US2006258570A1PendingUtilityA1

Decorin proteoglycan inhibitor of fibrinogen blood clotting

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Assignee: HOOK MAGNUSPriority: Jul 25, 2003Filed: Jul 24, 2006Published: Nov 16, 2006
Est. expiryJul 25, 2023(expired)· nominal 20-yr term from priority
Inventors:Magnus HookTracey Dugan
C07K 14/4725A61K 47/61A61K 38/1709
42
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Claims

Abstract

The present invention provides compositions and methods of inhibiting fibrin(ogen) clot formation by utilizing decorin proteoglycan as an anticoagulating and antithrombotic agent. The decorin proteoglycan comprises a decorin core protein or a fragment thereof covalently linked to a galactosaminoglycan polysaccharide. The decorin core protein acts as an anticoagulant and as a carrier for the delivery of an antithrombotic galactosaminoglycan to fibrinogen. Fibrin clotting is inhibited by the decorin proteoglycan in a concentration-dependent fashion.

Claims

exact text as granted — not AI-modified
1 . A method of inhibiting fibrin clot formation, comprising: 
 contacting fibrinogen in a biological sample with a recombinant anticoagulating and antithrombotic decorin proteoglycan comprising decorin core protein linked to a galactosaminoglycan polysaccharide within an N-terminal sequence thereof.    
     
     
         2 . The method of  claim 1 , wherein said galactosaminoglycan polysaccharide is covalently linked thereto.  
     
     
         3 . The method of  claim 1 , wherein said decorin proteoglycan comprises a fibrinogen-binding domain.  
     
     
         4 . The method of  claim 4 , wherein said N-terminus has the sequence of SEQ ID NO. 1.  
     
     
         5 . The method of  claim 1 , wherein said decorin core protein has the sequence of SEQ ID NO. 2.  
     
     
         6 . The method of  claim 1 , wherein said decorin proteoglycan is chemically derivatived.  
     
     
         7 . The method of  claim 1 , wherein said decorin core protein or N-terminus thereof contains a conservative amino acid substitution.  
     
     
         8 . The method of  claim 1 , wherein said galactosaminoglycan polysaccharide is heparin, heparan sulfate, chondroitin sulfate, dermatan sulfate, or combinations thereof.  
     
     
         9 . The method of  claim 1 , wherein said biological sample is a blood sample.  
     
     
         10 . The method of  claim 9 , wherein said decorin proteoglycan is attached to the surface of a medical device or a polymeric biomaterial.  
     
     
         11 . A method of inhibiting fibrin clot formation in a subject, comprising: 
 administering to said subject a pharmacologically effective amount of a recombinant anticoagulating and antithrombotic decorin proteoglycan comprising decorin core protein or a fragment thereof linked to a galactosaminoglycan polysaccharide.    
     
     
         12 . The method of  claim 11 , wherein said galactosaminoglycan polysaccharide is covalently linked thereto.  
     
     
         13 . The method of  claim 11 , wherein said decorin proteoglycan comprises a fibrinogen-binding domain.  
     
     
         14 . The method of  claim 11 , wherein said N-terminus has the sequence of SEQ ID NO. 1.  
     
     
         15 . The method of  claim 11 , wherein said decorin core protein has the sequence of SEQ ID NO. 2.  
     
     
         16 . The method of  claim 11 , wherein said decorin proteoglycan is chemically derivatived.  
     
     
         17 . The method of  claim 11 , wherein said decorin core protein or N-terminus thereof contains a conservative amino acid substitution.  
     
     
         18 . The method of  claim 11 , wherein said galactosaminoglycan polysaccharide is heparin, heparan sulfate, chondroitin sulfate, dermatan sulfate, or combinations thereof.  
     
     
         19 . The method of  claim 11 , wherein said subject is an animal or a human.  
     
     
         20 . The method of  claim 11 , wherein said decorin proteoglycan is attached to the surface of a medical device or a polymeric biomaterial.  
     
     
         21 . The method of  claim 11 , wherein said decorin proteoglycan is administered in a dosage of about 0.01 mg/kg to about 100 mg/kg of the subject's body weight.  
     
     
         22 . The method of  claim 11 , wherein said decorin proteoglycan is administered topically, orally, intravenously, or intraperitoneally.  
     
     
         23 . The method of  claim 11 , wherein said decorin proteoglycan is formulated as an ointment, a cream, a gel, a lotion, or wound dressings.

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