发明名称 |
Modular method to prepare tetrameric cytokines with improved pharmacokinetics by the dock-and-lock (DNL) technology |
摘要 |
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-α2b moieties, although other antibodies and cytokines have been used to form DNL complexes. |
申请公布号 |
AU2009233925(B2) |
申请公布日期 |
2014.03.13 |
申请号 |
AU20090233925 |
申请日期 |
2009.04.06 |
申请人 |
IBC PHARMACEUTICALS, INC. |
发明人 |
ROSSI, EDMUND A.;CHANG, CHIEN-HSING;GOLDENBERG, DAVID M. |
分类号 |
C07K16/30;A61K39/395;C07K16/46 |
主分类号 |
C07K16/30 |
代理机构 |
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代理人 |
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主权项 |
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地址 |
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