KR20040018379A - 보강제 및 HBV 백신 성분인 B형 간염 바이러스의pre S단백질 - Google Patents
보강제 및 HBV 백신 성분인 B형 간염 바이러스의pre S단백질 Download PDFInfo
- Publication number
- KR20040018379A KR20040018379A KR1020037015361A KR20037015361A KR20040018379A KR 20040018379 A KR20040018379 A KR 20040018379A KR 1020037015361 A KR1020037015361 A KR 1020037015361A KR 20037015361 A KR20037015361 A KR 20037015361A KR 20040018379 A KR20040018379 A KR 20040018379A
- Authority
- KR
- South Korea
- Prior art keywords
- hbv
- seq
- recombinant
- group
- gene
- Prior art date
Links
- 229960005486 vaccine Drugs 0.000 title claims abstract description 65
- 108010002730 protein S precursor Proteins 0.000 title claims abstract description 30
- 241000700721 Hepatitis B virus Species 0.000 title claims abstract description 19
- 239000002671 adjuvant Substances 0.000 title claims abstract description 19
- 239000000427 antigen Substances 0.000 claims abstract description 40
- 108091007433 antigens Proteins 0.000 claims abstract description 39
- 102000036639 antigens Human genes 0.000 claims abstract description 39
- 150000001413 amino acids Chemical group 0.000 claims abstract description 28
- 235000001014 amino acid Nutrition 0.000 claims abstract description 24
- 235000009582 asparagine Nutrition 0.000 claims abstract description 17
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims abstract description 16
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims abstract description 15
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 claims abstract description 9
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims abstract description 9
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 claims abstract description 9
- 235000004554 glutamine Nutrition 0.000 claims abstract description 9
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims abstract description 8
- 239000004475 Arginine Substances 0.000 claims abstract description 8
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000004471 Glycine Substances 0.000 claims abstract description 8
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 claims abstract description 8
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims abstract description 8
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims abstract description 8
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims abstract description 8
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims abstract description 8
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims abstract description 8
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims abstract description 8
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims abstract description 8
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims abstract description 8
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims abstract description 8
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims abstract description 8
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims abstract description 8
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims abstract description 8
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims abstract description 8
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims abstract description 8
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000004472 Lysine Substances 0.000 claims abstract description 8
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims abstract description 8
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims abstract description 8
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000004473 Threonine Substances 0.000 claims abstract description 8
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims abstract description 8
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims abstract description 8
- 235000004279 alanine Nutrition 0.000 claims abstract description 8
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims abstract description 8
- 235000009697 arginine Nutrition 0.000 claims abstract description 8
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims abstract description 8
- 235000018417 cysteine Nutrition 0.000 claims abstract description 8
- 235000013922 glutamic acid Nutrition 0.000 claims abstract description 8
- 239000004220 glutamic acid Substances 0.000 claims abstract description 8
- 229960000310 isoleucine Drugs 0.000 claims abstract description 8
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims abstract description 8
- 229930182817 methionine Natural products 0.000 claims abstract description 8
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims abstract description 8
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000004474 valine Substances 0.000 claims abstract description 8
- 102000005744 Glycoside Hydrolases Human genes 0.000 claims abstract description 4
- 108010031186 Glycoside Hydrolases Proteins 0.000 claims abstract description 4
