JP5079981B2 - アルファウイルス粒子及び調製方法 - Google Patents
アルファウイルス粒子及び調製方法 Download PDFInfo
- Publication number
- JP5079981B2 JP5079981B2 JP2004560855A JP2004560855A JP5079981B2 JP 5079981 B2 JP5079981 B2 JP 5079981B2 JP 2004560855 A JP2004560855 A JP 2004560855A JP 2004560855 A JP2004560855 A JP 2004560855A JP 5079981 B2 JP5079981 B2 JP 5079981B2
- Authority
- JP
- Japan
- Prior art keywords
- helper
- alphavirus
- nucleic acid
- cells
- rna
- 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
- 241000710929 Alphavirus Species 0.000 title claims description 188
- 239000002245 particle Substances 0.000 title claims description 56
- 238000002360 preparation method Methods 0.000 title description 8
- 210000004027 cell Anatomy 0.000 claims description 280
- 238000004520 electroporation Methods 0.000 claims description 123
- 150000007523 nucleic acids Chemical class 0.000 claims description 107
- 102000039446 nucleic acids Human genes 0.000 claims description 93
- 108020004707 nucleic acids Proteins 0.000 claims description 93
- 238000000034 method Methods 0.000 claims description 77
- 150000003839 salts Chemical class 0.000 claims description 60
- 108020004414 DNA Proteins 0.000 claims description 56
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 49
- 101710172711 Structural protein Proteins 0.000 claims description 43
- 230000002238 attenuated effect Effects 0.000 claims description 35
- 239000000243 solution Substances 0.000 claims description 35
- 210000003501 vero cell Anatomy 0.000 claims description 35
- 108090000288 Glycoproteins Proteins 0.000 claims description 31
- 102000003886 Glycoproteins Human genes 0.000 claims description 30
- 239000000203 mixture Substances 0.000 claims description 28
- 238000004806 packaging method and process Methods 0.000 claims description 26
- 239000011780 sodium chloride Substances 0.000 claims description 25
- 238000004519 manufacturing process Methods 0.000 claims description 22
- 230000010076 replication Effects 0.000 claims description 22
- 230000003612 virological effect Effects 0.000 claims description 21
- 239000001963 growth medium Substances 0.000 claims description 19
- 108090000565 Capsid Proteins Proteins 0.000 claims description 14
- 102100023321 Ceruloplasmin Human genes 0.000 claims description 14
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 claims description 12
- 229920000669 heparin Polymers 0.000 claims description 12
- 229960002897 heparin Drugs 0.000 claims description 12
- 238000005406 washing Methods 0.000 claims description 11
- 108091026890 Coding region Proteins 0.000 claims description 9
- 239000007864 aqueous solution Substances 0.000 claims description 9
- 108010053770 Deoxyribonucleases Proteins 0.000 claims description 8
- 102000016911 Deoxyribonucleases Human genes 0.000 claims description 8
- 241000710959 Venezuelan equine encephalitis virus Species 0.000 claims description 8
- 238000001042 affinity chromatography Methods 0.000 claims description 7
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 6
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 claims description 4
- 239000005695 Ammonium acetate Substances 0.000 claims description 4
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 claims description 4
- 102000053602 DNA Human genes 0.000 claims description 4
- 235000019257 ammonium acetate Nutrition 0.000 claims description 4
- 229940043376 ammonium acetate Drugs 0.000 claims description 4
- 239000001099 ammonium carbonate Substances 0.000 claims description 4
- 238000012258 culturing Methods 0.000 claims description 4
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 claims description 3
- 235000012538 ammonium bicarbonate Nutrition 0.000 claims description 3
- 238000011210 chromatographic step Methods 0.000 claims description 2
- 238000005342 ion exchange Methods 0.000 claims description 2
- 230000002209 hydrophobic effect Effects 0.000 claims 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 212
- 235000002639 sodium chloride Nutrition 0.000 description 79
- 239000002609 medium Substances 0.000 description 73
- 230000035772 mutation Effects 0.000 description 50
- 241000700605 Viruses Species 0.000 description 47
- 235000001014 amino acid Nutrition 0.000 description 46
- 239000013598 vector Substances 0.000 description 32
- 229940024606 amino acid Drugs 0.000 description 29
- 150000001413 amino acids Chemical class 0.000 description 29
- 108090000623 proteins and genes Proteins 0.000 description 28
- 238000013518 transcription Methods 0.000 description 26
- 230000035897 transcription Effects 0.000 description 26
- 230000000694 effects Effects 0.000 description 21
- 125000003275 alpha amino acid group Chemical group 0.000 description 19
- 102000004169 proteins and genes Human genes 0.000 description 18
- 230000002163 immunogen Effects 0.000 description 17
- 235000018102 proteins Nutrition 0.000 description 17
- 108020004705 Codon Proteins 0.000 description 16
- 210000000234 capsid Anatomy 0.000 description 16
- 239000002773 nucleotide Substances 0.000 description 15
- 125000003729 nucleotide group Chemical group 0.000 description 15
- 230000006870 function Effects 0.000 description 14
- 208000015181 infectious disease Diseases 0.000 description 14
- 230000002458 infectious effect Effects 0.000 description 14
- 238000000746 purification Methods 0.000 description 14
- 229960005486 vaccine Drugs 0.000 description 13
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 12
- 239000012091 fetal bovine serum Substances 0.000 description 12
- 210000002443 helper t lymphocyte Anatomy 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 11
- 230000002829 reductive effect Effects 0.000 description 11
- 230000001965 increasing effect Effects 0.000 description 10
