Novel treatment for eye disease

Abstract

This invention discloses methods, kits, and instructions to treat neovasculature diseases of the eye through the administration of a targeted photosensitizing agent and subsequent exposure to light of specific wavelength sufficient to photoactivate photosensitizing agent. The photosensitizing agent is bound to a composition that mediates site specific delivery to a neovasculature target tissue of a therapeutically effective amount of a photosensitizing agent that is activated by a relatively low fluence rate of light over a prolonged period of time. Diseases treatable under this invention, include: diabetic retinopathy; macular degeneration; and malignant uveal melanomas.

The invention claimed is:  
     
         1 . A method to treat neovascular disease of the eye, comprising: 
 administering a targeted photosensitizing compound which selectively binds to abnormal endothelium that lines or composes neovasculature tissue; and    illuminating the neovasculature tissue with light for a period of time sufficient to activate the photosensitizing compound thereby causing damage to neovasculature tissue.    
     
     
         2 . The method of  claim 1 , wherein said light is non-laser light.  
     
     
         3 . The method of  claim 1 , wherein said light is laser light.  
     
     
         4 . The method of  claim 1 , wherein the neovasculature tissue is present in retina, choroid or both.  
     
     
         5 . The method of  claim 1 , wherein the treated neovascular disease is diabetic retinopathy.  
     
     
         6 . The method of  claim 1 , wherein the treated neovascular disease is macular degeneration.  
     
     
         7 . The method of  claim 1 , wherein the treated neovascular tissue arises from tumors of the eye.  
     
     
         8 . The method of  claim 1 , wherein said tumors are benign.  
     
     
         9 . The method of  claim 1 , wherein said tumors are malignant.  
     
     
         10 . The method of  claim 9 , wherein said tumors are malignant uveal melanomas.  
     
     
         11 . The method of  claim 1 , wherein the targeted photosensitizing compound is bound to a first component of a bindable pair and wherein a second component of the bindable pair is selected from the group consisting of: receptor present on abnormal endothelium; ligand bindable to receptor present on abnormal endothelium; antigen present on abnormal endothelium; and antibody bindable to antigen present on abnormal endothelium.  
     
     
         12 . The method of  claim 11 , wherein the targeted photosensitizing compound is incorporated into a liposomal preparation.  
     
     
         13 . The method of  claim 11 , wherein the ligand is selected from the group consisting of: the ED-B domain of fibronectin; antibody specifically elicited to ED-B domain of fibronectin; VEGF; VEGF receptor; and ανβ3 integrin receptor.  
     
     
         14 . The method of  claim 1 , wherein the targeted photosensitizing compound is bound to a receptor composition that mimics a receptor present on abnormal endothelium.  
     
     
         15 . The method of  claim 14 , wherein the targeted photosensitizing compound is incorporated into a liposomal preparation.  
     
     
         16 . The method of  claim 1 , wherein the targeted photosensitizing compound is bound to a bi-specific antibody construct that further comprises both a ligand component and a receptor component.  
     
     
         17 . The method of  claim 16 , wherein the targeted photosensitizing compound is incorporated into a liposomal preparation.  
     
     
         18 . The method of  claim 1 , wherein the photosensitized neovasculature is illuminated for at least 4 minutes.  
     
     
         19 . The method of  claim 1 , wherein the photosensitized neovasculature is illuminated for at least 20 minutes.  
     
     
         20 . The method of  claim 1 , wherein the photosensitized neovasculature is illuminated for at least 1 hour.  
     
     
         21 . The method of  claim 1 , wherein the photosensitized neovasculature is illuminated for at least 24 hours.  
     
     
         22 . The method of  claim 1 , wherein the neovasculature tissue is treated with a total fluence of light irradiation from between about 240 J/cm 2  to about 900 J/cm 2 .  
     
     
         23 . The method of  claim 1 , wherein the non-laser light source is a light emitting diode.  
     
     
         24 . The method of  claim 1 , wherein the non-laser light source is ambient light.  
     
     
         25 . A method to treat neovascular disease of the eye, comprising: 
 administering a first targeted photosensitizing compound which selectively binds to a first targeted tissue; and    administering a second targeted photosensitizing compound which selectively binds to a second targeted tissue; and    illuminating the first and second targeted tissues with non-laser light for a period of time sufficient to activate said first and second photosensitizing compounds thereby causing damage to said first and second targeted tissue.    
     
     
         26 . The method of  claim 25 , wherein said first targeted tissues is abnormal endothelium that lines or composes neovasculature tissue; and said second targeted tissue is a tumor antigen.  
     
     
         27 . The method of  claim 26 , wherein said first targeted photosensitizing compound comprises a ligand selected from the group consisting of: the ED-B domain of fibronectin; antibody specifically elicited to EDB domain of fibronectin; VEGF; VEGF receptor; and ανβ3 integrin receptor.  
     
     
         28 . A kit to treat neovascular disease of the eye, comprising a targeted photosensitizing compound and instructions teaching a method according to  claim 1 .  
     
     
         29 . A kit according to  claim 28  wherein the targeted photosensitizing compound binds to a first component of a bindable pair and wherein a second component of the bindable pair is selected from the group consisting of: receptor present on abnormal endothelium; ligand bindable to receptor present on abnormal endothelium; antigen present on abnormal endothelium; and antibody bindable to antigen present on abnormal endothelium.  
     
     
         30 . A kit according to  claim 29 , wherein the targeted photosensitizing compound is incorporated into a liposomal preparation.  
     
     
         31 . A kit according to  claim 29 , wherein the ligand is selected from the group consisting of: the ED-B domain of fibronectin; antibody specifically elicited to ED-B domain of fibronectin; VEGF; VEGF receptor; and ανβ3 integrin receptor.  
     
     
         32 . A kit according to  claim 28 , wherein the targeted photosensitizing compound binds to a receptor composition that mimics a receptor present on abnormal endothelium.  
     
     
         33 . A kit according to  claim 32 , wherein the targeted photosensitizing compound is incorporated into a liposomal preparation.  
     
     
         34 . A kit according to  claim 28 , wherein the targeted photosensitizing compound binds to a bi-specific antibody construct that further comprises both a ligand component and a receptor component.  
     
     
         35 . A kit according to  claim 34 , wherein the targeted photosensitizing compound is incorporated into a liposomal preparation.  
     
     
         36 . A method of instructing a person to treat neovascular disease of the eye, comprising instructing a person to conduct a method according to  claim 1 .  
     
     
         37 . A method of instructing a person to treat neovascular disease of the eye, comprising instructing a person in the use of the kit of claim  28 .