Compositions, formulations and methods for treating ocular diseases

Abstract

Disclosed herein are compounds effective for activation of Tie-2 and inhibition of HPTP-beta. The compounds can provide effective therapy for conditions associated with angiogenesis, for example, ocular conditions. Formulations for increased solubility are disclosed. Combination therapy with antibodies and PK/PD data are also disclosed.

1 - 54 . (canceled) 
     
     
         55 . A method of treating an ocular edema in an eye of a subject in need thereof, the method comprising intravitreally administering to the subject a pharmaceutical formulation, wherein the pharmaceutical formulation comprises a therapeutically-effective amount of a Tie-2 activator,
 wherein the Tie-2 activator activates Tie-2 in the eye of the subject,   wherein the therapeutically-effective amount of the Tie-2 activator is from about 1 mg to about 10 mg;   wherein after administration of the pharmaceutical formulation to the subject, a visual acuity of the subject increases;   wherein the pharmaceutical formulation further comprises a solubilizing agent; and   wherein the method further comprises inhibiting VEGF in the eye of the subject.   
     
     
         56 . The method of  claim 55 , wherein the therapeutically-effective amount of the Tie-2 activator is about 1.5 mg. 
     
     
         57 . The method of  claim 55 , wherein the therapeutically-effective amount of the Tie-2 activator is about 6 mg. 
     
     
         58 . The method of  claim 55 , wherein the solubilizing agent is a polysorbate. 
     
     
         59 . The method of  claim 55 , wherein the ocular edema is diabetic macular edema. 
     
     
         60 . The method of  claim 55 , wherein a plasma concentration of the Tie-2 activator is not less than about 1 ng/mL about 2 hours after the administration of the pharmaceutical formulation. 
     
     
         61 . A method of activating Tie-2 in an eye of a subject in need thereof, the method comprising intravitreally administering to the subject a pharmaceutical formulation, wherein the pharmaceutical formulation comprises a therapeutically-effective amount of a Tie-2 activator,
 wherein the subject has an ocular edema;   wherein the therapeutically-effective amount of the Tie-2 activator is from about 1 mg to about 10 mg;   wherein after administration of the pharmaceutical formulation to the subject, a visual acuity of the subject increases;   wherein the pharmaceutical formulation further comprises a solubilizing agent; and   wherein the method further comprises inhibiting VEGF in the eye of the subject.   
     
     
         62 . The method of  claim 61 , wherein the therapeutically-effective amount of the Tie-2 activator is about 1.5 mg. 
     
     
         63 . The method of  claim 61 , wherein the therapeutically-effective amount of the Tie-2 activator is about 6 mg. 
     
     
         64 . The method of  claim 61 , wherein the solubilizing agent is a polysorbate. 
     
     
         65 . The method of  claim 61 , wherein the ocular edema is diabetic macular edema. 
     
     
         66 . The method of  claim 61 , wherein a plasma concentration of the Tie-2 activator is not less than about 1 ng/mL about 2 hours after the administration of the pharmaceutical formulation.