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CANCER CELL MOTILITY AND CANCER CELL INFILTRATION INHIBITOR

外国特許コード F110002750
整理番号 S2008-0392-C0
掲載日 2011年4月13日
出願国 世界知的所有権機関(WIPO)
国際出願番号 2009JP055479
国際公開番号 WO 2009119455
国際出願日 平成21年3月19日(2009.3.19)
国際公開日 平成21年10月1日(2009.10.1)
優先権データ
  • 特願2008-083588 (2008.3.27) JP
発明の名称 (英語) CANCER CELL MOTILITY AND CANCER CELL INFILTRATION INHIBITOR
発明の概要(英語) Provided are an antibody which binds specifically to PAR1 (protease-activated receptor 1) or a fragment of the preceding antibody which sustains similar characteristics thereto; a composition containing the same for inhibiting the motion activity and infiltration activity of cancer cells; and a medicinal composition for treating cancer and the like.
従来技術、競合技術の概要(英語) BACKGROUND ART
Ability and movement of the cells that have generated as a result of the invasive potential of the disease may typically have a cancer. 1 As one of the most conspicuous threat of cancer and metastasis. Cell motility by metastatic cancer cells can be transferred through a blood vessel from HCCs, after infiltration within the blood vessel, blood flow and metastasize to other tissues. PAR1 (Protease activated receptor 1: protease activated receptor 1) is, capable of being in motion and the invasive potential of cancer cells to activate 7 - transmembrane receptor, a variety of types of cancer (breast cancer, lung cancer, pancreatic cancer and prostate cancer) are involved in the metastasis of the present invention. In particular breast cancer, cancer having a metastatic potential of cultured cell lines and most of the PAR1 is expressed in, cancer-specific protease (MMP1: Matrix Metalloprotease 1: matrix metalloproteinase 1) by, of the PAR1 - terminal extracellular region N (R41 and S42 between) is cut PAR1 is activated has been known. PAR1 Is stimulated, and couples to the intracellular region of a PAR1 g Activation. As a result, intracellular Ca2+ concentration increases locally, this Ca2+ signal and cell invasion by cells capable of being in motion is believed to enhance the ability (see non-patent document 1).
PAR1 Is originally required for the platelets are activated thrombin-dependent receptor (thrombin receptor) were discovered as. Thrombin, PAR1 and MMP1 of the recognition site is formed by cutting the same. In addition, the activation of platelet thrombin receptor as in the case of cancer cells, Ca2+ activating signal. Current, cellular domains of PAR1 monoclonal antibody N powder and has a some embodiments, these antibodies inhibits platelet activation. However, these antibodies to cancer cell motility and invasion but the relation between the report, even in the PAR1 cancer cell motility and invasion-inhibiting antibody, PAR1 antibody or no report that used in the treatment of cancer.
In addition, PAR1 g of the synthesized peptides corresponding to the protein binding sites, which has a membrane permeability this peptide Pepducin made of a material that (see non-patent document 2). G protein a pepducin Covic et al. can be used as an antagonist of inhibiting the activity of PAR1 has succeeded in (the inhibitory effect of the pepducin 3-4μM). On the other hand, practical applications as anti-cancer agents is an antibody, as well as the inhibitory effect of the target molecule activity, immune system cells by antibody dependent cell-mediated cytotoxic activity effect can be expected. The antibody also may be, by genetic engineering is the art of making high affinity antibodies has been established, and ensured safety to the living organism such as an antibody as anti-cancer agents is very favorable to be applied. Therefore, the anti-cancer agent when it is used as PAR1 antibody, anti-cancer agents and more effective pepducin can be considered a lot.
PAR1 Th 56 th Tyr Trp from of the 52 epitope antibody is produced in a phage display library, the antibody, to inhibit the activity of the thrombin cutting PAR1. Wherein the antibody is of PAR1 to inhibit cleavage activity with respect to the (binding to PAR1), in particular 56 epitope Trp is included as the second important (see Patent Document 1) are. The current, the motility of cancer cells to inhibit the invasive and report or PAR1 antibody, PAR1 antibody epitope as effective inhibitory effect of the other peptide sequences is found no report of.
  • 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
  • TOHOKU UNIVERSITY
  • 発明者(英語)
  • GONDA, Kohsuke
  • HIGUCHI, Hideo
  • OHUCHI, Noriaki
  • TAKEDA, Motohiro
国際特許分類(IPC)
指定国 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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