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DRUG COMPLEX UPDATE

外国特許コード F170008956
整理番号 (S2015-1723-N0)
掲載日 2017年2月16日
出願国 世界知的所有権機関(WIPO)
国際出願番号 2016JP068934
国際公開番号 WO 2016208761
国際出願日 平成28年6月25日(2016.6.25)
国際公開日 平成28年12月29日(2016.12.29)
優先権データ
  • 特願2015-128028 (2015.6.25) JP
発明の名称 (英語) DRUG COMPLEX UPDATE
発明の概要(英語) [Problem] To provide a drug delivery system that can deliver a drug into a cell expressing a VEGF receptor.
[Solution] Provided is a VEGF binding peptide-drug complex which is incorporated into VEGF receptor-expressing cells by VEGF receptor endocytosis, by binding a drug to the C-terminal amino acid or the N-terminal amino acid of a VEGF binding peptide having a helix-loop-helix structure comprising an A block located on the N-terminal side comprising a peptide that forms an α-helix structure, a C block located on the C-terminal side comprising a peptide that forms an α-helix structure, and a B block comprising a peptide that connects the A block and C block by covalent bonds.
従来技術、競合技術の概要(英語) BACKGROUND ART
Vascular endothelial growth factor (VEGF: Vascular Endothelial Growth Facto r) is, promoting angiogenesis generally known as a protein. This VEGF is, vertebrate embryonic phase, formation of the circulatory system in the early childhood in the construction of many tissues is an important role, and after maturity, cancer growth, transition form-, promote the formation of chronic rheumatoid arthritis disease, diabetic retinopathy and the like can be also involved in the, in pathological conditions such as this has been regarded as important.
Is a transmembrane tyrosine kinase receptor VEGFR VEGF binding to and interaction with, exerts its biological effects. Therefore, the binding of VEGF and VEGFR to angiogenesis by inhibiting the interaction is suppressed, proliferation and the inhibition of metastasis of cancer, chronic rheumatoid arthritis and diabetic retinopathy, age related macular degeneration can lead to the pathology of the promotion of deterrence expected. In fact, be bonded to the VEGFR, inhibits the interaction or binding of the VEGF monoclonal antibody bevacizumab (trade name, Avastin) which uses a, metastatic breast cancer or metastatic colon cancer used as anticancer agents.
However, if the antagonist is a peptide, a three-dimensional structure generally restricted peptide has been selected. Regulating the three-dimensional structure of many peptides in the peptide by a disulfide bond to stabilize the tertiary structure. However, disulfide bonds under reducing conditions within the cell is cleaved to yield the three-dimensional structure and easily breaks was. In addition, be decomposed by protease in vivo, the disadvantage that the serum half-life may be short. Therefore, more stable peptides in vivo is demanded.
Does not have such a drawback as stabilized peptide, helix - loop - helix structure (structure Helix-Loop-Helix) a peptide having a disclosed Patent Document 1 or the like. Helix - loop - helix structure epitope, the amino acid sequence of the C-terminal N (N-terminal of the helix: A block) and, the amino acid sequence of the C-terminal C (C-terminal of the helix: block C) and, coupling the blocks C A block having a linker (block B). Block A and block C, due to the presence of α - helical coiled-coil linker structure respectively. This peptide is a low molecular weight while the structure is stable in solution at the secondary of taking a crystal structure, a portion that is exposed on the solvent side of the molecule chemically distinct nature of the functional groups easily introduced. Utilizing such a nature, helix - loop - helix structure with biological activity of the peptide with various properties have been proposed.
Under such circumstances, the present inventors, have a joining property VEGF, VEGF receptor and inhibit the binding of VEGF VEGF binding peptide complex has been proposed (patent document 2). This complex, helix - loop - helix having VEGF binding peptides having C-terminal of the structure, and thioredoxin was linked to the composite. VEGF VEGF VEGF-binding peptide and either do not inhibit the interaction of the receptor, or its inhibition ability is very small, and thus has a VEGF-binding peptide is not capable of exerting sufficient anticancer activity was considered. Therefore, such a large thioredoxin molecule has three-dimensional structure can be attached to the peptide binding VEGF is effected by steric hindrance, the binding of VEGF to VEGF receptor and to inhibit an interaction, inhibiting angiogenesis and, exhibit anticancer activity and the like has been for the purpose. However, both of them are coupled in this complex inhibition activity is far from being sufficient. In addition, increases the molecular weight of the complex, the binding of VEGF and weakening the binding peptide itself, and that is also a problem that it is difficult to manufacture, to overcome these problems a new cancer therapeutic agents is demanded.
  • 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
  • OSAKA PREFECTURE UNIVERSITY PUBLIC CORPORATION
  • 発明者(英語)
  • Ikuo Fujii
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

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