Detectors of serum biomarkers for predicting ovarian cancer recurrence

Abstract

Polypeptide marker antigens for detecting the presence of autoantibody biomarkers associated with ovarian cancer recurrence, each of the polypeptide marker antigens binding specifically to at least one autoantibody marker. An antibody binding assay for detecting the presence of autoantibody biomarkers associated with ovarian cancer recurrence, and methods for performing the assay. Methods for determining ovarian cancer recurrence in an ovarian cancer patient. A method for isolating antibodies specific for ovarian cancer by their affinity to the polypeptide marker antigens, and antibodies isolated by that method.

What is claimed is: 
     
         1 . A panel of polypeptide marker antigens for detecting the presence of autoantibody biomarkers associated with a risk of ovarian cancer recurrence, said panel of polypeptide marker antigens including SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, and SEQ ID NO: 10, each of said polypeptide marker antigens specifically binding at least one of said autoantibody biomarkers, each of said polypeptide marker antigens being further defined as either an isolated phage display antigen clone or an isolated polypeptide. 
     
     
         2 . An antibody binding assay for detecting the presence of autoantibody biomarkers associated with a risk of ovarian cancer recurrence, including least one polypeptide marker antigen specifically binding at least one of said autoantibody biomarkers. 
     
     
         3 . The assay of  claim 2 , wherein said at least one polypeptide marker antigen is selected from SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, and SEQ ID NO: 10, said at least one polypeptide marker antigen being further defined as either an isolated phage display antigen clone or an isolated polypeptide. 
     
     
         4 . The assay of  claim 3 , wherein said at least one polypeptide marker antigen is immobilized on a solid substrate. 
     
     
         5 . The assay of  claim 4 , wherein said solid substrate is selected from the group consisting of a nitrocellulose membrane, a nitrocellulose-based polymer surface, a glass surface, a silicon surface, a plastic surface, a filter, a biochip including signal transducing electronics, an ELISA plate, a spinning interferometry disc, a polystyrene bead, and a peptide-binding microsphere. 
     
     
         6 . The assay of  claim 3 , further including a signal generating system to produce a signal indicating the binding of said at least one autoantibody biomarker to said at least one polypeptide marker antigen. 
     
     
         7 . The assay of  claim 6 , further including a signal analysis system to quantitate the binding of said at least one autoantibody biomarker to said at least one polypeptide antigen marker on the basis of said signal produced by said signal generating system. 
     
     
         8 . The assay of  claim 6 , wherein said signal generating system includes a biomarker-binding antibody directed to said at least one autoantibody biomarker bound to said at least one polypeptide marker antigen. 
     
     
         9 . The assay of  claim 8 , wherein said biomarker-binding antibody is an anti-human immunoglobulin antibody. 
     
     
         10 . The assay of  claim 9 , wherein said anti-human immunoglobulin antibody is coupled to a first signal generator. 
     
     
         11 . The assay of  claim 10 , wherein said first signal generator is a first fluorescent dye. 
     
     
         12 . The assay of  claim 8 , wherein said signal generating system further includes a normalization reagent binding to said at least one polypeptide marker antigen. 
     
     
         13 . The assay of  claim 12 , wherein said normalization reagent is further defined as an antibody directed to a constant phage capsid protein. 
     
     
         14 . The assay of  claim 13 , wherein said anti-phage capsid protein is coupled to a second signal generator. 
     
     
         15 . The assay of  claim 14 , wherein said second signal generator is a second fluorescent dye. 
     
     
         16 . A method for treating ovarian cancer recurrence in an ovarian cancer patient, including the steps of:
 collecting a sample of a body fluid from an ovarian cancer patient;   exposing the sample of a body fluid to at least one polypeptide marker antigen selected from SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, and SEQ ID NO: 10, each of the polypeptide marker antigens binding specifically to an autoantibody biomarker associated with a risk of ovarian cancer recurrence;   quantitating the specific binding of an autoantibody biomarker by the at least one polypeptide marker antigen;   detecting the presence of the autoantibody biomarker in the sample of body fluid;   determining that the ovarian cancer patient is at risk of ovarian cancer recurrence; and   administering a treatment for recurrent ovarian cancer.   
     
     
         17 . The method of  claim 16 , wherein the body fluid is further defined as serum. 
     
     
         18 . The method of  claim 16 , wherein the quantitating step further includes the steps of indicating the binding of an autoantibody biomarker by the at least one polypeptide marker antigen with a signal generating system, and analyzing the signals produced by the signal generating system with a signal analysis system. 
     
     
         19 . The method of  claim 16 , wherein the treatment is further defined as a treatment selected from the group including prolonging first-line treatment, initiating maintenance treatment, and initiating second-line treatment. 
     
     
         20 . An isolated antibody specifically binding to an epitope of ovarian cancer tissue or ovarian cancer associated tissue, said antibody being isolated on the basis of its affinity for at least one polypeptide maker antigen selected from the group of polypeptides including SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, and SEQ ID NO: 10, each of said polypeptides being either an isolated phage display antigen clone or an isolated polypeptide. 
     
     
         21 . A method for isolating antibodies specifically reactive with ovarian cancer tissue or ovarian cancer associated tissue, including the steps of:
 immobilizing on a substrate at least one polypeptide marker antigen selected from the group of polypeptides including SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, and SEQ ID NO: 10, each of said polypeptides being either an isolated phage display antigen clone or an isolated polypeptide;   exposing a plurality of antibodies to the at least one polypeptide marker antigen;   washing unbound antibodies from the at least one polypeptide marker antigen;   detecting an antibody bound to the at least one polypeptide marker antigen; and   isolating said antibody bound to the at least one polypeptide marker antigen.   
     
     
         22 . The method of  claim 21 , wherein the exposing step is further defined as the step of exposing a plurality of hybridoma supernatants to the at least one peptide marker antigen, and the isolating step is further defined as isolating the hybridoma that produced the antibody bound to the at least one polypeptide marker antigen. 
     
     
         23 . The method of  claim 21 , wherein the isolating step is further defined as eluting bound antibody from the at least one polypeptide marker antigen.