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: 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 molecule selected from the group consisting of a GITR binding molecule, a 4-1BB agonist, an OX40 agonist, and combinations thereof and a Bruton's tyrosine kinase (BTK) inhibitor are described. In some embodiments, the invention provides pharmaceutical compositions comprising combinations of a molecule selected from the group consisting of a GITR binding molecule, a 4-1BB agonist, an OX40 agonist, and combinations thereof and a BTK inhibitor, and methods of treating a disease using a molecule selected from the group consisting of a GITR binding molecule, a 4-1BB agonist, an OX40 agonist, and combinations thereof and a BTK inhibitor, in particular a cancer or an immune, autoimmune, or inflammatory disease.

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: 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 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: Sole structures (200) for articles of footwear (800) include sipes (202, 204, 210B, 210, 220, 222) that define discrete hexagonally-shaped sole elements (212, 214) at the ground-engaging or ground-facing surface (200B). At least some of the arch-supporting hexagonally shaped sole elements (212) may be elongated in one direction as compared to at least some of the corresponding hexagonally shaped sole elements (212) in the heel and/or forefoot support areas (404). Additionally or alternatively, the sole structure (200) may include a perimeter rim (200P) and/or side wall (200W) integrally formed with and extending upward from a foot-supporting surface (200S) at least at a rear heel area of the sole structure (200). This perimeter rim (200P) and/or side wall (200W) forms a rear heel pocket (240) that engages at least a portion (304) of the heel area of the upper (e.g., the rear heel area) with an interior surface (200S) of the perimeter rim (200P) and/or side wall (200W).

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 cyclin-dependent kinase-4/6 (CDK4/6) inhibitor, and/or a Bruton's tyrosine kinase (BTK) inhibitor are described. In certain embodiments, the invention includes therapeutic combinations of a cyclin-dependent kinase-4/6 (CDK4/6) inhibitor and a BTK inhibitor, a PI3K-? inhibitor and a BTK inhibitor, a JAK-2 and a BTK inhibitor, and a JAK-2, PI3K-?, and BTK inhibitor.

Abstract: Therapeutic combinations of a Janus kinase-2 (JAK-2) inhibitor, a Bruton's tyrosine kinase (BTK) inhibitor, and/or a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the ?- and ?-isoforms and selective for both ?- and ?-isoforms, are described. In some embodiments, the invention provides pharmaceutical compositions comprising combinations of (1) a PI3K-?inhibitor and a BTK inhibitor, (2) a JAK-2 inhibitor and a BTK inhibitor, or (3) a JAK-2 inhibitor, PI3K-? inhibitor, and BTK inhibitor, and methods of using the pharmaceutical compositions for treating a disease, in particular a cancer.

Abstract: Therapeutic combinations of a Janus kinase-2 (JAK-2) inhibitor, a Bruton's tyrosine kinase (BTK) inhibitor, and/or a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the ?- and ?-isoforms and selective for both ?- and ?-isoforms, are described. In some embodiments, the invention provides pharmaceutical compositions comprising combinations of (1) a PI3K-? inhibitor and a BTK inhibitor, (2) a JAK-2 inhibitor and a BTK inhibitor, or (3) a JAK-2 inhibitor, PI3K-? inhibitor, and BTK inhibitor, and methods of using the pharmaceutical compositions for treating a disease, in particular a cancer.

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: 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: 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 cyclin-dependent kinase-4/6 (CDK4/6) inhibitor, and/or a Bruton's tyrosine kinase (BTK) inhibitor are described. In certain embodiments, the invention includes therapeutic combinations of a cyclin-dependent kinase-4/6 (CDK4/6) inhibitor and a BTK inhibitor, a PI3K-? inhibitor and a BTK inhibitor, a JAK-2 and a BTK inhibitor, and a JAK-2, PI3K-?, and BTK inhibitor.

Abstract: Therapeutic combinations of a Janus kinase-2 (JAK-2) inhibitor, a Bruton's tyrosine kinase (BTK) inhibitor, and/or a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the ?- and ?-isoforms and selective for both ?- and ?-isoforms, are described. In some embodiments, the invention provides pharmaceutical compositions comprising combinations of (1) a PI3K-? inhibitor and a BTK inhibitor, (2) a JAK-2 inhibitor and a BTK inhibitor, or (3) a JAK-2 inhibitor, PI3K-? inhibitor, and BTK inhibitor, and methods of using the pharmaceutical compositions for treating a disease, in particular a cancer.

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 proteasome inhibitor and a Bruton's tyrosine kinase (BTK) inhibitor are described. In some embodiments, the invention provides pharmaceutical compositions comprising combinations of a proteasome 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 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.