers for treatment of conditions and diseases |
| US10517889B2 (en) | 2017-09-08 | 2019-12-31 | Ionis Pharmaceuticals, Inc. | Modulators of SMAD7 expression |
| EP3682007A2 (en) * | 2017-09-14 | 2020-07-22 | Janssen BioPharma, Inc. | Galnac derivatives |
| BR112020003609A2 (pt) | 2017-09-29 | 2020-09-01 | Regeneron Pharmaceuticals, Inc. | sistema e método para formar uma emulsão |
| CN111417728A (zh) | 2017-09-29 | 2020-07-14 | 因特利亚治疗公司 | 用于ttr基因编辑及治疗attr淀粉样变性的组合物及方法 |
| WO2019073018A1 (en) | 2017-10-13 | 2019-04-18 | Roche Innovation Center Copenhagen A/S | METHODS OF IDENTIFYING ANTISENSE OLIGONUCLEOTIDE IMPROVED OLIGONUCLEOTIDE PHOSPHOROTHIOATE STEREODEFINIS VARIANTS USING PARTIALLY STEREODEFINIS OLIGONUCLEOTIDE SUB LIBRARIES |
| EP3645723A1 (en) | 2017-10-16 | 2020-05-06 | H. Hoffnabb-La Roche Ag | NUCLEIC ACID MOLECULE FOR REDUCTION OF PAPD5 AND PAPD7 mRNA FOR TREATING HEPATITIS B INFECTION |
| CA3078971A1 (en) | 2017-11-01 | 2019-05-09 | 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 |
| 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 |
| 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 |
| KR102834361B1 (ko) | 2017-12-01 | 2025-07-17 | 쑤저우 리보 라이프 사이언스 컴퍼니, 리미티드 | 핵산, 이를 포함하는 조성물과 컨쥬게이트, 및 그의 제조 방법과 용도 |
| 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 |
| 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 |
| US11414661B2 (en) | 2017-12-01 | 2022-08-16 | Suzhou Ribo Life Science Co., Ltd. | Nucleic acid, composition and conjugate containing nucleic acid, preparation method therefor and use thereof |
| JP7365052B2 (ja) | 2017-12-01 | 2023-10-19 | 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、当該核酸を含む組成物及び複合体ならびに調製方法と使用 |
| JP2021505175A (ja) | 2017-12-11 | 2021-02-18 | 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 | Fndc3bの発現を調節するためのオリゴヌクレオチド |
| 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 |
| CN111727252A (zh) | 2017-12-18 | 2020-09-29 | 阿尔尼拉姆医药品有限公司 | 高速泳动族盒-1(HMGB1)iRNA组合物及其使用方法 |
| WO2019126641A2 (en) | 2017-12-21 | 2019-06-27 | Ionis Pharmaceuticals, Inc. | Modulation of frataxin expression |
| CN111512160B (zh) | 2017-12-21 | 2024-04-09 | 豪夫迈·罗氏有限公司 | Htra1 rna拮抗剂的伴随诊断 |
| CA3085406A1 (en) | 2017-12-22 | 2019-06-27 | Roche Innovation Center Copenhagen A/S | Oligonucleotides comprising a phosphorodithioate internucleoside linkage |
| MX2020005754A (es) | 2017-12-22 | 2020-08-20 | Roche Innovation Ct Copenhagen As | Oligonucleotidos gapmeros que comprenden un enlace internucleosido fosforoditioato. |
| EP4092118A1 (en) | 2017-12-22 | 2022-11-23 | Roche Innovation Center Copenhagen A/S | Novel thiophosphoramidites |
| 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 |
| 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 |
| EP3732185B1 (en) | 2017-12-29 | 2025-02-26 | Suzhou Ribo Life Science Co., Ltd. | Conjugates and preparation and use thereof |
| CN111699258A (zh) | 2018-01-10 | 2020-09-22 | 哥本哈根罗氏创新中心 | 用于调控pias4表达的寡核苷酸 |
| EP3737424A4 (en) * | 2018-01-10 | 2021-10-27 | Translate Bio MA, Inc. | COMPOSITIONS AND METHODS TO FACILITATE THE DELIVERY OF SYNTHETIC NUCLEIC ACIDS INTO CELLS |
| WO2019140231A1 (en) | 2018-01-12 | 2019-07-18 | Bristol-Myers Squibb Company | Antisense oligonucleotides targeting alpha-synuclein and uses thereof |
| AU2019208011B2 (en) | 2018-01-12 | 2025-06-05 | Bristol-Myers Squibb Company | Antisense oligonucleotides targeting alpha-synuclein and uses thereof |
| 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 |
| AU2019207859A1 (en) | 2018-01-12 | 2020-07-02 | Roche Innovation Center Copenhagen A/S | Alpha-synuclein antisense oligonucleotides and uses thereof |
| CA3088522A1 (en) | 2018-01-15 | 2019-07-18 | Ionis Pharmaceuticals, Inc. | Modulators of dnm2 expression |
| WO2019141656A1 (en) | 2018-01-17 | 2019-07-25 | Roche Innovation Center Copenhagen A/S | Oligonucleotides for modulating erc1 expression |
| 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 |
| US11332733B2 (en) | 2018-02-12 | 2022-05-17 | lonis Pharmaceuticals, Inc. | Modified compounds and uses thereof |
| AU2019222767A1 (en) | 2018-02-14 | 2020-08-27 | Deep Genomics Incorporated | Oligonucleotide therapy for Wilson disease |
| US11058767B2 (en) | 2018-02-21 | 2021-07-13 | Bristol-Myers Squibb Company | CAMK2D antisense oligonucleotides and uses thereof |
| TWI840345B (zh) | 2018-03-02 | 2024-05-01 | 美商Ionis製藥公司 | Irf4表現之調節劑 |
| WO2019169243A1 (en) | 2018-03-02 | 2019-09-06 | Ionis Pharmaceuticals, Inc. | Compounds and methods for the modulation of amyloid-beta precursor protein |
| WO2019172286A1 (ja) | 2018-03-09 | 2019-09-12 | 第一三共株式会社 | 糖原病Ia型治療薬 |
| US11661601B2 (en) | 2018-03-22 | 2023-05-30 | Ionis Pharmaceuticals, Inc. | Methods for modulating FMR1 expression |
| CR20200453A (es) | 2018-04-05 | 2021-03-02 | Centre Leon Berard | Uso de inhibidores de fubp1 para el tratamiento de infección de virús de hepatitis b |
| PE20201349A1 (es) | 2018-04-11 | 2020-11-30 | 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 |
| EP3788169A4 (en) | 2018-05-04 | 2022-08-10 | Stoke Therapeutics, Inc. | Methods and compositions for treatment of cholesteryl ester storage disease |
| CN112105745A (zh) | 2018-05-07 | 2020-12-18 | 罗氏创新中心哥本哈根有限公司 | 用于寡核苷酸治疗剂的大规模平行发现方法 |
| 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 |
| UY38225A (es) | 2018-05-09 | 2019-11-29 | Ionis Pharmaceuticals Inc | Compuestos y métodos para reducir de la expresión de atxn3 |
| CU20200082A7 (es) * | 2018-05-09 | 2021-06-08 | Ionis Pharmaceuticals Inc | Compuestos y métodos para la reducción de la expresión de fxi |
| AU2019265904A1 (en) | 2018-05-11 | 2020-11-12 | 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 |
| WO2019241648A1 (en) | 2018-06-14 | 2019-12-19 | 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 |
| CR20210178A (es) | 2018-07-03 | 2021-05-11 | Hoffmann La Roche | OLIGONUCLEÓTIDOS PARA MODULAR LA EXPRESIÓN DE TAU (Divisional 2021-0058) |
| 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 |
| AU2019300324A1 (en) | 2018-07-13 | 2021-01-21 | F. Hoffmann-La Roche Ag | Oligonucleotides for modulating RTEL1 expression |
| US12496311B2 (en) | 2018-07-17 | 2025-12-16 | Aronora, Inc. | Methods for safely reducing thrombopoietin |
| EP3826645A4 (en) | 2018-07-25 | 2023-05-17 | Ionis Pharmaceuticals, Inc. | COMPOUNDS AND METHODS FOR REDUCING ATXN2 EXPRESSION |
| WO2020025527A1 (en) | 2018-07-31 | 2020-02-06 | Roche Innovation Center Copenhagen A/S | Oligonucleotides comprising a phosphorotrithioate internucleoside linkage |
| EP4122943B1 (en) | 2018-07-31 | 2024-05-29 | Roche Innovation Center Copenhagen A/S | Oligonucleotides comprising a phosphorotrithioate internucleoside linkage |
| EP3833397A4 (en) | 2018-08-08 | 2023-06-14 | Arcturus Therapeutics, Inc. | COMPOSITIONS AND AGENTS AGAINST NON-ALCOHOLIC STEATOHEPATITIS |
| KR20210093227A (ko) | 2018-08-10 | 2021-07-27 | 유니버시티 오브 매사추세츠 | Snp를 표적화하는 변형된 올리고뉴클레오티드 |
| BR112021001613A2 (pt) | 2018-08-13 | 2021-05-04 | Alnylam Pharmaceuticals, Inc. | agentes de ácido ribonucleico de fita dupla, célula, composições farmacêuticas, métodos de inibição da expressão gênica, de inibição da replicação e de tratar um sujeito, métodos para reduzir o nível de um antígeno e para reduzir a carga viral e uso de um agente de dsrna |
| EP3842534A4 (en) | 2018-08-21 | 2022-07-06 | Suzhou Ribo Life Science Co., Ltd. | NUCLEIC ACID, COMPOSITION AND CONJUGATE CONTAINING NUCLEIC ACID AND METHOD OF USE THEREOF |
| WO2020041769A1 (en) | 2018-08-23 | 2020-02-27 | University Of Massachusetts | O-methyl rich fully stabilized oligonucleotides |
| WO2020043750A1 (en) | 2018-08-28 | 2020-03-05 | Roche Innovation Center Copenhagen A/S | Neoantigen engineering using splice modulating compounds |
| US20210332367A1 (en) | 2018-09-18 | 2021-10-28 | 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 |
| AU2019362923B2 (en) * | 2018-10-18 | 2025-04-10 | ProGenis Pty Ltd | 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 |
| EP3877523A1 (en) | 2018-11-09 | 2021-09-15 | Novartis AG | Method for reducing the risk of a cardiovascular event with conjugated antisense compounds targeting apo(a) |
| TW202028222A (zh) | 2018-11-14 | 2020-08-01 | 美商Ionis製藥公司 | Foxp3表現之調節劑 |
| EP3880821A4 (en) | 2018-11-15 | 2023-01-25 | Ionis Pharmaceuticals, Inc. | IRF5 EXPRESSION MODULATORS |
| TWI841633B (zh) | 2018-11-21 | 2024-05-11 | 美商Ionis製藥公司 | 用於減少朊病毒表現之化合物及方法 |
| US12416004B2 (en) | 2018-11-23 | 2025-09-16 | Sanofi | RNA compositions and methods for inhibiting ANGPTL8 |
| AU2019390097A1 (en) | 2018-11-30 | 2021-07-15 | Kyowa Kirin Co., Ltd. | Nucleic acid conjugate |
| US12485136B2 (en) | 2018-12-03 | 2025-12-02 | Takeda Pharmaceuticals U.S.A., Inc. | Methods for the treatment of trinucleotide repeat expansion disorders associated with MLH3 activity |
| CA3123617A1 (en) | 2018-12-20 | 2020-06-25 | Praxis Precision Medicines, Inc. | Compositions and methods for the treatment of kcnt1 related disorders |
| IL283967B2 (en) | 2018-12-21 | 2025-03-01 | Ionis Pharmaceuticals Inc | Modulators of hsd17b13 expression |
| KR20210110839A (ko) * | 2018-12-28 | 2021-09-09 | 쑤저우 리보 라이프 사이언스 컴퍼니, 리미티드 | 핵산, 핵산을 함유하는 조성물 및 접합체, 이의 제조 방법 및 용도 |
| GB201821269D0 (en) | 2018-12-28 | 2019-02-13 | Nippon Shinyaku Co Ltd | Myostatin signal inhibitor |
| 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 |
| CN118562796A (zh) * | 2019-01-18 | 2024-08-30 | 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 |
| WO2020150636A1 (en) | 2019-01-18 | 2020-07-23 | University Of Massachusetts | Dynamic pharmacokinetic-modifying anchors |
