Novel human kunitz-type inhibitors and methods relating thereto

Abstract

The present invention provides isolated DNA molecules comprising a DNA segment encoding novel human Kunitz-type inhibitors. Also provided are DNA constructs comprising a first DNA segment encoding a novel human Kunitz-type inhibitor wherein said first DNA segment is operably linked to additional DNA segments required for the expression for the first DNA segment, as well as host cells containing such DNA constructs and methods for producing proteins from the host cells.

what is claimed is:  
     
         1 . An isolated human Kunitz-type inhibitor comprising the amino acid sequence of SEQ ID NO:15, wherein each Xaa is individually any amino acid except cysteine, and wherein the isolated human Kunitz-type inhibitor inhibits blood coagulation in a mammal.  
     
     
         2 . An isolated human Kunitz-type inhibitor according to  claim 1 , wherein said inhibitor is selected from the group consisting of the amino acid sequence of SEQ ID NO:2 from methionine, amino acid 1 to phenylalanine, amino acid number 235; the amino acid sequence of SEQ ID NO:2 from glutamic acid, amino acid number 34 to isoleucine, amino acid number 89; the amino acid sequence of SEQ ID NO:2 from glutamic acid, amino acid number 34 to lysine, amino acid 152 and the amino acid sequence of SEQ ID NO:2 from glutamic acid, amino acid number 34 to alanine, amino acid number 211.  
     
     
         3 . An isolated human Kunitz-type inhibitor according to  claim 1 , wherein said inhibitor further comprises the amino acid sequence of SEQ ID NO:12 or SEQ ID NO:13 at its amino-terminus.  
     
     
         4 . A pharmaceutical composition which comprises a human Kunitz-type inhibitor according to  claim 1  in combination with a pharmaceutically acceptable carrier or vehicle.  
     
     
         5 . A pharmaceutical composition according to  claim 4  wherein said Kunitz-type inhibitor is selected from the group consisting of the amino acid sequence of SEQ ID NO:2 from methionine, amino acid 1 to phenylalanine, amino acid number 235; the amino acid sequence of SEQ ID NO:2 from glutamic acid, amino acid number 34 to isoleucine, amino acid number 89; the amino acid sequence of SEQ ID NO:2 from glutamic acid, amino acid number 34 to lysine, amino acid 152 and the amino acid sequence of SEQ ID NO:2 from glutamic acid, amino acid number 34 to alanine, amino acid number 211.  
     
     
         6 . A pharmaceutical composition according to  claim 4  wherein said human Kunitz-type inhibitor further comprises the amino acid sequence of SEQ ID NO:12 or SEQ ID NO:13 at its amino-terminus.