JP2006502704A - Hiv調節/アクセサリータンパク質の融合タンパク質 - Google Patents
Hiv調節/アクセサリータンパク質の融合タンパク質 Download PDFInfo
- Publication number
- JP2006502704A JP2006502704A JP2004506348A JP2004506348A JP2006502704A JP 2006502704 A JP2006502704 A JP 2006502704A JP 2004506348 A JP2004506348 A JP 2004506348A JP 2004506348 A JP2004506348 A JP 2004506348A JP 2006502704 A JP2006502704 A JP 2006502704A
- Authority
- JP
- Japan
- Prior art keywords
- hiv
- fusion protein
- vector
- protein
- proteins
- 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.)
- Pending
Links
- 108020001507 fusion proteins Proteins 0.000 title claims abstract description 116
- 102000037865 fusion proteins Human genes 0.000 title claims abstract description 116
- 230000001105 regulatory effect Effects 0.000 title claims description 19
- 230000012743 protein tagging Effects 0.000 title 1
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 129
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 109
- 239000013598 vector Substances 0.000 claims abstract description 62
- 108010048209 Human Immunodeficiency Virus Proteins Proteins 0.000 claims abstract description 59
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 52
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 51
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 51
- 229960005486 vaccine Drugs 0.000 claims abstract description 30
- 238000000034 method Methods 0.000 claims abstract description 14
- 208000031886 HIV Infections Diseases 0.000 claims abstract description 9
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract 9
- 150000001413 amino acids Chemical class 0.000 claims description 65
- 108091026890 Coding region Proteins 0.000 claims description 26
- 210000004027 cell Anatomy 0.000 claims description 19
- 108020004414 DNA Proteins 0.000 claims description 17
- 230000003612 virological effect Effects 0.000 claims description 17
- 239000013603 viral vector Substances 0.000 claims description 16
- 241000700618 Vaccinia virus Species 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 241001465754 Metazoa Species 0.000 claims description 5
- 208000037357 HIV infectious disease Diseases 0.000 claims description 4
- 210000004102 animal cell Anatomy 0.000 claims description 4
- 230000004927 fusion Effects 0.000 claims description 4
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims description 4
- 108010089520 pol Gene Products Proteins 0.000 claims description 4
- 102100034353 Integrase Human genes 0.000 claims description 3
- 238000004113 cell culture Methods 0.000 claims description 3
- 108010078428 env Gene Products Proteins 0.000 claims description 3
- 241000587120 Vaccinia virus Ankara Species 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 230000036961 partial effect Effects 0.000 abstract description 2
- 238000011321 prophylaxis Methods 0.000 abstract 1
- 235000018102 proteins Nutrition 0.000 description 99
- 241000725303 Human immunodeficiency virus Species 0.000 description 73
- 101710149136 Protein Vpr Proteins 0.000 description 33
- 101710201961 Virion infectivity factor Proteins 0.000 description 27
- 101710149951 Protein Tat Proteins 0.000 description 25
- 235000001014 amino acid Nutrition 0.000 description 25
- 101000650854 Homo sapiens Small glutamine-rich tetratricopeptide repeat-containing protein alpha Proteins 0.000 description 24
- 230000000694 effects Effects 0.000 description 18
- 230000002829 reductive effect Effects 0.000 description 18
- 241000700605 Viruses Species 0.000 description 16
- 238000000137 annealing Methods 0.000 description 14
- 238000003776 cleavage reaction Methods 0.000 description 13
- 108091034117 Oligonucleotide Proteins 0.000 description 12
- 239000012634 fragment Substances 0.000 description 12
- 238000003752 polymerase chain reaction Methods 0.000 description 12