| EP3917540A1 (en) | 2019-01-31 | 2021-12-08 | Ionis Pharmaceuticals, Inc. | Modulators of yap1 expression |
| MX2021009949A (es) | 2019-02-20 | 2021-09-21 | Roche Innovation Ct Copenhagen As | Fosforamiditas novedosas. |
| BR112021016460A2 (pt) | 2019-02-20 | 2021-10-13 | Roche Innovation Center Copenhagen A/S | Oligonucleotídeo gapmer antissenso de fita simples, sal farmaceuticamente aceitável de um oligonucleotídeo, conjugado, composição farmacêutica e invenção |
| 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 |
| CN113474633A (zh) | 2019-02-26 | 2021-10-01 | 罗氏创新中心哥本哈根有限公司 | 寡核苷酸配制方法 |
| KR20210134686A (ko) | 2019-02-27 | 2021-11-10 | 아이오니스 파마수티컬즈, 인코포레이티드 | Malat1 발현의 조절인자 |
| WO2020172755A1 (en) * | 2019-02-28 | 2020-09-03 | Deep Genomics Incorporated | Ligand clusters and methods of their use and preparation |
| EP3923989A1 (en) * | 2019-03-21 | 2021-12-22 | Mitotherapeutix LLC | Multivalent ligand clusters for targeted delivery of therapeutic agents |
| TWI874376B (zh) | 2019-03-29 | 2025-03-01 | 美商Ionis製藥公司 | 用於調節ube3a-ats 之化合物及方法 |
| US20220177894A1 (en) | 2019-04-02 | 2022-06-09 | Proqr Therapeutics Ii B.V. | Antisense oligonucleotides for immunotherapy |
| WO2020206115A2 (en) | 2019-04-03 | 2020-10-08 | Bristol-Myers Squibb Company | Angptl2 antisense oligonucleotides and uses thereof |
| US20220251128A1 (en) * | 2019-05-17 | 2022-08-11 | Ionis Pharmaceuticals, Inc. | Synthesis of oligomeric compounds comprising phosphorothioate diester and phosphodiester linkages |
| CN117701564A (zh) | 2019-05-22 | 2024-03-15 | 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 |
| CA3139195A1 (en) * | 2019-05-22 | 2020-11-26 | Suzhou Ribo Life Science Co., Ltd. | Nucleic acid, pharmaceutical composition, conjugate, preparation method, and use |
| EP3974529A4 (en) | 2019-05-22 | 2024-02-07 | Suzhou Ribo Life Science Co., Ltd. | NUCLEIC ACID, PHARMACEUTICAL COMPOSITION, CONJUGATE, PROCESS OF PREPARATION 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 |
| JP7613751B2 (ja) | 2019-05-24 | 2025-01-15 | 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 |
| 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 |
| JP7614650B2 (ja) | 2019-05-24 | 2025-01-16 | 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並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 |
| CN113905744A (zh) | 2019-05-31 | 2022-01-07 | 阿利戈斯治疗公司 | 经修饰的间隙子寡核苷酸及其使用方法 |
| CN113874510A (zh) | 2019-06-04 | 2021-12-31 | 瑞泽恩制药公司 | 包括具有β滑移突变的人源化TTR基因座的非人动物和使用方法 |
| US20220363711A1 (en) | 2019-06-25 | 2022-11-17 | Amgen Inc. | Purification methods for carbohydrate-linked oligonucleotides |
| EP3956450B1 (en) | 2019-07-26 | 2025-08-13 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulating gfap |
| EP4007811A2 (en) | 2019-08-01 | 2022-06-08 | Alnylam Pharmaceuticals, Inc. | Carboxypeptidase b2 (cpb2) irna compositions and methods of use thereof |
| EP4007812A1 (en) | 2019-08-01 | 2022-06-08 | Alnylam Pharmaceuticals, Inc. | Serpin family f member 2 (serpinf2) irna compositions and methods of use thereof |
| MX2022001710A (es) | 2019-08-09 | 2022-05-10 | Univ Massachusetts | Oligonucleótidos modificados químicamente dirigidos a los snp. |
| EP4013870A1 (en) | 2019-08-13 | 2022-06-22 | Alnylam Pharmaceuticals, Inc. | Small ribosomal protein subunit 25 (rps25) irna agent compositions and methods of use thereof |
| JP2022544587A (ja) * | 2019-08-15 | 2022-10-19 | アイオーニス ファーマシューティカルズ, インコーポレーテッド | 結合修飾オリゴマー化合物及びその使用 |
| EP4022061A1 (en) | 2019-08-27 | 2022-07-06 | Sanofi | Compositions and methods for inhibiting pcsk9 |
| EP4023659A4 (en) | 2019-08-29 | 2024-02-28 | Suzhou Ribo Life Science Co., Ltd. | COMPOUND AND DRUG CONJUGATE, PRODUCTION METHOD AND USE THEREOF |
| EP4022062A1 (en) | 2019-08-30 | 2022-07-06 | Alnylam Pharmaceuticals, Inc. | Neurofilament light chain (nfl) as a biomarker for transthyretin amyloidosis polyneuropathy |
| KR20220058578A (ko) * | 2019-09-03 | 2022-05-09 | 아크투루스 쎄라퓨틱스, 인크. | 치료 활성 접합체의 아시알로당단백질 수용체 매개 전달 |
| CN114616332B (zh) | 2019-09-10 | 2024-09-20 | 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 |
| WO2021053126A1 (en) | 2019-09-20 | 2021-03-25 | F. Hoffmann-La Roche Ag | Method of treating hbv infection using a core protein allosteric modulator |
| US12503699B2 (en) | 2019-10-04 | 2025-12-23 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for silencing UGT1a1 gene expression |
| EP4045062A1 (en) | 2019-10-14 | 2022-08-24 | Astrazeneca AB | Modulators of pnpla3 expression |
| WO2021076828A1 (en) | 2019-10-18 | 2021-04-22 | Alnylam Pharmaceuticals, Inc. | Solute carrier family member irna compositions and methods of use thereof |
| KR20220084399A (ko) | 2019-10-22 | 2022-06-21 | 알닐람 파마슈티칼스 인코포레이티드 | 보체 성분 C3 iRNA 조성물 및 이의 사용 방법 |
| JP2023500661A (ja) | 2019-11-01 | 2023-01-10 | 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 | ハンチンチン(HTT)iRNA剤組成物およびその使用方法 |
| WO2021096763A1 (en) | 2019-11-13 | 2021-05-20 | Alnylam Pharmaceuticals, Inc. | Methods and compositions for treating an angiotensinogen- (agt-) associated disorder |
| WO2021102373A1 (en) | 2019-11-22 | 2021-05-27 | 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 |
| CN115151641A (zh) | 2019-12-13 | 2022-10-04 | 阿尔尼拉姆医药品有限公司 | 人类染色体9开放阅读框72(C9ORF72)iRNA剂组合物及其使用方法 |
| 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 |
| EP4077667A1 (en) | 2019-12-19 | 2022-10-26 | F. Hoffmann-La Roche AG | Use of sept9 inhibitors for treating hepatitis b virus infection |
| CN114829601A (zh) | 2019-12-19 | 2022-07-29 | 豪夫迈·罗氏有限公司 | Sbds抑制剂用于治疗乙型肝炎病毒感染的用途 |
| CN115516091A (zh) | 2019-12-19 | 2022-12-23 | 豪夫迈·罗氏有限公司 | Cops3抑制剂用于治疗乙型肝炎病毒感染的用途 |
| WO2021122869A1 (en) | 2019-12-19 | 2021-06-24 | F. Hoffmann-La Roche Ag | Use of scamp3 inhibitors for treating hepatitis b virus infection |
| EP4077671A1 (en) | 2019-12-19 | 2022-10-26 | F. Hoffmann-La Roche AG | Use of saraf inhibitors for treating hepatitis b virus infection |
| EP4081217A1 (en) | 2019-12-24 | 2022-11-02 | F. Hoffmann-La Roche AG | Pharmaceutical combination of antiviral agents targeting hbv and/or an immune modulator for treatment of hbv |
| IL294161A (en) | 2019-12-24 | 2022-08-01 | Hoffmann La Roche | Method of treating virus infection using a tlr7 agonist |
| WO2021130266A1 (en) | 2019-12-24 | 2021-07-01 | F. Hoffmann-La Roche Ag | Pharmaceutical combination of a therapeutic oligonucleotide targeting hbv and a tlr7 agonist for treatment of hbv |
| CN114929729B (zh) * | 2020-01-30 | 2024-12-03 | 卫材R&D管理有限公司 | 核酸复合体及包含该核酸复合体的医药组合物 |
| WO2021163066A1 (en) | 2020-02-10 | 2021-08-19 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for silencing vegf-a expression |
| JP7735288B2 (ja) | 2020-02-18 | 2025-09-08 | 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 | アポリポタンパク質C3(APOC3)iRNA組成物およびその使用法 |
| BR112022016238A2 (pt) | 2020-02-28 | 2022-10-11 | Ionis Pharmaceuticals Inc | Compostos e métodos para modular smn2 |
| IL296133A (en) | 2020-03-04 | 2022-11-01 | Verve Therapeutics Inc | Preparations and methods for administering targeted RNA |
| WO2021178607A1 (en) | 2020-03-05 | 2021-09-10 | Alnylam Pharmaceuticals, Inc. | Complement component c3 irna compositions and methods of use thereof for treating or preventing complement component c3-associated diseases |
| BR112022017822A2 (pt) | 2020-03-06 | 2022-11-08 | Alnylam Pharmaceuticals Inc | Composições de irna de cetoexocinase (khk) e métodos de uso das mesmas |
| AU2021232029A1 (en) | 2020-03-06 | 2022-10-06 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of transthyretin (TTR) |
| 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 |
| EP4126967A1 (en) | 2020-03-23 | 2023-02-08 | Amgen Inc. | Monoclonal antibodies to chemically-modified nucleic acids and uses thereof |
| CN115485381A (zh) * | 2020-03-26 | 2022-12-16 | 国立研究开发法人国立循环器病研究中心 | 以apoc3为靶点的反义核酸 |
| TW202204615A (zh) | 2020-03-26 | 2022-02-01 | 美商阿尼拉製藥公司 | 冠狀病毒iRNA組成物及其使用方法 |
| WO2021207167A1 (en) | 2020-04-06 | 2021-10-14 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for silencing myoc expression |
| WO2021206922A1 (en) | 2020-04-07 | 2021-10-14 | Alnylam Pharmaceuticals, Inc. | Transmembrane serine protease 2 (tmprss2) irna compositions and methods of use thereof |
| WO2021206917A1 (en) | 2020-04-07 | 2021-10-14 | Alnylam Pharmaceuticals, Inc. | ANGIOTENSIN-CONVERTING ENZYME 2 (ACE2) iRNA COMPOSITIONS AND METHODS OF USE THEREOF |
| WO2021207189A1 (en) | 2020-04-07 | 2021-10-14 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for silencing scn9a expression |
| CA3176196A1 (en) | 2020-04-21 | 2021-10-28 | 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 |
| CN115955972A (zh) | 2020-04-27 | 2023-04-11 | 阿尔尼拉姆医药品有限公司 | 载脂蛋白E(APOE)iRNA剂组合物及其使用方法 |
| JP2023523790A (ja) | 2020-04-30 | 2023-06-07 | 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 | 補体因子B(CFB)iRNA組成物およびその使用方法 |
| CA3181546A1 (en) | 2020-05-01 | 2021-11-04 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulating atxn1 |
| MX2022014151A (es) | 2020-05-11 | 2022-11-30 | Stoke Therapeutics Inc | Oligomeros antisentido de opa1 para tratamiento de afecciones y enfermedades. |
| EP4150077A1 (en) | 2020-05-15 | 2023-03-22 | Korro Bio, Inc. | Methods and compositions for the adar-mediated editing of transmembrane channel-like protein 1 (tmc1) |
| WO2021231680A1 (en) | 2020-05-15 | 2021-11-18 | Korro Bio, Inc. | Methods and compositions for the adar-mediated editing of methyl-cpg binding protein 2 (mecp2) |
| EP4150089A1 (en) | 2020-05-15 | 2023-03-22 | Korro Bio, Inc. | Methods and compositions for the adar-mediated editing of retinoschisin 1 (rs1) |
| 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) |
