Targeted Coagulation Factors and Method of Using the Same

Abstract

Targeted coagulation factors comprising a coagulation factor linked with at least one domain that specifically binds to a membrane protein on a blood cell is provided. The disclosed targeted coagulation factors increase the efficiency of coagulation factors and prolong their duration of action and thus, are an improvement for the treatment of hematological diseases such as hemophilia A.

1 . A targeted coagulation factor comprising a coagulation factor linked with at least one domain that specifically binds to a membrane protein on a blood cell. 
     
     
         2 . The targeted coagulation factor of  claim 1 , wherein the coagulation factor is a functional FVIII polypeptide or FIX. 
     
     
         3 . The targeted coagulation factor of  claim 1 , wherein the domain is an antibody fragment, a peptide, a peptide mimetic, or a small molecule. 
     
     
         4 . The targeted coagulation factor of  claim 1 , wherein the blood cell is a platelet and the membrane protein is GPIIb/IIIa. 
     
     
         5 . The targeted coagulation factor of  claim 4 , wherein the coagulation factor is a functional FVIII polypeptide. 
     
     
         6 . The targeted coagulation factor of  claim 4 , wherein the domain is a RGD peptide or a single chain fragment of an anti-GPIIb/IIIa antibody. 
     
     
         7 . The targeted coagulation factor of  claim 1 , wherein the coagulation factor is a functional FVIII polypeptide and the domain is an antibody fragment, a peptide, a peptide mimetic, or a small molecule that is linked with the B-domain of the FVIII. 
     
     
         8 . The targeted coagulation factor of  claim 7 , wherein the blood cell is a platelet and the domain is a RGD peptide or a single chain fragment of an anti-GPIIb/IIIa antibody. 
     
     
         9 . A pharmaceutical composition comprising a therapeutically effective amount of the targeted coagulation factor of  claim 1  and a pharmaceutically acceptable excipient or carrier. 
     
     
         10 . A method for treating hematological diseases comprising administering an effective amount of the targeted coagulation factor of  claim 1  to a patient in need thereof. 
     
     
         11 . A method for targeting a coagulation factor to the surface of a blood cell comprising linking the coagulation factor with at least one domain that binds to a membrane protein on a blood cell. 
     
     
         12 . The method of  claim 11 , wherein the coagulation factor is a functional FVIII polypeptide or FIX. 
     
     
         13 . The method of  claim 11 , wherein the blood cell is a platelet or a red blood cell. 
     
     
         14 . The method of  claim 11 , wherein the domain is an antibody fragment, a peptide, a peptide mimetic, or a small molecule. 
     
     
         15 . The method of  claim 11 , wherein the blood cell is a platelet and the membrane protein is GPIIb/IIIa. 
     
     
         16 . The method of  claim 15 , wherein the coagulation factor is a functional FVIII polypeptide. 
     
     
         17 . The method of  claim 15 , wherein the domain is a RGD peptide or a single chain fragment of an anti-GPIIb/IIIa antibody. 
     
     
         18 . The method of  claim 11 , wherein the coagulation factor is FVIII and the domain is an antibody fragment, a peptide, a peptide mimetic, or a small molecule that is linked with the B-domain of the FVIII. 
     
     
         19 . The method of  claim 18 , wherein the blood cell is a platelet and the domain is a RGD peptide or a single chain fragment of an anti-GPIIb/IIIa antibody. 
     
     
         20 . The method of  claim 11 , wherein the coagulation factor is further released from the surface of the blood cell.