JP6014763B2 - ヒトパピローマウイルスのウイルス様粒子の高効率精製方法 - Google Patents
ヒトパピローマウイルスのウイルス様粒子の高効率精製方法 Download PDFInfo
- Publication number
- JP6014763B2 JP6014763B2 JP2015525348A JP2015525348A JP6014763B2 JP 6014763 B2 JP6014763 B2 JP 6014763B2 JP 2015525348 A JP2015525348 A JP 2015525348A JP 2015525348 A JP2015525348 A JP 2015525348A JP 6014763 B2 JP6014763 B2 JP 6014763B2
- Authority
- JP
- Japan
- Prior art keywords
- hpv
- protein
- chromatography
- vlp
- heating
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 241000701806 Human papillomavirus Species 0.000 title claims description 285
- 238000000034 method Methods 0.000 title claims description 256
- 238000000746 purification Methods 0.000 title claims description 107
- 239000002245 particle Substances 0.000 title description 26
- 108090000623 proteins and genes Proteins 0.000 claims description 268
- 102000004169 proteins and genes Human genes 0.000 claims description 262
- 238000010438 heat treatment Methods 0.000 claims description 142
- 238000004587 chromatography analysis Methods 0.000 claims description 110
- 238000001816 cooling Methods 0.000 claims description 95
- 239000003638 chemical reducing agent Substances 0.000 claims description 93
- 210000004027 cell Anatomy 0.000 claims description 85
- 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 79
- 229960002897 heparin Drugs 0.000 claims description 78
- 229920000669 heparin Polymers 0.000 claims description 78
- 240000004808 Saccharomyces cerevisiae Species 0.000 claims description 20
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 claims description 20
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 claims description 9
- 238000001742 protein purification Methods 0.000 claims description 5
- 210000005253 yeast cell Anatomy 0.000 claims description 5
- OGMADIBCHLQMIP-UHFFFAOYSA-N 2-aminoethanethiol;hydron;chloride Chemical compound Cl.NCCS OGMADIBCHLQMIP-UHFFFAOYSA-N 0.000 claims description 4
- 238000004255 ion exchange chromatography Methods 0.000 claims description 4
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical group OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 claims description 4
- 241000238631 Hexapoda Species 0.000 claims description 3
- 241000235058 Komagataella pastoris Species 0.000 claims description 3
- 238000012258 culturing Methods 0.000 claims description 3
- 125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 claims description 2
- WAPPRYMYMNVAFR-UHFFFAOYSA-N 2-sulfanylethanol Chemical compound OCCS.OCCS WAPPRYMYMNVAFR-UHFFFAOYSA-N 0.000 claims description 2
- 241000894006 Bacteria Species 0.000 claims description 2
- 241000320412 Ogataea angusta Species 0.000 claims description 2
- PZBFGYYEXUXCOF-UHFFFAOYSA-N TCEP Chemical compound OC(=O)CCP(CCC(O)=O)CCC(O)=O PZBFGYYEXUXCOF-UHFFFAOYSA-N 0.000 claims description 2
- 239000007983 Tris buffer Substances 0.000 claims description 2
- 238000001042 affinity chromatography Methods 0.000 claims description 2
- 210000004102 animal cell Anatomy 0.000 claims description 2
- 238000013021 overheating Methods 0.000 claims description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 104
- 230000008569 process Effects 0.000 description 61
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 60
- 239000011780 sodium chloride Substances 0.000 description 52
- 238000001542 size-exclusion chromatography Methods 0.000 description 45
- 239000011347 resin Substances 0.000 description 41
- 229920005989 resin Polymers 0.000 description 41
- 238000004458 analytical method Methods 0.000 description 40
- 238000001262 western blot Methods 0.000 description 35
- 101100209954 Human papillomavirus type 16 L1 gene Proteins 0.000 description 34
- 239000012535 impurity Substances 0.000 description 28
- 238000010828 elution Methods 0.000 description 21
- 239000013592 cell lysate Substances 0.000 description 20
- 230000000694 effects Effects 0.000 description 20
- 238000012870 ammonium sulfate precipitation Methods 0.000 description 19
- 238000011068 loading method Methods 0.000 description 19
- 230000009257 reactivity Effects 0.000 description 19
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 16
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 16
- 235000011130 ammonium sulphate Nutrition 0.000 description 16
- 101000641175 Human papillomavirus type 18 Major capsid protein L1 Proteins 0.000 description 15
- 230000003053 immunization Effects 0.000 description 15
- 238000002649 immunization Methods 0.000 description 15
