ES2699891T3 - Métodos para tratar la esclerosis múltiple usando oligonucleótidos antisentido - Google Patents
Métodos para tratar la esclerosis múltiple usando oligonucleótidos antisentido Download PDFInfo
- Publication number
- ES2699891T3 ES2699891T3 ES15155831T ES15155831T ES2699891T3 ES 2699891 T3 ES2699891 T3 ES 2699891T3 ES 15155831 T ES15155831 T ES 15155831T ES 15155831 T ES15155831 T ES 15155831T ES 2699891 T3 ES2699891 T3 ES 2699891T3
- Authority
- ES
- Spain
- Prior art keywords
- pharmaceutical composition
- multiple sclerosis
- oligonucleotide
- human subject
- brain lesions
- 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
- 201000006417 multiple sclerosis Diseases 0.000 title claims abstract description 125
- 238000000034 method Methods 0.000 title claims abstract description 70
- 239000000074 antisense oligonucleotide Substances 0.000 title description 18
- 238000012230 antisense oligonucleotides Methods 0.000 title description 18
- 108020000948 Antisense Oligonucleotides Proteins 0.000 title description 13
- 108091034117 Oligonucleotide Proteins 0.000 claims abstract description 123
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 58
- 125000003729 nucleotide group Chemical group 0.000 claims abstract description 57
- 206010051290 Central nervous system lesion Diseases 0.000 claims abstract description 56
- 239000002773 nucleotide Substances 0.000 claims abstract description 55
- 229910052688 Gadolinium Inorganic materials 0.000 claims abstract description 42
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 claims abstract description 41
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims abstract description 34
- 239000003937 drug carrier Substances 0.000 claims abstract description 24
- 238000009825 accumulation Methods 0.000 claims abstract description 20
- 150000003839 salts Chemical class 0.000 claims abstract description 18
- LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical class CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 claims abstract description 17
- 239000005549 deoxyribonucleoside Substances 0.000 claims abstract description 17
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 17
- 230000001603 reducing effect Effects 0.000 claims abstract description 16
- -1 phosphorothioate diester Chemical class 0.000 claims abstract description 9
- 210000004369 blood Anatomy 0.000 claims description 37
- 239000008280 blood Substances 0.000 claims description 37
- 230000000737 periodic effect Effects 0.000 claims description 33
- 238000011282 treatment Methods 0.000 claims description 33
- 108091028664 Ribonucleotide Proteins 0.000 claims description 32
- 239000002336 ribonucleotide Substances 0.000 claims description 32
- 125000002652 ribonucleotide group Chemical class 0.000 claims description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical group O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 20
- 239000008215 water for injection Substances 0.000 claims description 18
- 230000002829 reductive effect Effects 0.000 claims description 15
- 230000000750 progressive effect Effects 0.000 claims description 10
- 201000008628 secondary progressive multiple sclerosis Diseases 0.000 claims description 8
- 208000007118 chronic progressive multiple sclerosis Diseases 0.000 claims description 7
- 159000000000 sodium salts Chemical class 0.000 claims description 5
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical class [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims description 2
- VKZRWSNIWNFCIQ-WDSKDSINSA-N (2s)-2-[2-[[(1s)-1,2-dicarboxyethyl]amino]ethylamino]butanedioic acid Chemical compound OC(=O)C[C@@H](C(O)=O)NCCN[C@H](C(O)=O)CC(O)=O VKZRWSNIWNFCIQ-WDSKDSINSA-N 0.000 claims 1
- 239000002342 ribonucleoside Substances 0.000 abstract 2
- 238000002595 magnetic resonance imaging Methods 0.000 description 65
- 230000003902 lesion Effects 0.000 description 44
- 208000007400 Relapsing-Remitting Multiple Sclerosis Diseases 0.000 description 34
- 108010008212 Integrin alpha4beta1 Proteins 0.000 description 24
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- 238000006243 chemical reaction Methods 0.000 description 18
- 239000003814 drug Substances 0.000 description 18
- 239000000902 placebo Substances 0.000 description 18
- 229940068196 placebo Drugs 0.000 description 18
- 210000003169 central nervous system Anatomy 0.000 description 17
- 230000000306 recurrent effect Effects 0.000 description 16
- 201000010099 disease Diseases 0.000 description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 15
