NO330715B1 - Anvendelse av ribavirin og interferon-alfa i kombinasjon for fremstilling av et farmasoytisk preparat for behandling av kronisk hepatitt-C-infeksjon hos pasienter som har HCV-genotype-1 med en virusmengde over 2 millioner kopier per ml serum. - Google Patents
Anvendelse av ribavirin og interferon-alfa i kombinasjon for fremstilling av et farmasoytisk preparat for behandling av kronisk hepatitt-C-infeksjon hos pasienter som har HCV-genotype-1 med en virusmengde over 2 millioner kopier per ml serum. Download PDFInfo
- Publication number
- NO330715B1 NO330715B1 NO20005755A NO20005755A NO330715B1 NO 330715 B1 NO330715 B1 NO 330715B1 NO 20005755 A NO20005755 A NO 20005755A NO 20005755 A NO20005755 A NO 20005755A NO 330715 B1 NO330715 B1 NO 330715B1
- Authority
- NO
- Norway
- Prior art keywords
- interferon
- alpha
- weeks
- patients
- hcv
- Prior art date
Links
- 238000011282 treatment Methods 0.000 title claims description 141
- 108010047761 Interferon-alpha Proteins 0.000 title claims description 83
- 102000006992 Interferon-alpha Human genes 0.000 title claims description 83
- 230000003612 virological effect Effects 0.000 title claims description 75
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 title claims description 71
- 229960000329 ribavirin Drugs 0.000 title claims description 71
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 title claims description 71
- 210000002966 serum Anatomy 0.000 title claims description 33
- 208000020403 chronic hepatitis C virus infection Diseases 0.000 title claims description 14
- 239000000825 pharmaceutical preparation Substances 0.000 title claims description 11
- 238000002360 preparation method Methods 0.000 title description 2
- 102100040018 Interferon alpha-2 Human genes 0.000 claims description 25
- 108010079944 Interferon-alpha2b Proteins 0.000 claims description 25
- 102000014150 Interferons Human genes 0.000 claims description 23
- 108010050904 Interferons Proteins 0.000 claims description 23
- 230000000840 anti-viral effect Effects 0.000 claims description 20
- 229940079322 interferon Drugs 0.000 claims description 20
- 208000015181 infectious disease Diseases 0.000 claims description 13
- 238000004519 manufacturing process Methods 0.000 claims description 11
- 230000003442 weekly effect Effects 0.000 claims description 10
- 238000003753 real-time PCR Methods 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 238000002648 combination therapy Methods 0.000 description 105
- 230000004044 response Effects 0.000 description 100
- 230000002459 sustained effect Effects 0.000 description 86
- 229940065638 intron a Drugs 0.000 description 72
- 238000009097 single-agent therapy Methods 0.000 description 36
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 30
- 238000001574 biopsy Methods 0.000 description 25
- 230000006872 improvement Effects 0.000 description 25
- 230000000694 effects Effects 0.000 description 23
- 239000000902 placebo Substances 0.000 description 21
- 229940068196 placebo Drugs 0.000 description 21
- 238000011529 RT qPCR Methods 0.000 description 18
- 208000006454 hepatitis Diseases 0.000 description 16
- 208000018191 liver inflammation Diseases 0.000 description 15
- 238000000034 method Methods 0.000 description 15
- 208000005176 Hepatitis C Diseases 0.000 description 14
- 230000009265 virologic response Effects 0.000 description 13
- 208000006154 Chronic hepatitis C Diseases 0.000 description 11
- 208000010710 hepatitis C virus infection Diseases 0.000 description 11
- 238000012317 liver biopsy Methods 0.000 description 11
- 238000007477 logistic regression Methods 0.000 description 10
- 210000004185 liver Anatomy 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- 241000700605 Viruses Species 0.000 description 8
- 201000010099 disease Diseases 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 206010016654 Fibrosis Diseases 0.000 description 7
