Claims for Patent: 10,478,439

Summary for Patent: 10,478,439

Title:	Use of inhibitors of bruton's tyrosine kinase (Btk)
Abstract:	Disclosed herein are methods for treating a cancer comprising: a. administering a Btk inhibitor to a subject sufficient to result in an increase or appearance in the blood of a subpopulation of lymphocytes defined by immunophenotyping; b. determining the expression profile of one or more biomarkers from one or more subpopulation of lymphocytes; and c. administering a second agent based on the determined expression profile.
Inventor(s):	Honigberg; Lee (San Francisco, CA), Loury; David J. (Incline Village, NV)
Assignee:	Pharmacyclics LLC (Sunnyvale, CA)
Application Number:	15/965,114
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,478,439
Patent Claims:	1. A method of inhibiting proliferation and survival of activated B-cells in a human subject suffering from a B-cell proliferative disorder, comprising: orally administering to the human subject suffering from a B-cell proliferative disorder a therapeutically effective amount of 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)pi- peridin-1-yl)prop-2-en-1-one (Compound 13), on a continuous once-daily regimen until progression of the disorder or unacceptable toxicity, wherein said administration of the therapeutically effective amount results in an AUC.sub.(0-24) of >about 100 ng*h/ml; and wherein said administration of the therapeutically effective amount results in >90% of the Btk active sites in the peripheral blood mononuclear cells of the human subject being occupied by Compound 13 twenty-four hours following said administration. 2. The method of claim 1, wherein the once daily regimen is continued for at least 6 months. 3. The method of claim 1, wherein the B-cell proliferative disorder is a hematological malignancy. 4. The method of claim 3, wherein the hematological malignancy is a non-Hodgkin lymphoma. 5. The method of claim 3, wherein the hematological malignancy is selected from the group consisting of chronic lymphocytic leukemia, small lymphocytic lymphoma, and Waldenstrom's macroglobulinemia. 6. The method of claim 3, wherein the hematological malignancy is selected from the group consisting of mantle cell lymphoma, follicular lymphoma, marginal zone lymphoma, and ABC-diffuse large B-cell lymphoma. 7. The method of claim 1, wherein the human subject has previously undergone a bone marrow transplant. 8. The method of claim 7, wherein the human subject has previously undergone an autologous bone marrow transplant. 9. The method of claim 3, wherein the hematological malignancy is relapsed or refractory. 10. A method of inhibiting proliferation and survival of activated B-cells in a human subject suffering from a B-cell proliferative disorder, comprising: orally administering to the human subject suffering from a B-cell proliferative disorder a therapeutically effective amount of 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl- )piperidin-1-yl)prop-2-en-1-one (Compound 13), wherein the therapeutically effective amount of Compound 13 is an amount that results in >90% of the Btk active sites in the peripheral blood mononuclear cells of the human subject being occupied by Compound 13 twenty-four hours following said administration, and wherein proliferation and survival of the activated B-cells in the human are inhibited. 11. The method of claim 10, wherein the B-cell proliferative disorder is a hematological malignancy. 12. The method of claim 11, wherein the hematological malignancy is a non-Hodgkin lymphoma. 13. The method of claim 11, wherein the hematological malignancy is selected from the group consisting of chronic lymphocytic leukemia, small lymphocytic lymphoma, and Waldenstrom's macroglobulinemia. 14. The method of claim 11, wherein the hematological malignancy is selected from the group consisting of mantle cell lymphoma, follicular lymphoma, marginal zone lymphoma, and ABC-diffuse large B-cell lymphoma. 15. The method of claim 10, wherein the human subject has previously undergone a bone marrow transplant. 16. The method of claim 15, wherein the human subject has previously undergone an autologous bone marrow transplant. 17. The method of claim 11, wherein the hematological malignancy is relapsed or refractory.