JP7407176B2 - ハウスダストダニアレルギーの処置および予防 - Google Patents
ハウスダストダニアレルギーの処置および予防 Download PDFInfo
- Publication number
- JP7407176B2 JP7407176B2 JP2021514485A JP2021514485A JP7407176B2 JP 7407176 B2 JP7407176 B2 JP 7407176B2 JP 2021514485 A JP2021514485 A JP 2021514485A JP 2021514485 A JP2021514485 A JP 2021514485A JP 7407176 B2 JP7407176 B2 JP 7407176B2
- Authority
- JP
- Japan
- Prior art keywords
- der
- seq
- amino acid
- acid sequence
- allergen
- 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
- 238000011282 treatment Methods 0.000 title claims description 13
- 230000002265 prevention Effects 0.000 title claims description 8
- 208000035533 House dust allergy Diseases 0.000 title description 9
- 239000013566 allergen Substances 0.000 claims description 131
- 239000012634 fragment Substances 0.000 claims description 79
- 108020001507 fusion proteins Proteins 0.000 claims description 66
- 102000037865 fusion proteins Human genes 0.000 claims description 66
- 150000001413 amino acids Chemical group 0.000 claims description 61
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 58
- 108010061573 Dermatophagoides pteronyssinus antigen p 5 Proteins 0.000 claims description 46
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 45
- 206010020751 Hypersensitivity Diseases 0.000 claims description 43
- 230000007815 allergy Effects 0.000 claims description 38
- 229920001184 polypeptide Polymers 0.000 claims description 38
- 108010061629 Dermatophagoides pteronyssinus antigen p 1 Proteins 0.000 claims description 30
- 108010061608 Dermatophagoides pteronyssinus antigen p 2 Proteins 0.000 claims description 30
- 230000002009 allergenic effect Effects 0.000 claims description 26
- 239000000428 dust Substances 0.000 claims description 25
- 108020004707 nucleic acids Proteins 0.000 claims description 22
- 102000039446 nucleic acids Human genes 0.000 claims description 22
- 150000007523 nucleic acids Chemical class 0.000 claims description 22
- 102000014914 Carrier Proteins Human genes 0.000 claims description 16
- 108010078791 Carrier Proteins Proteins 0.000 claims description 16
- 239000013598 vector Substances 0.000 claims description 15
- 125000000539 amino acid group Chemical group 0.000 claims description 13
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 13
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims description 9
- 108010055622 Dermatophagoides farinae antigen f 1 Proteins 0.000 claims description 8
- 108010082995 Dermatophagoides farinae antigen f 2 Proteins 0.000 claims description 8
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical group NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 108010082990 Dermatophagoides farinae antigen f 7 Proteins 0.000 claims description 5
- 241000238740 Dermatophagoides pteronyssinus Species 0.000 claims description 5
- 241000700739 Hepadnaviridae Species 0.000 claims description 5
- 241000700605 Viruses Species 0.000 claims description 5
- 241000238713 Dermatophagoides farinae Species 0.000 claims description 4
- 239000004471 Glycine Chemical group 0.000 claims description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical group C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 3
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical group C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims description 3
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 3
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Chemical group CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims description 3
- 239000004473 Threonine Chemical group 0.000 claims description 3
- 235000004279 alanine Nutrition 0.000 claims description 3
- 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 claims description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical group CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Chemical group CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 2
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 claims 1
- 229960004784 allergens Drugs 0.000 description 52
- 210000002966 serum Anatomy 0.000 description 49
- 241000283973 Oryctolagus cuniculus Species 0.000 description 38
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 34
- 208000026935 allergic disease Diseases 0.000 description 27
- 238000002347 injection Methods 0.000 description 27
- 239000007924 injection Substances 0.000 description 27
- 108010061638 Dermatophagoides pteronyssinus antigen p 7 Proteins 0.000 description 26
- 208000010668 atopic eczema Diseases 0.000 description 21
- 241000238711 Pyroglyphidae Species 0.000 description 20
- 229940046533 house dust mites Drugs 0.000 description 20
- 230000000172 allergic effect Effects 0.000 description 19
- 210000004027 cell Anatomy 0.000 description 18
- 238000002965 ELISA Methods 0.000 description 17
