JP5087201B2 - 抗原に小胞体シャペロンポリペプチドを連結した分子ワクチン - Google Patents
抗原に小胞体シャペロンポリペプチドを連結した分子ワクチン Download PDFInfo
- Publication number
- JP5087201B2 JP5087201B2 JP2002518253A JP2002518253A JP5087201B2 JP 5087201 B2 JP5087201 B2 JP 5087201B2 JP 2002518253 A JP2002518253 A JP 2002518253A JP 2002518253 A JP2002518253 A JP 2002518253A JP 5087201 B2 JP5087201 B2 JP 5087201B2
- Authority
- JP
- Japan
- Prior art keywords
- polypeptide
- cell
- cells
- nucleic acid
- crt
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims description 339
- 102000004196 processed proteins & peptides Human genes 0.000 title claims description 215
- 229920001184 polypeptide Polymers 0.000 title claims description 189
- 108010006519 Molecular Chaperones Proteins 0.000 title claims description 65
- 108091007433 antigens Proteins 0.000 title claims description 64
- 239000000427 antigen Substances 0.000 title claims description 62
- 102000036639 antigens Human genes 0.000 title claims description 62
- 210000002472 endoplasmic reticulum Anatomy 0.000 title description 65
- 108010008038 Synthetic Vaccines Proteins 0.000 title description 2
- 210000004027 cell Anatomy 0.000 claims description 221
- 108090000549 Calreticulin Proteins 0.000 claims description 182
- 102000004082 Calreticulin Human genes 0.000 claims description 181
- 150000007523 nucleic acids Chemical class 0.000 claims description 99
- 206010028980 Neoplasm Diseases 0.000 claims description 83
- 102000039446 nucleic acids Human genes 0.000 claims description 76
- 108020004707 nucleic acids Proteins 0.000 claims description 76
- 238000000034 method Methods 0.000 claims description 65
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 claims description 63
- 239000000203 mixture Substances 0.000 claims description 63
- 230000000890 antigenic effect Effects 0.000 claims description 54
- 230000014509 gene expression Effects 0.000 claims description 54
- 108091054437 MHC class I family Proteins 0.000 claims description 48
- 102000043129 MHC class I family Human genes 0.000 claims description 46
- 210000004443 dendritic cell Anatomy 0.000 claims description 43
- 229960005486 vaccine Drugs 0.000 claims description 40
- 230000028993 immune response Effects 0.000 claims description 36
- 210000000612 antigen-presenting cell Anatomy 0.000 claims description 35
- 239000013612 plasmid Substances 0.000 claims description 32
- 230000004927 fusion Effects 0.000 claims description 31
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 26
- 210000004881 tumor cell Anatomy 0.000 claims description 25
- 239000002245 particle Substances 0.000 claims description 21
- 239000012634 fragment Substances 0.000 claims description 19
- 241000700605 Viruses Species 0.000 claims description 17
- 230000004044 response Effects 0.000 claims description 17
- 230000002708 enhancing effect Effects 0.000 claims description 16
- 241000710960 Sindbis virus Species 0.000 claims description 15
- 239000008194 pharmaceutical composition Substances 0.000 claims description 15
- 239000013604 expression vector Substances 0.000 claims description 14
- 230000001939 inductive effect Effects 0.000 claims description 13
- 239000000126 substance Substances 0.000 claims description 13
- 241001465754 Metazoa Species 0.000 claims description 11
- 239000007924 injection Substances 0.000 claims description 11
- 238000002347 injection Methods 0.000 claims description 11
- 241000341655 Human papillomavirus type 16 Species 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 10
- 244000052769 pathogen Species 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 210000002889 endothelial cell Anatomy 0.000 claims description 7
- 125000000539 amino acid group Chemical group 0.000 claims description 6
- 230000001965 increasing effect Effects 0.000 claims description 6
- 241000894006 Bacteria Species 0.000 claims description 5
- 101000793651 Homo sapiens Calreticulin Proteins 0.000 claims description 5
- 230000001717 pathogenic effect Effects 0.000 claims description 5
- 210000001130 astrocyte Anatomy 0.000 claims description 4
- 210000003719 b-lymphocyte Anatomy 0.000 claims description 4
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical group [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052737 gold Inorganic materials 0.000 claims description 4
- 239000010931 gold Substances 0.000 claims description 4
- 210000002510 keratinocyte Anatomy 0.000 claims description 4
- 210000002540 macrophage Anatomy 0.000 claims description 4
- 210000000274 microglia Anatomy 0.000 claims description 4
- 210000001616 monocyte Anatomy 0.000 claims description 4
- 102000053922 human CALR Human genes 0.000 claims description 3
- 230000002601 intratumoral effect Effects 0.000 claims description 3
- 238000007920 subcutaneous administration Methods 0.000 claims description 3
- 210000005260 human cell Anatomy 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 230000001105 regulatory effect Effects 0.000 claims description 2
- 239000013603 viral vector Substances 0.000 claims description 2
- 210000003527 eukaryotic cell Anatomy 0.000 claims 1
- 238000007918 intramuscular administration Methods 0.000 claims 1
- 230000002101 lytic effect Effects 0.000 claims 1
- 241000699670 Mus sp. Species 0.000 description 125
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 106
- 108020004414 DNA Proteins 0.000 description 90
- 108090000623 proteins and genes Proteins 0.000 description 87
- 101710163595 Chaperone protein DnaK Proteins 0.000 description 63
- 101710178376 Heat shock 70 kDa protein Proteins 0.000 description 63
- 101710152018 Heat shock cognate 70 kDa protein Proteins 0.000 description 63
- 108020001507 fusion proteins Proteins 0.000 description 60
- 102000037865 fusion proteins Human genes 0.000 description 60
- 210000001744 T-lymphocyte Anatomy 0.000 description 59
- 102000004169 proteins and genes Human genes 0.000 description 59
- 239000013598 vector Substances 0.000 description 55
- 238000001727 in vivo Methods 0.000 description 48
- 229940022005 RNA vaccine Drugs 0.000 description 35
- 108700021021 mRNA Vaccine Proteins 0.000 description 35
- 108010041986 DNA Vaccines Proteins 0.000 description 32
- 229940021995 DNA vaccine Drugs 0.000 description 32
- 238000002965 ELISA Methods 0.000 description 29
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 description 28
- 238000002255 vaccination Methods 0.000 description 28
- 101000767631 Human papillomavirus type 16 Protein E7 Proteins 0.000 description 26
- 238000000338 in vitro Methods 0.000 description 26
- 239000012636 effector Substances 0.000 description 25
- 210000004988 splenocyte Anatomy 0.000 description 25
- 241000699666 Mus <mouse, genus> Species 0.000 description 24
- 150000001413 amino acids Chemical class 0.000 description 23
- 238000006467 substitution reaction Methods 0.000 description 23
- 238000002474 experimental method Methods 0.000 description 22
- 238000003556 assay Methods 0.000 description 21
- 230000000694 effects Effects 0.000 description 21
- 238000000684 flow cytometry Methods 0.000 description 21
- 239000013592 cell lysate Substances 0.000 description 17
- 241000701806 Human papillomavirus Species 0.000 description 16
- 102000002812 Heat-Shock Proteins Human genes 0.000 description 15
- 108010004889 Heat-Shock Proteins Proteins 0.000 description 15
- 241000282414 Homo sapiens Species 0.000 description 15
- 230000001640 apoptogenic effect Effects 0.000 description 15
- 206010056342 Pulmonary mass Diseases 0.000 description 14
- 210000004072 lung Anatomy 0.000 description 14
- 238000011282 treatment Methods 0.000 description 14
- 238000004458 analytical method Methods 0.000 description 13