- 238000000729 Fisher's exact test Methods 0.000 description 7
- 206010061218 Inflammation Diseases 0.000 description 7
- 230000007882 cirrhosis Effects 0.000 description 7
- 208000019425 cirrhosis of liver Diseases 0.000 description 7
- 230000004054 inflammatory process Effects 0.000 description 7
- 238000010606 normalization Methods 0.000 description 7
- 238000010839 reverse transcription Methods 0.000 description 7
- 108010078049 Interferon alpha-2 Proteins 0.000 description 6
- 238000002560 therapeutic procedure Methods 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 5
- 239000002299 complementary DNA Substances 0.000 description 5
- 238000011156 evaluation Methods 0.000 description 5
- 229920001223 polyethylene glycol Polymers 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- 239000000523 sample Substances 0.000 description 5
- 238000002105 Southern blotting Methods 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- -1 polyethylene Polymers 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 238000007476 Maximum Likelihood Methods 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229960003507 interferon alfa-2b Drugs 0.000 description 3
- 229940047124 interferons Drugs 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 230000002085 persistent effect Effects 0.000 description 3
- MIXCUJKCXRNYFM-UHFFFAOYSA-M sodium;diiodomethanesulfonate;n-propyl-n-[2-(2,4,6-trichlorophenoxy)ethyl]imidazole-1-carboxamide Chemical compound [Na+].[O-]S(=O)(=O)C(I)I.C1=CN=CN1C(=O)N(CCC)CCOC1=C(Cl)C=C(Cl)C=C1Cl MIXCUJKCXRNYFM-UHFFFAOYSA-M 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 238000011269 treatment regimen Methods 0.000 description 3
- 102100023915 Insulin Human genes 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 230000002596 correlated effect Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000012744 immunostaining Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 208000019423 liver disease Diseases 0.000 description 2
- 239000008176 lyophilized powder Substances 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 229920000233 poly(alkylene oxides) Polymers 0.000 description 2
- 229920000136 polysorbate Polymers 0.000 description 2
- 238000002203 pretreatment Methods 0.000 description 2
- 230000002285 radioactive effect Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 238000011144 upstream manufacturing Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- IWUCXVSUMQZMFG-SHXFMUIJSA-N 1-[(3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2,4-triazole-3-carboxamide Chemical compound N1=C(C(=O)N)N=CN1C1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-SHXFMUIJSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- VVLAIYIMMFWRFW-UHFFFAOYSA-N 2-hydroxyethylazanium;acetate Chemical compound CC(O)=O.NCCO VVLAIYIMMFWRFW-UHFFFAOYSA-N 0.000 description 1
- QTWJRLJHJPIABL-UHFFFAOYSA-N 2-methylphenol;3-methylphenol;4-methylphenol Chemical compound CC1=CC=C(O)C=C1.CC1=CC=CC(O)=C1.CC1=CC=CC=C1O QTWJRLJHJPIABL-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 241001227713 Chiron Species 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 108020003215 DNA Probes Proteins 0.000 description 1
- 239000003298 DNA probe Substances 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- SHIBSTMRCDJXLN-UHFFFAOYSA-N Digoxigenin Natural products C1CC(C2C(C3(C)CCC(O)CC3CC2)CC2O)(O)C2(C)C1C1=CC(=O)OC1 SHIBSTMRCDJXLN-UHFFFAOYSA-N 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 241000711549 Hepacivirus C Species 0.000 description 1
- 206010019837 Hepatocellular injury Diseases 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000037581 Persistent Infection Diseases 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 102000007397 Species specific proteins Human genes 0.000 description 1
