Antibodies binding to VISTA at acidic pH

Patent metadata

Field	Value
Publication number	US-12195535-B2
Application number	US-202318162991-A
Country	US
Kind code	B2
Filing date	Feb 1, 2023
Priority date	Mar 14, 2017
Publication date	Jan 14, 2025
Grant date	Jan 14, 2025

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.

First claim

The invention claimed is:

1. A nucleic acid comprising a polynucleotide sequence that encodes an antibody that specifically binds to human V-domain Ig Suppressor of T cell Activation (hVISTA), the antibody comprising 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 nucleic acid of claim 1 , wherein the polynucleotide sequence encodes an antibody 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 nucleic acid of claim 1 , wherein the polynucleotide sequence encodes an antibody 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 nucleic acid of claim 1 , wherein the polynucleotide sequence encodes an antibody 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 nucleic acid of claim 1 , wherein the polynucleotide sequence encodes an antibody wherein the VL comprises the amino acid sequence of SEQ ID NO: 68.

6. The nucleic acid of claim 2 , wherein the polynucleotide sequence encodes an antibody wherein the VL comprises the amino acid sequence of SEQ ID NO: 68.

7. The nucleic acid of claim 1 , wherein the polynucleotide sequence encodes an antibody 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.

8. The nucleic acid of claim 1 , wherein the polynucleotide sequence encodes an antibody wherein the VH comprises the amino acid sequence of SEQ ID NO: 55.

9. The nucleic acid of claim 1 , wherein the polynucleotide sequence encodes an antibody 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.

10. The nucleic acid of claim 1 , wherein the polynucleotide sequence encodes an antibody 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.

11. The nucleic acid of claim 1 , wherein the polynucleotide sequence encodes an antibody wherein the VH comprises the amino acid sequence of SEQ ID NO: 51.

12. The nucleic acid of claim 1 , wherein the polynucleotide sequence encodes an antibody 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.

13. The nucleic acid of claim 1 , wherein the polynucleotide sequence encodes an antibody 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.

14. The nucleic acid of claim 1 , wherein the polynucleotide sequence encodes an antibody wherein the VH comprises the amino acid sequence of SEQ ID NO: 11.

15. The nucleic acid of claim 1 , wherein the polynucleotide sequence encodes an antibody 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.

16. The nucleic acid of claim 1 , wherein the polynucleotide sequence encodes an antibody 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.

17. The nucleic acid of claim 1 , wherein the polynucleotide sequence encodes an antibody wherein the VH comprises the amino acid sequence of SEQ ID NO: 15.

18. The nucleic acid of claim 1 , wherein the polynucleotide sequence encodes an antibody 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.

19. The nucleic acid of claim 1 , wherein the polynucleotide sequence encodes an antibody 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.

20. The nucleic acid of claim 1 , wherein the polynucleotide sequence encodes an antibody wherein the VH comprises the amino acid sequence of SEQ ID NO: 39.

21. The nucleic acid of claim 1 , wherein the polynucleotide sequence encodes an antibody 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.

22. The nucleic acid of claim 1 , wherein the polynucleotide sequence encodes an antibody 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.

23. The nucleic acid of claim 1 , wherein the polynucleotide sequence encodes an antibody wherein the VH comprises the amino acid sequence of SEQ ID NO: 59.

24. The nucleic acid of claim 1 , wherein the polynucleotide sequence encodes an antibody 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.

25. The nucleic acid of claim 1 , wherein the polynucleotide sequence encodes an antibody wherein the antibody binds to h V

Assignees

• Five Prime Therapeutics Inc
• Bristol Myers Squibb Co

Inventors

• Johnston Robert J
• Rajpal Arvind
• Sheppard Paul O
• Borges Luis
• Rankin Andrew
• Bahjat Keith Sadoon
• Korman Alan J
• Deng Andy X
• Su lin hui
• RAKESTRAW Ginger

Classifications

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• C07K2317/732

  Antibody-dependent cellular cytotoxicity [ADCC] · CPC title

• C07K2317/622

  Single chain antibody (scFv) · CPC title

• C07K2317/34

  Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues · CPC title