- 230000000259 anti-tumor effect Effects 0.000 description 13
- 201000011510 cancer Diseases 0.000 description 13
- 230000002163 immunogen Effects 0.000 description 13
- 238000010186 staining Methods 0.000 description 13
- 108091026890 Coding region Proteins 0.000 description 12
- 102100028082 Tapasin Human genes 0.000 description 12
- 108010059434 tapasin Proteins 0.000 description 12
- 108010056891 Calnexin Proteins 0.000 description 11
- 102000034342 Calnexin Human genes 0.000 description 11
- 108091061960 Naked DNA Proteins 0.000 description 11
- 230000006870 function Effects 0.000 description 11
- 210000000822 natural killer cell Anatomy 0.000 description 11
- 238000001543 one-way ANOVA Methods 0.000 description 11
- 230000004614 tumor growth Effects 0.000 description 11
- 241000699660 Mus musculus Species 0.000 description 10
- 230000001772 anti-angiogenic effect Effects 0.000 description 10
- 210000001185 bone marrow Anatomy 0.000 description 10
- 230000009089 cytolysis Effects 0.000 description 10
- 230000003053 immunization Effects 0.000 description 10
- 230000003834 intracellular effect Effects 0.000 description 10
- 238000011580 nude mouse model Methods 0.000 description 10
- 230000037361 pathway Effects 0.000 description 10
- 210000001519 tissue Anatomy 0.000 description 10
- 102000004127 Cytokines Human genes 0.000 description 9
- 108090000695 Cytokines Proteins 0.000 description 9
- 102100037850 Interferon gamma Human genes 0.000 description 9
- 108010074328 Interferon-gamma Proteins 0.000 description 9
- 102000004388 Interleukin-4 Human genes 0.000 description 9
- 108090000978 Interleukin-4 Proteins 0.000 description 9
- 102000003855 L-lactate dehydrogenase Human genes 0.000 description 9
- 108700023483 L-lactate dehydrogenases Proteins 0.000 description 9
- 238000010586 diagram Methods 0.000 description 9
- 230000007246 mechanism Effects 0.000 description 9
- 239000002243 precursor Substances 0.000 description 9
- 230000005809 anti-tumor immunity Effects 0.000 description 8
- 230000014102 antigen processing and presentation of exogenous peptide antigen via MHC class I Effects 0.000 description 8
- 238000002649 immunization Methods 0.000 description 8
- 230000001404 mediated effect Effects 0.000 description 8
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 8
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 7
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 7
- 206010027476 Metastases Diseases 0.000 description 7
- 125000003275 alpha amino acid group Chemical group 0.000 description 7
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 7
- 241001493065 dsRNA viruses Species 0.000 description 7
- 239000001963 growth medium Substances 0.000 description 7
- 210000000987 immune system Anatomy 0.000 description 7
- 238000001990 intravenous administration Methods 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 210000002966 serum Anatomy 0.000 description 7
- 210000004989 spleen cell Anatomy 0.000 description 7
- 238000013518 transcription Methods 0.000 description 7
- 230000035897 transcription Effects 0.000 description 7
- 210000003462 vein Anatomy 0.000 description 7
- 230000003612 virological effect Effects 0.000 description 7
- 241000710929 Alphavirus Species 0.000 description 6
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 6
- 241000283973 Oryctolagus cuniculus Species 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- 230000003321 amplification Effects 0.000 description 6
- 238000004520 electroporation Methods 0.000 description 6
- 238000005516 engineering process Methods 0.000 description 6
- 239000012894 fetal calf serum Substances 0.000 description 6
- 238000012423 maintenance Methods 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- 230000009401 metastasis Effects 0.000 description 6
- 206010061289 metastatic neoplasm Diseases 0.000 description 6
- 238000003199 nucleic acid amplification method Methods 0.000 description 6
- 239000000816 peptidomimetic Substances 0.000 description 6
- 230000003248 secreting effect Effects 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 229930182555 Penicillin Natural products 0.000 description 5
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 5
- 108010004729 Phycoerythrin Proteins 0.000 description 5
- 230000024932 T cell mediated immunity Effects 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 230000036039 immunity Effects 0.000 description 5
- 230000006698 induction Effects 0.000 description 5
- 210000000207 lymphocyte subset Anatomy 0.000 description 5
- 239000003550 marker Substances 0.000 description 5
- 210000004088 microvessel Anatomy 0.000 description 5
- 229940049954 penicillin Drugs 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 230000002685 pulmonary effect Effects 0.000 description 5
- 230000010076 replication Effects 0.000 description 5
- 239000000523 sample Substances 0.000 description 5
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 238000001890 transfection Methods 0.000 description 5
- 108010078791 Carrier Proteins Proteins 0.000 description 4
- 206010008342 Cervix carcinoma Diseases 0.000 description 4
- 238000011238 DNA vaccination Methods 0.000 description 4
- 101150013359 E7 gene Proteins 0.000 description 4
- 102100039328 Endoplasmin Human genes 0.000 description 4
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 description 4
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 4
- 108010002350 Interleukin-2 Proteins 0.000 description 4
- 102000005431 Molecular Chaperones Human genes 0.000 description 4
- 241000710961 Semliki Forest virus Species 0.000 description 4
- 108091008874 T cell receptors Proteins 0.000 description 4
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 4
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 4
- 230000033115 angiogenesis Effects 0.000 description 4
- 230000006907 apoptotic process Effects 0.000 description 4
- 238000009566 cancer vaccine Methods 0.000 description 4
- 229940022399 cancer vaccine Drugs 0.000 description 4
- -1 capsids Proteins 0.000 description 4
- 238000009125 cardiac resynchronization therapy Methods 0.000 description 4
- 230000006037 cell lysis Effects 0.000 description 4
- 201000010881 cervical cancer Diseases 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 238000010276 construction Methods 0.000 description 4
- 230000002950 deficient Effects 0.000 description 4
- 238000012217 deletion Methods 0.000 description 4
- 230000037430 deletion Effects 0.000 description 4
- 238000010790 dilution Methods 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- 239000003797 essential amino acid Substances 0.000 description 4
- 235000020776 essential amino acid Nutrition 0.000 description 4
- 108010017007 glucose-regulated proteins Proteins 0.000 description 4
- 238000003306 harvesting Methods 0.000 description 4
- 230000001900 immune effect Effects 0.000 description 4
- 239000012642 immune effector Substances 0.000 description 4
- 229940121354 immunomodulator Drugs 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 230000021633 leukocyte mediated immunity Effects 0.000 description 4
- 230000001394 metastastic effect Effects 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 239000013642 negative control Substances 0.000 description 4
- 231100001221 nontumorigenic Toxicity 0.000 description 4
- 108091033319 polynucleotide Proteins 0.000 description 4
- 102000040430 polynucleotide Human genes 0.000 description 4
- 239000002157 polynucleotide Substances 0.000 description 4
- 239000013615 primer Substances 0.000 description 4
- 241000894007 species Species 0.000 description 4