- 240000004808 Saccharomyces cerevisiae Species 0.000 claims description 41
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 claims description 41
- 101150010882 S gene Proteins 0.000 claims description 37
- 239000013598 vector Substances 0.000 claims description 31
- 238000000034 method Methods 0.000 claims description 29
- 108090000623 proteins and genes Proteins 0.000 claims description 24
- 101710137302 Surface antigen S Proteins 0.000 claims description 20
- 229940024606 amino acid Drugs 0.000 claims description 19
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 claims description 16
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 claims description 16
- 229960001230 asparagine Drugs 0.000 claims description 16
- 229960002885 histidine Drugs 0.000 claims description 14
- 239000000203 mixture Substances 0.000 claims description 13
- 241001465754 Metazoa Species 0.000 claims description 11
- 241000700605 Viruses Species 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 229960003767 alanine Drugs 0.000 claims description 7
- 229960003121 arginine Drugs 0.000 claims description 7
- 229960002433 cysteine Drugs 0.000 claims description 7
- 230000000694 effects Effects 0.000 claims description 7
- 229960003136 leucine Drugs 0.000 claims description 7
- 241000124008 Mammalia Species 0.000 claims description 5
- 239000012744 reinforcing agent Substances 0.000 claims description 5
- 230000002708 enhancing effect Effects 0.000 claims description 4
- 230000036039 immunity Effects 0.000 claims description 3
- 244000144972 livestock Species 0.000 claims description 3
- 244000144977 poultry Species 0.000 claims description 3
- 230000009257 reactivity Effects 0.000 claims description 3
- 230000001131 transforming effect Effects 0.000 claims description 3
- 241000894006 Bacteria Species 0.000 claims description 2
- 241000233866 Fungi Species 0.000 claims description 2
- 241000287828 Gallus gallus Species 0.000 claims description 2
- 241000702670 Rotavirus Species 0.000 claims description 2
- 238000010171 animal model Methods 0.000 claims description 2
- 238000013518 transcription Methods 0.000 claims description 2
- 230000035897 transcription Effects 0.000 claims description 2
- 229960002989 glutamic acid Drugs 0.000 claims 5
- 229960002743 glutamine Drugs 0.000 claims 5
- 229960002449 glycine Drugs 0.000 claims 5
- 229960003646 lysine Drugs 0.000 claims 2
- 241000195493 Cryptophyta Species 0.000 claims 1
- 230000005847 immunogenicity Effects 0.000 abstract description 21
- 150000001508 asparagines Chemical class 0.000 abstract description 2
- 235000018102 proteins Nutrition 0.000 description 13
- 102000004169 proteins and genes Human genes 0.000 description 13
- 238000001262 western blot Methods 0.000 description 13
- 210000002966 serum Anatomy 0.000 description 12
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 12
- 241000699670 Mus sp. Species 0.000 description 11
- 239000001963 growth medium Substances 0.000 description 11
- 239000000969 carrier Substances 0.000 description 10
- 210000004027 cell Anatomy 0.000 description 10
- 230000001684 chronic effect Effects 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 8
- 230000014509 gene expression Effects 0.000 description 8
- 230000028993 immune response Effects 0.000 description 8
- 208000015181 infectious disease Diseases 0.000 description 8
- 108020004705 Codon Proteins 0.000 description 7
- 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 7
- 241000283973 Oryctolagus cuniculus Species 0.000 description 7
- 239000000523 sample Substances 0.000 description 7
- 239000001888 Peptone Substances 0.000 description 6
- 108010080698 Peptones Proteins 0.000 description 6
- 229940041514 candida albicans extract Drugs 0.000 description 6
- 208000006454 hepatitis Diseases 0.000 description 6
- 238000004255 ion exchange chromatography Methods 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- 235000019319 peptone Nutrition 0.000 description 6
- 239000002953 phosphate buffered saline Substances 0.000 description 6
- 239000012138 yeast extract Substances 0.000 description 6
- 241000700159 Rattus Species 0.000 description 5
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 239000008103 glucose Substances 0.000 description 5
- 230000013595 glycosylation Effects 0.000 description 5
- 238000006206 glycosylation reaction Methods 0.000 description 5
- 239000013642 negative control Substances 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- 239000013641 positive control Substances 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 229940021747 therapeutic vaccine Drugs 0.000 description 5
- 238000011282 treatment Methods 0.000 description 5
- 241000271566 Aves Species 0.000 description 4
- 238000002965 ELISA Methods 0.000 description 4
- 229940124872 Hepatitis B virus vaccine Drugs 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 238000000855 fermentation Methods 0.000 description 4
