DE69737126T2 - Hbv mutanten und methoden für deren nachweis - Google Patents
Hbv mutanten und methoden für deren nachweis Download PDFInfo
- Publication number
- DE69737126T2 DE69737126T2 DE69737126T DE69737126T DE69737126T2 DE 69737126 T2 DE69737126 T2 DE 69737126T2 DE 69737126 T DE69737126 T DE 69737126T DE 69737126 T DE69737126 T DE 69737126T DE 69737126 T2 DE69737126 T2 DE 69737126T2
- Authority
- DE
- Germany
- Prior art keywords
- hbv
- mutation
- polymerase
- amino acid
- dna
- 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.)
- Expired - Lifetime
Links
- 238000000034 method Methods 0.000 title claims description 17
- 230000002829 reductive effect Effects 0.000 claims abstract description 13
- 239000002777 nucleoside Substances 0.000 claims abstract description 8
- 150000003833 nucleoside derivatives Chemical class 0.000 claims abstract description 8
- GGXKWVWZWMLJEH-UHFFFAOYSA-N famcyclovir Chemical compound N1=C(N)N=C2N(CCC(COC(=O)C)COC(C)=O)C=NC2=C1 GGXKWVWZWMLJEH-UHFFFAOYSA-N 0.000 claims description 41
- 230000035772 mutation Effects 0.000 claims description 41
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 claims description 34
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 claims description 33
- 229960004396 famciclovir Drugs 0.000 claims description 28
- 150000001413 amino acids Chemical class 0.000 claims description 23
- 108700024845 Hepatitis B virus P Proteins 0.000 claims description 15
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 13
- 229940127073 nucleoside analogue Drugs 0.000 claims description 13
- 230000035945 sensitivity Effects 0.000 claims description 13
- 108090000623 proteins and genes Proteins 0.000 claims description 10
- 125000000539 amino acid group Chemical group 0.000 claims description 8
- JNTOCHDNEULJHD-UHFFFAOYSA-N Penciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(CCC(CO)CO)C=N2 JNTOCHDNEULJHD-UHFFFAOYSA-N 0.000 claims description 7
- 230000008859 change Effects 0.000 claims description 7
- 238000012216 screening Methods 0.000 claims description 7
- 238000012163 sequencing technique Methods 0.000 claims description 7
- 229960001627 lamivudine Drugs 0.000 claims description 6
- JTEGQNOMFQHVDC-NKWVEPMBSA-N lamivudine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 claims description 6
- 229960001179 penciclovir Drugs 0.000 claims description 6
- 102220512213 Adenine DNA glycosylase_L526M_mutation Human genes 0.000 claims description 5
- 239000003443 antiviral agent Substances 0.000 claims description 3
- 230000003247 decreasing effect Effects 0.000 claims description 3
- 108020004999 messenger RNA Proteins 0.000 claims description 3
- 238000009396 hybridization Methods 0.000 claims description 2
- 108091033319 polynucleotide Proteins 0.000 claims 3
- 102000040430 polynucleotide Human genes 0.000 claims 3
- 239000002157 polynucleotide Substances 0.000 claims 3
- 230000000840 anti-viral effect Effects 0.000 abstract description 14
- 238000003556 assay Methods 0.000 abstract description 8
- 208000002672 hepatitis B Diseases 0.000 abstract description 6
- 230000003612 virological effect Effects 0.000 abstract description 6
- 238000012544 monitoring process Methods 0.000 abstract description 4
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 3
- 230000001900 immune effect Effects 0.000 abstract description 3
- 230000036961 partial effect Effects 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 2
- 230000001747 exhibiting effect Effects 0.000 abstract 2
- 229940124597 therapeutic agent Drugs 0.000 abstract 1
- 241000700721 Hepatitis B virus Species 0.000 description 79
- 238000011282 treatment Methods 0.000 description 31
- 235000001014 amino acid Nutrition 0.000 description 25
- 108020004414 DNA Proteins 0.000 description 24
- 229940024606 amino acid Drugs 0.000 description 24
- IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 description 14
- 238000002560 therapeutic procedure Methods 0.000 description 14
- 238000003752 polymerase chain reaction Methods 0.000 description 13
- 238000012360 testing method Methods 0.000 description 13
- 239000002773 nucleotide Substances 0.000 description 10
- 125000003729 nucleotide group Chemical group 0.000 description 10
- 239000003795 chemical substances by application Substances 0.000 description 9
- 230000000694 effects Effects 0.000 description 8
- 210000002966 serum Anatomy 0.000 description 8