- 108020005719 Species specific proteins Proteins 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 108010006785 Taq Polymerase Proteins 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229920001400 block copolymer Polymers 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000001268 conjugating effect Effects 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 229930003836 cresol Natural products 0.000 description 1
- 230000001351 cycling effect Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 229940061607 dibasic sodium phosphate Drugs 0.000 description 1
- QONQRTHLHBTMGP-UHFFFAOYSA-N digitoxigenin Natural products CC12CCC(C3(CCC(O)CC3CC3)C)C3C11OC1CC2C1=CC(=O)OC1 QONQRTHLHBTMGP-UHFFFAOYSA-N 0.000 description 1
- SHIBSTMRCDJXLN-KCZCNTNESA-N digoxigenin Chemical compound C1([C@@H]2[C@@]3([C@@](CC2)(O)[C@H]2[C@@H]([C@@]4(C)CC[C@H](O)C[C@H]4CC2)C[C@H]3O)C)=CC(=O)OC1 SHIBSTMRCDJXLN-KCZCNTNESA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 238000003205 genotyping method Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 231100000437 hepatocellular injury Toxicity 0.000 description 1
- 230000008935 histological improvement Effects 0.000 description 1
- 229920001519 homopolymer Polymers 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 229940124622 immune-modulator drug Drugs 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 238000011221 initial treatment Methods 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 229950000038 interferon alfa Drugs 0.000 description 1
- 229960003521 interferon alfa-2a Drugs 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000002665 ion therapy Methods 0.000 description 1
- 238000009533 lab test Methods 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229940045641 monobasic sodium phosphate Drugs 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 230000003041 necroinflammatory effect Effects 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
- 229920001778 nylon Polymers 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229940068965 polysorbates Drugs 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000002250 progressing effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000005057 refrigeration Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000011268 retreatment Methods 0.000 description 1
- 238000012340 reverse transcriptase PCR Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 239000012064 sodium phosphate buffer Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000008227 sterile water for injection Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/21—Interferons [IFN]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/21—Interferons [IFN]
- A61K38/212—IFN-alpha
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Virology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Gastroenterology & Hepatology (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US7956698A | 1998-05-15 | 1998-05-15 | |
PCT/US1999/007037 WO1999059621A1 (en) | 1998-05-15 | 1999-05-13 | Combination therapy comprising ribavirin and interferon alpha in antiviral treatment naive patients having g chronic hepatitis c infection |
Publications (3)
Publication Number | Publication Date |
---|---|
NO20005755D0 NO20005755D0 (no) | 2000-11-14 |
NO20005755L NO20005755L (no) | 2001-01-12 |
NO330715B1 true NO330715B1 (no) | 2011-06-20 |
Family
ID=22151354
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO20005755A NO330715B1 (no) | 1998-05-15 | 2000-11-14 | Anvendelse av ribavirin og interferon-alfa i kombinasjon for fremstilling av et farmasoytisk preparat for behandling av kronisk hepatitt-C-infeksjon hos pasienter som har HCV-genotype-1 med en virusmengde over 2 millioner kopier per ml serum. |
Country Status (23)
Country | Link |
---|---|
EP (3) | EP0956861B1 (xx) |
JP (2) | JP5281726B2 (xx) |
KR (1) | KR100694345B1 (xx) |
CN (1) | CN1230198C (xx) |
AR (1) | AR019551A1 (xx) |
AT (1) | ATE216591T1 (xx) |
AU (2) | AU766597B2 (xx) |