- 230000001965 increasing effect Effects 0.000 description 15
- 230000003472 neutralizing effect Effects 0.000 description 15
- 241000699666 Mus <mouse, genus> Species 0.000 description 14
- 206010008342 Cervix carcinoma Diseases 0.000 description 13
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 13
- 201000010881 cervical cancer Diseases 0.000 description 13
- 238000002296 dynamic light scattering Methods 0.000 description 13
- 230000005847 immunogenicity Effects 0.000 description 13
- 238000001556 precipitation Methods 0.000 description 13
- 238000003453 ammonium sulfate precipitation method Methods 0.000 description 12
- 239000000872 buffer Substances 0.000 description 11
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 11
- 229920000053 polysorbate 80 Polymers 0.000 description 11
- 239000002244 precipitate Substances 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- 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 10
- 239000000427 antigen Substances 0.000 description 10
- 108091007433 antigens Proteins 0.000 description 10
- 102000036639 antigens Human genes 0.000 description 10
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 10
- 229910000397 disodium phosphate Inorganic materials 0.000 description 10
- 235000019800 disodium phosphate Nutrition 0.000 description 10
- 238000002474 experimental method Methods 0.000 description 10
- 239000000463 material Substances 0.000 description 10
- 210000002966 serum Anatomy 0.000 description 10
- 241000699670 Mus sp. Species 0.000 description 9
- 239000007853 buffer solution Substances 0.000 description 9
- 238000005277 cation exchange chromatography Methods 0.000 description 9
- 238000000502 dialysis Methods 0.000 description 9
- 230000036039 immunity Effects 0.000 description 8
- 238000011002 quantification Methods 0.000 description 8
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 7
- 238000002965 ELISA Methods 0.000 description 7
- 239000003729 cation exchange resin Substances 0.000 description 7
- 239000007788 liquid Substances 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 238000006386 neutralization reaction Methods 0.000 description 6
- 229960005486 vaccine Drugs 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 5
- 229940032077 cervical cancer vaccine Drugs 0.000 description 5
- 238000011084 recovery Methods 0.000 description 5
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- 108091028043 Nucleic acid sequence Proteins 0.000 description 4
- 229940098773 bovine serum albumin Drugs 0.000 description 4
- 238000005119 centrifugation Methods 0.000 description 4
- 238000011097 chromatography purification Methods 0.000 description 4
- 239000000356 contaminant Substances 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- 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 4
- 238000009826 distribution Methods 0.000 description 4
- 238000010218 electron microscopic analysis Methods 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 4
- 239000013604 expression vector Substances 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 239000002953 phosphate buffered saline Substances 0.000 description 4
- 229940124957 Cervarix Drugs 0.000 description 3
- 229940124897 Gardasil Drugs 0.000 description 3
- 101000641177 Human papillomavirus type 16 Major capsid protein L1 Proteins 0.000 description 3
- 241000722343 Human papillomavirus types Species 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- 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 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000000234 capsid Anatomy 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 238000011143 downstream manufacturing Methods 0.000 description 3
- 238000011835 investigation Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 230000003449 preventive effect Effects 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 238000005199 ultracentrifugation Methods 0.000 description 3
- 210000002845 virion Anatomy 0.000 description 3
- 208000002109 Argyria Diseases 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 241000341655 Human papillomavirus type 16 Species 0.000 description 2
- 241001631646 Papillomaviridae Species 0.000 description 2
- 241001112090 Pseudovirus Species 0.000 description 2
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
- 241000256251 Spodoptera frugiperda Species 0.000 description 2
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
