Granted Patent
B2
US 12,415,841 · App. 18/345,226 · Granted Sep 16, 2025
Delivery of card protein as therapy for occular inflammation
Inventors:
Cristhian J. Ildefonso (Gainesville, FL); Alfred S. Lewin (Gainesville, FL); Qiuhong Li (Gainesville, FL)
C07K14/4703A61K9/0048A61K48/005A61K38/00A61K48/00C07K2319/02C07K2319/03C07K2319/10C12N15/86C12N2740/15041C12N2750/14141
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Abstract
The present invention provides methods and compositions for treating and/or preventing age related macular degeneration and other conditions involving macular degeneration, ocular neovascularization, or ocular inflammation. In an exemplary embodiment, a method is disclosed that involves administering an expression vector that delivers a secretable and cell penetrating CARD to a subject in need of treatment or prevention of age-related macular degeneration or another condition involving macular degeneration or ocular neovascularization.
Claims (19)
1. A pharmaceutical composition for delivery into the suprachoroidal space comprising: i) a recombinant adeno-associated virus (rAAV) vector comprising an expression construct comprising (a) a nucleotide sequence encoding a fusion protein comprising a cell-penetrating peptide derived from the HIV Tat protein (Tat) which comprises amino acids 1-9 of the amino acid sequence of SEQ ID NO: 1 and a Caspase Activation and Recruitment Domain (CARD) which comprises amino acids 10-100 of the amino acid sequence of SEQ ID NO: 1, and (b) a nucleotide sequence encoding a secretion signal peptide, wherein the expression construct is flanked by inverted terminal repeat (ITR) regions; and ii) a carrier, a diluent and/or an excipient.
2. The pharmaceutical composition of claim 1 , wherein the secretion signal peptide is an IgK signal peptide.
3. The pharmaceutical composition of claim 1 , wherein the rAAV vector is an AAV1 vector or an AAV2 vector.
4. An ocular device loaded with the pharmaceutical composition of claim 1 .
5. A method for the amelioration or treatment of an ocular disease or ocular condition in a subject, the method comprising:
administering to the suprachoroidal space of the subject's eye a therapeutically effective amount of a recombinant adeno-associated virus (rAAV) vector comprising an expression construct comprising (a) a nucleotide sequence encoding a fusion protein comprising a cell-penetrating peptide derived from the HIV Tat protein (Tat) which comprises amino acids 1-9 of the amino acid sequence of SEQ ID NO: 1 and a Caspase Activation and Recruitment Domain (CARD) which comprises amino acids 10-100 of the amino acid sequence of SEQ ID NO: 1, and (b) a nucleotide sequence encoding a secretion signal peptide, wherein the expression construct is flanked by inverted terminal repeat (ITR) regions.
6. The method of claim 5 , wherein the ocular disease or ocular condition is selected from the group consisting of ocular inflammation, macular degeneration, age-related macular degeneration (AMD), geographic atrophy, wet AMD, dry AMD, drusen formation, dry eye, diabetic retinopathy, vitreoretinopathy, corneal inflammation, uveitis, ocular hypertension and glaucoma.
7. The method of claim 6 , wherein the ocular disease or ocular condition is glaucoma.
8. The method of claim 5 , wherein the secretion signal peptide is an IgK signal peptide.
9. The method of claim 5 , wherein the rAAV vector is an AAV1 vector or an AAV2 vector.
10. The method of claim 5 , wherein said method comprises treating a subject who exhibits one or more of the following symptoms: drusen formation, eye pain, eye redness, light sensitivity, tearing, or blurred vision.
11. The method of claim 5 , wherein said method comprises treating a subject who exhibits two or more of the following symptoms: drusen, eye pain, eye redness, light sensitivity, tearing, or blurred vision.
12. A nucleic acid comprising a nucleotide sequence encoding a fusion protein comprising (a) a cell-penetrating peptide derived from the HIV Tat protein (Tat) which comprises amino acids 1-9 of the amino acid sequence of SEQ ID NO: 1 and a Caspase Activation and Recruitment Domain (CARD) which comprises amino acids 10-100 of the amino acid sequence of SEQ ID NO: 1, and (b) a secretion signal peptide.
13. The nucleic acid of claim 12 , wherein the nucleotide sequence comprises: (a) nucleotides 1-27 of the nucleic acid sequence of SEQ ID NO: 2 and (ii) nucleotides 28-300 of the nucleic acid sequence of SEQ ID NO: 2; and (b) a nucleotide sequence encoding the secretion signal peptide.
14. The nucleic acid of claim 12 , wherein the secretion signal peptide is an IgK signal peptide.
15. An expression construct comprising the nucleic acid of claim 12 and a promoter.
16. A recombinant adeno-associated virus (rAAV) vector comprising the expression construct of claim 15 , wherein the expression construct is flanked by inverted terminal repeat (ITR) regions.
17. A method of preparing a recombinant adeno-associated virus (rAAV), the method comprising co-transfecting (i) a plasmid containing the nucleic acid of claim 12 , wherein the nucleic acid is flanked by AAV inverted terminal repeat (ITR) regions; and (ii) a plasmid carrying AAV encapsidation genes, into a cell line which is infected with a human helper virus.
18. The rAAV prepared by the method of claim 17 .
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Oct 17, 2023
From: ILDEFONSO, CRISTHIAN J.; LEWIN, ALFRED S.; LI, QIUHONG
To: UNIVERSITY OF FLORIDA RESEARCH FOUNDATION, INCORPORATED
Reel/Frame 065252/0780 →
Continuity (4)
Continuation
14775289
Provisional Application
61776076
· Mar 11, 2013
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