Therapeutic and Diagnostic Methods Using TIM-3

• US 20100247521A1
• Filed: 10/27/2008
• Published: 09/30/2010
• Est. Priority Date: 10/26/2007
• Status: Active Grant

• Current Assignee: Altor Bioscience, LLC
• Original Assignee: Altor BioScience Corporation (NantWorks, LLC)
• Inventors: Jones, Richard B., Ndhlovu, Lishomwa C., Rini, James, Nixon, Douglas F., Ostrowski, Mario
• Granted Patent: US 9,416,165 B2
• Time in Patent Office: Days
• US Class Current: 424/131.100
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/70503 Immunoglobulin superfamily
• CPC Class Codes: C07K 16/1009 Picornaviridae, e.g. hepatitis A virus
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C12N 2740/16011 Human Immunodeficiency Virus, HIV
• CPC Class Codes: C12N 2770/24211 Hepacivirus, e.g. hepatitis C virus, hepatitis G virus
• CPC Class Codes: G01N 2333/525 Tumor necrosis factor [TNF]
• CPC Class Codes: G01N 2333/57 IFN-gamma
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 2800/56 Staging of a disease; Further complications associated with the disease
• CPC Class Codes: G01N 33/56988 HIV or HTLV
• CPC Class Codes: G01N 33/576 for hepatitis
• CPC Class Codes: G01N 33/6863 Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors
• CPC Class Codes: G01N 33/6866 Interferon

Abstract

The application relates to methods of treating chronic viral infection by modulating Tim-3 activity. In addition, the present application relates to methods of diagnosing or monitoring immune system activity or function, chronic viral infection and inflammatory disease using Tim-3 expression.

Claims

1. A method for improving the function of functionally impaired T cells in a subject in need thereof comprising administering an effective amount of an inhibitor of Tim-3.

2. The method of claim 1, for treating a subject afflicted with a viral infection.

4. The method of claim 2 wherein the viral infection is an HIV infection or HCV infection.

6. The method of claim 1, wherein the inhibitor of Tim-3 is an antibody.

7. The method of claim 1, wherein the inhibitor of Tim-3 is a soluble form of Tim-3.

8. The method of claim 7, wherein the soluble form of Tim-3 comprises the amino acid sequence of SEQ ID NO:

2 or 6 or a variant thereof.

9. The method of claim 1, further comprising administering an effective amount of a chronic viral antigen.

10. The method of claim 9, wherein the chronic virus is HIV-1 or HCV.

11. The method of claim 9 for treating or preventing the chronic viral infection in the subject.

3. (canceled)

5. (canceled)

12-14. -14. (canceled)

15. A pharmaceutical composition comprising an inhibitor of Tim-3 and an antigen selected from an HIV-1 antigen, a human endogenous retrovirus (HERV) antigen and a long-interspersed nuclear element (LINE) antigen.

33. The pharmaceutical composition of claim 15, wherein the inhibitor of Tim-3 is a soluble form of Tim-3.

16. (canceled)

17. (canceled)

18. A method of detecting functionally impaired T cells in a subject, comprising the steps:

(a) determining the expression of Tim-3 on the surface of T cells in a sample from the subject; and

(b) comparing the expression of Tim-3 on the surface of the T cells from the sample with a control;

wherein a difference in expression of Tim-3 on the surface of T cells in the sample from the subject as compared to the control is indicative of the presence of functionally impaired T cells in the subject.

20. The method of claim 18, wherein the subject is infected with a chronic virus.

19. (canceled)

21-26. -26. (canceled)

27. A method of monitoring or assessing disease progression in a subject with a chronic viral infection, comprising:

(a) determining the expression of Tim-3 on the surface of T cells in a sample from the subject; and

(b) comparing the expression of Tim-3 on the surface of the T-cells from the sample with a control;

wherein an increase in expression of Tim-3 on the surface of T cells in the sample as compared to the control is indicative of disease progression, and wherein a decrease in expression of Tim-3 on the surface of T-cells in the sample as compared to the control is indicative of disease remission.

28. The method of claim 27, wherein the control comprises a sample from a previous time-point from the same subject.

29-32. -32. (canceled)