IP Library › Granted Patent US 11,603,406
Granted Patent B2
US 11,603,406 · App. 16/493,712 · Granted Mar 14, 2023

Antibodies binding to VISTA at acidic pH

Inventors: Robert J. Johnston (San Mateo, CA); Arvind Rajpal (San Francisco, CA); Paul O. Sheppard (Granite Falls, WA); Luis Borges (Houston, TX); Andrew Rankin (Redwood City, CA); Keith Sadoon Bahjat (Woodside, CA); Alan J. Korman (Piedmont, CA); Andy X. Deng (Princeton, NJ); Lin Hui Su (Somerville, MA); Ginger Rakestraw (Somerville, MA)
Assignees: Five Prime Therapeutics, Inc.; Bristol-Myers Squibb Company
C07K16/2812C07K2317/34C07K2317/622C07K2317/732C07K2317/76C07K2317/92C07K2317/94
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Quick Facts
Patent No.
US 11,603,406
App. No.
16/493,712
Granted
Mar 14, 2023
Kind
B2
Abstract

The present application relates to antibodies specifically binding to the V-domain immunoglobulin-containing suppressor of T-cell activation (VISTA) at acidic pH and their use in cancer treatment. In some embodiments, the antibodies bind specifically to human VISTA at acidic pH, but do not significantly bind to human VISTA at neutral or physiological pH.

Claims (39)

1. An isolated antibody that binds specifically to human V-domain Ig Suppressor of T cell Activation (hVISTA), wherein the antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises a heavy chain variable region (VH) comprising VH CDR1, CDR2 and CDR3, which comprise amino acid positions 26-35, 50-66, and 99-112, respectively, of SEQ ID NO: 15, SEQ ID NO: 51, SEQ ID NO: 11, SEQ ID NO: 55, SEQ ID NO: 59, SEQ ID NO: 39, SEQ ID NO: 63, SEQ ID NO: 71, SEQ ID NO: 75, SEQ ID NO: 83, SEQ ID NO: 79, SEQ ID NO: 87, SEQ ID NO: 193, SEQ ID NO: 201, SEQ ID NO: 197, SEQ ID NO: 213, SEQ ID NO: 185, SEQ ID NO: 237, SEQ ID NO: 257, SEQ ID NO: 245, SEQ ID NO: 241, SEQ ID NO: 269, SEQ ID NO: 289, SEQ ID NO: 273, SEQ ID NO: 285, SEQ ID NO: 265, SEQ ID NO: 301, SEQ ID NO: 293, SEQ ID NO: 313, SEQ ID NO: 277, or SEQ ID NO: 305; and wherein the light chain comprises a light chain variable region (VL) comprising VL CDR1, CDR2 and CDR3, which comprise amino acid positions 24-35, 51-57, and 90-98, respectively, of SEQ ID NO: 68.

2. The antibody of claim 1 , wherein the VH comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 15, SEQ ID NO: 51, SEQ ID NO: 11, SEQ ID NO: 55, SEQ ID NO: 59, SEQ ID NO: 39, SEQ ID NO: 63, SEQ ID NO: 71, SEQ ID NO: 75, SEQ ID NO: 83, SEQ ID NO: 79, SEQ ID NO: 87, SEQ ID NO: 193, SEQ ID NO: 201, SEQ ID NO: 197, SEQ ID NO: 213, SEQ ID NO: 185, SEQ ID NO: 237, SEQ ID NO: 257, SEQ ID NO: 245, SEQ ID NO: 241, SEQ ID NO: 269, SEQ ID NO: 289, SEQ ID NO: 273, SEQ ID NO: 285, SEQ ID NO: 265, SEQ ID NO: 301, SEQ ID NO: 293, SEQ ID NO: 313, SEQ ID NO: 277, or SEQ ID NO: 305.

3. The antibody of claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 15, SEQ ID NO: 51, SEQ ID NO: 11, SEQ ID NO: 55, SEQ ID NO: 59, SEQ ID NO: 39, SEQ ID NO: 63, SEQ ID NO: 71, SEQ ID NO: 75, SEQ ID NO: 83, SEQ ID NO: 79, or SEQ ID NO: 87, SEQ ID NO: 193, SEQ ID NO: 201, SEQ ID NO: 197, SEQ ID NO: 213, SEQ ID NO: 185, SEQ ID NO: 237, SEQ ID NO: 257, SEQ ID NO: 245, SEQ ID NO: 241, SEQ ID NO: 269, SEQ ID NO: 289, SEQ ID NO: 273, SEQ ID NO: 285, SEQ ID NO: 265, SEQ ID NO: 301, SEQ ID NO: 293, SEQ ID NO: 313, SEQ ID NO: 277, or SEQ ID NO: 305.

4. The antibody of claim 1 , wherein the VL comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 68.

5. The antibody of claim 2 , wherein the VL comprises the amino acid sequence of SEQ ID NO: 68.

6. The antibody of claim 2 , wherein the VL comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 68.

7. The antibody of claim 3 , wherein the VL comprises the amino acid sequence of SEQ ID NO: 68.

8. The antibody of claim 1 , wherein the VH comprises VH CDR1, CDR2 and CDR3 comprising the amino acid positions 26-35, 50-66, and 99-112, respectively, of SEQ ID NO: 55, and wherein the VH comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 55.

