US2016220540A1PendingUtilityA1

Compositions, formulations and methods for treating ocular diseases

Assignee: AERPIO THERAPEUTICS INCPriority: Mar 15, 2013Filed: Apr 14, 2016Published: Aug 4, 2016
Est. expiryMar 15, 2033(~6.6 yrs left)· nominal 20-yr term from priority
A61K 38/179A61K 31/428A61K 39/395C07D 417/04C07D 277/60C07D 277/30A61K 2039/54C07D 277/56C07K 16/22A61K 47/40A61K 47/26A61K 31/433A61K 31/426A61K 2039/505A61K 31/513A61K 31/496C07D 277/64A61K 31/427A61P 27/00A61K 39/3955A61K 47/6951A61K 31/506A61K 31/538A61K 9/0019A61K 31/497A61K 9/0051A61P 27/02C07D 417/12A61K 31/4439C07D 277/28
67
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Claims

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.

Claims

exact text as granted — not AI-modified
1 - 54 . (canceled) 
     
     
         55 . A method of treating a condition, the method comprising administering to a subject in need thereof:
 a) a therapeutically-effective amount of a Tie-2 activator or a pharmaceutically-acceptable salt thereof; and   b) a therapeutically-effective amount of an anti-VEGF binding agent.   
     
     
         56 . The method of  claim 55 , wherein the Tie-2 activator binds a phosphatase. 
     
     
         57 . The method of  claim 55 , wherein the Tie-2 activator inhibits a phosphatase. 
     
     
         58 . The method of  claim 55 , wherein the Tie-2 activator is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         59 . The method of  claim 55 , wherein the Tie-2 activator is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         60 . The method of  claim 55 , wherein the Tie-2 activator is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         61 . The method of  claim 55 , wherein the Tie-2 activator is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         62 . The method of  claim 55 , wherein the Tie-2 activator is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         63 . The method of  claim 55 , wherein the Tie-2 activator is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         64 . The method of  claim 55 , wherein the Tie-2 activator is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         65 . The method of  claim 55 , wherein the Tie-2 activator is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         66 . The method of  claim 55 , wherein the Tie-2 activator is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         67 . The method of  claim 55 , wherein the Tie-2 activator is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         68 . The method of  claim 55 , wherein the Tie-2 activator is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         69 . The method of  claim 55 , wherein the Tie-2 activator is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         70 . The method of  claim 55 , wherein the Tie-2 activator is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         71 . The method of  claim 55 , wherein the Tie-2 activator is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         72 . The method of  claim 55 , wherein the Tie-2 activator is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         73 . The method of  claim 55 , wherein the Tie-2 activator is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         74 . The method of  claim 55 , wherein the Tie-2 activator is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         75 . The method of  claim 55 , wherein the Tie-2 activator is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         76 . The method of  claim 55 , wherein the Tie-2 activator is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         77 . The method of  claim 55 , wherein the Tie-2 activator is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         78 . The method of  claim 55 , wherein the Tie-2 activator is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         79 . The method of  claim 55 , wherein the Tie-2 activator is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         80 . The method of  claim 55 , wherein the Tie-2 activator is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         81 . The method of  claim 55 , wherein the therapeutically-effective amount of the Tie-2 activator is about 5 mg to about 60 mg. 
     
     
         82 . The method of  claim 55 , wherein the therapeutically-effective amount of the Tie-2 activator is about 15 mg. 
     
     
         83 . The method of  claim 55 , wherein the therapeutically-effective amount of the Tie-2 activator is about 30 mg. 
     
     
         84 . The method of  claim 55 , wherein the therapeutically-effective amount of the anti-VEGF binding agent is about 0.5 mg to about 50 mg. 
     
     
         85 . The method of  claim 55 , wherein the anti-VEGF binding agent is ranibizumab. 
     
     
         86 . The method of  claim 85 , wherein the therapeutically-effective amount of ranibizumab is about 0.05 mg to about 1.5 mg. 
     
     
         87 . The method of  claim 55 , wherein the anti-VEGF binding agent is bevacizumab. 
     
     
         88 . The method of  claim 87 , wherein the therapeutically-effective amount of bevacizumab is about 0.1 mg to about 5 mg. 
     
     
         89 . The method of  claim 55 , wherein the anti-VEGF binding agent is aflibercept. 
     
     
         90 . The method of  claim 89 , wherein the therapeutically-effective amount of aflibercept is about 0.05 mg to about 5 mg. 
     
     
         91 . The method of  claim 55 , wherein the administration is intravitreal. 
     
     
         92 . The method of  claim 55 , wherein the administration is subcutaneous. 
     
     
         93 . The method of  claim 55 , wherein the subject is human. 
     
     
         94 . The method of  claim 55 , wherein the condition is an ocular condition. 
     
     
         95 . The method of  claim 55 , wherein the condition is diabetic macular edema. 
     