BR (1) | BR9910505A (xx) |
CA (1) | CA2331823A1 (xx) |
CZ (1) | CZ300540B6 (xx) |
DE (1) | DE69901321T2 (xx) |
DK (1) | DK0956861T3 (xx) |
ES (1) | ES2172288T3 (xx) |
HK (1) | HK1021131A1 (xx) |
HU (1) | HU230432B1 (xx) |
IL (3) | IL139220A0 (xx) |
MY (1) | MY129244A (xx) |
NO (1) | NO330715B1 (xx) |
NZ (1) | NZ507621A (xx) |
PT (1) | PT956861E (xx) |
SK (1) | SK288038B6 (xx) |
TW (1) | TWI277424B (xx) |
WO (1) | WO1999059621A1 (xx) |
Families Citing this family (40)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2354536A1 (en) * | 1998-12-18 | 2000-06-29 | Schering Corporation | Ribavirin-pegylated interferon alfa induction hcv combination therapy |
US20040010134A1 (en) | 2000-04-12 | 2004-01-15 | Rosen Craig A. | Albumin fusion proteins |
YU47802A (sh) * | 1999-12-23 | 2006-03-03 | Ribapharm | Postupci i kompozicije za levovirin |
JP4536194B2 (ja) * | 2000-02-17 | 2010-09-01 | 大日本住友製薬株式会社 | 安定な注射用製剤 |
MY164523A (en) | 2000-05-23 | 2017-12-29 | Univ Degli Studi Cagliari | Methods and compositions for treating hepatitis c virus |
YU92202A (sh) | 2000-05-26 | 2006-01-16 | Idenix (Cayman) Limited | Metode i smeše za lečenje flavi virusa i pesti virusa |
AU2002213343A1 (en) * | 2000-10-18 | 2002-04-29 | Schering Corporation | Ribavirin-pegylated interferon alfa HCV combination therapy |
US20030143197A1 (en) * | 2001-11-09 | 2003-07-31 | Moran S. Mark | Method for treating diseases with omega interferon |
DK1463751T3 (da) | 2001-12-21 | 2013-08-26 | Human Genome Sciences Inc | Albuminfusionsproteiner. |
CN104193791A (zh) | 2002-06-28 | 2014-12-10 | 埃迪尼克斯医药公司 | 用于治疗黄病毒感染的修饰的2’和3’-核苷前药 |
AU2003248748A1 (en) | 2002-06-28 | 2004-01-19 | Idenix (Cayman) Limited | 2'-c-methyl-3'-o-l-valine ester ribofuranosyl cytidine for treatment of flaviviridae infections |
US7608600B2 (en) | 2002-06-28 | 2009-10-27 | Idenix Pharmaceuticals, Inc. | Modified 2′ and 3′-nucleoside prodrugs for treating Flaviviridae infections |
CN1849142A (zh) | 2002-11-15 | 2006-10-18 | 埃迪尼克斯(开曼)有限公司 | 2′-支链核苷和黄病毒突变 |
AU2004224575A1 (en) * | 2003-03-28 | 2004-10-07 | Pharmasset Ltd. | Compounds for the treatment of flaviviridae infections |
WO2004110392A2 (en) * | 2003-04-01 | 2004-12-23 | Intermune, Inc. | Compositions and methods for treating coronavirus infection and sars |
BRPI0409484A (pt) * | 2003-04-17 | 2006-05-02 | Ares Trading Sa | interferon beta em sìndrome respiratória aguda severa (sars) |
EP3521297B1 (en) | 2003-05-30 | 2021-12-22 | Gilead Pharmasset LLC | Modified fluorinated nucleoside analogues |
WO2004108151A1 (en) * | 2003-06-09 | 2004-12-16 | Genome Institute Of Singapore | Inhibition of sars coronavirus infection with clinically approved antiviral drugs |
CA2535451A1 (en) * | 2003-08-13 | 2005-02-24 | Howard J. Smith & Associates Pty Ltd. | Method of treating viral infections |
AR045870A1 (es) * | 2003-10-11 | 2005-11-16 | Vertex Pharma | Terapia de combinacion para la infeccion de virus de hepatitis c |
ES2769377T3 (es) | 2004-09-14 | 2020-06-25 | Gilead Pharmasset Llc | Intermedios de D-ribonolactona con sustitución de 2-fluoro-2-alquilo |
TW201424733A (zh) * | 2004-10-29 | 2014-07-01 | Vertex Pharma | 劑量型式 |
CN101448497B (zh) * | 2006-01-09 | 2013-07-10 | 罗马克实验室有限公司 | 包含硝唑尼特、替唑尼特、或其混合物的组合物在制备治疗丙型肝炎药物中的应用 |
US7964580B2 (en) | 2007-03-30 | 2011-06-21 | Pharmasset, Inc. | Nucleoside phosphoramidate prodrugs |
CA2694440A1 (en) | 2007-07-25 | 2009-01-29 | Biolex Therapeutics, Inc. | Controlled release interferon drug products and treatment of hcv infection using same |
TW200946541A (en) | 2008-03-27 | 2009-11-16 | Idenix Pharmaceuticals Inc | Solid forms of an anti-HIV phosphoindole compound |
PA8855801A1 (es) | 2008-12-23 | 2010-07-27 | Sintesis de nucleosidos de purina | |
WO2010075517A2 (en) | 2008-12-23 | 2010-07-01 | Pharmasset, Inc. | Nucleoside analogs |
NZ593648A (en) | 2008-12-23 | 2013-09-27 | Gilead Pharmasset Llc | Nucleoside phosphoramidates |
