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BISPECIFIC ANTIBODY TARGETING HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR

外国特許コード F150008621
整理番号 (S2014-0534-N0)
掲載日 2015年12月16日
出願国 世界知的所有権機関(WIPO)
国際出願番号 2015JP055357
国際公開番号 WO 2015146438
国際出願日 平成27年2月25日(2015.2.25)
国際公開日 平成27年10月1日(2015.10.1)
優先権データ
  • 特願2014-064141 (2014.3.26) JP
発明の名称 (英語) BISPECIFIC ANTIBODY TARGETING HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR
発明の概要(英語) [Problem] To provide a bispecific antibody such as a bispecific antibody having a variety of high functionalities or a bispecific antibody produced using a novel antibody against human epidermal cell growth factor receptor 1 (EGFR), said novel antibody differing from antibody 528.
[Solution] A bispecific antibody etc. against anti-human epidermal cell growth factor receptor 1 and CD3 that includes an L-chain variable region (2L; SEQ ID NO:2) and an H-chain variable region (2H; SEQ ID NO:4) of anti-human epidermal cell growth factor receptor 1 antibody 225, and an L-chain humanized variable region (OL; SEQ ID NO:6) and an H-chain humanized variable region (OH; SEQ ID NO:8) of anti-CD3 antibody (OKT3).
従来技術、競合技術の概要(英語) BACKGROUND ART
Rheumatoid arthritis and cancer (malignant tumor) security against therapy, in recent years, immunotherapy has been used. Immunotherapy for cancer, cancer-specific cytotoxic activity antibody is being used. Such antibodies from the antibody medicament is, with fewer side effects, with the manufacturing of a therapeutic effect can be seen that the high on the other hand, an established animal cell is used to generate high costs for manufacture must be in question.
For this reason, the dose can be significantly reduced as produced at a lower cost, a very strong activity of the recombinant antibody has been tried to manufacture.
For example, one of such recombinant antibody is a bispecific antibody (Bispecific Antibody: BsAb) two different 2 is capable of binding to a specifically to an antigen and therefore, this making the specific anti-tumor having an effect as a therapeutic as enabling a utilization method, their study has been actively performed. (Diabody: Db) diabody such bispecific antibody is a minimum unit, derived from the same parent antibody variable region of the heavy chain (H chain) ('VH' by each) (V region) VH and the light chain variable region (L chain) ('VL' by each) (region V) non-covalently to each other VL heterodimer formed by utilizing the property that is devised (non-patent document 1) in. Also, other than the diabody-type bispecific antibody in the preparation of a bispecific antibody and the like, for example, non-patent document 2 and non-patent document 3 described.
The present inventors have, thus far, anti-human epidermal growth factor receptor antibody 528 and anti-CD3 antibody 1 OKT3 (Her1) that is produced using a diabody-type bispecific antibody (Ex3) and the antibody and a humanized diabody-type bispecific antibody is extremely potent anti-tumor effect (hExh3) has a finding (Patent Document 1). Further, this humanized diabody-type bispecific antibodies is based on the control of diverse structure and are highly functional bispecific antibody (Patent Document 2) have developed.
Further, the present inventors, humanized diabody-type bispecific antibody in a polypeptide constituting the powder side N L chain variable region 'LH-type' is characterized in that the LH-type bispecific antibody LH-type bispecific antibody and the high-functional bispecific antibodies were developed (Patent Document 3). In addition, antibody H chain or L chain 528 Her1 of the various amino acid mutations, substitutions these antibodies (patent document 4 and patent document 5) as well as an.
Described in the above-mentioned Patent Document 2-5 highly functional bispecific antibody is, respectively, anti-human epidermal growth factor receptor antibody OKT3 and anti-CD3 antibodies 1 and 528 of the chain L H chain variable region comprising the Fc region in addition to, the bispecific antibody. Such a structure having a humanized highly functional bispecific antibody is, compared with Ex3 significantly enhanced the cytotoxic activity, can be combined with bivalent to each antigen, such as by protease digestion with a minimum addition sequences Tag bispecific antibody is readily prepared, can be simply performed by the protein A purification. Further, antibody-dependent cellular cytotoxicity (ADCC) activity and complement-dependent cytotoxicity (CDC) effect of the action of the function of inducing effector induction and the like is newly applied.
  • 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)
  • KUMAGAI Izumi
  • ASANO Ryutaro
  • UMETSU Mitsuo
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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