- 108090000623 proteins and genes Proteins 0.000 description 15
- 210000004556 brain Anatomy 0.000 description 14
- 230000000694 effects Effects 0.000 description 13
- 102000004169 proteins and genes Human genes 0.000 description 13
- 210000004027 cell Anatomy 0.000 description 12
- 230000001186 cumulative effect Effects 0.000 description 12
- 229940079593 drug Drugs 0.000 description 12
- 108020004999 messenger RNA Proteins 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 230000006378 damage Effects 0.000 description 11
- 230000008569 process Effects 0.000 description 11
- 239000000047 product Substances 0.000 description 10
- 230000009467 reduction Effects 0.000 description 10
- 230000014509 gene expression Effects 0.000 description 9
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 8
- 230000008499 blood brain barrier function Effects 0.000 description 8
- 210000001218 blood-brain barrier Anatomy 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 210000000265 leukocyte Anatomy 0.000 description 8
- 230000001225 therapeutic effect Effects 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- 239000002253 acid Substances 0.000 description 7
- 230000000692 anti-sense effect Effects 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 230000006870 function Effects 0.000 description 7
- 229960005027 natalizumab Drugs 0.000 description 7
- 208000035824 paresthesia Diseases 0.000 description 7
- 239000012071 phase Substances 0.000 description 7
- 238000011084 recovery Methods 0.000 description 7
- 208000024891 symptom Diseases 0.000 description 7
- 102000006386 Myelin Proteins Human genes 0.000 description 6
- 108010083674 Myelin Proteins Proteins 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 238000013459 approach Methods 0.000 description 6
- 230000003376 axonal effect Effects 0.000 description 6
- 239000003246 corticosteroid Substances 0.000 description 6
- 238000010511 deprotection reaction Methods 0.000 description 6
- 230000006866 deterioration Effects 0.000 description 6
- 208000014674 injury Diseases 0.000 description 6
- 210000005012 myelin Anatomy 0.000 description 6
- 230000000926 neurological effect Effects 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 229940124597 therapeutic agent Drugs 0.000 description 6
- 206010003591 Ataxia Diseases 0.000 description 5
- 108010072051 Glatiramer Acetate Proteins 0.000 description 5
- 206010061218 Inflammation Diseases 0.000 description 5
- 241000701460 JC polyomavirus Species 0.000 description 5
- 208000027418 Wounds and injury Diseases 0.000 description 5
- FHEAIOHRHQGZPC-KIWGSFCNSA-N acetic acid;(2s)-2-amino-3-(4-hydroxyphenyl)propanoic acid;(2s)-2-aminopentanedioic acid;(2s)-2-aminopropanoic acid;(2s)-2,6-diaminohexanoic acid Chemical compound CC(O)=O.C[C@H](N)C(O)=O.NCCCC[C@H](N)C(O)=O.OC(=O)[C@@H](N)CCC(O)=O.OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 FHEAIOHRHQGZPC-KIWGSFCNSA-N 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000005859 coupling reaction Methods 0.000 description 5
- 229960003776 glatiramer acetate Drugs 0.000 description 5
- 238000003384 imaging method Methods 0.000 description 5
- 230000002757 inflammatory effect Effects 0.000 description 5
- 230000004054 inflammatory process Effects 0.000 description 5
- 238000007920 subcutaneous administration Methods 0.000 description 5
- 206010043554 thrombocytopenia Diseases 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- 108090000467 Interferon-beta Proteins 0.000 description 4
- 102000003996 Interferon-beta Human genes 0.000 description 4
- 102000002233 Myelin-Oligodendrocyte Glycoprotein Human genes 0.000 description 4
- 108010000123 Myelin-Oligodendrocyte Glycoprotein Proteins 0.000 description 4
- 208000002193 Pain Diseases 0.000 description 4
- 210000001744 T-lymphocyte Anatomy 0.000 description 4
- 230000001154 acute effect Effects 0.000 description 4
- 239000000427 antigen Substances 0.000 description 4
- 108091007433 antigens Proteins 0.000 description 4
- 102000036639 antigens Human genes 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 4
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 230000008878 coupling Effects 0.000 description 4
- 238000010168 coupling process Methods 0.000 description 4
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 description 4
- 201000002491 encephalomyelitis Diseases 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 4
- 230000005284 excitation Effects 0.000 description 4
