Anti-mesothelin antibodies and uses thereof

Abstract

The present invention provides recombinant antigen-binding regions and antibodies and functional fragments containing such antigen-binding regions that are specific for the membrane-anchored, 40 kDa mesothelin polypeptide, which is overexpressed in several tumors, such as pancreatic and ovarian tumors, mesothelioma and lung cancer cells. These antibodies, accordingly, can be used to treat these and other disorders and conditions. Antibodies of the invention also can be used in the diagnostics field, as well as for further investigating the role of mesothelin in the progression of disorders associated with cancer. The invention also provides nucleic acid sequences encoding the foregoing antibodies, vectors containing the same, pharmaceutical compositions and kits with instructions for use.

What we claim is: 
     
         1 . An isolated human or humanized antibody, antigen-binding region, or functional fragment thereof comprising an antigen-binding region that is specific for Mesothelin (SEQ ID NO:370), wherein said antibody or functional fragment thereof recognize an epitope of mesothelin that is not masked by another extracellular antigen. 
     
     
         2 . The isolated human or humanized antibody, antigen-binding region, or functional fragment thereof according to  claim 1 , wherein the another extracellular antigen is cancer antigen 125 (CA125) 
     
     
         3 . The isolated human or humanized antibody, antigen-binding region, or functional fragment thereof according to  claim 1  comprising a CDR region depicted in Table 7. 
     
     
         4 . The isolated human or humanized antibody, antigen-binding region, or functional fragment thereof according to  claim 1  comprising a heavy chain or light chain amino acid sequence selected from
 (i) a SEQ ID NO depicted in Table 7; or 
 (ii) a sequence having at least 60 percent sequence identity to a SEQ ID NO depicted in Table 7. 
 
     
     
         5 . The isolated human or humanized antibody, antigen-binding region, or functional fragment thereof according to  claim 1  that is an IgG. 
     
     
         6 . The isolated human or humanized antibody, antigen-binding region, or functional fragment thereof according to  claim 1  comprising a SEQ ID NO depicted in Table 7. 
     
     
         7 . The isolated human or humanized antibody, antigen-binding region, or functional fragment thereof according to  claim 1  that is a Fab or scFv antibody fragment. 
     
     
         8 . An isolated nucleic acid sequence that encodes an isolated human or humanized antibody, antigen-binding region, or functional fragment thereof according to  claim 1 . 
     
     
         9 . A nucleic acid sequence encoding a variable heavy chain of an isolated antibody or functional fragment thereof comprising (i) a sequence selected from the group consisting of a SEQ ID NO depicted in Table 7 or (ii) a nucleic acid sequence that hybridizes under high stringency conditions to the complementary strand of a SEQ ID NO depicted in Table 7, wherein said antibody or functional fragment thereof is specific for an epitope of Mesothelin. 
     
     
         10 . A vector comprising a nucleic acid sequence according to  claim 1 . 
     
     
         11 . An isolated cell comprising a vector according to  claim 10 . 
     
     
         12 . An isolated cell according to  claim 11 , wherein said isolated cell is bacterial or a mammalian cell. 
     
     
         13 . A pharmaceutical composition comprising an isolated human or humanized antibody, antigen-binding region, or functional fragment thereof according to  claim 1  and a pharmaceutically acceptable carrier or excipient therefore. 
     
     
         14 . A pharmaceutical composition according to  claim 13  adapted for treating an undesired presence of mesothelin. 
     
     
         15 . The isolated human or humanized antibody, antigen-binding region, or functional fragment thereof according to  claim 1  that is a synthetic human antibody.