- 230000007017 scission Effects 0.000 description 12
- 108020004705 Codon Proteins 0.000 description 9
- 108091006104 gene-regulatory proteins Proteins 0.000 description 9
- 102000034356 gene-regulatory proteins Human genes 0.000 description 9
- 230000028993 immune response Effects 0.000 description 9
- 230000003993 interaction Effects 0.000 description 9
- 208000030507 AIDS Diseases 0.000 description 8
- -1 Rev Proteins 0.000 description 8
- 101150040614 vpx gene Proteins 0.000 description 8
- 108091005804 Peptidases Proteins 0.000 description 7
- 239000004365 Protease Substances 0.000 description 7
- 230000002238 attenuated effect Effects 0.000 description 7
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 6
- 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 6
- 230000001413 cellular effect Effects 0.000 description 6
- 238000010367 cloning Methods 0.000 description 6
- 210000005260 human cell Anatomy 0.000 description 6
- 208000015181 infectious disease Diseases 0.000 description 6
- 238000003780 insertion Methods 0.000 description 6
- 230000037431 insertion Effects 0.000 description 6
- 230000023603 positive regulation of transcription initiation, DNA-dependent Effects 0.000 description 6
- 238000002255 vaccination Methods 0.000 description 6
- 101150060895 I4L gene Proteins 0.000 description 5
- 102000035195 Peptidases Human genes 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 238000010586 diagram Methods 0.000 description 5
- 108091008146 restriction endonucleases Proteins 0.000 description 5
- 239000000427 antigen Substances 0.000 description 4
- 108091007433 antigens Proteins 0.000 description 4
- 102000036639 antigens Human genes 0.000 description 4
- 230000000295 complement effect Effects 0.000 description 4
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 4
- 230000003053 immunization Effects 0.000 description 4
- 238000002649 immunization Methods 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 241000713340 Human immunodeficiency virus 2 Species 0.000 description 3
- 108700026244 Open Reading Frames Proteins 0.000 description 3
- 108010076039 Polyproteins Proteins 0.000 description 3
- 101710192141 Protein Nef Proteins 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 108091027070 Trans-activation response element (TAR) Proteins 0.000 description 3
- 239000003708 ampul Substances 0.000 description 3
- 230000003828 downregulation Effects 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 230000006801 homologous recombination Effects 0.000 description 3
- 238000002744 homologous recombination Methods 0.000 description 3
- 230000005847 immunogenicity Effects 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 229940021993 prophylactic vaccine Drugs 0.000 description 3
- 230000006337 proteolytic cleavage Effects 0.000 description 3
- 241001430294 unidentified retrovirus Species 0.000 description 3
- 230000029812 viral genome replication Effects 0.000 description 3
- 108091035707 Consensus sequence Proteins 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 101710177291 Gag polyprotein Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101710125418 Major capsid protein Proteins 0.000 description 2
- 238000012408 PCR amplification Methods 0.000 description 2
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 241000700647 Variola virus Species 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 239000013599 cloning vector Substances 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 238000001976 enzyme digestion Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 230000001506 immunosuppresive effect Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000001915 proofreading effect Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 2