- 230000004151 fermentation Effects 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 229930182830 galactose Natural products 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 206010008909 Chronic Hepatitis Diseases 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 102000014150 Interferons Human genes 0.000 description 3
- 108010050904 Interferons Proteins 0.000 description 3
- 102000000447 Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase Human genes 0.000 description 3
- 108010055817 Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase Proteins 0.000 description 3
- 241000235070 Saccharomyces Species 0.000 description 3
- 231100000354 acute hepatitis Toxicity 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 239000008121 dextrose Substances 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 210000003494 hepatocyte Anatomy 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 3
- 230000002458 infectious effect Effects 0.000 description 3
- 229940079322 interferon Drugs 0.000 description 3
- JTEGQNOMFQHVDC-NKWVEPMBSA-N lamivudine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 description 3
- 229960001627 lamivudine Drugs 0.000 description 3
- 239000002773 nucleotide Substances 0.000 description 3
- 125000003729 nucleotide group Chemical group 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 229940021993 prophylactic vaccine Drugs 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 108091008146 restriction endonucleases Proteins 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 238000000108 ultra-filtration Methods 0.000 description 3
- 210000005253 yeast cell Anatomy 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- QQAPDATZKKTBIY-YUMQZZPRSA-N Gln-Gly-Met Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CCSC)C(O)=O QQAPDATZKKTBIY-YUMQZZPRSA-N 0.000 description 2
- 101150045458 KEX2 gene Proteins 0.000 description 2
- 241000235058 Komagataella pastoris Species 0.000 description 2
- 101710084021 Large envelope protein Proteins 0.000 description 2
- 108010028921 Lipopeptides Proteins 0.000 description 2
- UZWMJZSOXGOVIN-LURJTMIESA-N Met-Gly-Gly Chemical compound CSCC[C@H](N)C(=O)NCC(=O)NCC(O)=O UZWMJZSOXGOVIN-LURJTMIESA-N 0.000 description 2
- AJHCSUXXECOXOY-UHFFFAOYSA-N N-glycyl-L-tryptophan Natural products C1=CC=C2C(CC(NC(=O)CN)C(O)=O)=CNC2=C1 AJHCSUXXECOXOY-UHFFFAOYSA-N 0.000 description 2
- 229920002684 Sepharose Polymers 0.000 description 2
- 230000024932 T cell mediated immunity Effects 0.000 description 2
- ARKBYVBCEOWRNR-UBHSHLNASA-N Trp-Ser-Ser Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O ARKBYVBCEOWRNR-UBHSHLNASA-N 0.000 description 2
- 210000004102 animal cell Anatomy 0.000 description 2
- 230000000692 anti-sense effect Effects 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 108010084389 glycyltryptophan Proteins 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 108010005942 methionylglycine Proteins 0.000 description 2
- 238000011587 new zealand white rabbit Methods 0.000 description 2
- 244000045947 parasite Species 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 238000006116 polymerization reaction Methods 0.000 description 2
- 108091033319 polynucleotide Proteins 0.000 description 2
- 102000040430 polynucleotide Human genes 0.000 description 2
- 239000002157 polynucleotide Substances 0.000 description 2
- 238000012453 sprague-dawley rat model Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 231100000820 toxicity test Toxicity 0.000 description 2
- 230000002463 transducing effect Effects 0.000 description 2
- 238000010200 validation analysis Methods 0.000 description 2
- 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 1
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- 241000224489 Amoeba Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 101710132601 Capsid protein Proteins 0.000 description 1
- 102100031673 Corneodesmosin Human genes 0.000 description 1
- 101710139375 Corneodesmosin Proteins 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 102000053602 DNA Human genes 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
- 229920002307 Dextran Polymers 0.000 description 1
- 238000009007 Diagnostic Kit Methods 0.000 description 1
- 101710091045 Envelope protein Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- 206010051814 Eschar Diseases 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 102000004366 Glucosidases Human genes 0.000 description 1
- 108010056771 Glucosidases Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 108010065920 Insulin Lispro Proteins 0.000 description 1
- 102100034349 Integrase Human genes 0.000 description 1
- 102000003777 Interleukin-1 beta Human genes 0.000 description 1
- 108090000193 Interleukin-1 beta Proteins 0.000 description 1
- 101710096444 Killer toxin Proteins 0.000 description 1
- PMGDADKJMCOXHX-UHFFFAOYSA-N L-Arginyl-L-glutamin-acetat Natural products NC(=N)NCCCC(N)C(=O)NC(CCC(N)=O)C(O)=O PMGDADKJMCOXHX-UHFFFAOYSA-N 0.000 description 1
