IP Library › Granted Patent US 10,273,281
Granted Patent B2
US 10,273,281 · App. 15/340,238 · Granted Apr 30, 2019

CD80 extracellular domain polypeptides and their use in cancer treatment

Inventors: Thomas Brennan (Cupertino, CA); David Bellovin (South San Francisco, CA); David Busha (Sausalito, CA); Barbara Sennino (San Francisco, CA)
Assignee: Five Prime Therapeutics, Inc.
C07K14/70532A61K38/1774A61K39/39558A61K45/06C07K16/00C07K16/2803A61K38/00C07K2317/41C07K2319/03C07K2319/30
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Quick Facts
Patent No.
US 10,273,281
App. No.
15/340,238
Granted
Apr 30, 2019
Kind
B2
Abstract

This application relates to CD80 (B7-1) extracellular domain (ECD) polypeptides and CD80-ECD fusion molecules and their use in treatment of cancer, both alone and in combination with other therapeutic agents, such as immune stimulating agents such as PD-1/PD-L1 inhibitors.

Claims (41)

1. A CD80 extracellular domain (ECD) fusion molecule comprising the amino acid sequence of SEQ ID NO:20, wherein the CD80 ECD fusion molecule comprises 15-60 molecules of sialic acid (SA).

2. The fusion molecule of claim 1 , wherein the fusion molecule comprises 15-40 molecules of SA.

3. The fusion molecule of claim 1 , wherein the fusion molecule comprises 15-30 molecules of SA.

4. The fusion molecule of claim 1 , wherein the fusion molecule comprises 20-30 molecules of SA.

5. The fusion molecule of claim 1 , wherein the fusion molecule alone does not cause significant release of interferon gamma or TNF alpha from T-cells in vitro.

6. The fusion molecule of claim 1 , wherein the fusion molecule alone causes less release of interferon gamma or TNF alpha from T-cells in vitro than TGN1412 alone.

7. The fusion molecule of claim 6 , wherein the fusion molecule alone is at least 1000-fold less potent at inducing interferon gamma or TNF alpha release compared to TGN1412 alone.

8. The fusion molecule of claim 1 , wherein the fusion molecule is capable of at least 90% tumor growth inhibition in at least one mouse syngeneic cancer model over a period of at least 1 week, 10 days, two weeks, or three weeks following administration of a single dose of the fusion molecule at 0.3 to 0.6 mg/kg.

9. The fusion molecule of claim 8 , wherein the mouse syngeneic cancer model is a CT26 tumor model.

10. A composition comprising (i) fusion molecules comprising the amino acid sequence of SEQ ID NO:20 and (ii) at least one pharmaceutically acceptable carrier, wherein the CD80 ECD fusion molecules comprise 15-60 moles of SA per mole of CD80 ECD fusion protein.

11. The composition of claim 10 , wherein the CD80 ECD fusion molecules comprise 15-40 moles of SA per mole of CD80 ECD fusion protein.

12. The composition of claim 10 , wherein the CD80 ECD fusion molecules comprise 15-30 moles of SA per mole of CD80 ECD fusion protein.

13. The composition of claim 10 , wherein the CD80 ECD fusion molecules comprise 20-30 moles of SA per mole of CD80 ECD fusion protein.

14. The composition of claim 10 , wherein the CD80 ECD fusion molecules comprise at least 20 moles of SA per mole of CD80 ECD fusion protein.

15. The composition of claim 10 , wherein the composition alone does not cause significant release of interferon gamma or TNF alpha from T-cells in vitro.

16. The composition of claim 10 , wherein the composition alone causes less release of interferon gamma or TNF alpha from T-cells in vitro than TGN1412 alone.

17. The composition of claim 16 , wherein the composition alone is at least 1000-fold less potent at inducing interferon gamma or TNF alpha release compared to TGN1412 alone.

18. The composition of claim 11 , wherein the composition alone does not cause significant release of interferon gamma or TNF alpha from T-cells in vitro.

19. The composition of claim 11 , wherein the composition alone causes less release of interferon gamma or TNF alpha from T-cells in vitro than TGN1412 alone.

20. The composition of claim 19 , wherein the composition alone is at least 1000-fold less potent at inducing interferon gamma or TNF alpha release compared to TGN1412 alone.

