发明授权
- 专利标题: Tetrameric cytokines with improved biological activity
- 专利标题(中): 具有改善的生物活性的四聚体细胞因子
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申请号: US14067296申请日: 2013-10-30
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公开(公告)号: US09498542B2公开(公告)日: 2016-11-22
- 发明人: Chien-Hsing Chang , David M. Goldenberg , Edmund A. Rossi
- 申请人: IBC Pharmaceuticals, Inc.
- 申请人地址: US NJ Morris Plains
- 专利权人: Immunomedics, Inc.
- 当前专利权人: Immunomedics, Inc.
- 当前专利权人地址: US NJ Morris Plains
- 代理商 Richard A. Nakashima
- 主分类号: A61K47/48
- IPC分类号: A61K47/48 ; C07K16/28 ; C07K16/18 ; C07K14/50 ; C07K14/52 ; C07K14/54 ; C07K14/53 ; C07K14/55 ; C07K14/56 ; C07K14/61 ; C07K14/62 ; C07K16/30 ; A61K39/395 ; A61K51/10 ; B82Y5/00 ; B82Y10/00 ; B82Y30/00 ; C07K16/44 ; C07K16/46 ; A61K39/00
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-α2b.
公开/授权文献
- US20140161766A1 Tetrameric Cytokines with Improved Biological Activity 公开/授权日:2014-06-12
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