Claims for Patent: 9,492,449

Summary for Patent: 9,492,449

Title:	Therapies for hematologic malignancies
Abstract:	The invention provides methods that relate to a novel therapeutic strategy for the treatment of hematological malignancies and inflammatory diseases. In particular, the method comprises administering a compound of formula A, ##STR00001## wherein R is H, halo, or C1-C6 alkyl; R' is C1-C6 alkyl; or a pharmaceutically acceptable salt thereof; and optionally a pharmaceutically acceptable excipient; and administering at least one additional therapeutic agent.
Inventor(s):	Gallatin; W. Michael (Mercer Island, WA), Ulrich; Roger G. (Foster City, CA), Giese; Neill A. (San Francisco, CA), Lannutti; Brian (Seattle, WA), Miller; Langdon (Lebanon, NJ), Jahn; Thomas M. (Seattle, WA)
Assignee:	Gilead Calistoga LLC (Foster City, CA)
Application Number:	13/417,185
Patent Claims:	1. A method to treat acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), comprising administering to a human in need of such treatment, an effective amount of a compound of formula I or formula II: ##STR00017## or a pharmaceutically acceptable salt thereof; and optionally a pharmaceutically acceptable excipient; and administering a monoclonal antibody, wherein the human is refractory to chemotherapy treatment or in relapse after treatment with chemotherapy. 2. The method according to claim 1, wherein the compound of formula I or formula II or a pharmaceutically acceptable salt thereof is predominantly the S-enantiomer. 3. The method according to claim 1, wherein the compound of formula I is ##STR00018## or a pharmaceutically acceptable salt thereof. 4. The method according to claim 1, wherein the compound of formula II is ##STR00019## or a pharmaceutically acceptable salt thereof. 5. The method according to claim 1, wherein the acute lymphocytic leukemia (ALL) is B-cell ALL or T-cell ALL. 6. The method according to claim 1, wherein the monoclonal antibody is selected from the group consisting of rituximab and ofatumumab. 7. The method according to claim 1, wherein the compound of formula I or formula II or a pharmaceutically acceptable salt thereof is administered with a group of agents selected from the group consisting of a-j: a) R-CHOP (rituximab-CHOP); b) R-hyperCVAD (rituximab-hyperCVAD); c) R-FCM (rituximab, fludarabine, cyclophosphamide, mitoxantrone); d) bortezomib and rituximab; e) temsirolimus and rituximab; f) Iodine-131 tositumomab)(Bexxar.RTM.) and CHOP; g) R-CVP (rituximab-CVP); h) R-ICE (rituximab-ICE); i) FCR (fludarabine, cyclophospharnide, rituximab); and j) FR (fludarabine, rituximab). 8. The method according to claim 1, wherein the compound of formula I or formula I or a pharmaceutically acceptable salt thereof maintains an average blood plasma concentration in the human between 100 nM and 1100 nM over a period of at least 12 hours from compound administration. 9. The method according to claim 1, wherein 50 mg to 150 tug of the compound of formula I or formula II or pharmaceutically acceptable salt thereof is administered to the human twice a day. 10. The method according to claim 1, wherein the compound of formula I or formula II or a pharmaceutically acceptable salt thereof and the monoclonal antibody are formulated for separate, sequential, or simultaneous administration to the human. 11. The method according to claim 1, wherein the monoclonal antibody is an anti-CD20 monoclonal antibody. 12. The method of claim 1, wherein the method is to treat chronic lymphocytic leukemia (CLL). 13. The method of claim 1, wherein the monoclonal antibody is rituximab. 14. The method according to claim 13, wherein the chemotherapy treatment comprises treatment with an alkylating agent. 15. A method to treat chronic lymphocytic leukemia (CLL), comprising administering to a human in need of such treatment, an effective amount of a compound of formula I: ##STR00020## or a pharmaceutically acceptable salt thereof; and optionally a pharmaceutically acceptable excipient; and administering rituximab, wherein the human is refractory to chemotherapy treatment or in relapse after treatment with chemotherapy. 16. The method according to claim 15, wherein the compound of formula I is ##STR00021## or a pharmaceutically acceptable salt thereof.