21. The composition of claim 10 , wherein the composition is capable of at least 90% tumor growth inhibition in at least one mouse syngeneic cancer model over a period of at least one week, 10 days, two weeks, or three weeks following administration of a single dose of the composition at 0.3 to 0.6 mg/kg.

22. The composition of claim 21 , wherein the mouse syngeneic cancer model is a CT26 tumor model.

23. A CD80 ECD fusion molecule comprising the amino acid sequence of SEQ ID NO: 21.

24. A composition comprising (i) CD80 ECD fusion molecules comprising the amino acid sequence of SEQ ID NO:20, and (ii) at least one pharmaceutically acceptable carrier,

wherein the CD80 ECD fusion molecules comprise at least 15 moles of SA per mole of CD80 ECD fusion protein.

25. The composition of claim 24 , wherein the CD80 ECD fusion molecules comprise at least 20 moles of SA per mole of CD80 ECD fusion protein.

26. The composition of claim 24 , wherein the composition alone does not cause significant release of interferon gamma or TNF alpha from T-cells in vitro.

27. The composition of claim 24 , wherein the composition alone causes less release of interferon gamma or TNF alpha from T-cells in vitro than TGN1412 alone.

28. The composition of claim 27 , wherein the composition alone is at least 1000-fold less potent at inducing interferon gamma or TNF alpha release compared to TGN1412 alone.

29. The composition of claim 24 , wherein the composition is capable of at least 90% tumor growth inhibition in the mouse CT26 tumor model over a period of at least one week, 10 days, two weeks, or three weeks following administration of a single dose of the composition at 0.3 to 0.6 mg/kg.

30. The composition of claim 14 , wherein the composition alone does not cause significant release of interferon gamma or TNF alpha from T-cell in vitro.

31. The composition of claim 14 , wherein the composition alone causes less release of interferon gamma or TNF alpha from T-cells in vitro than TGN1412 alone.

32. The composition of claim 31 , wherein the composition alone is at least 1000-fold less potent at inducing interferon gamma or TNF alpha release compared to TGN1412 alone.

33. The composition of claim 14 , wherein the composition is capable of at least 90% tumor growth inhibition in the mouse CT26 tumor model over a period of at least one week, 10 days, two weeks, or three weeks following administration of a single dose of the composition at 0.3 to 0.6 mg/kg.

34. The composition of claim 11 , wherein the composition is capable of at least 90% tumor growth inhibition in the mouse CT26 tumor model over a period of at least one week, 10 days, two weeks, or three weeks following administration of a single dose of the composition at 0.3 to 0.6 mg/kg.

35. A CD80 extracellular domain (ECD) fusion molecule comprising the amino acid sequence of SEQ ID NO:20.

36. The fusion molecule of claim 35 , wherein the fusion molecule alone does not cause significant release of interferon gamma or TNF alpha from T-cells in vitro.

37. The fusion molecule of claim 35 , wherein the fusion molecule alone causes less release of interferon gamma or TNF alpha from T-cells in vitro than TGN1412 alone.

38. The fusion molecule of claim 37 , wherein the fusion molecule alone is at least 1000-fold less potent at inducing interferon gamma or TNF alpha release compared to TGN1412 alone.

39. The fusion molecule of claim 35 , wherein the fusion molecule is capable of at least 90% tumor growth inhibition in at least one mouse syngeneic cancer model over a period of at least 1 week, 10 days, two weeks, or three weeks following administration of a single dose of the fusion molecule at 0.3 to 0.6 mg/kg.

40. The fusion molecule of claim 39 , wherein the mouse syngeneic cancer model is a CT26 tumor model.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 9, 2018
From: BRENNAN, THOMAS; BELLOVIN, DAVID; BUSHA, DAVID; SENNINO, BARBARA
To: FIVE PRIME THERAPEUTICS, INC.
Reel/Frame 045480/0057 →
Continuity (3)
Provisional Application 62249836 · Nov 2, 2015
Provisional Application 62373654 · Aug 11, 2016
Related Publication 20170145071A1 · May 25, 2017
Cited By (4)
US 12,478,675 US 12,589,132 US 12,662,523 US 12,692,307