Novel nucleic acid molecules and polypeptides encoding baboon TAFI

Abstract

The present invention relates to the isolation and identification of novel baboon nucleic acid molecules and proteins and polypeptides encoded by such nucleic acid molecules, or degenerate variants thereof, which proteins and polypeptides comprise novel baboon thrombin-activatable fibrinolysis inhibitors or “TAFI” enzyme molecules. Because the novel baboon TAFI proteins and polypeptides of the invention inhibit the breakdown of blood clots, they may be therapeutically useful for the treatment of blood disorders wherein clotting needs to be regulated or promoted, such as hemophilia or von Willebrand's disease or in other situations, such as trauma, wherein blood clotting or coagulation needs to be regulated or promoted. The sequences of the invention are also useful in screening methods for the identification of compounds that modulate the expression of the baboon TAFI nucleic acids and/or the activity of the baboon TAFI proteins and polypeptides of the invention. Such agonist or antagonist compounds may be useful in the treatment of various blood clotting disorders and conditions requiring hemostatic control such as hemophilia or various thrombotic diseases such as deep venous thrombosis, coronary artery disease, stroke associated with atrial fibrillation and recurrent thrombosis following stroke or myocardial infarction.

1 - 31 . (canceled)  
     
     
         32 . An isolated antibody or fragment thereof that specifically binds to a polypeptide selected from the group consisting of: 
 (a) an isolated polypeptide comprising amino acids 1 to 423 of SEQ ID NO:2;    (b) an isolated polypeptide comprising amino acids 2 to 423 of SEQ ID NO:2;    (c) an isolated polypeptide comprising amino acids 23 to 423 of SEQ ID NO:2    (d) an isolated polypeptide comprising the polypeptide sequence encoded by nucleotides 1 to 1269 of SEQ ID NO:1;    (e) an isolated polypeptide comprising the polypeptide sequence encoded by nucleotides 4 to 1269 of SEQ ID NO:1;    (f) an isolated polypeptide comprising the polypeptide sequence encoded by nucleotides 67 to 1269 of SEQ ID NO:1; and    (g) an isolated polypeptide comprising the polypeptide encoded by the btafi cDNA clone contained in ATCC Deposit No: PTA-3949.    
     
     
         33 . The isolated antibody or fragment thereof of  claim 32 , wherein said antibody is (a).  
     
     
         34 . The isolated antibody or fragment thereof of  claim 32 , wherein said antibody is (b).  
     
     
         35 . The isolated antibody or fragment thereof of  claim 32 , wherein said antibody is (c).  
     
     
         36 . The isolated antibody or fragment thereof of  claim 32 , wherein said antibody is (d).  
     
     
         37 . The isolated antibody or fragment thereof of  claim 32 , wherein said antibody is (e).  
     
     
         38 . The isolated antibody or fragment thereof of  claim 32 , wherein said antibody is (f).  
     
     
         39 . The isolated antibody or fragment thereof of  claim 32 , wherein said antibody is (g).  
     
     
         40 . The antibody according to  claim 32  which is polyclonal.  
     
     
         41 . The antibody according to  claim 32  which is monoclonal.  
     
     
         42 . The antibody according to  claim 32  which is chimeric.  
     
     
         43 . The antibody according to  claim 32  which is humanized.  
     
     
         44 . The antibody according to  claim 32  which is mammalian.  
     
     
         45 . The antibody according to  claim 32  which is human.  
     
     
         46 . A hybridoma cell which produces the antibody according to  claim 41 .  
     
     
         47 . The antibody of  claim 32 , wherein the fragment is selected from the group consisting of a) a Fab fragment; b) a F(ab′) 2 fragment, and c) a Fv fragment.  
     
     
         48 . The antibody of  claim 32  which is labeled.  
     
     
         49 . The antibody of  claim 48  wherein the label is selected from the group consisting of: a) an enzyme; b) a fluorescent label; and c) a radioactive isotope.  
     
     
         50 . The antibody of  claim 48  which specifically binds to said polypeptide in an ELISA.  
     
     
         51 . The antibody of  claim 48  which specifically binds to said polypeptide in a competitive-binding assay.  
     
     
         52 . The antibody of  claim 48  which specifically binds to said polypeptide in a radioimmunoassay.  
     
     
         53 . A kit for detecting a polypeptide comprising the sequence of SEQ ID NO:2 comprising: 
 a) the isolated antibody of  claim 32;  and    b) at least one component to detect binding of the isolated antibody to said polypeptide sequence.    
     
     
         54 . An isolated antibody obtained from an animal that has been immunized with a polypeptide encoded by the cDNA contained in ATCC deposit No. PTA-3949.  
     
     
         55 . An isolated antibody or fragment thereof that specifically binds to a polypeptide comprising an amino acid sequence selected from the group consisting of: 
 (a) an isolated polypeptide comprising amino acids 23 to 114 of SEQ ID NO:2;    (b) an isolated polypeptide comprising amino acids 115 to 423 of SEQ ID NO:2;    (c) an isolated polypeptide comprising the polypeptide sequence encoded by nucleotides 67 to 342 of SEQ ID NO:1; and    (d) an isolated polypeptide comprising the polypeptide sequence encoded by nucleotides 343 to 1269 of SEQ ID NO:1;    
     
     
         56 . The antibody according to  claim 55  which is polyclonal.  
     
     
         57 . The antibody according to  claim 55  which is monoclonal.  
     
     
         58 . The antibody of  claim 55 , wherein the fragment is selected from the group consisting of a) a Fab fragment; b) a F(ab′) 2 fragment, and c) a Fv fragment.