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 condition in a subject in need thereof, the method comprising topically administering to an eye of the subject a unit dosage form, wherein the unit dosage form comprises:
 a therapeutically-effective amount of a Tie-2 activator,   a cyclodextrin; and   an aqueous vehicle;   
       wherein the unit dosage form is formulated as a drop for topical administration to the eye of the subject; 
       wherein the unit dosage form comprises from about 0.1 mg/mL to about 100 mg/mL of the Tie-2 activator; 
       wherein the therapeutically-effective amount is from about 0.1 mg to about 100 mg; 
       wherein a plasma concentration in the subject of the Tie-2 activator is:
 a) for administration of a dose of about 5 mg, not less than about 1 ng/mL at about 0.25 hours after the administration; not less than about 1 ng/mL at about 1 hour after the administration; not less than about 1 ng/mL at about 2 hours after the administration; and about 0 ng/mL to about 30 ng/mL at about 4 hours after the administration; 
 b) for administration of a dose of about 15 mg, not less than about 1 ng/mL at about 0.25 hours after the administration; not less than about 1 ng/mL at about 1 hour after the administration; not less than about 1 ng/mL at about 2 hours after the administration; and about 0 ng/mL to about 40 ng/mL at about 4 hours after the administration; 
 c) for administration of a dose of about 22.5 mg, not less than about 1 ng/mL at about 0.25 hours after the administration; not less than about 1 ng/mL at about 1 hour after the administration; not less than about 1 ng/mL at about 2 hours after the administration; and not less than about 1 ng/mL at about 4 hours after the administration; or 
 d) for administration of a dose of about 30 mg, not less than about 1 ng/mL at about 0.25 hours after the administration; not less than about 1 ng/mL at about 1 hour after the administration; not less than about 1 ng/mL at about 2 hours after the administration; and not less than about 1 ng/mL at about 4 hours after the administration. 
 
     
     
         56 . The method of  claim 55 , wherein the Tie-2 activator binds HPTP-beta. 
     
     
         57 . The method of  claim 55 , wherein the Tie-2 activator inhibits HPTP-beta. 
     
     
         58 . The method of  claim 55 , wherein the Tie-2 activator comprises an amino acid backbone. 
     
     
         59 . The method of  claim 55 , wherein the therapeutically-effective amount is from about 0.5 mg to about 30 mg. 
     
     
         60 . The method of  claim 55 , wherein the therapeutically-effective amount is from about 0.05 mg to about 1.5 mg. 
     
     
         61 . The method of  claim 55 , wherein the cyclodextrin is 2-hydroxypropyl-β-cyclodextrin. 
     
     
         62 . The method of  claim 55 , wherein the cyclodextrin is sulfobutylether-β-cyclodextrin. 
     
     
         63 . The method of  claim 55 , wherein the subject is human. 
     
     
         64 . The method of  claim 55 , wherein the ocular condition is diabetic macular edema. 
     
     
         65 . The method of  claim 55 , wherein the ocular condition is diabetic retinopathy. 
     
     
         66 . The method of  claim 55 , wherein the ocular condition is macular degeneration. 
     
     
         67 . The method of  claim 55 , wherein the ocular condition is vascular leak. 
     
     
         68 . The method of  claim 55 , wherein the ocular condition is glaucoma. 
     
     
         69 . The method of  claim 55 , wherein the ocular condition is cancer.