- 230000005764 inhibitory process Effects 0.000 description 17
- 239000011780 sodium chloride Substances 0.000 description 17
- 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 14
- 239000002671 adjuvant Substances 0.000 description 14
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 13
- 239000004202 carbamide Substances 0.000 description 13
- 210000003651 basophil Anatomy 0.000 description 12
- 108090000623 proteins and genes Proteins 0.000 description 12
- 102000004169 proteins and genes Human genes 0.000 description 11
- 230000009257 reactivity Effects 0.000 description 11
- 229960005486 vaccine Drugs 0.000 description 11
- 235000018102 proteins Nutrition 0.000 description 10
- 238000003556 assay Methods 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 239000000872 buffer Substances 0.000 description 8
- 230000004913 activation Effects 0.000 description 7
- 229910052737 gold Inorganic materials 0.000 description 7
- 239000010931 gold Substances 0.000 description 7
- 238000009169 immunotherapy Methods 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 241000238710 Dermatophagoides Species 0.000 description 6
- 101150084935 PTER gene Proteins 0.000 description 6
- 102000007478 beta-N-Acetylhexosaminidases Human genes 0.000 description 6
- 108010085377 beta-N-Acetylhexosaminidases Proteins 0.000 description 6
- 230000000903 blocking effect Effects 0.000 description 6
- 230000037396 body weight Effects 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- 101150115433 SLC26A5 gene Proteins 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 229940035032 monophosphoryl lipid a Drugs 0.000 description 5
- 229930182490 saponin Natural products 0.000 description 5
- 150000007949 saponins Chemical class 0.000 description 5
- 235000017709 saponins Nutrition 0.000 description 5
- -1 Der f 5 Proteins 0.000 description 4
- 241000588724 Escherichia coli Species 0.000 description 4
- 241000238631 Hexapoda Species 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 4
- 239000007983 Tris buffer Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 238000011533 pre-incubation Methods 0.000 description 4
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 4
- 238000007430 reference method Methods 0.000 description 4
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 4
- 241000700721 Hepatitis B virus Species 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 230000003053 immunization Effects 0.000 description 3
- 238000002649 immunization Methods 0.000 description 3
- 230000002163 immunogen Effects 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 230000001225 therapeutic effect Effects 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
- 101710131943 40S ribosomal protein S3a Proteins 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 108010039939 Cell Wall Skeleton Proteins 0.000 description 2
- 102000009016 Cholera Toxin Human genes 0.000 description 2
- 108010049048 Cholera Toxin Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 229920002271 DEAE-Sepharose Polymers 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 241000283074 Equus asinus Species 0.000 description 2
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 2
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 108091006905 Human Serum Albumin Proteins 0.000 description 2
- 102000008100 Human Serum Albumin Human genes 0.000 description 2
- 102000009438 IgE Receptors Human genes 0.000 description 2
- 108010073816 IgE Receptors Proteins 0.000 description 2
- 102000013462 Interleukin-12 Human genes 0.000 description 2
- 108010065805 Interleukin-12 Proteins 0.000 description 2
- 102000000588 Interleukin-2 Human genes 0.000 description 2
- 108010002350 Interleukin-2 Proteins 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 241000235058 Komagataella pastoris Species 0.000 description 2
- 239000000020 Nitrocellulose Substances 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 239000013504 Triton X-100 Substances 0.000 description 2
- 229920004890 Triton X-100 Polymers 0.000 description 2
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 2
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical group [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 2
- ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 description 2
- 229940024545 aluminum hydroxide Drugs 0.000 description 2
- 230000005875 antibody response Effects 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 238000000376 autoradiography Methods 0.000 description 2
- 210000004520 cell wall skeleton Anatomy 0.000 description 2
- 239000013599 cloning vector Substances 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 238000000502 dialysis Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- 208000002672 hepatitis B Diseases 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 238000003119 immunoblot Methods 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 210000003000 inclusion body Anatomy 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000011859 microparticle Substances 0.000 description 2
