Methods and compositions related to long half-life coagulation complexes

Abstract

Disclosed herein are methods and compositions related to coagulation factor complexes comprising a coagulation factor; a fusion protein; and a modifying molecule, wherein the modifying molecule is coupled to the coagulation factor in such a way as to allow binding by the fusion protein, thereby creating a modified coagulation factor; wherein the modilied coagulation factor and the fusion protein interact in at least two independent sites.

1 . A coagulation factor complex comprising:
 a. a coagulation factor;   b. a fusion protein comprising a first protein fused to albumin, or an albumin fragment; and   c. a modifying molecule, wherein the modifying molecule is coupled to the coagulation factor in such a way as to allow binding by the fusion protein, thereby creating a modified coagulation factor;   wherein the modified coagulation factor and the fusion protein interact in at least two independent sites.   
     
     
         2 . The coagulation factor complex of  claim 1 , wherein at least one binding site of the modified coagulation factor is a natural binding site. 
     
     
         3 . The coagulation factor complex of  claim 1 , wherein at least one binding site of the fusion protein is provided by the modifying molecule. 
     
     
         4 . The coagulation factor complex of  claim 1 , wherein the coagulation factor is Factor VIII. 
     
     
         5 . The coagulation factor complex of  claim 1 , wherein the modified coagulation factor is modified Factor VIIa. 
     
     
         6 . The coagulation factor complex of  claim 1 , wherein the first protein of the fusion protein is a fragment of von Willebrand's factor. 
     
     
         7 . The coagulation factor complex of  claim 6 , wherein the fragment of von Willebrand's factor is a D′D3 fragment. 
     
     
         8 . The coagulation factor complex of  claim 6 , the first protein of the fusion protein is Tissue Factor (TF). 
     
     
         9 . The coagulation factor complex of  claim 1 , wherein the modified coagulation factor and the fusion protein form a non-covalant bond. 
     
     
         10 . The coagulation factor complex of  claim 1 , wherein the modified coagulation factor and the fusion protein interact covalently. 
     
     
         11 . The coagulation factor complex of  claim 10 , wherein the covalent bond is not a peptide bond. 
     
     
         12 . The coagulation factor complex of  claim 10 , wherein the covalent bond is not a peptide bond produced by translation of a nucleic acid. 
     
     
         13 . The coagulation factor complex of  claim 1 , wherein the modifying molecule comprises a fatty acid. 
     
     
         14 . The coagulation factor complex of  claim 1 , wherein the modifying molecule is produced by click chemistry. 
     
     
         15 . The coagulation factor complex of  claim 1 , wherein the coagulation factor is coupled to the fusion protein by click chemistry. 
     
     
         16 . The coagulation factor complex of  claim 1 , wherein the modifying molecule is attached to the coagulation factor through a polyethylene glycol chain. 
     
     
         17 . (canceled) 
     
     
         18 . (canceled) 
     
     
         19 . The coagulation factor complex of  claim 1 , wherein the first protein of the fusion protein is joined together with albumin via a linker. 
     
     
         20 . The coagulation factor complex of  claim 1 , wherein the coagulation factor comprises modified amino acids. 
     
     
         21 . The coagulation factor complex of  claim 1 , wherein the fusion protein comprises modified amino acids. 
     
     
         22 . The coagulation factor complex of  claim 1 , wherein half-life of the coagulation factor complex is at least 20% greater compared to a coagulation factor alone. 
     
     
         23 - 26 . (canceled)