Compositions and methods for treating ocular diseases and conditions
View Patent ↗The present invention relates to compositions and methods for prevention and treatment of diseases and conditions, particularly ocular diseases and conditions, characterized by aberrant fibrogenesis or scarring, inflammation, and/or aberrant neovascularization or angiogenesis. The compositions and methods of the invention utilize immune-derived moieties that are specifically reactive against the bioactive lipid, sphingosine-1-phosphate, and its variants, which moieties are capable of decreasing the effective concentration of bioactive lipid being targeted. In one embodiment, the immune-derived moiety is a humanized monoclonal antibody that is reactive against sphingosine-1-phosphate.
1. A method for treating an ocular disease or disorder correlated with an elevated level of sphingosine-1-phosphate (S1P), comprising delivering to a tissue of a target eye of a subject in need of such treatment an amount of a composition effective to treat the ocular disease or disorder, thereby treating the ocular disease or disorder in the target eye, wherein the composition comprises an antibody or antigen-binding antibody fragment reactive against S1P under physiological conditions, and wherein the ocular disease or disorder is selected from the group consisting of scar formation neovascularization angiogenesis or inflammation.
2. A method according to claim 1 wherein the ocular disease or disorder correlated with an elevated level of S1P is selected from the group consisting of age-related macular degeneration, choroidal neovascularization, chronic uveitis, chronic vitritis, corneal graft rejection, diabetic retinopathy, retinopathy of prematurity, sickle cell retinopathy, idiopathic polypoidal choroidal vasculopathy, an ischemic retinopathy, laser injury, retinal venous occlusive disease, neovascular glaucoma, macular pucker, cellophane retinopathy, ERM formation, contact lens ovenvear, tractional retinal detachment, proliferative vitreoretinopathy, traumatic ocular injury, ocular cicatricial pemphigoid, ocular histoplasmosis, retinal angiomatous proliferation, Stevens Johnson Syndrome, toxic epidermal necmlysis, pterygium, an infection of the cornea, and a consequence of ocular surgery.
3. A method according to claim 2 , wherein the infection of the cornea is selected from the group consisting of herpes simplex infection, herpes zoster infection, and a protozoan infection.
4. A method according to claim 2 , wherein the ocular surgery is selected from the group consisting of refractive surgery, vitrectomy, and glaucoma surgery.
5. A method according to claim 2 , wherein the ocular disease or disorder correlated with an elevated level of S1P is characterized at least in part by aberrant neovascularization, aberrant fibrogenesis, fibrosis, scarring, and/or inflammation.
6. A method according to claim 1 , wherein the composition is administered systemically, intraocularly, or topically.
7. A method according to claim 2 wherein the age-related macular degeneration is dry age-related macular degeneration.
8. A method according to claim 2 wherein the age-related macular degeneration is wet age-related macular degeneration.
9. A method according to claim 1 wherein the antibody is a monoclonal antibody.
10. A method according to claim 1 wherein the antibody is a humanized monoclonal antibody.
11. A method according to claim 1 wherein the antigen-binding antibody fragment is derived from a monoclonal antibody, optionally a humanized monoclonal antibody.