- 229920001220 nitrocellulos Polymers 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 229920002627 poly(phosphazenes) Polymers 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000013207 serial dilution Methods 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- 239000001488 sodium phosphate Substances 0.000 description 2
- 229910000162 sodium phosphate Inorganic materials 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- 229930003799 tocopherol Natural products 0.000 description 2
- 239000011732 tocopherol Substances 0.000 description 2
- 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 2
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 2
- 238000002255 vaccination Methods 0.000 description 2
- 210000005253 yeast cell Anatomy 0.000 description 2
- HNSDLXPSAYFUHK-UHFFFAOYSA-N 1,4-bis(2-ethylhexyl) sulfosuccinate Chemical compound CCCCC(CC)COC(=O)CC(S(O)(=O)=O)C(=O)OCC(CC)CCCC HNSDLXPSAYFUHK-UHFFFAOYSA-N 0.000 description 1
- 229910018626 Al(OH) Inorganic materials 0.000 description 1
- 206010002199 Anaphylactic shock Diseases 0.000 description 1
- 241000272478 Aquila Species 0.000 description 1
- 108010077805 Bacterial Proteins Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 206010010741 Conjunctivitis Diseases 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 108010061569 Dermatophagoides pteronyssinus antigen p 4 Proteins 0.000 description 1
- 241000255601 Drosophila melanogaster Species 0.000 description 1
- 101710146739 Enterotoxin Proteins 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 102000000704 Interleukin-7 Human genes 0.000 description 1
- 108010002586 Interleukin-7 Proteins 0.000 description 1
- 241000222722 Leishmania <genus> Species 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- NPPQSCRMBWNHMW-UHFFFAOYSA-N Meprobamate Chemical compound NC(=O)OCC(C)(CCC)COC(N)=O NPPQSCRMBWNHMW-UHFFFAOYSA-N 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 102000005877 Peptide Initiation Factors Human genes 0.000 description 1
- 108010044843 Peptide Initiation Factors Proteins 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 206010039085 Rhinitis allergic Diseases 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- 241000256251 Spodoptera frugiperda Species 0.000 description 1
- 241000255985 Trichoplusia Species 0.000 description 1
- UZQJVUCHXGYFLQ-AYDHOLPZSA-N [(2s,3r,4s,5r,6r)-4-[(2s,3r,4s,5r,6r)-4-[(2r,3r,4s,5r,6r)-4-[(2s,3r,4s,5r,6r)-3,5-dihydroxy-6-(hydroxymethyl)-4-[(2s,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,5-dihydroxy-6-(hy Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O)O[C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O)O[C@H]1CC[C@]2(C)[C@H]3CC=C4[C@@]([C@@]3(CC[C@H]2[C@@]1(C=O)C)C)(C)CC(O)[C@]1(CCC(CC14)(C)C)C(=O)O[C@H]1[C@@H]([C@@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O[C@H]4[C@@H]([C@@H](O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O)[C@H](O)[C@@H](CO)O4)O)[C@H](O)[C@@H](CO)O3)O)[C@H](O)[C@@H](CO)O2)O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UZQJVUCHXGYFLQ-AYDHOLPZSA-N 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- ZTOJFFHGPLIVKC-CLFAGFIQSA-N abts Chemical compound S/1C2=CC(S(O)(=O)=O)=CC=C2N(CC)C\1=N\N=C1/SC2=CC(S(O)(=O)=O)=CC=C2N1CC ZTOJFFHGPLIVKC-CLFAGFIQSA-N 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 229940074608 allergen extract Drugs 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- 201000010105 allergic rhinitis Diseases 0.000 description 1
- 229940037003 alum Drugs 0.000 description 1
- 229940024546 aluminum hydroxide gel Drugs 0.000 description 1
- SMYKVLBUSSNXMV-UHFFFAOYSA-K aluminum;trihydroxide;hydrate Chemical compound O.[OH-].[OH-].[OH-].[Al+3] SMYKVLBUSSNXMV-UHFFFAOYSA-K 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 238000005571 anion exchange chromatography Methods 0.000 description 1
- 230000002788 anti-peptide Effects 0.000 description 1
- 239000013011 aqueous formulation Substances 0.000 description 1
- 238000003491 array Methods 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 230000001851 biosynthetic effect Effects 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 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
- 239000013592 cell lysate Substances 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 239000013065 commercial product Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 238000004132 cross linking Methods 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
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000000147 enterotoxin Substances 0.000 description 1