ES2537785T3 (es) | 2009-05-08 | 2015-06-12 | Sciclone Pharmaceuticals, Inc. | Péptidos de alfa timosina como potenciadores de vacunas |
TWI576352B (zh) | 2009-05-20 | 2017-04-01 | 基利法瑪席特有限責任公司 | 核苷磷醯胺 |
US8618076B2 (en) | 2009-05-20 | 2013-12-31 | Gilead Pharmasset Llc | Nucleoside phosphoramidates |
ES2551944T3 (es) | 2010-03-31 | 2015-11-24 | Gilead Pharmasset Llc | (S)-2-(((S)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihidropirimidin-1-(2H)-il)-4-fluoro-3-hidroxi-4-metiltetrahidrofuran-2-il)metoxi)(fenoxi)fosforil)amino)propanoato de isopropilo cristalino |
MX2013003903A (es) * | 2010-10-05 | 2013-05-20 | Novartis Ag | Nuevos tratamientos de infeccion por el virus de hepatitis c. |
JP6069215B2 (ja) | 2010-11-30 | 2017-02-01 | ギリアド ファーマセット エルエルシー | 化合物 |
KR20190060879A (ko) * | 2011-03-02 | 2019-06-03 | 제롬 쉔타그 | 단독으로 또는 c형 간염 바이러스 감염과 결합되는 간 지방증의 치료를 위한 조성물, 방법 및 진단 |
DE202012013074U1 (de) | 2011-09-16 | 2014-10-29 | Gilead Pharmasset Lcc | Zusammensetzungen zur Behandlung von HCV |
US8889159B2 (en) | 2011-11-29 | 2014-11-18 | Gilead Pharmasset Llc | Compositions and methods for treating hepatitis C virus |
CN104144682A (zh) | 2013-01-31 | 2014-11-12 | 吉利德法莫赛特有限责任公司 | 两个抗病毒化合物的联用制剂 |
ES2900570T3 (es) | 2013-08-27 | 2022-03-17 | Gilead Pharmasset Llc | Formulación de combinación de dos compuestos antivirales |
Family Cites Families (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4211771A (en) | 1971-06-01 | 1980-07-08 | Robins Ronald K | Treatment of human viral diseases with 1-B-D-ribofuranosyl-1,2,4-triazole-3-carboxamide |
US4530901A (en) | 1980-01-08 | 1985-07-23 | Biogen N.V. | Recombinant DNA molecules and their use in producing human interferon-like polypeptides |
US6936694B1 (en) | 1982-05-06 | 2005-08-30 | Intermune, Inc. | Manufacture and expression of large structural genes |
US4492537A (en) | 1982-12-10 | 1985-01-08 | Awerkamp John B | Fluid-operated oil or water well pump |
US4766106A (en) | 1985-06-26 | 1988-08-23 | Cetus Corporation | Solubilization of proteins for pharmaceutical compositions using polymer conjugation |
US4917888A (en) | 1985-06-26 | 1990-04-17 | Cetus Corporation | Solubilization of immunotoxins for pharmaceutical compositions using polymer conjugation |
JP2514950B2 (ja) | 1986-03-10 | 1996-07-10 | エフ・ホフマン―ラ ロシユ アーゲー | 化学修飾蛋白質,その製造法および中間体 |
US5595732A (en) | 1991-03-25 | 1997-01-21 | Hoffmann-La Roche Inc. | Polyethylene-protein conjugates |
US5382657A (en) | 1992-08-26 | 1995-01-17 | Hoffmann-La Roche Inc. | Peg-interferon conjugates |
NZ276943A (en) | 1993-11-10 | 1998-02-26 | Schering Corp Substituted For | Alpha-interferon conjugated to a non-antigenic polymer (preferably a polyalkylene oxide) and its preparation |
US5766582A (en) | 1994-10-11 | 1998-06-16 | Schering Corporation | Stable, aqueous alfa interferon solution formulations |
US5824784A (en) * | 1994-10-12 | 1998-10-20 | Amgen Inc. | N-terminally chemically modified protein compositions and methods |
TW426523B (en) | 1995-04-06 | 2001-03-21 | Hoffmann La Roche | Interferon solution |
US6387365B1 (en) * | 1995-05-19 | 2002-05-14 | Schering Corporation | Combination therapy for chronic hepatitis C infection |
WO1997016204A1 (en) * | 1995-11-02 | 1997-05-09 | Schering Corporation | Continuous low-dose cytokine infusion therapy |
US5908621A (en) * | 1995-11-02 | 1999-06-01 | Schering Corporation | Polyethylene glycol modified interferon therapy |
TW517067B (en) | 1996-05-31 | 2003-01-11 | Hoffmann La Roche | Interferon conjugates |
JP2001514936A (ja) | 1997-08-13 | 2001-09-18 | ボストン サイエンティフィック コーポレイション | 水不溶性薬剤の装填および放出 |
DE69810822T2 (de) * | 1997-09-21 | 2003-11-20 | Schering Corp | Kombinationstherapie zur Entfernung von nachweisbarer HCV-RNS in Patienten mit chronischer Hepatitis C-Infection |
-
1999
- 1999-05-13 ES ES99303729T patent/ES2172288T3/es not_active Expired - Lifetime
