Abstract: Therapeutic methods of treating chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL) are described. In certain embodiments, the invention includes therapeutic methods of treating CLL and SLL using a BTK inhibitor. In certain embodiments, the invention includes therapeutic methods of treating subtypes of CLL and SLL using a BTK inhibitor, including subtypes of CLL in patients sensitive to thrombosis and subtypes of CLL that increase monocytes and NK cells in peripheral blood after treatment with a BTK inhibitor. In certain embodiments, the invention includes therapeutic methods of treating CLL and SLL using a combination of a BTK inhibitor and an anti-CD20 antibody.

Abstract: Therapeutic combinations of a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the ?- and ?-isoforms and selective for both ?- and ?-isoforms (PI3K-?,?, PI3K-?, and PI3K-?), 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-? inhibitor and a BTK inhibitor, a JAK-2 and a BTK inhibitor, and a BCL-2 and BTK inhibitor.

Abstract: Therapeutic combinations of a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the ?- and ?-isoforms and selective for both ?- and ?-isoforms (PI3K-?,?, PI3K-?, and PI3K-?), 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-? inhibitor and a BTK inhibitor, a JAK-2 and a BTK inhibitor, and a BCL-2 and BTK inhibitor.

Abstract: Therapeutic methods of treating chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL) are described. In certain embodiments, the invention includes therapeutic methods of treating CLL and SLL using a BTK inhibitor. In certain embodiments, the invention includes therapeutic methods of treating subtypes of CLL and SLL using a BTK inhibitor, including subtypes of CLL in patients sensitive to thrombosis and subtypes of CLL that increase monocytes and NK cells in peripheral blood after treatment with a BTK inhibitor. In certain embodiments, the invention includes therapeutic methods of treating CLL and SLL using a combination of a BTK inhibitor and an anti-CD20 antibody.

Abstract: In certain embodiments, the invention includes therapeutic methods of using a BTK inhibitor to treat solid tumor cancers by modulation of the tumor microenvironment, including macrophages, monocytes, mast cells, helper T cells, cytotoxic T cells, regulatory T cells, natural killer cells, myeloid-derived suppressor cells, regulatory B cells, neutrophils, dendritic cells, and fibroblasts.

Abstract: Therapeutic combinations of a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the ?- and ?-isoforms and selective for both ?- and ?-isoforms (PI3K-?,?, PI3K-?, and PI3K-?), 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-? inhibitor and a BTK inhibitor, a JAK-2 and a BTK inhibitor, and a BCL-2 and BTK inhibitor.

Abstract: Therapeutic combinations of a MEK inhibitor and a Bruton's tyrosine kinase (BTK) inhibitor are described. In some embodiments, the invention provides pharmaceutical compositions comprising combinations of a MEK inhibitor and a BTK inhibitor and methods of using the pharmaceutical compositions for treating a disease, in particular a cancer.

Abstract: In an embodiment, therapeutic methods and uses of Bruton's Tyrosine Kinase (BTK) inhibitors for treatment of cancer, inflammation, immune disorders, and autoimmune disorders, including dermatoses, and for transplantation prophylaxis, based on BTK occupancies and/or BTK resynthesis rates for B cells in various diseases, tissue compartments, including bone marrow and lymph nodes, are described. In an embodiment, dosing regimens for a BTK inhibitor for treatment of cancer, inflammation, immune disorders, and autoimmune disorders, including dermatoses, and for transplantation prophylaxis, based on BTK occupancies and/or BTK resynthesis rates for B cells in various diseases, tissue compartments, including bone marrow and lymph nodes, are described.

Abstract: Therapeutic methods of treating chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL) are described. In certain embodiments, the invention includes therapeutic methods of treating CLL and SLL using a BTK inhibitor. In certain embodiments, the invention includes therapeutic methods of treating subtypes of CLL and SLL using a BTK inhibitor, including subtypes of CLL in patients sensitive to thrombosis and subtypes of CLL that increase monocytes and NK cells in peripheral blood after treatment with a BTK inhibitor. In certain embodiments, the invention includes therapeutic methods of treating CLL and SLL using a combination of a BTK inhibitor and an anti-CD20 antibody.

Abstract: In some embodiments, the invention relates to the compounds of Formula (I) and (II) or a pharmaceutically acceptable salt thereof, or to pharmaceutical compositions comprising these compounds and to their use in therapy. In particular, in some embodiments, the present invention relates to the compounds of Formula (I) and (II), pharmaceutical compositions thereof, and the use of the compounds and pharmaceutical compositions in the treatment of a hyperproliferative disorder, an inflammatory disorder, an immune disorder, or an autoimmune disorder.

Abstract: Therapeutic combinations of an interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitor and a Bruton's tyrosine kinase (BTK) inhibitor are described. In some embodiments, the invention provides pharmaceutical compositions comprising combinations of an IRAK4 inhibitor and a BTK inhibitor, and methods of using the pharmaceutical compositions for treating a disease, in particular a cancer.

