IP Library › Granted Patent US 12,331,126
Granted Patent B2
US 12,331,126 · App. 18/658,421 · Granted Jun 17, 2025

OX40-binding polypeptides and uses thereof

Inventors: John C. Timmer (San Diego, CA); William Crago (San Diego, CA); Kyle Jones (San Marcos, CA); Katelyn Willis (San Diego, CA); Florian Sulzmaier (San Diego, CA); Bryan Becklund (San Diego, CA); Brendan P. Eckelman (Encinitas, CA)
Assignee: Inhibrx Biosciences, Inc.
C07K16/2875A61K35/17A61P35/00C12N15/85C07K2317/569C12N2015/8518
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Quick Facts
Patent No.
US 12,331,126
App. No.
18/658,421
Granted
Jun 17, 2025
Kind
B2
Abstract

Provided herein are VHH-containing polypeptides that bind OX40. In some embodiments, VHH-containing polypeptides that bind and agonize OX40 are provided. Uses of the VHH-containing polypeptides are also provided.

Claims (47)

1. An isolated nucleic acid that encodes a polypeptide comprising at least one VHH domain that binds OX40, wherein the VHH domain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 10, a CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 12, and wherein the VHH domain comprises a FR2 comprising the amino acid sequence of SEQ ID NO: 22.

2. The isolated nucleic acid of claim 1 , wherein the VHH domain comprises a FR3 comprising the amino acid sequence of SEQ ID NO: 23.

3. The isolated nucleic acid of claim 1 , wherein the VHH domain comprises the amino acid sequence of SEQ ID NO: 9.

4. The isolated nucleic acid of claim 1 , wherein the polypeptide comprises two, three, or four VHH domains.

5. The isolated nucleic acid of claim 4 , wherein each VHH domain binds OX40.

6. The isolated nucleic acid of claim 5 , wherein each VHH domain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 10, a CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 12, and wherein each VHH domain comprises a FR2 comprising the amino acid sequence of SEQ ID NO: 22.

7. The isolated nucleic acid of claim 6 , wherein each VHH domain comprises a FR3 comprising the amino acid sequence of SEQ ID NO: 23.

8. The isolated nucleic acid of claim 5 , wherein each VHH domain comprises the amino acid sequence of SEQ ID NO: 9.

9. The isolated nucleic acid of claim 4 , wherein the polypeptide comprises an Fc domain.

10. The isolated nucleic acid of claim 9 , wherein the Fc domain comprises an amino acid sequence selected from SEQ ID NOs: 25 and 26.

11. The isolated nucleic acid of claim 1 , wherein the polypeptide comprises an Fc domain.

12. The isolated nucleic acid of claim 11 , wherein the polypeptide comprising an Fc domain comprises an amino acid sequence selected from SEQ ID NOs: 25 and 26.

13. The isolated nucleic acid of claim 1 , wherein polypeptide comprises the amino acid sequence of SEQ ID NO: 14.

14. The isolated nucleic acid of claim 13 , wherein the polypeptide comprises an Fc domain.

15. A vector comprising the isolated nucleic acid of claim 14 .

16. A host cell comprising the vector of claim 15 .

17. A host cell comprising the isolated nucleic acid of claim 14 .

18. A vector comprising the isolated nucleic acid of claim 13 .

19. A host cell comprising the vector of claim 18 .

20. A host cell comprising the isolated nucleic acid of claim 13 .

21. The isolated nucleic acid of claim 1 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 15.

22. A vector comprising the isolated nucleic acid of claim 21 .

23. A host cell comprising the vector of claim 22 .

24. A host cell comprising the isolated nucleic acid of claim 21 .

25. A vector comprising the isolated nucleic acid of claim 1 .

26. A host cell comprising the vector of claim 25 .

27. A host cell comprising the isolated nucleic acid of claim 1 .

28. An isolated nucleic acid that encodes a polypeptide that binds OX40 consisting of the amino acid sequence of SEQ ID NO: 15.

29. A host cell that expresses a polypeptide comprising at least one VHH domain that binds OX40, wherein the VHH domain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 10, a CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 12, and wherein each VHH domain comprises a FR2 comprising the amino acid sequence of SEQ ID NO: 22.

30. The host cell of claim 29 , wherein the VHH domain comprises a FR3 comprising the amino acid sequence of SEQ ID NO: 23.

31. The host cell of claim 29 , wherein the VHH domain comprises the amino acid sequence of SEQ ID NO: 9.

32. The host cell of claim 29 , wherein the polypeptide comprises two, three, or four VHH domains.

33. The host cell of claim 32 , wherein each VHH domain binds OX40.

34. The host cell of claim 33 , wherein each VHH domain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 10, a CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 12, and wherein each VHH domain comprises a FR2 comprising the amino acid sequence of SEQ ID NO: 22.

35. The host cell of claim 34 , wherein each VHH domain comprises a FR3 comprising the amino acid sequence of SEQ ID NO: 23.

36. The host cell of claim 33 , wherein each VHH domain comprises the amino acid sequence of SEQ ID NO: 9.

37. The host cell of claim 32 , wherein the polypeptide comprises an Fc domain.

38. The host cell of claim 37 , wherein the Fc domain comprises an amino acid sequence selected from SEQ ID NOs: 25 and 26.

39. The host cell of claim 29 , wherein the polypeptide comprises an Fc domain.

40. The host cell of claim 39 , wherein the polypeptide comprising an Fc domain comprises an amino acid sequence selected from SEQ ID NOs: 25 and 26.

41. The host cell of claim 29 , wherein polypeptide comprises the amino acid sequence of SEQ ID NO: 14.

42. The host cell of claim 41 , wherein the polypeptide comprises an Fc domain.

43. The host cell of claim 29 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 15.

44. The host cell of claim 29 , which secretes the polypeptide.

45. The host cell of claim 29 , which is a primary human cell.

46. The host cell of claim 45 , which is a primary human T cell.

47. The host cell of claim 46 , which is a chimeric antigen receptor (CAR)-T cell.

Assignments (3)
SECURITY INTEREST Recorded Jan 14, 2025
From: INHIBRX BIOSCIENCES, INC.
To: OXFORD FINANCE LLC; OXFORD FINANCE LLC
Reel/Frame 069894/0045 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 10, 2024
From: INHIBRX, INC.
To: INHIBRX BIOSCIENCES, INC.
Reel/Frame 067679/0635 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 6, 2024
From: TIMMER, JOHN C.; CRAGO, WILLIAM; JONES, KYLE; WILLIS, KATELYN; SULZMAIER, FLORIAN; BECKLUND, BRYAN; ECKELMAN, BRENDEN P.
To: INHIBRX, INC.
Reel/Frame 067643/0315 →
Continuity (4)
Division 17818106 · Aug 8, 2022
Division 16538216 · Aug 12, 2019
Provisional Application 62718106 · Aug 13, 2018
Related Publication 20240409651A1 · Dec 12, 2024
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