- 230000001177 retroviral effect Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 230000017613 viral reproduction Effects 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- 241000702423 Adeno-associated virus - 2 Species 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 102000005927 Cysteine Proteases Human genes 0.000 description 1
- 108010005843 Cysteine Proteases Proteins 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 102100031780 Endonuclease Human genes 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 241000700662 Fowlpox virus Species 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 108700010908 HIV-1 proteins Proteins 0.000 description 1
- 229940033332 HIV-1 vaccine Drugs 0.000 description 1
- 108700020121 Human Immunodeficiency Virus-1 rev Proteins 0.000 description 1
- 108700020123 Human Immunodeficiency Virus-2 rev Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 101150002280 I5L gene Proteins 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 108091029795 Intergenic region Proteins 0.000 description 1
- 125000002061 L-isoleucyl group Chemical group [H]N([H])[C@]([H])(C(=O)[*])[C@](C([H])([H])[H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 102000043129 MHC class I family Human genes 0.000 description 1
- 108091054437 MHC class I family Proteins 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001183012 Modified Vaccinia Ankara virus Species 0.000 description 1
- 108091061960 Naked DNA Proteins 0.000 description 1
- 108091092724 Noncoding DNA Proteins 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 108090001074 Nucleocapsid Proteins Proteins 0.000 description 1
- 102000011931 Nucleoproteins Human genes 0.000 description 1
- 108010061100 Nucleoproteins Proteins 0.000 description 1
- 239000001888 Peptone Substances 0.000 description 1
- 108010080698 Peptones Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 108091027981 Response element Proteins 0.000 description 1
- 241000287219 Serinus canaria Species 0.000 description 1
- 108091027544 Subgenomic mRNA Proteins 0.000 description 1
- 230000005867 T cell response Effects 0.000 description 1
- 206010046865 Vaccinia virus infection Diseases 0.000 description 1
- 108020000999 Viral RNA Proteins 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000030741 antigen processing and presentation Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 210000005220 cytoplasmic tail Anatomy 0.000 description 1
- 230000001085 cytostatic effect Effects 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 108700004025 env Genes Proteins 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 101150106093 gpt gene Proteins 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 230000005937 nuclear translocation Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 235000019319 peptone Nutrition 0.000 description 1
- 238000009522 phase III clinical trial Methods 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 108700004029 pol Genes Proteins 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 230000001124 posttranscriptional effect Effects 0.000 description 1
- 229940024231 poxvirus vaccine Drugs 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 108700004030 rev Genes Proteins 0.000 description 1
- 101150098213 rev gene Proteins 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- FLNVBBPBGKOJHN-KKAOYSRWSA-N sivmac Chemical compound O=C([C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CS)NC(=O)[C@@H](N)CCCNC(N)=N)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)CC)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(O)=O FLNVBBPBGKOJHN-KKAOYSRWSA-N 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 108700004027 tat Genes Proteins 0.000 description 1
- 101150098170 tat gene Proteins 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 229940125575 vaccine candidate Drugs 0.000 description 1
- 208000007089 vaccinia Diseases 0.000 description 1