- 239000011347 resin Substances 0.000 description 10
- 229920005989 resin Polymers 0.000 description 10
- 239000001488 sodium phosphate Substances 0.000 description 10
- 229910000162 sodium phosphate Inorganic materials 0.000 description 10
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 241000710961 Semliki Forest virus Species 0.000 description 9
- 239000000872 buffer Substances 0.000 description 9
- 239000000427 antigen Substances 0.000 description 8
- 102000036639 antigens Human genes 0.000 description 8
- 108091007433 antigens Proteins 0.000 description 8
- 102000004127 Cytokines Human genes 0.000 description 7
- 108090000695 Cytokines Proteins 0.000 description 7
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 7
- 101710127721 Membrane protein Proteins 0.000 description 7
- 241000710960 Sindbis virus Species 0.000 description 7
- 238000004113 cell culture Methods 0.000 description 7
- 238000012217 deletion Methods 0.000 description 7
- 230000037430 deletion Effects 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 239000012510 hollow fiber Substances 0.000 description 7
- 230000001939 inductive effect Effects 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 102000004196 processed proteins & peptides Human genes 0.000 description 7
- 108090000765 processed proteins & peptides Proteins 0.000 description 7
- 210000002966 serum Anatomy 0.000 description 7
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 6
- 101800000980 Protease nsP2 Proteins 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 230000012010 growth Effects 0.000 description 6
- 230000001976 improved effect Effects 0.000 description 6
- 238000006467 substitution reaction Methods 0.000 description 6
- 241000271566 Aves Species 0.000 description 5
- 102000019034 Chemokines Human genes 0.000 description 5
- 108010012236 Chemokines Proteins 0.000 description 5
- 241000699800 Cricetinae Species 0.000 description 5
- 239000006145 Eagle's minimal essential medium Substances 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 239000004472 Lysine Substances 0.000 description 5
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 5
- 239000012634 fragment Substances 0.000 description 5
- 230000028993 immune response Effects 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 239000000411 inducer Substances 0.000 description 5
- 210000004779 membrane envelope Anatomy 0.000 description 5
- 229920001184 polypeptide Polymers 0.000 description 5
- 230000006798 recombination Effects 0.000 description 5
- 238000005215 recombination Methods 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 108091008146 restriction endonucleases Proteins 0.000 description 5
- 238000001890 transfection Methods 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 4
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 241000238631 Hexapoda Species 0.000 description 4
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 4
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
- 108090001074 Nucleocapsid Proteins Proteins 0.000 description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 4
- 239000004473 Threonine Substances 0.000 description 4
- 230000001464 adherent effect Effects 0.000 description 4
- 239000011324 bead Substances 0.000 description 4
- 239000006143 cell culture medium Substances 0.000 description 4
- 230000010261 cell growth Effects 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 230000002950 deficient Effects 0.000 description 4
- 238000010790 dilution Methods 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 210000002950 fibroblast Anatomy 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
- 210000001161 mammalian embryo Anatomy 0.000 description 4
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000012679 serum free medium Substances 0.000 description 4
- 239000004017 serum-free culture medium Substances 0.000 description 4
- 238000001542 size-exclusion chromatography Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 230000014616 translation Effects 0.000 description 4
- 239000013603 viral vector Substances 0.000 description 4
- 239000004475 Arginine Substances 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- 241000699802 Cricetulus griseus Species 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 3
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 3
- 101710125418 Major capsid protein Proteins 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- 108010076039 Polyproteins Proteins 0.000 description 3
- 108010076504 Protein Sorting Signals Proteins 0.000 description 3
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 3
- 108020000999 Viral RNA Proteins 0.000 description 3
- 241000710951 Western equine encephalitis virus Species 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- NWMHDZMRVUOQGL-CZEIJOLGSA-N almurtide Chemical compound OC(=O)CC[C@H](C(N)=O)NC(=O)[C@H](C)NC(=O)CO[C@@H]([C@H](O)[C@H](O)CO)[C@@H](NC(C)=O)C=O NWMHDZMRVUOQGL-CZEIJOLGSA-N 0.000 description 3
- NOFOAYPPHIUXJR-APNQCZIXSA-N aphidicolin Chemical compound C1[C@@]23[C@@]4(C)CC[C@@H](O)[C@@](C)(CO)[C@@H]4CC[C@H]3C[C@H]1[C@](CO)(O)CC2 NOFOAYPPHIUXJR-APNQCZIXSA-N 0.000 description 3
- SEKZNWAQALMJNH-YZUCACDQSA-N aphidicolin Natural products C[C@]1(CO)CC[C@]23C[C@H]1C[C@@H]2CC[C@H]4[C@](C)(CO)[C@H](O)CC[C@]34C SEKZNWAQALMJNH-YZUCACDQSA-N 0.000 description 3
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 3
- 239000013553 cell monolayer Substances 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 238000010367 cloning Methods 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000005090 green fluorescent protein Substances 0.000 description 3
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 3
- 230000005847 immunogenicity Effects 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 3
