Monoclonal antibodies against a complex of human ACT and a serine protease

Abstract

The invention concerns monoclonal antibodies against a complex of human ACT and a serine protease, preferably against a ACT-PSA, which have essentially no cross-reactivity with free, non-complexed human ACT and with free, non-complexed PSA, as well as diagnostic test methods for detecting serine protease-ACT complexes, in particular PSA-ACT, using these monoclonal antibodies.

What is claimed is:  
     
         1 . A monoclonal antibody which specifically binds a complex of human ACT and a serine protease having essentially no detectable cross-reactivity with non-complexed human ACT and free serine proteases.  
     
     
         2 . The antibody of  claim 1 , wherein said antibody has a higher affinity and specificity for PSA-ACT than for other serine protease-ACT complexes.  
     
     
         3 . The antibody of  claim 1 , wherein said antibody has an affinity for PSA-ACT at least 10-fold higher than for chymotrypsin-ACT and cathepsin G-ACT.  
     
     
         4 . The antibody of  claim 1 , wherein said antibody has essentially no cross-reactivity with other components in human serum.  
     
     
         5 . The antibody of  claim 1 , wherein said antibody has essentially no cross-reactivity with other components of samples of human origin such as plasma, serum, blood, seminal fluid, prostate fluid, seminal vesicle fluid, saliva, liquor, human milk, cysts, tissue homogenates, tissue sections and biopsy material.  
     
     
         6 . The antibody of  claim 1 , wherein said antibody has an affinity for PSA-ACT of more than 10 7 1/mol.  
     
     
         7 . The antibody of  claim 1 , wherein said antibody has an affinity for PSA of more than 10 9 1/mol.  
     
     
         8 . The antibody of  claim 1 , wherein said antibody is produced by a cell line from the group consisting of MAB<PSA-ACT>M4.6.374, MAB<PSA-ACT>M4.3.2 and MAB<PSA-ACT>M6.13.64 having the depository numbers DSM ACC 2281, DSM ACC 2283 and DSM ACC 2282.  
     
     
         9 . The antibody of  claim 1 , wherein said antibody binds in an equivalent manner to monoclonal antibodies produced by a cell line from the group consisting of MAB<PSA-ACT>M 4.6.374, MAB<PSA-ACT>M 4.3.2 and MAB<PSA-ACT>M 6.13.64 having the depository numbers DSM ACC 2281, DSM ACC 2283 and DSM ACC 2282.  
     
     
         10 . The antibody of  claim 1 , wherein said antibody is of the IgGl type.  
     
     
         11 . The antibody of  claim 1 , wherein said antibody is obtained by immunizing a suitable experimental animal and subsequently fusing the spleen cells of the immunized animal with myeloma cells.  
     
     
         12 . A method for the determination of a complex of ACT and a serine protease in a sample, said method comprising (a) incubating said sample with a monoclonal antibody which specifically binds a complex of human ACT and a serine protease having essentially no detectable cross-reactivity with non-complexed human ACT and free serine proteases and (b) measuring the amount of said antibody which binds to said complex.  
     
     
         13 . The method of  claim 12 , wherein the complex of ACT and a serine protease is PSA-ACT.  
     
     
         14 . The method of  claim 12 , wherein incubation step (a) further includes an antibody which binds PSA.  
     
     
         15 . A method for the determination of PSA-ACT in a sample, said method comprising (a) incubating said sample with a receptor which binds the neo-epitope of PSA-ACT and an antibody against PSA and (b) measuring the amount of said receptor which binds to said PSA-ACT.