Dosing methods for treating disease

Abstract

The invention relates to a method for treating disease such as viral infections, tumors, and cancers, comprising administering a TLR7 agonist or TLR7 agonist prodrug according to a cyclical dosing schedule having a dosing period and a resting period. For example, the method encompasses treating disease with: Formula (I) 5-amino-3-(2′-Q-acetyl-3′-deoxy-β-D-ri-bofuranosyl)-3H-thia-zolo[4,5-d]pyrimidin-2-one Tosylate according to a dosing schedule of every-other-day or a dosing schedule of three consecutive days of dosing followed by four consecutive days of not dosing.

1 . A method tor treating disease comprising the cyclic administration of a TLR7 agonist or TLR7 agonist prodrug to a patient in need thereof according to a dosing schedule having a dosing period of at least one day in which a therapeutically effective amount of the TLR7 agonist or TLR7 agonist prodrug is administered daily followed by at resting period of at least one day in which the TLR7 agonist or TLR7 agonist prodrug is not administered. 
     
     
         2 . The method of  claim 1 , wherein down-modulation of immune stimulation according to the dosing schedule is less than down-modulation of immune stimulation for the same TLR7 agonist or the same TLR7 agonist prodrug administered according to a once-a-day dosing schedule. 
     
     
         3 . The method of  claim 1 , wherein the dosing period is independently selected from 1, 2, 3, 4, and 5 days, and the resting period is independently selected from 1, 2, 3, 4, and 5 days. 
     
     
         4 . The method of  claim 3 , wherein the dosing period is 3 or 4 days and the resting period is 3 or 4 days. 
     
     
         5 . The method of  claim 4 , wherein the dosing period is 3 days. 
     
     
         6 . The method of  claim 4 , wherein the resting period is 4 days. 
     
     
         7 . The method of  claim 4 , wherein the dosing period is 3 days and the resting period is 4 days. 
     
     
         8 . The method of  claim 1 , wherein the TLR7 agonist or TLR7 agonist prodrug is: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         9 . The method of  claim 8 , wherein the TLR7 agonist or TLR7 agonist prodrug is: 
       
         
           
           
               
               
           
         
       
     
     
         10 . The method of  claim 3 , wherein the therapeutically effective amount of the TLR7 agonist or TLR7 agonist prodrug is from 0.01 mg/kg to 100 mg/kg. 
     
     
         11 . The method of  claim 3 , wherein the patient is a human. 
     
     
         12 . The method of  claim 3 , wherein the therapeutically effective amount of the TLR7 agonist or TLR7 agonist prodrug is from about 0.1 mg/day to about 10,000 mg/day. 
     
     
         13 . The method of  claim 1 , wherein the disease is asthma, allergy, a viral, bacterial or fungal infection, a tumor, or a cancer. 
     
     
         14 . The method of  claim 13 , wherein the disease is hepatitis C viral infection. 
     
     
         15 . The method of  claim 13 , wherein the cancer is selected from the group consisting of colon, bladder, lung, prostate, stomach, and pancreas carcinomas and lymphoblastic and myeloid leukemia. 
     
     
         16 . The method of  claim 3 , wherein the dosing period is 1 day and the testing period is 1 day. 
     
     
         17 . The method of  claim 16 , wherein the TLR7 agonist or TLR7 agonist prodrug is: 
       
         
           
           
               
               
           
         
       
       of a pharmaceutically acceptable salt thereof. 
     
     
         18 . The method of  claim 17 , wherein the TLR7 agonist or TLR7 agonist prodrug is: 
       
         
           
           
               
               
           
         
       
     
     
         19 . The method of  claim 16 , wherein the therapeutically effective amount of the TLR7 agonist or TLR7 agonist prodrug is from 0.01 mg/kg to 100 mg/kg. 
     
     
         20 . The method of  claim 16 , wherein the patient is human. 
     
     
         21 . The method of  claim 16 , wherein the therapeutically effective amount of the TLR7 agonist or TLR7 agonist prodrug is from about 0.1 mg/day to about 10,000 mg/day. 
     
     
         22 . The method of  claim 16 , wherein the disease is asthma, allergy, a viral, bacterial or fungal infection, a tumor, or a cancer. 
     
     
         23 . The method of  claim 22 , wherein the disease is hepatitis C viral infection. 
     
     
         24 . The method of  claim 22 , wherein the cancer is selected from the group consisting of colon, bladder, lung, prostate, stomach, and pancreas carcinomas and lymphoblastic and myeloid leukemia.