- 238000005571 anion exchange chromatography Methods 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 210000004748 cultured cell Anatomy 0.000 description 2
- 238000002270 exclusion chromatography Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 229940039096 human papillomavirus type 18 l1 protein Drugs 0.000 description 2
- 150000007523 nucleic acids Chemical group 0.000 description 2
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 239000012264 purified product Substances 0.000 description 2
- 238000004445 quantitative analysis Methods 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 230000014616 translation Effects 0.000 description 2
- 230000005186 women's health Effects 0.000 description 2
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 1
- 101710117545 C protein Proteins 0.000 description 1
- 108090000565 Capsid Proteins Proteins 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 102100023321 Ceruloplasmin Human genes 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 101150013191 E gene Proteins 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 101150038242 GAL10 gene Proteins 0.000 description 1
- 102100024637 Galectin-10 Human genes 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
- 101710121996 Hexon protein p72 Proteins 0.000 description 1
- 108700005307 Human papillomavirus HPV L1 Proteins 0.000 description 1
- 241000341657 Human papillomavirus type 18 Species 0.000 description 1
- 241000701830 Human papillomavirus type 31 Species 0.000 description 1
- 241000701790 Human papillomavirus type 45 Species 0.000 description 1
- 101150075239 L1 gene Proteins 0.000 description 1
- 244000199866 Lactobacillus casei Species 0.000 description 1
- 235000013958 Lactobacillus casei Nutrition 0.000 description 1
- 101710175243 Major antigen Proteins 0.000 description 1
- 101710125418 Major capsid protein Proteins 0.000 description 1
- 101710157639 Minor capsid protein Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 208000009608 Papillomavirus Infections Diseases 0.000 description 1
- 239000001888 Peptone Substances 0.000 description 1
- 108010080698 Peptones Proteins 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 101710136297 Protein VP2 Proteins 0.000 description 1
- 241001123227 Saccharomyces pastorianus Species 0.000 description 1
- 241000235088 Saccharomyces sp. Species 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 238000003917 TEM image Methods 0.000 description 1
- COQLPRJCUIATTQ-UHFFFAOYSA-N Uranyl acetate Chemical compound O.O.O=[U]=O.CC(O)=O.CC(O)=O COQLPRJCUIATTQ-UHFFFAOYSA-N 0.000 description 1
- 101000936049 Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961) Outer membrane lipoprotein Blc Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 150000001413 amino acids Chemical group 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 230000027455 binding Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000011210 chromatographic step Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000010835 comparative analysis Methods 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000011968 cross flow microfiltration Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000004191 hydrophobic interaction chromatography Methods 0.000 description 1
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 229940017800 lactobacillus casei Drugs 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 1
- 235000019319 peptone Nutrition 0.000 description 1
- IYDGMDWEHDFVQI-UHFFFAOYSA-N phosphoric acid;trioxotungsten Chemical compound O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.OP(O)(O)=O IYDGMDWEHDFVQI-UHFFFAOYSA-N 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 238000006479 redox reaction Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000014723 transformation of host cell by virus Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000012130 whole-cell lysate Substances 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
Images
Classifications
-
- 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
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/14—Extraction; Separation; Purification
- C07K1/16—Extraction; Separation; Purification by chromatography
-
- 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
- C07K14/01—DNA viruses
- C07K14/025—Papovaviridae, e.g. papillomavirus, polyomavirus, SV40, BK virus, JC virus
-
- 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
-