- 231100000655 enterotoxin Toxicity 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 230000002550 fecal effect Effects 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229940117681 interleukin-12 Drugs 0.000 description 1
- 229940100994 interleukin-7 Drugs 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000002617 leukotrienes Chemical class 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 238000011587 new zealand white rabbit Methods 0.000 description 1
- 239000007764 o/w emulsion Substances 0.000 description 1
- 238000006384 oligomerization reaction Methods 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 229960000502 poloxamer Drugs 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- YYGNTYWPHWGJRM-AAJYLUCBSA-N squalene Chemical compound CC(C)=CCC\C(C)=C\CC\C(C)=C\CC\C=C(/C)CC\C=C(/C)CCC=C(C)C YYGNTYWPHWGJRM-AAJYLUCBSA-N 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000006190 sub-lingual tablet Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 125000004354 sulfur functional group Chemical group 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 125000002640 tocopherol group Chemical class 0.000 description 1
- 235000019149 tocopherols Nutrition 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
- 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
- 125000001493 tyrosinyl group Chemical class [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 239000000277 virosome Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Classifications
-
- 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
- A61K39/35—Allergens
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/43504—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates
- C07K14/43513—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates from arachnidae
- C07K14/43531—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates from arachnidae from mites
-
- 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
- A61K39/385—Haptens or antigens, bound to carriers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- 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
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/62—DNA sequences coding for fusion proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55566—Emulsions, e.g. Freund's adjuvant, MF59
-
- 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
- A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
- A61K2039/6031—Proteins
- A61K2039/6075—Viral proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
- A61K2039/6031—Proteins
- A61K2039/6081—Albumin; Keyhole limpet haemocyanin [KLH]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- 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
-
- 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
- C12N2730/10134—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Genetics & Genomics (AREA)
- Immunology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Insects & Arthropods (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Microbiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- General Chemical & Material Sciences (AREA)
- Toxicology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pulmonology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Biomedical Technology (AREA)
- Virology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Description
X1-Y-X2 (I)
を有する1つまたは複数の融合タンパク質によって解決される
(式中、X1およびX2は、互いに融合したそれぞれ4~8つのアレルゲン断片またはそれらのバリアントを含み、ここで、前記アレルゲン断片は、Dermatophagoides属の少なくとも2つのアレルゲンに由来し、Yは担体タンパク質である)。
X1-Y-X2 (I)
を有する1つまたは複数の融合タンパク質に関する
(式中、X1およびX2は、互いに融合したそれぞれ4~8つのアレルゲン断片またはそれらのバリアントを含み、ここで、前記アレルゲン断片は、Dermatophagoides属の少なくとも2つのアレルゲンに由来し、Yは担体タンパク質である)。
VRNSWDTNWGDNGYGYFAANIDLMMIEEYPYVVILHNGVVQESYYRYVAREQSSRRPNAQRFGISNHGSEPSIIHRGKPFQLEAVFEANQNSKTAKHGSEPSIIHRGKPFQLEAVFEANQNSKTAKVRNSWDTNWGDNGYGYFAANIDLMMIEEYPYVVILHNGVVQESYYRYVAREQSSRRPNAQRFGISN
EVDVPGIDPNASHYMKSPLVKGQQYDIKYTWIVPKIAPKSENEVDVPGIDPNASHYMKSPLVKGQQYDIKYTWIVPKIAPKSENATESAYLAYRNQSLDLAEQELVDSASQHGSHGDTIPRGIEYIQTNASSINGNAPAEIDLRQMRTVTPIRMQGGSGSSWAFSGVAATESAYLAYRNQSLDLAEQELVDSASQHGSHGDTIPRGIEYIQTNASSINGNAPAEIDLRQMRTVTPIRMQGGSGSSWAFSG
YNYEFALESIKLLIKKLDELAKKVKAVNPDEYYYNYEFALESIKLLIKKLDELAKKVKAVNPDEYYYNYEFALESIKLLIKKLDELAKKVKAVNPDEYYGYFADPKDPHKFYISSNWEAVHKDSPGNTRWNEDEETSTGYFADPKDPHKFYISSNWEAVHKDSPGNTRWNEDEETSTGYFADPKDPHKFYISSNWEAVHKDSPGNTRWNEDEETST
DYQNEFDFLLMERIHEQIKKGELALFYLQDYQNEFDFLLMERIHEQIKKGELALFYLQDPIHYDKITEEINKAVDEAVAAIEKSETFDDPIHYDKITEEINKAVDEAVAAIEKSETFDEQYNLEMAKKSGDILERDLKKEEARVKKIEVEQYNLEMAKKSGDILERDLKKEEARVKKIEV
VRNSWDTTWGDSGYGYFQAGNNLMMIEQYPYVVIMQNGVVEERSYPYVAREQQCRRPNSQHYGISNHGSDPCIIHRGKPFNLEAIFDANQNTKTAKHGSDPCIIHRGKPFNLEAIFDANQNTKTAKVRNSWDTTWGDSGYGYFQAGNNLMMIEQYPYVVIMQNGVVEERSYPYVAREQQCRRPNSQHYGISN
EVDVPGIDTNACHYIKCPLVKGQQYDAKYTWNVPKIAPKSENEVDVPGIDTNACHYIKCPLVKGQQYDAKYTWNVPKIAPKSENATESAYLAYRNTSLDLSEQELVDCASQHGCHGDTIPRGIEYIQTSACRINSVNVPSELDLRSLRTVTPIRMQGGCGSCWAFSGVAATESAYLAYRNTSLDLSEQELVDCASQHGCHGDTIPRGIEYIQTSACRINSVNVPSELDLRSLRTVTPIRMQGGCGSCWAFSGVA