- AFLBTVGQCQLOFJ-AVGNSLFASA-N Lys-Pro-Arg Chemical compound NCCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCN=C(N)N)C(O)=O AFLBTVGQCQLOFJ-AVGNSLFASA-N 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 208000037581 Persistent Infection Diseases 0.000 description 1
- 108010015853 Pre-S vaccine Proteins 0.000 description 1
- 101710188315 Protein X Proteins 0.000 description 1
- 239000012614 Q-Sepharose Substances 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 101150075200 S-2 gene Proteins 0.000 description 1
- 101150027674 S1 gene Proteins 0.000 description 1
- 239000012506 Sephacryl® Substances 0.000 description 1
- 206010040880 Skin irritation Diseases 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
- 208000036142 Viral infection Diseases 0.000 description 1
- 108070000030 Viral receptors Proteins 0.000 description 1
- 241000235015 Yarrowia lipolytica Species 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 108010008355 arginyl-glutamine Proteins 0.000 description 1
- 238000003556 assay Methods 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
- 230000037396 body weight Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 210000000234 capsid Anatomy 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 229940028617 conventional vaccine Drugs 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- UQLDLKMNUJERMK-UHFFFAOYSA-L di(octadecanoyloxy)lead Chemical compound [Pb+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O UQLDLKMNUJERMK-UHFFFAOYSA-L 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 235000013681 dietary sucrose Nutrition 0.000 description 1
- 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 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- 231100000333 eschar Toxicity 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 125000003147 glycosyl group Chemical group 0.000 description 1
- 210000004209 hair Anatomy 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000004727 humoral immunity Effects 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 238000013411 master cell bank Methods 0.000 description 1
- 230000008774 maternal effect Effects 0.000 description 1
- 238000010339 medical test Methods 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 235000013594 poultry meat Nutrition 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000002250 progressing effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000000734 protein sequencing Methods 0.000 description 1
- 239000012521 purified sample Substances 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000011218 seed culture Methods 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000012798 spherical particle Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229960000814 tetanus toxoid Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000005030 transcription termination Effects 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 238000013060 ultrafiltration and diafiltration Methods 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/37—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from fungi
- C07K14/39—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from fungi from yeasts
- C07K14/395—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from fungi from yeasts from Saccharomyces
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
-
- 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
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55516—Proteins; Peptides
-
- 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
- C12N2730/00—Reverse transcribing DNA viruses
- C12N2730/00011—Details
- C12N2730/10011—Hepadnaviridae
- C12N2730/10111—Orthohepadnavirus, e.g. hepatitis B virus
- C12N2730/10122—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Mycology (AREA)
- Biophysics (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Genetics & Genomics (AREA)
- Animal Behavior & Ethology (AREA)
- Immunology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Virology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
Abstract
Description
작용부 | 특성 |
프로모터 | MfF alpha l promoter |
분비신호 | Killer toxin, IL-1 beta leader |
절단부위 | KEX2 |
삽입 유전자 | pre-S gene ( coding region for pre-S1 and - S2) |
전사 종결자 | GAPD terminator |
ura 유전자 | URA3 |
단계 | 총 단백질 | 총 pre-S | 특이 활성도(mg pre-S/ mg protein) | 정제수율 | 정제도 (Fold) |
여과 단계 | 309,440 mg | 347.8 mg | 0.00112 | 100% | 1 |
초미세 여과 단계 | 14,780 mg | 336.4 mg | 0.02276 | 96.7% | 20.3 |
이온교환 크로마토그래피 | 360 mg | 235.5 mg | 0.65417 | 67.7% | 584.1 |
크기차 분리 | 157.9 mg | 155.43 mg | 0.98486 | 44.7% | 878.9 |
1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | |
재조합 pre-S | Met | Gly | Gly | Trp | Ser | Ser | Lys | Pro | ND | Gln | Gly | Met | Gly | Thr |
유추한 아미노산 서열 | Met | Gly | Gly | Trp | Ser | Ser | Lys | Pro | Arg | Gln | Gly | Met | Gly | Thr |
Claims (43)
- 비당화 또는 일부 당화된 B 형 간염 바이러스의 변형된 pre-S.
