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ANTIBODY RECOGNIZING FOLATE RECEPTORS α AND β

Foreign code F150008058
File No. S2013-0319-C0
Posted date 2015年1月8日
Country 世界知的所有権機関(WIPO)
International application number 2013JP085026
International publication number WO 2014104270
Date of international filing 平成25年12月19日(2013.12.19)
Date of international publication 平成26年7月3日(2014.7.3)
Priority data
  • 特願2012-281525 (2012.12.25) JP
Title ANTIBODY RECOGNIZING FOLATE RECEPTORS α AND β
Abstract The purpose of the present invention is to provide an antibody that immunologically and specifically binds to folate receptor α and folate receptor β. Specifically disclosed is an antibody or a fragment thereof, wherein the amino acid sequences of the CDRH1, CDRH2 and CDRH3 of a heavy chain variable region (VH) are respectively the amino acid sequences of SEQ ID NOS:2, 4 and 6, and the amino acid sequences of the CDRL1, CDRL2 and CDRL3 of a light chain variable region (VL) are respectively the amino acid sequences of SEQ ID NOS:10, 12 and 14.
Outline of related art and contending technology BACKGROUND ART
(FR) folic acid receptor and oxidized form of folic acid receptor, a human cell is FR α, and the presence FR β FR γ isoforms are known (non-patent document 1). Is FR α, and expressed on the surface of epithelial cells, a variety of cancer cells to increase expression. Recently, anti-FR α antibody is used in the ovarian cancer patient clinical trials phase II in the United States, its effect could be confirmed (non-patent document 2). In addition, the patent document 1, anti-ovarian cancer antibody FR α treatment composition is disclosed. On the other hand, reduced expression of the healthy tissue FR β, synovial rheumatoid arthritis, osteoarthritis synovial, pulmonary fibrosis of lung tissue such as expressed on the surface of the inflamed tissue is seen in activated macrophages (non-patent document 3-5). Further, inventors of the present invention, anti-human FR β producing antibodies, cancer-associated macrophages present in the tissue in a variety of cancers FR β expression in many of the macrophage, and pancreatic cancer cancer FR β expression in macrophages increases the number of poor prognosis for life (non-patent document 6) shown. In addition, the present inventors, in malignant glioma xenograft model, using anti-FR β FR β antibody immunotoxins by removing macrophages, suppressed the growth of malignant glioma showed (non-patent document 7). Further, the patent document 2-4, FR-β antibodies and the antibody and the toxin can be connected to the FR-β antibody immunotoxins, as well as antibodies and immunotoxins containing the disclosed therapeutic agents. As described above, up to now such as anti-anti-antibody or antibody immunotoxins FR α FR β alone due to the use of anti-FR β antibody binding on the proliferation of cancer is known. However, anti-FR β that binds to anti-FR α that binds to the compound of the compound of the cancer by combination therapy using an anti-proliferative effect has not been reported. In addition, the FR α FR β and, at the amino acid level having a homology of about 70% is, so far and antibodies that recognize both FR α FR β has not been reported.
  • Applicant
  • ※All designated countries except for US in the data before July 2012
  • KAGOSHIMA UNIVERSITY
  • Inventor
  • MATSUYAMA, Takami
  • NAGAI, Taku
  • HASUI, Kazuhisa
  • TAKAO, Sonshin
IPC(International Patent Classification)
Specified countries 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 LT 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 TD TG
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