     
         96 . The method of  claim 55 , wherein the condition is diabetic retinopathy. 
     
     
         97 . The method of  claim 55 , wherein the condition is macular degeneration. 
     
     
         98 . The method of  claim 55 , wherein the condition is vascular leak. 
     
     
         99 . The method of  claim 55 , wherein the condition is glaucoma. 
     
     
         100 . The method of  claim 55 , wherein the condition is cancer. 
     
     
         101 . A method of treating a condition, the method comprising administering to a subject in need thereof:
 a) a therapeutically-effective amount of a HPTP-β binding agent or a pharmaceutically-acceptable salt thereof; and   b) a therapeutically-effective amount of an anti-VEGF binding agent.   
     
     
         102 . The method of  claim 101 , wherein the HPTP-β binding agent is an inhibitor of HPTP-β. 
     
     
         103 . The method of  claim 101 , wherein the HPTP-β binding agent inhibits a phosphatase. 
     
     
         104 . The method of  claim 101 , wherein the HPTP-β binding agent is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         105 . The method of  claim 101 , wherein the HPTP-β binding agent is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         106 . The method of  claim 101 , wherein the HPTP-β binding agent is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         107 . The method of  claim 101 , wherein the HPTP-β binding agent is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         108 . The method of  claim 101 , wherein the HPTP-β binding agent is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         109 . The method of  claim 101 , wherein the HPTP-β binding agent is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         110 . The method of  claim 101 , wherein the HPTP-β binding agent is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         111 . The method of  claim 101 , wherein the HPTP-β binding agent is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         112 . The method of  claim 101 , wherein the HPTP-β binding agent is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         113 . The method of  claim 101 , wherein the HPTP-β binding agent is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         114 . The method of  claim 101 , wherein the HPTP-β binding agent is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         115 . The method of  claim 101 , wherein the HPTP-β binding agent is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         116 . The method of  claim 101 , wherein the HPTP-β binding agent is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         117 . The method of  claim 101 , wherein the HPTP-β binding agent is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         118 . The method of  claim 101 , wherein the HPTP-β binding agent is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         119 . The method of  claim 101 , wherein the HPTP-β binding agent is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         120 . The method of  claim 101 , wherein the HPTP-β binding agent is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         121 . The method of  claim 101 , wherein the HPTP-β binding agent is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         122 . The method of  claim 101 , wherein the HPTP-β binding agent is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         123 . The method of  claim 101 , wherein the HPTP-β binding agent is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         124 . The method of  claim 101 , wherein the HPTP-β binding agent is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         125 . The method of  claim 101 , wherein the HPTP-β binding agent is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         126 . The method of  claim 101 , wherein the HPTP-β binding agent is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         127 . The method of  claim 101 , wherein the therapeutically-effective amount of the HPTP-β binding agent is about 5 mg to about 60 mg. 
     
     
         128 . The method of  claim 101 , wherein the therapeutically-effective amount of the HPTP-β binding agent is about 15 mg. 
     
     
         129 . The method of  claim 101 , wherein the therapeutically-effective amount of the HPTP-β binding agent is about 30 mg. 
     
     
         130 . The method of  claim 101 , wherein the therapeutically-effective amount of the anti-VEGF binding agent is about 0.5 mg to about 50 mg. 
     
     
         131 . The method of  claim 101 , wherein the anti-VEGF binding agent is ranibizumab. 
     
     
         132 . The method of  claim 131 , wherein the therapeutically-effective amount of ranibizumab is about 0.05 mg to about 1.5 mg. 
     
     
         133 . The method of  claim 101 , wherein the anti-VEGF binding agent is bevacizumab. 
     
     
         134 . The method of  claim 133 , wherein the therapeutically-effective amount of bevacizumab is about 0.1 mg to about 5 mg. 
     
     
         135 . The method of  claim 101 , wherein the anti-VEGF binding agent is aflibercept. 
     
     
         136 . The method of  claim 135 , wherein the therapeutically-effective amount of aflibercept is about 0.05 mg to about 5 mg. 
     
     
         137 . The method of  claim 101 , wherein the administration is intravitreal. 
     
     
         138 . The method of  claim 101 , wherein the administration is subcutaneous. 
     
     
         139 . The method of  claim 101 , wherein the subject is human. 
     
     
         140 . The method of  claim 101 , wherein the condition is an ocular condition. 
     
     
         141 . The method of  claim 101 , wherein the condition is diabetic macular edema. 
     
     
         142 . The method of  claim 101 , wherein the condition is diabetic retinopathy. 
     
     
         143 . The method of  claim 101 , wherein the condition is macular degeneration. 
     
     
         144 . The method of  claim 101 , wherein the condition is vascular leak. 
     
     
         145 . The method of  claim 101 , wherein the condition is glaucoma. 
     
     
         146 . The method of  claim 101 , wherein the condition is cancer.

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