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AssigneeYale University
InventorsAlan Garen, Ron Adelman, Zhiwei Hu
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Methods and compositions are provided for the treatment of diseases such as exudative macular degeneration, diabetic retinopathy, retinopathy of prematurity, choroidal neovascularization, retinal neovascularization, iris neovascularization, corneal neovascularization, ocular tumors, and other disorders of the eye, cancer, and inflammatory disorders. The method involves administering a conjugate, referred to as fVIIPD, containing a photosensitizer and a targeting molecule such as factor VII (“fVII”), fVIIa, or modified fVII, which binds with high affinity and specificity to tissue factor (TF). TF is more highly expressed, abnormally expressed or specifically expressed on endothelial cells lining the luminal surface of pathological neovasculature, than on normal vasculature, thus providing a specific and accessible therapeutic target. Following administration of fVIIPD, the compound specifically binds to the pathological neovasculature of the eye by interaction of the targeting molecule with TF expressed by endothelial cells within abnormal blood vessels. The photosensitizer may then be activated with a non-thermal laser light for selective destruction of abnormal vasculature.
A conjugate comprising a photosensitizer conjugated to a targeting molecule wherein the conjugate selectively targets a molecule expressed at a higher level on endothelial cells lining the luminal surface of pathological neovasculature, as compared to normal vasculature.
A method of treating a disorder characterized by uncontrolled or pathological angiogenesis comprising administering a conjugate comprising a photosensitizer conjugated to a targeting molecule, wherein the conjugate selectively targets a molecule expressed at a higher level on endothelial cells lining the luminal surface of pathological neovasculature, as compared to normal vasculature, in a pharmaceutically acceptable carrier for intravenous or intravitreous administration, and exposing the conjugate to a laser causing photoexcitation in an amount effective to kill cells at the site where the conjugate binds.
Dependencies are inferred from the claim text.