- IZOOGPBRAOKZFK-UHFFFAOYSA-K gadopentetate Chemical compound [Gd+3].OC(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O IZOOGPBRAOKZFK-UHFFFAOYSA-K 0.000 description 4
- 210000002865 immune cell Anatomy 0.000 description 4
- 229960001388 interferon-beta Drugs 0.000 description 4
- 210000004698 lymphocyte Anatomy 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 238000012544 monitoring process Methods 0.000 description 4
- 230000007971 neurological deficit Effects 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 238000012552 review Methods 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 210000000278 spinal cord Anatomy 0.000 description 4
- 230000014616 translation Effects 0.000 description 4
- 210000004885 white matter Anatomy 0.000 description 4
- ABEXEQSGABRUHS-UHFFFAOYSA-N 16-methylheptadecyl 16-methylheptadecanoate Chemical compound CC(C)CCCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCCCC(C)C ABEXEQSGABRUHS-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 108020003566 Antisense Oligodeoxyribonucleotides Proteins 0.000 description 3
- 201000004569 Blindness Diseases 0.000 description 3
- 206010010947 Coordination abnormal Diseases 0.000 description 3
- 208000032843 Hemorrhage Diseases 0.000 description 3
- 101000994375 Homo sapiens Integrin alpha-4 Proteins 0.000 description 3
- 102100034343 Integrase Human genes 0.000 description 3
- 101710203526 Integrase Proteins 0.000 description 3
- 102100032818 Integrin alpha-4 Human genes 0.000 description 3
- 108010005716 Interferon beta-1a Proteins 0.000 description 3
- 108010005714 Interferon beta-1b Proteins 0.000 description 3
- 241000764238 Isis Species 0.000 description 3
- 101710163270 Nuclease Proteins 0.000 description 3
- 208000003435 Optic Neuritis Diseases 0.000 description 3
- 108010083644 Ribonucleases Proteins 0.000 description 3
- 102000006382 Ribonucleases Human genes 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical group OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000003293 antisense oligodeoxyribonucleotide Substances 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000015271 coagulation Effects 0.000 description 3
- 238000005345 coagulation Methods 0.000 description 3
- 230000003920 cognitive function Effects 0.000 description 3
- 239000002872 contrast media Substances 0.000 description 3
- 229960001334 corticosteroids Drugs 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 238000003745 diagnosis Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 230000007717 exclusion Effects 0.000 description 3
- 238000009396 hybridization Methods 0.000 description 3
- 238000005417 image-selected in vivo spectroscopy Methods 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 238000012739 integrated shape imaging system Methods 0.000 description 3
- 108010044426 integrins Proteins 0.000 description 3
- 102000006495 integrins Human genes 0.000 description 3
- 229960004461 interferon beta-1a Drugs 0.000 description 3
- 229960003161 interferon beta-1b Drugs 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 230000009251 neurologic dysfunction Effects 0.000 description 3
- 208000015015 neurological dysfunction Diseases 0.000 description 3
- 230000036407 pain Effects 0.000 description 3
- 230000008506 pathogenesis Effects 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 159000000001 potassium salts Chemical class 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- 230000035945 sensitivity Effects 0.000 description 3
- 230000001568 sexual effect Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 238000005987 sulfurization reaction Methods 0.000 description 3
- 230000002459 sustained effect Effects 0.000 description 3
- 238000013519 translation Methods 0.000 description 3
- 238000011269 treatment regimen Methods 0.000 description 3
- KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Chemical compound C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 2
- KISWVXRQTGLFGD-UHFFFAOYSA-N 2-[[2-[[6-amino-2-[[2-[[2-[[5-amino-2-[[2-[[1-[2-[[6-amino-2-[(2,5-diamino-5-oxopentanoyl)amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)p Chemical compound C1CCN(C(=O)C(CCCN=C(N)N)NC(=O)C(CCCCN)NC(=O)C(N)CCC(N)=O)C1C(=O)NC(CO)C(=O)NC(CCC(N)=O)C(=O)NC(CCCN=C(N)N)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 KISWVXRQTGLFGD-UHFFFAOYSA-N 0.000 description 2
- 206010003694 Atrophy Diseases 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 206010006784 Burning sensation Diseases 0.000 description 2
- 108090000994 Catalytic RNA Proteins 0.000 description 2