- 108700026220 vif Genes Proteins 0.000 description 1
- 101150059019 vif gene Proteins 0.000 description 1
- 229960004854 viral vaccine Drugs 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 108700026215 vpr Genes Proteins 0.000 description 1
- 101150024249 vpr gene Proteins 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
Images
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
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
- A61K39/21—Retroviridae, e.g. equine infectious anemia virus
-
- 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
- A61P31/18—Antivirals for RNA viruses for HIV
-
- 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
- A61P37/04—Immunostimulants
-
- 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
- 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
- C07K14/08—RNA viruses
- C07K14/15—Retroviridae, e.g. bovine leukaemia virus, feline leukaemia virus human T-cell leukaemia-lymphoma virus
- C07K14/155—Lentiviridae, e.g. human immunodeficiency virus [HIV], visna-maedi virus or equine infectious anaemia virus
- C07K14/16—HIV-1 ; HIV-2
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/525—Virus
- A61K2039/5256—Virus expressing foreign proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/53—DNA (RNA) vaccination
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/40—Fusion polypeptide containing a tag for immunodetection, or an epitope for immunisation
-
- 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
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/24011—Poxviridae
- C12N2710/24111—Orthopoxvirus, e.g. vaccinia virus, variola
- C12N2710/24141—Use of virus, viral particle or viral elements as a vector
- C12N2710/24143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
-
- 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
- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/16011—Human Immunodeficiency Virus, HIV
- C12N2740/16311—Human Immunodeficiency Virus, HIV concerning HIV regulatory proteins
- C12N2740/16322—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
-
- 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
- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/16011—Human Immunodeficiency Virus, HIV
- C12N2740/16311—Human Immunodeficiency Virus, HIV concerning HIV regulatory proteins
- C12N2740/16334—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Virology (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Public Health (AREA)
- Biophysics (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Mycology (AREA)
- Communicable Diseases (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Epidemiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Gastroenterology & Hepatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- AIDS & HIV (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Plant Pathology (AREA)
- Oncology (AREA)
- Physics & Mathematics (AREA)
- Tropical Medicine & Parasitology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
Description
Francisら、AIDS Res.Hum.Retroviruses 1998;14(Suppl 3)(5):S325−31 Millerら、Nature Medicine 1997,3,389−94、Calarotaら、Lancet 1998,351,1320−5、Ayyavooら、AIDS,2000,14,1−9 Osterhausら、Vaccine 1999,17,2713−4 van Baalenら、J.Gen.Virol 1997,78,1913−8;Addoら、PNAS,2001,98,1781−6 Howcroftら、Science,1993,260,1320−2;Schwartzら、Nature Med.1996,2,338−42;Swannら、Virology,2001,282,267−77;Janvierら、J.Virol.,2001,78,3971−6;Weissmannら、PNAS 1998,95,11601−6 Cohenら、PNAS,1999,96,10842−10847 Ayyavooら、Nature Med.,1997,3:1117−1123 Zhangら、Virology,1997,230,103−12
+P1−−−P2−−−P3−−−P4−−−P5*−−−P6*−−−P7*+
[式中、P1〜P7は、Vif、Vpr、Vpx、Vpu、Tat、RevおよびNefから選択される異なるHIVタンパク質を表す]
を持ち、本融合タンパク質は、少なくとも4種類の前記HIVタンパク質、すなわちP1〜P4と、要すればさらに1つ(P5*)、2つ(P5*−−−P6*)または3つ(P5*−−−P6*−−−P7*)追加の前記HIVタンパク質を含む。略号「−−−」は、独立して、0個またはn個の追加アミノ酸を意味する。「−−−」が0個のアミノ酸を意味する場合、隣り合うHIVタンパク質は、アミノ酸を追加せずに互いに直接融合される。「−−−」が1〜n個のアミノ酸を意味する場合、隣り合うHIVタンパク質は1〜n個のアミノ酸によって隔てられる。追加アミノ酸数の上限、すなわち整数nは、細胞中で産生または発現されうる融合タンパク質の最大サイズに依存する。