- 229960000310 isoleucine Drugs 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 210000001672 ovary Anatomy 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 239000011535 reaction buffer Substances 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 230000000717 retained effect Effects 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 238000013519 translation Methods 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- 241000701161 unidentified adenovirus Species 0.000 description 3
- 210000002845 virion Anatomy 0.000 description 3
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 241000178568 Aura virus Species 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 101710132601 Capsid protein Proteins 0.000 description 2
- 102000053642 Catalytic RNA Human genes 0.000 description 2
- 108090000994 Catalytic RNA Proteins 0.000 description 2
- 241001502567 Chikungunya virus Species 0.000 description 2
- 101710094648 Coat protein Proteins 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 241000710945 Eastern equine encephalitis virus Species 0.000 description 2
- 206010066919 Epidemic polyarthritis Diseases 0.000 description 2
- 208000000832 Equine Encephalomyelitis Diseases 0.000 description 2
- 241000206602 Eukaryota Species 0.000 description 2
- 241000231322 Fort Morgan virus Species 0.000 description 2
- 230000010337 G2 phase Effects 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- 229920002683 Glycosaminoglycan Polymers 0.000 description 2
- 102100021181 Golgi phosphoprotein 3 Human genes 0.000 description 2
- 101710154606 Hemagglutinin Proteins 0.000 description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 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
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- 241000608292 Mayaro virus Species 0.000 description 2
- 108060004795 Methyltransferase Proteins 0.000 description 2
- 241000710949 Middelburg virus Species 0.000 description 2
- 108700015872 N-acetyl-nor-muramyl-L-alanyl-D-isoglutamine Proteins 0.000 description 2
- 101710141454 Nucleoprotein Proteins 0.000 description 2
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 2
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 101710083689 Probable capsid protein Proteins 0.000 description 2
- 101710176177 Protein A56 Proteins 0.000 description 2
- 108091028733 RNTP Proteins 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 241000710942 Ross River virus Species 0.000 description 2
- 229920002684 Sepharose Polymers 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- 241000710924 Togaviridae Species 0.000 description 2
- 241000608278 Una virus Species 0.000 description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
- 108010087302 Viral Structural Proteins Proteins 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000003957 anion exchange resin Substances 0.000 description 2
- 230000000692 anti-sense effect Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 230000022131 cell cycle Effects 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000011109 contamination Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000011026 diafiltration Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 230000009977 dual effect Effects 0.000 description 2
- 230000005684 electric field Effects 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 238000001638 lipofection Methods 0.000 description 2
- 108010026228 mRNA guanylyltransferase Proteins 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910001629 magnesium chloride Inorganic materials 0.000 description 2
- 235000011147 magnesium chloride Nutrition 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 230000007918 pathogenicity Effects 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 239000001103 potassium chloride Substances 0.000 description 2
- 235000011164 potassium chloride Nutrition 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- XKMLYUALXHKNFT-UHFFFAOYSA-N rGTP Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O XKMLYUALXHKNFT-UHFFFAOYSA-N 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 108091092562 ribozyme Proteins 0.000 description 2
- 239000012266 salt solution Substances 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- ATHGHQPFGPMSJY-UHFFFAOYSA-N spermidine Chemical compound NCCCCNCCCN ATHGHQPFGPMSJY-UHFFFAOYSA-N 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 238000002255 vaccination Methods 0.000 description 2
- 239000004474 valine Substances 0.000 description 2
- YHQZWWDVLJPRIF-JLHRHDQISA-N (4R)-4-[[(2S,3R)-2-[acetyl-[(3R,4R,5S,6R)-3-amino-4-[(1R)-1-carboxyethoxy]-5-hydroxy-6-(hydroxymethyl)oxan-2-yl]amino]-3-hydroxybutanoyl]amino]-5-amino-5-oxopentanoic acid Chemical compound C(C)(=O)N([C@@H]([C@H](O)C)C(=O)N[C@H](CCC(=O)O)C(N)=O)C1[C@H](N)[C@@H](O[C@@H](C(=O)O)C)[C@H](O)[C@H](O1)CO YHQZWWDVLJPRIF-JLHRHDQISA-N 0.000 description 1
- YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- 241000256118 Aedes aegypti Species 0.000 description 1
- 241000256173 Aedes albopictus Species 0.000 description 1
- 241001302714 Aedes pseudoscutellaris Species 0.000 description 1
- 241000256182 Anopheles gambiae Species 0.000 description 1
- 244000105975 Antidesma platyphyllum Species 0.000 description 1
- 241000180579 Arca Species 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 241000231314 Babanki virus Species 0.000 description 1
- 241000710946 Barmah Forest virus Species 0.000 description 1
- 241000608319 Bebaru virus Species 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000231316 Buggy Creek virus Species 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 108010039939 Cell Wall Skeleton Proteins 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 108700010070 Codon Usage Proteins 0.000 description 1
