Chimeric cytokine formulations for ocular delivery

Abstract

Featured herein are vehicle formulations and formulations containing a chimeric cytokine designed for e.g., ocular delivery.

What is claimed is: 
     
         1 . An aqueous formulation comprising
 sodium citrate or sodium phosphate at a concentration of 8 to 12 mM;   sorbitol at 4% to 6% (w/v); and   poloxamer 188 at a concentration of 0.08% to 0.12% (w/v);   wherein the formulation has a pH of 5.5 to 7.5 and   wherein the formulation is effective for treating an ocular disorder.   
     
     
         2 . (canceled) 
     
     
         3 . The formulation of  claim 1 , wherein the formulation is substantially free of a therapeutic protein. 
     
     
         4 . The formulation of  claim 1 , wherein the formulation comprises
 sodium citrate at a concentration of 9 to 11 mM;   sorbitol at 4.5 to 5.5% (w/v); and   poloxamer 188 at a concentration of 0.09 to 0.11%.   
     
     
         5 - 6 . (canceled) 
     
     
         7 . The formulation of  claim 1 , further comprising sodium carboxymethyl cellulose at a concentration of 0.1-1%. 
     
     
         8 . The aqueous formulation of  claim 1 , comprising
 sodium citrate at a concentration of 9-11 mM;   sorbitol at 4.5-5.5% (w/v); and   poloxamer 188 at a concentration of 0.09-0.11%,   wherein the formulation has a pH of 5.7 to 6.3,   wherein the formulation is substantially free of therapeutic protein, and   wherein the formulation is effective for treating an ocular disorder.   
     
     
         9 . The formulation of  claim 8 , wherein the ocular disorder is dry eye disease. 
     
     
         10 - 11 . (canceled) 
     
     
         12 . An aqueous formulation comprising
 1-50 mg/ml of an IL-1β/IL-1Ra chimeric cytokine protein selected from P01, P02, P03, P04, P05, P06, or P07;   a buffering agent selected from sodium citrate and sodium phosphate;   sorbitol, e.g., at a concentration of 3.5-6.5% (w/v); and   poloxamer 188, e.g., at a concentration of 0.07-0.13% (w/v);   wherein the formulation has a pH of 5.5 to 7.5.   
     
     
         13 . The formulation of  claim 12 , wherein the chimeric cytokine protein is P05. 
     
     
         14 - 33 . (canceled) 
     
     
         34 . The formulation of  claim 1 , wherein the formulation does not comprise a viscosity agent. 
     
     
         35 . The formulation of  claim 12 , wherein the formulation further comprises an amino acid. 
     
     
         36 . The formulation of  claim 35 , wherein the formulation comprises one or more of arginine, glutamic acid, histidine, and methionine. 
     
     
         37 . The formulation of  claim 36 , wherein methionine is present in the formulation at a concentration of 1 to 20 mM. 
     
     
         38 . The formulation of  claim 37 , wherein the formulation has reduced oxidation, compared to a corresponding formulation that does not comprise methionine, when the formulation is subjected to storage for at least 4 weeks at 25° C. 
     
     
         39 . The formulation of  claim 38 , wherein the formulation has reduced oxidation, compared to a corresponding formulation that does not comprise methionine, when the formulation is subjected to storage in a multidose container. 
     
     
         40 - 59 . (canceled) 
     
     
         60 . The formulation of  claim 12 , wherein the formulation is packaged in a blow fill seal container. 
     
     
         61 - 63 . (canceled) 
     
     
         64 . A method of treating an ocular disorder, the method comprising administering to a subject having the ocular disorder an aqueous formulation comprising
 sodium citrate or sodium phosphate at a concentration of 8 mM to 12 mM;   sorbitol at 4% to 6% (w/v); and   poloxamer 188 at a concentration of 0.08% to 0.12% (w/v);   wherein the formulation has a pH of 5.5 to 7.5 and is substantially free of therapeutic protein,   
       thereby treating the ocular disorder. 
     
     
         65 - 76 . (canceled) 
     
     
         77 . A container or device comprising the formulation of  claim 1 . 
     
     
         78 . The container or device of  claim 77 , wherein the container or device has been stored at 25° C. for at least two weeks and the formulation is substantially free of particulates. 
     
     
         79 - 87 . (canceled) 
     
     
         88 . The formulation of  claim 8 , further comprising carboxymethyl cellulose. 
     
     
         89 . The formulation of  claim 12 , further comprising carboxymethyl cellulose. 
     
     
         90 . The formulation of  claim 12 , wherein the formulation does not comprise a viscosity agent. 
     
     
         91 . A method of treating an ocular disorder, the method comprising administering to a subject having the ocular disorder the formulation of  claim 12 , thereby treating the ocular disorder. 
     
     
         92 . The container or device of  claim 77 , wherein the container or device comprises a multidose container. 
     
     
         93 . The container or device of  claim 77 , wherein the container or device comprises a blow fill seal container. 
     
     
         94 . A container or device comprising the formulation of  claim 12 .