- 제 1항에 있어서, 상기 변형된 pre-S는 천연형 pre-S의 15 또는 123번째 아미노산에 위치한 1종 이상의 아스파라진이 알라닌, 아르기닌, 시스테인, 글루타민, 글루타민산, 글리신, 히스티딘, 이소루신, 루신, 라이신, 메티오닌, 페닐알라닌, 프롤린, 세린, 트레오닌 트립토판, 티로신 및 발린으로 이루어진 군으로부터 선택된 아미노산으로 치환된 변이체 pre-S인 것인 B 형 간염 바이러스의 변형된 pre-S.
- 제 2항에 있어서, 상기 천연형 pre-S는 adr, ayw, adw, adw2, 및 adyw 서브타입으로 이루어진 군으로부터 선택된 HBV로부터 유래된 것인 B 형 간염 바이러스의 변형된 pre-S.
- 제 1항에 있어서, 상기 변형된 pre-S는 Pre-S-15m (서열번호: 9), Pre-S-123m (서열번호: 10) 및 Pre-S-dm (서열번호: 11)로 이루어진 군으로부터 선택된 것인 B 형 간염 바이러스의 변형된 pre-S.
- 제 1항에 있어서, 상기 변형된 pre-S는 천연형 pre-S 또는 재조합 pre-S를 글리코시데이즈로 처리하여 제조한 것인 B 형 간염 바이러스의 변형된 pre-S.
- 제 2항의 B 형 간염 바이러스의 변형된 pre-S를 암호화하는 변이체 pre-S 유전자.
- 제 6항에 있어서, 상기 천연형 pre-S는 adr, ayw, adw, adw2, 및 adyw 서브타입 중 1종의 것으로부터 유래된 것인 변이체 pre-S 유전자.
- 제 6항에 있어서, 상기 변이체 pre-S 유전자는 서열번호: 9의 Pre-S-15m, 서열번호: 10의 Pre-S-123m 또는 서열번호: 11의 Pre-S-dm 중 1종을 암호화는 것인 변이체 pre-S 유전자.
- (a) 프로모터;(b) HBV pre-S 유전자; 및(c) 전사종결자;를 포함하는 재조합 벡터.
- 제 9항에 있어서, 상기 pre-S 유전자는 adr, ayw, adw, adw2, 및 adyw 서브타입으로 이루어진 군으로부터 선택된 HBV로부터 유래된 것인 재조합 벡터.
- 제 9항에 있어서, 상기 pre-S 유전자는 천연형 pre-S의 15 또는 123번째 아미노산에 위치한 1종 이상의 아스파라진이 알라닌, 아르기닌, 시스테인, 글루타민, 글루타민산, 글리신, 히스티딘, 이소루신, 루신, 라이신, 메티오닌, 페닐알라닌, 프롤린, 세린, 트레오닌 트립토판, 티로신 및 발린으로 이루어진 군으로부터 선택된 아미노산으로 치환된 변이체 pre-S를 암호화하는 것인 재조합 벡터.
- 제 9항에 있어서, 상기 pre-S 유전자는 Pre-S-15m (서열번호: 9), Pre-S-123m (서열번호: 10) 및 Pre-S-dm (서열번호: 11)로 이루어진 군으로부터 선택된 변이체 pre-S를 암호화하는 것인 재조합 벡터.