Abstract: Therapeutic compositions and methods of using the compositions, including combinations of a Bruton's tyrosine kinase (BTK) inhibitor, a phosphomositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the ?- and ?-isoforms and selective for both y- and ?-isoforms (PI3K-?,?, PI3K-?, and PI3K-?, a programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitor, and/or a Janus kinase-2 (JAK-2) inhibitor are described. In certain embodiments, the invention includes therapeutic methods of using a PD-1 monoclonal antibody and a BTK inhibitor. In other embodiments, the invention includes therapeutic methods of using a PD-L1 monoclonal antibody and a BTK inhibitor. In other embodiments, the invention includes therapeutic methods of using a PD-1 inhibitor, a BTK inhibitor, and a PI3K˜? inhibitor. In other embodiments, the invention includes therapeutic methods of using a PD-L1 inhibitor, a BTK inhibitor, and a PI3K˜? inhibitor.

Abstract: In certain embodiments, the invention includes therapeutic methods of using a BTK inhibitor to treat solid tumor cancers by modulation of the tumor microenvironment, including macrophages, monocytes, mast cells, helper T cells, cytotoxic T cells, regulatory T cells, natural killer cells, myeloid-derived suppressor cells, regulatory B cells, neutrophils, dendritic cells, and fibroblasts.

Abstract: In some embodiments, the invention relates to compositions, methods, and kits for assessment of drug target occupancy in Bruton's tyrosine kinase (BTK) in a selective and sensitive manner for use with BTK inhibitor therapy in the treatment of Bruton's tyrosine kinase (BTK) mediated disorders, including cancers, inflammatory diseases, and immune and autoimmune diseases.

Abstract: Therapeutic combinations of a MEK inhibitor and a Bruton's tyrosine kinase (BTK) inhibitor are described. In some embodiments, the invention provides pharmaceutical compositions comprising combinations of a MEK inhibitor and a BTK inhibitor and methods of using the pharmaceutical compositions for treating a disease, in particular a cancer.

Abstract: Therapeutic combinations of an antifolate compound and a Bruton's tyrosine kinase (BTK) inhibitor are described. In some embodiments, the invention provides pharmaceutical compositions comprising combinations of an antifolate compound and a BTK inhibitor, and methods of treating a disease using an antifolate compound and a BTK inhibitor, in particular a cancer or an immune, autoimmune, or inflammatory disease. In some embodiments, the invention provides pharmaceutical compositions comprising combinations of an antifolate compound, a PD-1 or a PD-L1 inhibitor, and a BTK inhibitor, and methods of treating a disease using an antifolate compound, a PD-1 or a PD-L1 inhibitor, and a BTK inhibitor, in particular a cancer or an immune, autoimmune, or inflammatory disease.

Abstract: In some embodiments, the invention includes a therapeutic combination of a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the ?- and ?-isoforms and selective for both ?- and ?-isoforms, and a Bruton's tyrosine kinase (BTK) inhibitor. In some embodiments, the invention includes therapeutic methods of using a BTK inhibitor and a PI3K-? inhibitor to treat solid tumor cancers by modulation of the tumor microenvironment, including macrophages, monocytes, mast cells, helper T cells, cytotoxic T cells, regulatory T cells, natural killer cells, myeloid-derived suppressor cells, regulatory B cells, neutrophils, dendritic cells, and fibroblasts.

Abstract: In some embodiments, the invention relates to the compounds of Formula (I) and (II) or a pharmaceutically acceptable salt thereof, or to pharmaceutical compositions comprising these compounds and to their use in therapy. In particular, in some embodiments, the present invention relates to the compounds of Formula (I) and (II), pharmaceutical compositions thereof, and the use of the compounds and pharmaceutical compositions in the treatment of a hyperproliferative disorder, an inflammatory disorder, an immune disorder, or an autoimmune disorder.

Abstract: In an embodiment, therapeutic methods and uses of Bruton's Tyrosine Kinase (BTK) inhibitors for treatment of cancer, inflammation, immune disorders, and autoimmune disorders, including dermatoses, and for transplantation prophylaxis, based on BTK occupancies and/or BTK resynthesis rates for B cells in various diseases, tissue compartments, including bone marrow and lymph nodes, are described. In an embodiment, dosing regimens for a BTK inhibitor for treatment of cancer, inflammation, immune disorders, and autoimmune disorders, including dermatoses, and for transplantation prophylaxis, based on BTK occupancies and/or BTK resynthesis rates for B cells in various diseases, tissue compartments, including bone marrow and lymph nodes, are described.

Abstract: Therapeutic methods of treating chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL) are described. In certain embodiments, the invention includes therapeutic methods of treating CLL and SLL using a BTK inhibitor. In certain embodiments, the invention includes therapeutic methods of treating subtypes of CLL and SLL using a BTK inhibitor, including subtypes of CLL in patients sensitive to thrombosis and subtypes of CLL that increase monocytes and NK cells in peripheral blood after treatment with a BTK inhibitor. In certain embodiments, the invention includes therapeutic methods of treating CLL and SLL using a combination of a BTK inhibitor and an anti-CD20 antibody.