- 238000001514 detection method Methods 0.000 description 7
- 208000015181 infectious disease Diseases 0.000 description 7
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 7
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 6
- 108700026244 Open Reading Frames Proteins 0.000 description 6
- KGSIOVLUJYQLKR-UHFFFAOYSA-N [[4-(2-amino-6-oxo-3h-purin-9-yl)-2-(hydroxymethyl)butoxy]-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound N1C(N)=NC(=O)C2=C1N(CCC(CO)COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C=N2 KGSIOVLUJYQLKR-UHFFFAOYSA-N 0.000 description 6
- 239000000427 antigen Substances 0.000 description 6
- 102000036639 antigens Human genes 0.000 description 6
- 108091007433 antigens Proteins 0.000 description 6
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 5
- 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 5
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 5
- 108010082126 Alanine transaminase Proteins 0.000 description 5
- 241000700605 Viruses Species 0.000 description 5
- 230000003321 amplification Effects 0.000 description 5
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 5
- 238000003199 nucleic acid amplification method Methods 0.000 description 5
- 238000002054 transplantation Methods 0.000 description 5
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 4
- 108091035707 Consensus sequence Proteins 0.000 description 3
- 239000004471 Glycine Substances 0.000 description 3
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 3
- 241000700584 Simplexvirus Species 0.000 description 3
- 230000000692 anti-sense effect Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000010367 cloning Methods 0.000 description 3
- 229960002963 ganciclovir Drugs 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 238000012423 maintenance Methods 0.000 description 3
- 229930182817 methionine Natural products 0.000 description 3
- 230000010076 replication Effects 0.000 description 3
- 241000272525 Anas platyrhynchos Species 0.000 description 2
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 102000053602 DNA Human genes 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 238000012300 Sequence Analysis Methods 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- GXDLGHLJTHMDII-WISUUJSJSA-N Thr-Ser Chemical group C[C@@H](O)[C@H](N)C(=O)N[C@@H](CO)C(O)=O GXDLGHLJTHMDII-WISUUJSJSA-N 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 241001492404 Woodchuck hepatitis virus Species 0.000 description 2
- 101150003160 X gene Proteins 0.000 description 2
- 235000009582 asparagine Nutrition 0.000 description 2
- 229960001230 asparagine Drugs 0.000 description 2
- 210000001124 body fluid Anatomy 0.000 description 2
- 239000010839 body fluid Substances 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 238000003018 immunoassay Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000011866 long-term treatment Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000007899 nucleic acid hybridization Methods 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- ZJAOAACCNHFJAH-UHFFFAOYSA-N phosphonoformic acid Chemical compound OC(=O)P(O)(O)=O ZJAOAACCNHFJAH-UHFFFAOYSA-N 0.000 description 2
- 238000002203 pretreatment Methods 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000003757 reverse transcription PCR Methods 0.000 description 2
- 238000011269 treatment regimen Methods 0.000 description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
- SNBCLPGEMZEWLU-QXFUBDJGSA-N 2-chloro-n-[[(2r,3s,5r)-3-hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl]acetamide Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CNC(=O)CCl)[C@@H](O)C1 SNBCLPGEMZEWLU-QXFUBDJGSA-N 0.000 description 1
- NKDFYOWSKOHCCO-YPVLXUMRSA-N 20-hydroxyecdysone Chemical compound C1[C@@H](O)[C@@H](O)C[C@]2(C)[C@@H](CC[C@@]3([C@@H]([C@@](C)(O)[C@H](O)CCC(C)(O)C)CC[C@]33O)C)C3=CC(=O)[C@@H]21 NKDFYOWSKOHCCO-YPVLXUMRSA-N 0.000 description 1
- XWHHYOYVRVGJJY-QMMMGPOBSA-N 4-fluoro-L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(F)C=C1 XWHHYOYVRVGJJY-QMMMGPOBSA-N 0.000 description 1
- 208000007788 Acute Liver Failure Diseases 0.000 description 1
- 206010000804 Acute hepatic failure Diseases 0.000 description 1
- 241000242757 Anthozoa Species 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 101710132601 Capsid protein Proteins 0.000 description 1
- 235000014653 Carica parviflora Nutrition 0.000 description 1
