US2019201430A1PendingUtilityA1

Treating ocular neovascularization

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Assignee: MASSACHUSETTS EYE & EAR INFIRMARYPriority: Jan 2, 2014Filed: Oct 12, 2018Published: Jul 4, 2019
Est. expiryJan 2, 2034(~7.4 yrs left)· nominal 20-yr term from priority
Inventors:Demetrios VavvasJoan W. MillerKimio Takeuchi
C07H 19/052A61K 31/515A61K 31/436A61K 31/616A61K 45/06A61K 31/683A61P 27/02A61K 31/6615A61K 31/519A61K 9/0048A61K 31/7056A61K 31/4439A61K 31/7004C07F 9/117A61K 31/155
54
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Claims

Abstract

Methods of treating ocular neovascularization, e.g., associated with wet age-related macular degeneration (AMD), using activators of AMP-activated protein kinase (AMPK) and/or of Phosphatase and tensin homolog deleted on chromosome 10 (PTEN).

Claims

exact text as granted — not AI-modified
1 - 17 . (canceled) 
     
     
         18 . A method of treating ocular neovascularization characterized by surface, corneal, retinal, choroidal, uveal, or iris neovascularization in a mammal, the method comprising:
 identifying a mammal in need of reduced or delayed ocular neovascularization; and   administering to the mammal an effective amount of one or both of:   (i) an amp-activated protein kinase (AMPK) activator, or   (ii) a Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) activator,   in combination with one or more anti-VEGF therapies.   
     
     
         19 . The method of  claim 18 , wherein the one or more anti-VEGF therapies is a monoclonal antibody or aptamer that binds and inhibits VEGF. 
     
     
         20 . The method of  claim 19 , wherein the one or more anti-VEGF therapies is selected from the group consisting of Avastin (Bevacizumab), Lucentis (Ranibizumab), Eylea (Aflibercept), Zaltrap (Aflibercept), and Macugen (Pegaptanib). 
     
     
         21 . The method of  claim 18 , wherein the mammal has retinopathy, symptoms associated with microangiopathy, neovascular glaucoma, corneal graft rejection, glaucoma, herpetic and infectious keratitis, ocular ischemia, neovascular glaucoma, corneal, uveal and iris neovascularization, orbital and eyelid tumors, Stevens Johnson Syndrome, ocular cicatricial pemphigoid, wounds or other injuries, and ocular surface diseases in a mammal. 
     
     
         22 . The method of  claim 21 , wherein the mammal has a retinopathy selected from the group consisting of retinopathy of prematurity (ROP); retina vein occlusion; sickle cell retinopathy; Stargardt's disease; choroidal neovascularization; and radiation retinopathy. 
     
     
         23 . The method of  claim 21 , wherein the mammal has an injury that is a chemical injury due to exposure to irritants, acids or bases. 
     
     
         24 . The method of  claim 18 , wherein the mammal has endophthalmitis, macular edema, conjunctivitis, episcleritis, keratitis, optic neuritis, orbital pseudotumor, retinal vasculitis, or scleritis. 
     
     
         25 . The method of  claim 18 , comprising administering an AMPK activator selected from the group consisting of guanidine; galegine; phenobarbital; A-769662; PT1; and salicylate. 
     
     
         26 . The method of  claim 18 , comprising administering a PTEN activator selected from the group consisting of di-C8-phosphatidylinositol 4,5-P2 (PI(4,5)P2) and PI(5)P. 
     
     
         27 . The method of  claim 18 , comprising administering an AMPK activator selected from the group consisting of 5-Aminoimidazole-4-carboxamide riboside (AICA riboside or AICAR); ZMP; guanidine; galegine; metformin (dimethylbiguanide); phemformin (phenethylbiguanide); pemetrexed; pioglitazone; troglitazone; phenobarbital; A-769662; PT1; and salicylate. 
     
     
         28 . The method of  claim 18 , comprising administering a PTEN activator selected from the group consisting of di-C8-phosphatidylinositol 4,5-P2 (PI(4,5)P2) and PI(5)P. 
     
     
         29 . A method of treating wet age-related macular degeneration (AMD) in a mammal, the method comprising:
 identifying a mammal who has wet AMD; and   administering to the mammal a therapeutically effective amount of one or both of:   (i) an amp-activated protein kinase (AMPK) activator, or   (ii) a Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) activator,   in combination with one or more anti-VEGF therapies.   
     
     
         30 . The method of  claim 29 , wherein the one or more anti-VEGF therapies is a monoclonal antibody or aptamer that binds and inhibits VEGF. 
     
     
         31 . The method of  claim 30 , wherein the one or more anti-VEGF therapies is selected from the group consisting of Avastin (Bevacizumab), Lucentis (Ranibizumab), Eylea (Aflibercept), Zaltrap (Aflibercept), and Macugen (Pegaptanib). 
     
     
         32 . The method of  claim 29 , wherein the mammal has retinopathy, symptoms associated with microangiopathy, neovascular glaucoma, corneal graft rejection, glaucoma, herpetic and infectious keratitis, ocular ischemia, neovascular glaucoma, corneal, uveal and iris neovascularization, orbital and eyelid tumors, Stevens Johnson Syndrome, ocular cicatricial pemphigoid, wounds or other injuries, and ocular surface diseases in a mammal. 
     
     
         33 . The method of  claim 32 , wherein the mammal has a retinopathy selected from the group consisting of retinopathy of prematurity (ROP); retina vein occlusion; sickle cell retinopathy; Stargardt's disease; choroidal neovascularization; and radiation retinopathy. 
     
     
         34 . The method of  claim 32 , wherein the mammal has an injury that is a chemical injury due to exposure to irritants, acids or bases. 
     
     
         35 . The method of  claim 29 , wherein the mammal has endophthalmitis, macular edema, conjunctivitis, episcleritis, keratitis, optic neuritis, orbital pseudotumor, retinal vasculitis, or scleritis. 
     
     
         36 . The method of  claim 29 , comprising administering an AMPK activator selected from the group consisting of guanidine; galegine; phenobarbital; A-769662; PT1; and salicylate. 
     
     
         37 . The method of  claim 29 , comprising administering a PTEN activator selected from the group consisting of di-C8-phosphatidylinositol 4,5-P2 (PI(4,5)P2) and PI(5)P. 
     
     
         38 . The method of  claim 29 , comprising administering an AMPK activator selected from the group consisting of 5-Aminoimidazole-4-carboxamide riboside (AICA riboside or AICAR); ZMP; guanidine; galegine; metformin (dimethylbiguanide); phemformin (phenethylbiguanide); pemetrexed; pioglitazone; troglitazone; phenobarbital; A-769662; PT1; and salicylate. 
     
     
         39 . The method of  claim 29 , comprising administering a PTEN activator selected from the group consisting of di-C8-phosphatidylinositol 4,5-P2 (PI(4,5)P2) and PI(5)P.

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