- 102000053642 Catalytic RNA Human genes 0.000 description 2
- 206010071068 Clinically isolated syndrome Diseases 0.000 description 2
- 206010010774 Constipation Diseases 0.000 description 2
- 208000011231 Crohn disease Diseases 0.000 description 2
- 208000019505 Deglutition disease Diseases 0.000 description 2
- 208000016192 Demyelinating disease Diseases 0.000 description 2
- 206010012305 Demyelination Diseases 0.000 description 2
- 208000003164 Diplopia Diseases 0.000 description 2
- 206010013700 Drug hypersensitivity Diseases 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 206010016059 Facial pain Diseases 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- 206010067142 Immediate post-injection reaction Diseases 0.000 description 2
- 206010021639 Incontinence Diseases 0.000 description 2
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 208000007101 Muscle Cramp Diseases 0.000 description 2
- 206010052904 Musculoskeletal stiffness Diseases 0.000 description 2
- 208000000112 Myalgia Diseases 0.000 description 2
- 102000017099 Myelin-Associated Glycoprotein Human genes 0.000 description 2
- 108010013731 Myelin-Associated Glycoprotein Proteins 0.000 description 2
- 239000004743 Polypropylene Substances 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 208000034189 Sclerosis Diseases 0.000 description 2
- 208000005392 Spasm Diseases 0.000 description 2
- 206010044565 Tremor Diseases 0.000 description 2
- 206010047513 Vision blurred Diseases 0.000 description 2
- 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 2
- 230000005856 abnormality Effects 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- 230000007815 allergy Effects 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 230000037007 arousal Effects 0.000 description 2
- 230000037444 atrophy Effects 0.000 description 2
- 230000006472 autoimmune response Effects 0.000 description 2
- 230000000740 bleeding effect Effects 0.000 description 2
- 210000000133 brain stem Anatomy 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 230000002490 cerebral effect Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 230000001149 cognitive effect Effects 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 239000002131 composite material Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 210000000877 corpus callosum Anatomy 0.000 description 2
- 229940109239 creatinine Drugs 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 231100000517 death Toxicity 0.000 description 2
- 230000003210 demyelinating effect Effects 0.000 description 2
- 238000006642 detritylation reaction Methods 0.000 description 2
- 238000007435 diagnostic evaluation Methods 0.000 description 2
- 229960005215 dichloroacetic acid Drugs 0.000 description 2
- 238000011143 downstream manufacturing Methods 0.000 description 2
- 229940000406 drug candidate Drugs 0.000 description 2
- 210000003038 endothelium Anatomy 0.000 description 2
- 210000003989 endothelium vascular Anatomy 0.000 description 2
- 230000005713 exacerbation Effects 0.000 description 2
- 210000004884 grey matter Anatomy 0.000 description 2
- 210000005260 human cell Anatomy 0.000 description 2
- 230000002519 immonomodulatory effect Effects 0.000 description 2
- 239000003018 immunosuppressive agent Substances 0.000 description 2
- 229940124589 immunosuppressive drug Drugs 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- 201000001881 impotence Diseases 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 208000027866 inflammatory disease Diseases 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 230000002427 irreversible effect Effects 0.000 description 2
- 208000028756 lack of coordination Diseases 0.000 description 2
- 230000033001 locomotion Effects 0.000 description 2
- 208000018883 loss of balance Diseases 0.000 description 2
- 210000003563 lymphoid tissue Anatomy 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 229940126601 medicinal product Drugs 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 239000002547 new drug Substances 0.000 description 2
- 239000002777 nucleoside Substances 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 150000008300 phosphoramidites Chemical class 0.000 description 2
- 229920001155 polypropylene Polymers 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 206010036807 progressive multifocal leukoencephalopathy Diseases 0.000 description 2
- 230000004952 protein activity Effects 0.000 description 2
- 230000004461 rapid eye movement Effects 0.000 description 2