- 102000012410 DNA Ligases Human genes 0.000 description 1
- 108010061982 DNA Ligases Proteins 0.000 description 1
- 230000004543 DNA replication Effects 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010019663 Hepatic failure Diseases 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 208000005331 Hepatitis D Diseases 0.000 description 1
- 206010019754 Hepatitis cholestatic Diseases 0.000 description 1
- 208000037262 Hepatitis delta Diseases 0.000 description 1
- 101100020228 Homo sapiens KLHL31 gene Proteins 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 102100033584 Kelch-like protein 31 Human genes 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 108010059712 Pronase Proteins 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 229930006000 Sucrose Natural products 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
- 108010006785 Taq Polymerase Proteins 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- YSGAPESOXHFTQY-IHRRRGAJSA-N Tyr-Met-Asp Chemical compound CSCC[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N YSGAPESOXHFTQY-IHRRRGAJSA-N 0.000 description 1
- 206010057362 Underdose Diseases 0.000 description 1
- 206010058874 Viraemia Diseases 0.000 description 1
- 108700005077 Viral Genes Proteins 0.000 description 1
- 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 1
- 231100000836 acute liver failure Toxicity 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 229940121357 antivirals Drugs 0.000 description 1
- 108010040443 aspartyl-aspartic acid Proteins 0.000 description 1
- 108010058966 bacteriophage T7 induced DNA polymerase Proteins 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- 108020001778 catalytic domains Proteins 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000009104 chemotherapy regimen Methods 0.000 description 1
- 231100000838 cholestatic hepatitis Toxicity 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- SUYVUBYJARFZHO-UHFFFAOYSA-N dATP Natural products C1=NC=2C(N)=NC=NC=2N1C1CC(O)C(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 SUYVUBYJARFZHO-UHFFFAOYSA-N 0.000 description 1
- SUYVUBYJARFZHO-RRKCRQDMSA-N dATP Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 SUYVUBYJARFZHO-RRKCRQDMSA-N 0.000 description 1
- HAAZLUGHYHWQIW-KVQBGUIXSA-N dGTP Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 HAAZLUGHYHWQIW-KVQBGUIXSA-N 0.000 description 1
- NHVNXKFIZYSCEB-XLPZGREQSA-N dTTP Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)C1 NHVNXKFIZYSCEB-XLPZGREQSA-N 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
- 229960005542 ethidium bromide Drugs 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229960005102 foscarnet Drugs 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 208000005252 hepatitis A Diseases 0.000 description 1
- 208000029570 hepatitis D virus infection Diseases 0.000 description 1
- 230000008935 histological improvement Effects 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 231100000835 liver failure Toxicity 0.000 description 1
- 208000007903 liver failure Diseases 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 238000012153 long-term therapy Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- ADKOXSOCTOWDOP-UHFFFAOYSA-L magnesium;aluminum;dihydroxide;trihydrate Chemical compound O.O.O.[OH-].[OH-].[Mg+2].[Al] ADKOXSOCTOWDOP-UHFFFAOYSA-L 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- MVMXJBMAGBRAHD-UHFFFAOYSA-N picoperine Chemical compound C=1C=CC=NC=1CN(C=1C=CC=CC=1)CCN1CCCCC1 MVMXJBMAGBRAHD-UHFFFAOYSA-N 0.000 description 1
- -1 plants Natural products 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 102000054765 polymorphisms of proteins Human genes 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- FQENQNTWSFEDLI-UHFFFAOYSA-J sodium diphosphate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]P([O-])(=O)OP([O-])([O-])=O FQENQNTWSFEDLI-UHFFFAOYSA-J 0.000 description 1
- 229940048086 sodium pyrophosphate Drugs 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 235000019818 tetrasodium diphosphate Nutrition 0.000 description 1
- 239000001577 tetrasodium phosphonato phosphate Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 235000011178 triphosphate Nutrition 0.000 description 1
- 239000001226 triphosphate Substances 0.000 description 1
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 1
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/10—Transferases (2.)