- 102000012410 DNA Ligases Human genes 0.000 description 1
- 108010061982 DNA Ligases Proteins 0.000 description 1
- 238000007399 DNA isolation Methods 0.000 description 1
- 101710177611 DNA polymerase II large subunit Proteins 0.000 description 1
- 101710184669 DNA polymerase II small subunit Proteins 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 101710201734 E3 protein Proteins 0.000 description 1
- 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 1
- 241000710188 Encephalomyocarditis virus Species 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000283074 Equus asinus Species 0.000 description 1
- 241000465885 Everglades virus Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 241000710781 Flaviviridae Species 0.000 description 1
- 101710177291 Gag polyprotein Proteins 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102100041003 Glutamate carboxypeptidase 2 Human genes 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 229920002971 Heparan sulfate Polymers 0.000 description 1
- 241000710948 Highlands J virus Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000892862 Homo sapiens Glutamate carboxypeptidase 2 Proteins 0.000 description 1
- -1 Hydroxyphosphoryloxy Chemical group 0.000 description 1
- 208000036747 Infectious transmissions Diseases 0.000 description 1
- 101710125507 Integrase/recombinase Proteins 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 102000013462 Interleukin-12 Human genes 0.000 description 1
- 108010065805 Interleukin-12 Proteins 0.000 description 1
- 102000004388 Interleukin-4 Human genes 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 description 1
- 241000231318 Kyzylagach virus Species 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241000713333 Mouse mammary tumor virus Species 0.000 description 1
- 241000868135 Mucambo virus Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 108700020354 N-acetylmuramyl-threonyl-isoglutamine Proteins 0.000 description 1
- 241001460678 Napo <wasp> Species 0.000 description 1
- 241000608287 Ndumu virus Species 0.000 description 1
- 108091092724 Noncoding DNA Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 241000709664 Picornaviridae Species 0.000 description 1
- 241000868134 Pixuna virus Species 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 244000028344 Primula vulgaris Species 0.000 description 1
- 235000016311 Primula vulgaris Nutrition 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 101710185720 Putative ethidium bromide resistance protein Proteins 0.000 description 1
- 102000009609 Pyrophosphatases Human genes 0.000 description 1
- 108010009413 Pyrophosphatases Proteins 0.000 description 1
- 108091034057 RNA (poly(A)) Proteins 0.000 description 1
- 108010009460 RNA Polymerase II Proteins 0.000 description 1
- 102000009572 RNA Polymerase II Human genes 0.000 description 1
- 108010078067 RNA Polymerase III Proteins 0.000 description 1
- 102000014450 RNA Polymerase III Human genes 0.000 description 1
- 238000002123 RNA extraction Methods 0.000 description 1
- 108010065868 RNA polymerase SP6 Proteins 0.000 description 1
- 239000013614 RNA sample Substances 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 241000607715 Serratia marcescens Species 0.000 description 1
- 108010034546 Serratia marcescens nuclease Proteins 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 241000256251 Spodoptera frugiperda Species 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
- 101710137500 T7 RNA polymerase Proteins 0.000 description 1
- BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 description 1
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 1
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 1
- 241000202380 Toxorhynchites amboinensis Species 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 241000711975 Vesicular stomatitis virus Species 0.000 description 1
- 108010067674 Viral Nonstructural Proteins Proteins 0.000 description 1
- 108010067390 Viral Proteins Proteins 0.000 description 1
- 241000231320 Whataroa virus Species 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001412 amines Chemical group 0.000 description 1
- 125000000539 amino acid group Chemical class 0.000 description 1
- 235000012501 ammonium carbonate Nutrition 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 238000004002 angle-resolved photoelectron spectroscopy Methods 0.000 description 1
- 235000021120 animal protein Nutrition 0.000 description 1
- 238000005571 anion exchange chromatography Methods 0.000 description 1
- 239000003011 anion exchange membrane Substances 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 244000309743 astrovirus Species 0.000 description 1
- 108010028263 bacteriophage T3 RNA polymerase Proteins 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000007910 cell fusion Effects 0.000 description 1
- 210000004520 cell wall skeleton Anatomy 0.000 description 1
- 108091092356 cellular DNA Proteins 0.000 description 1
- 239000012501 chromatography medium Substances 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000013065 commercial product Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- IDLFZVILOHSSID-OVLDLUHVSA-N corticotropin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](N)CO)C1=CC=C(O)C=C1 IDLFZVILOHSSID-OVLDLUHVSA-N 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 210000004748 cultured cell Anatomy 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
- 230000006378 damage Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 229940079920 digestives acid preparations Drugs 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 235000013601 eggs Nutrition 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 108700014844 flt3 ligand Proteins 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 229940044627 gamma-interferon Drugs 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 235000009424 haa Nutrition 0.000 description 1
