Compositions and methods for the treatment of immune related diseases

Patent metadata

Field	Value
Publication number	US-9499596-B2
Application number	US-201213648191-A
Country	US
Kind code	B2
Filing date	Oct 9, 2012
Priority date	Apr 9, 2008
Publication date	Nov 22, 2016
Grant date	Nov 22, 2016

Abstract

The present invention relates to compositions and methods of using those compositions for the diagnosis and treatment of immune related diseases.

First claim

What is claimed:

1. A method for increasing immune system function and/or activity in a subject, the method comprising administering to the subject an anti-TIGIT antibody, or antigen-binding fragment thereof, comprising:
(a) a light chain comprising an HVR-L1 comprising SEQ ID NO: 23, an HVR-L2 comprising SEQ ID NO: 24, and an HVR-L3 comprising SEQ ID NO: 25, and a heavy chain comprising an HVR-H1 comprising SEQ ID NO: 26, an HVR-H2 comprising SEQ ID NO: 27, and an HVR-H3 comprising SEQ ID NO: 28, or
(b) a light chain comprising an HVR-L1 comprising SEQ ID NO: 31, an HVR-L2 comprising SEQ ID NO: 32, and an HVR-L3 comprising SEQ ID NO: 33, and a heavy chain comprising an HVR-H1 comprising SEQ ID NO: 34, an HVR-H2 comprising SEQ ID NO: 35, and an HVR-H3 comprising SEQ ID NO: 36,
wherein the anti-TIGIT antibody, or antigen-binding fragment thereof, decreases the binding of TIGIT to one or more of PVR, PVRL3, and PVRL2.

2. A method of treating and/or lessening the severity of an immune-related disease relating to aberrant immune cell response in a subject, the method comprising administering to the subject an anti-TIGIT antibody, or antigen-binding fragment thereof, comprising:
(a) a light chain comprising an HVR-L1 comprising SEQ ID NO: 23, an HVR-L2 comprising SEQ ID NO: 24, and an HVR-L3 comprising SEQ ID NO: 25, and a heavy chain comprising an HVR-H1 comprising SEQ ID NO: 26, an HVR-H2 comprising SEQ ID NO: 27, and an HVR-H3 comprising SEQ ID NO: 28, or
(b) a light chain comprising an HVR-L1 comprising SEQ ID NO: 31, an HVR-L2 comprising SEQ ID NO: 32, and an HVR-L3 comprising SEQ ID NO: 33, and a heavy chain comprising an HVR-H1 comprising SEQ ID NO: 34, an HVR-H2 comprising SEQ ID NO: 35, and an HVR-H3 comprising SEQ ID NO: 36,
wherein the anti-TIGIT antibody, or antigen-binding fragment thereof, decreases the activity of TIGIT in the subject, and wherein the immune-related disease is cancer.

3. The method of claim 1 or 2 , wherein the subject is a mammal.

4. The method of claim 3 , wherein the mammal is a human.

5. A method of increasing or stimulating proliferation of a T cell or proinflammatory cytokine release by a dendritic cell in a subject, the method comprising administering to the subject an antagonist of TIGIT activity, wherein the antagonist of TIGIT activity is an anti-TIGIT antibody, or antigen-binding fragment thereof, comprising:
(a) a light chain comprising an HVR-L1 comprising SEQ ID NO: 23, an HVR-L2 comprising SEQ ID NO: 24, and an HVR-L3 comprising SEQ ID NO: 25, and a heavy chain comprising an HVR-H1 comprising SEQ ID NO: 26, an HVR-H2 comprising SEQ ID NO: 27, and an HVR-H3 comprising SEQ ID NO: 28, or
(b) a light chain comprising an HVR-L1 comprising SEQ ID NO: 31, an HVR-L2 comprising SEQ ID NO: 32, and an HVR-L3 comprising SEQ ID NO: 33, and a heavy chain comprising an HVR-H1 comprising SEQ ID NO: 34, an HVR-H2 comprising SEQ ID NO: 35, and an HVR-H3 comprising SEQ ID NO: 36.

6. A method of increasing or stimulating proliferation of a T cell or proinflammatory cytokine release by a dendritic cell in vitro, wherein the method comprises contacting a co-culture of T cells and dendritic cells with an antagonist of TIGIT activity, and wherein the antagonist of TIGIT activity is an anti-TIGIT antibody, or antigen-binding fragment thereof, comprising:
(a) a light chain comprising an HVR-L1 comprising SEQ ID NO: 23, an HVR-L2 comprising SEQ ID NO: 24, and an HVR-L3 comprising SEQ ID NO: 25, and a heavy chain comprising an HVR-H1 comprising SEQ ID NO: 26, an HVR-H2 comprising SEQ ID NO: 27, and an HVR-H3 comprising SEQ ID NO: 28, or
(b) a light chain comprising an HVR-L1 comprising SEQ ID NO: 31, an HVR-L2 comprising SEQ ID NO: 32, and an HVR-L3 comprising SEQ ID NO: 33, and a heavy chain comprising an HVR-H1 comprising SEQ ID NO: 34, an HVR-H2 comprising SEQ ID NO: 35, and an HVR-H3 comprising SEQ ID NO: 36.