9. The antibody of claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 55.

10. The antibody of claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 55 and the VL comprises the amino acid sequence of SEQ ID NO: 68.

11. The antibody of claim 1 , wherein the VH comprises VH CDR1, CDR2 and CDR3 comprising the amino acid positions 26-35, 50-66, and 99-112, respectively, of SEQ ID NO: 51, and wherein the VH comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 51.

12. The antibody of claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 51.

13. The antibody of claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 51 and the VL comprises the amino acid sequence of SEQ ID NO: 68.

14. The antibody of claim 1 , wherein the VH comprises VH CDR1, CDR2 and CDR3 comprising the amino acid positions 26-35, 50-66, and 99-112, respectively, of SEQ ID NO: 11, and wherein the VH comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 11.

15. The antibody of claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 11.

16. The antibody of claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 11 and the VL comprises the amino acid sequence of SEQ ID NO: 68.

17. The antibody of claim 1 , wherein the VH comprises VH CDR1, CDR2 and CDR3 comprising the amino acid positions 26-35, 50-66, and 99-112, respectively, of SEQ ID NO: 15, and wherein the VH comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 15.

18. The antibody of claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 15.

19. The antibody of claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 15 and the VL comprises the amino acid sequence of SEQ ID NO: 68.

20. The antibody of claim 1 , wherein the VH comprises VH CDR1, CDR2 and CDR3 comprising the amino acid positions 26-35, 50-66, and 99-112, respectively, of SEQ ID NO: 39, and wherein the VH comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 39.

21. The antibody of claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 39.

22. The antibody of claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 39 and the VL comprises the amino acid sequence of SEQ ID NO: 68.

23. The antibody of claim 1 , wherein the VH comprises VH CDR1, CDR2 and CDR3 comprising the amino acid positions 26-35, 50-66, and 99-112, respectively, of SEQ ID NO: 59, and wherein the VH comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 59.

24. The antibody of claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 59.

25. The antibody of claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 59 and the VL comprises the amino acid sequence of SEQ ID NO: 68.

26. The antibody of claim 1 , wherein the antibody binds to hVISTA in acidic pH conditions with a K D of 10 −8 M or less, wherein acidic pH conditions are conditions having a pH of 6.0 to 6.5.

27. The antibody of claim 1 , wherein the antibody does not detectably bind to hVISTA in physiological conditions as measured by surface plasmon resonance (SPR), wherein physiological conditions are conditions having a pH of 7.4.

28. The antibody of claim 1 , wherein the heavy chain comprises a human IgG1, IgG2 or IgG4 heavy chain constant region.

29. The antibody of claim 28 , wherein the heavy chain comprises a human IgG4 heavy chain constant region comprising an S228P substitution, wherein S228 is numbered according to EU index.

30. The antibody of claim 1 , wherein the heavy chain comprises a heavy chain constant region comprising the amino acid sequence of SEQ ID NO: 163, 182, 183, or 184, optionally further comprising a C-terminal lysine residue.

31. The antibody of claim 1 , wherein the heavy chain comprises a heavy chain constant region comprising the amino acid sequence of SEQ ID NO: 163, 182, 183, or 184 and optionally further comprising a C-terminal lysine residue, and wherein the light chain comprises a light chain constant region comprising the amino acid sequence of SEQ ID NO: 164.

32. The antibody of claim 31 , wherein the heavy chain comprises a heavy chain constant region comprising the amino acid sequence of SEQ ID NO: 163, optionally further comprising a C-terminal lysine residue.

33. The antibody of claim 1 , wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 57, optionally further comprising a C-terminal lysine residue, and wherein the light chain comprises the amino acid sequence of SEQ ID NO: 58.

34. The antibody of claim 1 , wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 13, optionally further comprising a C-terminal lysine residue, and wherein the light chain comprises the amino acid sequence of SEQ ID NO: 14.

35. The antibody of claim 1 , wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 17, optionally further comprising a C-terminal lysine residue, and wherein the light chain comprises the amino acid sequence of SEQ ID NO: 18.

36. The antibody of claim 1 , wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 41, optionally further comprising a C-terminal lysine residue, and wherein the light chain comprises the amino acid sequence of SEQ ID NO: 42.

37. The antibody of claim 1 , wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 53, optionally further comprising a C-terminal lysine residue, and wherein the light chain comprises the amino acid sequence of SEQ ID NO: 54.

38. The antibody of claim 1 , wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 61, optionally further comprising a C-terminal lysine residue, and wherein the light chain comprises the amino acid sequence of SEQ ID NO: 62.

39. A composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 14, 2020
From: BORGES, LUIS; RANKIN, ANDREW
To: FIVE PRIME THERAPEUTICS, INC.
Reel/Frame 052660/0239 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 14, 2020
From: JOHNSTON, ROBERT J.; RAJPAL, ARVIND; KORMAN, ALAN J.; SHEPPARD, PAUL O.; BAHJAT, KEITH SADOON; DENG, ANDY X.; SU, LIN HUI; RAKESTRAW, GINGER
To: BRISTOL-MYERS SQUIBB COMPANY
Reel/Frame 052660/0323 →
Continuity (3)
Provisional Application 62636746 · Feb 28, 2018
Provisional Application 62471196 · Mar 14, 2017
Related Publication 20200055936A1 · Feb 20, 2020