YNFETAVSTIEILVKDLAELAKKVKAVKSDDYNFETAVSTIEILVKDLAELAKKVKAVKSDDYNFETAVSTIEILVKDLAELAKKVKAVKSDDGYFADPKDPCKFYICSNWEAIHKSCPGNTRWNEKELTCTGYFADPKDPCKFYICSNWEAIHKSCPGNTRWNEKELTCTGYFADPKDPCKFYICSNWEAIHKSCPGNTRWNEKELTCT
DYQNEFDFLLMQRIHEQMRKGEEALLHLQDYQNEFDFLLMQRIHEQMRKGEEALLHLQDPIHYDKITEEINKAIDDAIAAIEQSETIDDPIHYDKITEEINKAIDDAIAAIEQSETIDERYNVEIALKSNEILERDLKKEEQRVKKIEVERYNVEIALKSNEILERDLKKEEQRVKKIEV
GGWSSKPRKGMGTNLSVPNPLGFFPDHQLDPAFGANSNNPDWDFNPIKDHWPAANQVGVGAFGPGLTPPHGGILGWSPQAQGILTTVSTIPPPASTNRQSGRQPTPISPPLRDSHPQAMQWNSTAFHQALQDPRVRGLYFPAGGSSSGTVNPAPNIASHISSISARTGDPVTN
VRNSWDTNWGDNGYGYFAANIDLMMIEEYPYVVILHNGVVQESYYRYVAREQSSRRPNAQRFGISNHGSEPSIIHRGKPFQLEAVFEANQNSKTAKHGSEPSIIHRGKPFQLEAVFEANQNSKTAKVRNSWDTNWGDNGYGYFAANIDLMMIEEYPYVVILHNGVVQESYYRYVAREQSSRRPNAQRFGISNGGWSSKPRKGMGTNLSVPNPLGFFPDHQLDPAFGANSNNPDWDFNPIKDHWPAANQVGVGAFGPGLTPPHGGILGWSPQAQGILTTVSTIPPPASTNRQSGRQPTPISPPLRDSHPQAMQWNSTAFHQALQDPRVRGLYFPAGGSSSGTVNPAPNIASHISSISARTGDPVTNEVDVPGIDPNASHYMKSPLVKGQQYDIKYTWIVPKIAPKSENEVDVPGIDPNASHYMKSPLVKGQQYDIKYTWIVPKIAPKSENATESAYLAYRNQSLDLAEQELVDSASQHGSHGDTIPRGIEYIQTNASSINGNAPAEIDLRQMRTVTPIRMQGGSGSSWAFSGVAATESAYLAYRNQSLDLAEQELVDSASQHGSHGDTIPRGIEYIQTNASSINGNAPAEIDLRQMRTVTPIRMQGGSGSSWAFSG
YNYEFALESIKLLIKKLDELAKKVKAVNPDEYYYNYEFALESIKLLIKKLDELAKKVKAVNPDEYYYNYEFALESIKLLIKKLDELAKKVKAVNPDEYYGYFADPKDPHKFYISSNWEAVHKDSPGNTRWNEDEETSTGYFADPKDPHKFYISSNWEAVHKDSPGNTRWNEDEETSTGYFADPKDPHKFYISSNWEAVHKDSPGNTRWNEDEETSTGGWSSKPRKGMGTNLSVPNPLGFFPDHQLDPAFGANSNNPDWDFNPIKDHWPAANQVGVGAFGPGLTPPHGGILGWSPQAQGILTTVSTIPPPASTNRQSGRQPTPISPPLRDSHPQAMQWNSTAFHQALQDPRVRGLYFPAGGSSSGTVNPAPNIASHISSISARTGDPVTNDYQNEFDFLLMERIHEQIKKGELALFYLQDYQNEFDFLLMERIHEQIKKGELALFYLQDPIHYDKITEEINKAVDEAVAAIEKSETFDDPIHYDKITEEINKAVDEAVAAIEKSETFDEQYNLEMAKKSGDILERDLKKEEARVKKIEVEQYNLEMAKKSGDILERDLKKEEARVKKIEV
VRNSWDTNWGDNGYGYFAANIDLMMIEEYPYVVILHNGVVQESYYRYVAREQSSRRPNAQRFGISNVRNSWDTNWGDNGYGYFAANIDLMMIEEYPYVVILHNGVVQESYYRYVAREQSSRRPNAQRFGISNHGSEPSIIHRGKPFQLEAVFEANQNSKTAKHGSEPSIIHRGKPFQLEAVFEANQNSKTAKGGWSSKPRKGMGTNLSVPNPLGFFPDHQLDPAFGANSNNPDWDFNPIKDHWPAANQVGVGAFGPGLTPPHGGILGWSPQAQGILTTVSTIPPPASTNRQSGRQPTPISPPLRDSHPQAMQWNSTAFHQALQDPRVRGLYFPAGGSSSGTVNPAPNIASHISSISARTGDPVTNEVDVPGIDPNASHYMKSPLVKGQQYDIKYTWIVPKIAPKSENEVDVPGIDPNASHYMKSPLVKGQQYDIKYTWIVPKIAPKSENATESAYLAYRNQSLDLAEQELVDSASQHGSHGDTIPRGIEYIQTNASSINGNAPAEIDLRQMRTVTPIRMQGGSGSSWAFSGVAATESAYLAYRNQSLDLAEQELVDSASQHGSHGDTIPRGIEYIQTNASSINGNAPAEIDLRQMRTVTPIRMQGGSGSSWAFSG
VRNSWDTNWGDNGYGYFAANIDLMMIEEYPYVVILHNGVVQESYYRYVAREQSSRRPNAQRFGISNVRNSWDTNWGDNGYGYFAANIDLMMIEEYPYVVILHNGVVQESYYRYVAREQSSRRPNAQRFGISNHGSEPSIIHRGKPFQLEAVFEANQNSKTAKHGSEPSIIHRGKPFQLEAVFEANQNSKTAKGGWSSKPRKGMGTNLSVPNPLGFFPDHQLDPAFGANSNNPDWDFNPIKDHWPAANQVGVGAFGPGLTPPHGGILGWSPQAQGILTTVSTIPPPASTNRQSGRQPTPISPPLRDSHPQAMQWNSTAFHQALQDPRVRGLYFPAGGSSSGTVNPAPNIASHISSISARTGDPVTNATESAYLAYRNQSLDLAEQELVDSASQHGSHGDTIPRGIEYIQTNASSINGNAPAEIDLRQMRTVTPIRMQGGSGSSWAFSGVAEVDVPGIDPNASHYMKSPLVKGQQYDIKYTWIVPKIAPKSENEVDVPGIDPNASHYMKSPLVKGQQYDIKYTWIVPKIAPKSENATESAYLAYRNQSLDLAEQELVDSASQHGSHGDTIPRGIEYIQTNASSINGNAPAEIDLRQMRTVTPIRMQGGSGSSWAFSG
YNYEFALESIKLLIKKLDELAKKVKAVNPDEYYYNYEFALESIKLLIKKLDELAKKVKAVNPDEYYYNYEFALESIKLLIKKLDELAKKVKAVNPDEYYGYFADPKDPHKFYICSNWEAVHKDCPGNTGYFADPKDPHKFYICSNWEAVHKDCPGNTGGWSSKPRKGMGTNLSVPNPLGFFPDHQLDPAFGANSNNPDWDFNPIKDHWPAANQVGVGAFGPGLTPPHGGILGWSPQAQGILTTVSTIPPPASTNRQSGRQPTPISPPLRDSHPQAMQWNSTAFHQALQDPRVRGLYFPAGGSSSGTVNPAPNIASHISSISARTGDPVTNKFYICSNWEAVHKDCPGNTRWNEDEETCTKFYICSNWEAVHKDCPGNTRWNEDEETCTDYQNEFDFLLMERIHEQIKKGELALFYLQDYQNEFDFLLMERIHEQIKKGELALFYLQDPIHYDKITEEINKAVDEAVAAIEKSETFDDPIHYDKITEEINKAVDEAVAAIEKSETFDEQYNLEMAKKSGDILERDLKKEEARVKKIEVEQYNLEMAKKSGDILERDLKKEEARVKKIEV
YNYEFALESIKLLIKKLDELAKKVKAVNPDEYYYNYEFALESIKLLIKKLDELAKKVKAVNPDEYYYNYEFALESIKLLIKKLDELAKKVKAVNPDEYYYNYEFALESIKLLIKKLDELAKKVKAVNPDEYYDPIHYDKITEEINKAVDEAVAAIEKSETFDDPIHYDKITEEINKAVDEAVAAIEKSETFDGGWSSKPRKGMGTNLSVPNPLGFFPDHQLDPAFGANSNNPDWDFNPIKDHWPAANQVGVGAFGPGLTPPHGGILGWSPQAQGILTTVSTIPPPASTNRQSGRQPTPISPPLRDSHPQAMQWNSTAFHQALQDPRVRGLYFPAGGSSSGTVNPAPNIASHISSISARTGDPVTNDYQNEFDFLLMERIHEQIKKGELALFYLQDYQNEFDFLLMERIHEQIKKGELALFYLQDPIHYDKITEEINKAVDEAVAAIEKSETFDDPIHYDKITEEINKAVDEAVAAIEKSETFDEQYNLEMAKKSGDILERDLKKEEARVKKIEVEQYNLEMAKKSGDILERDLKKEEARVKKIEV
YNYEFALESIKLLIKKLDELAKKVKAVNPDEYYYNYEFALESIKLLIKKLDELAKKVKAVNPDEYYYNYEFALESIKLLIKKLDELAKKVKAVNPDEYYYNYEFALESIKLLIKKLDELAKKVKAVNPDEYYDYQNEFDFLLMERIHEQIKKGELALFYLQDYQNEFDFLLMERIHEQIKKGELALFYLQGGWSSKPRKGMGTNLSVPNPLGFFPDHQLDPAFGANSNNPDWDFNPIKDHWPAANQVGVGAFGPGLTPPHGGILGWSPQAQGILTTVSTIPPPASTNRQSGRQPTPISPPLRDSHPQAMQWNSTAFHQALQDPRVRGLYFPAGGSSSGTVNPAPNIASHISSISARTGDPVTNDPIHYDKITEEINKAVDEAVAAIEKSETFDDPIHYDKITEEINKAVDEAVAAIEKSETFDDPIHYDKITEEINKAVDEAVAAIEKSETFDDPIHYDKITEEINKAVDEAVAAIEKSETFDEQYNLEMAKKSGDILERDLKKEEARVKKIEVEQYNLEMAKKSGDILERDLKKEEARVKKIEV