図1:図1は、オリゴヌクレオチドのアニーリングを表す略図である。この図は4つのオリゴヌクレオチドのアニーリングを示している。各オリゴヌクレオチドは一本鎖であり、相補的末端によってアニールすることができる。プルーフリーディング活性を示すポリメラーゼ(例えばPfxポリメラーゼ)を使ってギャップを埋める。
HIVゲノムの単一遺伝子は、標準的PCRプロトコールを用いるPCRにより、ゲノムDNAから調製するか、またはオーバーラップ配列を介したオリゴヌクレオチドのアニーリングと、その結果生じた一本鎖ギャップの充填とに基づく技術によって合成的に調製した。
Claims (24)
- Vif、Vpr、Vpu、Vpx、Rev、TatおよびNefから選択される少なくとも4つのHIVタンパク質のアミノ酸配列、または1種以上の前記タンパク質のアミノ酸配列の誘導体を含む融合タンパク質であって、天然のN末端およびC末端を持つ個々のHIVタンパク質にはプロセシングされない融合タンパク質。
- HIVタンパク質がVif、Vpr、Vpx、Vpu、RevおよびTatから選択される、請求項1記載の融合タンパク質。
- HIVタンパク質Vif、Vpr、Vpu、RevおよびTatのアミノ酸配列、または1種以上の前記タンパク質のアミノ酸配列の誘導体を含む、請求項1又は2記載の融合タンパク質。
- 少なくとも2つのHIVタンパク質のアミノ酸配列が追加アミノ酸なしで互いに融合される、請求項1〜3のいずれか1つに記載の融合タンパク質。
- 少なくとも2つのHIVタンパク質のアミノ酸配列が少なくとも1つの追加アミノ酸によって隔てられる、請求項1〜4のいずれか1つに記載の融合タンパク質。
- 少なくとも1つのHIVタンパク質のアミノ酸配列が、Vif、Vpr、Vpx、Vpu、Rev、TatおよびNefから選択されるHIVタンパク質ではない融合パートナーに融合される、請求項1〜5のいずれか1つに記載の融合タンパク質。
- 請求項1〜6のいずれか1つに記載の融合タンパク質をコードする核酸。
- 核酸がDNAである、請求項7記載の核酸。
- DNAからの融合タンパク質の発現が、真核プロモーター、原核プロモーターおよびウイルスプロモーターから選択される調節要素によって制御される、請求項8記載の核酸。
- ウイルスプロモーターがポックスウイルスプロモーターである、請求項9記載の核酸。
- Gag、PolおよびEnvから選択される少なくとも1つの追加HIVタンパク質のコード配列をさらに含む、請求項7〜10のいずれか1つに記載の核酸。
- HIV Gag、PolおよびEnvタンパク質のコード配列を含む、請求項11記載の核酸。
- 請求項7〜12のいずれか1つに記載の核酸を含むベクター。
- ベクターがウイルスベクターである、請求項13記載のベクター。
- ウイルスベクターがポックスウイルスベクター、特にワクシニアウイルスベクターである、請求項14記載のベクター。
- ワクシニアウイルスベクターが変異ワクシニアウイルスアンカラ(MVA)である、請求項15記載のベクター。
- MVAがヨーロピアン・コレクション・オブ・アニマル・セル・カルチャーズ(ECACC)に受託番号V00120707として寄託されているMVA−575、およびECACCに受託番号V00083008として寄託されているMVA−BNから選択される、請求項16記載のベクター。
- 請求項1〜6のいずれか1つに記載のタンパク質を製造する方法であって、
請求項7〜12のいずれか1つに記載の核酸もしくは請求項13記載のベクターを宿主細胞にトランスフェクトする工程、または
宿主細胞に請求項14〜17のいずれか1つに記載のウイルスベクターを感染させる工程と、
トランスフェクトした宿主細胞または感染させた宿主細胞中で、融合タンパク質を発現させる工程と、
融合タンパク質を回収する工程と、
を含む、上記方法。 - 請求項7〜12のいずれか1つに記載の核酸もしくは請求項13に記載のベクターをトランスフェクトするか、または請求項14〜17のいずれか1つに記載のウイルスベクターに感染させた宿主細胞。
- 医薬としての、請求項1〜6のいずれか1つに記載の融合タンパク質、請求項7〜12のいずれか1つに記載の核酸、または請求項13〜17のいずれか1つに記載のベクター。
- ワクチンとしての、請求項1〜6のいずれか1つに記載の融合タンパク質、請求項7〜12のいずれか1つに記載の核酸、または請求項13〜17のいずれか1つに記載のベクター。
- 請求項1〜6のいずれか1つに記載の融合タンパク質、請求項7〜12のいずれか1つに記載の核酸、または請求項13〜17のいずれか1つに記載のベクターを含むワクチン。
- ワクチンの製造を目的とする、請求項1〜6のいずれか1つに記載の融合タンパク質、請求項7〜12のいずれか1つに記載の核酸、または請求項13〜17のいずれか1つに記載のベクターの使用方法。
- ヒトを含む動物をHIV感染から保護する方法であって、この保護を必要とする、ヒトを含む動物に、請求項1〜6のいずれか1つに記載の融合タンパク質、請求項7〜12のいずれか1つに記載の核酸、または請求項13〜17のいずれか1つに記載のベクターを投与することによってHIV感染から保護する上記方法。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DKPA200200754 | 2002-05-16 | ||
PCT/EP2003/005039 WO2003097675A1 (en) | 2002-05-16 | 2003-05-14 | Fusion protein of hiv regulatory/accessory proteins |
Related Child Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2009114359A Division JP2009178165A (ja) | 2002-05-16 | 2009-05-11 | Hiv調節/アクセサリータンパク質の融合タンパク質 |
JP2009290256A Division JP2010099084A (ja) | 2002-05-16 | 2009-12-22 | Hiv調節/アクセサリータンパク質の融合タンパク質 |
Publications (1)
Publication Number | Publication Date |
---|---|
JP2006502704A true JP2006502704A (ja) | 2006-01-26 |
Family
ID=29433046
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2004506348A Pending JP2006502704A (ja) | 2002-05-16 | 2003-05-14 | Hiv調節/アクセサリータンパク質の融合タンパク質 |
JP2009114359A Pending JP2009178165A (ja) | 2002-05-16 | 2009-05-11 | Hiv調節/アクセサリータンパク質の融合タンパク質 |
JP2009290256A Pending JP2010099084A (ja) | 2002-05-16 | 2009-12-22 | Hiv調節/アクセサリータンパク質の融合タンパク質 |
Family Applications After (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2009114359A Pending JP2009178165A (ja) | 2002-05-16 | 2009-05-11 | Hiv調節/アクセサリータンパク質の融合タンパク質 |
JP2009290256A Pending JP2010099084A (ja) | 2002-05-16 | 2009-12-22 | Hiv調節/アクセサリータンパク質の融合タンパク質 |
Country Status (24)
Country | Link |
---|---|
US (7) | US20050222388A1 (ja) |
EP (2) | EP1506223B1 (ja) |
JP (3) | JP2006502704A (ja) |
KR (4) | KR101196178B1 (ja) |
CN (3) | CN101108882A (ja) |
AT (2) | ATE310016T1 (ja) |
AU (2) | AU2003240638B2 (ja) |
BR (1) | BR0309963A (ja) |