- 230000033764 rhythmic process Effects 0.000 description 2
- 108091092562 ribozyme Proteins 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 229940126586 small molecule drug Drugs 0.000 description 2
- 238000010532 solid phase synthesis reaction Methods 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 230000032258 transport Effects 0.000 description 2
- 206010044652 trigeminal neuralgia Diseases 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- 230000004393 visual impairment Effects 0.000 description 2
- PGOHTUIFYSHAQG-LJSDBVFPSA-N (2S)-6-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-3-sulfanylpropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-oxopentanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-oxopentanoyl]amino]-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-carboxybutanoyl]amino]-5-oxopentanoyl]amino]hexanoic acid Chemical compound CSCC[C@H](N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(O)=O PGOHTUIFYSHAQG-LJSDBVFPSA-N 0.000 description 1
- 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 1
- ALZJFXRZNCPILQ-GJMOJQLCSA-N (4r,5r,6r)-4,5,6,7-tetrahydroxy-1-methoxyheptan-3-one Chemical compound COCCC(=O)[C@H](O)[C@H](O)[C@H](O)CO ALZJFXRZNCPILQ-GJMOJQLCSA-N 0.000 description 1
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 description 1
- 125000002103 4,4'-dimethoxytriphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)(C1=C([H])C([H])=C(OC([H])([H])[H])C([H])=C1[H])C1=C([H])C([H])=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
- LLQHSBBZNDXTIV-UHFFFAOYSA-N 6-[5-[[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]methyl]-4,5-dihydro-1,2-oxazol-3-yl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC1CC(=NO1)C1=CC2=C(NC(O2)=O)C=C1 LLQHSBBZNDXTIV-UHFFFAOYSA-N 0.000 description 1
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 description 1
- 108010082126 Alanine transaminase Proteins 0.000 description 1
- 208000007848 Alcoholism Diseases 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 208000000044 Amnesia Diseases 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 108091023037 Aptamer Proteins 0.000 description 1
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 1
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 208000019838 Blood disease Diseases 0.000 description 1
- 108700031361 Brachyury Proteins 0.000 description 1
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 206010051288 Central nervous system inflammation Diseases 0.000 description 1
- 238000007445 Chromatographic isolation Methods 0.000 description 1
- 206010053567 Coagulopathies Diseases 0.000 description 1
- 108091027757 Deoxyribozyme Proteins 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- GTAXGNCCEYZRII-UHFFFAOYSA-N Eperisone hydrochloride Chemical compound Cl.C1=CC(CC)=CC=C1C(=O)C(C)CN1CCCCC1 GTAXGNCCEYZRII-UHFFFAOYSA-N 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 208000034826 Genetic Predisposition to Disease Diseases 0.000 description 1
- 206010018341 Gliosis Diseases 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
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 102000018713 Histocompatibility Antigens Class II Human genes 0.000 description 1
- 108010027412 Histocompatibility Antigens Class II Proteins 0.000 description 1
- 101001002508 Homo sapiens Immunoglobulin-binding protein 1 Proteins 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
- 102100021042 Immunoglobulin-binding protein 1 Human genes 0.000 description 1
- 206010022004 Influenza like illness Diseases 0.000 description 1
- 108010041012 Integrin alpha4 Proteins 0.000 description 1
- 208000030979 Language Development disease Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 208000008238 Muscle Spasticity Diseases 0.000 description 1
- 102000047918 Myelin Basic Human genes 0.000 description 1
- 101710107068 Myelin basic protein Proteins 0.000 description 1
- 208000003926 Myelitis Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 206010033557 Palpitations Diseases 0.000 description 1
- 208000007542 Paresis Diseases 0.000 description 1
- 108091093037 Peptide nucleic acid Proteins 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 206010053395 Progressive multiple sclerosis Diseases 0.000 description 1
- 206010067063 Progressive relapsing multiple sclerosis Diseases 0.000 description 1
- 102000016202 Proteolipids Human genes 0.000 description 1
- 108010010974 Proteolipids Proteins 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- 102000004167 Ribonuclease P Human genes 0.000 description 1
