Treatment method

Abstract

The present invention relates to methods of treating a disease, and methods for reduction of the formation of anti-drug antibodies (ADAs) in response to the administration of a therapeutic agent. The invention further relates to methods of treating a disease, particularly a B-cell proliferative disorder, and methods for reduction of adverse effects in response to the administration of a therapeutic agent, particularly a T-cell activating therapeutic agent.

1 . A Type II anti-CD20 antibody for use in a method of treating a disease in a subject, the method comprising a treatment regimen comprising
 (i) administration to the subject of the Type II anti-CD20 antibody,   and consecutively after a period of time   (ii) administration to the subject of a therapeutic agent,   wherein the period of time between the administration of the Type II anti-CD20 antibody and the administration of the therapeutic agent is sufficient for reduction of the number of B-cells in the subject in response to the administration of the Type II anti-CD20 antibody.   
     
     
         2 . The Type II anti-CD20 antibody of  claim 1 , wherein the treatment regimen effectively reduces the formation of anti-drug antibodies (ADAs) in the subject in response to the administration of the therapeutic agent as compared to a corresponding treatment regimen without the administration of the anti-CD20 antibody. 
     
     
         3 . The Type II anti-CD20 antibody of  claim 1  or  2 , wherein the treatment regimen effectively reduces cytokine release associated with the administration of the therapeutic agent in the subject as compared to a corresponding treatment regimen without the administration of the Type II anti-CD20 antibody. 
     
     
         4 . The Type II anti-CD20 antibody of  claim 3 , wherein the therapeutic agent is a T cell activating therapeutic agent. 
     
     
         5 . A Type II anti-CD20 antibody for use in a method for (i) reducing the formation of anti-drug antibodies (ADAs) against a therapeutic agent in a subject and/or (ii) reducing cytokine release associated with the administration a therapeutic agent, particularly a T-cell activating therapeutic agent, in a subject, comprising administration of the Type II anti-CD20 antibody to the subject prior to administration of the therapeutic agent. 
     
     
         6 . The Type II anti-CD20 antibody of  claim 5 , wherein the period of time between the administration of the Type II anti-CD20 antibody and administration of the therapeutic agent is sufficient for reduction of the number of B-cells in the subject in response to the administration of the Type II anti-CD20 antibody. 
     
     
         7 . The Type II anti-CD20 antibody of any one of the preceding claims, wherein the anti-CD20 antibody comprises a heavy chain variable region comprising the heavy chain CDR (HCDR) 1 of SEQ ID NO: 4, the HCDR2 of SEQ ID NO: 5, and the HCDR3 of SEQ ID NO: 6; and a light chain variable region comprising the light chain CDR (LCDR) 1 of SEQ ID NO: 7, the LCDR2 of SEQ ID NO: 8 and the LCDR3 of SEQ ID NO: 9. 
     
     
         8 . The Type II anti-CD20 antibody of any one of the preceding claims, wherein the anti-CD20 antibody comprises the heavy chain variable region sequence of SEQ ID NO: 10 and the light chain variable region sequence of SEQ ID NO: 11. 
     
     
         9 . The Type II anti-CD20 antibody of any one of the preceding claims, wherein the anti-CD20 antibody is an IgG antibody, particularly an IgG 1  antibody, and wherein at least about 40% of the N-linked oligosaccharides in the Fc region of the anti-CD20 antibody are non-fucosylated. 
     
     
         10 . The Type II anti-CD20 antibody of any one of the preceding claims, wherein the anti-CD20 antibody is obinutuzumab. 
     
     
         11 . The Type II anti-CD20 antibody of any one of the preceding claims, wherein the therapeutic agent comprises a polypeptide. 
     
     
         12 . The Type II anti-CD20 antibody of any one of the preceding claims, wherein the therapeutic agent comprises an antibody. 
     
     
         13 . The Type II anti-CD20 antibody of  claim 12 , wherein the antibody comprised in the therapeutic agent specifically binds to carcinoembryonic antigen (CEA). 
     
     
         14 . The Type II anti-CD20 antibody of  claim 13 , wherein the antibody comprised in the therapeutic agent comprises
 (i) a heavy chain variable region comprising the heavy chain CDR (HCDR) 1 of SEQ ID NO: 14, the HCDR2 of SEQ ID NO: 15, and the HCDR3 of SEQ ID NO: 16; and a light chain variable region comprising the light chain CDR (LCDR) 1 of SEQ ID NO: 17, the LCDR2 of SEQ ID NO: 18 and the LCDR3 of SEQ ID NO: 19; or   (ii) a heavy chain variable region sequence of SEQ ID NO: 20 and a light chain variable region sequence of SEQ ID NO: 21.   
     
     
         15 . The Type II anti-CD20 antibody of  claim 12 , wherein the antibody comprised in the therapeutic agent specifically binds to CD3, particularly CD3ε. 
     
     
         16 . The Type II anti-CD20 antibody of  claim 15 , wherein the antibody comprised in the therapeutic agent comprises
 (i) a heavy chain variable region comprising the heavy chain CDR (HCDR) 1 of SEQ ID NO: 32, the HCDR2 of SEQ ID NO: 33, and the HCDR3 of SEQ ID NO: 34; and a light chain variable region comprising the light chain CDR (LCDR) 1 of SEQ ID NO: 35, the LCDR2 of SEQ ID NO: 36 and the LCDR3 of SEQ ID NO: 37; or   (ii) a heavy chain variable region sequence of SEQ ID NO: 38 and a light chain variable region sequence of SEQ ID NO: 39.   
     
     
         17 . The Type II anti-CD20 antibody of  claim 12 , wherein the antibody comprised in the therapeutic agent specifically binds to CD20. 
     
     
         18 . The Type II anti-CD20 antibody of  claim 15 , wherein the antibody comprised in the therapeutic agent comprises
 (i) a heavy chain variable region comprising the heavy chain CDR (HCDR) 1 of SEQ ID NO: 4, the HCDR2 of SEQ ID NO: 5, and the HCDR3 of SEQ ID NO: 6; and a light chain variable region comprising the light chain CDR (LCDR) 1 of SEQ ID NO: 7, the LCDR2 of SEQ ID NO: 8 and the LCDR3 of SEQ ID NO: 9; or   (ii) a heavy chain variable region sequence of SEQ ID NO: 10 and a light chain variable region sequence of SEQ ID NO: 11.   
     
     
         19 . The Type II anti-CD20 antibody of any one of the preceding claims, wherein the therapeutic agent comprises a cytokine, particularly interleukin-2. 
     
     
         20 . The Type II anti-CD20 antibody of  claim 19 , wherein the cytokine is a mutant human IL-2 polypeptide comprising the amino acid substitutions F42A, Y45A and L72G (numbering relative to the human IL-2 sequence SEQ ID NO: 12). 
     
     
         21 . The Type II anti-CD20 antibody of any one of the preceding claims, wherein the therapeutic agent comprises an immunoconjugate comprising an antibody as defined in  claim 14 , and a cytokine as defined in  claim 20 . 
     
     
         22 . The Type II anti-CD20 antibody of any one of  claims 1  to  16 , wherein the therapeutic agent comprises a bispecific antibody comprising an antibody as defined in  claim 14  and an antibody as defined in  claim 16 . 
     
     
         23 . The Type II anti-CD20 antibody of any one of  claims 1  to  12  and  16  to  18 , wherein the therapeutic agent comprises a bispecific antibody comprising an antibody as defined in  claim 16  and an antibody as defined in  claim 20 .