Treatment of ocular neovascularization using anti-VEGF proteins

A method for the treatment of ocular neovascularization in a human subject having ocular neovascularization, the method comprising:

• administering to an eye of the human subject a single dose of a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a recombinant virus comprising a nucleic acid sequence encoding an anti-Vascular Endothelial Growth Factor (VEGF) protein, wherein the single dose comprises at least 1 ×1010 and at most 1×1013 vector genomes of the recombinant virus and is sufficient to reduce the ocular neovascularization in the subject for at least one year after the administration of the pharmaceutical composition, wherein between about 5 to 10 days prior to the administration of the pharmaceutical composition a first intravitreal injection of an anti-VEGF agent is administered into the eye of the subject in an amount such that at the time of the administration of the pharmaceutical composition the anti-VEGF agent is present in the eye of the subject at a concentration sufficient to prevent progression of the ocular neovascularization,
• wherein the subject does not require rescue treatment with an anti-VEGF agent to arrest or reverse progression of the ocular neovascularization at any time after about 90 days and for at least one year following the administration of the pharmaceutical composition, and
• wherein the nucleic acid sequence comprises in the following order:
• a) a first ITR sequence;
• b) a promoter sequence;
• c) an intron sequence;
• d) a first UTR sequence;
• e) the sequence encoding the anti-VEGF protein;
• f) a second UTR sequence;
• g) a poly A sequence;
• and
• h) a second ITR sequence,
• wherein the promoter sequence and the sequence encoding the anti-VEGF protein are separated by a sequence that is 300 base pairs or more.