Her-2 binding antagonists

Abstract

There is disclosed a pharmaceutical composition for treating solid tumors that overexpress HER-2, comprising an agent selected from the group consisting of (a) an isolated polypeptide having from about 50 to 79 amino acids taken from the sequence of SEQ ID NO:1, wherein the polypeptide binds to the extracellular domain ECD of HER-2 at an affinity of at least 10 8 , (b) an isolated and glycosylated polypeptide having from about 300 to 419 amino acids taken from the sequence of SEQ ID NO:2, wherein the C terminal 79 amino acids are present, and wherein at least three N-linked glycosylation sites are present, (c) a monoclonal antibody that binds to the ECD of HER-2, and (d) combinations thereof, with the proviso that the agent cannot be the monoclonal antibody alone, and pharmaceutically acceptable carrier.

1 .- 26 . (canceled) 
     
     
         27 . A method for determining the prognosis of tumor treatment for a tumor that overexpresses p185HER-2, comprising:
 obtaining a bodily fluid or tumor tissue sample derived from a tumor-bearing subject; and   measuring, using the fluid or tissue sample, an amount of p68HER-2 present using an anti-p68HER-2 antibody-based assay, wherein presence of p68HER-2 correlates with improved treatment prognosis, wherein a method for determining the prognosis of tumor treatment for a tumor that overexpresses p185HER-2 is afforded.   
     
     
         28 . The method of  claim 27 , wherein measuring, using the fluid or tissue sample, an amount of p68HER-2 comprises measuring the amount of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, or a fragment of SEQ ID NO:2 of about 80 to 419 contiguous residues in length, wherein the C terminal 79 contiguous amino acids are present. 
     
     
         29 . The method of  claim 27 , wherein measuring, using the fluid or tissue sample, an amount of p68HER-2 comprises measuring the amount of a polypeptide comprising the amino acid sequence of SEQ ID NO:1, or a fragment of SEQ ID NO:1 of about 50 to 79 contiguous residues in length. 
     
     
         30 . The method of  claim 27 , wherein the bodily fluid is selected from the group consisting of blood, serum, urine, lymph, saliva, tumor tissue, and combinations thereof. 
     
     
         31 . The method of  claim 27 , wherein the anti-p68HER-2 antibody-based assay is at least one selected from the group consisting of ELISA, immunoprecipitation, immunohistocytochemistry, and Western analysis. 
     
     
         32 . The method of  claim 27 , further comprising measuring the amount of p185HER-2 ECD in the bodily fluid. 
     
     
         33 . The method of  claim 30 , comprising determining a ratio between the amount of p68HER-2 and p185HER-2, whereby the higher the p68HER-2 to p185HER-2 ratio, the better the prognosis of the patient. 
     
     
         34 . The method of  claim 27 , wherein the tumor that overexpresses p185HER-2 is selected from the group consisting of breast cancer, small cell lung carcinoma, ovarian cancer and colon cancer.