Protein sustained-release injectable formulation

Abstract

The present invention provides sustained-release pharmaceutical formulations for administering proteins to the eye. In particular, the invention provides formulations comprising single chain antibodies and hydrophobic polyester hexylsubstituted poly(lactic acid) (hexPLA). The invention further provides processes for the production of sustained-release pharmaceutical formulations and medical uses thereof.

What is claimed is: 
     
         1 . A sustained-release pharmaceutical formulation for ocular administration to a subject, comprising a single chain antibody (scFv) and hexylsubstituted poly(lactic acid) (hexPLA), wherein the single chain antibody comprises an amino acid sequence having at least 95% identity to the sequence of SEQ ID NO: 1. 
     
     
         2 . The formulation of  claim 1 , wherein the scFv is present in a final concentration of at least about 1.25% (w/w). 
     
     
         3 . The formulation of  claim 1 , wherein the scFv is present in a final concentration of at least about 2.5% (w/w). 
     
     
         4 . The formulation of  claim 1 , wherein the scFv is present in a final concentration of at least about 5.0% (w/w). 
     
     
         5 . The formulation of  claim 1 , wherein the hexPLA is present at a molecular weight of at least about 1500 g/mol. 
     
     
         6 . The formulation of  claim 1 , wherein the hexPLA is present at a molecular weight of at least about 2500 g/mol. 
     
     
         7 . The formulation of  claim 1 , wherein the hexPLA is present at a molecular weight of at least about 3500 g/mol. 
     
     
         8 . An intravitreal sustained-release depot comprising the formulation of  claim 1 . 
     
     
         9 . A delivery system comprising the sustained-release pharmaceutical formulation of  claim 1  and a syringe. 
     
     
         10 . The formulation of  claim 1 , wherein the single chain antibody is present in a final concentration in the range of 1.25% to 5.0% (w/w) and the hexPLA is present at a molecular weight in the range of 2500 g/mol to 5000 g/mol. 
     
     
         11 . A method of treating an ocular disorder in a patient, comprising administering to the patient an effective amount of the sustained-release pharmaceutical formulation of  claim 1 . 
     
     
         12 . The method of  claim 11 , wherein the ocular disorder is a retinal disorder. 
     
     
         13 . A process for the preparation of a sustained-release pharmaceutical formulation, the process comprising cryo-milling a single chain antibody and hexylsubstituted poly(lactic acid) (hexPLA), wherein the single chain antibody comprises an amino acid sequence having at least 95% identity to the sequence of SEQ ID NO: 1. 
     
     
         14 . The process of  claim 13 , wherein the single chain antibody is present in a final concentration in the range of 1.25% to 5.0% (w/w) and the hexPLA is present at a molecular weight in the range of 2500 g/mol to 5000 g/mol. 
     
     
         15 . A stable single chain antibody formulation, comprising a single chain antibody and hexylsubstituted poly(lactic acid) (hexPLA), wherein the single chain antibody is stable at 37° C., and wherein the single chain antibody comprises an amino acid sequence having at least 95% identity to the sequence of SEQ ID NO: 1. 
     
     
         16 . The formulation of  claim 15 , wherein the single chain antibody is present in a final concentration in the range of 1.25% to 5.0% (w/w) and the hexPLA is present at a molecular weight in the range of 2500 g/mol to 5000 g/mol.