IP Library › Granted Patent US 12,390,539
Granted Patent B2
US 12,390,539 · App. 17/612,653 · Granted Aug 19, 2025

Minigene therapy

Inventors: Guangping Gao (Worcester, MA); Hemant Khanna (Worcester, MA)
Assignee: University of Massachusetts
A61K48/0058A61K35/76A61P27/02C07K14/705C12N5/0621C12N7/00C12N15/113C12N15/86C12N2310/10C12N2750/14122C12N2750/14142C12N2830/008
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Quick Facts
Patent No.
US 12,390,539
App. No.
17/612,653
Granted
Aug 19, 2025
Kind
B2
Abstract

Aspects of the disclosure relate to compositions and methods useful for treating ocular ciliopathies, for example Leber congenital amaurosis (LCA). In some embodiments, the disclosure provides isolated nucleic acids comprising a transgene encoding a CEP290 protein fragment, and methods of treating ocular ciliopathies using the same.

Claims (18)

1. An isolated nucleic acid comprising a transgene encoding a CEP290 fragment having the amino acid sequence set forth in SEQ ID NO: 19 operably linked to a promoter, wherein the promoter is a retinoschisin promoter, K12 promoter, a rhodopsin promoter, a rhodopsin kinase promoter, or an interphotoreceptor retinoid-binding protein proximal (IRBP) promoter, optionally wherein the rhodopsin kinase promoter is a GRK1 promoter.

2. The isolated nucleic acid of claim 1 , wherein the CEP290 fragment is encoded by a nucleic acid having the sequence set forth in SEQ ID NO: 19.

3. The isolated nucleic acid of claim 1 , wherein the transgene is flanked by adeno-associated virus (AAV) inverted terminal repeats (ITRs).

4. A recombinant adeno-associated virus (rAAV) comprising:

(i) a capsid protein; and,

(ii) the isolated nucleic acid of claim 1 .

5. The rAAV of claim 4 , wherein the capsid protein is AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAVrh8, AAV9, or AAV10 capsid protein, optionally wherein the capsid protein comprises the sequence set forth in SEQ ID NO: 9.

6. A composition comprising the rAAV of claim 4 , and a pharmaceutically acceptable excipient.

7. A recombinant adeno-associated virus (rAAV) vector comprising an expression cassette comprising a nucleic acid encoding the amino acid sequence set forth in SEQ ID NO: 19 operably linked to a promoter, wherein the expression cassette is flanked by adeno-associated virus 2 (AAV2) inverted terminal repeats (ITRs).

8. The rAAV vector of claim 7 , wherein the nucleic acid comprises the sequence set forth in SEQ ID NO: 29 or 34.

9. The rAAV vector of claim 7 , wherein the expression cassette comprises an intron positioned between the promoter and the nucleic acid sequence encoding the amino acid sequence set forth in SEQ ID NO: 19, optionally wherein the intron comprises a chicken beta-actin intron, a synthetic intron, or a MBL intron.

10. A recombinant adeno-associated virus (rAAV) comprising:

(i) a nucleic acid encoding the amino acid sequence set forth in SEQ ID NO: 19 operably linked to a promoter, wherein the expression cassette is flanked by adeno-associated virus 2 (AAV2) inverted terminal repeats (ITRs); and

(ii) one or more AAV capsid proteins.

11. The rAAV of claim 10 , wherein the one or more AAV capsid proteins are AAV 8 capsid proteins or AAV5 capsid proteins.

12. The rAAV of claim 10 , wherein the promoter is a rhodopsin kinase (RK) promoter or a chicken beta-actin promoter.

13. The rAAV of claim 10 further comprising an intron positioned between the promoter and the nucleic acid sequence encoding the amino acid sequence set forth in SEQ ID NO: 19.

14. The rAAV of claim 13 , wherein the intron comprises a chicken beta-actin intron, a synthetic intron, or a MBL intron.

Assignments (4)
RELEASE OF SECURITY INTEREST Recorded Jul 17, 2023
From: HERCULES CAPITAL, INC.
To: IVERIC BIO, INC.; IVERIC BIO GENE THERAPY LLC; ORION OPHTHALMOLOGY LLC
Reel/Frame 064286/0472 →
PARTIAL RELEASE OF SECURITY INTEREST Recorded Jun 9, 2023
From: HERCULES CAPITAL, INC.
To: IVERIC BIO, INC.
Reel/Frame 063942/0664 →
SECURITY INTEREST Recorded Aug 5, 2022
From: IVERIC BIO, INC.
To: HERCULES CAPITAL, INC.
Reel/Frame 061088/0048 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 15, 2022
From: GAO, GUANGPING; KHANNA, HEMANT
To: UNIVERSITY OF MASSACHUSETTS
Reel/Frame 059262/0927 →
Continuity (4)
Provisional Application 62967521 · Jan 29, 2020
Provisional Application 62899601 · Sep 12, 2019
Provisional Application 62850405 · May 20, 2019
Related Publication 20220233720A1 · Jul 28, 2022
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