- 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
-
- 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
- C12N2710/20011—Papillomaviridae
- C12N2710/20034—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
-
- 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
- C12N2710/20011—Papillomaviridae
- C12N2710/20051—Methods of production or purification of viral material
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Virology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Gastroenterology & Hepatology (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Analytical Chemistry (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR10-2012-0083472 | 2012-07-30 | ||
| KR20120083472 | 2012-07-30 | ||
| KR10-2013-0085605 | 2013-07-19 | ||
| KR1020130085605A KR101559622B1 (ko) | 2012-07-30 | 2013-07-19 | 인유두종바이러스 바이러스 유사입자의 고효율 정제방법 |
| PCT/KR2013/006823 WO2014021604A1 (ko) | 2012-07-30 | 2013-07-30 | 인유두종바이러스 바이러스 유사입자의 고효율 정제방법 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2015524817A JP2015524817A (ja) | 2015-08-27 |
| JP6014763B2 true JP6014763B2 (ja) | 2016-10-25 |
Family
ID=50266708
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015525348A Active JP6014763B2 (ja) | 2012-07-30 | 2013-07-30 | ヒトパピローマウイルスのウイルス様粒子の高効率精製方法 |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US9994618B2 (pt-PT) |
| EP (1) | EP2881401B1 (pt-PT) |
| JP (1) | JP6014763B2 (pt-PT) |
| KR (1) | KR101559622B1 (pt-PT) |
| CN (1) | CN104507956B (pt-PT) |
| AU (1) | AU2013297306B2 (pt-PT) |
| BR (1) | BR112015002126B1 (pt-PT) |
| CA (1) | CA2880420C (pt-PT) |
| CL (1) | CL2015000037A1 (pt-PT) |
| MX (1) | MX361186B (pt-PT) |
| WO (1) | WO2014021604A1 (pt-PT) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MA40624A (fr) * | 2014-09-11 | 2016-03-17 | Cadila Healthcare Ltd | Antigènes supérieurs du papillomavirus présentant des propriétés immunologiques supérieures et vaccin les contenant |
| WO2016104923A1 (ko) * | 2014-12-26 | 2016-06-30 | 아이진 주식회사 | 인유두종 바이러스의 바이러스 유사 입자 제조방법 |
| CN105176934B (zh) * | 2015-10-16 | 2018-09-18 | 西南大学柑桔研究所 | 柑桔黄化脉明病毒长期离体保存方法 |
| CN109750050B (zh) * | 2017-11-07 | 2023-08-18 | 上海泽润生物科技有限公司 | 重组人乳头瘤病毒45亚型蛋白表达 |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2268787T3 (es) | 1997-09-05 | 2007-03-16 | Medimmune, Inc. | Metodo in vitro de desmontaje/embalaje de particulas similares a virus (vlp) de papilomavirus. |
| US7351533B2 (en) | 1997-09-05 | 2008-04-01 | Medimmune, Inc. | In vitro method for disassmbly/reassembly of papillomavirus virus-like particles (VLPs). Homogeneous VLP and cavsomere compositions produced by said methods: use thereof as vehicle for improved purification, and delivery of active agents |
| SI1105466T1 (sl) * | 1998-08-14 | 2006-08-31 | Merck & Co Inc | Postopek za ciscenje virusu podobnih delcev humanega papilomskega virusa |
| US6245568B1 (en) * | 1999-03-26 | 2001-06-12 | Merck & Co., Inc. | Human papilloma virus vaccine with disassembled and reassembled virus-like particles |
| US6436402B1 (en) | 1999-10-15 | 2002-08-20 | Merck & Co., Inc. | Process for making human papillomavirus virus-like particles with improved properties |
| CA2875298A1 (en) | 1999-12-09 | 2001-06-14 | Medimmune, Inc. | In vitro method for disassembly/reassembly of papillomavirus virus-like particles (vlps) |
| GB0206360D0 (en) * | 2002-03-18 | 2002-05-01 | Glaxosmithkline Biolog Sa | Viral antigens |
| CN101153280B (zh) | 2006-09-29 | 2015-08-19 | 厦门大学 | 从原核生物中纯化人乳头瘤病毒晚期蛋白l1的方法 |
| CN101139570A (zh) | 2007-04-16 | 2008-03-12 | 马润林 | 一种hpv l1蛋白原核表达的高密度发酵方法 |
| DK2910566T5 (en) | 2007-05-29 | 2016-11-07 | Univ Xiamen | Truncated L1 protein of human papillomavirus 11 |
| KR100959145B1 (ko) | 2008-03-21 | 2010-05-25 | 중앙대학교 산학협력단 | 인유두종바이러스 바이러스 유사 입자의 생산 및 정제 방법 |
| JP6022159B2 (ja) * | 2008-07-31 | 2016-11-09 | グラクソスミスクライン バイオロジカルズ ソシエテ アノニム | 抗ｈｐｖワクチン |
| US9566323B2 (en) * | 2009-06-19 | 2017-02-14 | Eyegene Inc. | Vaccine for cervical cancer |
| KR101178056B1 (ko) | 2011-12-19 | 2012-08-28 | 아이진 주식회사 | 자궁경부암 백신 |
-
2013
- 2013-07-19 KR KR1020130085605A patent/KR101559622B1/ko active IP Right Grant
- 2013-07-30 BR BR112015002126-3A patent/BR112015002126B1/pt active IP Right Grant
- 2013-07-30 EP EP13824788.7A patent/EP2881401B1/en active Active
- 2013-07-30 US US14/418,004 patent/US9994618B2/en active Active
- 2013-07-30 JP JP2015525348A patent/JP6014763B2/ja active Active
- 2013-07-30 AU AU2013297306A patent/AU2013297306B2/en active Active