- C12N9/12—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
- C12N9/1241—Nucleotidyltransferases (2.7.7)
- C12N9/1276—RNA-directed DNA polymerase (2.7.7.49), i.e. reverse transcriptase or telomerase
-
- 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
- C12N2730/00—Reverse transcribing DNA viruses
- C12N2730/00011—Details
- C12N2730/10011—Hepadnaviridae
- C12N2730/10111—Orthohepadnavirus, e.g. hepatitis B virus
- C12N2730/10122—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Virology (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Enzymes And Modification Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AUPO3519A AUPO351996A0 (en) | 1996-11-08 | 1996-11-08 | Viral variants and methods for detecting same |
| AUPO351996 | 1996-11-08 | ||
| PCT/AU1997/000520 WO1998021317A1 (en) | 1996-11-08 | 1997-08-15 | Viral variants and methods for detecting same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69737126D1 DE69737126D1 (de) | 2007-02-01 |
| DE69737126T2 true DE69737126T2 (de) | 2007-10-04 |
Family
ID=3797830
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69737126T Expired - Lifetime DE69737126T2 (de) | 1996-11-08 | 1997-08-15 | Hbv mutanten und methoden für deren nachweis |
Country Status (9)
| Country | Link |
|---|---|
| US (4) | US6555311B1 (enExample) |
| EP (1) | EP0964916B1 (enExample) |
| JP (4) | JP2001503277A (enExample) |
| AT (1) | ATE348880T1 (enExample) |
| AU (1) | AUPO351996A0 (enExample) |
| CA (1) | CA2270178C (enExample) |
| DE (1) | DE69737126T2 (enExample) |
| ES (1) | ES2279542T3 (enExample) |
| WO (1) | WO1998021317A1 (enExample) |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA973367B (en) | 1996-04-19 | 1997-11-18 | Innogenetics Nv | Method for typing and detecting HBV. |
| USRE40233E1 (en) | 1996-11-08 | 2008-04-08 | Melbourne Health | Viral variants and methods for detecting same |
| AUPO351996A0 (en) * | 1996-11-08 | 1996-12-05 | Western Health Care Network | Viral variants and methods for detecting same |
| AUPP706098A0 (en) * | 1998-11-11 | 1998-12-03 | North Western Health Care Network | Biological compositions, components thereof and uses therefor |
| AUPP967999A0 (en) * | 1999-04-09 | 1999-05-06 | North Western Health Care Network | Viral variants |
| AR028149A1 (es) * | 1999-07-08 | 2003-04-30 | Innogenetics Nv | Deteccion de la resistencia a los farmacos contra la hepatitis b |
| AUPQ810900A0 (en) | 2000-06-09 | 2000-07-06 | Austin and Repatriation Medical Centre, The | Viral variants and methods of using same |
| SG90149A1 (en) * | 2000-07-18 | 2002-07-23 | Government Of The Republic Of | Diagnostic assay |
| US6697858B1 (en) * | 2000-08-14 | 2004-02-24 | Telephony@Work | Call center |
| US7405039B2 (en) | 2002-02-07 | 2008-07-29 | Austin Health | Viral variants with altered susceptibility to nucleoside analogs and uses thereof |
| JP4502642B2 (ja) * | 2002-02-07 | 2010-07-14 | メルボルン ヘルス | ヌクレオシドアナログに対する感受性の変化を有するウイルス変種およびその使用 |
| AU2002308114A1 (en) | 2002-03-29 | 2003-10-13 | Innogenetics N.V. | Hbv drug resistance drug resistance detection methods |