| WO2021231673A1 (en) | 2020-05-15 | 2021-11-18 | Korro Bio, Inc. | Methods and compositions for the adar-mediated editing of leucine rich repeat kinase 2 (lrrk2) |
| WO2021231692A1 (en) | 2020-05-15 | 2021-11-18 | Korro Bio, Inc. | Methods and compositions for the adar-mediated editing of otoferlin (otof) |
| CA3162416C (en) | 2020-05-15 | 2023-07-04 | Korro Bio, Inc. | Methods and compositions for the adar-mediated editing of argininosuccinate synthetase (ass1) |
| EP4150078A1 (en) | 2020-05-15 | 2023-03-22 | Korro Bio, Inc. | Methods and compositions for the adar-mediated editing of argininosuccinate lyase (asl) |
| 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 |
| EP4162050A1 (en) | 2020-06-09 | 2023-04-12 | 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 |
| WO2021249484A1 (zh) * | 2020-06-10 | 2021-12-16 | 南京明德新药研发有限公司 | 缀合基团及其缀合物 |
| CN116209760A (zh) | 2020-06-18 | 2023-06-02 | 阿尔尼拉姆医药品有限公司 | 黄嘌呤脱氢酶(XDH)iRNA组合物及其使用方法 |
| US20230263897A1 (en) * | 2020-06-24 | 2023-08-24 | Sapreme Technologies B.V. | Conjugate of galnac and saponin, therapeutic composition comprising said conjugate and a galnac-oligonucleotide conjugate |
| AR122731A1 (es) | 2020-06-26 | 2022-10-05 | Hoffmann La Roche | Oligonucleótidos mejorados para modular la expresión de fubp1 |
| TW202216996A (zh) | 2020-06-29 | 2022-05-01 | 美商Ionis製藥公司 | 調節plp1之化合物及方法 |
| 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 |
| JP2023540429A (ja) | 2020-07-10 | 2023-09-25 | アンセルム(アンスティチュート・ナシオナル・ドゥ・ラ・サンテ・エ・ドゥ・ラ・ルシェルシュ・メディカル) | てんかんを治療するための方法及び組成物 |
| UY39344A (es) | 2020-07-28 | 2022-02-25 | Ionis Pharmaceuticals Inc | Compuestos y métodos para reducir la expresión de app |
| CA3186935A1 (en) | 2020-08-07 | 2022-02-10 | Paymaan JAFAR-NEJAD | Compounds and methods for modulating scn2a |
| IL300360A (en) * | 2020-08-13 | 2023-04-01 | Amgen Inc | RNAi constructs and methods to inhibit MARC1 expression |
| EP4200419A2 (en) | 2020-08-21 | 2023-06-28 | F. Hoffmann-La Roche AG | Use of a1cf inhibitors for treating hepatitis b virus infection |
| EP4217489A1 (en) | 2020-09-24 | 2023-08-02 | Alnylam Pharmaceuticals, Inc. | Dipeptidyl peptidase 4 (dpp4) irna compositions and methods of use thereof |
| JP2023544413A (ja) | 2020-10-05 | 2023-10-23 | 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 | Gタンパク質共役受容体75(GPR75)iRNA組成物およびその使用方法 |
| WO2022079222A1 (en) | 2020-10-16 | 2022-04-21 | Sanofi | Novel rna compositions and methods for inhibiting angptl3 |
| WO2022079221A1 (en) | 2020-10-16 | 2022-04-21 | Sanofi | Rna compositions and methods for inhibiting lipoprotein(a) |
| EP4232582A1 (en) | 2020-10-23 | 2023-08-30 | Alnylam Pharmaceuticals, Inc. | Mucin 5b (muc5b) irna compositions and methods of use thereof |
| TW202237841A (zh) | 2020-11-13 | 2022-10-01 | 美商艾拉倫製藥股份有限公司 | 凝血因子V(F5)iRNA組成物及其使用方法 |
| WO2022109139A1 (en) | 2020-11-18 | 2022-05-27 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulating angiotensinogen expression |
| CA3202708A1 (en) | 2020-11-23 | 2022-05-27 | Alpha Anomeric Sas | Nucleic acid duplexes |
| EP4259795A1 (en) | 2020-12-08 | 2023-10-18 | 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 |
| IL303800A (en) | 2020-12-18 | 2023-08-01 | Ionis Pharmaceuticals Inc | Compounds and methods for modulating factor xii |
| US20250304966A1 (en) | 2020-12-23 | 2025-10-02 | Argonaute RNA Limited | Treatment of cardiovascular disease |
| EP4273245A4 (en) | 2020-12-29 | 2024-12-11 | Suzhou Ribo Life Science Co., Ltd. | NUCLEIC ACID, PHARMACEUTICAL COMPOSITION AND SIRNA CONJUGATE WITH THE NUCLEIC ACID, MANUFACTURING PROCESS THEREOF AND USE THEREOF |
| WO2022150260A1 (en) | 2021-01-05 | 2022-07-14 | Alnylam Pharmaceuticals, Inc. | COMPLEMENT COMPONENT 9 (C9) iRNA COMPOSITIONS AND METHODS OF USE THEREOF |
| WO2022162157A1 (en) * | 2021-01-30 | 2022-08-04 | E-Therapeutics Plc | Conjugated oligonucleotide compounds, methods of making and uses thereof |
| EP4175964A1 (en) * | 2021-01-30 | 2023-05-10 | E-Therapeutics plc | Conjugated oligonucleotide compounds, methods of making and uses thereof |
| EP4357334A3 (en) * | 2021-01-30 | 2024-08-07 | E-Therapeutics plc | Conjugated oligonucleotide compounds, methods of making and uses thereof |
| 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 |
| WO2022162161A1 (en) * | 2021-01-30 | 2022-08-04 | E-Therapeutics Plc | Conjugated oligonucleotide compounds, methods of making and uses thereof |
| 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 |
| EP4291654A2 (en) | 2021-02-12 | 2023-12-20 | 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 |
| US20250034561A1 (en) * | 2021-02-18 | 2025-01-30 | Oneglobe Holdings Limited | Novel Compositions for Conjugating Oligonucleotides and Carbohydrates |
| WO2022182864A1 (en) | 2021-02-25 | 2022-09-01 | Alnylam Pharmaceuticals, Inc. | Prion protein (prnp) irna compositions and methods and methods of use thereof |
| WO2022182574A1 (en) | 2021-02-26 | 2022-09-01 | Alnylam Pharmaceuticals, Inc. | KETOHEXOKINASE (KHK) iRNA COMPOSITIONS AND METHODS OF USE THEREOF |
| MX2023010249A (es) | 2021-03-04 | 2023-09-15 | Alnylam Pharmaceuticals Inc | Composiciones de arni de proteina similar a la angiopoyetina 3 (angptl3) y metodos para usarlas. |
| WO2022189861A1 (en) | 2021-03-08 | 2022-09-15 | Tollys | Carbohydrate conjugates of tlr3 ligands and uses thereof |
| TW202305132A (zh) | 2021-03-08 | 2023-02-01 | 法商施維雅藥廠 | 用於抑制α-突觸核蛋白表達之反義寡核苷酸 |
| WO2022192519A1 (en) | 2021-03-12 | 2022-09-15 | Alnylam Pharmaceuticals, Inc. | Glycogen synthase kinase 3 alpha (gsk3a) irna compositions and methods of use thereof |
| AU2022246786A1 (en) | 2021-03-29 | 2023-10-05 | Alnylam Pharmaceuticals, Inc. | Huntingtin (htt) irna agent compositions and methods of use thereof |
| WO2022212153A1 (en) | 2021-04-01 | 2022-10-06 | Alnylam Pharmaceuticals, Inc. | Proline dehydrogenase 2 (prodh2) irna compositions and methods of use thereof |
| JP2024514880A (ja) | 2021-04-14 | 2024-04-03 | ディセルナ ファーマシューティカルズ インコーポレイテッド | Pnpla3発現を調節するための組成物及び方法 |
| JP2024517686A (ja) | 2021-04-26 | 2024-04-23 | 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 | 膜貫通プロテアーゼ、セリン6(TMPRSS6)iRNA組成物およびその使用方法 |
| EP4330396A1 (en) | 2021-04-29 | 2024-03-06 | 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 |
| JP2024522068A (ja) | 2021-05-18 | 2024-06-11 | 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 | ナトリウム-グルコース共輸送体2(sglt2)irna組成物およびその使用方法 |
| US20240263177A1 (en) | 2021-05-20 | 2024-08-08 | 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 |
| EP4347823A1 (en) | 2021-06-02 | 2024-04-10 | Alnylam Pharmaceuticals, Inc. | Patatin-like phospholipase domain containing 3 (pnpla3) irna compositions and methods of use thereof |
| CN117561334A (zh) | 2021-06-04 | 2024-02-13 | 阿尔尼拉姆医药品有限公司 | 人染色体9开放阅读框72(C9ORF72)iRNA药剂组合物和其使用方法 |
| EP4351541A2 (en) | 2021-06-08 | 2024-04-17 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for treating or preventing stargardt's disease and/or retinal binding protein 4 (rbp4)-associated disorders |
| AU2022293556A1 (en) | 2021-06-18 | 2024-01-18 | Ionis Pharmaceuticals, Inc. | Compounds and methods for reducing ifnar1 expression |
| IL309334A (en) | 2021-06-23 | 2024-02-01 | Univ Massachusetts | Anti-FLT1 optimized oligonucleotide compounds for the treatment of preeclampsia and other angiogenic disorders |
| MX2024000085A (es) * | 2021-06-24 | 2024-01-18 | Lilly Co Eli | Terapeutica con arn novedosos y usos de estos. |
| JP2024522852A (ja) * | 2021-06-24 | 2024-06-21 | イーライ リリー アンド カンパニー | 新規治療用送達部分及びその使用 |
| US20230194709A9 (en) | 2021-06-29 | 2023-06-22 | Seagate Technology Llc | Range information detection using coherent pulse sets with selected waveform characteristics |
| WO2023278410A1 (en) | 2021-06-29 | 2023-01-05 | Korro Bio, Inc. | Methods and compositions for adar-mediated editing |
| JP2024527304A (ja) | 2021-06-30 | 2024-07-24 | 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 | アンジオテンシノーゲン(agt)関連障害を治療するための方法および組成物 |
| CN117377765A (zh) * | 2021-07-02 | 2024-01-09 | 上海拓界生物医药科技有限公司 | 一种核酸配体及其缀合物、其制备方法和用途 |
| TW202317147A (zh) | 2021-07-08 | 2023-05-01 | 日商日本新藥股份有限公司 | 析出抑制劑 |
| CN118201606A (zh) | 2021-07-08 | 2024-06-14 | 日本新药株式会社 | 肾毒性减轻剂 |
| CN118475355A (zh) | 2021-07-08 | 2024-08-09 | 日本新药株式会社 | 肾毒性减轻剂 |
| WO2023003805A1 (en) | 2021-07-19 | 2023-01-26 | Alnylam Pharmaceuticals, Inc. | Methods and compositions for treating subjects having or at risk of developing a non-primary hyperoxaluria disease or disorder |
| AU2022316139A1 (en) | 2021-07-23 | 2024-01-18 | Alnylam Pharmaceuticals, Inc. | Beta-catenin (ctnnb1) irna compositions and methods of use thereof |
| WO2023009687A1 (en) | 2021-07-29 | 2023-02-02 | Alnylam Pharmaceuticals, Inc. | 3-hydroxy-3-methylglutaryl-coa reductase (hmgcr) irna compositions and methods of use thereof |
| AR126675A1 (es) | 2021-08-03 | 2023-11-01 | Alnylam Pharmaceuticals Inc | COMPOSICIONES DE ARNi CONTRA LA TRANSTIRRETINA (TTR) Y SUS MÉTODOS DE USO |
| WO2023015223A2 (en) * | 2021-08-03 | 2023-02-09 | Verve Therapeutics, Inc. | Compositions and methods for targeted rna delivery |
| WO2023014765A1 (en) | 2021-08-04 | 2023-02-09 | Alnylam Pharmaceuticals, Inc. | iRNA COMPOSITIONS AND METHODS FOR SILENCING ANGIOTENSINOGEN (AGT) |
| TW202334413A (zh) | 2021-08-13 | 2023-09-01 | 美商艾拉倫製藥股份有限公司 | 第十二因子(F12)iRNA組成物及其使用方法 |
| 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 |
| EP4402263A2 (en) | 2021-09-14 | 2024-07-24 | Argonaute Rna Limited | Treatment of cardiovascular disease |
| WO2023044370A2 (en) | 2021-09-17 | 2023-03-23 | Alnylam Pharmaceuticals, Inc. | Irna compositions and methods for silencing complement component 3 (c3) |
