Anti-PVRIG antibodies and methods of use

Patent metadata

Field	Value
Publication number	US-11623955-B2
Application number	US-202016748695-A
Country	US
Kind code	B2
Filing date	Jan 21, 2020
Priority date	Feb 19, 2015
Publication date	Apr 11, 2023
Grant date	Apr 11, 2023

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 NK-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 ii) a light chain variable domain comprising the vlCDR1, vlCDR2, and vlCDR3 from SEQ ID NO: 1453, wherein a subset of said NK-cells of said patient are activated.

2. A method according to claim 1 wherein said anti-PVRIG antibody comprises the heavy chain variable domain of SEQ ID NO: 1434 and the light chain variable domain of SEQ ID NO:1453.

3. A method according to claim 2 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.

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

5. A method according to claim 1 wherein said NK-cells are CD16+ lymphocytes.

6. A method according to claim 1 wherein said NK-cells are CD56+ NK cells.

7. A method according to claim 1 wherein said activation is measured as an increase in expression of one or more activation makers.

8. A method according to claim 7 wherein said activation markers are selected from the group consisting of CD107a, CD137, CD69, granzyme, and perforin.

9. A method according to claim 1 wherein said activation is measured as an increase in proliferation of said NK-cells.

10. A method according to claim 1 wherein said activation is measured as an increase in secretion of one or more cytokines.

11. A method according to claim 10 wherein said one or more cytokines is selected from the group consisting of IFNγ and TNF.

12. A method according to claim 1 wherein said activation is measured as an increase in direct killing of target cells.

13. A method of activating NK-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 ii) a light chain variable domain comprising the vlCDR1, vlCDR2, and vlCDR3 from SEQ ID NO: 1462, wherein a subset of said NK-cells of said patient are activated.

14. A method according to claim 13 wherein said anti-PVRIG antibody comprises the heavy chain variable domain of SEQ ID NO: 1447 and the light chain variable domain of SEQ ID NO: 1462.

15. A method according to claim 14 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.

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

17. A method according to claim 13 wherein said activation markers are selected from the group consisting of CD107a, CD137, CD69, granzyme, and perforin.

18. A method according to claim 13 wherein said activation is measured as an increase in proliferation of said NK-cells.

19. A method according to claim 13 wherein said activation is measured as an increase in secretion of one or more cytokines.

20. A method according to claim 19 , wherein said one or more cytokines is selected from the group consisting of IFNγ and TNF.

21. A method according to claim 13 wherein said activation is measured as an increase in direct killing of target cells.

22. A method of activating NK-cells of a patient with cancer comprising administering an anti-PD-1 antibody and an anti-PVRIG antibody to said patient, wherein said anti-PVRIG antibody comprises: a) a heavy chain variable domain comprising: i) a vhCDR1 comprising SEQ ID NO:885; ii) a vhCDR2 comprising SEQ ID NO:886; iii) a vhCDR3 comprising SEQ ID NO:887; and b) a light chain variable domain comprising: i) a vlCDR1 comprising SEQ ID NO:889; ii) a vlCDR2 comprising SEQ ID NO:890; iii) a vlCDR3 comprising SEQ ID NO:891, wherein a subset of said T-cells of said patient are activated.

23. A method according to claim 22 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.

24. A method according to claim 23 wherein said anti-PVRIG antibody comprises the CL region of human kappa 2 light chain.

25. A method according to claim 22 wherein said activation markers are selected from the group consisting of CD107a, CD137, CD69, granzyme, and perforin.

26. A method according to claim 22 wherein said activation is measured as an increase in proliferation of said NK-cells.

27. A method according to claim 22 wherein said activation is measured as an increase in secretion of one or more cytokines.

28. A method according to claim 27 , wherein said one or more cytokines is selected from the group consisting of IFNγ and TNF.

29. A method according to claim 22 wherein said activation is measured as an increase in direct killing of target cells.

30. A method of activating NK-cells of a patient with cancer comprising administering an anti-PVRIG antibody to said patient, wherein said anti-PVRIG antibody comprises: a) a heavy chain comprising: i) a VH-CH1-hinge-CH2-CH3, wherein the VH is SEQ ID NO: 1434 and wherein the CH1-hinge-CH2-CH3 region is from IgG4; and b) a light chain comprising: i) a VL-CL, wherein the VL is SEQ ID NO: 1453 and wherein the CL region is from human kappa 2 light chain.

31. A method according to claim 30 wherein said hinge region optionally comprises mutations.

32. A method of activating NK-cells of a patient with cancer comprising administering an anti-PD-1 antibody and an anti-PVRIG antibody to said patient, wherein said anti-PVRIG antibody comprises: a) a heavy chain comprising: i) a VH-CH1-hinge-CH2-CH3, wherein the VH is SEQ ID NO: 1447 and wherein the CH1-hinge-CH2-CH3 region is from IgG4; and b) a light chain comprising: i) a VL-CL, wherein the VL is SEQ ID NO: 1462 and wherein the CL region is from human kappa 2 light chain.

33. A method according to claim 32 wherein said hinge region optionally comprises mutations.

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