Acerta Pharma B.v.

Gilead Calistoga LLC

Roger G Ulrich

Brian Lannutti

Wayne Philip Rothbaum

Tjeerd Barf

Allard Kaptein

Ahmed Hamdy

Raquel Izumi

Todd Covey

Dave Johnson

W Michael Gallatin

Neill A Giese

Langdon Miller

Thomas M Jahn

Jerry B Evarts

David M Johnson

Neill Giese

Michael W Gallatin

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.

Methods of treating chronic lymphocytic leukemia and small lymphocytic leukemia using a BTK inhibitor

Therapeutic combinations of a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the &#x3b3;- and &#x3b4;-isoforms and selective for both &#x3b3;- and &#x3b4;-isoforms (PI3K-&#x3b3;,&#x3b4;, PI3K-&#x3b3;, and PI3K-&#x3b4;), 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-&#x3b4; inhibitor and a BTK inhibitor, a JAK-2 and a BTK inhibitor, and a BCL-2 and BTK inhibitor.

Therapeutic combinations of a BTK inhibitor, a PI3K inhibitor, a JAK-2 inhibitor, and/or a BCL-2 inhibitor

In some embodiments, the invention includes a therapeutic combination of a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the &#x3b3;- and &#x3b4;-isoforms and selective for both &#x3b3;- and &#x3b4;-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-&#x3b4; 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.

Therapeutic combination of PI3K inhibitor and a BTK inhibitor

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, 

Therapies for hematologic malignancies

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 &#x3b3;- and &#x3b4;-isoforms and selective for both &#x3b3;- and &#x3b4;-isoforms, are described. In some embodiments, the invention provides pharmaceutical compositions comprising combinations of (1) a PI3K-&#x3b4; inhibitor and a BTK inhibitor, (2) a JAK-2 inhibitor and a BTK inhibitor, or (3) a JAK-2 inhibitor, PI3K-&#x3b4; inhibitor, and BTK inhibitor, and methods of using the pharmaceutical compositions for treating a disease, in particular a cancer.

Therapeutic combinations of a BTK inhibitor, a PI3K inhibitor and/or a JAK-2 inhibitor

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 administration of a compound of formula A, 

The invention provides methods to treat certain liver disorders by administering a compound that inhibits PD K isoforms, particularly the delta isoform. It further provides specific compounds useful for these methods and ways to identify subjects who are particularly suitable for receiving these treatments.

Treatment of liver disorders with PI3K inhibitors

The invention provides compounds, compositions and methods to treat certain inflammatory conditions and/or oncology by administering a compound that inhibits PI3K isoforms, particularly the delta isoform. It further provides specific stereoisomers of a compound useful for these methods. In particular, the compound is an optically active atropisomer of 2-((6-amino-9H-purin-9-yl)methyl)-5-methyl-3-o-tolylquinazolin-4(3H)-one. 

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Foster City, CA, United States of America

Roger G Ulrich