Pharmacyclics, Inc.

Janssen Pharmaceutica Nv

Cornell University

Betty Chang

Joseph J Buggy

Tarak D Mody

John C Byrd

Sriram Balasubramanian

Natarajan Muthusamy

Amy Jo Johnson

Jason A Dubovsky

Susanne M Steggerda

Hsin-Kang Hsieh

Ling Xue

Leo Cheung

Hsu-Ping Kuo

Described herein are mutations that confer resistance to treatment with a BTK inhibitor. Described herein are modified BTK polypeptides that exhibit decreased inhibition (i.e. are resistant) to a covalent and/or irreversible BTK inhibitor. Also described herein modifications of PLCy2 and CARD 11 polypeptides that confer resistance to treatment with a BTK inhibitor. Described herein are diagnostic methods for detecting the modified polypeptides and nucleic acids encoding the modified polypeptides and applications of the methods thereof. Described herein are compositions, combinations, and kits containing the modified polypeptides and methods of using the modified polypeptides. Also described herein are methods of using modified BTK polypeptides as screening agents for the identification and design of second-generation BTK inhibitors.

Mutations associated with resistance to inhibitors of Bruton's Tyrosine Kinase (BTK)

Disclosed herein are methods, compositions, and kits for treating a B-cell malignancy comprising administering a combination of a BTK inhibitor (e.g. ibrutinib) and a PIM inhibitor. Also disclosed herein are methods, compositions, and kits for treating a BTK-resistant B-cell malignancy comprising administering a combination of a BTK inhibitor (e.g. ibrutinib) and a PIM inhibitor.

Bruton's tyrosine kinase inhibitor combinations and uses thereof

Described herein are methods and compositions comprising a covalent TEC family kinase inhibitor for use in adjuvant therapy, including adjuvant cancer therapy, vaccination and treatment of immune disorders and pathogenic infections.

TEC family kinase inhibitor adjuvant therapy

Growing community of inventors

Cupertino, CA, United States of America

Betty Chang