| WO2023041079A1 (zh) * | 2021-09-18 | 2023-03-23 | 上海金中锘美生物医药科技有限公司 | Lpa抑制剂及其用途 |
| CA3232420A1 (en) | 2021-09-20 | 2023-03-23 | Alnylam Pharmaceuticals, Inc. | Inhibin subunit beta e (inhbe) modulator compositions and methods of use thereof |
| EP4380624A1 (en) * | 2021-09-23 | 2024-06-12 | Shanghai Argo Biopharmaceutical Co., Ltd. | Multivalent ligand clusters with diamine scaffold for targeted delivery of therapeutic agents |
| MX2024004011A (es) | 2021-10-01 | 2024-07-01 | Adarx Pharmaceuticals Inc | Composiciones moduladoras de precalicreína y métodos de uso de estas. |
| 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 |
| IL312399A (en) | 2021-10-29 | 2024-06-01 | Alnylam Pharmaceuticals Inc | Complement factor B (CFB) iRNA compositions and methods of using them |
| 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 |
| AU2022384619A1 (en) | 2021-11-11 | 2024-04-11 | F. Hoffmann-La Roche Ag | Pharmaceutical combinations for treatment of hbv |
| CN119452086A (zh) | 2021-12-03 | 2025-02-14 | 奎里斯公司 | 具有修饰的主链化学的gapmer反义寡核苷酸 |
| GB202117758D0 (en) | 2021-12-09 | 2022-01-26 | Ucl Business Ltd | Therapeutics for the treatment of neurodegenerative disorders |
| EP4450624A4 (en) * | 2021-12-16 | 2025-03-26 | Tuojie Biotech (Shanghai) Co., Ltd. | LPA-TARGETTING SIRNA AND CONJUGATE |
| WO2023109935A1 (zh) * | 2021-12-16 | 2023-06-22 | 上海拓界生物医药科技有限公司 | 一种dsRNA、其制备方法及应用 |
| JP2024546993A (ja) | 2021-12-17 | 2024-12-26 | エフ. ホフマン-ラ ロシュ アーゲー | Rtel1及びfubp1を調節するためのオリゴヌクレオチドの組み合わせ |
| JP2025504845A (ja) * | 2022-01-20 | 2025-02-19 | 上海拓界生物医薬科技有限公司 | dsRNA、その使用及び調製方法 |
| EP4469575A2 (en) | 2022-01-24 | 2024-12-04 | Alnylam Pharmaceuticals, Inc. | Heparin sulfate biosynthesis pathway enzyme irna agent compositions and methods of use thereof |
| 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 |
| EP4471140A1 (en) * | 2022-01-30 | 2024-12-04 | Rona Bioscience, Limited | Targeting ligand containing n-acetylgalactosamine |
| 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 |
| CN118891366A (zh) | 2022-03-16 | 2024-11-01 | 第一三共株式会社 | 抑制转铁蛋白受体2的表达的siRNA |
| IL315546A (en) | 2022-03-16 | 2024-11-01 | Empirico Inc | GALNAC compositions to improve siRNA bioavailability |
| TW202400786A (zh) | 2022-03-16 | 2024-01-01 | 日商第一三共股份有限公司 | 具有RNAi活性的化學修飾寡核苷酸 |
| AU2023245603A1 (en) | 2022-03-28 | 2024-11-07 | Empirico Inc. | Modified oligonucleotides |
| 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 |
| WO2024059165A1 (en) | 2022-09-15 | 2024-03-21 | Alnylam Pharmaceuticals, Inc. | 17b-hydroxysteroid dehydrogenase type 13 (hsd17b13) irna compositions and methods of use thereof |
| IL319629A (en) | 2022-09-23 | 2025-05-01 | 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 |
| WO2024108217A1 (en) | 2022-11-18 | 2024-05-23 | Genkardia Inc. | Methods and compositions for preventing, treating, or reversing cardiac diastolic dysfunction |
| CN120548185A (zh) * | 2022-11-23 | 2025-08-26 | 普雷策尔治疗有限公司 | 用于治疗癌症和代谢疾病的组合物及方法 |
| CN120225676A (zh) | 2022-12-02 | 2025-06-27 | 上海舶望制药有限公司 | 双环脱碱基核酸类似物以及由它们制备的寡聚化合物 |
| EP4653532A2 (en) | 2022-12-19 | 2025-11-26 | Arnatar Therapeutics, Inc | Advanced rna targeting (arnatar) |
| ES3030929T3 (en) | 2022-12-19 | 2025-07-02 | Arnatar Therapeutics Inc | Arnatar compounds and methods for enhanced cellular uptake |
| AR131419A1 (es) * | 2022-12-21 | 2025-03-19 | Lilly Co Eli | TERAPÉUTICOS NOVEDOSOS DE iARN DE FAS Y USOS DE ESTOS |
| KR20250134232A (ko) * | 2023-01-10 | 2025-09-10 | 오스퍼바이오 테라퓨틱스 인크. | 사용하기 위한 변형된 다중-세그먼트화 안티센스 올리고뉴클레오티드 |
| AR131799A1 (es) | 2023-02-09 | 2025-04-30 | Alnylam Pharmaceuticals Inc | Moléculas de reversir y métodos para su uso |
| 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 |
| WO2024220930A2 (en) | 2023-04-20 | 2024-10-24 | 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 |
| TW202513798A (zh) * | 2023-05-31 | 2025-04-01 | 大陸商上海拓界生物醫藥科技有限公司 | 一種靶向LPA的dsRNA及其應用 |
| WO2024255761A1 (zh) * | 2023-06-12 | 2024-12-19 | 大睿生物 | 包含糖的寡核苷酸递送配体 |
| CN119698475A (zh) | 2023-06-13 | 2025-03-25 | 昂拓生物医药有限公司 | 血管紧张素原的高效rna靶向(arnatar) |
| 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 |
| WO2025015335A1 (en) | 2023-07-13 | 2025-01-16 | Korro Bio, Inc. | Rna-editing oligonucleotides 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 |
| WO2025021831A1 (en) * | 2023-07-24 | 2025-01-30 | 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 |
| US20250243487A1 (en) | 2023-09-14 | 2025-07-31 | Ionis Pharmaceuticals, Inc. | Compounds and Methods for Reducing APOCIII Expression |
| 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 |
| WO2025064821A2 (en) * | 2023-09-21 | 2025-03-27 | Ionis Pharmaceuticals, Inc. | Compounds and methods for inhibiting lpa |
| WO2025064819A1 (en) * | 2023-09-21 | 2025-03-27 | 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 |
| TW202530408A (zh) * | 2023-09-29 | 2025-08-01 | 美商英西特羅公司 | 用於治療非酒精性脂肪肝病的組合物與方法 |
| 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 |
| WO2025096809A1 (en) | 2023-10-31 | 2025-05-08 | Korro Bio, Inc. | Oligonucleotides comprising phosphoramidate internucleotide linkages |
| WO2025113470A1 (en) * | 2023-11-27 | 2025-06-05 | Shanghai Argo Biopharmaceutical Co., Ltd. | Compositions and methods for inhibiting expression of transthyretin (ttr) |
| 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 |
| 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 |
| WO2025152969A1 (zh) * | 2024-01-15 | 2025-07-24 | 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 |
| WO2025155911A1 (en) | 2024-01-18 | 2025-07-24 | Proqr Therapeutics Ii B.V. | Antisense oligonucleotides for the treatment of hurler syndrome |
| 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 |
| 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 |
| US20250297260A1 (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 |
Family Cites Families (380)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3687808A (en) | 1969-08-14 | 1972-08-29 | Univ Leland Stanford Junior | Synthetic polynucleotides |
| US4500707A (en) | 1980-02-29 | 1985-02-19 | University Patents, Inc. | Nucleosides useful in the preparation of polynucleotides |
| US5132418A (en) | 1980-02-29 | 1992-07-21 | University Patents, Inc. | Process for preparing polynucleotides |
| US4458066A (en) | 1980-02-29 | 1984-07-03 | University Patents, Inc. | Process for preparing 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 |
| US5034506A (en) | 1985-03-15 | 1991-07-23 | Anti-Gene Development Group | Uncharged morpholino-based polymers having achiral intersubunit linkages |
| US5166315A (en) | 1989-12-20 | 1992-11-24 | Anti-Gene Development Group | Sequence-specific binding polymers for duplex nucleic acids |
| US5405938A (en) | 1989-12-20 | 1995-04-11 | Anti-Gene Development Group | Sequence-specific binding polymers for duplex nucleic acids |
| 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 |
| US5185444A (en) | 1985-03-15 | 1993-02-09 | Anti-Gene Deveopment Group | Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages |
| EP0260032B1 (en) | 1986-09-08 | 1994-01-26 | Ajinomoto Co., Inc. | Compounds for the cleavage at a specific position of RNA, oligomers employed for the formation of said compounds, and starting materials for the synthesis of said oligomers |
| 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 |
| 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 |
| WO1989005358A1 (en) | 1987-11-30 | 1989-06-15 | University Of Iowa Research Foundation | Dna and rna 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 |
| WO1989009221A1 (en) | 1988-03-25 | 1989-10-05 | 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 |
| US5399676A (en) | 1989-10-23 | 1995-03-21 | Gilead Sciences | Oligonucleotides with inverted polarity |
| US5721218A (en) | 1989-10-23 | 1998-02-24 | Gilead Sciences, Inc. | Oligonucleotides with inverted polarity |
| ATE190981T1 (de) | 1989-10-24 | 2000-04-15 | Isis Pharmaceuticals Inc | 2'-modifizierte nukleotide |
| 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 |
| 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 |
| US5459255A (en) | 1990-01-11 | 1995-10-17 | Isis Pharmaceuticals, Inc. | N-2 substituted purines |
| US5587361A (en) | 1991-10-15 | 1996-12-24 | Isis Pharmaceuticals, Inc. | Oligonucleotides having phosphorothioate linkages of high chiral purity |
| US5670633A (en) | 1990-01-11 | 1997-09-23 | Isis Pharmaceuticals, Inc. | Sugar modified oligonucleotides that detect and modulate gene expression |
| US6005087A (en) | 1995-06-06 | 1999-12-21 | Isis Pharmaceuticals, Inc. | 2'-modified oligonucleotides |
| US5457191A (en) | 1990-01-11 | 1995-10-10 | Isis Pharmaceuticals, Inc. | 3-deazapurines |
| US7101993B1 (en) | 1990-01-11 | 2006-09-05 | Isis Pharmaceuticals, Inc. | Oligonucleotides containing 2′-O-modified purines |
| US5646265A (en) | 1990-01-11 | 1997-07-08 | Isis Pharmceuticals, Inc. | Process for the preparation of 2'-O-alkyl purine phosphoramidites |
| US5623065A (en) | 1990-08-13 | 1997-04-22 | Isis Pharmaceuticals, Inc. | Gapped 2' modified oligonucleotides |
| US5587470A (en) | 1990-01-11 | 1996-12-24 | Isis Pharmaceuticals, Inc. | 3-deazapurines |
| US5681941A (en) | 1990-01-11 | 1997-10-28 | Isis Pharmaceuticals, Inc. | Substituted purines and oligonucleotide cross-linking |
| US5859221A (en) | 1990-01-11 | 1999-01-12 | 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 |
| DE69032425T2 (de) | 1990-05-11 | 1998-11-26 | Microprobe Corp., Bothell, Wash. | Teststreifen zum Eintauchen für Nukleinsäure-Hybridisierungsassays und Verfahren zur kovalenten Immobilisierung von Oligonucleotiden |