- 108090000621 Ribonuclease P Proteins 0.000 description 1
- 206010040030 Sensory loss Diseases 0.000 description 1
- 102000008063 Small Heat-Shock Proteins Human genes 0.000 description 1
- 108010088928 Small Heat-Shock Proteins Proteins 0.000 description 1
- 108020004459 Small interfering RNA Proteins 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 230000005867 T cell response Effects 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- 108091036066 Three prime untranslated region Proteins 0.000 description 1
- 108010000499 Thromboplastin Proteins 0.000 description 1
- 102100030859 Tissue factor Human genes 0.000 description 1
- 238000008050 Total Bilirubin Reagent Methods 0.000 description 1
- 108090000340 Transaminases Proteins 0.000 description 1
- 102000003929 Transaminases Human genes 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 108010000134 Vascular Cell Adhesion Molecule-1 Proteins 0.000 description 1
- 102100023543 Vascular cell adhesion protein 1 Human genes 0.000 description 1
- 208000012886 Vertigo Diseases 0.000 description 1
- 108020000999 Viral RNA Proteins 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 206010047571 Visual impairment Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000004847 absorption spectroscopy Methods 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000009798 acute exacerbation Effects 0.000 description 1
- 230000006022 acute inflammation Effects 0.000 description 1
- 208000038016 acute inflammation Diseases 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 201000007930 alcohol dependence Diseases 0.000 description 1
- 102000013640 alpha-Crystallin B Chain Human genes 0.000 description 1
- 108010051585 alpha-Crystallin B Chain Proteins 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 230000002502 anti-myelin effect Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 210000001772 blood platelet Anatomy 0.000 description 1
- 230000003925 brain function Effects 0.000 description 1
- 229920005557 bromobutyl Polymers 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 229940124558 contraceptive agent Drugs 0.000 description 1
- 239000003433 contraceptive agent Substances 0.000 description 1
- 229940039231 contrast media Drugs 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000035487 diastolic blood pressure Effects 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 201000005311 drug allergy Diseases 0.000 description 1
- 206010013663 drug dependence Diseases 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 239000003596 drug target Substances 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 230000008497 endothelial barrier function Effects 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 208000012997 experimental autoimmune encephalomyelitis Diseases 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000005308 flint glass Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000009368 gene silencing by RNA Effects 0.000 description 1
- 230000007387 gliosis Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 238000005534 hematocrit Methods 0.000 description 1
- 208000014951 hematologic disease Diseases 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- 208000018706 hematopoietic system disease Diseases 0.000 description 1
- 208000031169 hemorrhagic disease Diseases 0.000 description 1
- 230000002008 hemorrhagic effect Effects 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 229920001903 high density polyethylene Polymers 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000004700 high-density polyethylene Substances 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 229940124622 immune-modulator drug Drugs 0.000 description 1
- 230000004957 immunoregulator effect Effects 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 208000016290 incoordination Diseases 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 238000007477 logistic regression Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 231100000863 loss of memory Toxicity 0.000 description 1
- 208000018769 loss of vision Diseases 0.000 description 1
- 231100000864 loss of vision Toxicity 0.000 description 1
- 238000012792 lyophilization process Methods 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 230000005415 magnetization Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000036630 mental development Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 108091070501 miRNA Proteins 0.000 description 1
