Diagnosis of carcinomas

Abstract

The invention is directed to compositions and methods for the detection of a malignant condition, and relates to the discovery of soluble and cell surface forms of HE4a polypeptides, including HE4a that is overexpressed in ovarian carcinomas. In particular the invention provides a nucleic acid sequence encoding HE4a, and also provides a method of screening for the presence of a malignant condition in a subject by detecting reactivity of an antibody specific for a HE4a polypeptide with a molecule naturally occurring in soluble and/or cell surface form in a sample from such a subject, and by hybridization screening using an HE4a nucleotide sequence, as well as other related advantages.

1 - 72 . (canceled) 
     
     
         73 . A polypeptide that specifically binds with HE4a, the polypeptide comprising an immunoglobulin variable region that specifically binds with an HE4a polypeptide having an amino acid sequence comprising the sequence set forth in SEQ ID NO:11. 
     
     
         74 . The polypeptide of  claim 73 , wherein the immunoglobulin variable region does not specifically bind with an HE4 polypeptide having the amino acid sequence SEQ ID NO:9. 
     
     
         75 . The polypeptide of  claim 73 , further comprising an immunoglobulin Fc domain. 
     
     
         76 . The polypeptide of  claim 73 , being an antibody. 
     
     
         77 . The polypeptide of  claim 76 , being a single chain antibody. 
     
     
         78 . The polypeptide of  claim 76 , being an F(ab′) 2  fragment of an antibody. 
     
     
         79 . The polypeptide of  claim 76 , wherein the antibody is a recombinant antibody. 
     
     
         80 . The polypeptide of  claim 76 , wherein the polypeptide is biotinylated. 
     
     
         81 . The polypeptide of  claim 73 , further comprising a detectable protein domain fused with the immunoglobulin variable region. 
     
     
         82 . The polypeptide of  claim 81 , wherein the detectable protein domain comprises a biotin mimetic sequence. 
     
     
         83 . The polypeptide of  claim 81 , wherein the detectable protein domain comprises a site that is covalently modifiable with a detectable labeling moiety. 
     
     
         84 . The polypeptide of  claim 81 , wherein the detectable labeling moiety is biotin. 
     
     
         85 . The polypeptide of  claim 81 , wherein the detectable protein domain exhibits enzymatic modification of a detectable substrate. 
     
     
         86 . The polypeptide of  claim 81 , wherein the detectable protein domain binds with a solid-phase support. 
     
     
         87 . The polypeptide of  claim 81 , wherein the detectable protein domain is bound with a solid-phase support. 
     
     
         88 . A monoclonal antibody preparation comprising the polypeptide of  claim 76 . 
     
     
         89 . A hybridoma that secretes the polypeptide of  claim 76 . 
     
     
         90 . A yeast two-hybrid system, the system comprising a first yeast that produces the polypeptide of  claim 83  and a second yeast that produces an enzyme that covalently modifies the detectable protein domain with the detectable labeling moiety. 
     
     
         91 . The polypeptide of  claim 73 , wherein the immunoglobulin variable region binds with the HE4a polypeptide with a K a  not less than 10 5 M −1 . 
     
     
         92 . An antibody that specifically binds with an HE4a polypeptide having an amino acid sequence comprising the sequence set forth in SEQ ID NO:11. 
     
     
         93 . The antibody of  claim 92 , wherein the antibody does not specifically bind with an HE4 polypeptide having the amino acid sequence SEQ ID NO:9. 
     
     
         94 . The antibody of  claim 92 , having a detectable protein domain fused with the variable region of the antibody. 
     
     
         95 . The antibody of  claim 94 , wherein the detectable protein domain is biotinylated.