Anti-cxcr3 antibodies and methods of use thereof

Abstract

The present disclosure provides anti-CXCR3 antibodies and methods of using the antibodies to diagnose and/or treat CXCR3-associated disorders such as diabetes mellitus type I (T1D), particularly new-onset T1D. In certain embodiments, disclosed herein are CXCR3 neutralizing antibodies.

1 . An antibody or antigen binding fragment capable of binding to CXCR3, wherein the antibody or fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), and wherein:
 a) the heavy chain variable region comprises three complementarity determining regions (CDRs) that are at least about 95% identical to the three CDRs from any one of SEQ ID NO: 2, 4, 6, and 8; and/or the light chain variable region comprises three CDRs that are at least about 95% identical to the three CDRs from any one of SEQ ID NO: 3, 5, 7, and 9,   b) the heavy chain variable region comprises three CDRs that are at least about 95% identical to the three CDRs from any one of SEQ ID NO: 10, 12, 14, and 16; and/or the light chain variable region comprises three CDRs that are at least about 95% identical to the three CDRs from any one of SEQ ID NO: 11, 13, 15, and 17,   c) the heavy chain variable region comprises three CDRs that are at least about 95% identical to the three CDRs from any one of SEQ ID NO: 18, 20, 22, 24, and 26-33; and/or the light chain variable region comprises three CDRs that are at least about 95% identical to the three CDRs from any one of SEQ ID NO: 19, 21, 23, 25, and 34-37,   d) the heavy chain variable region comprises three CDRs that are at least about 95% identical to the three CDRs from any one of SEQ ID NO: 38, 40, 42, 44, 46-48, and 63-66; and/or the light chain variable region comprises three CDRs that are at least about 95% identical to the three CDRs from any one of SEQ ID NO: 39, 41, 43, 45, 49-54, and 67-70,   
       or
 e) the heavy chain variable region comprises three CDRs that are at least about 95% identical to the three CDRs from any one of SEQ ID NO: 55, 57, 59, and 61; and/or the light chain variable region comprises three CDRs that are at least about 95% identical to the three CDRs from any one of SEQ ID NO: 56, 58, 60, and 62. 
 
     
     
         2 - 37 . (canceled) 
     
     
         38 . An antibody or antigen binding fragment capable of binding to CXCR3, wherein the antibody or fragment comprises a heavy chain variable region (VH) and a light chain variable region (VL), and wherein:
 a) the heavy chain variable region comprises a sequence at least about 90% identical to any one of SEQ ID NO: 2, 4, 6, and 8; and/or the light chain variable region comprises a sequence at least about 90% identical to any one of SEQ ID NO: 3, 5, 7, and 9,   b) the heavy chain variable region comprises a sequence at least about 90% identical to any one of SEQ ID NO: 10, 12, 14, and 16; and/or the light chain variable region comprises a sequence at least about 90% identical to any one of SEQ ID NO: 11, 13, 15, and 17,   c) the heavy chain variable region comprises a sequence at least about 90% identical to any one of SEQ ID NO: 18, 20, 22, 24, and 26-33; and/or the light chain variable region comprises a sequence at least about 90% identical to any one of SEQ ID NO: 19, 21, 23, 25, and 34-37,   d) the heavy chain variable region comprises a sequence at least about 90% identical to any one of SEQ ID NO: 38, 40, 42, 44, 46-48, and 63-66; and/or the light chain variable region comprises a sequence at least about 90% identical to any one of SEQ ID NO: 39, 41, 43, 45, 49-54, and 67-70,   
       or
 e) the heavy chain variable region comprises a sequence at least about 90% identical to any one of SEQ ID NO: 55, 57, 59, and 61; and/or the light chain variable region comprises a sequence at least about 90% identical to any one of SEQ ID NO: 56, 58, 60, and 62. 
 
     
     
         39 - 49 . (canceled)