Human serpin polypeptides

Abstract

This invention relates to Thypin, a new member of the human serpin polypeptide family, methods of making Thypin polypeptides and using these polypeptides to treat various medical disorders and to methods of screening for compounds that agonize or antagonize Thypin polypeptide activities.

1 . An isolated nucleic acid molecule having at least 15 nucleotides, wherein said nucleic acid molecule is capable of hybridizing under highly stringent conditions with the nucleotide sequence of SEQ ID NO:1 or its complement, and further wherein said highly stringent conditions comprise hybridizing at 42° C. in 50% formamide and 6×SSC and washing at 68° C. in 0.2×SSC.  
     
     
         2 . An isolated nucleic acid molecule according to  claim 1 , wherein said nucleic acid molecule is capable of encoding a Thypin polypeptide having the amino acid sequence shown in SEQ ID NO:2 or a variant thereof.  
     
     
         3 . (canceled)  
     
     
         4 . An isolated genomic nucleic acid corresponding to the nucleic acid of any of claims  1  through  2 .  
     
     
         5 - 9 . (canceled)  
     
     
         10 . An isolated antibody that binds specifically with a polypeptide of SEQ ID NO:2.  
     
     
         11 . The antibody of  claim 10  wherein the antibody is a monoclonal antibody.  
     
     
         12 . The antibody of  claim 10  wherein the antibody is a human antibody.  
     
     
         13 . The antibody of  claim 10  wherein the antibody is a humanized antibody.  
     
     
         14 . The antibody of  claim 10  wherein the antibody inhibits the activity of the polypeptide of SEQ ID NO:2.  
     
     
         15 . A method of designing an inhibitor of the polypeptide of SEQ ID NO:2, the method comprising the steps of determining the three-dimensional structure of such polypeptide, analyzing the three-dimensional structure for the likely binding sites of substrates, synthesizing a molecule that incorporates a predicted reactive site, and determining the polypeptide-inhibiting activity of the molecule.  
     
     
         16 . A method for identifying compounds that alter Thypin polypeptide activity comprising 
 (a) mixing a test compound with the polypeptide of SEQ ID NO:2; and    (b) determining whether the test compound alters the Thypin polypeptide activity of said polypeptide.    
     
     
         17 . A method for identifying compounds that inhibit the binding activity of Thypin polypeptides comprising: 
 (a) mixing a test compound with the polypeptide of SEQ ID NO:2 and a binding partner of said polypeptide; and    (b) determining whether the test compound inhibits the binding activity of said polypeptide.    
     
     
         18 . A method for increasing protease inhibitory activity comprising providing at least one compound selected from the group consisting of the polypeptide of SEQ ID NO:2 and agonists of said polypeptides.  
     
     
         19 . The method of  claim 18  wherein the method comprises increasing protease inhibitory activity in a patient by administering to said patient at least one compound selected from the group consisting of the polypeptide of SEQ ID NO:2 and agonists of said polypeptides.  
     
     
         20 . A method for decreasing protease inhibitory activity comprising providing at least one antagonist of the polypeptide of SEQ ID NO:2.  
     
     
         21 . The method of  claim 20  wherein the method comprises decreasing protease inhibitory activity in a patient by administering at least one antagonist of the polypeptide of SEQ ID NO:2 to said patient.  
     
     
         22 . The method of  claim 20  wherein the antagonist is an antibody that specifically binds with and inhibits the activity of said polypeptide.  
     
     
         23 . A method for treating a Thypin-mediated disorder comprising administering at least one compound selected from the group consisting of the polypeptide of SEQ ID NO:2, agonists and antagonists of said polypeptides.