CA (1) | CA2483640A1 (ja) |
CY (1) | CY1108638T1 (ja) |
DE (2) | DE60302356T2 (ja) |
DK (2) | DK1652857T3 (ja) |
EA (1) | EA007154B1 (ja) |
ES (2) | ES2313166T3 (ja) |
HK (1) | HK1076822A1 (ja) |
IL (3) | IL164178A0 (ja) |
MX (1) | MXPA04010683A (ja) |
NO (1) | NO20045229L (ja) |
NZ (2) | NZ536499A (ja) |
PL (2) | PL397252A1 (ja) |
PT (1) | PT1652857E (ja) |
SI (2) | SI1506223T1 (ja) |
UA (3) | UA92788C2 (ja) |
WO (1) | WO2003097675A1 (ja) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2009544318A (ja) * | 2006-07-27 | 2009-12-17 | リゴサイト ファーマシューティカルズ インコーポレイテッド | キメラウイルス様粒子 |
JP2009544322A (ja) * | 2006-07-27 | 2009-12-17 | リゴサイト ファーマシューティカルズ インコーポレイテッド | キメラウイルス様粒子 |
US8920812B2 (en) | 2009-11-03 | 2014-12-30 | Takeda Vaccines, Inc. | Chimeric RSV-F polypeptide and lentivirus or alpha-retrovirus Gag-based VLPS |
Families Citing this family (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7501127B2 (en) | 2002-05-16 | 2009-03-10 | Bavarian Nordic A/S | Intergenic regions as novel sites for insertion of HIV DNA sequences in the genome of Modified Vaccinia virus Ankara |
NZ536499A (en) | 2002-05-16 | 2008-04-30 | Bavarian Nordic As | Fusion protein comprising the amino acid sequence of at least four different HIV proteins selected from Vif, Vpr, Vpu, Vpx, Rev, Tat and Nef, wherein the fusion protein is not processed to individual HIV proteins having the natural N and C termini |
ATE520708T1 (de) | 2003-03-28 | 2011-09-15 | Us Gov Health & Human Serv | Immunogenetische hiv-1 multi-klade, multivalente konstrukte und deren verwendung |
IL286053B2 (en) * | 2005-10-18 | 2023-03-01 | Nat Jewish Health | A process for making red blood cells using immortal hematopoietic stem cells and erythropoietin |
KR20170078862A (ko) | 2008-05-16 | 2017-07-07 | 타이가 바이오테크놀로지스, 인코포레이티드 | 항체 및 그 제조 방법 |
CA2731767C (en) | 2008-07-21 | 2016-12-06 | Taiga Biotechnologies, Inc. | Differentiated anucleated cells and method for preparing the same |
EP3916010A1 (en) | 2008-08-28 | 2021-12-01 | Taiga Biotechnologies, Inc. | Modulators of myc, methods of using the same and methods of identifying agents that modulate myc |
CA2767924A1 (en) * | 2009-10-08 | 2011-04-14 | Bavarian Nordic A/S | Generation of a broad t-cell response in humans against hiv |
US9358281B2 (en) * | 2009-10-09 | 2016-06-07 | New York University | Methods, agents and peptides for inducing an innate immune response in HIV vaccination |
EP2620446A1 (en) | 2012-01-27 | 2013-07-31 | Laboratorios Del Dr. Esteve, S.A. | Immunogens for HIV vaccination |
EP3868387A1 (en) | 2012-07-20 | 2021-08-25 | Taiga Biotechnologies, Inc. | Enhanced reconstitution and autoreconstitution of the hematopoietic compartment |
US9365825B2 (en) | 2013-03-11 | 2016-06-14 | Taiga Biotechnologies, Inc. | Expansion of adult stem cells in vitro |
US10272115B2 (en) | 2013-03-11 | 2019-04-30 | Taiga Biotechnologies, Inc. | Production and use of red blood cells |
WO2015192339A1 (zh) * | 2014-06-18 | 2015-12-23 | 中山大学 | 一种嵌合载体及其制备方法和应用 |
CN104130331B (zh) * | 2014-06-19 | 2017-06-06 | 中山大学 | 一种抗hiv‑1病毒药物及其制备和应用 |
FR3042121A1 (fr) | 2015-10-08 | 2017-04-14 | Jean-Marc Limacher | Composition anti-tumorale |
CN105330729A (zh) * | 2015-11-18 | 2016-02-17 | 南京医科大学 | 一种人类免疫缺陷病毒Vpr蛋白的制备方法 |
CN113786476A (zh) | 2016-12-02 | 2021-12-14 | 泰加生物工艺学公司 | 纳米颗粒调配物 |
US10149898B2 (en) | 2017-08-03 | 2018-12-11 | Taiga Biotechnologies, Inc. | Methods and compositions for the treatment of melanoma |
CN116322757A (zh) | 2019-11-14 | 2023-06-23 | 埃利克斯疗法公司 | 用于疫苗的剂量方案 |
Family Cites Families (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0942747A1 (en) * | 1996-08-26 | 1999-09-22 | Chiron Corporation | Postinfection human immunodeficiency virus (hiv) vaccination therapy |
GB9720585D0 (en) | 1997-09-26 | 1997-11-26 | Smithkline Beecham Biolog | Vaccine |
