Antibodies to human ErbB4

Abstract

The present invention concerns methods and means for controlling excessive proliferation and/or migration of smooth muscle cells, and in particular for treating stenosis, by using antagonists of a native ErbB4 receptor. The invention further concerns a method for the identification of ErbB4 agonists and antagonists capable of inhibiting or enhancing the proliferation or migration of smooth muscle cells.

1 . An antibody, or an antigen-binding fragment thereof, that binds essentially the same epitope of ErbB4 as an antibody produced by a hybridoma selected from the group consisting of HER4.10H1.1A1 (ATCC Accession Number PTA-2828), HER4.1C6.A11 (ATCC Accession Number PTA-2829), HER4.3B9.2C9 (ATCC Accession Number PTA-2826), HER4.1A6.5B3 (ATCC Accession Number PTA-2827) and HER4.8B1.2H2 (ATCC Accession Number PTA-2825). 
     
     
         2 . The antibody, or antigen binding fragment thereof, of  claim 1  that specifically binds to human ErbB4 of SEQ ID NO:2 with a K d  less than 100 nM. 
     
     
         3 . The antibody, or antigen binding fragment thereof, of  claim 1  that specifically binds to human ErbB4 of SEQ ID NO:2 with a K d  less than 50 nM. 
     
     
         4 . The antibody, or antigen binding fragment thereof, of  claim 1  that specifically binds to human ErbB4 of SEQ ID NO:2 with a K d  less than 10 nM. 
     
     
         5 . The antibody, or antigen binding fragment thereof, of  claim 1 , wherein the antibody is a humanized antibody. 
     
     
         6 . The antibody, or antigen binding fragment thereof, of  claim 1 , wherein the antibody is a human antibody. 
     
     
         7 . The antibody, or binding fragment thereof, of  claim 1  which specifically binds to human ErbB4 of SEQ ID NO:2 and which reduces heregulin binding thereto. 
     
     
         8 . The antibody, or binding fragment thereof, of  claim 1  which specifically binds to human ErbB4 of SEQ ID NO:2 and which reduces heregulin-induced tyrosine phosphorylation thereof. 
     
     
         9 . A composition comprising an antibody, or an antigen-binding fragment thereof, that binds essentially the same epitope of ErbB4 as an antibody produced by a hybridoma selected from the group consisting of HER4.10H1.1A1 (ATCC Accession Number PTA-2828), HER4.1C6.A11 (ATCC Accession Number PTA-2829), HER4.3B9.2C9 (ATCC Accession Number PTA-2826), HER4.1A6.5B3 (ATCC Accession Number PTA-2827) and HER4.8B1.2H2 (ATCC Accession Number PTA-2825). 
     
     
         10 . The composition of  claim 9 , wherein said antibody or antigen binding fragment thereof specifically binds to human ErbB4 of SEQ ID NO:2 with a K d  less than 100 nM. 
     
     
         11 . The composition of  claim 9 , wherein said antibody or antigen binding fragment thereof specifically binds to human ErbB4 of SEQ ID NO:2 with a K d  less than 50 nM. 
     
     
         12 . The composition of  claim 9 , wherein said antibody or antigen binding fragment thereof specifically binds to human ErbB4 of SEQ ID NO:2 with a K d  less than 10 nM. 
     
     
         13 . The composition of  claim 9 , wherein said antibody, or antigen binding fragment thereof, is a humanized antibody. 
     
     
         14 . The composition of  claim 9 , wherein said antibody, or antigen binding fragment thereof, is a human antibody. 
     
     
         15 . The composition of  claim 9 , wherein said antibody, or binding fragment thereof, specifically binds to human ErbB4 of SEQ ID NO:2 and reduces heregulin binding thereto. 
     
     
         16 . The composition of  claim 9 , wherein said antibody specifically binds to human ErbB4 of SEQ ID NO:2 and reduces heregulin-induced tyrosine phosphorylation thereof. 
     
     
         17 . An antibody that binds essentially the same epitope of ErbB4 as an antibody produced by a hybridoma selected from the group consisting of HER4.10H1.1A1 (ATCC Accession Number PTA-2828), HER4.1C6.A11 (ATCC Accession Number PTA-2829), HER4.3B9.2C9 (ATCC Accession Number PTA-2826), HER4.1A6.5B3 (ATCC Accession Number PTA-2827) and HER4.8B1.2H2 (ATCC Accession Number PTA-2825). 
     
     
         18 . A composition comprising an antibody that binds essentially the same epitope of ErbB4 as an antibody produced by a hybridoma selected from the group consisting of HER4.10H1.1A1 (ATCC Accession Number PTA-2828), HER4.1C6.A11 (ATCC Accession Number PTA-2829), HER4.3B9.2C9 (ATCC Accession Number PTA-2826), HER4.1A6.5B3 (ATCC Accession Number PTA-2827) and HER4.8B1.2H2 (ATCC Accession Number PTA-2825).