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Title:
薬物動態が改善された四量体サイトカインをドック・アンド・ロック(DNL)技術により調製するためのモジュール法
Document Type and Number:
Japanese Patent JP2011517684
Kind Code:
A
Abstract:
The present invention concerns methods and compositions for forming cytokine-antibody complexes using dock-and-lock technology. In preferred embodiments, the cytokine-MAb DNL complex comprises an IgG antibody attached to two AD (anchor domain) moieties and four cytokines, each attached to a DDD (docking and dimerization domain) moiety. The DDD moieties form dimers that bind to the AD moieties, resulting in a 2:1 ratio of DDD to AD. The cytokine-MAb complex exhibits improved pharmacokinetics, with a significantly longer serum half-life than naked cytokine or PEGylated cytokine. The cytokine-MAb complex also exhibits significantly improved in vitro and in vivo efficacy compared to cytokine alone, antibody alone, unconjugated cytokine plus antibody or cytokine-MAb DNL complexes incorporating an irrelevant antibody. Most preferably, the complex comprises an anti-CD20 IgG antibody conjugated to four IFN-a2b moieties, although other antibodies and cytokines have been used to form DNL complexes.

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Inventors:
Chang, Shen-Shin
Goldenberg, david, em
Rossi, Edmond, A
Application Number:
JP2011504101A
Publication Date:
June 16, 2011
Filing Date:
April 06, 2009
Export Citation:
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Assignee:
Ivy Pharmaceuticals, Inc.
International Classes:
C07K19/00; A61K38/21; A61K38/22; A61K38/23; A61K38/48; A61K39/395; A61K47/42; A61K47/48; A61P1/04; A61P1/16; A61P3/10; A61P5/14; A61P5/16; A61P5/40; A61P7/02; A61P7/04; A61P7/06; A61P9/00; A61P11/00; A61P13/12; A61P17/00; A61P17/06; A61P19/02; A61P21/00; A61P21/04; A61P25/00; A61P25/14; A61P29/00; A61P35/00; A61P35/02; A61P37/02; A61P37/06; C07K14/52; C07K16/24; C12N15/09
Domestic Patent References:
JP2003507012A2003-02-25
Foreign References:
WO2007046893A22007-04-26
WO2007075270A22007-07-05
Other References:
JPN6013062262; Ｔｈｅ　Ｊｏｕｒｎａｌ　ｏｆ　Ｎｕｃｌｅａｒ　Ｍｅｄｉｃｉｎｅ Ｖｏｌ．４９，Ｎｏ．１, 200801, ｐ．１５８-１６３
JPN6013062262; Ｔｈｅ　Ｊｏｕｒｎａｌ　ｏｆ　Ｎｕｃｌｅａｒ　Ｍｅｄｉｃｉｎｅ Ｖｏｌ．４９，Ｎｏ．１, 200801, ｐ．１５８-１６３
Attorney, Agent or Firm:
Ryoichi Takaoka



 
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