- 238000004191 hydrophobic interaction chromatography Methods 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229940117681 interleukin-12 Drugs 0.000 description 1
- 229940028885 interleukin-4 Drugs 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- JMUHBNWAORSSBD-WKYWBUFDSA-N mifamurtide Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCCCCCCCCCC)COP(O)(=O)OCCNC(=O)[C@H](C)NC(=O)CC[C@H](C(N)=O)NC(=O)[C@H](C)NC(=O)[C@@H](C)O[C@H]1[C@H](O)[C@@H](CO)OC(O)[C@@H]1NC(C)=O JMUHBNWAORSSBD-WKYWBUFDSA-N 0.000 description 1
- 229960005225 mifamurtide Drugs 0.000 description 1
- 108700007621 mifamurtide Proteins 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 229940035032 monophosphoryl lipid a Drugs 0.000 description 1
- 231100000219 mutagenic Toxicity 0.000 description 1
- 230000003505 mutagenic effect Effects 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 238000007899 nucleic acid hybridization Methods 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 229920001481 poly(stearyl methacrylate) Polymers 0.000 description 1
- 229920002492 poly(sulfone) Polymers 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- GUUBJKMBDULZTE-UHFFFAOYSA-M potassium;2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid;hydroxide Chemical compound [OH-].[K+].OCCN1CCN(CCS(O)(=O)=O)CC1 GUUBJKMBDULZTE-UHFFFAOYSA-M 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 235000019419 proteases Nutrition 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 239000002510 pyrogen Substances 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000003161 ribonuclease inhibitor Substances 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229940063673 spermidine Drugs 0.000 description 1
- 229940031439 squalene Drugs 0.000 description 1
- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000004114 suspension culture Methods 0.000 description 1
- 230000001360 synchronised effect Effects 0.000 description 1
- 229960000187 tissue plasminogen activator Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- XETCRXVKJHBPMK-MJSODCSWSA-N trehalose 6,6'-dimycolate Chemical compound C([C@@H]1[C@H]([C@H](O)[C@@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](COC(=O)C(CCCCCCCCCCC3C(C3)CCCCCCCCCCCCCCCCCC)C(O)CCCCCCCCCCCCCCCCCCCCCCCCC)O2)O)O1)O)OC(=O)C(C(O)CCCCCCCCCCCCCCCCCCCCCCCCC)CCCCCCCCCCC1CC1CCCCCCCCCCCCCCCCCC XETCRXVKJHBPMK-MJSODCSWSA-N 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 244000052613 viral pathogen Species 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 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
- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
-
- 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
-
- 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
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- 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
- C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
- C12N2770/00011—Details
- C12N2770/36011—Togaviridae
- C12N2770/36111—Alphavirus, e.g. Sindbis virus, VEE, EEE, WEE, Semliki
- C12N2770/36141—Use of virus, viral particle or viral elements as a vector
- C12N2770/36143—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
- C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
- C12N2770/00011—Details
- C12N2770/36011—Togaviridae
- C12N2770/36111—Alphavirus, e.g. Sindbis virus, VEE, EEE, WEE, Semliki
- C12N2770/36151—Methods of production or purification of viral material
-
- 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
- C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
- C12N2770/00011—Details
- C12N2770/36011—Togaviridae
- C12N2770/36111—Alphavirus, e.g. Sindbis virus, VEE, EEE, WEE, Semliki
- C12N2770/36161—Methods of inactivation or attenuation
- C12N2770/36162—Methods of inactivation or attenuation by genetic engineering
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Virology (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Medicinal Chemistry (AREA)
- Immunology (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Plant Pathology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US43305802P | 2002-12-13 | 2002-12-13 | |
| US60/433,058 | 2002-12-13 | ||
| PCT/US2003/039725 WO2004055167A2 (en) | 2002-12-13 | 2003-12-12 | Alphavirus particles and methods for preparation |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012152561A Division JP5727420B2 (ja) | 2002-12-13 | 2012-07-06 | アルファウイルス粒子及び調製方法 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2006509524A JP2006509524A (ja) | 2006-03-23 |
| JP2006509524A5 JP2006509524A5 (https=) | 2007-02-01 |
| JP5079981B2 true JP5079981B2 (ja) | 2012-11-21 |
Family
ID=32595112
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2004560855A Expired - Lifetime JP5079981B2 (ja) | 2002-12-13 | 2003-12-12 | アルファウイルス粒子及び調製方法 |
| JP2012152561A Expired - Lifetime JP5727420B2 (ja) | 2002-12-13 | 2012-07-06 | アルファウイルス粒子及び調製方法 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012152561A Expired - Lifetime JP5727420B2 (ja) | 2002-12-13 | 2012-07-06 | アルファウイルス粒子及び調製方法 |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US7078218B2 (https=) |
| EP (3) | EP3246399B1 (https=) |
| JP (2) | JP5079981B2 (https=) |
| AU (1) | AU2003297041B2 (https=) |
| BR (2) | BR122019005271B1 (https=) |
| CA (2) | CA2807515C (https=) |
| DK (3) | DK3246399T3 (https=) |
| ES (3) | ES2630222T3 (https=) |
| IL (1) | IL169076A (https=) |
| NZ (1) | NZ540657A (https=) |
| WO (1) | WO2004055167A2 (https=) |
| ZA (1) | ZA200505517B (https=) |
Families Citing this family (45)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6783939B2 (en) * | 2000-07-07 | 2004-08-31 | Alphavax, Inc. | Alphavirus vectors and virosomes with modified HIV genes for use in vaccines |
