VEGF Antagonist Formulations

Abstract

Formulations of a vascular endothelial growth factor (VEGF)-specific fusion protein antagonist are provided including a pre-lyophilized formulation, a reconstituted lyophilized formulation, and a stable liquid formulation. Preferably, the fusion protein has the sequence of SEQ ID NO:4.

1 .- 20 . (canceled) 
     
     
         21 . A vial comprising a formulation comprising:
 10-50 mg/ml of a vascular endothelial growth factor (VEGF) antagonist fusion protein comprising amino acids 27-457 of SEQ ID NO: 4,   
       a buffer comprising histidine, 
       a stabilizing agent comprising a sugar, an amino acid or both,
 wherein there is no detectable degradation of said VEGF antagonist fusion protein after 6 months of storage at 2-8° C. 
 
     
     
         22 . The vial of  claim 21 , wherein said buffer comprises 5-50 mM histidine. 
     
     
         23 . The vial of  claim 22 , wherein said formulation has a pH of 6.0-6.5. 
     
     
         24 . The vial of  claim 23 , wherein said formulation has a pH of 6.0. 
     
     
         25 . The vial of  claim 23 , wherein said formulation has a pH of 6.2. 
     
     
         26 . The vial of  claim 22 , wherein said stabilizing agent comprises a sugar. 
     
     
         27 . The vial of  claim 26 , wherein said sugar comprises a sugar selected from group consisting of dextrose, ribose, fructose, mannitol, inositol, sorbitol, trehalose, sucrose, and lactose. 
     
     
         28 . The vial of  claim 26 , wherein said sugar comprises sucrose, trehalose, or mannitol. 
     
     
         29 . The vial of  claim 26 , wherein said sugar comprises sucrose. 
     
     
         30 . The vial of  claim 29 , wherein said sugar comprises 5-30% sucrose. 
     
     
         31 . The vial of  claim 29 , wherein said sugar comprises 5-20% sucrose. 
     
     
         32 . The vial of  claim 26 , wherein said sugar comprises trehalose. 
     
     
         33 . The vial of  claim 22 , wherein said formulation further comprises a tonicity agent. 
     
     
         34 . The vial of  claim 33 , wherein said tonicity agent is sodium chloride. 
     
     
         35 . The vial of  claim 33 , wherein said tonicity agent is 40 mM sodium chloride. 
     
     
         36 . The vial of  claim 21 , wherein said formulation comprises 40 mg/ml of said VEGF antagonist fusion protein. 
     
     
         37 . The vial of  claim 28 , wherein said buffer comprises 10 mM histidine. 
     
     
         38 . A pre-filled syringe comprising a formulation comprising:
 10-50 mg/ml of a vascular endothelial growth factor (VEGF) antagonist fusion protein comprising amino acids 27-457 of SEQ ID NO: 4,   a buffer comprising histidine,   a stabilizing agent comprising a sugar, an amino acid or both,   wherein there is no detectable degradation of said VEGF antagonist fusion protein after 6 months of storage at 2-8° C.   
     
     
         39 . The pre-filled syringe of  claim 38 , wherein said buffer comprises 5-50 mM histidine. 
     
     
         40 . The pre-filled syringe of  claim 39 , wherein said formulation has a pH of 6.0-6.5. 
     
     
         41 . The pre-filled syringe of  claim 40 , wherein said formulation has a pH of 6.0. 
     
     
         42 . The pre-filled syringe of  claim 40 , wherein said formulation has a pH of 6.2. 
     
     
         43 . The pre-filled syringe of  claim 39 , wherein said stabilizing agent comprises a sugar. 
     
     
         44 . The pre-filled syringe of  claim 43 , wherein said sugar comprises a sugar selected from group consisting of dextrose, ribose, fructose, mannitol, inositol, sorbitol, trehalose, sucrose, and lactose. 
     
     
         45 . The pre-filled syringe of  claim 43 , wherein said sugar comprises sucrose, trehalose, or mannitol. 
     
     
         46 . The pre-filled syringe of  claim 43 , wherein said sugar comprises sucrose. 
     
     
         47 . The pre-filled syringe of  claim 46 , wherein said sugar comprises 5-30% sucrose. 
     
     
         48 . The pre-filled syringe of  claim 46 , wherein said sugar comprises 5-20% sucrose. 
     
     
         49 . The pre-filled syringe of  claim 43 , wherein said sugar comprises trehalose. 
     
     
         50 . The pre-filled syringe of  claim 39 , wherein said formulation further comprises a tonicity agent. 
     
     
         51 . The pre-filled syringe of  claim 50 , wherein said tonicity agent is sodium chloride. 
     
     
         52 . The pre-filled syringe of  claim 39 , wherein said tonicity agent is 40 mM sodium chloride. 
     
     
         53 . The pre-filled syringe of  claim 38 , wherein said formulation comprises 40 mg/ml of said VEGF antagonist fusion protein. 
     
     
         54 . The pre-filled syringe of  claim 45 , wherein said buffer comprises 10 mM histidine.