• IGF-1R is implicated in several cancers. Due to the similarity of the structures of IGF-1R and the insulin receptor (IR), especially in the regions of the ATP binding site and tyrosine kinase regions, synthesizing selective inhibitors of IGF-1R is difficult. 
• Cross-talk between type I insulin–like growth factor receptor (IGF-IR) and HER2 and elevated IGF-IR signaling have been implicated in tumor cell resistance to Herceptin therapy. 
• The industry's 20 biggest-selling cancer drugs generated combined sales of $53 billion in 2013, with Roche's Rituxan, Avastin and Herceptin franchises extending their lead at the top of this league table. With combined sales of around $21 billion, these three drugs alone accounted for approximately 40 percent of the combined value of the 20 biggest-selling products. Roche generated 2013 sales of around $6.57 billion and is expected to generate 2018 sales of around $5.38 from Herceptin (forecasted by Bloomberg).
   

    
• A bispecific antibody (Bi-Ab) against HER2 and IGF-IR is generated by engineering Herceptin and an humanized IGF-IR mAb (IP00339). The said Bi-Ab effectively inhibited proliferation of HER2- and IGF-IR–overexpressing ovarian cancer SKOV-3 cells in vitro and in vivo. 
    
• This Bi-Ab has superior antitumor activity compared to monospecific antibodies, and co-targeting HER2 and IGF-IR will be clinically beneficial in minimizing the acquired resistance to Herceptin therapy. 
       

The invention provides a humanized bi-specific antibody targeting HER2 and insulin-like growth factor type I (IGF-IR).

Patents have been granted in US, PRC, and Germany.