| ES2330202T5 (es) | 2001-09-06 | 2014-01-20 | Alphavax, Inc. | Sistemas vectores basados en replicones de alfavirus |
| US7078218B2 (en) | 2002-12-13 | 2006-07-18 | Alphavax, Inc. | Alphavirus particles and methods for preparation |
| US20040208848A1 (en) * | 2002-12-13 | 2004-10-21 | Smith Jonathan F. | Multi-antigenic alphavirus replicon particles and methods |
| US7442381B2 (en) * | 2003-03-20 | 2008-10-28 | Alphavax, Inc. | Alphavirus replicons and helper constructs |
| DE602004021260D1 (de) | 2003-07-11 | 2009-07-09 | Alphavax Inc | Cytomegalovirusimpfstoffe, die auf dem alphavirus basieren |
| CN1989250B (zh) | 2004-05-18 | 2013-11-20 | 阿尔法瓦克斯公司 | Tc-83衍生的甲病毒属载体、颗粒和方法 |
| EP1773403B1 (en) * | 2004-07-09 | 2018-04-25 | The University of North Carolina At Chapel Hill | Alphavirus-based adjuvants |
| EP1812564A2 (en) * | 2004-11-11 | 2007-08-01 | Solvay Pharmaceuticals B.V. | Defective influenza virus particles |
| EP1856250B1 (en) * | 2005-02-15 | 2013-07-24 | The University of North Carolina At Chapel Hill | New live virus vaccines |
| US7759104B2 (en) * | 2005-07-14 | 2010-07-20 | Mayo Foundation For Medical Education And Research | Paramyxoviridae virus preparations |
| US20100233209A1 (en) * | 2005-08-11 | 2010-09-16 | Higgs Stephen T | Chikungunya virus infectious clones and uses therefor |
| US9066847B2 (en) | 2007-01-05 | 2015-06-30 | Aceirx Pharmaceuticals, Inc. | Storage and dispensing devices for administration of oral transmucosal dosage forms |
| US8865743B2 (en) | 2006-01-06 | 2014-10-21 | Acelrx Pharmaceuticals, Inc. | Small volume oral transmucosal dosage forms containing sufentanil for treatment of pain |
| US8202535B2 (en) | 2006-01-06 | 2012-06-19 | Acelrx Pharmaceuticals, Inc. | Small-volume oral transmucosal dosage forms |
| US8753308B2 (en) | 2006-01-06 | 2014-06-17 | Acelrx Pharmaceuticals, Inc. | Methods for administering small volume oral transmucosal dosage forms using a dispensing device |
| US8252329B2 (en) * | 2007-01-05 | 2012-08-28 | Acelrx Pharmaceuticals, Inc. | Bioadhesive drug formulations for oral transmucosal delivery |
| US8357114B2 (en) | 2006-01-06 | 2013-01-22 | Acelrx Pharmaceuticals, Inc. | Drug dispensing device with flexible push rod |
| US20070299687A1 (en) * | 2006-06-23 | 2007-12-27 | Pamela Palmer | Inpatient system for patient-controlled delivery of oral transmucosal medications dosed as needed |
| CA2663295C (en) | 2006-09-12 | 2020-03-10 | Alphavax, Inc. | Alphavirus replicon particles matched to protein antigens as immunological adjuvants |
| ES2746960T3 (es) | 2006-09-12 | 2020-03-09 | Alphavax Inc | Partículas de replicón de alfavirus que codifican IL-12 como adyuvantes inmunológicos |
| DK2099485T3 (en) * | 2006-11-03 | 2018-05-22 | Alphavax Inc | Alphavirus and alphavirus replica particle formulations and associated methods |
| US20080294361A1 (en) * | 2007-05-24 | 2008-11-27 | Popp Shane M | Intelligent execution system for the monitoring and execution of vaccine manufacturing |
| US8460913B2 (en) | 2007-06-21 | 2013-06-11 | Alpha Vax, Inc. | Promoterless cassettes for expression of alpha virus structural proteins |
| CA2704153A1 (en) * | 2007-09-26 | 2009-04-02 | Vanderbilt University | Vaccine for rsv and mpv |
| CA2720166A1 (en) * | 2008-04-04 | 2009-10-08 | David B. Weiner | Consensus sequences of chikungunya viral proteins, nucleic acid molecules encoding the same, and compositions and methods for using the same |
| US20100040650A1 (en) * | 2008-05-30 | 2010-02-18 | Crowe Jr James E | Virus-Like paramyxovirus particles and vaccines |
| US8945592B2 (en) | 2008-11-21 | 2015-02-03 | Acelrx Pharmaceuticals, Inc. | Sufentanil solid dosage forms comprising oxygen scavengers and methods of using the same |
| US8680258B2 (en) | 2008-12-01 | 2014-03-25 | Alphavax, Inc. | Use of microRNAs to control virus helper nucleic acids |
| AU2010234362B2 (en) | 2009-04-08 | 2015-11-26 | Alphavax, Inc. | Alphavirus replicon particles expressing TRP2 |
| WO2012001196A2 (es) | 2010-06-28 | 2012-01-05 | Proyecto De Biomedicina Cima, S.L. | Vectores alfavirales y usos de los mismos para la expresión de genes heterólogos |
| PL2852671T3 (pl) | 2012-05-21 | 2019-06-28 | The Regents Of The University Of California | Wytwarzanie ludzkich komórek ips z użyciem syntetycznego samoreplikującego się rna |
| TWI676636B (zh) | 2013-07-12 | 2019-11-11 | Ｖｌｐ醫療股份有限公司 | 包含ｐｄ－１抗原或ｐｄ－１配體抗原的類病毒粒子 |
| EP3634449A4 (en) | 2017-05-08 | 2021-03-17 | Gritstone Oncology, Inc. | ALPHAVIRUS NEOANTIGEN VECTORS |
| SG11202005792RA (en) | 2017-12-20 | 2020-07-29 | Vlp Therapeutics Llc | Alphavirus replicon particle |
| NL2022538B1 (en) | 2019-02-08 | 2020-08-19 | Academisch Ziekenhuis Groningen | Methods for providing purified viral particles of Semliki Forest Virus (SFV), preparations obtainable thereby, and uses thereof. |
| MX2021014525A (es) | 2019-05-30 | 2022-03-17 | Gritstone Bio Inc | Adenovirus modificados. |
| MX2022007905A (es) | 2019-12-31 | 2022-08-25 | Elixirgen Therapeutics Inc | Administracion transitoria basada en temperatura de acidos nucleicos y proteinas a celulas y tejidos. |
| TWI891771B (zh) | 2020-04-17 | 2025-08-01 | 美商Ｖｌｐ醫療股份有限公司 | 冠狀病毒疫苗 |
| AU2021264216A1 (en) | 2020-04-30 | 2022-11-10 | Vlp Therapeutics, Inc. | Cytokine immunotherapy |
| US20220010286A1 (en) * | 2020-07-10 | 2022-01-13 | Boehringer Ingelheim International Gmbh | Process for producing a purified rhabdovirus from cell culture |
| CN116438308A (zh) | 2020-08-06 | 2023-07-14 | 磨石生物公司 | 多表位疫苗盒 |
| CN119563028A (zh) | 2022-05-12 | 2025-03-04 | 尚威天成信使核糖核酸治疗公司 | 具有分泌抗原和免疫调节物的合成自扩增mRNA分子 |
| EP4541899A1 (en) * | 2022-06-17 | 2025-04-23 | Nippon Medical School Foundation | Method for producing high-titer viral vector |
