COMPOSITIONS AND METHODS FOR REDUCING OCULAR NEOVASCULARIZATION
The present disclosure provides pharmaceutical compositions and methods thereof for the prevention or treatment of ocular neovascularization, such as AMD, in a subject, by administering to the subject a pharmaceutical composition comprising a rAAV vector having a nucleic acid sequence that encodes an anti-VEGF agent.
1 . A method of treating an eye disease or condition, the method comprising administering a unit dose of a pharmaceutical composition by intravitreal injection to an eye of a primate subject in need thereof, wherein of the pharmaceutical suspension comprises:
(a) a rAAV2 variant comprising an amino acid sequence LGETTRP (SEQ ID NO: 1) inserted between positions 587 and 588 of capsid protein VP1, a nucleic acid comprising a sequence having at least 95% homology to SEQ ID NO: 9 and a sequence having at least 95% homology to SEQ ID NO: 10, and
(b) a pharmaceutically acceptable excipient.
2 . The method of claim 1 , wherein the unit dose is between 2E12 to 6E12 vector genomes.
3 . (canceled)
4 . The method of claim 1 , wherein the subject is a human.
5 . The method of claim 1 , wherein the eye condition or disease is neovascular (wet) age-related macular degeneration (AMD), macular edema following retinal vein occlusion, diabetic macular edema (DME), retinal vein occlusion, or diabetic retinopathy associated with DME.
6 . The method of claim 1 , wherein the eye condition or disease is choroidal neovascularization or AMD.
7 . The method of claim 1 , wherein administering the suspension results in a reduction in percentage of grade IV lesions by at least 5% as compared to a vehicle control, as measured by color fundus photography.
8 . The method of claim 7 , wherein the reduction in percentage of grade IV lesions is at least 10%.
9 . The method of claim 1 , wherein the unit dose comprises has a volume that is not more than 100 µL.
10 . The method of claim 1 , wherein the unit dose comprises has a volume that is not more than 50 µL.
11 . (canceled)
12 . The method of claim 1 , wherein the subject is responsive to at least one of ranibizumab, bevacizumab, and sVEGFR-1.
13 . The method of claim 1 , wherein the subject has been pre-treated with ranibizumab or bevacizumab.
14 - 15 . (canceled)
16 . The method of claim 1 , wherein the administering by injection occurs not more than once in at least 2 years.
17 . The method of claim 1 , wherein the administering by injection occurs not more than once in at least 5 years.
18 . The method of claim 1 , wherein the administering is a one-time administration.
19 . The method of claim 1 , further comprising agitating the suspension to ensure even distribution prior to the administering step.
20 . The method of claim 1 , further comprising warming the suspension to room temperature prior to the administering step.
21 . The method of claim 1 , wherein the suspension further comprises a surfactant.
22 . The method of claim 21 , wherein the surfactant is selected from polysorbates, sodium dodecyl sulfate, sodium lauryl sulfate, lauryl dimethyl amine oxide, polyethoxylated alcohols, polyoxyethylene sorbitan, octoxynol, Brij, pluronic, and polyoxyl castor oil.
23 . The method of claim 1 , wherein the suspension further comprises phenol, mannitol, sorbitol, or sodium chloride.
24 . The method of claim 1 , further comprising administering an antibiotic solution or an atropine sulfate ointment after the injection.
25 . The method of claim 24 , wherein the antibiotic solution comprises ciprofloxacin.
26 - 67 . (canceled)
68 . The method of claim 1 , wherein the rAAV2 variant comprises a nucleic acid comprising the sequence of SEQ ID NO: 9 and the sequence of SEQ ID NO: 10.