Monoclonal antibodies against her2 antigens, and uses therefor

Abstract

The present invention provides and includes monoclonal antibodies (mAbs) preferentially selective for HER2 antigens, hybridoma lines that secrete these HER2 antibodies or antibody fragments, and the use of such antibodies and antibody fragments to detect HER2 antigens, particularly those expressed by cancer cells. The present invention also includes antibodies that are specific for or show preferential binding to a soluble or secreted form of HER2. The present invention also includes an antibody or antibody fragment that is capable of reducing the activity of HER2 in at least one form, including a soluble form or a secreted form. The present invention further includes chimeric antibodies, processes for producing monoclonal and chimeric antibodies or monoclonal or chimeric antibodies, and their therapeutic uses, particularly in the detection of cancer most preferentially in human breast, stomach, and colon. The present invention further includes methods and kits for the immunodetection and immunotherapy of cells for samples which express HER2 antigens.

1 . An antibody for a HER2 antigen, comprising one or more of the heavy chain CDR antigen binding site sequences CDR1, CDR2 and CDR3 as set forth in  FIG. 2 , and one or more of the light chain CDR antigen binding site sequences CDR1, CDR2 and CDR3 as set forth in  FIG. 3 . 
     
     
         2 . An antibody specific for a HER2 antigen, comprising one or more of the heavy chain CDR antigen binding site sequences set forth in  FIG. 2 , and one or more of the light chain CDR antigen binding site sequences set forth in  FIG. 3 . 
     
     
         3 . An antibody according to  claim 1  wherein said HER2 antigen is a soluble protein having a molecular weight of about 185 kilodaltons as measured by gradient polyacrylamide gel electrophoresis. 
     
     
         4 . An antibody according to  claim 1  immobilized on a solid phase. 
     
     
         5 . An antibody according to  claim 1  which is detectably labeled. 
     
     
         6 . An antibody according to  claim 1  conjugated to a cytotoxic radionuclide. 
     
     
         7 . An antibody according to  claim 1  conjugated to a cytotoxic drug. 
     
     
         8 . An antibody according to  claim 1  conjugated to a cytotoxic protein. 
     
     
         9 . A composition comprising an antibody according to  claim 6  in combination with a pharmaceutically acceptable carrier. 
     
     
         10 . An antibody capable of preferentially binding to a soluble form of HER2 antigen. 
     
     
         11 . An antibody according to  claim 10 , wherein said preferential binding is relative to a membrane form of HER2. 
     
     
         12 . An isolated DNA sequence which encodes the heavy chain of an antibody molecule, wherein said antibody molecule has specificity for HER2 and wherein the variable domain of said heavy chain comprises a CDR having the antigen binding site sequences CDR1, CDR2 and CDR3 set forth in  FIG. 2 . 
     
     
         13 . (canceled) 
     
     
         14 . A vector containing the DNA sequence of  claim 12 . 
     
     
         15 . A host cell transformed with the vector of  claim 14 . 
     
     
         16 . A process for the production of an antibody molecule having specificity for HER2, comprising culturing the host cell of  claim 15  and isolating the antibody molecule. 
     
     
         17 . An immunoassay for detecting a HER2 antigen which binds to a monoclonal antibody having the one or more of the heavy chain CDR antigen binding site sequences set forth in  FIG. 2 , and one or more of the light chain CDR antigen binding site sequences set forth in  FIG. 3 , comprising: (a) contacting said sample with an effective binding amount of the antibody according to  claim 1 ; and (b) detecting said antigen by detecting the binding of the antibody to the HER2 antigen. 
     
     
         18 . The immunoassay of  claim 17 , wherein the assay is used to detect cancer cells expressing a HER2 antigen, said cancer cells being selected from the group consisting of human breast, stomach, and colon; and in particular breast. 
     
     
         19 - 50 . (canceled)