Claims for Patent: 11,672,803

Summary for Patent: 11,672,803

Title:	Use of inhibitors of Brutons 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):	Joseph J. Buggy
Assignee:	Pharmacyclics LLC
Application Number:	US16/926,280
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 11,672,803
Patent Claims:	1. A method for treating chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in an individual comprising: orally administering to the individual a therapeutically effective amount of an irreversible inhibitor of Bruton's tyrosine kinase (Btk) on a continuous daily regimen until progression of the CLL or SLL or unacceptable toxicity; wherein lymphocytosis is not considered progression of the CLL or SLL, and wherein the irreversible inhibitor of Btk is a small organic molecule having the structure: wherein Z′ is an optionally substituted fused heterocyclic ring system comprising from 2-4 nitrogen heteroatoms; wherein the optionally substituted fused heterocyclic ring system consists a 5-membered ring comprising at least one nitrogen heteroatom fused to a 6-membered ring comprising at least one nitrogen heteroatom; and wherein the irreversible inhibitor of Btk forms a covalent bond with Cys481 of a Bruton's tyrosine kinase. 2. The method of claim 1, wherein said administration of the therapeutically effective amount is an amount that results in >90% of the Btk active sites in the peripheral blood mononuclear cells of the individual being occupied by the irreversible inhibitor of Btk twenty-four hours following said administration. 3. The method of claim 1, wherein the therapeutically effective amount is determined by measuring pharmacodynamic parameters of the irreversible inhibitor of Btk. 4. The method of claim 1, wherein the therapeutically effective amount of the irreversible inhibitor of Btk is a fixed dose. 5. The method of claim 1, wherein said administration of the therapeutically effective amount results in an AUC(0-24) of about >100 ng*h·ml. 6. The method of claim 1, wherein the individual has CLL and the inhibitor of Btk is orally administered to the individual once daily. 7. The method of claim 1, wherein the individual has SLL and the inhibitor of Btk is orally administered to the individual once daily. 8. A method for treating chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in an individual comprising: orally administering to the individual a therapeutically effective amount of an irreversible inhibitor of Bruton's tyrosine kinase (Btk) on a continuous daily regimen until progression of the CLL or SLL or unacceptable toxicity; wherein: lymphocytosis is not considered progression of the CLL or SLL; said administration of the therapeutically effective amount is an amount that results in >90% of the Btk active sites in the peripheral blood mononuclear cells of the individual being occupied by the irreversible inhibitor of Btk twenty-four hours following said administration; and the irreversible inhibitor of Btk is a small organic molecule having the structure: wherein Z′ is an optionally substituted fused heterocyclic ring system comprising from 2-4 nitrogen heteroatoms; and wherein the optionally substituted fused heterocyclic ring system consists a 5-membered ring comprising at least one nitrogen heteroatom fused to a 6-membered ring comprising at least one nitrogen heteroatom. 9. The method of claim 1, wherein the fused heterocyclic ring system is selected from: 10. The method of claim 1, wherein the fused heterocyclic ring system comprises 2 nitrogen heteroatoms. 11. The method of claim 10, wherein the fused heterocyclic ring system is selected from: 12. The method of claim 1, wherein the fused heterocyclic ring system comprises 3 nitrogen heteroatoms. 13. The method of claim 12, wherein the fused heterocyclic ring system is selected from: 14. The method of claim 1, wherein the fused heterocyclic ring system comprises 4 nitrogen heteroatoms. 15. The method of claim 14, wherein the fused heterocyclic ring system is selected from: 16. The method of claim 15, wherein the irreversible inhibitor of Btk is 17. The method of claim 8, wherein the fused heterocyclic ring system is selected from: 18. The method of claim 8, wherein the fused heterocyclic ring system comprises 2 nitrogen heteroatoms. 19. The method of claim 18, wherein the fused heterocyclic ring system is selected from: 20. The method of claim 8, wherein the fused heterocyclic ring system comprises 3 nitrogen heteroatoms. 21. The method of claim 20, wherein the fused heterocyclic ring system is selected from: 22. The method of claim 8, wherein the fused heterocyclic ring system comprises 4 nitrogen heteroatoms. 23. The method of claim 22, wherein the fused heterocyclic ring system is selected from: 24. The method of claim 23, wherein the irreversible inhibitor of Btk is