Granted Patent B2

US 12,454,701 · App. 17/299,434 · Granted Oct 28, 2025

Inventors: Timothy J. Miller (New York, NY); Linas Padegimas (Mayfield, OH)

Assignee: Abeona Therapeutics Inc.

C12N15/86A61K48/0058C07K14/005C07K14/4712C07K14/705C12N9/2411C12N9/2465C12Y302/0102C12Y302/01022C12N2750/14122C12N2750/14143C12N2750/14171

Abstract

Claims (38)

1. A nucleic acid encoding an AAV capsid protein comprising a VP1 portion, a VP2 portion, and a VP3 portion, wherein the VP3 portion comprises the amino acid sequence of SEQ ID NO: 41.

2. The nucleic acid of claim 1 , wherein the encoded AAV capsid protein comprises the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, or SEQ ID NO: 34.

3. The nucleic acid of claim 1 , wherein the nucleic acid comprises a sequence at least 95% identical to the nucleotide sequence selected from SEQ ID NOS: 18 and 20-23.

4. The nucleic acid of claim 3 , wherein the nucleic acid sequence is 100% identical to the nucleotide sequence selected from SEQ ID NOS: 18 and 20-23.

5. A vector comprising the nucleic acid of claim 1 .

6. An AAV capsid protein encoded by the nucleic acid of claim 1 .

7. The AAV capsid protein of claim 6 , wherein the protein comprises the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, or SEQ ID NO: 34.

8. An AAV viral vector comprising an AAV capsid protein and an AAV vector genome, wherein the AAV capsid protein comprises a VP1 portion, a VP2 portion, and a VP3 portion, wherein the VP3 portion comprises the amino acid sequence of SEQ ID NO: 41, and wherein the AAV vector genome comprises in 5′ to 3′ orientation,

(a) a first AAV inverted terminal repeat,

(b) a promoter,

(c) a heterologous nucleic acid,

(d) a poly-A tail, and

(e) a second AAV inverted terminal repeat,

wherein the heterologous nucleic acid is operably linked to the promoter.

9. The AAV viral vector of claim 8 , wherein the promoter is a constitutive promoter.

10. The AAV viral vector of claim 8 , wherein the heterologous nucleic acid encodes a polypeptide.

11. The AAV viral vector of claim 8 , wherein the heterologous nucleic acid encodes an mRNA, antisense RNA, microRNA, or RNAi.

12. The AAV viral vector of claim 8 , wherein the AAV capsid protein comprises the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, or SEQ ID NO: 34.

13. An AAV viral vector comprising:

(i) an AAV capsid protein having the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, or SEQ ID NO: 34, and

(ii) an AAV vector genome, wherein the AAV vector genome comprises in 5′ to 3′ orientation,

(a) a first AAV inverted terminal repeat,

(b) a promoter,

(c) a heterologous nucleic acid,

(d) a poly-A tail, and

(e) a second AAV inverted terminal repeat.

14. The AAV viral vector of claim 13 , wherein the heterologous nucleic acid encodes an mRNA, siRNA, gRNA, or microRNA.

15. The AAV viral vector of claim 13 , wherein the heterologous nucleic acid encodes a polypeptide.

16. The AAV viral vector of claim 15 , wherein the heterologous nucleic acid encodes a cystic fibrosis transmembrane conductance regulator (CFTR), a CLN3 protein, an alpha-galactosidase A (GLA), or an acid alpha-glucosidase (GAA).

17. The AAV viral vector of claim 16 , wherein the heterologous nucleic acid encodes a CFTR.

18. The AAV viral vector of claim 17 , wherein the CFTR comprises an amino acid sequence encoded by SEQ ID NO: 4.

19. The AAV viral vector of claim 15 , wherein the heterologous nucleic acid encodes a protein comprising an amino acid sequence with at least 70%, 80%, 90%, or 99% identity with any one of SEQ ID NOs: 8, 11, and 14.

20. The AAV viral vector of claim 15 , wherein the heterologous nucleic acid comprises a sequence with at least 70%, 80%, 90%, or 99% identity with any one of SEQ ID NOs: 4, 5, 6, 7, 9, 10, 12, and 13.

21. The AAV viral vector of claim 8 , wherein the promoter is a Rous sarcoma virus (RSV) LTR promoter, a cytomegalovirus (CMV) promoter, an SV40 promoter, a dihydrofolate reductase promoter, a beta-actin promoter, a phosphoglycerol kinase (PGK) promoter, a U6 promoter, an H1 promoter, a CAG promoter, a hybrid chicken beta-actin promoter, an MeCP2 promoter, an EF1 promoter, a ubiquitous chicken β-actin hybrid (CBh) promoter, a U1a promoter, a U1b promoter, an MeCP2 promoter, an MeP418 promoter, an MeP426 promoter, a minimal MeCP2 promoter, a VMD2 promoter, an mRho promoter, EF1a promoter, Ubc promoter, human β-actin promoter, TRE promoter, Ac5 promoter, Polyhedrin promoter, CaMKIIa promoter, Gal1 promoter, TEF1 promoter, GDS promoter, ADH1 promoter, Ubi promoter, or α-1-antitrypsin (hAAT) promoter.

22. A method of introducing a heterologous nucleic acid to a cell in a subject, comprising administering the AAV viral vector of claim 8 to the subject, wherein the AAV viral vector comprises the heterologous nucleic acid.

23. The method of claim 22 , wherein the AAV viral vector is administered to the subject orally, rectally, transmucosally, inhalationally, transdermally, parenterally, intravenously, subcutaneously, intradermally, intramuscularly, intrapleurally, intracerebrally, intrathecally, intracerebrally, intraventricularly, intranasally, intra-aurally, intra-ocularly, peri-ocularly, topically, intralymphatically, intracistemally, subretinally, or intravitreally.

24. The method of claim 22 , wherein the subject has Stargardt disease, amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), Fabry disease, Pompe disease, CLN3 disease (or Juvenile Neuronal Ceroid Lipofuscinosis), recessive dystrophic epidermolysis bullosa (RDEB), juvenile Batten disease, autosomal dominant disorder, muscular dystrophy, hemophilia A, hemophilia B, multiple sclerosis, diabetes mellitus, Gaucher disease cancer, arthritis, muscle wasting, heart disease, intimal hyperplasia, epilepsy, Huntington's disease, Parkinson's disease, Alzheimer's disease, cystic fibrosis, thalassemia, Hurler's Syndrome, Sly syndrome, Scheie Syndrome, Hurler-Scheie Syndrome, Hunter's Syndrome, Sanfilippo Syndrome A (mucopolysaccharidosis IIIA or MPS IIIA), Sanfilippo Syndrome B (mucopolysaccharidosis IIIB or MPS IIIB), Sanfilippo Syndrome C, Sanfilippo Syndrome D, Morquio Syndrome, Maroteaux-Lamy Syndrome, Krabbe's disease, phenylketonuria, Batten's disease, spinal cerebral ataxia, LDL receptor deficiency, hyperammonemia, arthritis, macular degeneration, retinitis pigmentosa, ceroid lipofuscinosis, neuronal, 1 (CLN1), or adenosine deaminase deficiency.

25. The method of claim 22 , wherein the subject is a mammal.

Assignments (2)

Continuity (5)

References Cited (120)