| US5608046A (en) | 1990-07-27 | 1997-03-04 | Isis Pharmaceuticals, Inc. | Conjugated 4'-desmethyl nucleoside analog compounds |
| US5677437A (en) | 1990-07-27 | 1997-10-14 | Isis Pharmaceuticals, Inc. | Heteroatomic oligonucleoside linkages |
| US5541307A (en) | 1990-07-27 | 1996-07-30 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogs and solid phase synthesis thereof |
| US5223618A (en) | 1990-08-13 | 1993-06-29 | Isis Pharmaceuticals, Inc. | 4'-desmethyl nucleoside analog compounds |
| US5489677A (en) | 1990-07-27 | 1996-02-06 | Isis Pharmaceuticals, Inc. | Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms |
| US5610289A (en) | 1990-07-27 | 1997-03-11 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogues |
| US5618704A (en) | 1990-07-27 | 1997-04-08 | Isis Pharmacueticals, Inc. | Backbone-modified oligonucleotide analogs and preparation thereof through radical coupling |
| US5623070A (en) | 1990-07-27 | 1997-04-22 | Isis Pharmaceuticals, Inc. | Heteroatomic oligonucleoside linkages |
| US5386023A (en) | 1990-07-27 | 1995-01-31 | Isis Pharmaceuticals | Backbone modified oligonucleotide analogs and preparation thereof through reductive coupling |
| US5614617A (en) | 1990-07-27 | 1997-03-25 | Isis Pharmaceuticals, Inc. | Nuclease resistant, pyrimidine modified oligonucleotides that detect and modulate gene expression |
| US5602240A (en) | 1990-07-27 | 1997-02-11 | Ciba Geigy Ag. | Backbone modified oligonucleotide analogs |
| US5378825A (en) | 1990-07-27 | 1995-01-03 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogs |
| PT98562B (pt) | 1990-08-03 | 1999-01-29 | Sanofi Sa | Processo para a preparacao de composicoes que compreendem sequencias de nucleo-sidos com cerca de 6 a cerca de 200 bases resistentes a nucleases |
| 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 |
| AU662298B2 (en) | 1990-09-20 | 1995-08-31 | 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 |
| ES2103918T3 (es) | 1991-10-17 | 1997-10-01 | Ciba Geigy Ag | Nucleosidos biciclicos, oligonucleotidos, procedimiento para su obtencion y productos intermedios. |
| US5594121A (en) | 1991-11-07 | 1997-01-14 | Gilead Sciences, Inc. | Enhanced triple-helix and double-helix formation with oligomers containing modified purines |
| JP3739785B2 (ja) | 1991-11-26 | 2006-01-25 | アイシス ファーマシューティカルズ,インコーポレイティド | 修飾されたピリミジンを含有するオリゴマーを使用する増強された三重らせんおよび二重らせんの成形 |
| 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 |
| DK0618925T4 (da) * | 1991-12-24 | 2012-07-09 | Isis Pharmaceuticals Inc | Antisense-oligonukleotider |
| 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 |
| EP0652890B1 (en) | 1992-07-27 | 1998-01-14 | HYBRIDON, Inc. | Oligonucleotide alkylphosphonothioates |
| EP0673559A1 (en) | 1992-12-14 | 1995-09-27 | Honeywell Inc. | Motor system with individually controlled redundant windings |
| DE69400208T2 (de) | 1993-01-25 | 1996-11-28 | Hybridon Inc | Olionukleotidalkylphosphonate und -phosphonothioate |
| US5476925A (en) | 1993-02-01 | 1995-12-19 | Northwestern University | Oligodeoxyribonucleotides including 3'-aminonucleoside-phosphoramidate linkages and terminal 3'-amino groups |
| GB9304620D0 (en) | 1993-03-06 | 1993-04-21 | Ciba Geigy Ag | Compounds |
| GB9304618D0 (en) | 1993-03-06 | 1993-04-21 | Ciba Geigy Ag | Chemical compounds |
| DE69404289T2 (de) | 1993-03-30 | 1998-02-19 | Sanofi Sa | Acyclische nucleosid analoge und sie enthaltende oligonucleotidsequenzen |
| ATE160572T1 (de) | 1993-03-31 | 1997-12-15 | Sanofi Sa | Oligonucleotide mit amidverkettungen die phosphoesterverkettungen einsetzen |
| 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 |
| CA2178729A1 (en) | 1993-12-09 | 1995-06-15 | Eric B. Kmiec | Compounds and methods for site-directed mutations in eukaryotic cells |
| US5446137B1 (en) | 1993-12-09 | 1998-10-06 | Behringwerke Ag | Oligonucleotides containing 4'-substituted nucleotides |
| 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 |
| 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 |
| US20030119724A1 (en) | 1995-11-22 | 2003-06-26 | Ts`O Paul O.P. | Ligands to enhance cellular uptake of biomolecules |
| US5998203A (en) | 1996-04-16 | 1999-12-07 | Ribozyme Pharmaceuticals, Inc. | Enzymatic nucleic acids containing 5'-and/or 3'-cap structures |
| WO2005121370A2 (en) | 2004-06-03 | 2005-12-22 | Isis Pharmaceuticals, Inc. | Oligomeric compounds that facilitate risc loading |
| US6620916B1 (en) | 1996-09-26 | 2003-09-16 | Ajinomoto Co., Inc. | Modified physiologically active proteins and medicinal compositions containing the same |
| 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 |
| US6770748B2 (en) | 1997-03-07 | 2004-08-03 | Takeshi Imanishi | Bicyclonucleoside and oligonucleotide analogue |
| 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 |
| WO1999014226A2 (en) | 1997-09-12 | 1999-03-25 | Exiqon A/S | Bi- and tri-cyclic nucleoside, nucleotide and oligonucleotide 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 |
| JP2004505885A (ja) | 1998-08-19 | 2004-02-26 | ノース アメリカン ワクチン, インコーポレイテッド | N−アクリロイル化ポリサッカリドを用いて産生されたワクチンとして有用な免疫原性β−プロピオンアミド連結ポリサッカリド−タンパク質結合体 |
| PL346645A1 (en) * | 1998-08-19 | 2002-02-25 | North American Vaccine | 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 |
| ATE287897T2 (de) | 1999-02-12 | 2005-02-15 | Sankyo Co | Analoga von nukleosiden und oligonukleotiden |
| 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 |
| EP1210363A2 (en) | 1999-07-16 | 2002-06-05 | 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 |
| WO2001042499A1 (en) | 1999-12-09 | 2001-06-14 | Sankyo Company, Limited | Method of testing remedy or preventive for hyperlipemia |
| EP1244667B1 (en) | 1999-12-30 | 2006-04-05 | K.U. Leuven Research & Development | Cyclohexene nucleic acids |
| US6602857B1 (en) | 2000-01-18 | 2003-08-05 | Isis Pharmaceuticals, Inc. | Antisense modulation of PTP1B expression |
| US20020055479A1 (en) | 2000-01-18 | 2002-05-09 | Cowsert Lex M. | Antisense modulation of PTP1B expression |
| US7179796B2 (en) | 2000-01-18 | 2007-02-20 | Isis Pharmaceuticals, Inc. | Antisense modulation of PTP1B expression |
| US6261840B1 (en) | 2000-01-18 | 2001-07-17 | 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 |
| AU2001241541A1 (en) | 2000-02-17 | 2001-08-27 | Millennium Predictive Medicine, Inc. | Novel genes, compositions, kits, and methods for identification, assessment, prevention, and therapy of human prostate cancer |
| US7053199B2 (en) | 2000-08-29 | 2006-05-30 | Takeshi Imanishi | Nucleoside analogs and oligonucleotide derivatives containing these analogs |
| US6426220B1 (en) | 2000-10-30 | 2002-07-30 | Isis Pharmaceuticals, Inc. | Antisense modulation of calreticulin expression |
| US6906182B2 (en) | 2000-12-01 | 2005-06-14 | Cell Works Therapeutics, Inc. | Conjugates of glycosylated/galactosylated peptide, bifunctional linker, and nucleotidic monomers/polymers, and related compositions and method of use |
| WO2002087541A1 (en) | 2001-04-30 | 2002-11-07 | Protiva Biotherapeutics Inc. | Lipid-based formulations for gene transfer |
| CA2450022A1 (en) | 2001-06-08 | 2002-12-19 | Sankyo Company, Limited | Method of testing drug for treating or preventing diseases such as hyperlipemia |
| 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 |
| JP2005504020A (ja) | 2001-07-03 | 2005-02-10 | アイシス・ファーマシューティカルス・インコーポレーテッド | ヌクレアーゼ耐性キメラオリゴヌクレオチド |
| 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 |
| JP2005514005A (ja) | 2001-09-04 | 2005-05-19 | エクシコン エ/エス | 新規のlna組成物およびその使用 |
| US7439043B2 (en) | 2001-10-10 | 2008-10-21 | Neose Technologies, Inc. | Galactosyl nucleotide sugars |
| CA2464542C (en) | 2001-11-16 | 2015-01-20 | Genentech, Inc. | Composition comprising and method of using angiopoietin-like protein 3 angptl3 |
| 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 |
| US8729036B2 (en) | 2002-08-07 | 2014-05-20 | 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 |
| US20060035344A1 (en) | 2002-10-18 | 2006-02-16 | Pachuk Catherine J | Double-stranded rna structures and constructs, and methods for generating and using the same |
| WO2004044136A2 (en) | 2002-11-05 | 2004-05-27 | Isis Pharmaceuticals, Inc. | Compositions comprising alternating 2’-modified nucleosides for use in gene modulation |
| AU2003291753B2 (en) | 2002-11-05 | 2010-07-08 | Isis Pharmaceuticals, Inc. | Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation |
| US7511131B2 (en) | 2002-11-13 | 2009-03-31 | Genzyme Corporation | Antisense modulation of apolipoprotein B expression |
| EP2336318B1 (en) | 2002-11-13 | 2013-04-24 | Genzyme Corporation | Antisense modulation of apolipoprotein b expression |
| US20060009410A1 (en) | 2002-11-13 | 2006-01-12 | Crooke Rosanne M | Effects of apolipoprotein B inhibition on gene expression profiles in animals |
| EP1560931B1 (en) | 2002-11-14 | 2011-07-27 | Dharmacon, Inc. | Functional and hyperfunctional sirna |
| 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 |
| CA2886504C (en) | 2002-12-20 | 2019-01-08 | Celera Corporation | Wdr12 polymorphisms associated with myocardial infarction, methods of detection and uses thereof |
| US20070015927A1 (en) | 2003-01-09 | 2007-01-18 | Kim Byeang H | 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 |
| EP2216407B1 (en) | 2003-03-07 | 2016-01-13 | Alnylam Pharmaceuticals, Inc. | Therapeutic compositions |
| CA2488224A1 (en) * | 2003-04-03 | 2004-10-21 | Alnylam Pharmaceuticals, Inc. | Irna conjugates |
| US7598227B2 (en) | 2003-04-16 | 2009-10-06 | Isis Pharmaceuticals Inc. | Modulation of apolipoprotein C-III expression |
| AU2004233092C9 (en) | 2003-04-17 | 2010-10-28 | Alnylam Pharmaceuticals, Inc. | Modified iRNA agents |
