Anti-alphabeta3 humanized monoclonal antibodies

Abstract

This invention relates to novel humanized and other recombinant or engineered antibodies or monoclonal antibodies to the vitronectin α v β 3 receptor and to the genes encoding same. Such antibodies are useful for the therapeutic and/or prophylactic treatment of α v β 3 -mediated disorders, such as restenosis, in human patients.

1 . An isolated nucleic acid molecule encoding a heavy chain of an altered antibody specifically reactive with the human α v β 3  protein receptor and capable of neutralizing said receptor wherein said heavy chain comprises the complementarity determining region sequences corresponding to amino acids 31-35, amino acids 50-66, and amino acids 99-106 of SEQ ID NO:5. 
     
     
         2 . The isolated nucleic acid of  claim 1 , comprising SEQ ID NO:4. 
     
     
         3 . A recombinant plasmid comprising the nucleic acid sequence of  claim 1 . 
     
     
         4 . A host cell comprising the plasmid of  claim 1 . 
     
     
         5 . A process for the production of a human antibody specific for the human α v β 3  receptor comprising culturing the host cell of  claim 4  in a medium under suitable conditions of time temperature and pH and recovering the antibody so produced. 
     
     
         6 . An isolated nucleic acid molecule encoding a light chain of an altered wherein said light chain comprises the complementarity determining region sequences corresponding to amino acids 24-34, amino acids 50-66, and amino acids 89-97 of SEQ ID NO:10. 
     
     
         7 . The isolated nucleic acid molecule of  claim 6 , comprising SEQ ID NO:9 
     
     
         8 . The isolated nucleic acid molecule of  claim 6 , comprising SEQ ID NO: 14. 
     
     
         9 . A recombinant plasmid comprising the nucleic acid sequence of  claim 6 . 
     
     
         10 . A host cell comprising the plasmid of  claim 9 . 
     
     
         11 . A process for the production of a human antibody specific for the human α v β 3  receptor comprising culturing the host cell of  claim 10  in a medium under suitable conditions of time temperature and pH and recovering the antibody so produced.