Fas binding antibodies

Abstract

The disclosed invention relates to monoclonal antibodies (MAbs) which recognize human fatty acid synthase (hFAS) and are distinct from previously known anti-hFAS antibodies. Compositions, devices and kits comprising the MAbs are provided along with methods of using the MAbs in a variety of applications.

1 . A monoclonal antibody, or fragment thereof, which specifically binds human fatty acid synthase (hFAS) that is not the monoclonal antibody known as M3 or M6. 
     
     
         2 . The monoclonal antibody, or fragment thereof, of  claim 1  which binds an hFAS polypeptide of about 250 kD and/or a proteolytic product of hFAS of about 134 kD. 
     
     
         3 . The monoclonal antibody, or fragment thereof, of  claim 1  which binds a different population of polypeptides in a lysate of MCF-7 human breast cancer cells than the monoclonal antibody known as M3 or M6, or
 which binds a different population of hFAS polypeptides digested with trypsin than the monoclonal antibody known as M3 or M6. 
 
     
     
         4 . The monoclonal antibody, or fragment thereof, of  claim 1  which binds human fatty acid synthase (hFAS) with binding characteristics similar to the monoclonal antibody known as M3 and which
 a) binds full length hFAS with greater affinity compared to M3; or 
 b) binds full length hFAS with reduced affinity compared to M3. 
 
     
     
         5 . The monoclonal antibody, or fragment thereof, of  claim 4  which does not bind an hFAS polypeptide fragment of about 70 kD in a population of hFAS polypeptides digested with trypsin, or
 which also binds an hFAS polypeptide fragment of about 50 kD in a population of hFAS polypeptides digested with trypsin. 
 
     
     
         6 . The monoclonal antibody, or fragment thereof, of  claim 4  wherein the antibody is 34-6E7, deposited as hybridoma clone 34-6E7-2G10-15 with the ATCC on Aug. 17, 2006 and assigned accession number ______, or 63-2D8, deposited as hybridoma clone 63-2D8-2E2-1D2 with the ATCC on Aug. 17, 2006 and assigned accession number ______, or 63-4G4, deposited as hybridoma clone 34-63-4G4-B3-2F3 with the ATCC on Aug. 17, 2006 and assigned accession number ______, or 63-3C10, deposited as hybridoma clone 63-3C10-2B8 with the ATCC on Aug. 17, 2006 and assigned accession number ______. 
     
     
         7 . The monoclonal antibody, or fragment thereof, of  claim 1  which binds human fatty acid synthase (hFAS) with binding characteristics similar to the monoclonal antibody known as M6 and which
 a) does not bind a polypeptide of about 60 kD in a lysate of human MCF-7 breast cancer cells; or 
 b) binds a polypeptide of about 40 kD in a lysate of human MCF-7 breast cancer cells. 
 
     
     
         8 . The monoclonal antibody, or fragment thereof, of  claim 1  which binds human fatty acid synthase (hFAS) with binding characteristics similar to the monoclonal antibody known as M6 and which
 a) does not bind a polypeptide of about 45 kD, about 34 kD, about 16 kD, about 37 kD, about 28 kD, or about 7 kD in a lysate of human ZR-75-1 breast cancer cells digested with trypsin; or 
 b) binds a polypeptide of about 115 kD, about 90 kD, about 50 kD about 85 kD, about 78 kD, about 50 kD, about 40 kD, or about 17 kD in a lysate of human ZR-75-1 breast cancer cells digested with trypsin. 
 
     
     
         9 . The monoclonal antibody, or fragment thereof, of  claim 1  which binds human fatty acid synthase (hFAS) with binding characteristics similar to the monoclonal antibody known as M6 and which
 a) does not bind a polypeptide of about 125 kD, about 32 kD, or about 9 kD in a lysate of human MCF-7 breast cancer cells; or 
 b) binds a polypeptide of about 85 kD, about 50 kD, about 43 kD, or about 24 kD in a lysate of human ZR-75-1 breast cancer cells digested with trypsin. 
 
     
     
         10 . A cell line which expresses an antibody of  claim 1 . 
     
     
         11 . A composition comprising a complex of an antibody, or fragment thereof, according to  claim 1  and an hFAS polypeptide, wherein said antibody, or fragment thereof, is optionally labeled. 
     
     
         12 . A method of detecting a FAS polypeptide by immunohistochemistry, said method comprising detecting said polypeptide in a sample by use of an antibody, or fragment thereof, according to  claim 1 . 
     
     
         13 . A device or kit comprising an antibody, or fragment thereof, according to  claim 1 , said device or kit optionally comprising a label to detect said antibody, or fragment thereof, or a complex comprising said antibody. 
     
     
         14 . The device of  claim 13 , wherein said device is a lateral flow device which detects the presence of hFAS in a sample by use of a sandwich assay or a competition assay. 
     
     
         15 . A method of detecting the presence of an hFAS polypeptide, said method comprising
 forming a complex comprising an antibody, or fragment thereof, of  claim 1  and an hFAS polypeptide; and   detecting said complex, optionally in the form of an enzyme linked immunosorbent assay (ELISA) or radioimmune assay (RIA).   
     
     
         16 . The method of  claim 15  wherein said hFAS polypeptide is in a sample from an individual and detection of said complex indicates the presence of cancer in said subject. 
     
     
         17 . A method of monitoring the course, or recurrence, of a disease in a subject, said method comprising
 determining the level of an hFAS polypeptide in a sample from said subject based on formation of a complex comprising an antibody, or fragment thereof, of  claim 1  and said hFAS polypeptide;   wherein said determining is optionally in the form of an enzyme linked immunosorbent assay (ELISA) or radioimmune assay (RIA) and   wherein the level of hFAS indicates the course, or recurrence, of said disease.   
     
     
         18 . The method of  claim 17  wherein said disease is cancer. 
     
     
         19 . A method of determining whether to administer a FAS inhibitor to a subject, said method comprising
 determining the level of an hFAS polypeptide in a sample from said subject based on formation of a complex comprising an antibody, or fragment thereof, of  claim 1  and said hFAS polypeptide; and   determining whether to administer a FAS inhibitor based on the level of hFAS detected   wherein said determining is optionally in the form of an enzyme linked immunosorbent assay (ELISA) or radioimmune assay (RIA).   
     
     
         20 . A method of providing chemoprotection to a subject with pre-malignant cells, said method comprising
 determining the level of an hFAS polypeptide in a sample from said subject based on formation of a complex comprising an antibody, or fragment thereof, of  claim 1  and said hFAS polypeptide; and   administering an FAS inhibitor to said subject based upon the level of hFAS detected to provide chemoprotection to said subject,   wherein said determining is optionally in the form of an enzyme linked immunosorbent assay (ELISA) or radioimmune assay (RIA).