发明名称 |
Tetrameric cytokines with improved biological activity |
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 either 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. In more preferred embodiment the cytokine is G-CSF, erythropoietin or INF-alpha2b. |
申请公布号 |
US8597659(B2) |
申请公布日期 |
2013.12.03 |
申请号 |
US201113219940 |
申请日期 |
2011.08.29 |
申请人 |
CHANG CHIEN-HSING;GOLDENBERG DAVID M.;ROSSI EDMUND A.;IBC PHARMACEUTICALS, INC. |
发明人 |
CHANG CHIEN-HSING;GOLDENBERG DAVID M.;ROSSI EDMUND A. |
分类号 |
A61K39/44;A61K38/18;A61K38/20;A61K38/21;A61K39/00;A61K39/385;A61K39/395;C07K14/505;C07K14/535;C07K14/56;C07K16/28;C07K16/30;C07K16/44 |
主分类号 |
A61K39/44 |
代理机构 |
|
代理人 |
|
主权项 |
|
地址 |
|