Invention Grant
US07906118B2 Modular method to prepare tetrameric cytokines with improved pharmacokinetics by the dock-and-lock (DNL) technology
有权
通过对接和锁定(DNL)技术制备具有改善的药代动力学的四聚体细胞因子的模块化方法
- Patent Title: Modular method to prepare tetrameric cytokines with improved pharmacokinetics by the dock-and-lock (DNL) technology
- Patent Title (中): 通过对接和锁定(DNL)技术制备具有改善的药代动力学的四聚体细胞因子的模块化方法
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Application No.: US12418877Application Date: 2009-04-06
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Publication No.: US07906118B2Publication Date: 2011-03-15
- Inventor: Chien-Hsing Chang , David M. Goldenberg , Edmund A. Rossi
- Applicant: Chien-Hsing Chang , David M. Goldenberg , Edmund A. Rossi
- Applicant Address: US NJ Morris Plains
- Assignee: IBC Pharmaceuticals, Inc.
- Current Assignee: IBC Pharmaceuticals, Inc.
- Current Assignee Address: US NJ Morris Plains
- Agent Richard A. Nakashima
- Main IPC: A61K39/395
- IPC: A61K39/395 ; A61K39/44 ; A61K38/19 ; A61K38/21 ; A61K38/20 ; C07K14/00 ; C07K14/52 ; C07K16/46 ; C12P21/08

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 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 a most preferred embodiment the complex comprises an anti-CD20 IgG antibody conjugated to four IFN-α2b moieties, although other antibodies and cytokines have been used to form effect DNL complexes.
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