PVRIG polypeptides and methods of treatment

Patent metadata

Field	Value
Publication number	US-11795209-B2
Application number	US-202016775133-A
Country	US
Kind code	B2
Filing date	Jan 28, 2020
Priority date	Feb 19, 2015
Publication date	Oct 24, 2023
Grant date	Oct 24, 2023

Abstract

The present invention is directed to PVRIG polypeptides and their uses.

First claim

The invention claimed is:

1. A method of screening for anti-PVRIG antibodies and fragments thereof, wherein the method comprises:
i) providing a first cell comprising an exogenous recombinant nucleic acid encoding a human PVRIG polypeptide, wherein the first cell expresses the human PVRIG polypeptide;
ii) contacting the first cell with a second cell comprising another exogenous recombinant nucleic acid encoding a human PVRL2 polypeptide, wherein the second cell expresses the human PVRL2 polypeptide, in the presence of a candidate agent comprising an antibody or fragment thereof; and
iii) determining whether the first cell binds to the second cell as an indication of whether the candidate agent comprising an antibody or fragment thereof comprises an anti-PVRIG antibody or a fragment thereof that inhibits the binding of PVRIG with PVRL2.

2. A method of screening for anti-PVRIG antibodies and fragments thereof, wherein the method comprises:
i) providing a cell comprising an exogenous recombinant nucleic acid encoding a human PVRIG polypeptide, wherein the cell expresses the human PVRIG polypeptide;
ii) contacting the cell with a PVRL2 polypeptide, in the presence of a candidate agent comprising an antibody or fragment thereof; and
iii) determining whether the cell binds to the PVRL2 polypeptide as an indication of whether the candidate agent comprising an antibody or fragment thereof comprises an anti-PVRIG antibody or a fragment thereof that inhibits the binding of PVRIG with PVRL2.

3. A method of screening for anti-PVRIG antibodies and fragments thereof, wherein the method comprises:
i) providing a cell comprising an exogenous recombinant nucleic acid encoding a human PVRL2 polypeptide, wherein the cell expresses the human PVRL2 polypeptide;
ii) contacting the cell with a PVRIG polypeptide, in the presence of a candidate agent comprising an antibody or fragment thereof, and
iii) determining whether the cell binds to the PVRIG polypeptide as an indication of whether the candidate agent comprising an antibody or fragment thereof comprises an anti-PVRIG antibody or a fragment thereof that inhibits the binding of PVRIG with PVRL2.

4. A method according to claim 1 , wherein a plurality of candidate agents comprising antibodies or fragments thereof are tested.

5. A method according to claim 1 , wherein said method further comprises: a) contacting said candidate agent comprising an antibody or fragment thereof with a population of T-cells and/or NK cells under conditions wherein said T-cells and/or NK cells would normally be activated; and b) determining the effect of said candidate agent comprising an antibody or fragment thereof on activation of said T cells and/or NK cells.

6. A method according to claim 1 , wherein said method further comprises: a) contacting said candidate agent comprising an antibody or fragment thereof with a population of T-cells and/or NK cells; and b) determining the effect of said candidate agent comprising an antibody or fragment thereof on IFNγ production.

7. A method according to claim 5 , wherein said determination is done by measuring the presence or absence of increased expression of a protein selected from the group consisting of IFNγ, TNFα, GM-CSF, CD25, CD137, CD69, PD1, CD107A, HLA-DR, IL-2, IL-6, IL-4, IL-5, IL-10, and IL-13, wherein increased expression is an indication of activation.

8. A method according to claim 2 , wherein a plurality of candidate agents comprising antibodies or fragments thereof are tested.

9. A method according to claim 2 , wherein said method further comprises: a) contacting said candidate agent comprising an antibody or fragment thereof with a population of T-cells and/or NK cells under conditions wherein said T-cells and/or NK cells would normally be activated; and b) determining the effect of said candidate agent comprising an antibody or fragment thereof on activation of said T cells and/or NK cells.

10. A method according to claim 2 , wherein said method further comprises: a) contacting said candidate agent comprising an antibody or fragment thereof with a population of T-cells and/or NK cells; and b) determining the effect of said candidate agent comprising an antibody or fragment thereof on IFNγ production.

11. A method according to claim 9 , wherein said determination is done by measuring the presence or absence of increased expression of a protein selected from the group consisting of IFNγ, TNFα, GM-CSF, CD25, CD137, CD69, PD1, CD107A, HLA-DR, IL-2, IL-6, IL-4, IL-5, IL-10, and IL-13, wherein increased expression is an indication of activation.

12. A method according to claim 3 , wherein a plurality of candidate agents comprising antibodies or fragments thereof are tested.

13. A method according to claim 3 , wherein said method further comprises: a) contacting said candidate agent comprising an antibody or fragment thereof with a population of T-cells and/or NK cells under conditions wherein said T-cells and/or NK cells would normally be activated; and b) determining the effect of said candidate agent comprising an antibody or fragment thereof on activation of said T cells and/or NK cells.

14. A method according to claim 3 , wherein said method further comprises: a) contacting said candidate agent comprising an antibody or fragment thereof with a population of T-cells and/or NK cells; and b) determining the effect of said candidate agent comprising an antibody or fragment thereof on IFNγ production.

15. A method according to claim 13 , wherein said determination is done by measuring the presence or absence of increased expression of a protein selected from the group consisting of IFNγ, TNFα, GM-CSF, CD25, CD137, CD69, PD1, CD107A, HLA-DR, IL-2, IL-6, IL-4, IL-5, IL-10, and IL-13, wherein increased expression is an indication of activation.

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
• Toporik Amir
• Kliger Yossef
• Levy Ofer
• Machlenkin Arthur
• Nemzer Sergey
• Benita Yair
• Novik Amit

Classifications

• G01N33/575

  for cancer · CPC title

• C07K16/106 Primary

  Picornaviridae (F), e.g. hepatitis A virus · CPC title

• C07K16/1009 Primary

  Chemistry & Metallurgy · mapped topic

• C07K7/06

  having 5 to 11 amino acids · CPC title

• C07K14/70503

  Immunoglobulin superfamily · CPC title