- 2013-07-30 MX MX2015001413A patent/MX361186B/es active IP Right Grant
- 2013-07-30 CN CN201380040425.9A patent/CN104507956B/zh active Active
- 2013-07-30 WO PCT/KR2013/006823 patent/WO2014021604A1/ko active Application Filing
- 2013-07-30 CA CA2880420A patent/CA2880420C/en active Active
-
2015
- 2015-01-08 CL CL2015000037A patent/CL2015000037A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CN104507956B (zh) | 2018-11-06 |
| MX361186B (es) | 2018-11-29 |
| KR101559622B1 (ko) | 2015-10-13 |
| JP2015524817A (ja) | 2015-08-27 |
| CN104507956A (zh) | 2015-04-08 |
| EP2881401B1 (en) | 2018-04-25 |
| EP2881401A4 (en) | 2016-04-13 |
| CA2880420A1 (en) | 2014-02-06 |
| MX2015001413A (es) | 2015-11-18 |
| KR20140018794A (ko) | 2014-02-13 |
| CA2880420C (en) | 2018-02-27 |
| EP2881401A1 (en) | 2015-06-10 |
| AU2013297306B2 (en) | 2016-09-29 |
| WO2014021604A1 (ko) | 2014-02-06 |
| AU2013297306A1 (en) | 2015-02-05 |
| BR112015002126A2 (pt) | 2017-07-04 |
| CL2015000037A1 (es) | 2015-07-31 |
| BR112015002126B1 (pt) | 2022-10-04 |
| US9994618B2 (en) | 2018-06-12 |
| US20150266927A1 (en) | 2015-09-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2154147B1 (en) | A truncated l1 protein of human papillomavirus 16 | |
| EP2716653B1 (en) | Truncated human papillomavirus type 33 protein l1 | |
| RU2642287C2 (ru) | Химерная частица hpv | |
| Pineo et al. | Immunogenic assessment of plant‐produced human papillomavirus type 16 L1/L2 chimaeras | |
| JP6014763B2 (ja) | ヒトパピローマウイルスのウイルス様粒子の高効率精製方法 | |
| Baek et al. | Production and purification of human papillomavirus type 33 L1 virus-like particles from Spodoptera frugiperda 9 cells using two-step column chromatography | |
| US10513541B2 (en) | Mutant of L1 protein of human papillomavirus type 11 | |
| Chen et al. | Human papillomavirus L1 protein expressed in Escherichia coli self-assembles into virus-like particles that are highly immunogenic | |
| US20080213293A1 (en) | Prevention and Treatment of Recurrent Respiratory Papillomatosis | |
| Fernández-San Millán et al. | Human papillomavirus-like particles vaccine efficiently produced in a non-fermentative system based on insect larva | |
| US10125175B2 (en) | Method for enhancing immunogenicity of epitope peptide of HPV antigen, virus-like particle, and method for preparing HPV vaccine | |
| Kwag et al. | The production and immunogenicity of human papillomavirus type 58 virus-like particles produced in Saccharomyces cerevisiae | |
| JP2017528137A (ja) | 卓越した免疫学的特性を有する卓越したヒトパピローマウイルス抗原及びそれを含むワクチン | |
| EP2479186B1 (en) | Genes encoding major capsid protein L1 of human papilloma viruses | |
| Kim et al. | Comparison of the size distributions and immunogenicity of human papillomavirus type 16 L1 virus-like particles produced in insect and yeast cells | |
| US11213580B2 (en) | Mutant of L1 protein of human papillomavirus type 16 | |
| Chang et al. | Effects of downstream processing on structural integrity and immunogenicity in the manufacture of papillomavirus type 16 L1 virus-like particles | |
| Wang et al. | Stop codon mutagenesis for homogenous expression of human papillomavirus L1 protein in Escherichia coli | |
| RU2546242C1 (ru) | РЕКОМБИНАНТНЫЙ ШТАММ ДРОЖЖЕЙ Hansenula polymorpha - ПРОДУЦЕНТ ГЛАВНОГО КАПСИДНОГО БЕЛКА L1 ВИРУСА ПАПИЛЛОМЫ ЧЕЛОВЕКА ТИПА 18 | |
| RU2546243C1 (ru) | Рекомбинантная вакцина для профилактики папилломавирусной инфекции человека и способ ее получения | |
| Kim et al. | A method for removing contaminating protein during purification of human papillomavirus type 18 L1 protein from Saccharomyces cerevisiae | |
| RU2546241C1 (ru) | РЕКОМБИНАНТНЫЙ ШТАММ ДРОЖЖЕЙ Hansenula polymorpha - ПРОДУЦЕНТ ГЛАВНОГО КАПСИДНОГО БЕЛКА L1 ВИРУСА ПАПИЛЛОМЫ ЧЕЛОВЕКА ТИПА 16 | |
| CN117187262A (zh) | 重组人乳头瘤病毒蛋白表达 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20150129 |
|
| RD01 | Notification of change of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7426 Effective date: 20150602 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20150603 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20160202 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20160502 |
|
| 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: 20160913 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20160926 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 6014763 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313113 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| 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 |