Anti-PVRIG antibodies and methods of use

Patent metadata

Field	Value
Publication number	US-11220542-B2
Application number	US-201615277980-A
Country	US
Kind code	B2
Filing date	Sep 27, 2016
Priority date	Feb 19, 2015
Publication date	Jan 11, 2022
Grant date	Jan 11, 2022

Abstract

The present invention is directed to anti-PVRIG antibodies and methods of using same.

First claim

The invention claimed is:

1. A method of activating T-cells of a patient with cancer comprising administering an anti-PVRIG antibody to said patient, wherein said anti-PVRIG antibody comprises:
a) the vhCDR1, vhCDR2, and vhCDR3 from SEQ ID NO:1434 and
b) the vlCDR1, vlCDR2, and vlCDR3 from SEQ ID NO:1453,

wherein said CDRs comprise from 0 to 4 substitutions and wherein no individual CDR comprises more than 1 substitution, and wherein the vhCDR3 and vlCDR3 comprise no substitutions, and
wherein a subset of said T-cells of said patient are activated.

2. A method according to claim 1 wherein said anti-PVRIG antibody comprises the CH1-hinge-CH2-CH3 region from IgG1, IgG2, IgG3, or IgG4, wherein said hinge region optionally comprises mutations.

3. A method according to claim 1 wherein said anti-PVRIG antibody comprises the CL region of human kappa 2 light chain.

4. A method according to claim 1 wherein said T-cells are cytotoxic T-cells (CTLs).

5. A method according to claim 1 wherein said T-cells are selected from the group consisting of CD4+ T-cells and CD8+ T-cells.

6. A method according to claim 1 wherein said activation is measured as an increase in interferon-γ production and/or an increase in cytokine secretion.

7. A method of activating T-cells of a patient with cancer comprising administering an anti-PVRIG antibody to said patient, wherein said anti-PVRIG antibody comprises:
i) a heavy chain variable domain comprising a sequence exhibiting at least 90% identity to SEQ ID NO:1434, wherein each individual vhCDR from SEQ ID NO:1434 comprises no more than 1 substitution, and wherein the vhCDR3 comprises no substitutions, and
ii) a light chain variable domain comprising a sequence exhibiting at least 90% identity to SEQ ID NO:1453, wherein each individual v1CDR from SEQ ID NO:1453 comprises no more than 1 substitution, and wherein the vlCDR3 comprises no substitutions, and

wherein a subset of said T-cells of said patient are activated.

8. A method according to claim 7 wherein said anti-PVRIG antibody comprises the CH1-hinge-CH2-CH3 region from IgG1, IgG2, IgG3, or IgG4, wherein said hinge region optionally comprises mutations.

9. A method according to claim 7 wherein said anti-PVRIG antibody comprises the CL region of human kappa 2 light chain.

10. A method according to claim 7 wherein said T-cells are cytotoxic T-cells (CTLs).

11. A method according to claim 7 wherein said T-cells are selected from the group consisting of CD4+ T-cells and CD8+ T-cells.

12. A method according to claim 7 wherein said activation is measured as an increase in interferon-γ production and/or an increase in cytokine secretion.

13. A method of activating T-cells of a patient with cancer comprising administering an anti-PVRIG antibody to said patient, wherein said anti-PVRIG antibody comprises:
i) a heavy chain variable domain comprising the vhCDR1, vhCDR2, and vhCDR3 from SEQ ID NO:1434 and wherein said heavy chain variable domain comprises a sequence exhibiting at least 90% identity to SEQ ID NO:1434, wherein each individual vhCDR from SEQ ID NO:1434 comprises no more than 1 substitution, and wherein the vhCDR3 comprises no substitutions, and
ii) a light chain variable domain comprising the vlCDR1, vlCDR2, and vlCDR3 from SEQ ID NO:1453 and wherein said light chain variable domain comprises a sequence exhibiting at least 90% identity to SEQ ID NO:1453, wherein each individual vlCDR from SEQ ID NO:1453 comprises no more than 1 substitution, and wherein the vlCDR3 comprises no substitutions, and

wherein a subset of said T-cells of said patient are activated.

14. A method according to claim 13 wherein said anti-PVRIG antibody comprises the CH1-hinge-CH2-CH3 region from IgG1, IgG2, IgG3, or IgG4, wherein said hinge region optionally comprises mutations.