VRNSWDTTWGDSGYGYFQAGNNLMMIEQYPYVVIMQNGVVEERSYPYVAREQQSRRPNSQHYGISNHGSDPSIIHRGKPFNLEAIFDANQNTKTAKHGSDPSIIHRGKPFNLEAIFDANQNTKTAKVRNSWDTTWGDSGYGYFQAGNNLMMIEQYPYVVIMQNGVVEERSYPYVAREQQSRRPNSQHYGISNGGWSSKPRKGMGTNLSVPNPLGFFPDHQLDPAFGANSNNPDWDFNPIKDHWPAANQVGVGAFGPGLTPPHGGILGWSPQAQGILTTVSTIPPPASTNRQSGRQPTPISPPLRDSHPQAMQWNSTAFHQALQDPRVRGLYFPAGGSSSGTVNPAPNIASHISSISARTGDPVTNEVDVPGIDTNASHYIKSPLVKGQQYDAKYTWNVPKIAPKSENEVDVPGIDTNASHYIKSPLVKGQQYDAKYTWNVPKIAPKSENATESAYLAYRNTSLDLSEQELVDSASQHGSHGDTIPRGIEYIQTSASRINSVNVPSELDLRSLRTVTPIRMQGGSGSSWAFSGVAATESAYLAYRNTSLDLSEQELVDSASQHGSHGDTIPRGIEYIQTSASRINSVNVPSELDLRSLRTVTPIRMQGGSGSSWAFSG
YNFETAVSTIEILVKDLAELAKKVKAVKSDDYNFETAVSTIEILVKDLAELAKKVKAVKSDDYNFETAVSTIEILVKDLAELAKKVKAVKSDDGYFADPKDPSKFYISSNWEAIHKSSPGNTRWNEKELTSTGYFADPKDPSKFYISSNWEAIHKSSPGNTRWNEKELTSTGYFADPKDPSKFYISSNWEAIHKSSPGNTRWNEKELTSTGGWSSKPRKGMGTNLSVPNPLGFFPDHQLDPAFGANSNNPDWDFNPIKDHWPAANQVGVGAFGPGLTPPHGGILGWSPQAQGILTTVSTIPPPASTNRQSGRQPTPISPPLRDSHPQAMQWNSTAFHQALQDPRVRGLYFPAGGSSSGTVNPAPNIASHISSISARTGDPVTNDYQNEFDFLLMQRIHEQMRKGEEALLHLQDYQNEFDFLLMQRIHEQMRKGEEALLHLQDPIHYDKITEEINKAIDDAIAAIEQSETIDDPIHYDKITEEINKAIDDAIAAIEQSETIDERYNVEIALKSNEILERDLKKEEQRVKKIEVERYNVEIALKSNEILERDLKKEEQRVKKIEV
目的のアレルゲン配列にまたがるペプチドは、ExPASYサーバーからのProtScaleバイオインフォマティクスツールによって決定したアミノ酸の表面露出の予測に基づいて同定した(http://web.expasy.org/protscale/)。ペプチドがその配列にシステイン残基を含有していない場合は、キーホールリンペットヘモシアニン(KLH)にペプチドが結合できるようにするために、ペプチドのN末端またはC末端にシステインを付加した。ペプチドを、Applied BiosystemsペプチドシンセサイザーModel 433A(Foster City、米国)を使用して合成し、続いて、分取高速液体クロマトグラフィー(HPLC)(Dionex、Thermofischer Scientific、米国)(Fockeら、FASEB J.2001;15(11):2042~4ページ)によって精製した。ペプチドのサイズと同一性は、質量分析法(Bruker、オーストリア)によって確認した。
融合タンパク質Der p 1-2 C3およびDer p 5 7 21 23_P6(大)をコードする遺伝子(大腸菌発現向けにコドン最適化した)を合成し(ATG:biosynthetics、Merzhausen、ドイツおよびGenScript、Piscataway、米国)、pET-27b(Novagen、ドイツ)のNdeI/XhoI部位に挿入した。組換えタンパク質を、大腸菌株BL21-Gold(DE3)において発現させた。Der p 1-2 C3(図1を参照されたい;配列番号27)の発現を、細菌培養物に0.5mM IPTGを添加し、37℃で3時間インキュベートすることにより、OD600が0.4で誘導した。Der p 5 7 21 23_P6(大)(図1を参照されたい;配列番号28)を、1mM IPTGを添加し、培養物を37℃で2.5時間インキュベートすることにより、OD600が0.6で誘導した。
実施例2の構築物のIgE反応性を、イムノブロットによって決定した(Curin Mら Sci Rep.22(2017):12135ページ)。0.5μgの精製nDer p 1(天然分離株;受託番号:PDB:3RVW_A;参照方法:Hales,B.J.ら Clin Exp Allergy.30(2000):934~943ページ)、rDer p 2(組換えにより産生したDer p 2;Chen KWら、Allergy.67(2012):609~21ページに公開の配列;参照方法:Chen,K.ら Mol Immunol.45(2008):2486~2498ページ)、rDer p 5(GeneBank:X17699;参照方法:Weghofer Mら Int Arch Allergy Immunol.147(2008):101~9ページ)、rDer p 7(GeneBank:U37044;参照方法:Resch Yら Clin Exp Allergy.41(2011):1468~77ページ)、rDer p 21(GeneBank:DQ354124;参照方法:Weghofer Mら Allergy.63(2008):758~67ページ)、rDer p 23(GeneBank:EU414751.1;参照方法:Weghofer Mら J Immunol.190(2013):3059~67ページ)、Der p 1-2 C3(実施例2を参照されたい)、Der p 5 7 21 23_P6(大)(実施例2を参照されたい)を含有する一定分量を、および対照目的の場合は、BSAを、ニトロセルロース膜(Schleicher & Schuell、ドイツ)上にドットした。膜をゴールドバッファ(50mMリン酸ナトリウム[pH7.4]、0.5%[v/v]Tween-20、0.5%[w/v]BSA、および0.05%[w/v]アジ化ナトリウム)で20分間、3回ブロッキングし、次いで、ハウスダストダニアレルギー患者の血清(ゴールドバッファで1:10に希釈)と、および非アレルギーのヒトからの血清(ゴールドバッファで1:10に希釈)と、4℃で一晩インキュベートした。結合したIgEを、1:10に希釈した125I標識抗ヒトIgE Abs(Demeditec Diagnostics、Kiel、ドイツ)で検出し、前記のようにオートラジオグラフィー(Kodak XOMATフィルム)によって視覚化した(Curinら Sci Rep.22(2017):12135ページ)。
ブロッキング抗体がアレルギーの免疫療法において主要な役割を果たすことが示されたので、ブロッキング抗体を誘導するペプチドの能力に関する情報は重要である。
本発明の構築物、特にDer p 1-2 C3およびDer p 5 7 21 23_P6(大)のアレルゲン活性を試験するために、ヒト高親和性IgE受容体FcεRIを発現するラット好塩基球白血病細胞(RBL)(1×105/ウェル)に、ハウスダストダニアレルギー患者からの血清を1:10の希釈率で一晩ロードした。細胞をタイロードバッファ(Sigma、オーストリア)で3回洗浄し、アレルゲン(それぞれ、100ng/mL、10ng/mL、および1ng/mLのnDer p 1、rDer p 2、rDer p 5、rDer p 7、rDer p 21、rDer p 23、Der p 1-2 C3およびDer p 5 7 21 23_P6(大))の連続希釈に1時間曝露した。アレルゲンを含まない血清または血清を含まないアレルゲンを陰性対照として使用した。上清を前記のようにβ-ヘキソサミニダーゼ活性について分析した(Hartlら Allergy 59(2004):65~73ページ)。実験は3回繰返しで実施し、結果を、1%Triton X-100の添加後に放出された総β-ヘキソサミニダーゼの平均百分率+/-平均のSE(SEM)として提示する(図4および5を参照されたい)。
2匹のニュージーランドシロウサギの群を、種々の用量のBM35(配列番号27および28のアミノ酸配列を1:1の重量比で含む融合タンパク質を含む調製物)で、および、製造業者の指示に従って市販の調製物(表IIIを参照されたい)で、それぞれ皮下免疫した。対照ウサギを、アレルゲンnDer p 1、rDer p 2、rDer p 5、rDer p 7、rDer p 21およびrDer p 23で免疫した。
Claims (13)
- 式(I)
X1-Y-X2 (I)
を有する融合タンパク質
(式中、
X1およびX2は、互いに融合したそれぞれ4~8つのアレルゲン断片またはそれらのバリアントを含み、ここで、前記アレルゲン断片は、Der p 1、Der p 2、Der p 5、Der p7、Der p 21およびDer p 23からなる群から選択される少なくとも2つのアレルゲンに由来し、
Yは担体タンパク質である)であって、
前記融合タンパク質が、配列番号18、配列番号19、配列番号20、配列番号21、配列番号22、配列番号23、配列番号24および/または配列番号25からなる群から選択されるアミノ酸配列を有する少なくとも1つのポリペプチドを含み、
a)Der p 1のアレルゲン断片が、
TNACSINGNAPAEIDLRQMRTVTPIRMQGGCGSCWAFSGVA(配列番号1)、ATESAYLAYRNQSLDLAEQELVDCASQHGCHGDTIPRGIEYIQ(配列番号2)、HNGVVQESYYRYVAREQSCRRPNAQRFGISN(配列番号3)、VRNSWDTNWGDNGYGYFAANIDLMMIEEYPYVVIL(配列番号4)、TNASSINGNAPAEIDLRQMRTVTPIRMQGGSGSSWAFSGVA(配列番号5)、ATESAYLAYRNQSLDLAEQELVDSASQHGSHGDTIPRGIEYIQ(配列番号6)およびHNGVVQESYYRYVAREQSSRRPNAQRFGISN(配列番号7)
からなる群から選択されるアミノ酸配列と、少なくとも90%同一であるアミノ酸配列からなり、ならびに/または
b)Der p 2のアレルゲン断片が、
CHGSEPCIIHRGKPFQLEAVFEANQNSKTAK(配列番号8)、EVDVPGIDPNACHYMKCPLVKGQQYDIKYTWIVPKIAPKSEN(配列番号9)、HGSEPSIIHRGKPFQLEAVFEANQNSKTAK(配列番号10)およびEVDVPGIDPNASHYMKSPLVKGQQYDIKYTWIVPKIAPKSEN(配列番号11)
からなる群から選択されるアミノ酸配列と、少なくとも90%同一であるアミノ酸配列からなり、ならびに/または
c)Der p 5のアレルゲン断片が、
DYQNEFDFLLMERIHEQIKKGELALFYLQ(配列番号12)およびEQYNLEMAKKSGDILERDLKKEEARVKKIEV(配列番号13)
からなる群から選択されるアミノ酸配列と、少なくとも90%同一であるアミノ酸配列からなり、ならびに/または
d)Der p 7のアレルゲン断片が、