| AU2003213874B2 (en) * | 2002-04-12 | 2008-12-04 | Austin Health | Hepatitis B viral variants with redused susceptibility to nucleoside analogs and uses thereof |
| EP2033967A1 (en) | 2002-04-12 | 2009-03-11 | Melbourne Health | Hepatitis B viral variants with reduced susceptibility to nucleoside analogs and uses thereof |
| EP2292801B1 (en) | 2002-06-14 | 2018-08-08 | Gen-Probe Incorporated | Compositions and methods for detecting hepatitis b virus |
| US20050053916A1 (en) * | 2002-10-01 | 2005-03-10 | Korba Brent E. | Diagnostic for long term response of HBV carrier to 3TC therapy |
| WO2006097285A1 (en) | 2005-03-15 | 2006-09-21 | Innogenetics N.V. | Hepatitis-b viral variants with reduced susceptibility to nucleoside analogs and uses thereof |
| ES2470318T3 (es) | 2005-03-15 | 2014-06-23 | Rheinische Friedrich-Wilhelms-Universit�T Bonn | Variantes del virus de la hepatitis B resistentes a ciertos análogos nucle�sidos, pero sensibles a otros, y usos de las mismas |
| US8211443B2 (en) | 2005-04-08 | 2012-07-03 | Melbourne Health | Variants of hepatitis B virus with resistance to anti-viral nucleoside agents and applications thereof |
| EP1874923A4 (en) | 2005-04-08 | 2010-08-04 | Melbourne Health | VARIANTS OF THE HEPATITIS B VIRUS WITH RESISTANCE TO ANTIVIRAL NUCLEOSIDAGENTS AND APPLICATIONS THEREOF |
| KR100790226B1 (ko) | 2005-11-03 | 2008-01-02 | 연세대학교 산학협력단 | 독성 간염 유발 감수성을 검출하는 방법 |
| US20230148447A9 (en) | 2008-12-11 | 2023-05-11 | Pacific Biosciences Of California, Inc. | Classification of nucleic acid templates |
| US9175338B2 (en) * | 2008-12-11 | 2015-11-03 | Pacific Biosciences Of California, Inc. | Methods for identifying nucleic acid modifications |
| EP2370598B1 (en) * | 2008-12-11 | 2017-02-15 | Pacific Biosciences Of California, Inc. | Classification of nucleic acid templates |
| US9611510B2 (en) | 2011-04-06 | 2017-04-04 | The University Of Chicago | Composition and methods related to modification of 5-methylcytosine (5-mC) |
| US9238836B2 (en) | 2012-03-30 | 2016-01-19 | Pacific Biosciences Of California, Inc. | Methods and compositions for sequencing modified nucleic acids |
| US9175348B2 (en) | 2012-04-24 | 2015-11-03 | Pacific Biosciences Of California, Inc. | Identification of 5-methyl-C in nucleic acid templates |
| CN115003685A (zh) * | 2019-12-07 | 2022-09-02 | Isa制药有限公司 | 乙型肝炎病毒相关疾病的治疗 |
| CN115561456B (zh) * | 2021-07-01 | 2025-10-31 | 黄温雅 | 体外定量b肝病毒大表面蛋白的套组以及用于处理肝病的生物指标组及单株抗体组 |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5595739A (en) * | 1993-05-07 | 1997-01-21 | Abbott Laboratories | Hepatitis B virus mutants, reagents and methods for detection |
| ZA973367B (en) * | 1996-04-19 | 1997-11-18 | Innogenetics Nv | Method for typing and detecting HBV. |
| USRE40233E1 (en) * | 1996-11-08 | 2008-04-08 | Melbourne Health | Viral variants and methods for detecting same |
| AUPO351996A0 (en) * | 1996-11-08 | 1996-12-05 | Western Health Care Network | Viral variants and methods for detecting same |
| AUPP967999A0 (en) * | 1999-04-09 | 1999-05-06 | North Western Health Care Network | Viral variants |