- 230000002269 spontaneous effect Effects 0.000 description 4
- 229960005322 streptomycin Drugs 0.000 description 4
- 230000008685 targeting Effects 0.000 description 4
- 241000701161 unidentified adenovirus Species 0.000 description 4
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 3
- 238000001712 DNA sequencing Methods 0.000 description 3
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 102000003886 Glycoproteins Human genes 0.000 description 3
- 108090000288 Glycoproteins Proteins 0.000 description 3
- 101000839464 Leishmania braziliensis Heat shock 70 kDa protein Proteins 0.000 description 3
- 102100035133 Lysosome-associated membrane glycoprotein 1 Human genes 0.000 description 3
- 101710116782 Lysosome-associated membrane glycoprotein 1 Proteins 0.000 description 3
- 102000043131 MHC class II family Human genes 0.000 description 3
- 108091054438 MHC class II family Proteins 0.000 description 3
- 108010023335 Member 2 Subfamily B ATP Binding Cassette Transporter Proteins 0.000 description 3
- 108700026244 Open Reading Frames Proteins 0.000 description 3
- 241001631646 Papillomaviridae Species 0.000 description 3
- 102000003992 Peroxidases Human genes 0.000 description 3
- 229920001213 Polysorbate 20 Polymers 0.000 description 3
- 108010065868 RNA polymerase SP6 Proteins 0.000 description 3
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 3
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 3
- 230000005867 T cell response Effects 0.000 description 3
- 210000000173 T-lymphoid precursor cell Anatomy 0.000 description 3
- 230000030741 antigen processing and presentation Effects 0.000 description 3
- 230000005975 antitumor immune response Effects 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 210000004204 blood vessel Anatomy 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 238000010367 cloning Methods 0.000 description 3
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 238000001415 gene therapy Methods 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 230000028996 humoral immune response Effects 0.000 description 3
- 238000003018 immunoassay Methods 0.000 description 3
- 238000009169 immunotherapy Methods 0.000 description 3
- 239000007927 intramuscular injection Substances 0.000 description 3
- 238000010255 intramuscular injection Methods 0.000 description 3
- 238000007912 intraperitoneal administration Methods 0.000 description 3
- 238000007913 intrathecal administration Methods 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- 125000005647 linker group Chemical group 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 210000004877 mucosa Anatomy 0.000 description 3
- 108010091748 peptide A Proteins 0.000 description 3
- 108040007629 peroxidase activity proteins Proteins 0.000 description 3
- 229910052698 phosphorus Inorganic materials 0.000 description 3
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 3
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 229940023143 protein vaccine Drugs 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 238000011200 topical administration Methods 0.000 description 3
- 241001430294 unidentified retrovirus Species 0.000 description 3
- 238000005406 washing Methods 0.000 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 description 2
- 102100030346 Antigen peptide transporter 1 Human genes 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 2
- 101150010856 CRT gene Proteins 0.000 description 2
- 102000053602 DNA Human genes 0.000 description 2
- 241000702421 Dependoparvovirus Species 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 101710113864 Heat shock protein 90 Proteins 0.000 description 2
- 102000008949 Histocompatibility Antigens Class I Human genes 0.000 description 2
- 101001044447 Homo sapiens Interferon kappa Proteins 0.000 description 2
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 2
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- 102100022469 Interferon kappa Human genes 0.000 description 2
- 125000003412 L-alanyl group Chemical group [H]N([H])[C@@](C([H])([H])[H])(C(=O)[*])[H] 0.000 description 2
- 125000000415 L-cysteinyl group Chemical group O=C([*])[C@@](N([H])[H])([H])C([H])([H])S[H] 0.000 description 2
- 229930182816 L-glutamine Natural products 0.000 description 2
- 102000004856 Lectins Human genes 0.000 description 2
- 108090001090 Lectins Proteins 0.000 description 2
- 241000589242 Legionella pneumophila Species 0.000 description 2
- 239000012097 Lipofectamine 2000 Substances 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 241000714177 Murine leukemia virus Species 0.000 description 2
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 2
- 239000004677 Nylon Substances 0.000 description 2
- 241000223960 Plasmodium falciparum Species 0.000 description 2
- 108010076504 Protein Sorting Signals Proteins 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 2
- 201000000582 Retinoblastoma Diseases 0.000 description 2
- 241000713311 Simian immunodeficiency virus Species 0.000 description 2
- 108700009124 Transcription Initiation Site Proteins 0.000 description 2
- 206010046865 Vaccinia virus infection Diseases 0.000 description 2
- 241000710959 Venezuelan equine encephalitis virus Species 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 230000001464 adherent effect Effects 0.000 description 2
- 125000006295 amino methylene group Chemical group [H]N(*)C([H])([H])* 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 238000003149 assay kit Methods 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 230000036770 blood supply Effects 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 210000002798 bone marrow cell Anatomy 0.000 description 2
- AIYUHDOJVYHVIT-UHFFFAOYSA-M caesium chloride Chemical compound [Cl-].[Cs+] AIYUHDOJVYHVIT-UHFFFAOYSA-M 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 239000002458 cell surface marker Substances 0.000 description 2
- 230000010307 cell transformation Effects 0.000 description 2
- 230000007969 cellular immunity Effects 0.000 description 2
- 230000036755 cellular response Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 239000000356 contaminant Substances 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 238000012137 double-staining Methods 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 238000001502 gel electrophoresis Methods 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 2
- 239000001307 helium Substances 0.000 description 2
- 229910052734 helium Inorganic materials 0.000 description 2
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 2
- 210000002443 helper t lymphocyte Anatomy 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 238000009396 hybridization Methods 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 230000002055 immunohistochemical effect Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 239000002523 lectin Substances 0.000 description 2
- 210000002414 leg Anatomy 0.000 description 2
- 229940115932 legionella pneumophila Drugs 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 238000007834 ligase chain reaction Methods 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 210000003141 lower extremity Anatomy 0.000 description 2
- 208000037841 lung tumor Diseases 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 239000006166 lysate Substances 0.000 description 2
- 230000010534 mechanism of action Effects 0.000 description 2
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 229940022007 naked DNA vaccine Drugs 0.000 description 2
- 230000001338 necrotic effect Effects 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 229920001778 nylon Polymers 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 2