IT1297090B1 (it) | 1997-12-01 | 1999-08-03 | Barbara Ensoli | Tat di hiv-1 o suoi derivati, da soli od in combinazione, a scopo vaccinale, profilattico e terapeutico, contro l'aids i tumori e le |
FR2773156B1 (fr) * | 1997-12-26 | 2000-03-31 | Biovacs Inc | Nouveaux immunogenes anti-retroviraux (toxoides), nouveaux procedes de preparation et application a la prevention et au traitement du sida |
FI105105B (fi) | 1998-02-27 | 2000-06-15 | Finnish Immunotechnology Ltd O | Itsereplikoiva DNA-vektori immunisoimiseksi HIV:ta vastaan |
US7935805B1 (en) * | 1998-12-31 | 2011-05-03 | Novartis Vaccines & Diagnostics, Inc | Polynucleotides encoding antigenic HIV Type C polypeptides, polypeptides and uses thereof |
CN1326873C (zh) | 2000-01-31 | 2007-07-18 | 史密丝克莱恩比彻姆生物有限公司 | 用于hiv预防或治疗性免疫的疫苗 |
WO2001092470A2 (en) * | 2000-03-02 | 2001-12-06 | Emory University | Dna expression vectors and methods of use |
US6544780B1 (en) * | 2000-06-02 | 2003-04-08 | Genphar, Inc. | Adenovirus vector with multiple expression cassettes |
AU8349301A (en) * | 2000-07-14 | 2002-01-30 | Univ Pennsylvania | Dna vaccines encoding hiv accessory proteins |
AU2872202A (en) * | 2000-11-01 | 2002-05-15 | Us Gov Health & Human Serv | Expression vectors able to elicit improved immune response and methods of using same |
US7628980B2 (en) * | 2000-11-23 | 2009-12-08 | Bavarian Nordic A/S | Modified vaccinia virus ankara for the vaccination of neonates |
NZ536499A (en) * | 2002-05-16 | 2008-04-30 | Bavarian Nordic As | Fusion protein comprising the amino acid sequence of at least four different HIV proteins selected from Vif, Vpr, Vpu, Vpx, Rev, Tat and Nef, wherein the fusion protein is not processed to individual HIV proteins having the natural N and C termini |
-
2003
- 2003-05-14 NZ NZ536499A patent/NZ536499A/en not_active IP Right Cessation
- 2003-05-14 JP JP2004506348A patent/JP2006502704A/ja active Pending
- 2003-05-14 NZ NZ556144A patent/NZ556144A/en not_active IP Right Cessation
- 2003-05-14 CA CA002483640A patent/CA2483640A1/en not_active Abandoned
- 2003-05-14 KR KR1020117017944A patent/KR101196178B1/ko not_active IP Right Cessation
- 2003-05-14 ES ES05017695T patent/ES2313166T3/es not_active Expired - Lifetime
- 2003-05-14 CN CNA2007101039526A patent/CN101108882A/zh active Pending
- 2003-05-14 EA EA200401504A patent/EA007154B1/ru not_active IP Right Cessation
- 2003-05-14 PL PL397252A patent/PL397252A1/pl not_active Application Discontinuation
- 2003-05-14 DK DK05017695T patent/DK1652857T3/da active
- 2003-05-14 MX MXPA04010683A patent/MXPA04010683A/es active IP Right Grant
- 2003-05-14 IL IL16417803A patent/IL164178A0/xx active IP Right Grant
- 2003-05-14 UA UAA200811374A patent/UA92788C2/ru unknown
- 2003-05-14 PT PT05017695T patent/PT1652857E/pt unknown
- 2003-05-14 UA UA20041109408A patent/UA85373C2/ru unknown
- 2003-05-14 US US10/514,740 patent/US20050222388A1/en not_active Abandoned
- 2003-05-14 UA UA20041109410A patent/UA82998C2/ru unknown
- 2003-05-14 DE DE60302356T patent/DE60302356T2/de not_active Expired - Lifetime
- 2003-05-14 DK DK03730029T patent/DK1506223T3/da active
- 2003-05-14 SI SI200330168T patent/SI1506223T1/sl unknown
- 2003-05-14 DE DE60323407T patent/DE60323407D1/de not_active Expired - Lifetime
- 2003-05-14 CN CNA200710000639XA patent/CN1982332A/zh active Pending
- 2003-05-14 EP EP03730029A patent/EP1506223B1/en not_active Expired - Lifetime
- 2003-05-14 KR KR1020047017968A patent/KR100996330B1/ko not_active IP Right Cessation
- 2003-05-14 ES ES03730029T patent/ES2253675T3/es not_active Expired - Lifetime
- 2003-05-14 EP EP05017695A patent/EP1652857B9/en not_active Expired - Lifetime
- 2003-05-14 AT AT03730029T patent/ATE310016T1/de active
- 2003-05-14 WO PCT/EP2003/005039 patent/WO2003097675A1/en active Application Filing
- 2003-05-14 KR KR1020107008995A patent/KR20100063126A/ko not_active Application Discontinuation
