IP Library › Granted Patent US 12,331,081
Granted Patent B2
US 12,331,081 · App. 18/788,938 · Granted Jun 17, 2025

Capsid variants and methods of using the same

Inventors: Ina Chen (Sommerville, MA); Jeff Gerold (Cambridge, MA); Jerrah Holth (Sudbury, MA); Sylvain Lapan (Brookline, MA); Kathy S. Lin (Sommerville, MA); Samuel Wolock (Cambridge, MA)
Assignee: DYNO THERAPEUTICS, INC.
C07K14/015A61K48/0058C12N15/86C12N2750/14122C12N2750/14143C12N2750/14145
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Quick Facts
Patent No.
US 12,331,081
App. No.
18/788,938
Granted
Jun 17, 2025
Kind
B2
Abstract

The disclosure is directed in part to variant capsid polypeptides that can be used to deliver payloads.

Claims (38)

1. A variant adeno-associated virus (AAV) capsid polypeptide having at least 95% sequence identity to SEQ ID NO: 2 and comprising:

(a) a leucine at a position corresponding to V596 as compared to SEQ ID NO: 1;

(b) a serine at a position corresponding to N598 as compared to SEQ ID NO: 1; and

(c) an alanine at a position corresponding to I601 as compared to SEQ ID NO: 1.

2. The variant AAV capsid polypeptide of claim 1 , which has at least 96% sequence identity to SEQ ID NO: 2.

3. The variant AAV capsid polypeptide of claim 1 , which has at least 98% sequence identity to SEQ ID NO: 2.

4. The variant AAV capsid polypeptide of claim 1 , which has at least 99% sequence identity to SEQ ID NO: 2.

5. The variant AAV capsid polypeptide of claim 1 , which further comprises an alanine at a position corresponding to W595 as compared to SEQ ID NO: 1.

6. The variant AAV capsid polypeptide of claim 5 , which has at least 98% sequence identity to SEQ ID NO: 2.

7. The variant AAV capsid polypeptide of claim 5 , which has at least 99% sequence identity to SEQ ID NO: 2.

8. The variant AAV capsid polypeptide of claim 1 , which further comprises a valine at a position corresponding to T593 as compared to SEQ ID NO: 1.

9. The variant AAV capsid polypeptide of claim 8 , which has at least 98% sequence identity to SEQ ID NO: 2.

10. The variant AAV capsid polypeptide of claim 8 , which has at least 99% sequence identity to SEQ ID NO: 2.

11. The variant AAV capsid polypeptide of claim 8 , which further comprises an isoleucine at a position corresponding to Q592 as compared to SEQ ID NO: 1.

12. The variant AAV capsid polypeptide of claim 11 , which has at least 98% sequence identity to SEQ ID NO: 2.

13. The variant AAV capsid polypeptide of claim 11 , which has at least 99% sequence identity to SEQ ID NO: 2.

14. The variant AAV capsid polypeptide of claim 1 , which further comprises a valine at a position corresponding to Q579 as compared to SEQ ID NO: 1.

15. The variant AAV capsid polypeptide of claim 14 , which has at least 98% sequence identity to SEQ ID NO: 2.

16. The variant AAV capsid polypeptide of claim 14 , which has at least 99% sequence identity to SEQ ID NO: 2.

17. The variant AAV capsid polypeptide of claim 14 , which further comprises a valine at a position corresponding to T593 as compared to SEQ ID NO: 1.

18. The variant AAV capsid polypeptide of claim 17 , which has at least 98% sequence identity to SEQ ID NO: 2.

19. The variant AAV capsid polypeptide of claim 17 , which has at least 99% sequence identity to SEQ ID NO: 2.

20. The variant AAV capsid polypeptide of claim 1 , which comprises the mutation set of any one of SEQ ID NOs: 15, 17, 20, 22, 26, 27, and 33.

21. The variant AAV capsid polypeptide of claim 1 , which comprises the amino acid sequence of any one of SEQ ID NOs: 15, 17, 20, 22, 26, 27, 33, and 35.

22. A recombinant AAV virus particle comprising the variant AAV capsid polypeptide of claim 1 .

23. The recombinant AAV virus particle of claim 22 , further comprising a nucleic acid molecule comprising a promoter operably linked to a heterologous transgene.

24. A recombinant AAV virus particle comprising the variant AAV capsid polypeptide of claim 5 .

25. The recombinant AAV virus particle of claim 24 , further comprising a nucleic acid molecule comprising a promoter operably linked to a heterologous transgene.

26. An isolated cell comprising the variant AAV capsid polypeptide of claim 1 .

27. An isolated cell comprising the variant AAV capsid polypeptide of claim 5 .

28. An isolated cell comprising the variant AAV capsid polypeptide of claim 8 .

29. An isolated cell comprising the variant AAV capsid polypeptide of claim 14 .

30. A recombinant AAV comprising:

(a) an AAV capsid comprising AAV capsid polypeptides, each having at least 95% sequence identity to SEQ ID NO: 2 and comprising:

(i) a leucine at a position corresponding to V596 as compared to SEQ ID NO: 1;

(ii) a serine at a position corresponding to N598 as compared to SEQ ID NO: 1; and

(iii) an alanine at a position corresponding to I601 as compared to SEQ ID NO: 1; and

(b) a minigene having AAV inverted terminal repeats and a transgene comprising a heterologous gene operably linked to regulatory sequences which direct expression of the heterologous gene in a host cell.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 10, 2025
From: CHEN, INA; GEROLD, JEFF; HOLTH, JERRAH; LAPAN, SYLVAIN; LIN, KATHY S.; WOLOCK, SAMUEL
To: DYNO THERAPEUTICS, INC.
Reel/Frame 070170/0884 →
Continuity (5)
Continuation 18323135 · May 24, 2023
Continuation PCTUS2022077804 · Oct 7, 2022
Provisional Application 63262341 · Oct 10, 2021
Provisional Application 63262330 · Oct 8, 2021
Related Publication 20240417430A1 · Dec 19, 2024
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