| AUPQ810900A0 (en) * | 2000-06-09 | 2000-07-06 | Austin and Repatriation Medical Centre, The | Viral variants and methods of using same |
| US7405039B2 (en) * | 2002-02-07 | 2008-07-29 | Austin Health | Viral variants with altered susceptibility to nucleoside analogs and uses thereof |
| AU2002308114A1 (en) * | 2002-03-29 | 2003-10-13 | Innogenetics N.V. | Hbv drug resistance drug resistance detection methods |
| EP2033967A1 (en) * | 2002-04-12 | 2009-03-11 | Melbourne Health | Hepatitis B viral variants with reduced susceptibility to nucleoside analogs and uses thereof |
| JP2007509614A (ja) * | 2003-10-21 | 2007-04-19 | メルボルン ヘルス | Ｈｂｖ変種の検出および適用 |
| ES2470318T3 (es) * | 2005-03-15 | 2014-06-23 | Rheinische Friedrich-Wilhelms-Universit�T Bonn | Variantes del virus de la hepatitis B resistentes a ciertos análogos nucle�sidos, pero sensibles a otros, y usos de las mismas |
| WO2006097285A1 (en) * | 2005-03-15 | 2006-09-21 | Innogenetics N.V. | Hepatitis-b viral variants with reduced susceptibility to nucleoside analogs and uses thereof |
| EP1874923A4 (en) * | 2005-04-08 | 2010-08-04 | Melbourne Health | VARIANTS OF THE HEPATITIS B VIRUS WITH RESISTANCE TO ANTIVIRAL NUCLEOSIDAGENTS AND APPLICATIONS THEREOF |
| US8211443B2 (en) * | 2005-04-08 | 2012-07-03 | Melbourne Health | Variants of hepatitis B virus with resistance to anti-viral nucleoside agents and applications thereof |
| CN101548014B (zh) * | 2006-06-06 | 2012-07-04 | 墨尔本保健公司 | 抗病毒抗性突变的检测和应用 |
-
1996
- 1996-11-08 AU AUPO3519A patent/AUPO351996A0/en not_active Abandoned
-
1997
- 1997-08-15 WO PCT/AU1997/000520 patent/WO1998021317A1/en not_active Ceased
- 1997-08-15 CA CA2270178A patent/CA2270178C/en not_active Expired - Lifetime
- 1997-08-15 EP EP97934385A patent/EP0964916B1/en not_active Expired - Lifetime
- 1997-08-15 AT AT97934385T patent/ATE348880T1/de active
- 1997-08-15 DE DE69737126T patent/DE69737126T2/de not_active Expired - Lifetime
- 1997-08-15 ES ES97934385T patent/ES2279542T3/es not_active Expired - Lifetime
- 1997-08-15 JP JP52194498A patent/JP2001503277A/ja not_active Withdrawn
-
1999
- 1999-05-06 US US09/306,420 patent/US6555311B1/en not_active Ceased
-
2002
- 2002-10-01 US US10/260,451 patent/US20030124096A1/en not_active Abandoned
-
2008
- 2008-01-24 JP JP2008014075A patent/JP2008154590A/ja active Pending
- 2008-05-09 US US12/117,869 patent/US20100203506A1/en not_active Abandoned
-
2011
- 2011-12-16 JP JP2011276121A patent/JP2012055322A/ja active Pending
-
2012
- 2012-07-12 US US13/547,392 patent/US20130171620A1/en not_active Abandoned
-
2015
- 2015-02-02 JP JP2015018686A patent/JP2015107127A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| ES2279542T3 (es) | 2007-08-16 |
| EP0964916B1 (en) | 2006-12-20 |
| US6555311B1 (en) | 2003-04-29 |
| JP2015107127A (ja) | 2015-06-11 |
| EP0964916A4 (en) | 2001-09-26 |
| CA2270178A1 (en) | 1998-05-22 |
| EP0964916A1 (en) | 1999-12-22 |
| CA2270178C (en) | 2012-06-12 |
| WO1998021317A1 (en) | 1998-05-22 |
| US20030124096A1 (en) | 2003-07-03 |
| JP2012055322A (ja) | 2012-03-22 |
| AUPO351996A0 (en) | 1996-12-05 |
| US20130171620A1 (en) | 2013-07-04 |
| HK1027374A1 (en) | 2001-01-12 |