| CN115948351B (zh) * | 2022-12-01 | 2023-11-14 | 杭州养生堂生物医药有限公司 | 一种分离纯化cvb1的方法 |
Family Cites Families (55)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1247080A (en) * | 1983-03-08 | 1988-12-20 | Commonwealth Serum Laboratories Commission | Antigenically active amino acid sequences |
| US4650764A (en) * | 1983-04-12 | 1987-03-17 | Wisconsin Alumni Research Foundation | Helper cell |
| US5173418A (en) | 1985-05-10 | 1992-12-22 | Benzon Pharma, A/S | Production in Escherichia coli of extracellular Serratia spp. hydrolases |
| US5091309A (en) * | 1986-01-16 | 1992-02-25 | Washington University | Sindbis virus vectors |
| US5217879A (en) * | 1989-01-12 | 1993-06-08 | Washington University | Infectious Sindbis virus vectors |
| US5091205A (en) | 1989-01-17 | 1992-02-25 | Union Carbide Chemicals & Plastics Technology Corporation | Hydrophilic lubricious coatings |
| US5185440A (en) | 1989-06-20 | 1993-02-09 | North Carolina State University | cDNA clone coding for Venezuelan equine encephalitis virus and attenuating mutations thereof |
| SE9003978D0 (sv) | 1990-12-13 | 1990-12-13 | Henrik Garoff | Dna expressionssystem baserade paa ett virus replikon |
| US6770283B1 (en) * | 1990-12-13 | 2004-08-03 | Bioption Ab | DNA expression systems based on alphaviruses |
| WO1994017813A1 (en) * | 1993-02-08 | 1994-08-18 | Paravax, Inc. | Defective sindbis virus vectors that express toxoplasma gondii p30 antigens |
| US20020102273A1 (en) * | 1995-08-08 | 2002-08-01 | Robert B. Grieve | Use of alphavirus expression vectors to produce parasite anitgens |
| US6015686A (en) | 1993-09-15 | 2000-01-18 | Chiron Viagene, Inc. | Eukaryotic layered vector initiation systems |
| SE9401091D0 (sv) | 1994-03-31 | 1994-03-31 | Bioption Ab | Alphavirus cDNA vectors |
| SE9401709D0 (sv) * | 1994-05-18 | 1994-05-18 | Mathilda Sjoeberg | Improved alphavirus vectors for expression of heterologous DNA |
| US5505947A (en) * | 1994-05-27 | 1996-04-09 | The University Of North Carolina At Chapel Hill | Attenuating mutations in Venezuelan Equine Encephalitis virus |
| AU4594996A (en) | 1994-11-30 | 1996-06-19 | Chiron Viagene, Inc. | Recombinant alphavirus vectors |
| US5755770A (en) | 1995-01-31 | 1998-05-26 | Boston Scientific Corporatiion | Endovascular aortic graft |
| US5703057A (en) * | 1995-04-07 | 1997-12-30 | Board Of Regents The University Of Texas System | Expression library immunization |
| US5792462A (en) | 1995-05-23 | 1998-08-11 | University Of North Carolina At Chapel Hill | Alphavirus RNA replicon systems |
| US5639650A (en) | 1995-05-23 | 1997-06-17 | The University Of North Carolina At Chapel Hill | cDNA clone for South African Arbovirus No. 86 |
| US5840839A (en) * | 1996-02-09 | 1998-11-24 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Alternative open reading frame DNA of a normal gene and a novel human cancer antigen encoded therein |
| US6451592B1 (en) * | 1996-04-05 | 2002-09-17 | Chiron Corporation | Recombinant alphavirus-based vectors with reduced inhibition of cellular macromolecular synthesis |
| US5853719A (en) * | 1996-04-30 | 1998-12-29 | Duke University | Methods for treating cancers and pathogen infections using antigen-presenting cells loaded with RNA |
| IL127692A0 (en) * | 1996-07-01 | 1999-10-28 | Rhone Poulenc Rorer Sa | Method for producing recombinant adenovirus |
| US5827658A (en) * | 1996-08-09 | 1998-10-27 | The United States Of America As Reprsented By The Department Of Health And Human Services | Isolation of amplified genes via cDNA subtractive hybridization |
| US5824046A (en) | 1996-09-27 | 1998-10-20 | Scimed Life Systems, Inc. | Covered stent |
| US5726022A (en) * | 1996-11-18 | 1998-03-10 | Lifespan Biosciences, Inc. | Subtractive hybridization and capture methods and kits for differential isolation of nucleic acids including disease-associated sequences |
| WO1998022588A2 (en) * | 1996-11-20 | 1998-05-28 | Introgen Therapeutics, Inc. | An improved method for the production and purification of adenoviral vectors |
| US5811407A (en) * | 1997-02-19 | 1998-09-22 | The University Of North Carolina At Chapel Hill | System for the in vivo delivery and expression of heterologous genes in the bone marrow |
| US5958738A (en) * | 1997-03-24 | 1999-09-28 | Roche Diagnostics Corporation | Procedure for subtractive hybridization and difference analysis |
| US6261570B1 (en) * | 1997-05-20 | 2001-07-17 | The United States Of America As Represented By The Secretary Of The Army | Live attenuated virus vaccines for western equine encephalitis virus, eastern equine encephalitis virus, and venezuelan equine encephalitis virus IE and IIIA variants |
| GB9716611D0 (en) * | 1997-08-07 | 1997-10-08 | Cantab Pharmaceuticals Res Ltd | Virus preparations and methods |
| AUPO856097A0 (en) | 1997-08-14 | 1997-09-04 | Commonwealth Scientific And Industrial Research Organisation | Vector |
| US6197502B1 (en) * | 1997-11-17 | 2001-03-06 | Cytos Biotechnology Ag | Expression cloning processes for the discovery characterization, and isolation of genes encoding polypeptides with a predetermined property |
| GB9804632D0 (en) * | 1998-03-05 | 1998-04-29 | Cantab Pharma Res | Virus preparations and methods |
| FI106618B (fi) | 1998-03-30 | 2001-03-15 | Sandvik Tamrock Oy | Sovitelma painenestekäyttöisen iskulaitteen, kuten esimerkiksi rikotuslaitteen yhteydessä |
| CA2327835C (en) * | 1998-04-08 | 2010-09-21 | University Of North Carolina At Chapel Hill | Methods and modified cells for the treatment of cancer |
| US6844188B1 (en) * | 1998-04-08 | 2005-01-18 | University Of North Carolina At Chapel Hill | Methods and modified cells for the treatment of cancer |
