Vegf antagonist formulations suitable for intravitreal administration

Abstract

Ophthalmic formulations of a vascular endothelial growth factor (VEGF)-specific fusion protein antagonist are provided suitable for intravitreal administration to the eye. The ophthalmic formulations include a stable liquid formulation and a lyophilizable formulation. Preferably, the protein antagonist has an amino acid sequence of SEQ ID NO:4.

We claim: 
     
         1 . A prefilled glass syringe suitable for intravitreal administration containing a stable ophthalmic formulation comprising a vascular endothelial growth factor (VEGF) antagonist, an organic co-solvent, a buffer, and a stabilizing agent, wherein the VEGF antagonist is a protein produced in a Chinese Hamster Ovary (CHO) cell. 
     
     
         2 . The prefilled glass syringe of  claim 1 , wherein 90% or more of the weight of the protein is not present as an aggregate. 
     
     
         3 . The prefilled glass syringe of  claim 2 , wherein the protein is a fusion protein comprising the immunoglobulin-like (Ig) domain 2 of a first VEGF receptor and Ig domain 3 of a second VEGF receptor, and a multimerizing component. 
     
     
         4 . The prefilled glass syringe of  claim 3 , wherein the first VEGF receptor is the human Flt1 and the second VEGF receptor is the human Flk1 or the human Flt4. 
     
     
         5 . The prefilled glass syringe of  claim 4 , wherein the fusion protein comprises an amino acid sequence of SEQ ID NO:4. 
     
     
         6 . The prefilled glass syringe of  claim 5 , wherein the VEGF antagonist is a dimer of the fusion protein. 
     
     
         7 . The prefilled syringe of  claim 1 , wherein the organic co-solvent is selected from the group consisting of polysorbate 20, polysorbate 80, polyethylene glycol (PEG), PEG3350, and propylene glycol. 
     
     
         8 . The prefilled syringe of  claim 1 , wherein the stabilizing agent is selected from the group consisting of sucrose, sorbitol, glycerol, trehalose, and mannitol. 
     
     
         9 . The prefilled syringe of  claim 1 , wherein the buffer comprises phosphate. 
     
     
         10 . The prefilled syringe of  claim 4  comprising (a) 1-100 mg/ml of the VEGF antagonist; (b) 0.01-5% of the organic co-solvent; (c) 5-40 mM of the buffer; and (d) 1.0-10% of the stabilizing agent. 
     
     
         11 . The prefilled syringe of  claim 11 , wherein the organic co-solvent is polysorbate 20, the buffer is phosphate, and the stabilizing agent is sucrose.