Top > Search of International Patents > HIGHLY-FUNCTIONAL IgG2 BISPECIFIC ANTIBODY

HIGHLY-FUNCTIONAL IgG2 BISPECIFIC ANTIBODY

Foreign code F150008620
File No. (S2014-0533-N0)
Posted date Dec 16, 2015
Country WIPO
International application number 2015JP055341
International publication number WO 2015146437
Date of international filing Feb 25, 2015
Date of international publication Oct 1, 2015
Priority data
  • P2014-062066 (Mar 25, 2014) JP
Title HIGHLY-FUNCTIONAL IgG2 BISPECIFIC ANTIBODY
Abstract [Problem] To provide a highly-functional bispecific antibody in which superior cytotoxic activity functions such as an anti-tumor effect are maintained and functions are improved, and in particular, to provide an LH bispecific antibody.
[Solution] A bispecific antibody etc. against anti-human epidermal growth factor receptor 1 and CD3 and includes: a variable region containing an L-chain humanized variable region (5L; SEQ ID NO:2) and an H-chain humanized variable region (5H; SEQ ID NO:4) of antibody 528 of anti-human epidermal growth factor receptor 1, 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; a hinge region; and an Fc region. The bispecific antibody etc. is characterized in that the Fc region is derived from a human IgG2 subclass.
Outline of related art and contending technology 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 composed of the medicament, with fewer side effects, high free with the therapeutic effect can be seen that 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) (V region) and light chain VH ('VH' by each other) the variable region of (L chain) (region V) VL ('VL' by each) non-covalently to each other to form a heterodimer is devised utilizing a property that the (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 LH-type bispecific antibody and-type bispecific antibody highly functional bispecific antibody (Patent Document 3) was developed. 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 antibody 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.
Scope of claims (In Japanese)請求の範囲 [請求項1]
抗ヒト上皮細胞成長因子受容体1抗体528のL鎖のヒト型化可変領域(5L:配列番号2)及びH鎖のヒト型化可変領域(5H:配列番号4)、抗CD3抗体OKT3のL鎖のヒト型化可変領域(OL:配列番号6)及びH鎖のヒト型化可変領域(OH:配列番号8)を含む可変領域、ヒンジ領域、並びに、Fc領域を含む、抗ヒト上皮細胞成長因子受容体1及びCD3に対する二重特異性抗体であって、該Fc領域がヒトIgG2サブクラスに由来することを特徴とする、前記抗体。

[請求項2]
各ポリペプチドにおいて、L鎖可変領域がH鎖可変領域のN末側にあること(LH型)を特徴とする、請求項1記載の抗体。

[請求項3]
IgG型タイプの免疫グロブリン分子と同じドメイン数を有する、請求項1又は2に記載の抗体。

[請求項4]
(OL5H)-(ペプチドリンカー)-(5LOH)で示される構造を有するシングルポリペプチド鎖がヒンジ領域を介してヒト抗体のFc領域に結合した構造を有している、請求項3に記載の抗体。

[請求項5]
請求項1~4のいずれか一項に記載された抗体を構成する一本鎖ポリペプチド。

[請求項6]
請求項5記載のポリペプチドをコードする核酸分子。

[請求項7]
請求項6記載の核酸を含有する複製可能なクローニングベクター又は発現ベクター。

[請求項8]
プラスミドベクターである、請求項7記載のベクター。

[請求項9]
請求項7又は8記載のベクターで形質転換された宿主細胞。

[請求項10]
哺乳動物細胞である請求項9記載の宿主細胞。

[請求項11]
請求項9記載の宿主細胞を培養して宿主細胞中で該核酸を発現せしめ、請求項4に記載の一本鎖ポリペプチドを回収し、精製し、得られた該一本鎖ポリペプチドを会合させ、形成された抗体を分離・回収することを特徴とする、請求項1~4のいずれか一項に記載の抗体の製造方法。

[請求項12]
請求項1~4のいずれか一項に記載の抗体を有効成分として含有することを特徴とする医薬組成物。

[請求項13]
腫瘍細胞を排除する、殺傷する、傷害する及び/又は減少せしめるためのものであることを特徴とする請求項12記載の医薬組成物。

  • Applicant
  • ※All designated countries except for US in the data before July 2012
  • TOHOKU UNIVERSITY
  • Inventor
  • KUMAGAI Izumi
  • ASANO Ryutaro
  • UMETSU Mitsuo
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 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
Please contact us by facsimile if you have any interests on this patent.

PAGE TOP

close
close
close
close
close
close