- 230000012846 protein folding Effects 0.000 description 2
- 238000003908 quality control method Methods 0.000 description 2
- 238000003127 radioimmunoassay Methods 0.000 description 2
- 230000003362 replicative effect Effects 0.000 description 2
- 108091008146 restriction endonucleases Proteins 0.000 description 2
- 230000001177 retroviral effect Effects 0.000 description 2
- 230000007017 scission 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
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
- 238000003153 stable transfection Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 210000002303 tibia Anatomy 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 238000012384 transportation and delivery Methods 0.000 description 2
- 231100000588 tumorigenic Toxicity 0.000 description 2
- 230000000381 tumorigenic effect Effects 0.000 description 2
- 208000007089 vaccinia Diseases 0.000 description 2
- 230000029812 viral genome replication Effects 0.000 description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
- AWNBSWDIOCXWJW-WTOYTKOKSA-N (2r)-n-[(2s)-1-[[(2s)-1-(2-aminoethylamino)-1-oxopropan-2-yl]amino]-3-naphthalen-2-yl-1-oxopropan-2-yl]-n'-hydroxy-2-(2-methylpropyl)butanediamide Chemical compound C1=CC=CC2=CC(C[C@H](NC(=O)[C@@H](CC(=O)NO)CC(C)C)C(=O)N[C@@H](C)C(=O)NCCN)=CC=C21 AWNBSWDIOCXWJW-WTOYTKOKSA-N 0.000 description 1
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- 101710197241 Accessory gland-specific peptide 70A Proteins 0.000 description 1
- 241000701242 Adenoviridae Species 0.000 description 1
- 102400000068 Angiostatin Human genes 0.000 description 1
- 108010079709 Angiostatins Proteins 0.000 description 1
- 108090000672 Annexin A5 Proteins 0.000 description 1
- 102000004121 Annexin A5 Human genes 0.000 description 1
- 102100030343 Antigen peptide transporter 2 Human genes 0.000 description 1
- 241000701412 Baculoviridae Species 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- 241000588832 Bordetella pertussis Species 0.000 description 1
- 241001148111 Brucella suis Species 0.000 description 1
- 101100071585 Caenorhabditis elegans hsp-16.2 gene Proteins 0.000 description 1
- 102100029968 Calreticulin Human genes 0.000 description 1
- 101710098119 Chaperonin GroEL 2 Proteins 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 241000606161 Chlamydia Species 0.000 description 1
- 241001647372 Chlamydia pneumoniae Species 0.000 description 1
- 241000606153 Chlamydia trachomatis Species 0.000 description 1
- 102100031186 Chromogranin-A Human genes 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 239000003155 DNA primer Substances 0.000 description 1
- 241000450599 DNA viruses Species 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
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 102000007260 Deoxyribonuclease I Human genes 0.000 description 1
- 108010008532 Deoxyribonuclease I Proteins 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 241000605310 Ehrlichia chaffeensis Species 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 102400001047 Endostatin Human genes 0.000 description 1
- 108010079505 Endostatins Proteins 0.000 description 1
- 108010009900 Endothelial Protein C Receptor Proteins 0.000 description 1
- 102100030024 Endothelial protein C receptor Human genes 0.000 description 1
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 108010040476 FITC-annexin A5 Proteins 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 241000713813 Gibbon ape leukemia virus Species 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 108010027992 HSP70 Heat-Shock Proteins Proteins 0.000 description 1
- 102000018932 HSP70 Heat-Shock Proteins Human genes 0.000 description 1
- 241000700586 Herpesviridae Species 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101000812663 Homo sapiens Endoplasmin Proteins 0.000 description 1
- 206010020429 Human ehrlichiosis Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- 125000000570 L-alpha-aspartyl group Chemical group [H]OC(=O)C([H])([H])[C@]([H])(N([H])[H])C(*)=O 0.000 description 1
- 125000002059 L-arginyl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])C([H])([H])C([H])([H])N([H])C(=N[H])N([H])[H] 0.000 description 1
- 125000000010 L-asparaginyl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])C(=O)N([H])[H] 0.000 description 1
- 125000002066 L-histidyl group Chemical group [H]N1C([H])=NC(C([H])([H])[C@](C(=O)[*])([H])N([H])[H])=C1[H] 0.000 description 1
- 125000002061 L-isoleucyl group Chemical group [H]N([H])[C@]([H])(C(=O)[*])[C@](C([H])([H])[H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000003440 L-leucyl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])C(C([H])([H])[H])([H])C([H])([H])[H] 0.000 description 1
- 125000001176 L-lysyl group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C([H])([H])C([H])([H])C([H])([H])C(N([H])[H])([H])[H] 0.000 description 1
- 125000002842 L-seryl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])O[H] 0.000 description 1
- 125000000769 L-threonyl group Chemical group [H]N([H])[C@]([H])(C(=O)[*])[C@](O[H])(C([H])([H])[H])[H] 0.000 description 1
- 125000002707 L-tryptophyl group Chemical group [H]C1=C([H])C([H])=C2C(C([C@](N([H])[H])(C(=O)[*])[H])([H])[H])=C([H])N([H])C2=C1[H] 0.000 description 1
- 125000003580 L-valyl group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(C([H])([H])[H])(C([H])([H])[H])[H] 0.000 description 1
- 241000186779 Listeria monocytogenes Species 0.000 description 1
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 1
- 102000011202 Member 2 Subfamily B ATP Binding Cassette Transporter Human genes 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 102100026262 Metalloproteinase inhibitor 2 Human genes 0.000 description 1
- 108060004795 Methyltransferase Proteins 0.000 description 1
- 101000793654 Mus musculus Calreticulin Proteins 0.000 description 1
- 241000186359 Mycobacterium Species 0.000 description 1
- 241000186367 Mycobacterium avium Species 0.000 description 1
- 108700009457 Mycobacterium tuberculosis HSP70 Proteins 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 206010029113 Neovascularisation Diseases 0.000 description 1
- 102000007999 Nuclear Proteins Human genes 0.000 description 1
- 108010089610 Nuclear Proteins Proteins 0.000 description 1
- 108020004711 Nucleic Acid Probes Proteins 0.000 description 1
- 108700001237 Nucleic Acid-Based Vaccines Proteins 0.000 description 1
- 108091005461 Nucleic proteins Proteins 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241000526686 Paracoccidioides brasiliensis Species 0.000 description 1
- 241000701945 Parvoviridae Species 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 241000700625 Poxviridae Species 0.000 description 1
- 101710132595 Protein E7 Proteins 0.000 description 1
- 108010066717 Q beta Replicase Proteins 0.000 description 1
- 101000793674 Rattus norvegicus Calreticulin Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 241000606695 Rickettsia rickettsii Species 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 241001138501 Salmonella enterica Species 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 101710172711 Structural protein Proteins 0.000 description 1
- 101800000849 Tachykinin-associated peptide 2 Proteins 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 241000656145 Thyrsites atun Species 0.000 description 1
- 108010031372 Tissue Inhibitor of Metalloproteinase-2 Proteins 0.000 description 1
- 241000710924 Togaviridae Species 0.000 description 1
- 241000223997 Toxoplasma gondii Species 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 208000002687 Venezuelan Equine Encephalomyelitis Diseases 0.000 description 1
- 108020005202 Viral DNA Proteins 0.000 description 1
- 108010067674 Viral Nonstructural Proteins Proteins 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 108010042591 activated protein C receptor Proteins 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 108700010877 adenoviridae proteins Proteins 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000002622 anti-tumorigenesis Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 210000002565 arteriole Anatomy 0.000 description 1
- FZCSTZYAHCUGEM-UHFFFAOYSA-N aspergillomarasmine B Natural products OC(=O)CNC(C(O)=O)CNC(C(O)=O)CC(O)=O FZCSTZYAHCUGEM-UHFFFAOYSA-N 0.000 description 1
- 102000015736 beta 2-Microglobulin Human genes 0.000 description 1
- 108010081355 beta 2-Microglobulin Proteins 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 229960001561 bleomycin Drugs 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 238000006664 bond formation reaction Methods 0.000 description 1
- 210000005178 buccal mucosa Anatomy 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 238000009435 building construction Methods 0.000 description 1
- 101150039352 can gene Proteins 0.000 description 1
- 238000005251 capillar electrophoresis Methods 0.000 description 1
- 210000000234 capsid Anatomy 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000009614 chemical analysis method Methods 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 229940038705 chlamydia trachomatis Drugs 0.000 description 1
- 229960005091 chloramphenicol Drugs 0.000 description 1
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000000139 costimulatory effect Effects 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 238000002784 cytotoxicity assay Methods 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000003936 denaturing gel electrophoresis Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000009025 developmental regulation Effects 0.000 description 1
- 102000038379 digestive enzymes Human genes 0.000 description 1
- 108091007734 digestive enzymes Proteins 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000001976 enzyme digestion Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethyl mercaptane Natural products CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 238000010304 firing Methods 0.000 description 1
- 238000002825 functional assay Methods 0.000 description 1
- 238000001476 gene delivery Methods 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 210000002767 hepatic artery Anatomy 0.000 description 1
- 244000052637 human pathogen Species 0.000 description 1
- 230000004727 humoral immunity Effects 0.000 description 1
- 230000008348 humoral response Effects 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 230000000951 immunodiffusion Effects 0.000 description 1
- 238000000760 immunoelectrophoresis Methods 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000011532 immunohistochemical staining Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 230000010039 intracellular degradation Effects 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 229960000318 kanamycin Drugs 0.000 description 1
- 229930027917 kanamycin Natural products 0.000 description 1
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 1
- 229930182823 kanamycin A Natural products 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 238000011005 laboratory method Methods 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 108010026228 mRNA guanylyltransferase Proteins 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000004779 membrane envelope Anatomy 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 230000011278 mitosis Effects 0.000 description 1
- 102000035118 modified proteins Human genes 0.000 description 1
- 108091005573 modified proteins Proteins 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 210000002850 nasal mucosa Anatomy 0.000 description 1
- 210000005170 neoplastic cell Anatomy 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 239000002853 nucleic acid probe Substances 0.000 description 1
- 229940023146 nucleic acid vaccine Drugs 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 238000006384 oligomerization reaction Methods 0.000 description 1
- 231100000590 oncogenic Toxicity 0.000 description 1
- 230000002246 oncogenic effect Effects 0.000 description 1
- 108091008819 oncoproteins Proteins 0.000 description 1
- 102000027450 oncoproteins Human genes 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 238000002559 palpation Methods 0.000 description 1
- 229960002566 papillomavirus vaccine Drugs 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000007918 pathogenicity Effects 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000008196 pharmacological composition Substances 0.000 description 1
- NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 238000002731 protein assay Methods 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000000163 radioactive labelling Methods 0.000 description 1
- 238000002601 radiography Methods 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000017248 retroviral genome replication Effects 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 229940075118 rickettsia rickettsii Drugs 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 238000003345 scintillation counting Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 125000003003 spiro group Chemical group 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 150000003557 thiazoles Chemical class 0.000 description 1
- 150000003556 thioamides Chemical class 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000005030 transcription termination Effects 0.000 description 1
- 230000002463 transducing effect Effects 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 108010060757 vasostatin Proteins 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/001102—Receptors, cell surface antigens or cell surface determinants
- A61K39/001103—Receptors for growth factors
- A61K39/001106—Her-2/neu/ErbB2, Her-3/ErbB3 or Her 4/ErbB4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- 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
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4725—Proteoglycans, e.g. aggreccan
-
- 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
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/70539—MHC-molecules, e.g. HLA-molecules
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/515—Animal cells
- A61K2039/5154—Antigen presenting cells [APCs], e.g. dendritic cells or macrophages
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing 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
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/35—Fusion polypeptide containing a fusion for enhanced stability/folding during expression, e.g. fusions with chaperones or thioredoxin
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Biochemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- General Chemical & Material Sciences (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Epidemiology (AREA)
- Cell Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US22290200P | 2000-08-03 | 2000-08-03 | |
| US60/222,902 | 2000-08-03 | ||
| PCT/US2001/024134 WO2002012281A2 (en) | 2000-08-03 | 2001-08-02 | Molecular vaccine linking an endoplasmic reticulum chaperone polypeptide to an antigen |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2008197856A Division JP2009017883A (ja) | 2000-08-03 | 2008-07-31 | 抗原に小胞体シャペロンポリペプチドを連結した分子ワクチン |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2004527213A JP2004527213A (ja) | 2004-09-09 |
| JP2004527213A5 JP2004527213A5 (enExample) | 2008-09-18 |
| JP5087201B2 true JP5087201B2 (ja) | 2012-12-05 |
Family
ID=22834209
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2002518253A Expired - Lifetime JP5087201B2 (ja) | 2000-08-03 | 2001-08-02 | 抗原に小胞体シャペロンポリペプチドを連結した分子ワクチン |
| JP2008197856A Pending JP2009017883A (ja) | 2000-08-03 | 2008-07-31 | 抗原に小胞体シャペロンポリペプチドを連結した分子ワクチン |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2008197856A Pending JP2009017883A (ja) | 2000-08-03 | 2008-07-31 | 抗原に小胞体シャペロンポリペプチドを連結した分子ワクチン |
Country Status (8)
| Country | Link |
|---|---|
| US (3) | US7342002B2 (enExample) |
| EP (1) | EP1363938B1 (enExample) |
| JP (2) | JP5087201B2 (enExample) |
| AU (1) | AU2001278117A1 (enExample) |
| CA (1) | CA2417214C (enExample) |
| DK (1) | DK1363938T3 (enExample) |
| ES (1) | ES2454640T3 (enExample) |
| WO (1) | WO2002012281A2 (enExample) |
Families Citing this family (44)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050100928A1 (en) * | 1999-09-16 | 2005-05-12 | Zycos Inc., A Delaware Corporation | Nucleic acids encoding polyepitope polypeptides |
| US8128922B2 (en) * | 1999-10-20 | 2012-03-06 | Johns Hopkins University | Superior molecular vaccine linking the translocation domain of a bacterial toxin to an antigen |
| WO2002009645A2 (en) * | 2000-08-01 | 2002-02-07 | The Johns Hopkins University | Intercellular transport protein linked to an antigen as a molecular vaccine |
| EP1363938B1 (en) | 2000-08-03 | 2013-12-11 | Johns Hopkins University | Molecular vaccine linking an endoplasmic reticulum chaperone polypeptide to an antigen |
| WO2002061113A2 (en) | 2001-02-01 | 2002-08-08 | The Johns Hopkins University | Nucleic acid derived vaccine that encodes an antigen linked to a polypeptide that promotes antigen presentation |
| WO2004092221A1 (ja) * | 2003-04-18 | 2004-10-28 | Sekisui Chemical Co. Ltd. | 免疫原及び免疫用組成物、並びにそれらを使用する抗体の製造方法 |
| EP1644048B1 (en) * | 2003-05-05 | 2015-04-29 | Johns Hopkins University | Anti-cancer dna vaccine employing plasmids encoding signal sequence, mutant oncoprotein antigen, and heat shock protein |
| CN1833030B (zh) | 2003-05-22 | 2014-07-23 | 美国弗劳恩霍夫股份有限公司 | 用于表达、传递及纯化目标多肽的重组载体分子 |
| WO2005081716A2 (en) * | 2003-11-24 | 2005-09-09 | The Johns Hopkins University | DNA VACCINES TARGETING ANTIGENS OF THE SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS (SARS-CoV) |
| JP2007528838A (ja) * | 2003-12-24 | 2007-10-18 | ライデン ユニバーシティ メディカル センター | 腫瘍特異的ワクチンとしての合成タンパク質 |
| KR101215780B1 (ko) | 2004-10-15 | 2012-12-26 | 죠 지바 | 동물의 면역 방법, 면역용 조성물, 항체의 제조 방법,하이브리도마의 제조 방법 및 모노클로날 항체의 제조 방법 |
| WO2006073970A2 (en) | 2005-01-06 | 2006-07-13 | The Johns Hopkins University | Rna interference that blocks expression of pro-apoptotic proteins potentiates immunity induced by dna and transfected dendritic cell vaccines |
| WO2006081323A2 (en) * | 2005-01-26 | 2006-08-03 | The Johns Hopkins University | Anti-cancer dna vaccine employing plasmids encoding mutant oncoprotein antigen and calreticulin |
| EP1919504B1 (en) * | 2005-08-03 | 2013-10-16 | iBio, Inc. | Antibody to bacillus anthracis protective antigen |
| WO2007095320A2 (en) * | 2006-02-13 | 2007-08-23 | Fraunhofer Usa, Inc. | Hpv antigens, vaccine compositions, and related methods |
| WO2008048344A2 (en) * | 2006-02-13 | 2008-04-24 | Fraunhofer Usa, Inc. | Bacillus anthracis antigens, vaccine compositions, and related methods |
| US20100330105A1 (en) * | 2006-08-22 | 2010-12-30 | John Hopkins University | Anticancer Combination Therapies |
| WO2008046251A1 (fr) * | 2006-10-19 | 2008-04-24 | Sunbio Biotech Pharmaceuticals(Tianjin) Co., Ltd. | Protéines hybrides contenant un domaine n de la calréticuline humaine et des protéines e6 ou e7 du papillomavirus humain de type 16, et utilisations associées |
| US9085638B2 (en) | 2007-03-07 | 2015-07-21 | The Johns Hopkins University | DNA vaccine enhancement with MHC class II activators |
| US20080260765A1 (en) * | 2007-03-15 | 2008-10-23 | Johns Hopkins University | HPV DNA Vaccines and Methods of Use Thereof |
| WO2008119024A1 (en) * | 2007-03-27 | 2008-10-02 | University Of Florida Research Foundation Inc. | Modified antigen presenting cells and methods of use |
| US8404252B2 (en) | 2007-07-11 | 2013-03-26 | Fraunhofer Usa, Inc. | Yersinia pestis antigens, vaccine compositions, and related methods |
| JP2011518115A (ja) * | 2008-01-28 | 2011-06-23 | タップイミューン インコーポレイテッド | 免疫応答を増強するためのタパシン増加 |
| WO2009114085A2 (en) | 2008-03-03 | 2009-09-17 | The University Of Miami | Allogeneic cancer cell-based immunotherapy |
| AU2009226077B2 (en) | 2008-03-20 | 2012-04-19 | University Of Miami | Heat shock protein gp96 vaccination and methods of using same |
| US20090285861A1 (en) * | 2008-04-17 | 2009-11-19 | Tzyy-Choou Wu | Tumor cell-based cancer immunotherapeutic compositions and methods |
| WO2010030861A2 (en) * | 2008-09-11 | 2010-03-18 | Calretex, Llc | Compositions and methods for purifying calreticulin |
| WO2010037046A1 (en) | 2008-09-28 | 2010-04-01 | Fraunhofer Usa, Inc. | Humanized neuraminidase antibody and methods of use thereof |
| US8784819B2 (en) | 2009-09-29 | 2014-07-22 | Ibio Inc. | Influenza hemagglutinin antibodies, compositions and related methods |
| US10487332B2 (en) * | 2010-07-06 | 2019-11-26 | Glaxosmithkline Biologicals Sa | Immunisation of large mammals with low doses of RNA |
| AU2012220592A1 (en) * | 2011-02-23 | 2013-09-12 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Service | Combined cell based GP96-IG-SIV/HIV, recombinant GP120 protein vaccination for protection from SIV/HIV |
| LT2714071T (lt) * | 2011-05-24 | 2019-10-10 | Biontech Rna Pharmaceuticals Gmbh | Individualizuotos vakcinos nuo vėžio |
| JP5981921B2 (ja) * | 2011-09-02 | 2016-08-31 | 株式会社カネカ | 小胞体シャペロンプロモータを用いた外来遺伝子を発現するトランスジェニック鳥類 |
| WO2013093629A2 (en) * | 2011-12-20 | 2013-06-27 | Netherlands Cancer Institute | Modular vaccines, methods and compositions related thereto |
| AU2013351542B2 (en) | 2012-11-28 | 2018-08-09 | BioNTech SE | Individualized vaccines for cancer |
| WO2014164727A1 (en) * | 2013-03-12 | 2014-10-09 | Wisconsin Alumni Research Foundation | A method of treating fungal infection |
| US10676723B2 (en) | 2015-05-11 | 2020-06-09 | David Gordon Bermudes | Chimeric protein toxins for expression by therapeutic bacteria |
| WO2017155981A1 (en) * | 2016-03-07 | 2017-09-14 | Massachusetts Institute Of Technology | Protein-chaperoned t-cell vaccines |
| US11129906B1 (en) | 2016-12-07 | 2021-09-28 | David Gordon Bermudes | Chimeric protein toxins for expression by therapeutic bacteria |
| US11180535B1 (en) | 2016-12-07 | 2021-11-23 | David Gordon Bermudes | Saccharide binding, tumor penetration, and cytotoxic antitumor chimeric peptides from therapeutic bacteria |
| WO2018224166A1 (en) | 2017-06-09 | 2018-12-13 | Biontech Rna Pharmaceuticals Gmbh | Methods for predicting the usefulness of disease specific amino acid modifications for immunotherapy |
| JP7722629B2 (ja) | 2017-07-04 | 2025-08-13 | キュアバック エスイー | 新規核酸分子 |
| CN109182339A (zh) * | 2018-09-06 | 2019-01-11 | 青岛农业大学 | 一种许氏平鮋钙网蛋白基因及应用 |
| EP4061405A1 (en) | 2019-11-18 | 2022-09-28 | Janssen Biotech, Inc. | Vaccines based on mutant calr and jak2 and their uses |
Family Cites Families (78)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5744133A (en) | 1986-08-13 | 1998-04-28 | Transgene S.A. | Expression of a tumor-specific antigen by a recombinant vector virus and use thereof in preventitive or curative treatment of the corresponding tumor |
| US4898730A (en) | 1987-03-13 | 1990-02-06 | The University Of British Columbia | Method to stimulate the immune response to specific antigens |
| US5582831A (en) | 1991-11-26 | 1996-12-10 | Yeda Research And Development Co., Ltd. | Anti-tumor vaccines |
| ATE127345T1 (de) | 1988-06-15 | 1995-09-15 | Whitehead Biomedical Inst | Stressproteine und verwendungen dafür. |
| US5217879A (en) | 1989-01-12 | 1993-06-08 | Washington University | Infectious Sindbis virus vectors |
| DE3907721A1 (de) | 1989-03-10 | 1990-09-20 | Behringwerke Ag | Immunogene regionen auf dem e7-protein des humanen papillomvierus typ 16 |
| US5545727A (en) | 1989-05-10 | 1996-08-13 | Somatogen, Inc. | DNA encoding fused di-alpha globins and production of pseudotetrameric hemoglobin |
| US5348945A (en) | 1990-04-06 | 1994-09-20 | Wake Forest University | Method of treatment with hsp70 |
| US5821088A (en) | 1990-05-11 | 1998-10-13 | Siga Pharmaceuticals, Inc. | Use of gram-positive bacteria to express recombinant proteins |
| AU8762991A (en) | 1990-09-26 | 1992-04-15 | Bristol-Myers Squibb Company | Human papilloma viral protein expression for use in vaccine compositions |
| US5674486A (en) | 1991-06-25 | 1997-10-07 | San Diego Regional Cancer Center | Cancer immunotherapy with carrier cells |
| ES2193133T3 (es) | 1991-07-13 | 2003-11-01 | Dade Behring Marburg Gmbh | Uso de peptidos derivados de los genes e6 y e7 de hpv-16 para fines. |
| GB9207701D0 (en) | 1992-04-08 | 1992-05-27 | Cancer Res Campaign Tech | Papillomavirus e7 protein |
| IL106760A (en) | 1992-08-25 | 1999-12-31 | Miles Inc | Protein-nucleic acid hybrid construct for translocating an exogenous nucleic acid into a target cell and nucleus |
| US5618536A (en) | 1992-09-03 | 1997-04-08 | The United States Of America As Represented By The Department Of Health And Human Services | Chimeric papillomavirus-like particles |
| US5997869A (en) | 1993-03-15 | 1999-12-07 | The United States Of America As Represented By The Department Of Health And Human Services | Peptides containing a fusion joint of a chimeric protein encoded by DNA spanning a tumor-associated chromosomal translocation and their use as immunogens |
| GB9306731D0 (en) | 1993-03-31 | 1993-05-26 | Cancer Res Campaign Tech | Vaccines |
| US5426097A (en) | 1993-04-06 | 1995-06-20 | The Trustees Of Columbia University In The City Of New York | Calreticulin: a novel antithrombotic agent |
| EP0700445B1 (en) | 1993-06-04 | 2002-01-23 | Whitehead Institute For Biomedical Research | Stress proteins and uses therefor |
| US5646008A (en) | 1993-06-22 | 1997-07-08 | The Regent Of The University Of Michigan | Vertebrate apoptosis gene: compositions and methods |
| US5591716A (en) | 1993-11-19 | 1997-01-07 | New York University | Beneficial wound healing applications of calreticulin and other hyaluronan-associated proteins |
| EP0659438A1 (en) | 1993-12-23 | 1995-06-28 | Boehringer Mannheim Gmbh | Conjugates consisting of peptidic T cell antigens and cell binding groups, and their use for therapy |
| US5750119A (en) | 1994-01-13 | 1998-05-12 | Mount Sinai School Of Medicine Of The City University Of New York | Immunotherapeutic stress protein-peptide complexes against cancer |
| AUPM566794A0 (en) | 1994-05-17 | 1994-06-09 | University Of Queensland, The | Process and product |
| US5854202A (en) | 1995-01-24 | 1998-12-29 | Dedhar; Shoukat | Peptide fragments of calreticulin, peptide mimetics thereof, and pharmaceutical compostions comprising same |
| WO1996036643A1 (en) | 1995-05-17 | 1996-11-21 | University Of Alberta | Method of inhibiting restenosis using calreticulin |
| US5792462A (en) * | 1995-05-23 | 1998-08-11 | University Of North Carolina At Chapel Hill | Alphavirus RNA replicon systems |
| JPH11510046A (ja) | 1995-07-21 | 1999-09-07 | ローヌ−プーラン ローラー ファーマシューティカルズ インコーポレイテッド | アデノ関連ウイルスリポソーム及び樹状細胞をトランスフェクトして特異性免疫を刺激することにおけるそれらの使用 |
| JP4163253B2 (ja) | 1995-08-18 | 2008-10-08 | スローン−ケッタリング インスティチュート フォー キャンサー リサーチ | 熱ショックタンパク質に基づくワクチンおよび免疫療法 |
| US5935576A (en) | 1995-09-13 | 1999-08-10 | Fordham University | Compositions and methods for the treatment and prevention of neoplastic diseases using heat shock proteins complexed with exogenous antigens |
| US5837251A (en) | 1995-09-13 | 1998-11-17 | Fordham University | Compositions and methods using complexes of heat shock proteins and antigenic molecules for the treatment and prevention of neoplastic diseases |
| DE19534348C2 (de) | 1995-09-15 | 1997-07-10 | Wieland Heinrich Prof Dr Med | Verfahren zur Bestimmung von Autoimmunphänomenen |
| WO1997020854A1 (en) * | 1995-12-05 | 1997-06-12 | University Of Massachusetts | Recombinant gas vesicles and uses thereof |
| AU734196B2 (en) | 1996-03-28 | 2001-06-07 | Whitehead Institute | Opsonin-enhanced cells, and methods of modulating an immune response to an antigen |
| DE69723434T2 (de) | 1996-04-26 | 2004-05-19 | Rijksuniversiteit Te Leiden | Verfahren zur selektion und produktion von t-zell-peptide epitope und vakzine mit diese epitope |
| US5951975A (en) | 1996-06-28 | 1999-09-14 | University Of Pittsburgh | Induction of CTLs specific for natural antigens by cross priming immunization |
| EP0950061A4 (en) | 1996-09-20 | 2000-04-12 | Univ New Mexico | Heat shock protein complexes |
| US5962318A (en) | 1996-11-15 | 1999-10-05 | St. Jude Children's Research Hospital | Cytotoxic T lymphocyte-mediated immunotherapy |
| DE69735376T2 (de) | 1996-11-26 | 2006-12-14 | Stressgen Biotechnologies Corp., Victoria | Fusionsproteine, die stressproteine beinhalten, zum hervorrufen einer immunantwort |
| US6046158A (en) | 1996-12-20 | 2000-04-04 | Board Of Regents The University Of Texas Systems | Unique dendritic cell-associated C-type lectins, dectin-1 and dectin-2; compositions and uses thereof |
| US6017735A (en) | 1997-01-23 | 2000-01-25 | Marie Curie Cancer Care | Materials and methods for intracellular transport and their uses |
| US6017540A (en) | 1997-02-07 | 2000-01-25 | Fordham University | Prevention and treatment of primary and metastatic neoplastic diseases and infectious diseases with heat shock/stress protein-peptide complexes |
| US5830464A (en) | 1997-02-07 | 1998-11-03 | Fordham University | Compositions and methods for the treatment and growth inhibition of cancer using heat shock/stress protein-peptide complexes in combination with adoptive immunotherapy |
| AU7022898A (en) | 1997-04-23 | 1998-11-13 | Ontario Cancer Treatment & Research Foundation | Calreticulin-deficient cells |
| US6319503B1 (en) | 1998-02-19 | 2001-11-20 | Proteinix Company | Heat shock fusion-based vaccine system |
| HUP0003601A3 (en) | 1997-08-05 | 2003-03-28 | Stressgen Biotechnologies Corp | Immune responses against hpv antigens elicited by compositions comprising an hpv antigen and a stress protein or an expression vector capable of expression of these proteins |
| WO1999007869A1 (en) | 1997-08-05 | 1999-02-18 | University Of Florida | Live recombinant vaccine comprising inefficiently or non-replicating virus |
| US6007821A (en) | 1997-10-16 | 1999-12-28 | Fordham University | Method and compositions for the treatment of autoimmune disease using heat shock proteins |
| US6331388B1 (en) | 1997-10-17 | 2001-12-18 | Wisconsin Alumni Research Foundation | Immune response enhancer |
| US5948646A (en) | 1997-12-11 | 1999-09-07 | Fordham University | Methods for preparation of vaccines against cancer comprising heat shock protein-peptide complexes |
| US6534482B1 (en) | 1998-05-13 | 2003-03-18 | Epimmune, Inc. | Expression vectors for stimulating an immune response and methods of using the same |
| IL140239A0 (en) | 1998-06-17 | 2002-02-10 | Beth Israel Hospital | Anti-angiogenic proteins and methods of use thereof |
| AU766403C (en) | 1998-09-04 | 2004-05-27 | Aventis Pasteur Limited | Treatment of cervical cancer |
| US7001995B1 (en) | 1999-08-25 | 2006-02-21 | Merck & Co., Inc. | Synthetic human papillomavirus genes |