15. A method according to claim 13 wherein said anti-PVRIG antibody comprises the CL region of human kappa 2 light chain.

16. A method according to claim 13 wherein said T-cells are cytotoxic T-cells (CTLs).

17. A method according to claim 13 wherein said T-cells are selected from the group consisting of CD4+ T-cells and CD8+ T-cells.

18. A method according to claim 13 wherein said activation is measured as an increase in interferon-γ production and/or an increase in cytokine secretion.

19. A method of activating T-cells of a patient with cancer comprising administering an anti-PVRIG antibody to said patient, wherein said anti-PVRIG antibody comprises:
a) the vhCDR1, vhCDR2, and vhCDR3 from SEQ ID NO:1447 and
b) the vlCDR1, vlCDR2, and vlCDR3 from SEQ ID NO:1462,

wherein said CDRs comprise from 0 to 4 substitutions, and no said CDR comprises more than 1 substitution, and wherein the vhCDR3 and vlCDR3 comprise no substitutions, and
wherein a subset of said T-cells of said patient are activated.

20. A method according to claim 19 wherein said anti-PVRIG antibody comprises the CH1-hinge-CH2-CH3 region from IgG1, IgG2, IgG3, or IgG4, wherein said hinge region optionally comprises mutations.

21. A method according to claim 19 wherein said anti-PVRIG antibody comprises the CL region of human kappa 2 light chain.

22. A method according to claim 19 wherein said T-cells are cytotoxic T-cells (CTLs).

23. A method according to claim 19 wherein said T-cells are selected from the group consisting of CD4+ T-cells and CD8+ T-cells.

24. A method according to claim 19 wherein said activation is measured as an increase in interferon-γ production and/or an increase in cytokine secretion.

25. A method of activating T-cells of a patient with cancer comprising administering an anti-PVRIG antibody to said patient, wherein said anti-PVRIG antibody comprises:
i) a heavy chain variable domain comprising a sequence exhibiting at least 90% identity to SEQ ID NO:1447, wherein each individual vhCDR from SEQ ID NO:1447 comprises no more than 1 substitution, and wherein the vhCDR3 comprises no substitutions, and
ii) a light chain variable domain comprising a sequence exhibiting at least 90% identity to SEQ ID NO:1462, wherein each individual vlCDR from SEQ ID NO:1462 comprises no more than 1 substitution, and wherein the vlCDR3 comprises no substitutions, and

wherein a subset of said T-cells of said patient are activated.

26. A method according to claim 25 wherein said anti-PVRIG antibody comprises the CH1-hinge-CH2-CH3 region from IgG1, IgG2, IgG3, or IgG4, wherein said hinge region optionally comprises mutations.

27. A method according to claim 25 wherein said anti-PVRIG antibody comprises the CL region of human kappa 2 light chain.

28. A method according to claim 25 wherein said T-cells are cytotoxic T-cells (CTLs).

29. A method according to claim 25 wherein said T-cells are selected from the group consisting of CD4+ T-cells and CD8+ T-cells.

30. A method according to claim 25 wherein said activation is measured as an increase in interferon-γ production and/or an increase in cytokine secretion.

31. A method of activating T-cells of a patient with cancer comprising administering an anti-PVRIG antibody to said patient, wherein said anti-PVRIG antibody comprises:
i) a heavy chain variable domain comprising the vhCDR1, vhCDR2, and vhCDR3 from SEQ ID NO:1447 and wherein said heavy chain variable domain comprises a sequence exhib

Assignees

• Compugen Ltd

Inventors

• White Mark
• Kumar Sandeep
• Chan Christopher
• Liang Spencer
• Stapleton Lance
• Drake Andrew W
• Gozlan Yosi
• Vaknin Ilan
• Sameah-Greenwald Shirley
• Dassa Liat
• Tiran Zohar
• Cojocaru Gad S
• Presta Leonard
• Theolis Richard

Classifications

• G01N33/5758

  involving compounds serving as markers for tumours, cancers or neoplasias, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides or metabolites · CPC title

• G01N2333/47

  Assays involving proteins of known structure or function as defined in the subgroups · CPC title

• C07K2317/74

  Inducing cell proliferation · CPC title

• C07K2317/70

  characterized by effect upon binding to a cell or to an antigen · CPC title

• C07K2317/55

  Fab or Fab' · CPC title