Claims for Patent: 7,173,016

Summary for Patent: 7,173,016

Title:	Composition and method for treating graft-versus-host disease
Abstract:	Compositions and methods are provided for prevention and clinical treatment of various forms of graft-versus-host disease (GVHD) by using inhibitors of adenosine deaminase (ADA). In particular, various formulations and dosing regimens of ADA inhibitors such as pentostatin are provided for the treatment of all forms of GVHD, especially steroid-refractory acute and chronic GVHD.
Inventor(s):	DiMartino; Jorge (San Carlos, CA), Nelson; John Tippett (Danville, CA)
Assignee:	Mayne Pharma (USA) Inc. (Paramus, NJ)
Application Number:	11/208,046
Patent Claims:	1. A method for treating graft-versus-host disease (GVHD) in a recipient of an organ or tissue transplant, comprises: administering to the transplant recipient an adenosine deaminase inhibitor in a pharmaceutically effective amount after the transplantation. 2. The method of claim 1, wherein the adenosine deaminase inhibitor is selected from the group consisting of pentostatin, fludarabine monophosphate, and cladribine. 3. The method of claim 1, wherein the adenosine deaminase inhibitor is administered orally to the patieiit transplant recipient. 4. The method of claim 1, wherein the adenosine deaminase inhibitor is administered parenterally to the patient transplant recipient. 5. The method of claim 1, wherein the adenosine deaminase inhibitor is administered to the patient transplant recipient via intravenous infusion or injection. 6. The method of claim 1, wherein the patient transplant recipient has acute GVHD. 7. The method of claim 6, wherein the patient transplant recipient has steroid-refractory acute GVHD. 8. The method of claim 6, wherein the patient transplant recipient has failed at least one immunosuppressive regimen selected from the group consisting of prednisone, methylprednisolone, cyclophosphamide, cyclosporin A, FK506, thalidomide, azathioprine, and daclizumab. 9. The method of claim 7, wherein the transplant recipient has has received hematopoietic stem cell transplant or bone marrow transplant and has failed to respond to treatment with at least about 2 mg/Kg of methylprednisolone or equivalent corticosteroid. 10. The method of claim 7, wherein the transplant recipient has received hematopoietic stem cell transplant or bone marrow transplant and manifests grade 2 or greater acute GVHD. 11. The method of claim 10, wherein the adenosine deaminase inhibitor is pentostatin. 12. The method of claim 11, wherein pentostatin is administered at about 0.05 5 mg/m.sup.2/day to the transplant recipient. 13. The method of claim 11, wherein pentostatin is administered at about 0.1 2 mg/m.sup.2/day to the transplant recipient. 14. The method of claim 11, wherein pentostatin is administered to the transplant recipient by intravenous infusion at about 0.1 2 mg/m.sup.2/day. 15. The method of claim 11, wherein pentostatin is administered to the transplant recipient by intravenous infusion at about 0.5 1.5 mg/m.sup.2/day. 16. The method of claim 11, wherein pentostatin is administered intravenously or orally at about 1 10 mg/m.sup.2/day for 3 consecutive days to the transplant recipient. 17. The method of claim 11, wherein pentostatin is administered intravenously or orally at about 0.1 2 mg/m.sup.2/day for 3 consecutive days to the transplant recipient. 18. The method of claim 11, wherein pentostatin is administered at about 0.1 2 mg/m.sup.2/day as a 20 minute intravenous (IV) infusion on days 1, 2 and 3. 19. The method of claim 6, further comprising: monitoring the improvement of the acute GVHD symptoms in the skin, mouth, fascia, and liver. 20. The method of claim 19, further comprising: repeating the treatment with pentostatin at least once. 21. The method of claim 1, wherein the transplant recipient has chronic GVHD. 22. The method of claim 21, wherein the transplant recipient has steroid-refractory chronic GVHD. 23. The method of claim 21, wherein the transplant recipient has also failed at least one immunosuppressive regimen selected from the group consisting of prednisone, methyiprednisolone, cyclophosphamide, cyclosporin A, FK506, thalidomide, azathioprine, and daclizumab. 24. The method of claim 22, wherein the transplant recipient has received hematopoietic stem cell transplant and has also failed to respond to treatment with at least about 2 mg/Kg of methyiprednisolone or equivalent corticosteroid. 25. The method of claim 23, wherein the adenosine deaminase inhibitor is pentostatin. 26. The method of claim 25, wherein pentostatin is administered at about 0.05 5 mg/m.sup.2/day to the transplant recipient. 27. The method of claim 25, wherein pentostatin is administered at about 0.05 5 mg/m.sup.2/day biweekly to the transplant recipient. 28. The method of claim 25, wherein pentostatin is administered at about 0.1 2 mg/m.sup.2/day to the transplant recipient. 29. The method of claim 25, wherein pentostatin is administered intravenously or orally to the transplant recipient at about 1 10 mg/m.sup.2/day. 30. The method of claim 25, wherein pentostatin is administered intravenously or orally to the transplant recipient at about 2 6 mg/m.sup.2/day. 31. The method of claim 25, wherein pentostatin is administered intravenously or orally to the transplant recipient at about 2 4 mg/m.sup.2/day. 32. The method of claim 25, wherein pentostatin is administered to the transplant recipient at about 0.1 2 mg/m.sup.2/day for 3 consecutive days. 33. The method of claim 21, further comprising: repeating the treatment with pentostatin at least once. 34. The method of claim 1, wherein the transplant recipient has been transplanted with hematopoietic stem cells or bone marrow and treated in a myeloablative conditioning regimen. 35. The method of claim 1, wherein the transplant recipient has been transplanted with hematopoietic stem cells or bone marrow and treated in a nonmycloablative conditioning regimen. 36. The method of claim 1, wherein the adenosine deaminase inhibitor is pentostatin and is orally administered to the transplant recipient at about 1 10 mg/m.sup.2/day. 37. The method of claim 1, wherein the adenosine deaminase inhibitor is pentostatin and is orally administered to the transplant recipient at about 2 6 mg/m.sup.2/day.

Details for Patent 7,173,016

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Hoffmann-la Roche Inc.	ZENAPAX	daclizumab	Injection	103749	12/10/1997		2021-10-12
Biogen Inc.	ZINBRYTA	daclizumab	Injection	761029	05/27/2016		2021-10-12
Biogen Inc.	ZINBRYTA	daclizumab	Injection	761029	05/26/2017		2021-10-12