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Last Updated: December 2, 2021

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Claims for Patent: 7,998,481

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Summary for Patent: 7,998,481
Title:Modulation of NKG2D for treating or preventing solid organ allograft rejection
Abstract: The present invention relates to methods and compositions for treating and/or preventing autoimmune and/or inflammatory disease. In particular, the present invention provides therapeutics for impairing the expansion and function of autoreactive T cells, NK cells and/or NKT cells, by modulating NKG2D.
Inventor(s): Kang; Sang-Mo (San Francisco, CA), Lanier; Lewis L. (San Francisco, CA)
Assignee: The Regents of the University of California (Oakland, CA)
Application Number:11/429,354
Patent Claims:1. A method for prolonging survival of a solid organ allograft, the method comprising repeatedly administering an agent that reduces ligand-induced NKG2D activation of cells to a mammalian subject in need thereof, under conditions suitable for prolonging survival of a solid organ allograft, wherein said allograft is selected from the group consisting of a cardiac allograft, a lung allograft, a cardiac/lung allograft, a kidney allograft, a pancreas allograft, a kidney/pancreas allograft, a liver allograft, and an intestine allograft, and wherein said agent is an antibody that binds NKG2D or an NKG2D-binding fragment thereof.

2. The method of claim 1, wherein said graft is a cardiac/lung allograft.

3. The method of claim 1, wherein said graft is a cardiac allograft.

4. The method of claim 1, wherein said administering is done prior to and after transplantation of said allograft.

5. The method of claim 1, wherein the cells are selected from the group consisting of NKG2D+ CD8+ T cells, NKG2D+ CD4+ T cells, NKG2D+ .gamma.6 T cells, NKG2D+ NK cells, and macrophages.

6. The method of claim 1, wherein said antibody reduces the interaction of NKG2D with DAP10.

7. The method of claim 1, wherein said antibody reduces the amount of NKG2D on the surface of the cells.

8. The method of claim 1, wherein said antibody increases the rate at which cell-surface NKG2D is internalized.

9. The method of claim 1, wherein said antibody is a monoclonal antibody.

10. The method of claim 9, wherein said monoclonal antibody is a human antibody, a humanized antibody, or a chimeric antibody.

11. The method of claim 1, further comprising administering an adjunct therapy to said subject.

12. The method of claim 11, wherein said adjunct therapy comprises an immunomodulatory agent.

13. The method of claim 12, wherein said immunomodulatory agent is selected from the group consisting of, cyclosporin A, tacrolimus, sirolimus, everolimus, basiliximab, daclizumab, mycophenolate mofetil, mycophenolate sodium, azathioprine and FTY-720.

14. The method of claim 12, wherein said adjunct therapy comprises one or more of an antibiotic, an anti-fungal medication, an anti-ulcer medication and a diuretic.

15. A method of prolonging survival of a solid organ allograft, the method comprising administering an agent that reduces ligand-induced NKG2D activation of cells to a mammalian subject in need thereof for a prolonged period of time so as to prolong survival of a solid organ allograft, wherein said allograft is selected from the group consisting of a cardiac allograft, a lung allograft, a cardiac/lung allograft, a kidney allograft, a pancreas allograft, a kidney/pancreas allograft, a liver allograft, and an intestine allograft, and wherein said agent is selected from the group consisting of a monoclonal antibody that binds NKG2D, and an NKG2D-binding fragment thereof.

16. The method of claim 15, wherein said administering is done prior to and after transplantation of said allograft.

17. The method of claim 15, wherein said agent is an antibody that binds NKG2D.

18. The method of claim 15, wherein said antibody reduces the interaction of NKG2D with DAP10.

19. The method of claim 15, wherein said antibody reduces the amount of NKG2D on the surface of the cells.

20. The method of claim 15, wherein said antibody increases the rate at which cell-surface NKG2D is internalized.

21. The method of claim 15, wherein said agent is an NKG2D-binding fragment of said monoclonal antibody.

22. The method of claim 15, wherein said monoclonal antibody is a human antibody, a humanized antibody, or a chimeric antibody.

23. The method of claim 15, further comprising administering an adjunct therapy to said subject.

24. The method of claim 23, wherein said adjunct therapy comprises an immunomodulatory agent.

25. The method of claim 24, wherein said immunomodulatory agent is selected from the group consisting of, cyclosporin A, tacrolimus, sirolimus, everolimus, basiliximab, daclizumab, mycophenolate mofetil, mycophenolate sodium, azathioprine and FTY-720.

26. The method of claim 25, wherein said adjunct therapy comprises one or more of an antibiotic, an anti-fungal medication, an anti-ulcer medication and a diuretic.

Details for Patent 7,998,481

Applicant Tradename Biologic Ingredient Dosage Form BLA Approval Date Patent No. Expiredate
Hoffmann-la Roche Inc. ZENAPAX daclizumab Injection 103749 1997-12-10 ⤷  Free Forever Trial 2024-04-05
Novartis Pharmaceuticals Corporation SIMULECT basiliximab For Injection 103764 1998-05-12 ⤷  Free Forever Trial 2024-04-05
Novartis Pharmaceuticals Corporation SIMULECT basiliximab For Injection 103764 2003-01-02 ⤷  Free Forever Trial 2024-04-05
Biogen Inc. ZINBRYTA daclizumab Injection 761029 2016-05-27 ⤷  Free Forever Trial 2024-04-05
>Applicant >Tradename >Biologic Ingredient >Dosage Form >BLA >Approval Date >Patent No. >Expiredate

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