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

Abstract

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

We claim: 
     
         1 . A method of treating, stabilizing or lessening the severity or progression of a disease or disorder selected from the group consisting of B-cell non-Hodgkin's lymphoma, chronic lymphocytic leukemia and Waldenstrom's macroglobulinemia, the method comprising administering to a patient in need thereof a pharmaceutically acceptable composition comprising N-(3-(5-fluoro-2-(4-(2-methoxyethoxy)phenylamino)pyrimidin-4-ylamino)phenyl)acrylamide (1): 
       
         
           
           
               
               
           
         
       
     
     
         2 . The method according to  claim 1 , wherein the B-cell non-Hodgkin's lymphoma is indolent. 
     
     
         3 . The method according to  claim 2 , wherein the B-cell non-Hodgkin's lymphoma is selected from follicular lymphoma and marginal zone lymphoma. 
     
     
         4 . The method according to  claim 1 , wherein the B-cell non-Hodgkin's lymphoma is aggressive. 
     
     
         5 . The method according to  claim 4 , wherein the B-cell non-Hodgkin's lymphoma is selected from diffuse large B-cell lymphoma and mantle cell lymphoma. 
     
     
         6 . The method according to  claim 1 , wherein the pharmaceutically acceptable composition is formulated as an oral dosage form. 
     
     
         7 . The method according to  claim 6 , wherein the pharmaceutically acceptable composition is administered once a day. 
     
     
         8 . The method according to  claim 6 , wherein the pharmaceutically acceptable composition is administered twice a day. 
     
     
         9 . The method according to  claim 7  or  8 , wherein the pharmaceutically acceptable composition is administered for at least one 28-day cycle. 
     
     
         10 . The method according to  claim 9 , wherein the patient has failed at least one prior therapy. 
     
     
         11 . The method according to  claim 1 , wherein Compound 1 is in the form of a benzenesulfonic acid salt. 
     
     
         12 . The method according to  claim 11 , wherein the composition comprises from about 10% to about 50% N-(3-(5-fluoro-2-(4-(2-methoxyethoxy)phenylamino)pyrimidin-4-ylamino)phenyl)acrylamide besylate. 
     
     
         13 . The method according to  claim 12 , wherein the composition comprises about 10% N-(3-(5-fluoro-2-(4-(2-methoxyethoxy)phenylamino)pyrimidin-4-ylamino)phenyl)acrylamide besylate. 
     
     
         14 . The method according to  claim 12 , wherein the composition comprises about 42% N-(3-(5-fluoro-2-(4-(2-methoxyethoxy)phenylamino)pyrimidin-4-ylamino)phenyl)acrylamide besylate. 
     
     
         15 . The method according to  claim 1 , wherein the composition comprises from about 5% to about 15% by weight of wetting agent. 
     
     
         16 . The method according to  claim 12 , wherein the composition comprises about 10% by weight of wetting agent. 
     
     
         17 . The method according to  claim 15  or  16 , wherein the wetting agent is selected from poloxamer, polyoxyethylene ethers, polyoxyethylene sorbitan fatty acid esters polyoxyethylene fatty acid esters, polyethylene glycol fatty acid esters, polyoxyethylene hydrogenated castor oil, polyoxyethylene alkyl ether, polysorbates, cetyl alcohol, glycerol fatty acid esters, polyoxymethylene stearate, sodium lauryl sulfate, sorbitan fatty acid esters, sucrose fatty acid esters, benzalkonium chloride, polyethoxylated castor oil, and docusate sodium. 
     
     
         18 . The method according to  claim 17 , wherein the wetting agent is a poloxamer. 
     
     
         19 . The method according to  claim 18 , wherein the poloxamer is poloxamer 407. 
     
     
         20 . A method of preventing, treating, stabilizing or lessening the severity or progression of a disease or disorder selected from the group consisting of B-cell non-Hodgkin's lymphoma, chronic lymphocytic leukemia and Waldenstrom's macroglobulinemia, the method comprising administering to a patient in need thereof a composition comprising a therapeutically effective amount of Compound 1, wherein the therapeutically effective amount is about 125 mg to about 1250 mg. 
     
     
         21 . The method of  claim 20 , wherein the therapeutically effective amount is about 125 mg to about 1000 mg. 
     
     
         22 . The method of  claim 20 , wherein the therapeutically effective amount is about 125 mg to about 750 mg. 
     
     
         23 . The method of  claim 20 , wherein the therapeutically effective amount is about 125 mg to about 625 mg. 
     
     
         24 . The method of  claim 20 , wherein the therapeutically effective amount is about 250 mg to about 1250 mg. 
     
     
         25 . The method of  claim 20 , wherein the therapeutically effective amount is about 250 mg to about 1000 mg. 
     
     
         26 . The method of  claim 20 , wherein the therapeutically effective amount is about 250 mg to about 750 mg. 
     
     
         27 . The method of  claim 20 , wherein the therapeutically effective amount is about 250 mg to about 625 mg. 
     
     
         28 . The method of  claim 20 , wherein the therapeutically effective amount is about 250 mg to about 400 mg. 
     
     
         29 . The method of  claim 20 , wherein the therapeutically effective amount is about 400 mg to about 1250 mg. 
     
     
         30 . The method of  claim 20 , wherein the therapeutically effective amount is about 400 mg to about 1000 mg. 
     
     
         31 . The method of  claim 20 , wherein the therapeutically effective amount is about 400 mg to about 750 mg. 
     
     
         32 . The method of  claim 20 , wherein the therapeutically effective amount is about 400 mg to about 625 mg. 
     
     
         33 . The method of  claim 20 , wherein the therapeutically effective amount is about 625 mg to about 1250 mg. 
     
     
         34 . The method of  claim 20 , wherein the therapeutically effective amount is about 625 mg to about 1000 mg. 
     
     
         35 . The method of  claim 20 , wherein the therapeutically effective amount is about 625 mg to about 750 mg. 
     
     
         36 . The method of  claim 20 , wherein the therapeutically effective amount is about 750 mg to about 1250 mg. 
     
     
         37 . The method of  claim 20 , wherein the therapeutically effective amount is about 750 mg to about 1000 mg. 
     
     
         38 . The method of  claim 20 , wherein the therapeutically effective amount is about 1000 mg to about 1250 mg. 
     
     
         39 . The method of  claim 20 , wherein the therapeutically effective amount is about 375 mg BID. 
     
     
         40 . The method of  claim 20 , wherein the therapeutically effective amount is about 500 mg BID.