Linkers for binding drugs to cell binding agents are modified to hydrophilic linkers by incorporating a polyethylene glycol spacer. The potency or the efficacy of the cell-binding agent-drug conjugates is surprisingly enhanced several folds in a variety of cancer cell types, including those expressing a low number of antigens on the cell surface or cancer cells that are resistant to treatment. A method for preparing maytansinoids bearing a thioether moiety and a reactive group which allows the maytansinoid to be linked to a cell-binding agent in essentially a single step is also provided.
申请公布号
EP2276506(A1)
申请公布日期
2011.01.26
申请号
EP20090739778
申请日期
2009.04.30
申请人
IMMUNOGEN, INC.
发明人
SINGH, RAJEEVA;KOVTUN, YELENA;WILHELM, SHARON, D.;CHARI, RAVI, V., J.