Methods of treating a disease or disorder associated with bruton's tyrosine kinase

Abstract

The present invention provides methods of treating, stabilizing or lessening the severity or progression of a disease or disorder associated with BTK.

1 . A method of treating, stabilizing or lessening the severity or progression of one or more diseases and conditions associated with BTK comprising administering to a patient in need thereof an irreversible BTK inhibitor and an anti-CD20 antibody, wherein the irreversible BTK inhibitor has not more than about 50% inhibition of a kinase selected from c-Kit, PDGFRa, RIPK2, HCK, EPHA6, LYN, CSK, LCK, ZAK/MLTK, LYN B, FRK/PTK5, FYN, BRAF, RIPK3, ARAF and SRMS, or combinations thereof. 
     
     
         2 . The method according to  claim 1 , wherein the irreversible BTK inhibitor has not more than about 30% inhibition of a kinase selected from c-Kit, RIPK2, HCK, EPHA6, LYN, CSK, ZAK/MLTK, LYN B, FRK/PTK5, FYN, BRAF, RIPK3, ARAF and SRMS, or combinations thereof. 
     
     
         3 . The method according to  claim 1 , wherein the irreversible BTK inhibitor has not more than about 10% inhibition of a kinase selected from EPHA6, LYN B, FRK/PTK5, BRAF, RIPK3, ARAF and SRMS, or combinations thereof. 
     
     
         4 . The method according to  claim 1 , wherein the irreversible BTK inhibitor has a percent inhibition of LYN that is not more than about 20-30%. 
     
     
         5 . The method according to  claim 1 , wherein the anti-CD20 antibody is selected from rituximab and ofatumumab. 
     
     
         6 - 22 . (canceled) 
     
     
         23 . A system for treating, stabilizing or lessening the severity of one or more diseases or conditions associated with BTK, the system comprising Compound 1, or a pharmaceutically acceptable salt thereof, an anti-CD20 antibody and at least one additional therapeutic agent selected from fludarabine, cyclophosphamide and bendamustine. 
     
     
         24 . The system according to  claim 23 , wherein the anti-CD20 antibody is selected from rituximab and ofatumumab.