- 2003-05-14 CN CNB038111195A patent/CN1325512C/zh not_active Expired - Fee Related
- 2003-05-14 SI SI200331443T patent/SI1652857T1/sl unknown
- 2003-05-14 AT AT05017695T patent/ATE407143T1/de active
- 2003-05-14 BR BR0309963-6A patent/BR0309963A/pt not_active IP Right Cessation
- 2003-05-14 AU AU2003240638A patent/AU2003240638B2/en not_active Ceased
- 2003-05-14 PL PL03372092A patent/PL372092A1/xx not_active IP Right Cessation
- 2003-05-14 KR KR1020127021229A patent/KR20120106894A/ko not_active Application Discontinuation
-
2004
- 2004-09-21 IL IL164178A patent/IL164178A/en not_active IP Right Cessation
- 2004-11-29 NO NO20045229A patent/NO20045229L/no not_active Application Discontinuation
-
2005
- 2005-09-30 HK HK05108707A patent/HK1076822A1/xx not_active IP Right Cessation
-
2006
- 2006-07-18 US US11/488,803 patent/US7569228B2/en not_active Expired - Fee Related
-
2008
- 2008-12-03 CY CY20081101401T patent/CY1108638T1/el unknown
- 2008-12-04 AU AU2008252074A patent/AU2008252074B2/en not_active Ceased
-
2009
- 2009-02-26 IL IL197304A patent/IL197304A0/en unknown
- 2009-05-11 JP JP2009114359A patent/JP2009178165A/ja active Pending
- 2009-06-24 US US12/490,424 patent/US8143054B2/en not_active Expired - Fee Related
- 2009-11-03 US US12/611,164 patent/US8147839B2/en not_active Expired - Fee Related
- 2009-11-03 US US12/611,188 patent/US8137931B2/en not_active Expired - Fee Related
- 2009-12-22 JP JP2009290256A patent/JP2010099084A/ja active Pending
-
2012
- 2012-02-14 US US13/372,723 patent/US8435535B2/en not_active Expired - Fee Related
- 2012-02-14 US US13/372,706 patent/US8389275B2/en not_active Expired - Fee Related
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2009544318A (ja) * | 2006-07-27 | 2009-12-17 | リゴサイト ファーマシューティカルズ インコーポレイテッド | キメラウイルス様粒子 |
JP2009544322A (ja) * | 2006-07-27 | 2009-12-17 | リゴサイト ファーマシューティカルズ インコーポレイテッド | キメラウイルス様粒子 |
US9439959B2 (en) | 2006-07-27 | 2016-09-13 | Takeda Vaccines, Inc. | Chimeric influenza virus-like particles |
US8920812B2 (en) | 2009-11-03 | 2014-12-30 | Takeda Vaccines, Inc. | Chimeric RSV-F polypeptide and lentivirus or alpha-retrovirus Gag-based VLPS |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US8435535B2 (en) | Fusion proteins of HIV regulatory/accessory proteins | |
US20200071724A1 (en) | Intergenic Sites Between Conserved Genes in the Genome of Modified Vaccinia Ankara (MVA) Vaccinia Virus | |
JP4421188B2 (ja) | 変性ワクシニアアンカラウイルス変異体 | |
JP4989224B2 (ja) | Dnaワクチン組成物およびその使用方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20060509 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20090217 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20090511 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20090511 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20090825 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20091222 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100112 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20100112 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20100202 |
|
A912 | Re-examination (zenchi) completed and case transferred to appeal board |
Free format text: JAPANESE INTERMEDIATE CODE: A912 Effective date: 20100312 |
|
RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20100527 |
|
RD03 | Notification of appointment of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7423 Effective date: 20110121 |
|
RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20110121 |
|
RD02 | Notification of acceptance of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7422 Effective date: 20110216 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20111213 |
|
RD03 | Notification of appointment of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7423 Effective date: 20120116 |
|
RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20120116 |