Treatment of ocular neovascularization using anti-vegf proteins

Abstract

The present disclosure provides compositions and methods for the prevention or treatment of ocular neovascularization, such as AMD, in a human subject, by administering subretinally a pharmaceutical composition comprising a pharmaceutically effective amount of a vector comprising a nucleic acid encoding soluble Fms-related tyrosine kinase-1 (sFlt-1) protein to the human subject.

1 - 41 . (canceled) 
     
     
         42 . A method for the treatment of ocular neovascularization in an eye of a human subject suffering from ocular neovascularization, the method comprising:
 i) administering a first dose of a Vascular Endothelial Growth Factor (VEGF) inhibitor to the eye of the human subject, said first dose being sufficient to prevent progression of the ocular neovascularization for a first time period;   ii) during the first time period, administering to the eye of the human subject a unit dose comprising at least 1×10 6  and at most 1×10 15  vector genomes of a recombinant adeno-associated virus (rAAV) and a pharmaceutically acceptable carrier, wherein the rAAV comprises a nucleic acid sequence encoding an anti-VEGF protein; and   iii) administering one or two doses of a VEGF inhibitor in within the 30 day interval following administration of the rAAV.   
     
     
         43 . The method of  claim 42 , wherein the anti-VEGF protein comprises a sequence having at least 90% sequence identity to SEQ ID NO: 121. 
     
     
         44 . The method of  claim 42 , wherein the anti-VEGF protein is aflibercept. 
     
     
         45 . The method of  claim 42 , wherein the step of administering the rAAV is performed only once in at least 18 months. 
     
     
         46 . The method of  claim 42 , wherein the unit dose comprises at least 1×10 8  and at most 3×10 13  vector genomes. 
     
     
         47 . The method of  claim 44 , wherein the unit dose comprises at least 1×10 9  and at most 3×10 13  vector genomes. 
     
     
         48 . The method of  claim 42 , further comprising the step of measuring visual acuity by Early Treatment Diabetic Retinopathy Study (ETDRS) letters after the administering of the pharmaceutical composition, wherein a reduction in neovascularization is observed by Fluorescein Angiography (FA) following the administering of the rAAV, or wherein the best corrected visual acuity (BCVA) of the human subject decreases by fewer than 15 letters as measured by ETDRS letters following the administering of the pharmaceutical composition, or wherein the BCVA of the human subject improves by at least 1 line as measured by ETDRS letters following the administering of the unit dose. 
     
     
         49 . The method of  claim 42 , wherein the unit dose of rAAV is administered by subretinal ij ection. 
     
     
         50 . The method of  claim 42 , wherein the VEGF-inhibitor is selected from the group consisting of bevacizumab, ranibizumab, and aflibercept. 
     
     
         51 . The method of  claim 42 , wherein the step of administering a first does of a VEGF inhibitor is performed at least 24 hours prior to the step of administering the rAAV. 
     
     
         52 . The method of  claim 42 , wherein the step of administering a first does of a VEGF inhibitor is performed at least 5 days prior to the step of administering the rAAV. 
     
     
         53 . The method of  claim 42 , wherein the step of administering a first does of a VEGF inhibitor is performed between 1 and 30 days prior to the step of administering the rAAV. 
     
     
         54 . The method of  claim 42 , wherein the step of administering a first does of a VEGF inhibitor is performed between 5 and 10 days prior to the step of administering the rAAV.