IP Library › Granted Patent US 12,201,697
Granted Patent B2
US 12,201,697 · App. 17/407,718 · Granted Jan 21, 2025

AAV-IDUA vector for treatment of MPS I-associated blindness

Inventors: Matthew Louis Hirsch (Chapel Hill, NC); Richard Jude Samulski (Chapel Hill, NC)
Assignee: The University of North Carolina at Chapel Hill
A61K48/00A61K9/0019A61K9/0048A61K35/76A61P27/00C07K14/00C12N9/2402C12N9/2411C12N15/86C12Y302/01076C12N2710/10044C12N2750/14141C12N2750/14143C12N2800/22
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Quick Facts
Patent No.
US 12,201,697
App. No.
17/407,718
Granted
Jan 21, 2025
Kind
B2
Abstract

This invention relates to viral vectors for delivery of alpha-L-iduronidase to the cornea of a subject and methods of using the same for treatment and prevention of corneal clouding and blindness in a subject due to mucopolysaccharidosis I.

Claims (17)

1. A recombinant nucleic acid comprising a sequence encoding human alpha-L-iduronidase (IDUA), wherein the nucleotide sequence has been codon-optimized for expression in human cells, and wherein the recombinant nucleic acid comprises a nucleotide sequence at least 90% identical to SEQ ID NO:1.

2. The recombinant nucleic acid of claim 1 , comprising the nucleotide sequence of SEQ ID NO: 1.

3. An adeno-associated virus (AAV) vector genome comprising the nucleic acid of claim 1 .

4. The AAV vector genome of claim 3 , wherein the nucleic acid is operably linked to a constitutive promoter.

5. A cell in vitro comprising the AAV vector genome of claim 3 .

6. The cell of claim 5 , wherein the vector genome is stably incorporated into the cell genome.

7. An AAV particle comprising the AAV vector genome of claim 3 .

8. The AAV particle of claim 7 , wherein the AAV particle is an AAV2, AAV8, or AAV9 particle.

9. The AAV particle of claim 7 , wherein the AAV particle is a chimeric AAV8/AAV9 particle.

10. A pharmaceutical formulation comprising the AAV particle of claim 7 and a pharmaceutically acceptable carrier.

11. A method of delivering IDUA to the cornea of a subject, comprising administering to the cornea of the subject an effective amount of the AAV particle of claim 7 , thereby delivering IDUA to the cornea of the subject.

12. A method of treating mucopolysaccharidosis I (MPS I)-associated corneal clouding in a subject in need thereof, comprising administering to the cornea of the subject a therapeutically effective amount of the AAV particle of claim 7 , thereby treating MPS I-associated corneal clouding in the subject.

13. A method of delivering IDUA to a cornea in vitro or ex vivo, comprising contacting the cornea with an effective amount of the AAV particle of claim 7 , thereby delivering IDUA to the cornea.

14. The method of claim 13 , further comprising transplanting the cornea to a subject in need thereof.

15. The method of claim 11 , wherein the AAV particle is administered to the cornea by intrastromal injection.

16. The method of claim 11 , wherein the AAV particle is administered to the cornea topically.

17. The method of claim 11 , wherein the subject is a human subject.

Assignments (1)
CHANGE OF NAME Recorded Nov 10, 2023
From: GRAYBUG VISION, INC.
To: CALCIMEDICA, INC.
Reel/Frame 065537/0884 →
Continuity (3)
Division 16076654
Provisional Application 62298126 · Feb 22, 2016
Related Publication 20220047721A1 · Feb 17, 2022
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