Her1 antigen binding proteins binding to the beta-hairpin of her1

Abstract

The invention relates to anti-HER1 antigen binding proteins, e.g. anti-HER1 antibodies, that bind to the beta-hairpin of HER1, methods for selecting these antigen binding proteins, their preparation and use as medicament.

1 . A method for selecting an antigen binding protein that binds to human HER1, wherein the antigen binding protein binds within an amino acid sequence of PPLMLYNPTTYQMDVNPEGK (SEQ ID NO:1) of human HER1;
 wherein   a) at least one polypeptide selected from the group consisting of:   
       
         
           
                 
                 
               
                     
                   SEQ ID NO: 12 
                 
                     
                   TtSlyDcas-HER1, 
                 
                     
                     
                 
                     
                   SEQ ID NO: 13 
                 
                     
                   TtSlyDcys-HER1, 
                 
                     
                     
                 
                     
                   SEQ ID NO: 14 
                 
                     
                   TtSlyD(GSG)-HER1, 
                 
                     
                     
                 
                     
                   SEQ ID NO: 15 
                 
                     
                   TtSlyD(CC)-HER1, 
                 
                     
                     
                 
                     
                   SEQ ID NO: 16 
                 
                     
                   TtSlyD(SS)-HER1, 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   SEQ ID NO: 18 
                 
                     
                   TgSlyDcys-HER1, 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
         
           which comprises the amino acid sequence of SEQ ID NO:1; 
         
         is used to select antigen binding proteins, which show binding to the at least one polypeptide under a) 
         and thereby selecting an antigen binding protein that binds within an amino acid sequence of PPLMLYNPTTYQMDVNPEGK (SEQ ID NO:1) of human HER1. 
       
     
     
         2 . (canceled) 
     
     
         3 . The method of  claim 1 , wherein the antigen binding protein is an antibody. 
     
     
         4 - 20 . (canceled) 
     
     
         21 . The method of  claim 1 , wherein the antigen binding protein binds to a polypeptide of 
       
         
           
                 
                 
               
                     
                   SEQ ID NO: 13 
                 
                     
                   TtSlyDcys-Her1. 
                 
             
                
                
               
            
           
         
       
     
     
         22 . The method of  claim 21 , wherein the antigen binding protein binds to a polypeptide of 
       
         
           
                 
                 
               
                     
                   SEQ ID NO: 13 
                 
                     
                   TtSlyDcys-Her1 
                 
             
                
                
               
            
           
         
         with an at least 50 times higher ELISA signal when compared to the binding to a polypeptide of 
       
       
         
           
                 
                 
               
                     
                   SEQ ID NO: 11 
                 
                     
                   TtSlyDcas 
                 
             
                
                
               
            
           
         
         in an ELISA assay, wherein TtSlyDcys-HER1 and TtSlyDcas were immobilized at a concentration of 0.5 μg/ml. 
       
     
     
         23 . The method of  claim 1 , wherein the antigen binding protein binds within an amino acid sequence of PPLMLYNPTTYQMDVNPEGK (SEQ ID NO:1) which is comprised in a polypeptide of SEQ ID NO: 13 (TtSlyDcys-Her1). 
     
     
         24 . The method of  claim 21 , wherein the antigen binding protein is an antibody. 
     
     
         25 . The method of  claim 24 , wherein the antibody does not induce phosphorylation of HER1 in A549 cancer cells (ATCC CCL-185) in the absence of EGF. 
     
     
         26 . The method of  claim 24 , wherein the antibody shows more than 70 percent internalization of HER1 in the presence of EGF after 2 h after incubation with the antibody in a Western Blot assay with HER1 expressing A549 cells (ATCC CCL-185) and shows less than 55 percent internalization of HER1 in the absence of EGF after 2 h after incubation with the antibody in a Western Blot assay with HER1 expressing A549 cells. 
     
     
         27 . The method of  claim 24 , wherein the antibody is a human, humanized, or chimeric antibody. 
     
     
         28 . The method of  claim 24 , wherein the antibody is a full length IgG1 antibody or IgG4 antibody. 
     
     
         29 . The method of  claim 24 , wherein the antibody is a Fab fragment.