| 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 |
| US7399853B2 (en) | 2003-04-28 | 2008-07-15 | Isis Pharmaceuticals | Modulation of glucagon receptor expression |
| US7750142B2 (en) | 2003-04-28 | 2010-07-06 | Isis Pharmaceuticals, Inc. | 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 |
| ATE555118T1 (de) | 2003-08-28 | 2012-05-15 | Takeshi Imanishi | Neue synthetische nukleidsäuren vom typ mit quervernetzter n-o-bindung |
| BRPI0413930A (pt) * | 2003-09-18 | 2006-10-24 | Isis Pharmaceuticals Inc | composto oligomérico ou sal farmaceuticamente aceitável deste, composição farmacêutica ou veterinária, métodos para inibir a expressão de eif4e em uma célula, tecido ou órgão, para diminuir a proliferação de uma célula em que eif4e é expressado, e para prevenir ou tratar uma condição ou doença métodos para prevenir ou diminuir a angiogênese, e o crescimento de tumor em um paciente, oligonucleotìdeo de anti-sentido, composição farmacêutica ou veterinária, e, uso de um composto oligomérico ou sal farmaceuticamente aceitável deste |
| JP5379347B2 (ja) | 2003-09-18 | 2013-12-25 | 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 | 4’−チオヌクレオシドおよびオリゴマー化合物 |
| WO2005038013A1 (en) * | 2003-10-07 | 2005-04-28 | Isis Pharmaceuticals, Inc. | Artisense 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 |
| EP2363480A3 (en) | 2004-01-20 | 2015-10-07 | Isis Pharmaceuticals, Inc. | Modulation of glucocorticoid receptor expression |
| CA2559962C (en) * | 2004-02-05 | 2011-03-15 | Japan Science And Technology Agency | Linker compound, ligand complex and process for producing them |
| 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 |
| EP1752536A4 (en) | 2004-05-11 | 2008-04-16 | Alphagen Co Ltd | POLYNUCLEOTIDE CAUSING RNA INTERFERENCE AND METHOD OF REGULATING GENE EXPRESSION WITH THE USE OF THE SAME |
| NZ552957A (en) | 2004-07-20 | 2011-06-30 | Genentech Inc | Compositions and methods of using angiopoietin-like 4 protein |
| ATE456579T1 (de) | 2004-07-20 | 2010-02-15 | Genentech Inc | Angiopoietin-like 4 protein hemmer kombinationen und deren verwendung |
| JP5192234B2 (ja) | 2004-08-10 | 2013-05-08 | 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 | 化学修飾オリゴヌクレオチド |
| ES2663810T3 (es) * | 2004-08-10 | 2018-04-17 | Kastle Therapeutics, Llc | Métodos para modular los niveles de lipoproteínas y colesterol en humanos |
| US20090203132A1 (en) | 2004-09-09 | 2009-08-13 | Swayze Eric E | Pyrrolidinyl groups for attaching conjugates to oligomeric compounds |
| US20060089325A1 (en) | 2004-10-13 | 2006-04-27 | Sanjay Bhanot | Antisense modulation of PTP1B expression |
| WO2006047842A2 (en) | 2004-11-08 | 2006-05-11 | 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 |
| EP1841867A1 (en) | 2005-01-24 | 2007-10-10 | Avaris AB | COMPLEX CONTAINING SiRNA, ShRNA OR ANTISENSE MOLECULE AND FUNCTIONAL ENTITY, FOR IMPROVED SPECIFICITY AND DELIVERY |
| WO2007031081A2 (en) * | 2005-09-15 | 2007-03-22 | Santaris Pharma A/S | RNA ANTAGONIST COMPOUNDS FOR THE INHIBITION OF APO-Bl00 EXPRESSION |
| EP1941040A1 (en) | 2005-09-19 | 2008-07-09 | Johnson & Johnson Pharmaceutical Research & Development L.L.C. | Modulation of glucocorticoid receptor expression |
| EP2388326A1 (en) | 2005-09-19 | 2011-11-23 | Isis Pharmaceuticals, Inc. | Modulation of glucagon receptor expression |
| EP2161038B1 (en) * | 2006-01-26 | 2013-12-25 | Isis Pharmaceuticals, Inc. | Compositions and their uses directed to Huntingtin |
| JP5342881B2 (ja) | 2006-01-27 | 2013-11-13 | 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 | 6−修飾された二環式核酸類似体 |
| US7569686B1 (en) | 2006-01-27 | 2009-08-04 | Isis Pharmaceuticals, Inc. | Compounds and methods for synthesis of bicyclic nucleic acid analogs |
| CN101489565A (zh) * | 2006-05-05 | 2009-07-22 | Isis药物公司 | 调节pcsk9表达的化合物和方法 |
| EP2505646A1 (en) | 2006-05-05 | 2012-10-03 | Isis Pharmaceuticals, Inc. | Compounds and methods for modulating expression of CRP |
| US7666854B2 (en) | 2006-05-11 | 2010-02-23 | Isis Pharmaceuticals, Inc. | Bis-modified bicyclic nucleic acid analogs |
| US7547684B2 (en) | 2006-05-11 | 2009-06-16 | Isis Pharmaceuticals, Inc. | 5′-modified bicyclic nucleic acid analogs |
| EP2057284A4 (en) | 2006-08-04 | 2011-06-29 | Isis Pharmaceuticals Inc | COMPOSITIONS AND METHODS OF MODULATING JNK PROTEINS |
| CN101500548A (zh) | 2006-08-18 | 2009-08-05 | 弗·哈夫曼-拉罗切有限公司 | 用于体内递送多核苷酸的多缀合物 |
| US8658211B2 (en) | 2006-08-18 | 2014-02-25 | Arrowhead Madison Inc. | Polyconjugates for in vivo delivery of polynucleotides |
| AU2007299705B2 (en) | 2006-09-22 | 2012-09-06 | Dharmacon, Inc. | Duplex oligonucleotide complexes and methods for gene silencing by RNA interference |
| JP5665317B2 (ja) | 2006-10-18 | 2015-02-04 | 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 | アンチセンス化合物 |
| US8093222B2 (en) | 2006-11-27 | 2012-01-10 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
| EP2455471A3 (en) | 2006-11-27 | 2012-09-12 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
| MX2009006082A (es) | 2006-12-08 | 2009-08-18 | Lexicon Pharmaceuticals Inc | Anticuerpos monoclonales contra la proteina 3 similar a angiopoyetina (angptl3). |
| CA2839162A1 (en) * | 2006-12-20 | 2008-06-26 | Xoma Technology Ltd. | Methods for the treatment of il-1-.beta. related diseases |
| WO2008101157A1 (en) | 2007-02-15 | 2008-08-21 | Isis Pharmaceuticals, Inc. | 5'-substituted-2'-f modified nucleosides and oligomeric compounds prepared therefrom |
| EP2129402A2 (en) | 2007-02-16 | 2009-12-09 | KTB Tumorforschungsgesellschaft mbH | Receptor and antigen targeted prodrug |
| CA2678774A1 (en) | 2007-03-01 | 2008-09-04 | Advanced Vision Therapies, Inc. | Treatment of diseases characterized by inflammation |
| JP2010519911A (ja) | 2007-03-02 | 2010-06-10 | エムディーアールエヌエー,インコーポレイテッド | Myc遺伝子の発現を抑制するための核酸化合物およびその使用 |
| US8877917B2 (en) | 2007-04-23 | 2014-11-04 | Alnylam Pharmaceuticals, Inc. | Glycoconjugates of RNA interference agents |
| EP2170917B1 (en) | 2007-05-30 | 2012-06-27 | Isis Pharmaceuticals, Inc. | N-substituted-aminomethylene bridged bicyclic nucleic acid analogs |
| EP2173760B2 (en) | 2007-06-08 | 2015-11-04 | Isis Pharmaceuticals, Inc. | Carbocyclic bicyclic nucleic acid analogs |
| US20090004140A1 (en) | 2007-06-26 | 2009-01-01 | Yao-Ling Qiu | 4-substituted pyrrolidine as anti-infectives |
| CA2692579C (en) | 2007-07-05 | 2016-05-03 | Isis Pharmaceuticals, Inc. | 6-disubstituted bicyclic nucleic acid analogs |
| AU2008286771B2 (en) | 2007-08-15 | 2013-08-15 | Isis Pharmaceuticals, Inc. | Tetrahydropyran nucleic acid analogs |
| US8742079B2 (en) * | 2007-08-20 | 2014-06-03 | Protalix Ltd. | Saccharide-containing protein conjugates and uses thereof |
| WO2009046141A2 (en) | 2007-10-01 | 2009-04-09 | Isis Pharmaceuticals, Inc. | Antisense modulation of fibroblast growth factor receptor 4 expression |
| NZ585250A (en) | 2007-11-09 | 2012-06-29 | Isis Pharmaceuticals Inc | Antisense modulation of factor 7 expression |
| WO2009067647A1 (en) | 2007-11-21 | 2009-05-28 | Isis Pharmaceuticals, Inc. | Carbocyclic alpha-l-bicyclic nucleic acid analogs |
| EP4074344A1 (en) * | 2007-12-04 | 2022-10-19 | Arbutus Biopharma Corporation | Targeting lipids |
| US20110027248A1 (en) | 2007-12-27 | 2011-02-03 | Hiroyuki Yoneyama | Sugar Chain-Related Gene and Use Thereof |
| JP2011511004A (ja) | 2008-01-31 | 2011-04-07 | 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 | PCSK9遺伝子を標的とするdsRNAを送達するための最適化された方法 |
| EP2265627A2 (en) | 2008-02-07 | 2010-12-29 | 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 |
| EP2274425A2 (en) | 2008-04-11 | 2011-01-19 | Alnylam Pharmaceuticals Inc. | Site-specific delivery of nucleic acids by combining targeting ligands with endosomolytic components |
| 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 |
| US8216786B2 (en) | 2008-07-09 | 2012-07-10 | 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 |
| JP2012513953A (ja) | 2008-09-23 | 2012-06-21 | アルニラム ファーマスーティカルズ インコーポレイテッド | 付加環化を用いたモノマーおよびオリゴヌクレオチドの化学修飾 |
| EP2361256B1 (en) | 2008-09-24 | 2013-04-10 | Isis Pharmaceuticals, Inc. | Cyclohexenyl nucleic acid analogs |
| WO2010036698A1 (en) | 2008-09-24 | 2010-04-01 | Isis Pharmaceuticals, Inc. | Substituted alpha-l-bicyclic nucleosides |
| AU2009305636A1 (en) | 2008-10-15 | 2010-04-22 | Ionis Pharmaceuticals, Inc. | Modulation of Factor 11 expression |
| PT2937418T (pt) * | 2008-10-20 | 2018-01-23 | Alnylam Pharmaceuticals Inc | Composições e métodos de inibição da expressão de transtirretina |
| EP2358398A2 (en) | 2008-10-24 | 2011-08-24 | Isis Pharmaceuticals, Inc. | Oligomeric compounds and methods |
| US20120059045A1 (en) | 2008-10-24 | 2012-03-08 | Isis Pharmaceuticals, Inc. | Methods of using oligomeric compounds comprising 2'-substituted nucleosides |
| EA037404B1 (ru) | 2008-11-10 | 2021-03-24 | Арбутус Биофарма Корпорэйшн | Липиды и композиции для доставки лекарственных средств |
| CA2750561C (en) | 2009-01-26 | 2017-10-10 | Protiva Biotherapeutics, Inc. | Compositions and methods for silencing apolipoprotein c-iii expression |
| EP2391343B1 (en) | 2009-01-29 | 2017-03-01 | Arbutus Biopharma Corporation | Improved lipid formulation for the delivery of nucleic acids |
| EP2669290A1 (en) | 2009-03-02 | 2013-12-04 | 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 |
| MX2011010930A (es) | 2009-04-15 | 2012-04-30 | Isis Pharmaceuticals Inc | Modulacion de respuestas inflamatorias a través de factor xi. |
| CA3042927C (en) | 2009-05-05 | 2022-05-17 | Arbutus Biopharma Corporation | Lipid compositions for the delivery of therapeutic agents |