- 1999-05-13 BR BR9910505-5A patent/BR9910505A/pt not_active Application Discontinuation
- 1999-05-13 MY MYPI99001891A patent/MY129244A/en unknown
- 1999-05-13 EP EP99303729A patent/EP0956861B1/en not_active Expired - Lifetime
- 1999-05-13 CA CA002331823A patent/CA2331823A1/en not_active Abandoned
- 1999-05-13 HU HU0103423A patent/HU230432B1/hu unknown
- 1999-05-13 EP EP10181927A patent/EP2305287A1/en not_active Withdrawn
- 1999-05-13 AU AU38600/99A patent/AU766597B2/en not_active Withdrawn - After Issue
- 1999-05-13 EP EP01130613A patent/EP1213029A1/en not_active Withdrawn
- 1999-05-13 PT PT99303729T patent/PT956861E/pt unknown
- 1999-05-13 IL IL13922099A patent/IL139220A0/xx unknown
- 1999-05-13 AT AT99303729T patent/ATE216591T1/de active
- 1999-05-13 DE DE69901321T patent/DE69901321T2/de not_active Expired - Lifetime
- 1999-05-13 DK DK99303729T patent/DK0956861T3/da active
- 1999-05-13 CZ CZ20004177A patent/CZ300540B6/cs not_active IP Right Cessation
- 1999-05-13 SK SK1710-2000A patent/SK288038B6/sk not_active IP Right Cessation
- 1999-05-13 TW TW088107774A patent/TWI277424B/zh not_active IP Right Cessation
- 1999-05-13 CN CNB998085960A patent/CN1230198C/zh not_active Expired - Lifetime
- 1999-05-13 WO PCT/US1999/007037 patent/WO1999059621A1/en active Application Filing
- 1999-05-13 KR KR1020007012784A patent/KR100694345B1/ko not_active IP Right Cessation
- 1999-05-13 JP JP2000549285A patent/JP5281726B2/ja not_active Expired - Lifetime
- 1999-05-14 AR ARP990102303A patent/AR019551A1/es unknown
- 1999-11-20 HK HK99105377A patent/HK1021131A1/xx not_active IP Right Cessation
-
2000
- 2000-10-18 NZ NZ507621A patent/NZ507621A/xx not_active IP Right Cessation
- 2000-10-23 IL IL139220A patent/IL139220A/en not_active IP Right Cessation
- 2000-11-14 NO NO20005755A patent/NO330715B1/no not_active IP Right Cessation
-
2005
- 2005-10-10 AU AU2005220271A patent/AU2005220271B9/en not_active Expired
-
2010
- 2010-07-27 IL IL207259A patent/IL207259A/en not_active IP Right Cessation
-
2011
- 2011-04-07 JP JP2011085606A patent/JP2011173898A/ja not_active Withdrawn
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
NO330715B1 (no) | Anvendelse av ribavirin og interferon-alfa i kombinasjon for fremstilling av et farmasoytisk preparat for behandling av kronisk hepatitt-C-infeksjon hos pasienter som har HCV-genotype-1 med en virusmengde over 2 millioner kopier per ml serum. | |
US6472373B1 (en) | Combination therapy for eradicating detectable HCV-RNA in antiviral treatment naive patients having chronic hepatitis C infection | |
US6172046B1 (en) | Combination therapy for eradicating detectable HCV-RNA in patients having chronic Hepatitis C infection | |
AU749924B2 (en) | Combination therapy for eradicating detectable HCV-RNA in patients having chronic hepatitis C infection | |
US20020127203A1 (en) | Ribavirin-pegylated interferon alfa HCV combination therapy | |
WO2000037110A2 (en) | Ribavirin-pegylated interferon alfa induction hcv combination therapy | |
US6824768B2 (en) | Ribavirin-pegylated interferon alfa induction HCV combination therapy | |
WO2000037097A1 (en) | Ribavirin-interferon alfa induction hcv combination therapy | |
MXPA00011198A (en) | Combination therapy comprising ribavirin and interferon alpha in antiviral treatment naive patients having g chronic hepatitis c infection | |
MXPA98007284A (en) | Combination therapy to eradicate vhc-rna detectable in patients who have infection of hepatitis c cron | |
AU2005218024A1 (en) | Combination therapy for eradicating detectable HCV-RNA in patients having chronic Hepatitis C infection |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
CHAD | Change of the owner's name or address (par. 44 patent law, par. patentforskriften) |
Owner name: MERCK SHARP AND DOHME CORP Free format text: NEW ADDRESS: 126 EAST LINCOLN AVENUE, US-NJ07065 RAHWAY, US |
|
MK1K | Patent expired |