| JP2001503277A (ja) | 2001-03-13 |
| ATE348880T1 (de) | 2007-01-15 |
| JP2008154590A (ja) | 2008-07-10 |
| DE69737126D1 (de) | 2007-02-01 |
| US20100203506A1 (en) | 2010-08-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE69737126T2 (de) | Hbv mutanten und methoden für deren nachweis | |
| Tillmann et al. | Mutational pattern of hepatitis B virus on sequential therapy with famciclovir and lamivudine in patients with hepatitis B virus reinfection occurring under HBIg immunoglobulin after liver transplantation | |
| DE3049831C2 (de) | Vektoren enthaltend eine f}r das Oberfl{chenantigen des Hepatites B-Virus kodierende Nucleotidsequenz, Verwendung dieser Vektoren zur Herstellung von Peptiden, Impfstoffe enhaltend dabei erhaltende Peptide als Antigen | |
| DE3788902T3 (de) | Hepatitis-Delta-Diagnostika und Impfstoffe, ihre Herstellung und Verwendung. | |
| DE69637264T2 (de) | Virales Material und Multiple-Sklerose assoziierte Nukleotidfragmente mit diagnostischen, prophylaktischen und therapeutischen Verwendungen | |
| DE69533863T2 (de) | MSRV1 Virus der mit Multipler Sklerose verbunden ist, seine nukleären Bestandteile und Verwendungen | |
| DE69324678T2 (de) | Verfahren zur typisierung von hcv-isolaten | |
| DE69435023T2 (de) | Sequenzen der genotype des hepatitis-c-virus sowie ihre verwendung als arzneimittel und diagnostika | |
| DE3886363T3 (de) | NANBV-Diagnostika | |
| DE69130071T3 (de) | Zusammensetzung verwendbar als therapeutisches mittel gegen chronische virale leberkrankheiten | |
| DE69028951T2 (de) | Oligonukleotiden-Sequenzen zur Amplifizierung von HIV-2 und SIV Retrovirusgenomen, ihre Verwendung zur In-vitro-Diagnostik von durch diese Viren verursachten Infektionen | |
| DE60034673T2 (de) | Screeningverfahren auf Anti-Protease Resistenz HIV-2-haltiger Zellen, ausgehend von biologischen Patientenproben | |
| DE69122098T2 (de) | Methoden zur verhinderung von viralen replikationen | |
| DE69738419T2 (de) | Testverfahren zur suche heteroduplexer dna (hta) für die genotypisierung von hcv | |
| AU734831C (en) | Viral variants and methods for detecting same | |
| DE3853672T2 (de) | Nichtzurückschlagende RNS-Viren. | |
| EP1638994B1 (de) | NEUE OBERFLÄCHENPROTEIN- (HbsAg-) VARIANTE DES HEPATITIS B VIRUS | |
| EP1638995A1 (de) | NEUE OBERFLÄCHENPROTEIN-(HBsAG-) VARIANTE DES HEPATITIS B VIRUS | |
| DE602004005026T2 (de) | RT-PCR-Verfahren zum quantitativen Nachweis von HDV | |
| Robinson et al. | The hepadna viruses of animals | |
| DE69726602T2 (de) | Hepatitis b inhibitoren | |
| USRE40233E1 (en) | Viral variants and methods for detecting same | |
| WO1982003408A1 (fr) | Procede de preparation d'un adn-hybride, contenant le genome complementaire du virus de l'hepatite a, l'adn-hybride lui-meme, le vecteur plasmidique le contenant, les proteines specifiques du virus codees par l'adn-hybride et des vaccins les contenant | |
| EP2220493A1 (de) | Neue oberflächen-protein-mutante des hepatitis b virus hbv surface antigen (hbsag) | |
| AU780978B2 (en) | Viral variants and methods for detecting same |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition |