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BACTERIAL TOXIN VACCINE

Foreign code F110006029
File No. S2008-0581
Posted date 2011年12月27日
Country 世界知的所有権機関(WIPO)
International application number 2009JP058345
International publication number WO 2009133882
Date of international filing 平成21年4月28日(2009.4.28)
Date of international publication 平成21年11月5日(2009.11.5)
Priority data
  • 特願2008-120573 (2008.5.2) JP
Title BACTERIAL TOXIN VACCINE
Abstract The object aims to produce a bacterial toxin protein such as Siga-toxin protein with high efficiency by using a plant cell. A bacterial toxin protein such as Siga-toxin protein can be produced in a plant cell by transforming the plant cell with a DNA construct which comprises DNA encoding a hybrid protein composed of bacterial toxin proteins linked in tandem via a peptide having any one of the following characteristic properties (A) and (B): (A) the number of amino acid residues is 12 to 30; and (B) the proline content is 20 to 35%.
Outline of related art and contending technology BACKGROUND ART
Shiga toxin (Stx, verotoxin) is, in the gastrointestinal tract of the pathogenic E. coli enterohemorrhagic E. coli (enterohemorrhagic Escherichia coli) in protein produced by a pyrogenic exotoxin. Shiga toxins, hemorrhagic colitis, hemolytic uremic syndrome, encephalopathy and others. Shiga toxins, divided into Stx2 large and Stx1, each divided into further sub-class. As Stx2, and Stx2e for example swine edema causes soft rot. Pig edema disease that is, 1-2 week after weaning the piglets are high known to be generated. Edema are inoculated with a mortality rate due to infection, and a high 50-90%. In addition, the cholera toxin (CT), protein produced by Vibrio cholerae toxin-in. Is CT, severe diarrhea and emesis are known to cause. In addition, E. coli heat labile toxin (LT) is, enterotoxigenic E. coli (enterotoxigenic Escherichia coli) in toxin-protein produced. LT is, diarrhea and emesis are known to cause. Stx, LT, of any bacterial toxins CT, involved in cell adhesion to the 5 subunit B subunit A toxicity 1 - fold amount by weight of laminates of known amount. In addition, CT and LT is, structurally functionally similar to the known.
These bacterial toxins as a method for preventing disease, a vaccine, or administered by injection or nasal spray, or orally administered in a known method. For example, the detoxified protein Stx2e and produced using recombinant Escherichia coli strain, a technique is adminstered by injection (non-patent document 1) are known. However, by the recombinant E. coli, and production of detoxified protein Stx2e is not sufficient and a problem in that the administration of the vaccine is by injection, such as human labor problem. In addition, orally administered vaccine with respect to the method, from the viewpoint of husbandry and reduce which are of interest in the art. In view of these circumstances, a bacterial toxin protein, to the plant using a transgenic technology for the production of the development of a technique is being performed. For example, LT B subunit protein encoding DNA (LTB) include, for transgenic plants expressing the DNA described in (patent document 1, patent document 2). In addition, CT LT protein or encoding a protein for a transgenic plant expressing the DNA described in (Patent Document 3). However, these techniques, a sufficient amount of protein production was not a problem. In addition, an example in which the lettuce produced LTB is reported (non-patent document 2). In this study, codon modified LT B subunit gene of the protein, the cauliflower mosaic virus promoter in plant 35S RNA to a high expression promoter and (CaMV35S), an enhancer Kozak sequence may be used, are expressed in lettuce. As a result, lettuce LT B subunit protein of about 2.0 mass % of the total soluble protein accumulation have been reported. However, the amount of accumulation of the protein of this size, using transgenic plant bacterial disease which is insufficient for efficiently controlling considered. That is, a bacterial toxin protein of interest in a plant cell with good efficiency, needs to be stored. The inventors of the present invention, the secretion signal peptide at the amino terminal end of vegetable origin added to the Stx2e protein, plant-derived alcohol dehydrogenase gene of the 5 '- untranslated region (ADH5' UTR) can be expressed by using, a lettuce plant of the Stx2e protein with good efficiency and the like, accumulated at high concentrations in the plant can be found, performing a patent application (patent document 4).
  • Applicant
  • ※All designated countries except for US in the data before July 2012
  • IDEMITSU KOSAN CO., LTD.
  • NATIONAL UNIVERSITY CORPORATION NARA INSTITUTE OF SCIENCE AND TECHNOLOGY
  • Inventor
  • SAWADA, Kazutoshi
  • YOSHIDA, Kazuya
  • MATSUI, Takeshi
IPC(International Patent Classification)
Specified countries National States: AE AG AL AM AO AT AU AZ BA BB BG BH BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IS JP KE KG KM KN KP KR KZ LA LC LK LR LS LT LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PG PH PL PT RO RS RU SC SD SE SG SK SL SM ST SV SY TJ TM TN TR TT TZ UA UG US UZ VC VN ZA ZM ZW
ARIPO: BW GH GM KE LS MW MZ NA SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ MD RU TJ TM
EPO: AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LT LU LV MC MK MT NL NO PL PT RO SE SI SK TR
OAPI: BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG
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