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 binding domain, which inhibits VEGF-Axxx binding to VEGFR-2. Examples of such binding proteins are proteins which comprise an ankyrin repeat domain with the desired binding specificity. 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 - 20 . (canceled) 
     
     
         21 . A recombinant binding protein comprising at least one ankyrin repeat domain,
 wherein said repeat domain binds VEGF-A165 with a Kd below 10 −7 M and   wherein said repeat domain competes for binding to VEGF-A165 with an ankyrin repeat domain selected from the group consisting of SEQ ID NOs:16, 22, 23, 29, 30, 33, 34, 36, 39 and 40.   
     
     
         22 . The binding protein of  claim 21 , wherein said ankyrin repeat domain competes for binding to VEGF-A165 with the ankyrin repeat domain of SEQ ID NO:29. 
     
     
         23 . A recombinant binding protein comprising at least one ankyrin repeat domain,
 wherein said repeat domain binds VEGF-A165 with a Kd below 10 −7  and wherein said ankyrin repeat domain comprises an amino acid sequence that has at least 75% amino acid sequence identity with one ankyrin repeat domain selected from the group consisting of SEQ ID NOs:14 to 40.   
     
     
         24 . The binding protein of  claim 23 , wherein said ankyrin repeat domain comprises an amino acid sequence that has at least 80% amino acid sequence identity with one ankyrin repeat domain selected from the group consisting of SEQ ID NOs:14 to 40. 
     
     
         25 . The binding protein of  claim 23 , wherein said ankyrin repeat domain comprises an amino acid sequence that has at least 85% amino acid sequence identity with one ankyrin repeat domain selected from the group consisting of SEQ ID NOs:14 to 40. 
     
     
         26 . The binding protein of  claim 23 , wherein said ankyrin repeat domain comprises an amino acid sequence that has at least 90% amino acid sequence identity with one ankyrin repeat domain selected from the group consisting of SEQ ID NOs:14 to 40. 
     
     
         27 . The binding protein of  claim 23 , wherein said ankyrin repeat domain comprises an amino acid sequence that has at least 75% amino acid sequence identity with the ankyrin repeat domain of SEQ ID NO:29. 
     
     
         28 . A pharmaceutical composition comprising the binding protein of  claim 21 , and optionally a pharmaceutical acceptable carrier and/or diluent. 
     
     
         29 . A pharmaceutical composition comprising the binding protein of  claim 23 , and optionally a pharmaceutical acceptable carrier and/or diluent. 
     
     
         30 . A nucleic acid encoding a binding protein comprising at least one ankyrin repeat domain, wherein said repeat domain binds VEGF-A165 with a Kd below 10 −7 M. 
     
     
         31 . A pharmaceutical composition comprising the nucleic acid of  claim 30 , and optionally a pharmaceutical acceptable carrier and/or diluent. 
     
     
         32 . A method of treating pathological angiogenesis in a mammal including man, comprising administering to a patient in need thereof an effective amount of a binding protein comprising at least one ankyrin repeat domain, wherein said repeat domain binds VEGF-A165 with a Kd below 10 −7 M. 
     
     
         33 . A method of treating pathological angiogenesis in a mammal including man, comprising administering to a patient in need thereof an effective amount of a nucleic acid encoding a binding protein comprising at least one ankyrin repeat domain, wherein said repeat domain binds VEGF-A165 with a Kd below 10 −7 M