アミノ酸配列DPIHYDKITEEINKAVDEAVAAIEKSETFD(配列番号14)と、少なくとも90%同一であるアミノ酸配列からなり、ならびに/または
e)Der p 21のアレルゲン断片が、
アミノ酸配列YNYEFALESIKLLIKKLDELAKKVKAVNPDEYY(配列番号15)と、少なくとも90%同一であるアミノ酸配列からなり、ならびに/または
f)Der p 23のアレルゲン断片が、
GYFADPKDPHKFYICSNWEAVHKDCPGNTRWNEDEETCT(配列番号16)およびGYFADPKDPHKFYISSNWEAVHKDSPGNTRWNEDEETST(配列番号17)
からなる群から選択されるアミノ酸配列と、少なくとも90%同一であるアミノ酸配列からなり、ならびに/または
g)Der f 1のアレルゲン断片が、
TSACRINSVNVPSELDLRSLRTVTPIRMQGGCGSCWAFSGVA(配列番号38)、ATESAYLAYRNTSLDLSEQELVDCASQHGCHGDTIPRGIEYIQ(配列番号39)、QNGVVEERSYPYVAREQQCRRPNSQHYGISN(配列番号40)およびVRNSWDTTWGDSGYGYFQAGNNLMMIEQYPYVVIM(配列番号41)
からなる群から選択されるアミノ酸配列と、少なくとも90%同一であるアミノ酸配列からなり、ならびに/または
h)Der f 2のアレルゲン断片が、
HGSDPCIIHRGKPFNLEAIFDANQNTKTAK(配列番号42)およびEVDVPGIDTNACHYIKCPLVKGQQYDAKYTWNVPKIAPKSEN(配列番号43)
からなる群から選択されるアミノ酸配列と、少なくとも90%同一であるアミノ酸配列からなり、ならびに/または
i)Der f 5のアレルゲン断片が、
DYQNEFDFLLMQRIHEQMRKGEEALLHLQ(配列番号44)およびERYNVEIALKSNEILERDLKKEEQRVKKIEV(配列番号45)
からなる群から選択されるアミノ酸配列と、少なくとも90%同一であるアミノ酸配列からなり、ならびに/または
j)Der f 7のアレルゲン断片が、
アミノ酸配列DPIHYDKITEEINKAIDDAIAAIEQSETID(配列番号46)であり、ならびに/または
k)Der f 21のアレルゲン断片が、
アミノ酸配列YNFETAVSTIEILVKDLAELAKKVKAVKSDD(配列番号47)と、少なくとも90%同一であるアミノ酸配列からなり、ならびに/または
l)Der f 23のアレルゲン断片が、
アミノ酸配列GYFADPKDPCKFYICSNWEAIHKSCPGNTRWNEKELTCT(配列番号48)である、融合タンパク質。 - 前記少なくとも2つのアレルゲンが、Dermatophagoides pteronyssinusおよび/またはDermatophagoides farinaeのものである、請求項1に記載の融合タンパク質。
- 前記少なくとも2つのアレルゲンのアレルゲン断片が、25~50個のアミノ酸残基、好ましくは28~48個のアミノ酸残基、より好ましくは30~45個のアミノ酸残基からなる、請求項1又は2に記載の融合タンパク質。
- アレルゲン断片のシステイン残基のうちの少なくとも1個が、セリン、スレオニン、グリシン、アラニンまたはロイシンで置換されている、請求項1から3のいずれか一項に記載の融合タンパク質。
- 担体タンパク質が、hepadnaviridae科のウイルスの表面ポリペプチドまたは前記表面ポリペプチドの断片である、請求項1から4のいずれか一項に記載の融合タンパク質。
- 配列番号27のアミノ酸配列または配列番号28のアミノ酸配列を含む、請求項1から5のいずれか一項に記載の融合タンパク質。
- 請求項1から6のいずれか一項に記載の融合タンパク質をコードする核酸分子。
- 請求項7に記載の核酸分子を含むベクター。
- 請求項7に記載の核酸分子または請求項8に記載のベクターを含む宿主細胞。
- 請求項1から6のいずれか一項に記載の少なくとも1つの融合タンパク質、または請求項7に記載の少なくとも1つの核酸分子を含む医薬調製物。
- 調製物に含まれている2つの融合タンパク質または核酸分子が、1:10~10:1の重量比を有する、請求項10に記載の医薬調製物。
- 前記調製物が、配列番号27のアミノ酸配列を含む融合タンパク質および/もしくは配列番号28のアミノ酸配列を含む融合タンパク質、または、
配列番号27のアミノ酸配列を含む融合タンパク質および/もしくは配列番号28のアミノ酸配列を含む融合タンパク質をコードする核酸分子
を含む、
請求項10または11に記載の医薬調製物。 - ハウスダストダニのアレルゲンによって引き起こされるアレルギーの処置または予防に使用するための、請求項1から6のいずれか一項に記載の融合タンパク質、請求項7に記載の核酸分子、または請求項10に記載の医薬調製物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP18173258.7 | 2018-05-18 | ||
EP18173258.7A EP3569612A1 (en) | 2018-05-18 | 2018-05-18 | Treatment and prevention of house dust mite allergies |
PCT/EP2019/062800 WO2019219907A1 (en) | 2018-05-18 | 2019-05-17 | Treatment and prevention of house dust mite allergies |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2021524280A JP2021524280A (ja) | 2021-09-13 |
JP7407176B2 true JP7407176B2 (ja) | 2023-12-28 |
Family
ID=62530077
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2021514485A Active JP7407176B2 (ja) | 2018-05-18 | 2019-05-17 | ハウスダストダニアレルギーの処置および予防 |
Country Status (16)
Country | Link |
---|---|
US (1) | US11771760B2 (ja) |
EP (2) | EP3569612A1 (ja) |
JP (1) | JP7407176B2 (ja) |
KR (1) | KR20210010931A (ja) |
CN (1) | CN112313245A (ja) |
AU (1) | AU2019270472A1 (ja) |
BR (1) | BR112020023466A2 (ja) |
CA (1) | CA3100175A1 (ja) |
CU (1) | CU20200085A7 (ja) |
IL (1) | IL278831A (ja) |
MA (1) | MA52622A (ja) |
MX (1) | MX2020012098A (ja) |
SG (1) | SG11202011123QA (ja) |
TW (1) | TW202010751A (ja) |
WO (1) | WO2019219907A1 (ja) |
ZA (1) | ZA202007022B (ja) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112225816A (zh) * | 2020-09-30 | 2021-01-15 | 四川携光生物技术有限公司 | 一种新型的吸入性过敏原融合蛋白及其构建方法、应用 |
WO2024098216A1 (en) * | 2022-11-07 | 2024-05-16 | Worg Pharmaceuticals (Zhejiang) Co., Ltd | Vaccine for treating allergies |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2013504307A (ja) | 2009-09-10 | 2013-02-07 | バイオメイ アクツェンゲゼルシャフト | アレルギー治療用低アレルゲン性ハイブリッドポリペプチド |
JP2014518635A (ja) | 2011-06-09 | 2014-08-07 | ビオマイ アクチエンゲゼルシャフト | アレルギーワクチンとしてのペプチド担体融合タンパク質 |
Family Cites Families (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA1331443C (en) | 1987-05-29 | 1994-08-16 | Charlotte A. Kensil | Saponin adjuvant |
US5057540A (en) | 1987-05-29 | 1991-10-15 | Cambridge Biotech Corporation | Saponin adjuvant |
AUPM873294A0 (en) | 1994-10-12 | 1994-11-03 | Csl Limited | Saponin preparations and use thereof in iscoms |
UA56132C2 (uk) | 1995-04-25 | 2003-05-15 | Смітклайн Бічем Байолоджікалс С.А. | Композиція вакцини (варіанти), спосіб стабілізації qs21 відносно гідролізу (варіанти), спосіб приготування композиції вакцини |
CN1326564C (zh) | 1997-04-01 | 2007-07-18 | 科里克萨有限公司 | 单磷酰基脂质a的水性免疫佐剂组合物 |
US7439233B1 (en) * | 1999-02-25 | 2008-10-21 | Tai June Yoo | Vaccine for house dust mite allergen using naked DNA |
AT503690A1 (de) * | 2006-06-09 | 2007-12-15 | Biomay Ag | Hypoallergene moleküle |
EP1908776A1 (en) * | 2006-10-06 | 2008-04-09 | Stallergenes Sa | Mite fusion proteins |
ES2638271T3 (es) * | 2008-03-25 | 2017-10-19 | Bial Industrial Farmaceutica, S.A. | Proteínas híbridas hipoalergénicas de alérgenos de ácaros del grupo 1 y 2 principales para uso en el tratamiento de alergias |
