Abstract: Disclosed are methods for the treatment of a coronavirus infection in a mammal comprising the step of administering to the mammal a therapeutically effective amount of ibrutinib. Also disclosed are disclosed methods of treating a subject for a clinical condition associated with hypercytokinemia, the method comprising: administering to the subject ibrutinib; wherein the subject is identified to have a higher level of at least one pro-inflammatory cytokine in a test sample obtained from the subject compared to a control sample or a reference value, to treat the subject for a mild, moderate, critical or severe form of a clinical condition associated with hypercytokinemia.This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.

Abstract: Described herein is a mutation that confers resistance to the treatment with a BTK inhibitor. Described herein is a modified PLC?2 polypeptide that is modified at amino acid position 742, 845, or 1140 and the modified PLC?2 polypeptide exhibits decreased inhibition (e.g., resistance) to a covalent and/or irreversible BTK inhibitor. Described herein are diagnostic methods for detecting the modified polypeptide and nucleic acid encoding the modified polypeptide and applications of the methods thereof. Described herein are compositions, combinations, and kits containing the modified polypeptide and methods of using the modified polypeptide. Also described herein are methods of using the modified polypeptide as screening agents for the identification and design of inhibitors of PLC?2.

Abstract: Described herein is a mutation that confers resistance to the treatment with a BTK inhibitor. Described herein is a modified PLC?2 polypeptide that is modified at amino acid position 742, 845, or 1140 and the modified PLC?2 polypeptide exhibits decreased inhibition (e.g., resistance) to a covalent and/or irreversible BTK inhibitor. Described herein are diagnostic methods for detecting the modified polypeptide and nucleic acid encoding the modified polypeptide and applications of the methods thereof. Described herein are compositions, combinations, and kits containing the modified polypeptide and methods of using the modified polypeptide. Also described herein are methods of using the modified polypeptide as screening agents for the identification and design of inhibitors of PLC?2.

Abstract: Biomarkers and methods are disclosed that identify patients being treated with a BTK inhibitor that have acquired a mutation that will cause resistance to the BTK inhibitor. Therefore, also disclosed is a method for treating a hematological cancer in the patient that involves detecting an acquired mutation that causes resistance to a BTK inhibitor and then selecting an alternative treatment if resistance is detected.

Abstract: Described herein is a mutation that confers resistance to the treatment with a BTK inhibitor. Described herein is a modified PLC?2 polypeptide that is modified at amino acid position 742, 845, or 1140 and the modified PLC?2 polypeptide exhibits decreased inhibition (e.g., resistance) to a covalent and/or irreversible BTK inhibitor. Described herein are diagnostic methods for detecting the modified polypeptide and nucleic acid encoding the modified polypeptide and applications of the methods thereof. Described herein are compositions, combinations, and kits containing the modified polypeptide and methods of using the modified polypeptide. Also described herein are methods of using the modified polypeptide as screening agents for the identification and design of inhibitors of PLC?2.