| US8128922B2 (en) * | 1999-10-20 | 2012-03-06 | Johns Hopkins University | Superior molecular vaccine linking the translocation domain of a bacterial toxin to an antigen |
| US6734173B1 (en) * | 1999-10-20 | 2004-05-11 | Johns Hopkins University | HSP DNA vaccines |
| DE60038622D1 (de) | 1999-10-20 | 2008-05-29 | Univ Johns Hopkins Med | Chimäre immunogene zusammensetzungen und dafür kodierende nukleinsäure |
| US20010034042A1 (en) | 2000-01-20 | 2001-10-25 | Srivastava Pramod K. | Complexes of peptide-binding fragments of heat shock proteins and their use as immunotherapeutic agents |
| US6967075B2 (en) | 2000-04-07 | 2005-11-22 | Schering Corporation | HCV replicase complexes |
| US7030219B2 (en) * | 2000-04-28 | 2006-04-18 | Johns Hopkins University | B7-DC, Dendritic cell co-stimulatory molecules |
| KR100919266B1 (ko) | 2000-06-26 | 2009-09-30 | 엔벤타 바이오파마슈티컬스 코포레이션 | 인간 파필로마 바이러스 치료법 |
| WO2002009645A2 (en) | 2000-08-01 | 2002-02-07 | The Johns Hopkins University | Intercellular transport protein linked to an antigen as a molecular vaccine |
| EP1363938B1 (en) | 2000-08-03 | 2013-12-11 | Johns Hopkins University | Molecular vaccine linking an endoplasmic reticulum chaperone polypeptide to an antigen |
| JP3930243B2 (ja) * | 2000-11-06 | 2007-06-13 | 本田技研工業株式会社 | マグネットポンプ |
| CN100523215C (zh) | 2000-12-01 | 2009-08-05 | 马普科技促进协会 | 介导rna干涉的小rna分子 |
| US7892730B2 (en) | 2000-12-22 | 2011-02-22 | Sagres Discovery, Inc. | Compositions and methods for cancer |
| WO2002061113A2 (en) | 2001-02-01 | 2002-08-08 | The Johns Hopkins University | Nucleic acid derived vaccine that encodes an antigen linked to a polypeptide that promotes antigen presentation |
| WO2002074920A2 (en) | 2001-03-16 | 2002-09-26 | Johns Hopkins University | A replication-defective alphavirus vaccine linking antigen with an immunogenicity-potentiating polypeptide and a method of delivery the same |
| US20030144221A1 (en) | 2001-07-17 | 2003-07-31 | Isis Pharmaceuticals Inc. | Antisense modulation of BCL2-associated X protein expression |
| EP1417353A4 (en) | 2001-07-20 | 2005-08-03 | Univ Texas | METHODS AND COMPOSITIONS ASSOCIATED WITH HPV ASSOCIATED PENCILS AND CANNULAR WELLS, INCLUDING CIN |
| US20060040262A1 (en) | 2002-12-27 | 2006-02-23 | Morris David W | Novel compositions and methods in cancer |
| AU2003224732A1 (en) | 2002-03-25 | 2003-10-13 | The Trustees Of Boston University | Method of using anti-apoptotic factors in gene expression |
| CA2499837C (en) | 2002-10-03 | 2013-12-03 | Wyeth Holdings Corporation | Human papillomavirus polypeptides and immunogenic compositions |
| US20070026076A1 (en) * | 2003-02-24 | 2007-02-01 | Tzyy-Choou Wu | Molecular vaccines employing nucleic acid encoding anti-apoptotic proteins |
| EP1644048B1 (en) | 2003-05-05 | 2015-04-29 | Johns Hopkins University | Anti-cancer dna vaccine employing plasmids encoding signal sequence, mutant oncoprotein antigen, and heat shock protein |
| WO2005081716A2 (en) | 2003-11-24 | 2005-09-09 | The Johns Hopkins University | DNA VACCINES TARGETING ANTIGENS OF THE SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS (SARS-CoV) |
| WO2006073970A2 (en) | 2005-01-06 | 2006-07-13 | The Johns Hopkins University | Rna interference that blocks expression of pro-apoptotic proteins potentiates immunity induced by dna and transfected dendritic cell vaccines |
| WO2006081323A2 (en) | 2005-01-26 | 2006-08-03 | The Johns Hopkins University | Anti-cancer dna vaccine employing plasmids encoding mutant oncoprotein antigen and calreticulin |
-
2001
- 2001-08-02 EP EP01956081.2A patent/EP1363938B1/en not_active Expired - Lifetime
- 2001-08-02 US US10/343,448 patent/US7342002B2/en not_active Expired - Lifetime
- 2001-08-02 JP JP2002518253A patent/JP5087201B2/ja not_active Expired - Lifetime
- 2001-08-02 WO PCT/US2001/024134 patent/WO2002012281A2/en not_active Ceased
- 2001-08-02 CA CA2417214A patent/CA2417214C/en not_active Expired - Lifetime
- 2001-08-02 DK DK01956081.2T patent/DK1363938T3/en active
- 2001-08-02 AU AU2001278117A patent/AU2001278117A1/en not_active Abandoned
- 2001-08-02 ES ES01956081.2T patent/ES2454640T3/es not_active Expired - Lifetime
-
2008
- 2008-01-15 US US12/014,541 patent/US8007781B2/en not_active Expired - Fee Related
- 2008-07-31 JP JP2008197856A patent/JP2009017883A/ja active Pending
-
2012
- 2012-05-03 US US13/463,250 patent/US20130203961A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| WO2002012281A2 (en) | 2002-02-14 |
| JP2004527213A (ja) | 2004-09-09 |
| DK1363938T3 (en) | 2014-03-24 |
| EP1363938A2 (en) | 2003-11-26 |
| US8007781B2 (en) | 2011-08-30 |
| US20090148471A1 (en) | 2009-06-11 |
| CA2417214C (en) | 2016-06-21 |
| ES2454640T3 (es) | 2014-04-11 |
| US20050054820A1 (en) | 2005-03-10 |
| WO2002012281A3 (en) | 2003-07-10 |
| CA2417214A1 (en) | 2002-02-14 |
| JP2009017883A (ja) | 2009-01-29 |
| US20130203961A1 (en) | 2013-08-08 |
| US7342002B2 (en) | 2008-03-11 |
| EP1363938B1 (en) | 2013-12-11 |
| WO2002012281A9 (en) | 2003-03-06 |
| AU2001278117A1 (en) | 2002-02-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7342002B2 (en) | Molecular vaccine linking an endoplasmic chaperone polypeptide to an antigen | |
| EP1222289B1 (en) | Chimeric immunogenic compositions and nucleic acids encoding them | |
| AU2021232660B2 (en) | HPV vaccines | |
| Velders et al. | Defined flanking spacers and enhanced proteolysis is essential for eradication of established tumors by an epitope string DNA vaccine | |
| US7318928B2 (en) | Molecular vaccine linking intercellular spreading protein to an antigen | |
| US10166276B2 (en) | Compositions and methods for treatment of non-hodgkins lymphoma | |
| Cheng et al. | Enhancement of sindbis virus self-replicating RNA vaccine potency by targeting antigen to endosomal/lysosomal compartments | |
| Hung et al. | A DNA vaccine encoding a single-chain trimer of HLA-A2 linked to human mesothelin peptide generates anti-tumor effects against human mesothelin-expressing tumors | |
| KR20020068040A (ko) | 키메라 면역원성 조성물 및 그들을 암호화하는 핵산 | |
| EP1644048B1 (en) | Anti-cancer dna vaccine employing plasmids encoding signal sequence, mutant oncoprotein antigen, and heat shock protein | |
| WO2019101062A1 (zh) | 重组疫苗及其应用 | |
| US20080260765A1 (en) | HPV DNA Vaccines and Methods of Use Thereof | |
| JP2008528004A (ja) | 突然変異癌タンパク質抗原およびカルレティキュリンをコードするプラスミドを用いる抗癌ｄｎａワクチン | |
| US20080095789A1 (en) | Vaccine | |
| Gérard et al. | Recombinant human papillomavirus type 16 E7 protein as a model antigen to study the vaccine potential in control and E7 transgenic mice | |
| JP2005526511A (ja) | ワクチン | |
| Li | Development of multiple formulations of heat shock protein based vaccines for cancer immunotherapy | |
| MXPA02003986A (en) | Chimeric immunogenic compositions and nucleic acids encoding them |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20080731 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20080731 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20110426 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20110725 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20120117 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120517 |
|
| A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20120724 |
|
| 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: 20120814 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20120910 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 Ref document number: 5087201 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20150914 Year of fee payment: 3 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| EXPY | Cancellation because of completion of term |