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PEPTIDE/β-1,3-GLUCAN COMPLEX AND PRODUCTION METHOD THEREFOR, AND PHARMACEUTICAL COMPOSITION CONTAINING PEPTIDE/β-1,3-GLUCAN COMPLEX

外国特許コード F150008549
整理番号 AF11-11WO
掲載日 2015年11月26日
出願国 世界知的所有権機関(WIPO)
国際出願番号 2014JP084374
国際公開番号 WO 2015118789
国際出願日 平成26年12月25日(2014.12.25)
国際公開日 平成27年8月13日(2015.8.13)
優先権データ
  • 特願2014-021333 (2014.2.6) JP
発明の名称 (英語) PEPTIDE/β-1,3-GLUCAN COMPLEX AND PRODUCTION METHOD THEREFOR, AND PHARMACEUTICAL COMPOSITION CONTAINING PEPTIDE/β-1,3-GLUCAN COMPLEX
発明の概要(英語) This peptide/β-1,3-glucan complex contains β-1,3-glucan and a peptide/polynucleotide conjugate in which an antigenic peptide is bonded via a covalent bond to a polynucleotide or a derivative thereof. The polynucleotide or derivative thereof of the peptide/polynucleotide conjugate bonds via a hydrogen bond with β-1,3-glucan, forming a complex having a triple helix structure comprising a single molecular chain of the polynucleotide or derivative thereof and a double molecular chain of the β-1,3-glucan. Alternately, the side chain of the β-1,3-glucan and the antigenic peptide are bonded via a covalent bond created through either a cycloaddition reaction between an alkyne and an azide derivative, or a reaction between a maleimide group or a vinyl sulfone group and a thiol group.
従来技術、競合技術の概要(英語) BACKGROUND ART
Is the basic principle of the vaccine preventing infection, human pseudo-infection, to induce acquired immunity, against certain pathogens antibody production or to induce cell-mediated immunity. In acquired immunity, immunity is responsible for ' storage'T cells and B cells play a central role, by reconstruction DNA that the diversity of the variable regions of an antibody, specific to an antigen for an infinite number allows an immunological reaction are known. On the other hand, leukocytes, macrophages, dendritic cells such as phagocytic cells play a central role in the innate immunity is, conventional, phagocytose pathogens or foreign matter and non-specific processes, established immune to '' serves only as a is thought to play a, the progress of the studies related to the molecular mechanism of innate immunity, innate immunity in the, self, non-self-specific recognition by the part and the, the point-to-innate immune adaptive immune was demonstrated to be essential. More specifically, dendritic cells, macrophages, antigen presenting cells such as B Toll-like receptor (TLR) present in the family, react with the various etiologic agents, induces the production of cytokines, naive T cells to promote differentiation to Th1 cells, such as the activation of killer T cells through, to induce immune, a recent study has revealed.
A series of TLR family that is recognized by a component of a pathogen-state laser, in which one of 1, TLR9 is a ligand, which has the sequence CpG DNA. CpG sequences, guanine and cytosine (C) the center (g) are arranged in the base sequence of 6 bases, in a mammal to a less extent, frequently in microorganisms include the nucleotide sequence. In addition, in a mammal, most of the present few CpG sequences are methylated. There is little in mammalian non-methylated CpG sequence, has a strong immunostimulatory activity (for example, see non-patent document 1-3). Is captured within the cell by endocytosis CpG DNA, present in the phagosome to the endoplasmic reticulum as recognized by the TLR9, Th1 to strongly induce the reaction. Th1 The reaction is carried out, to suppress the allergic reaction Th2 with predominance, strong have anti-tumor activity. Therefore, CpG DNA is, in addition to the prevention of infection, allergic diseases, tumor diseases are expected to be used as adjuvants (for example see non-patent document 4).
However, when used as an adjuvant to the immune therapy CpG DNA, and nuclease degradation in the cytoplasm or in the plasma, the unspecific binding of the protein while avoiding, how to reach the interior of a target cell CpG DNA becomes a problem.
The inventors of the present invention, a new gene β - 1 as a carrier, a polysaccharide having 3 - glucan skeleton (hereinafter, 'β - 1, 3 - glucan' is abbreviated.) Focusing on, so far, β - 1, 3 - glucan (antisense DNA, CpG DNA) a nucleic acid drug including a variety of nucleic acid and a new type of complex has been found to form (for example, Patent Document 1, 2, see non-patent document 5-7).
3 Β - 1 naturally present in the double helix, 3 - glucans, such as dimethyl sulfoxide (DMSO) non-polar protic organic solvent, or dissolved in a more alkali 0.1N 1 after dissociation of a double stranded, single-stranded nucleic acid 1 was added, by returning the solvent water or neutral, 1 nucleic acid molecule β - 1, the double helix glucan 2 3 3 - and molecules the inventors found that a complex is formed. In this case, the double helix β - 1 in complex with 3, 3 - glucan molecule nucleic acid molecules, mainly through hydrophobic interaction and hydrogen bonding to form intermolecular bonds believed (see non-patent document 8).
As described above, nucleic acid β - 1, 3 - glucans by compounding, hydrolysis or of the nucleic acid molecule by a nuclease, nonspecific binding of plasma proteins and nucleic acids such as, protein and nucleic acid molecules in vivo while suppressing undesirable interactions, to reach the interior of the cell the nucleic acid has become possible. Β - 1, glucan and the nucleic acid complex of 3 -, 3 and further comprising a protein having antigenicity using the ternary complex, intracellular CpG DNA delivery to a successful (for example, Patent Document 3, 4, see non-patent document 9-11).
  • 出願人(英語)
  • ※2012年7月以前掲載分については米国以外のすべての指定国
  • JAPAN SCIENCE AND TECHNOLOGY AGENCY
  • 発明者(英語)
  • SAKURAI Kazuo
  • MOCHIZUKI Shin-ichi
  • MORISHITA Hiromi
国際特許分類(IPC)
指定国 National States: AE AG AL AM AO AT AU AZ BA BB BG BH BN BR BW BY BZ CA CH CL 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 IR IS JP KE KG KN KP KR KZ LA LC LK LR LS LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PA PE PG PH PL PT QA RO RS RU RW SA SC SD SE SG SK SL SM ST SV SY TH TJ TM TN TR TT TZ UA UG US UZ VC VN ZA ZM ZW
ARIPO: BW GH GM KE LR LS MW MZ NA RW SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ RU TJ TM
EPO: AL 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 RS SE SI SK SM TR
OAPI: BF BJ CF CG CI CM GA GN GQ GW KM ML MR NE SN ST TD TG
参考情報 (研究プロジェクト等) CREST Development of the Foundation for Nano-Interface Technology AREA
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