Pdgfr beta-specific inhibitors

Abstract

The invention is directed to novel PDGFRβ-specific antagonists. The antagonists include antibodies, which can be bispecific. The antibodies are used to reduce or inhibit tumor growth and or to treat an angiogenic disease. The invention also includes combinations of PDGFRβ-specific antagonists with VEGFR antagonists for such treatments. The antagonists can further be administered in combination with other anti-angiogenic or anti-neoplastic drugs.

1 .- 18 . (canceled) 
     
     
         19 . A method of reducing tumor growth in a patient comprising administering to the patient an effective amount of the antibody, or fragment thereof that binds human PDGFRβ, comprising SYAIS (SEQ ID NO:20) at CDRH1; RIIPILGIANYAQKFQG (SEQ ID NO:22) at CDRH2; DMGSRNYYYFY (SEQ ID NO:24) at CDRH3; RASQSVGRYLA (SEQ ID NO:28) at CDRL1; GASNRAT (SEQ ID NO:30) at CDRL2; and QQRSNWPLT (SEQ ID NO:32) at CDRL3. 
     
     
         20 .- 32 . (canceled) 
     
     
         33 . The method of  claim 19 , wherein the tumor growth is in ovarian or lung tumors. 
     
     
         34 . A method of reducing tumor growth in a patient comprising administering to the patient an effective amount of the antibody, or fragment thereof that binds human PDGFRβ, comprising a VL comprising the amino acid sequence: 
       
         
           
                 
               
                   (SEQ ID NO: 26) 
                 
                 
               
                   EIVLTQSPATLSLSPGERATLSCRASQSVGRYLAWYQQKPGQAPRILIYG 
                 
                     
                 
                   ASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPLTFGG 
                 
                     
                 
                   GTKVEIK, 
                 
             
                
               
            
             
                
                
                
                
                
               
            
           
         
       
       and a VH comprising the amino acid sequence: 
       
         
           
                 
               
                   (SEQ ID NO: 18) 
                 
                 
               
                   QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGR 
                 
                     
                 
                   IIPILGIANYAQKFQGRVTITADKSTSTAYMELSSLRSEDTAVYYCARDM 
                 
                     
                 
                   GSRNYYYFYWGQGTLVTVSS. 
                 
             
                
               
            
             
                
                
                
                
                
               
            
           
         
       
     
     
         35 . The method of  claim 34 , wherein the tumor growth is in ovarian or lung tumors.