Dosage and administration of non-fucosylated anti-cd40 antibody

Abstract

This invention relates methods of using a non-fucosylated anti-CD40 antibody for treatment of cancer and chronic infectious diseases.

What is claimed is: 
     
         1 . A method of treating cancer, the method comprising the steps of administering an anti-CD40 antibody to a patient in need of such treatment,
 wherein the anti-CD40 antibody comprises the heavy chain variable region of SEQ ID NO:1 and the light chain variable region of SEQ ID NO:2, and a human constant region; wherein the constant region has an N-glycoside-linked sugar chain at residue N297 according to the EU index as set forth in Kabat and less than 5% of the N-glycoside-linked sugar chains comprise a fucose residue; and   wherein the anti-CD40 antibody is administered at a dose level between 0.1-2000 μg/kg patient body weight.   
     
     
         2 . The method of  claim 1 , wherein the dose level is between 10-1000 μg/kg. 
     
     
         3 . The method of  claim 1 , wherein the dose level is between 50-800 μg/kg. 
     
     
         4 . The method of  claim 1 , wherein the dose level is between 75-600 μg/kg. 
     
     
         5 . The method of  claim 1 , wherein the dose level is between 100-500 μg/kg. 
     
     
         6 . The method of  claim 1 , wherein the dose level is a range selected from the group consisting of 100-300 μg/kg, 300-500 μg/kg, 500-700 μg/kg, 700-900 μg/kg, and 900-1100 μg/kg. 
     
     
         7 . The method of  claim 1 , wherein the dose level is a range selected from the group consisting of 100-150 μg/kg, 150-200 μg/kg, 200-250 μg/kg, 250-300 μg/kg, 300-350 μg/kg, 350-400 μg/kg, 400-450 μg/kg, 450-500 μg/kg, 500-550 μg/kg, 550-600 μg/kg, 600-650 μg/kg, 650-700 μg/kg, 700-750 μg/kg, 750-800 μg/kg, 800-850 μg/kg, 850-900 μg/kg, 900-950 μg/kg, 950-1000 μg/kg, 1000-1050 μg/kg, and 1050-1100 μg/kg. 
     
     
         8 . The method of  claim 1 , wherein the dose level is a member of the group consisting of about 60 μg/kg, about 100 μg/kg, about 150 μg/kg, about 200 μg/kg, about 250 μg/kg, about 300 μg/kg, about 350 μg/kg, about 400 μg/kg, about 450 μg/kg, about 500 μg/kg, about 550 μg/kg, about 600 μg/kg, about 650 μg/kg, about 700 μg/kg, about 750 μg/kg, about 800 μg/kg, about 850 μg/kg, about 900 μg/kg, about 950 μg/kg, about 1000-1050 μg/kg, about 1050 μg/kg, and 1110 μg/kg. 
     
     
         9 . The method of  claim 1 , wherein the anti-CD40 antibody is administered every three weeks. 
     
     
         10 . The method of  claim 1 , wherein the anti-CD40 antibody is administered every six weeks. 
     
     
         11 . The method of  claim 1 , wherein the patient has a CD40 positive cancer. 
     
     
         12 . The method of  claim 1 , wherein the patient has a CD40 negative cancer. 
     
     
         13 . A method of treating cancer, the method comprising the steps of administering an anti-CD40 antibody and an anti-CTLA4 antibody to a patient in need of such treatment,
 wherein the anti-CD40 antibody comprises the heavy chain variable region of SEQ ID NO:1 and the light chain variable region of SEQ ID NO:2, and a human constant region; wherein the constant region glycosylated at residue N297 according to the EU index as set forth in Kabat and less than 5% of the glycosylated things comprise a fucose residue.   
     
     
         14 . The method of  claim 13 , wherein the anti-CTLA4 antibody is selected from the group consisting of ipilimumab and tremelimumab. 
     
     
         15 . A method of treating cancer, the method comprising the steps of administering an anti-CD40 antibody and an anti-PD1 antibody to a patient in need of such treatment,
 wherein the anti-CD40 antibody comprises the heavy chain variable region of SEQ ID NO:1 and the light chain variable region of SEQ ID NO:2, and a human constant region; wherein the constant region glycosylated at residue N297 according to the EU index as set forth in Kabat and less than 5% of the glycosylated things comprise a fucose residue.   
     
     
         16 . The method of  claim 15 , wherein the anti-PD1 antibody is selected from the group consisting of nivolumab, pidilizumab, and pembrolizumab. 
     
     
         17 . A method of treating cancer, the method comprising the steps of administering an anti-CD40 antibody and an anti-PD-L1 antibody to a patient in need of such treatment,
 wherein the anti-CD40 antibody comprises the heavy chain variable region of SEQ ID NO:1 and the light chain variable region of SEQ ID NO:2, and a human constant region; wherein the constant region glycosylated at residue N297 according to the EU index as set forth in Kabat and less than 5% of the glycosylated things comprise a fucose residue.   
     
     
         18 . The method of  claim 17 , wherein the anti-PD-L1 antibody is selected from the group consisting of MEDI4736 and MPDL3280A. 
     
     
         19 . The method of  claim 1 , wherein the cancer is a hematologic cancer. 
     
     
         20 . The method of  claim 1 , wherein the cancer is a solid tumor. 
     
     
         21 . The method of  claim 13 ,  15  or  17 , wherein the cancer is a hematologic cancer. 
     
     
         22 . The method of  claim 13 ,  15  or  17 , wherein the cancer is a solid tumor.