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.

1 : An isolated human or humanized antibody 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 exhibits invariant binding of Mesothelin. 
     
     
         2 : An isolated antigen-binding region of an antibody according to  claim 1  or a functional fragment thereof. 
     
     
         3 : An isolated antigen-binding region according to  claim 2 , which comprises a CDR region as depicted in Table 7. 
     
     
         4 : An isolated antigen-binding region according to  claim 2 , which comprises a heavy chain or light chain amino acid sequence selected from the group consisting of the
 (i) SEQ ID NO's depicted in table 7; and   (ii) a sequence having at least 60 percent sequence identity in the CDR regions with the CDR regions depicted in SEQ ID NO's depicted in table 7.   
     
     
         5 : An isolated antibody to according to  claim 1 , which is an IgG. 
     
     
         6 : An isolated antigen-binding region according to  claim 2 , comprising one or more of the Sequences as depicted in table 7. 
     
     
         7 : An isolated functional fragment according to  claim 2 , which is a Fab or scFv antibody fragment. 
     
     
         8 : An isolated nucleic acid sequence that encodes an antigen binding region of a human antibody according to  claim 1  or functional fragment thereof. 
     
     
         9 : A nucleic acid sequence encoding a variable heavy chain of an isolated antibody or functional fragment thereof, which comprises (i) a sequence selected from the group consisting of SEQ ID NOS as depicted in table 7 or (ii) a nucleic acid sequence that hybridizes under high stringency conditions to the complementary strand of SEQ ID NO as 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 any one of  claim 9 . 
     
     
         11 : An isolated cell comprising a vector according to  claim 10 . 
     
     
         12 : An isolated cell according to  claim 11 , wherein said cell is bacterial or a mammalian cell. 
     
     
         13 : A pharmaceutical composition comprising an antibody or functional fragment according to  claim 1 , and a pharmaceutically acceptable carrier or excipient therefore. 
     
     
         14 : A method for treating a disorder or condition associated with the undesired presence of mesothelin, comprising administering to a subject in need thereof an effective amount of the pharmaceutical composition according to  claim 13 . 
     
     
         15 : A human antibody according to  claim 1 , wherein the human antibody is a synthetic human antibody.