- 239000002679 microRNA Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000007658 neurological function Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 229940127285 new chemical entity Drugs 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 230000000474 nursing effect Effects 0.000 description 1
- 229940046166 oligodeoxynucleotide Drugs 0.000 description 1
- 229940127234 oral contraceptive Drugs 0.000 description 1
- 239000003539 oral contraceptive agent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 101710135378 pH 6 antigen Proteins 0.000 description 1
- 230000001769 paralizing effect Effects 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000035778 pathophysiological process Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 210000005105 peripheral blood lymphocyte Anatomy 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- DQDAYGNAKTZFIW-UHFFFAOYSA-N phenprocoumon Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC)C1=CC=CC=C1 DQDAYGNAKTZFIW-UHFFFAOYSA-N 0.000 description 1
- 229960004923 phenprocoumon Drugs 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 206010063401 primary progressive multiple sclerosis Diseases 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 208000037821 progressive disease Diseases 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000000275 quality assurance Methods 0.000 description 1
- 108010061338 ranpirnase Proteins 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 208000020029 respiratory tract infectious disease Diseases 0.000 description 1
- 238000004370 retrospective diagnosis Methods 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 238000005096 rolling process Methods 0.000 description 1
- IXGZXXBJSZISOO-UHFFFAOYSA-N s-(2-phenylacetyl)sulfanyl 2-phenylethanethioate Chemical compound C=1C=CC=CC=1CC(=O)SSC(=O)CC1=CC=CC=C1 IXGZXXBJSZISOO-UHFFFAOYSA-N 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 230000006403 short-term memory Effects 0.000 description 1
- 208000013220 shortness of breath Diseases 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 239000004055 small Interfering RNA Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 208000018198 spasticity Diseases 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000035488 systolic blood pressure Effects 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 229940079023 tysabri Drugs 0.000 description 1
- 238000002562 urinalysis Methods 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 208000019206 urinary tract infection Diseases 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 231100000889 vertigo Toxicity 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 208000029257 vision disease Diseases 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
Classifications
-
- 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
- C12N15/1138—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 receptors or cell surface proteins
-
- 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
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
- 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
- C12N2310/30—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
- 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
- C12N2310/33—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
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Immunology (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Microbiology (AREA)
- Hospice & Palliative Care (AREA)
- Transplantation (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US13297308P | 2008-06-23 | 2008-06-23 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2699891T3 true ES2699891T3 (es) | 2019-02-13 |
Family
ID=41550900
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES15155831T Active ES2699891T3 (es) | 2008-06-23 | 2009-06-23 | Métodos para tratar la esclerosis múltiple usando oligonucleótidos antisentido |
| ES09798248.2T Active ES2532404T3 (es) | 2008-06-23 | 2009-06-23 | Métodos para tratar la esclerosis múltiple usando oligonucleótidos antisentido |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES09798248.2T Active ES2532404T3 (es) | 2008-06-23 | 2009-06-23 | Métodos para tratar la esclerosis múltiple usando oligonucleótidos antisentido |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US8415314B2 (enExample) |
| EP (2) | EP2937358B1 (enExample) |
| JP (2) | JP5988581B2 (enExample) |
| AU (1) | AU2009271678B2 (enExample) |
| CA (1) | CA2728562C (enExample) |
| DK (2) | DK2318424T3 (enExample) |
| ES (2) | ES2699891T3 (enExample) |
