IP Library › Granted Patent US 12,385,070
Granted Patent B2
US 12,385,070 · App. 18/344,732 · Granted Aug 12, 2025

Homology directed repair compositions for the treatment of hemoglobinopathies

Inventors: Andrew Scharenberg (Seattle, WA); Kyle Jacoby (Seattle, WA); Hans-Peter Kiem (Seattle, WA); David J. Rawlings (Seattle, WA); Christopher Lux (Bremerton, WA); Sowmya Pattabhi (Bellevue, WA); Olivier M. Humbert (Seattle, WA)
Assignees: Seattle Children's Hospital; Fred Hutchinson Cancer Center
C12N15/907A61K35/28A61P9/00C07K14/805C12N15/11C12N15/86C12N2310/20C12N2750/14143C12N2800/80
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Quick Facts
Patent No.
US 12,385,070
App. No.
18/344,732
Granted
Aug 12, 2025
Kind
B2
Abstract

The present disclosure provides improved compositions for the homology directed repair of the human globin locus for the prevention, treatment, or amelioration of at least one symptom of a hemoglobinopathy.

Claims (27)

1. A DNA donor repair template comprising: a 5′ homology arm, a selection cassette, an erythroid expression control sequence, and a 3′ homology arm, wherein the DNA donor repair template has a sequence with at least 95% sequence identity to SEQ ID NOs: 17, 18, 19, 20, or 21.

2. The DNA donor repair template of claim 1 , wherein the DNA donor repair template comprises a sequence having at least 95% sequence identity to the sequence as set forth in SEQ ID NO: 17.

3. The DNA donor repair template of claim 1 , wherein the DNA donor repair template has a sequence as set forth in SEQ ID NO: 17.

4. The DNA donor repair template of claim 1 , wherein the DNA donor repair template comprises a sequence having at least 95% sequence identity to the sequence as set forth in SEQ ID NO: 18.

5. The DNA donor repair template of claim 1 , wherein the DNA donor repair template has a sequence as set forth in SEQ ID NO: 18.

6. The DNA donor repair template of claim 1 , wherein the DNA donor repair template comprises a sequence having at least 95% sequence identity to the sequence as set forth in SEQ ID NO: 19.

7. The DNA donor repair template of claim 1 , wherein the DNA donor repair template has a sequence as set forth in SEQ ID NO: 19.

8. The DNA donor repair template of claim 1 , wherein the DNA donor repair template comprises a sequence having at least 95% sequence identity to the sequence as set forth in SEQ ID NO: 20.

9. The DNA donor repair template of claim 1 , wherein the DNA donor repair template has a sequence as set forth in SEQ ID NO: 20.

10. The DNA donor repair template of claim 1 , wherein the DNA donor repair template comprises a sequence having at least 95% sequence identity to the sequence as set forth in SEQ ID NO: 21.

11. The DNA donor repair template of claim 1 , wherein the DNA donor repair template has a sequence as set forth in SEQ ID NO: 21.

12. A viral vector comprising the DNA donor repair template of claim 1 .

13. The viral vector of claim 12 , wherein the viral vector is a recombinant adeno-associated viral vector (rAAV) or a retrovirus.

14. The viral vector of claim 13 , wherein the rAAV has one or more ITRs from AAV2.

15. The viral vector of claim 13 , wherein the rAAV has a serotype selected from the group consisting of: AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, and AAV10.

16. The viral vector of claim 13 , wherein the rAAV has an AAV6 serotype.

17. The viral vector of claim 13 , wherein the retrovirus is a lentivirus.

18. The viral vector of claim 17 , wherein the lentivirus is an integrase deficient lentivirus.

19. A cell comprising the DNA donor repair template of claim 1 .

20. The cell of claim 19 , wherein the DNA donor repair template has been inserted into a human gamma globin gene target site by homology directed repair.

21. The cell of claim 20 , wherein the target site is an engineered nuclease target site set forth in SEQ ID NO: 7 or SEQ ID NO: 8.

22. The cell of claim 19 , wherein the cell is a hematopoietic cell.

23. The cell of claim 19 , wherein the cell is CD34+ cell.

24. The cell of claim 19 , wherein the cell is CD133+ cell.

25. A cell comprising the viral vector of claim 12 .

26. A composition comprising the DNA donor repair template of claim 1 and a physiologically acceptable excipient.

27. A composition comprising a cell of claim 19 and a physiologically acceptable excipient.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 23, 2025
From: KIEM, HANS-PETER; HUMBERT, OLIVIER M.
To: FRED HUTCHINSON CANCER RESEARCH CENTER
Reel/Frame 072650/0486 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 23, 2025
From: SCHARENBERG, ANDREW; JACOBY, KYLE; RAWLINGS, DAVID J.; LUX, CHRISTOPHER; PATTABHI, SOWMYA
To: SEATTLE CHILDREN'S HOSPITAL (DBA SEATTLE CHILDREN'S RESEARCH INSTITUTE)
Reel/Frame 072650/0601 →
MERGER AND CHANGE OF NAME Recorded Oct 23, 2025
From: FRED HUTCHINSON CANCER RESEARCH CENTER; SEATTLE CANCER CARE ALLIANCE
To: FRED HUTCHINSON CANCER CENTER
Reel/Frame 072650/0680 →
Continuity (3)
Continuation 16608182
Provisional Application 62488927 · Apr 24, 2017
Related Publication 20240124896A1 · Apr 18, 2024
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