EP2727934B1 (en) * | 2012-09-20 | 2016-06-15 | Universidad de Cartagena | Fusion proteins with representation of different allergens: vaccine proposal for mite allergies |
WO2015070925A1 (en) * | 2013-11-15 | 2015-05-21 | Biomay Ag | Fusion proteins |
GB201602850D0 (en) * | 2016-02-18 | 2016-04-06 | Bial Ind Farmaceutica S A | Fusion proteins |
-
2018
- 2018-05-18 EP EP18173258.7A patent/EP3569612A1/en not_active Withdrawn
-
2019
- 2019-05-14 TW TW108116548A patent/TW202010751A/zh unknown
- 2019-05-17 MA MA052622A patent/MA52622A/fr unknown
- 2019-05-17 SG SG11202011123QA patent/SG11202011123QA/en unknown
- 2019-05-17 US US17/055,817 patent/US11771760B2/en active Active
- 2019-05-17 JP JP2021514485A patent/JP7407176B2/ja active Active
- 2019-05-17 CN CN201980039448.5A patent/CN112313245A/zh active Pending
- 2019-05-17 MX MX2020012098A patent/MX2020012098A/es unknown
- 2019-05-17 WO PCT/EP2019/062800 patent/WO2019219907A1/en active Application Filing
- 2019-05-17 AU AU2019270472A patent/AU2019270472A1/en active Pending
- 2019-05-17 CA CA3100175A patent/CA3100175A1/en active Pending
- 2019-05-17 EP EP19724826.3A patent/EP3794020A1/en active Pending
- 2019-05-17 CU CU2020000085A patent/CU20200085A7/es unknown
- 2019-05-17 BR BR112020023466-4A patent/BR112020023466A2/pt unknown
- 2019-05-17 KR KR1020207036528A patent/KR20210010931A/ko unknown
-
2020
- 2020-11-11 ZA ZA2020/07022A patent/ZA202007022B/en unknown
- 2020-11-18 IL IL278831A patent/IL278831A/en unknown
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2013504307A (ja) | 2009-09-10 | 2013-02-07 | バイオメイ アクツェンゲゼルシャフト | アレルギー治療用低アレルゲン性ハイブリッドポリペプチド |
JP2014518635A (ja) | 2011-06-09 | 2014-08-07 | ビオマイ アクチエンゲゼルシャフト | アレルギーワクチンとしてのペプチド担体融合タンパク質 |
Non-Patent Citations (2)
Title |
---|
BANERJEE S. et al.,CONVERSION OF DER P 23, A NEW MAJOR HOUSE DUST MITE ALLERGEN, INTO A HYPOALLERGENIC VACCINE,J Immunol, 2014, vol. 192, no. 10, p. 4867-4875 |
CURIN M. et al.,Similar localization of conformational IgE epitopes on the house dust mite allergens Der p 5 and Der p 21 despite limited IgE cross-reactivity,ALLERGY, Epub 2018 Feb 21, vol. 73, no. 8, p. 1653-1661 |
Also Published As
Publication number | Publication date |
---|---|
MA52622A (fr) | 2021-03-24 |
US11771760B2 (en) | 2023-10-03 |
BR112020023466A2 (pt) | 2021-03-30 |
IL278831A (en) | 2021-01-31 |
SG11202011123QA (en) | 2020-12-30 |
CA3100175A1 (en) | 2019-11-21 |
AU2019270472A1 (en) | 2020-11-26 |
CN112313245A (zh) | 2021-02-02 |
WO2019219907A1 (en) | 2019-11-21 |
MX2020012098A (es) | 2021-03-09 |
CU20200085A7 (es) | 2021-08-06 |
EP3794020A1 (en) | 2021-03-24 |
JP2021524280A (ja) | 2021-09-13 |
EP3569612A1 (en) | 2019-11-20 |
TW202010751A (zh) | 2020-03-16 |
US20210128718A1 (en) | 2021-05-06 |
KR20210010931A (ko) | 2021-01-28 |
ZA202007022B (en) | 2023-05-31 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6300907B2 (ja) | イエダニアレルギーの処置のための連続したオーバーラップペプチド | |
JP7407176B2 (ja) | ハウスダストダニアレルギーの処置および予防 | |
WO2023064708A1 (en) | Vaccine compositions against sars-cov-2 variants of concern to prevent infection and treat long-haul covid | |
EP4313138A1 (en) | Sars-cov-2 subunit vaccine | |
JP2010535504A5 (ja) | ||
KR20180038557A (ko) | 타겟 폴리펩티드를 제시하기 위한 폴리펩티드 캐리어 및 이의 용도 | |
US10195266B2 (en) | Versatile influenza virus vaccine composition | |
US11872279B2 (en) | SARS-CoV-2 antigens and uses thereof | |
RU2815386C2 (ru) | Лечение и профилактика аллергии на клещей домашней пыли | |
EP1317484B1 (en) | Variants of the phleum pratense phl p 1 allergenic protein | |
JP2022553258A (ja) | インフルエンザウイルスワクチン及びその使用 | |
US11926651B2 (en) | Polypeptide construct comprising fragments of allergens | |
WO2015077442A2 (en) | Grass pollen immunogens and methods and uses for immune response modulation | |
CN115850398B (zh) | 新型冠状病毒奥密克戎系列变异株的多肽组合物及其应用 | |
WO2024098216A1 (en) | Vaccine for treating allergies | |
EP2281836B9 (en) | Hybrid proteins from Parietaria judaica major allergens and uses thereof | |
US20140328881A1 (en) | Hypoallergenic variants of phl p 5, the major allergen from phleum pratense | |
AU2014352986A1 (en) | Pan pollen immunogens and methods and uses thereof for immune response modulation |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20220516 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20230523 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20230818 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20231017 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20231121 |
|
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: 20231128 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20231122 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20231218 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 7407176 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |