Modified binding proteins inhibiting the vegf-a receptor interaction

Abstract

The present invention relates to binding proteins specific for VEGF-A, in particular to recombinant binding proteins comprising a polyethylene glycol moiety and a binding domain, which inhibits VEGF-Axxx binding to VEGFR-2. Examples of such recombinant binding proteins are proteins which comprise an ankyrin repeat domain with the desired binding specificity, and a polyethylene glycol moiety. The binding proteins are useful in the treatment of cancer and other pathological conditions, e.g. eye diseases such as age-related macular degeneration.

1 - 15 . (canceled) 
     
     
         16 . A method of treating a pathological condition in a mammal including a human, comprising administering to a mammal in need thereof an effective amount of a recombinant binding protein, wherein the pathological condition is a condition which responds to the inhibition of vascular endothelial growth factor-A165 (VEGF-A165) or vascular endothelial growth factor receptor-2 (VEGFR-2), and wherein said binding protein comprises an ankyrin repeat domain and a polyethylene glycol, wherein said ankyrin repeat domain is selected from the group consisting of (1) amino acids 1 to 159 of SEQ ID NO:1, (2) amino acids 1 to 159 of SEQ ID NO:2, (3) amino acids 1 to 126 of SEQ ID NO:3, (4) amino acids 1 to 126 of SEQ ID NO:4, (5) amino acids 1 to 126 of SEQ ID NO:5, (6) amino acids 1 to 126 of SEQ ID NO:6, and (7) amino acids 1 to 159 of SEQ ID NO:7. 
     
     
         17 . The method of  claim 16 , wherein said pathological condition is pathological angiogenesis or vascular leakage. 
     
     
         18 . The method of  claim 16 , wherein said pathological condition is a vascular disease. 
     
     
         19 . The method of  claim 18 , wherein said vascular disease is a vascular disease of the eye. 
     
     
         20 . The method of  claim 18 , wherein said pathological condition is an ocular neovascularization disease. 
     
     
         21 . The method of  claim 16 , wherein said pathological condition is a retinal ischemic disease. 
     
     
         22 . The method of  claim 16 , wherein said pathological condition is cancer.