| WO (1) | WO2010008474A2 (enExample) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010008474A2 (en) | 2008-06-23 | 2010-01-21 | Teva Pharmaceutical Industries, Ltd. | Methods for treating multiple sclerosis using antisense oligonucleotides |
| AU2011301712C1 (en) * | 2010-09-17 | 2017-01-05 | Antisense Therapeutics Ltd | Method for reducing the number of certain circulating leukocytes in a human subject |
| AU2016259971B2 (en) | 2015-05-11 | 2021-12-09 | ProGenis Pty Ltd | Multiple sclerosis treatment |
| AU2018286483C1 (en) * | 2017-06-16 | 2024-10-31 | Antisense Therapeutics Ltd | Methods for treating multiple sclerosis using antisense oligonucleotides |
| BR112020022519A2 (pt) * | 2018-05-04 | 2021-02-09 | Antisense Therapeutics Ltd | usos e métodos terapêuticos |
| CA3138945A1 (en) * | 2019-05-06 | 2020-11-12 | Antisense Therapeutics Ltd | Methods for treating muscular dystrophy using inhibitory oligonucleotides to cd49d |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6242591B1 (en) * | 1997-10-15 | 2001-06-05 | Isis Pharmaceuticals, Inc. | Synthesis of sulfurized 2'-substituted oligonucleotides |
| US5968826A (en) * | 1998-10-05 | 1999-10-19 | Isis Pharmaceuticals Inc. | Antisense inhibition of integrin α4 expression |
| US20070237717A1 (en) * | 2004-04-05 | 2007-10-11 | Roland Martin | Methods for Selection of Subjects for Multiple Sclerosis Therapy |
| WO2006086821A1 (en) * | 2004-10-20 | 2006-08-24 | Antisense Therapeutics Ltd | ANTISENS MODULATION OF INTEGRIN α4 EXPRESSION |
| WO2010008474A2 (en) | 2008-06-23 | 2010-01-21 | Teva Pharmaceutical Industries, Ltd. | Methods for treating multiple sclerosis using antisense oligonucleotides |
-
2009
- 2009-06-23 WO PCT/US2009/003760 patent/WO2010008474A2/en not_active Ceased
- 2009-06-23 CA CA2728562A patent/CA2728562C/en active Active
- 2009-06-23 ES ES15155831T patent/ES2699891T3/es active Active
- 2009-06-23 JP JP2011516297A patent/JP5988581B2/ja not_active Expired - Fee Related
- 2009-06-23 EP EP15155831.9A patent/EP2937358B1/en active Active
- 2009-06-23 AU AU2009271678A patent/AU2009271678B2/en not_active Ceased
- 2009-06-23 EP EP09798248.2A patent/EP2318424B1/en not_active Not-in-force
- 2009-06-23 DK DK09798248T patent/DK2318424T3/en active
- 2009-06-23 US US12/456,883 patent/US8415314B2/en not_active Expired - Fee Related
- 2009-06-23 ES ES09798248.2T patent/ES2532404T3/es active Active
- 2009-06-23 DK DK15155831.9T patent/DK2937358T3/da active
-
2013
- 2013-03-22 US US13/848,811 patent/US8759314B2/en active Active
-
2014
- 2014-10-09 JP JP2014208153A patent/JP6131230B2/ja not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| WO2010008474A2 (en) | 2010-01-21 |
| WO2010008474A4 (en) | 2011-01-27 |
| CA2728562C (en) | 2018-10-23 |
| JP6131230B2 (ja) | 2017-05-17 |
| EP2318424A2 (en) | 2011-05-11 |
| EP2937358B1 (en) | 2018-09-19 |
| JP2011525531A (ja) | 2011-09-22 |
| AU2009271678A1 (en) | 2010-01-21 |
| JP5988581B2 (ja) | 2016-09-07 |
| EP2318424A4 (en) | 2012-12-26 |
| ES2532404T3 (es) | 2015-03-26 |
| US8759314B2 (en) | 2014-06-24 |
| CA2728562A1 (en) | 2010-01-21 |
| EP2937358A1 (en) | 2015-10-28 |
| EP2318424B1 (en) | 2015-02-25 |
| DK2937358T3 (da) | 2019-01-02 |
| JP2015044824A (ja) | 2015-03-12 |
| US20100119480A1 (en) | 2010-05-13 |
| US8415314B2 (en) | 2013-04-09 |
| AU2009271678B2 (en) | 2013-09-19 |
| WO2010008474A3 (en) | 2010-04-22 |
| DK2318424T3 (en) | 2015-04-07 |
| US20130345293A1 (en) | 2013-12-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6250078B2 (ja) | 真核細胞におけるエキソンスキッピングの誘導 | |
| EP2791335B1 (en) | Chimeric double-stranded nucleic acid | |
| ES2471978T3 (es) | Compuestos y procedimientos para modular la expresión de ApoB | |
| ES2699891T3 (es) | Métodos para tratar la esclerosis múltiple usando oligonucleótidos antisentido | |
| KR20240103025A (ko) | 안지오텐시노겐(agt) 단백질의 발현을 저해하는 조성물 및 방법 | |
| AU2018286483B2 (en) | Methods for treating multiple sclerosis using antisense oligonucleotides | |
| KR20220061915A (ko) | Cd49d에 대한 억제성 올리고뉴클레오티드를 사용하는 근이영양증의 치료 방법 | |
| US20250197859A1 (en) | Compositions and methods for the treatment of angiopoietin like 7 (angptl7) related diseases | |
| US20250179503A1 (en) | Methods of using oligomeric compounds to treat scn2a-related disorders | |
| TW202442241A (zh) | 用於治療多囊性腎病之方法 | |
| CN119112932A (zh) | 治疗用途和方法 | |
| CA2725534A1 (en) | Inhibition of emmprin to treat multiple sclerosis | |
| WO2022158608A1 (ja) | 良性成人型家族性ミオクローヌスてんかんの予防又は治療剤 | |
| EP4473113A2 (en) | Methods for the treatment of scn2a-related disorders |