| US6146874A (en) * | 1998-05-27 | 2000-11-14 | University Of Florida | Method of preparing recombinant adeno-associated virus compositions |
| CA2336587A1 (en) * | 1998-07-10 | 2000-01-20 | U.S. Medical Research Institute Of Infectious Diseases | Botulinum neurotoxin vaccine |
| EP1117430A1 (en) * | 1998-10-05 | 2001-07-25 | Genzyme Corporation | Genes differentially expressed in cancer cells to design cancer vaccines |
| US6329201B1 (en) * | 1998-12-31 | 2001-12-11 | Chiron Corporation | Compositions and methods for packaging of alphavirus vectors |
| US6242259B1 (en) * | 1998-12-31 | 2001-06-05 | Chiron Corporation | Compositions and methods for packing of alphavirus vectors |
| DE60044125D1 (de) | 1999-04-14 | 2010-05-20 | Novartis Vaccines & Diagnostic | Zusammensetzungen und verfahren zur auslösung einer immunantwort auf basis alphavirus-vektoren-systeme |
| ES2243274T3 (es) | 1999-07-02 | 2005-12-01 | Endotex Interventional Systems, Inc. | Stent flexible y estirable en forma de hoja. |
| US6767699B2 (en) | 2000-05-31 | 2004-07-27 | Chiron Corporation | Method for the quantitation of alphavirus replicon particles |
| US6783939B2 (en) * | 2000-07-07 | 2004-08-31 | Alphavax, Inc. | Alphavirus vectors and virosomes with modified HIV genes for use in vaccines |
| US6982087B2 (en) | 2000-09-07 | 2006-01-03 | The University Of North Carolina At Chapel Hill | Vectors derived from South African Arbovirus No. 86 |
| CA2434546C (en) * | 2001-01-12 | 2012-09-11 | Chiron Corporation | Induction of immune response by a replication-defective venezuelan equine encephalitis-sindbis chimeric virus replicon particle encoding an antigen |
| JP4608210B2 (ja) * | 2001-05-31 | 2011-01-12 | ノバルティス バクシンズ アンド ダイアグノスティックス，インコーポレーテッド | キメラアルファウイルスレプリコン粒子 |
| ES2330202T5 (es) | 2001-09-06 | 2014-01-20 | Alphavax, Inc. | Sistemas vectores basados en replicones de alfavirus |
| WO2004055161A2 (en) * | 2002-12-12 | 2004-07-01 | The Board Of Regents Of The University Of Texas System | Large scale production of packaged alphavirus replicons |
| US7078218B2 (en) | 2002-12-13 | 2006-07-18 | Alphavax, Inc. | Alphavirus particles and methods for preparation |
| US7442381B2 (en) | 2003-03-20 | 2008-10-28 | Alphavax, Inc. | Alphavirus replicons and helper constructs |
| DE602004021260D1 (de) * | 2003-07-11 | 2009-07-09 | Alphavax Inc | Cytomegalovirusimpfstoffe, die auf dem alphavirus basieren |
-
2003
- 2003-12-12 US US10/734,609 patent/US7078218B2/en not_active Expired - Lifetime
- 2003-12-12 ES ES10011537.7T patent/ES2630222T3/es not_active Expired - Lifetime
- 2003-12-12 DK DK17163152.6T patent/DK3246399T3/da active
- 2003-12-12 EP EP17163152.6A patent/EP3246399B1/en not_active Expired - Lifetime
- 2003-12-12 ES ES03813433.4T patent/ES2552687T3/es not_active Expired - Lifetime
- 2003-12-12 CA CA2807515A patent/CA2807515C/en not_active Expired - Lifetime
- 2003-12-12 BR BR122019005271-9A patent/BR122019005271B1/pt active IP Right Grant
- 2003-12-12 AU AU2003297041A patent/AU2003297041B2/en not_active Expired
- 2003-12-12 WO PCT/US2003/039725 patent/WO2004055167A2/en not_active Ceased
- 2003-12-12 BR BRPI0317276A patent/BRPI0317276B8/pt active IP Right Grant
- 2003-12-12 DK DK10011537.7T patent/DK2290054T3/en active
- 2003-12-12 JP JP2004560855A patent/JP5079981B2/ja not_active Expired - Lifetime
- 2003-12-12 NZ NZ540657A patent/NZ540657A/en not_active IP Right Cessation
- 2003-12-12 DK DK03813433.4T patent/DK1590451T3/en active
- 2003-12-12 CA CA2509979A patent/CA2509979C/en not_active Expired - Lifetime
- 2003-12-12 EP EP03813433.4A patent/EP1590451B1/en not_active Expired - Lifetime
- 2003-12-12 ES ES17163152T patent/ES2890023T3/es not_active Expired - Lifetime
- 2003-12-12 EP EP10011537.7A patent/EP2290054B1/en not_active Expired - Lifetime
-
2005
- 2005-06-08 IL IL169076A patent/IL169076A/en active IP Right Grant
-
2006
- 2006-01-24 ZA ZA200505517A patent/ZA200505517B/en unknown
-
2012
- 2012-07-06 JP JP2012152561A patent/JP5727420B2/ja not_active Expired - Lifetime
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5727420B2 (ja) | アルファウイルス粒子及び調製方法 | |
| CA2567254C (en) | Tc-83-derived alphavirus vectors, particles and methods | |
| CN101802199B (zh) | 用于α病毒结构蛋白表达的无启动子盒 | |
| JP2021507713A (ja) | アルファウイルスレプリコン粒子 | |
| US20060099587A1 (en) | Alphavirus vectors having attentuated virion structural proteins | |
| HK1082524B (en) | Alphavirus particles and methods for preparation | |
| WO2004000872A2 (en) | Improved alphavirus vectors having attenuated virion structural proteins |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20051221 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20051221 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20061206 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20061206 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20090811 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20091110 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20091117 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100203 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20101207 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20110210 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20110218 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120110 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20120409 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20120416 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120706 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20120731 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20120830 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20150907 Year of fee payment: 3 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 5079981 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| EXPY | Cancellation because of completion of term |