| ES2804764T3 (es) | 2009-06-01 | 2021-02-09 | Halo Bio Rnai Therapeutics Inc | Polinucleótidos para la interferencia de ARN multivalente, composiciones y métodos de uso de los mismos |
| HRP20211619T1 (hr) | 2009-06-10 | 2022-02-04 | Arbutus Biopharma Corporation | Poboljšana formulacija lipida |
| NZ597504A (en) | 2009-06-15 | 2013-10-25 | Alnylam Pharmaceuticals Inc | Lipid formulated dsrna targeting the pcsk9 gene |
| CA2767225A1 (en) | 2009-07-06 | 2011-01-13 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for enhancing production of a biological product |
| US9512164B2 (en) | 2009-07-07 | 2016-12-06 | Alnylam Pharmaceuticals, Inc. | Oligonucleotide end caps |
| WO2011005860A2 (en) | 2009-07-07 | 2011-01-13 | Alnylam Pharmaceuticals, Inc. | 5' phosphate mimics |
| EP2454369A4 (en) | 2009-07-16 | 2013-07-03 | Isis Pharmaceuticals Inc | MODULATION OF FACTOR 7 EXPRESSION |
| EP2462153B1 (en) | 2009-08-06 | 2015-07-29 | 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 |
| WO2011038356A2 (en) | 2009-09-25 | 2011-03-31 | Johns Hopkins University | Novel liver-targeting agents and their synthesis |
| US8598334B2 (en) | 2009-10-16 | 2013-12-03 | Glaxo Group Limited | HBV antisense inhibitors |
| 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 |
| 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 |
| EP2496238A4 (en) * | 2009-11-03 | 2013-10-02 | Alnylam Pharmaceuticals Inc | FORMULATED LIPID COMPOSITIONS AND METHODS FOR INHIBITING TRANSTHYRETIN EXPRESSION (TTR) |
| WO2011072290A2 (en) | 2009-12-11 | 2011-06-16 | The Regents Of The University Of Michigan | Targeted dendrimer-drug conjugates |
| CN111700901A (zh) | 2010-01-08 | 2020-09-25 | Ionis制药公司 | 血管生成素样3表达的调节 |
| US9198972B2 (en) | 2010-01-28 | 2015-12-01 | Alnylam Pharmaceuticals, Inc. | Monomers and oligonucleotides comprising cycloaddition adduct(s) |
| NZ601737A (en) * | 2010-02-24 | 2013-06-28 | Arrowhead Res Corp | Compositions for targeted delivery of sirna |
| US9193752B2 (en) | 2010-03-17 | 2015-11-24 | 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 |
| US8349308B2 (en) | 2010-03-26 | 2013-01-08 | 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 |
| WO2011133876A2 (en) | 2010-04-22 | 2011-10-27 | Alnylam Pharmaceuticals, Inc. | Oligonucleotides comprising acyclic and abasic nucleosides and analogs |
| US9725479B2 (en) | 2010-04-22 | 2017-08-08 | Ionis Pharmaceuticals, Inc. | 5′-end derivatives |
| WO2011139702A2 (en) | 2010-04-28 | 2011-11-10 | Isis Pharmaceuticals, Inc. | Modified nucleosides and oligomeric compounds prepared therefrom |
| EP3091027B1 (en) | 2010-04-28 | 2018-01-17 | Ionis Pharmaceuticals, Inc. | 5' modified nucleosides and oligomeric compounds prepared therefrom |
| MX343559B (es) * | 2010-04-29 | 2016-11-10 | Ionis Pharmaceuticals Inc | Modulacion de la expresion de transtiretina. |
| US20130236968A1 (en) | 2010-06-21 | 2013-09-12 | Alnylam Pharmaceuticals, Inc. | Multifunctional copolymers for nucleic acid delivery |
| JP2013541334A (ja) | 2010-09-15 | 2013-11-14 | アルニラム ファーマスーティカルズ インコーポレイテッド | 修飾されたiRNA剤 |
| US8603994B2 (en) | 2010-11-11 | 2013-12-10 | Valted, Llc | 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 |
| US8501930B2 (en) | 2010-12-17 | 2013-08-06 | Arrowhead Madison Inc. | Peptide-based in vivo siRNA delivery system |
| EP3192800A1 (en) | 2010-12-17 | 2017-07-19 | Arrowhead Pharmaceuticals, Inc. | Galactose cluster-pharmacokinetic modulator targeting moiety for sirna |
| BR122020024394B1 (pt) | 2010-12-29 | 2021-05-11 | F. Hoffmann-La Roche Ag | conjugado e composição farmacêutica |
| 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) |
| CN105886506A (zh) | 2011-04-13 | 2016-08-24 | Isis制药公司 | Ptp1b 表达的反义调节 |
| ES2856266T3 (es) * | 2011-04-21 | 2021-09-27 | Glaxo Group Ltd | Modulación de la expresión del virus de la hepatitis B (VHB) |
| TW201303013A (zh) | 2011-04-21 | 2013-01-16 | Isis Pharmaceuticals Inc | B型肝炎病毒(hbv)表現之調節 |
| KR20190062511A (ko) | 2011-04-27 | 2019-06-05 | 아이오니스 파마수티컬즈, 인코포레이티드 | 아포지방단백질 ciii (apociii) 발현의 조정 |
| 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 |
| JP6110372B2 (ja) | 2011-06-21 | 2017-04-05 | 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Alnylam Pharmaceuticals, Inc. | アンジオポエチン様3(ANGPTL3)iRNA組成物及びその使用方法 |
| RU2631805C2 (ru) | 2011-06-21 | 2017-09-26 | Элнилэм Фармасьютикалз, Инк. | Композиции и способы ингибирования экспрессии генов аполипопротеина с-iii (арос3) |
| 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 |
| JP2014531476A (ja) | 2011-08-26 | 2014-11-27 | アローヘッド リサーチ コーポレイション | インビボ核酸送達のためのポリ(ビニルエステル)ポリマー |
| WO2013033230A1 (en) | 2011-08-29 | 2013-03-07 | Isis Pharmaceuticals, Inc. | Oligomer-conjugate complexes and their use |
| EP2758533B1 (en) | 2011-09-20 | 2018-04-11 | Ionis Pharmaceuticals, Inc. | Antisense modulation of gcgr expression |
| US8901098B2 (en) | 2011-10-25 | 2014-12-02 | Isis Pharmaceuticals, Inc. | Antisense modulation of GCCR expression |
| PE20142362A1 (es) | 2011-11-18 | 2015-01-30 | Alnylam Pharmaceuticals Inc | Agentes de iarn, composiciones y metodos de uso de los mismos para tratar enfermedades asociadas con transtiretina (ttr) |
| WO2013119979A1 (en) | 2012-02-08 | 2013-08-15 | Isis Pharmaceuticals, Inc. | Methods and compositions for modulating factor vii expression |
| US9340784B2 (en) | 2012-03-19 | 2016-05-17 | Ionis 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 |
| EP2839006B1 (en) | 2012-04-20 | 2018-01-03 | 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 |
| 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 |
| EP3358013B1 (en) | 2012-05-02 | 2020-06-24 | Sirna Therapeutics, Inc. | Short interfering nucleic acid (sina) compositions |
| 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) |
| US20150322428A1 (en) | 2012-06-18 | 2015-11-12 | Isis Pharmaceuticals, Inc. | Compounds and methods for improved cellular uptake of antisense compounds |
| CA2879693A1 (en) | 2012-08-06 | 2014-02-13 | Alnylam Pharmaceuticals, Inc. | Carbohydrate conjugated rna agents and process for their preparation |
| WO2014059353A2 (en) | 2012-10-11 | 2014-04-17 | Isis Pharmaceuticals, Inc. | Oligomeric compounds comprising bicyclic nucleosides and uses thereof |
| RU2015119411A (ru) | 2012-11-15 | 2017-01-10 | Рош Инновейшен Сентер Копенгаген А/С | Конъюгаты антисмысловых соединений, направленные на аполипопротеин в |
| WO2014118267A1 (en) | 2013-01-30 | 2014-08-07 | Santaris Pharma A/S | Lna oligonucleotide carbohydrate conjugates |
| WO2014118272A1 (en) | 2013-01-30 | 2014-08-07 | Santaris Pharma A/S | Antimir-122 oligonucleotide carbohydrate conjugates |
| PL2992098T3 (pl) * | 2013-05-01 | 2019-09-30 | Ionis Pharmaceuticals, Inc. | Kompozycje i sposoby modulowania ekspresji hbv i ttr |
| KR20200085922A (ko) | 2013-05-16 | 2020-07-15 | 다이니뽄 스미토모 세이야쿠 가부시키가이샤 | 신경 전구 세포를 사용한 세포 치료에 있어서의 이식 보조제 |
| AU2014284152B2 (en) | 2013-06-21 | 2020-01-23 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulation of target nucleic acids |
| SG10201908122XA (en) | 2013-06-27 | 2019-10-30 | Roche Innovation Ct Copenhagen As | Antisense oligomers and conjugates targeting pcsk9 |
| EP3730614A3 (en) | 2013-07-02 | 2020-12-30 | Ionis Pharmaceuticals, Inc. | Modulators of growth hormone receptor |
| EP3019200B1 (en) | 2013-07-11 | 2022-03-23 | Alnylam Pharmaceuticals, Inc. | Oligonucleotide-ligand conjugates and process for their preparation |
| SI3043827T1 (sl) | 2013-09-13 | 2019-08-30 | Ionis Pharmaceuticals, Inc. | Modulatorji komplementnega faktorja B |
| US9943604B2 (en) | 2013-09-20 | 2018-04-17 | Ionis Pharmaceuticals, Inc. | Targeted therapeutic nucleosides and their use |
| KR20160083876A (ko) | 2013-11-14 | 2016-07-12 | 로슈 이노베이션 센터 코펜하겐 에이/에스 | ApoB 안티센스 접합체 화합물 |
| 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 |
| 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 |
| EP4534092A3 (en) | 2014-05-01 | 2025-07-02 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating pkk expression |
| MX373283B (es) | 2014-05-01 | 2020-05-20 | Ionis Pharmaceuticals Inc | Composiciones y metodos para modular la expresion del receptor de la hormona del crecimiento. |
| EP4223315A3 (en) | 2014-05-01 | 2023-08-23 | Ionis Pharmaceuticals, Inc. | Method for synthesis of reactive conjugate clusters |
| PH12016502062B1 (en) | 2014-05-01 | 2023-01-27 | Ionis Pharmaceuticals Inc | Compositions and methods for modulating complement factor b expression |
| EP3137605B1 (en) | 2014-05-01 | 2020-10-28 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating angiopoietin-like 3 expression |
| US10570169B2 (en) | 2014-05-22 | 2020-02-25 | Ionis 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 |
| KR20250078597A (ko) * | 2015-11-06 | 2025-06-02 | 아이오니스 파마수티컬즈, 인코포레이티드 | 아포리포프로테인 (a) 발현 조정 |
| SMT202400375T1 (it) * | 2015-11-06 | 2024-11-15 | Ionis Pharmaceuticals Inc | Composti antisenso coniugati per uso in terapia |
-
2014
- 2014-05-01 PL PL14791344T patent/PL2992098T3/pl unknown
- 2014-05-01 SG SG11201508870VA patent/SG11201508870VA/en unknown
- 2014-05-01 KR KR1020187013079A patent/KR102138781B1/ko active Active
- 2014-05-01 US US14/888,318 patent/US9714421B2/en not_active Expired - Fee Related
- 2014-05-01 CN CN201480035633.4A patent/CN105378082B/zh active Active
- 2014-05-01 KR KR1020157033029A patent/KR102424855B1/ko active Active
- 2014-05-01 RU RU2015151204A patent/RU2686080C2/ru active
- 2014-05-01 IL IL315582A patent/IL315582A/en unknown
- 2014-05-01 US US14/267,842 patent/US9127276B2/en active Active
- 2014-05-01 ME MEP-2019-157A patent/ME03390B/me unknown
- 2014-05-01 PT PT147911879T patent/PT2992009T/pt unknown