7. The method of claim 5 or 6 , wherein the T cell is an activated T cell.

8. The method of claim 5 or 6 , wherein the method blocks regulatory T (T reg ) cell-mediated suppression of T cell proliferation.

9. A method of stimulating a CD226-PVR interaction and/or a CD96-PVR interaction in a subject, the method comprising administering to the subject an antagonist of TIGIT activity, wherein the antagonist of TIGIT activity is an anti-TIGIT antibody, or antigen-binding fragment thereof, comprising:
(a) a light chain comprising an HVR-L1 comprising SEQ ID NO: 23, an HVR-L2 comprising SEQ ID NO: 24, and an HVR-L3 comprising SEQ ID NO: 25, and a heavy chain comprising an HVR-H1 comprising SEQ ID NO: 26, an HVR-H2 comprising SEQ ID NO: 27, and an HVR-H3 comprising SEQ ID NO: 28, or
(b) a light chain comprising an HVR-L1 comprising SEQ ID NO: 31, an HVR-L2 comprising SEQ ID NO: 32, and an HVR-L3 comprising SEQ ID NO: 33, and a heavy chain comprising an HVR-H1 comprising SEQ ID NO: 34, an HVR-H2 comprising SEQ ID NO: 35, and an HVR-H3 comprising SEQ ID NO: 36.

10. A method of increasing or stimulating a T cell immune response in a subject, the method comprising administering to the subject an antagonist of TIGIT activity, wherein the antagonist of TIGIT activity is an anti-TIGIT antibody, or antigen-binding fragment thereof, comprising:
(a) a light chain comprising an HVR-L1 comprising SEQ ID NO: 23, an HVR-L2 comprising SEQ ID NO: 24, and an HVR-L3 comprising SEQ ID NO: 25, and a heavy chain comprising an HVR-H1 comprising SEQ ID NO: 26, an HVR-H2 comprising SEQ ID NO: 27, and an HVR-H3 comprising SEQ ID NO: 28, or
(b) a light chain comprising an HVR-L1 comprising SEQ ID NO: 31, an HVR-L2 comprising SEQ ID NO: 32, and an HVR-L3 comprising SEQ ID NO: 33, and a heavy chain comprising an HVR-H1 comprising SEQ ID NO: 34, an HVR-H2 comprising SEQ ID NO: 35, and an HVR-H3 comprising SEQ ID NO: 36.

11. A method of increasing or stimulating proinflammatory cytokine production from a dendritic cell in a subject, the method comprising administering to the subject an antagonist of TIGIT activity, wherein the antagonist of TIGIT activity is an anti-TIGIT antibody, or antigen-binding fragment thereof, comprising:
(a) a light chain comprising an HVR-L1 comprising SEQ ID NO: 23, an HVR-L2 comprising SEQ ID NO: 24, and an HVR-L3 comprising SEQ ID NO: 25, and a heavy chain comprising an HVR-H1 comprising SEQ ID NO: 26, an HVR-H2 comprising SEQ ID NO: 27, and an HVR-H3 comprising SEQ ID NO: 28, or
(b) a light chain comprising an HVR-L1 comprising SEQ ID NO: 31, an HVR-L2 comprising SEQ ID NO: 32, and an HVR-L3 comprising SEQ ID NO: 33, and a heavy chain comprising an HVR-H1 comprising SEQ ID NO: 34, an HVR-H2 comprising SEQ ID NO: 35, and an HVR-H3 comprising SEQ ID NO: 36.

12. A method of stimulating a CD226-PVR interaction and/or a CD96-PVR interaction in vitro, wherein the method comprises contacting a co-culture of T cells and dendritic cells with an antagonist of TIGIT activity, and wherein the antagonist of TIGIT activity is an anti-TIGIT antibody, or antigen-binding fragment thereof, comprising:
(a) a light chain comprising an HVR-L1 comprising SEQ ID NO: 23, an HVR-L2 comprising SEQ ID NO: 24, and an HVR-L3 comprising SEQ ID NO: 25, and a heavy chain comprising an HVR-H1 comprising SEQ ID NO: 26, an HVR-H2 comprising SEQ ID NO: 27, and an HVR-H3 comprising SEQ ID NO: 28, or
(b) a light chain comprising an HVR-L1 comprising SEQ ID NO: 31, an HVR-L2 comprising SEQ ID NO: 32, and an HVR-L3 comprising SEQ ID NO: 33, and a heavy chain comprising an HVR-H1 comprising SEQ ID NO: 34, an HVR-H2 comprising SEQ ID NO: 35, and an HVR-H3 comprising SEQ ID NO: 36.

13. A method of increasing or stimulating a T cell immune response in vitro, wherein the me

Assignees

• Genentech Inc

Inventors

• Clark Hilary
• Eaton Dan
• Gonzalez Lino
• Grogan Jane
• Hackney Jason
• Bowles Kristin
• Yu Xin

Classifications

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title