Granted Patent B2

US 12,410,446 · App. 18/051,821 · Granted Sep 9, 2025

Inventors: Charles David Pauza (Rockville, MD); Haishan Li (Rockville, MD); Tyler Lahusen (Rockville, MD); Mei-Ling Liou (Rockville, MD)

Assignee: AMERICAN GENE TECHNOLOGIES INTERNATIONAL INC.

C12N15/86A61K31/675A61K31/7105A61K38/16C12N5/0636C12N15/113A61K2039/5158A61K48/00C12N5/00C12N2310/14C12N2310/141C12N2310/531

Abstract

Claims (31)

1. A viral vector comprising:

an EF-1 alpha promoter and

at least one encoded shRNA or microRNA that, when expressed, inhibits production of farnesyl diphosphate synthase (FDPS),

wherein the at least one encoded shRNA or microRNA comprises a sequence having at least 80 percent identity with SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, or SEQ ID NO: 10.

2. The viral vector of claim 1 , wherein the at least one encoded shRNA or microRNA activates a gamma delta T cell (GD T cell).

3. An immunotherapy-based system comprising:

(a) at least one helper plasmid comprising DNA sequences for expressing a functional protein derived from each of a gag, pol, and rev gene;

(b) an envelope plasmid comprising a DNA sequence for expressing an envelope protein capable of infecting a target cell; and

(c) a therapeutic vector comprising:

an EF-1 alpha promoter and

at least one encoded shRNA or microRNA that, when expressed, inhibits production of farnesyl diphosphate synthase (FDPS),

wherein the at least one encoded shRNA or microRNA comprises a sequence having at least 80 percent identity with SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, or SEQ ID NO: 10.

4. The immunotherapy-based system of claim 3 , wherein the target cell is a cancer cell.

5. The immunotherapy-based system of claim 4 , wherein the at least one encoded shRNA or microRNA activates a GD T cell.

6. A method of treating a condition associated with the mevalonate pathway in a subject in patients in need thereof, the method comprising administering or having administered a therapeutically-effective amount of an immunotherapy-based composition comprising:

(a) at least one helper plasmid comprising DNA sequences for expressing a functional protein derived from each of a gag, pol, and rev gene;

(b) an envelope plasmid comprising a DNA sequence for expressing an envelope protein capable of infecting a target cell; and

(c) a therapeutic vector comprising:

an EF-1 alpha promoter and

at least one encoded shRNA or microRNA that, when expressed, inhibits production of farnesyl diphosphate synthase (FDPS),

wherein the at least one encoded shRNA or microRNA comprises a sequence having at least 80 percent identity with SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, or SEQ ID NO: 10.

7. The method of claim 6 , wherein the at least one encoded shRNA or microRNA activates a GD T cell.

8. The method of claim 6 , wherein the condition associated with the mevalonate pathway is a cancer, and wherein the target cell is a cancer cell.

9. The method of claim 8 , wherein the at least one encoded shRNA or microRNA activates a GD T cell.

10. A method of treating a condition associated with the mevalonate pathway in a subject in patients in need thereof, the method comprising administering or having administered a therapeutically-effective amount of a viral vector comprising:

an EF-1 alpha promoter and

at least one encoded shRNA or microRNA that, when expressed, inhibits production of farnesyl diphosphate synthase (FDPS),

wherein the at least one encoded shRNA or microRNA comprises a sequence having at least 80 percent identity with SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, or SEQ ID NO: 10.

11. The method of claim 10 , wherein the condition associated with the mevalonate pathway is a cancer.

12. A method of treating a condition associated with the mevalonate pathway in a subject in patients in need thereof, the method comprising administering or having administered a therapeutically-effective amount of a viral vector comprising at least one encoded shRNA or microRNA that, when expressed, inhibits production of farnesyl diphosphate synthase (FDPS) and activates a GD T cell, wherein the at least one encoded shRNA or microRNA comprises a sequence having at least 80 percent identity with SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, or SEQ ID NO: 10.

13. The method of claim 12 , wherein the condition associated with the mevalonate pathway is a cancer.

Assignments (1)

Continuity (8)

References Cited (400)