- 제 9항에 있어서, 상기 벡터는 pIL20-pre-S (adr) 또는 pIL20-pre-S (ayw)인 재조합 벡터.
- 제 9항의 재조합 벡터를 포함하는 형질전환체.
- 제 14항에 있어서, 상기 pre-S 유전자는 adr, ayw, adw, adw2, 및 adyw 서브타입으로 이루어진 군으로부터 선택된 HBV로부터 유래된 것인 형질전환체.
- 제 14항에 있어서, 상기 pre-S 유전자는 천연형 pre-S의 15 또는 123번째 아미노산에 위치한 1종 이상의 아스파라진이 알라닌, 아르기닌, 아스파라긴, 시스테인, 글루타민, 글루타민산, 글리신, 히스티딘, 이소루신, 루신, 라이신, 메티오닌,페닐알라닌, 프롤린, 세린, 트레오닌 트립토판, 티로신 및 발린으로 이루어진 군으로부터 선택된 아미노산으로 치환된 변이체 pre-S를 암호화하는 것인 형질전환체
- 제 14항에 있어서, 상기 pre-S 유전자는 Pre-S-15m (서열번호: 9), Pre-S-123m (서열번호: 10) 및 Pre-S-dm (서열번호: 11)로 이루어진 군으로부터 선택된 변이체 pre-S를 암호화하는 것인 형질전환체.
- 제 14항에 있어서, 상기 형질전환체는 효모인 것인 형질전환체.
- 제 14항에 있어서, 상기 형질전환체는 사카로마이세스 세레비지아 2805/pIL20-pre-S (KCTC 0987BP) 및 사카로마이세스 세레비지아 2805/pIL20-pre-S (ayw) (KCTC 1004BP)로 이루어진 군으로부터 선택된 것인 형질전환체.
- 제 14항의 형질전환체로부터 생산되는 재조합 pre-S.
- 제 20항에 있어서, 상기 재조합 pre-S는 완전히 당화되거나, 일부 당화되거나 또는 당화되지 않은 것인 재조합 pre-S.
- 제 20항에 있어서, 상기 재조합 pre-S는 글리코시데이즈로 더욱 처리된 것인 재조합 pre-S.
- HBV pre-S를 포함하는 보강제.
- 제 23항에 있어서, 상기 pre-S는 일부 당화되거나 또는 당화되지 않은 것인 보강제.
- 제 23항에 있어서, 상기 pre-S는 천연형 pre-S의 15 또는 123번째 아미노산에 위치한 1종 이상의 아스파라진이 알라닌, 아르기닌, 시스테인, 글루타민, 글루타민산, 글리신, 히스티딘, 이소루신, 루신, 라이신, 메티오닌, 페닐알라닌, 프롤린, 세린, 트레오닌 트립토판, 티로신 및 발린으로 이루어진 군으로부터 선택된 아미노산으로 치환된 변이체 pre-S인 것인 보강제.
- 제 23항에 있어서, 상기 pre-S는 Pre-S-15m (서열번호: 9), Pre-S-123m (서열번호: 10) 및 Pre-S-dm (서열번호: 11)로 이루어진 군으로부터 선택된 것인 보강제.
- pre-S를 포함하는 HBV 백신.
- 제 27항에 있어서, 상기 HBV 백신은 HBV의 S 항원을 더욱 포함하는 것인 HBV 백신.
- 제 27항에 있어서, 상기 pre-S는 재조한 pre-S 단백질인 것인 HBV 백신.
- 제 27항에 있어서, 상기 pre-S는 완전히 당화되거나, 일부 당화되거나 또는 당화되지 않은 것인 HBV 백신.
- 제 27항에 있어서, 상기 pre-S는 천연형 pre-S의 15 또는 123번째 아미노산에 위치한 1종 이상의 아스파라진이 알라닌, 아르기닌, 시스테인, 글루타민, 글루타민산, 글리신, 히스티딘, 이소루신, 루신, 라이신, 메티오닌, 페닐알라닌, 프롤린, 세린, 트레오닌 트립토판, 티로신 및 발린으로 이루어진 군으로부터 선택된 아미노산으로 치환된 변이체 pre-S인 것인 HBV 백신.
