Claims for Patent: 11,166,951

Summary for Patent: 11,166,951

Title:	Therapeutic combinations of a BTK inhibitor, a PI3K inhibitor, a JAK-2 inhibitor, and/or a BCL-2 inhibitor
Abstract:	Therapeutic combinations of a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the γ- and δ-isoforms and selective for both γ- and δ-isoforms (PI3K-γ,δ, PI3K-γ, and PI3K-δ), a Janus kinase-2 (JAK-2) inhibitor, a Bruton's tyrosine kinase (BTK) inhibitor, and/or a B-cell lymphoma-2 (BCL-2) inhibitor are described. In some embodiments, the invention provides therapeutic combinations of a PI3K-δ inhibitor and a BTK inhibitor, a JAK-2 and a BTK inhibitor, and a BCL-2 and BTK inhibitor.
Inventor(s):	Ahmed Hamdy, Wayne Rothbaum, Raquel Izumi, Brian Lannutti, Todd Covey, Roger Ulrich, Dave Johnson, Tjeerd Barf, Allard Kaptein
Assignee:	Acerta Pharma BV
Application Number:	US15/982,525
Patent Claims:	1. A method of treating a hematological malignancy, comprising administering, to a human subject in need thereof, therapeutically effective amounts of (1) a B-cell lymphoma 2 (BCL-2) inhibitor of the formula: or a pharmaceutically acceptable salt thereof, and (2) a Bruton's tyrosine kinase (BTK) inhibitor of the formula: or a pharmaceutically acceptable salt thereof; wherein the hematological malignancy is chronic lymphocytic leukemia or small lymphocytic leukemia. 2. The method of claim 1, wherein the BCL-2 inhibitor is administered before administration of the BTK inhibitor. 3. The method of claim 1, wherein the BCL-2 inhibitor is administered concurrently with the administration of the BTK inhibitor. 4. The method of claim 1, wherein the BCL-2 inhibitor is administered to the subject after administration of the BTK inhibitor. 5. The method of claim 1, wherein the method further comprises the step of administering to the human a therapeutically effective amount of an anti-CD20 antibody selected from the group consisting of rituximab, obinutuzumab, ofatumumab, veltuzumab, tositumomab, ibritumomab, and fragments, derivatives, conjugates, variants, radioisotope-labeled complexes, and biosimilars thereof. 6. The method of claim 1, wherein the therapeutically effective amount of the BTK inhibitor is 100 mg. 7. The method of claim 1, wherein the therapeutically effective amount of the BTK inhibitor is 100 mg administered twice per day. 8. The method of claim 1, wherein the therapeutically effective amount of the BCL-2 inhibitor is 400 mg. 9. The method of claim 1, wherein the hematological malignancy is chronic lymphocytic leukemia. 10. The method of claim 9, wherein the chronic lymphocytic leukemia is relapsed or refractory chronic lymphocytic leukemia. 11. The method of claim 10, wherein the human subject is a human subject with a 17p chromosomal deletion. 12. The method of claim 10, wherein the human subject is a human subject with an 11q chromosomal deletion. 13. The method of claim 10, wherein the relapsed or refractory chronic lymphocytic leukemia is due to a 17p chromosomal deletion in the human subject. 14. The method of claim 10, wherein the relapsed or refractory chronic lymphocytic leukemia is due to an 11q chromosomal deletion in the human subject. 15. The method of claim 1, wherein the free form of the BCL-2 inhibitor is administered. 16. The method of claim 1, wherein the pharmaceutically acceptable salt of the BCL-2 inhibitor is administered. 17. The method of claim 1, wherein the free form of the BTK inhibitor is administered. 18. The method of claim 1, wherein the pharmaceutically acceptable salt of the BTK inhibitor is administered.