- 2014-05-01 BR BR122018009831-7A patent/BR122018009831B1/pt active IP Right Grant
- 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 PT PT14791344T patent/PT2992098T/pt unknown
- 2014-05-01 JP JP2016512051A patent/JP6769866B2/ja active Active
- 2014-05-01 CN CN201910037432.2A patent/CN110066795A/zh active Pending
- 2014-05-01 KR KR1020247009422A patent/KR20240042220A/ko active Pending
- 2014-05-01 RS RS20190682A patent/RS58981B1/sr unknown
- 2014-05-01 KR KR1020217033430A patent/KR102482890B1/ko active Active
- 2014-05-01 HR HRP20201378TT patent/HRP20201378T1/hr unknown
- 2014-05-01 SI SI201431660T patent/SI2992009T1/sl unknown
- 2014-05-01 KR KR1020217003080A patent/KR20210014758A/ko not_active Ceased
- 2014-05-01 CA CA2921162A patent/CA2921162A1/en active Pending
- 2014-05-01 PL PL14791187T patent/PL2992009T3/pl unknown
- 2014-05-01 MY MYPI2015703904A patent/MY178929A/en unknown
- 2014-05-01 KR KR1020157033031A patent/KR20160002977A/ko not_active Ceased
- 2014-05-01 BR BR112015027319A patent/BR112015027319A8/pt active Search and Examination
- 2014-05-01 AU AU2014259755A patent/AU2014259755B2/en active Active
- 2014-05-01 RU RU2015151200A patent/RU2699985C2/ru active
- 2014-05-01 AU AU2014259750A patent/AU2014259750B2/en active Active
- 2014-05-01 SI SI201431207T patent/SI2992098T1/sl unknown
- 2014-05-01 WO PCT/US2014/036460 patent/WO2014179625A1/en not_active Ceased
- 2014-05-01 KR KR1020207021245A patent/KR20200090966A/ko not_active Ceased
- 2014-05-01 RU RU2018112167A patent/RU2018112167A/ru not_active Application Discontinuation
- 2014-05-01 UA UAA201708429A patent/UA120287C2/uk unknown
- 2014-05-01 EP EP14791863.5A patent/EP2992097B1/en active Active
- 2014-05-01 BR BR112015027321A patent/BR112015027321A8/pt not_active Application Discontinuation
- 2014-05-01 EP EP22181753.9A patent/EP4155403A1/en active Pending
- 2014-05-01 HU HUE14791344A patent/HUE043697T2/hu unknown
- 2014-05-01 KR KR1020237024621A patent/KR102712053B1/ko active Active
- 2014-05-01 MA MA60161A patent/MA60161B1/fr unknown
- 2014-05-01 KR KR1020157033027A patent/KR101857707B1/ko active Active
- 2014-05-01 RU RU2019124314A patent/RU2019124314A/ru unknown
- 2014-05-01 EP EP14791344.6A patent/EP2992098B1/en active Active
- 2014-05-01 JP JP2016512054A patent/JP6995478B2/ja active Active
- 2014-05-01 RU RU2015151199A patent/RU2697152C2/ru active
- 2014-05-01 CN CN201910036892.3A patent/CN110042098B/zh active Active
- 2014-05-01 NZ NZ740338A patent/NZ740338A/en unknown
- 2014-05-01 CN CN202011081520.1A patent/CN112921036B/zh active Active
- 2014-05-01 NZ NZ631512A patent/NZ631512A/en unknown
- 2014-05-01 KR KR1020217009333A patent/KR20210037752A/ko not_active Ceased
- 2014-05-01 CA CA2921509A patent/CA2921509C/en active Active
- 2014-05-01 AU AU2014259756A patent/AU2014259756B2/en active Active
- 2014-05-01 SG SG10201801813YA patent/SG10201801813YA/en unknown
- 2014-05-01 MX MX2015015239A patent/MX373334B/es active IP Right Grant
- 2014-05-01 CA CA2921514A patent/CA2921514C/en active Active
- 2014-05-01 CN CN201910037434.1A patent/CN110079524B/zh active Active
- 2014-05-01 CN CN202110394825.6A patent/CN113293163A/zh active Pending
- 2014-05-01 AU AU2014259757A patent/AU2014259757B2/en not_active Ceased
- 2014-05-01 CA CA2921518A patent/CA2921518A1/en not_active Abandoned
- 2014-05-01 PE PE2016001724A patent/PE20161430A1/es unknown
- 2014-05-01 PE PE2015002330A patent/PE20152002A1/es unknown
- 2014-05-01 LT LTEP14791344.6T patent/LT2992098T/lt unknown
- 2014-05-01 JP JP2016512055A patent/JP6456362B2/ja not_active Expired - Fee Related
- 2014-05-01 EP EP19206748.6A patent/EP3633039A1/en not_active Withdrawn
- 2014-05-01 SG SG10201801507RA patent/SG10201801507RA/en unknown
- 2014-05-01 DK DK14791344.6T patent/DK2992098T3/da active
- 2014-05-01 CN CN201480035625.XA patent/CN105377887B/zh active Active
- 2014-05-01 KR KR1020227025268A patent/KR102651423B1/ko active Active
- 2014-05-01 CN CN201480035624.5A patent/CN105392488B/zh active Active
- 2014-05-01 WO PCT/US2014/036463 patent/WO2014179627A2/en not_active Ceased
- 2014-05-01 BR BR112015027322A patent/BR112015027322A8/pt not_active Application Discontinuation
- 2014-05-01 CN CN201480035618.XA patent/CN105378085B/zh active Active
- 2014-05-01 ES ES14791187T patent/ES2819213T3/es active Active
- 2014-05-01 MX MX2016012654A patent/MX381034B/es unknown
- 2014-05-01 EP EP14792010.2A patent/EP2991661B1/en active Active
- 2014-05-01 CA CA2921167A patent/CA2921167C/en active Active
- 2014-05-01 CR CR20190269A patent/CR20190269A/es unknown
- 2014-05-01 ES ES19164959T patent/ES2885174T3/es active Active
- 2014-05-01 CN CN201480035635.3A patent/CN108064162B/zh active Active
- 2014-05-01 EP EP20205948.1A patent/EP3828275A1/en active Pending
- 2014-05-01 RS RS20201052A patent/RS60796B1/sr unknown
- 2014-05-01 CN CN202010402246.7A patent/CN111593051A/zh active Pending
- 2014-05-01 RU RU2015151202A patent/RU2670614C9/ru active
- 2014-05-01 EP EP24189241.3A patent/EP4438129A3/en active Pending
- 2014-05-01 MX MX2015015263A patent/MX373306B/es active IP Right Grant
- 2014-05-01 LT LTEP14791187.9T patent/LT2992009T/lt unknown
- 2014-05-01 AU AU2014259759A patent/AU2014259759B2/en not_active Expired - Fee Related
- 2014-05-01 UA UAA201511840A patent/UA121017C2/uk unknown
- 2014-05-01 ES ES14791557T patent/ES2778442T3/es active Active
- 2014-05-01 MX MX2015015234A patent/MX2015015234A/es active IP Right Grant
- 2014-05-01 NZ NZ631537A patent/NZ631537A/en unknown
- 2014-05-01 KR KR1020227045740A patent/KR20230006933A/ko not_active Ceased
- 2014-05-01 BR BR112015027377-7A patent/BR112015027377B1/pt active IP Right Grant
- 2014-05-01 MY MYPI2018000863A patent/MY198359A/en unknown
- 2014-05-01 NZ NZ753018A patent/NZ753018A/en unknown
- 2014-05-01 EA EA201891479A patent/EA036584B1/ru unknown
- 2014-05-01 WO PCT/US2014/036452 patent/WO2014179620A1/en not_active Ceased
- 2014-05-01 JP JP2016512053A patent/JP6387084B2/ja active Active
- 2014-05-01 EP EP14791557.3A patent/EP2991656B1/en active Active
- 2014-05-01 EP EP19164959.9A patent/EP3524680B1/en active Active
- 2014-05-01 ES ES14791344T patent/ES2730015T3/es active Active
- 2014-05-01 DK DK19164959.9T patent/DK3524680T3/da active
- 2014-05-01 KR KR1020247032116A patent/KR20240147701A/ko active Pending
- 2014-05-01 PT PT191649599T patent/PT3524680T/pt unknown
- 2014-05-01 SG SG11201508800WA patent/SG11201508800WA/en unknown
- 2014-05-01 EP EP14791187.9A patent/EP2992009B1/en active Active
- 2014-05-01 RU RU2019110030A patent/RU2019110030A/ru unknown
- 2014-05-01 SG SG10201906382QA patent/SG10201906382QA/en unknown
- 2014-05-01 HR HRP20190987TT patent/HRP20190987T1/hr unknown
- 2014-05-01 CN CN202111358415.2A patent/CN114058617A/zh active Pending
- 2014-05-01 KR KR1020197019617A patent/KR102212275B1/ko active Active
- 2014-05-01 EP EP25155370.7A patent/EP4529927A3/en active Pending
- 2014-05-01 IL IL284593A patent/IL284593B2/en unknown
- 2014-05-01 HU HUE14791187A patent/HUE050394T2/hu unknown
- 2014-05-01 DK DK14791557.3T patent/DK2991656T3/da active
- 2014-05-01 NZ NZ631552A patent/NZ631552A/en not_active IP Right Cessation
- 2014-05-01 MX MX2015015264A patent/MX2015015264A/es active IP Right Grant
- 2014-05-01 IL IL296543A patent/IL296543B2/en unknown
- 2014-05-01 WO PCT/US2014/036462 patent/WO2014179626A2/en not_active Ceased
- 2014-05-01 MX MX2015015220A patent/MX384824B/es unknown
- 2014-05-01 WO PCT/US2014/036466 patent/WO2014179629A2/en not_active Ceased
- 2014-05-01 CN CN202411684710.0A patent/CN119913147A/zh active Pending
- 2014-05-01 KR KR1020217039866A patent/KR102558571B1/ko active Active
- 2014-05-01 RU RU2015151203A patent/RU2650510C2/ru active
- 2014-05-01 EP EP19160031.1A patent/EP3546579A1/en active Pending
- 2014-05-01 EA EA201592093A patent/EA031393B1/ru unknown
- 2014-05-01 EP EP19217148.6A patent/EP3690049A1/en active Pending
- 2014-05-01 KR KR1020157033028A patent/KR102315836B1/ko active Active
- 2014-05-01 DK DK14791187.9T patent/DK2992009T3/da active
- 2014-05-01 JP JP2016512052A patent/JP6216444B2/ja active Active
- 2014-05-01 SM SM20190316T patent/SMT201900316T1/it unknown
- 2014-12-30 US US14/586,751 patent/US9181549B2/en active Active
- 2014-12-30 US US14/586,826 patent/US9163239B2/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 IL242132A patent/IL242132B/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
- 2015-10-28 DO DO2015000268A patent/DOP2015000268A/es unknown
- 2015-10-29 PH PH12015502493A patent/PH12015502493B1/en unknown
- 2015-10-30 MX MX2020002184A patent/MX2020002184A/es unknown
- 2015-10-30 CL CL2015003217A patent/CL2015003217A1/es unknown
- 2015-10-30 MX MX2020004209A patent/MX2020004209A/es unknown
- 2015-10-30 MX MX2021008901A patent/MX2021008901A/es unknown
- 2015-10-30 MX MX2021008899A patent/MX2021008899A/es unknown
- 2015-10-30 MX MX2019010441A patent/MX2019010441A/es unknown
- 2015-10-30 MX MX2019010443A patent/MX2019010443A/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
- 2022-10-21 US US17/970,887 patent/US20230151365A1/en active Pending
- 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
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2730015T3 (es) | Composiciones y métodos para modular expresión de HBV y de TTR | |
| WO2015042447A1 (en) | Targeted therapeutic nucleosides and their use | |
| HK40053557A (en) | Compositions and methods for modulating ttr expression | |
| HK1221485B (en) | Compositions and methods for modulating hbv and ttr expression | |
| HK40011555B (en) | Compositions and methods for modulating ttr expression | |
| HK40011555A (en) | Compositions and methods for modulating ttr expression |