- 제 27항에 있어서, 상기 pre-S는 adr, ayw, adw, adw2, 및 adyw 서브타입으로 이루어진 군으로부터 선택된 HBV로부터 유래된 것인 HBV 백신.
- 제 27항에 있어서, 상기 pre-S는 Pre-S-15m (서열번호: 9), Pre-S-123m (서열번호: 10) 및 Pre-S-dm (서열번호: 11)로 이루어진 군으로부터 선택된 것인 HBV 백신.
- HBV pre-S를 포함하는, HBV, HBV 표면 항원 또는 pre-S 유전자에 의해 번역되는 항원에 대한 항체 검출용 진단 조성물.
- 제 34항에 있어서, 상기 pre-S는 adr, ayw, adw, adw2, 및 adyw 서브타입으로 이루어진 군으로부터 선택된 HBV로부터 유래된 것인 진단 조성물.
- (a) pre-S를 암호화하는 유전자를 벡터내 삽입하고;(b) 상기 pre-S 유전자를 포함하는 벡터를 숙주세포에 형질전환하고; 및(c) 형질전환체는 배지에서 배양하여 pre-S를 생산하는;것을 포함하는 HBV pre-S 생산방법.
- 제 23항의 보강제를 포유류 또는 조류에 항체-증강효과를 갖는 함량으로 투여하는 것을 포함하는, 항원에 대한 항체반응성 증강 방법.
- 제 37항에 있어서, 상기 항원은 바이로스, 세균, 효모 또는 진균으로부터 유래된 것인 방법.
- 제 38항에 있어서, 상기 바이러스는 HIV, HBV, HCV, 또는 로타바이러스인 것인 방법.
- 제 37항에 있어서, 상기 포유류는 사람, 가축동물, 실험용 동물, 가금 동물및 포획한 야생 동물로 이루어진 군으로부터 선택된 것인 방법.
- 제 37항에 있어서, 상기 조류는 닭 또는 그외 가금 조류인 것인 방법.
- 청구항 27항의 HBV 백신을 투여하는 것을 포함하는, HBV에 대한 면역성을 형성시키는 방법.
- 제 42항에 있어서, 상기 방법은 HBV S 항원을 투여하는 것을 더욱 포함하는 방법.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR20010029002 | 2001-05-25 | ||
KR1020010029002 | 2001-05-25 |
Publications (2)
Publication Number | Publication Date |
---|---|
KR20040018379A true KR20040018379A (ko) | 2004-03-03 |
KR100587944B1 KR100587944B1 (ko) | 2006-06-08 |
Family
ID=19709949
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1020037015361A KR100587944B1 (ko) | 2001-05-25 | 2002-05-02 | 보강제 및 HBV 백신 성분인 B형 간염 바이러스의pre S단백질 |
Country Status (7)
Country | Link |
---|---|
US (1) | US20040137016A1 (ko) |
EP (1) | EP1390397B1 (ko) |
KR (1) | KR100587944B1 (ko) |
AT (1) | ATE409705T1 (ko) |
DE (1) | DE60229126D1 (ko) |
ES (1) | ES2315405T3 (ko) |
WO (1) | WO2002094866A1 (ko) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8748373B2 (en) * | 2007-02-21 | 2014-06-10 | Fox Chase Cancer Center | Hepatitis B virus compositions and methods of use |
CA2756206A1 (en) * | 2009-03-27 | 2010-09-30 | Academia Sinica | Methods and compositions for immunization against virus |
WO2012146630A1 (en) | 2011-04-29 | 2012-11-01 | F. Hoffmann-La Roche Ag | N-terminal acylated polypeptides, methods for their production and uses thereof |
US20180228804A1 (en) * | 2014-10-07 | 2018-08-16 | Myr Gmbh | Combination therapy of hbv and hdv infection |
CN114729010A (zh) * | 2019-08-29 | 2022-07-08 | 维尔生物科技有限公司 | 乙型肝炎病毒疫苗 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4847080A (en) * | 1984-03-07 | 1989-07-11 | New York Blood Center, Inc. | Pre-S gene coded peptide hepatitis B immunogens, vaccines, diagnostics, and synthetic lipide vesicle carriers |
US4816564A (en) * | 1986-01-31 | 1989-03-28 | Merck & Co., Inc. | Method for producing hepatitis B virus proteins in yeast |
JPS62236496A (ja) * | 1986-04-07 | 1987-10-16 | Green Cross Corp:The | HBsAgの製造方法 |
-
2002
- 2002-05-02 AT AT02771774T patent/ATE409705T1/de not_active IP Right Cessation
- 2002-05-02 WO PCT/KR2002/000820 patent/WO2002094866A1/en not_active Application Discontinuation
- 2002-05-02 ES ES02771774T patent/ES2315405T3/es not_active Expired - Lifetime
- 2002-05-02 KR KR1020037015361A patent/KR100587944B1/ko active IP Right Grant
- 2002-05-02 EP EP02771774A patent/EP1390397B1/en not_active Expired - Lifetime
- 2002-05-02 DE DE60229126T patent/DE60229126D1/de not_active Expired - Lifetime
-
2003
- 2003-11-24 US US10/720,662 patent/US20040137016A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
KR100587944B1 (ko) | 2006-06-08 |
EP1390397A1 (en) | 2004-02-25 |
DE60229126D1 (de) | 2008-11-13 |
ATE409705T1 (de) | 2008-10-15 |
EP1390397B1 (en) | 2008-10-01 |
WO2002094866A1 (en) | 2002-11-28 |
US20040137016A1 (en) | 2004-07-15 |
ES2315405T3 (es) | 2009-04-01 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP0522030B1 (en) | Hepatitis b vaccine | |
AP56A (en) | Hepatitis B virus surface antigens and hybrid antigehs containing them. | |
US11471527B2 (en) | Virus-like particles including HBs-L antigen protein for causing immune response against HBV | |
JP3616390B2 (ja) | B型肝炎のウイルスに対する細胞障害性tリンパ球の応答を誘発するペプチド | |
HU196625B (en) | Process for producing hepatitis b virus vaccine | |
KR100587944B1 (ko) | 보강제 및 HBV 백신 성분인 B형 간염 바이러스의pre S단백질 | |
US5639637A (en) | Hepatitis B vaccine | |
EP1256804B1 (en) | HBcAg expression and diagnostic and therapeutic uses | |
JP7295536B2 (ja) | B型肝炎ワクチン | |
RU2362586C2 (ru) | Фармацевтические композиции для терапевтического применения | |
KR102084912B1 (ko) | B형 간염 바이러스 표면 항원의 입체 에피토프 및 이에 특이적으로 결합하는 항체 | |
CN100355777C (zh) | 乙型肝炎病毒pre-S突变蛋白及其制备方法与应用 | |
ES2393963T3 (es) | Expresión de HBcAg y utilizaciones terapéuticas y de diagnóstico | |
US5989865A (en) | Hepatitis B vaccine | |
AU642729C (en) | Hepatitis B vaccine |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A201 | Request for examination | ||
E902 | Notification of reason for refusal | ||
E701 | Decision to grant or registration of patent right | ||
GRNT | Written decision to grant | ||
FPAY | Annual fee payment |
Payment date: 20130530 Year of fee payment: 8 |
|
FPAY | Annual fee payment |
Payment date: 20140530 Year of fee payment: 9 |
|
FPAY | Annual fee payment |
Payment date: 20150601 Year of fee payment: 10 |
|
FPAY | Annual fee payment |
Payment date: 20160601 Year of fee payment: 11 |
|
FPAY | Annual fee payment |
Payment date: 20170601 Year of fee payment: 12 |
|
FPAY | Annual fee payment |
Payment date: 20180525 Year of fee payment: 13 |