Anti-ifnar1 antibodies with reduced fc ligand affinity

Abstract

The invention provides anti-IFNAR1 antibodies with reduced affinity for Fc receptors and/or ligands and methods of making and using such antibodies.

1 . A modified IgG class monoclonal antibody specific for IFNAR1, wherein said antibody comprises in the Fc region at least one amino acid substitution selected from the group consisting of L234F, L235E, and P331S, as numbered by the EU index as set forth in Kabat and wherein said antibody exhibits reduced affinity for at least one Fc ligand compared to an unmodified antibody. 
     
     
         2 - 3 . (canceled) 
     
     
         4 . The antibody of  claim 1 , wherein said antibody comprises an amino acid substitution of P331S. 
     
     
         5 . The antibody of  claim 1 , wherein said antibody comprises the amino acid substitutions: L234F and L235E. 
     
     
         6 . The antibody of  claim 1 , wherein said antibody comprises the amino acid substitutions: L234F, L235E, and P331S. 
     
     
         7 . (canceled) 
     
     
         8 . The antibody of  claim 1 , wherein, said antibody comprises an amino acid substitution of L235E of the Fc region. 
     
     
         9 . The antibody of  claim 1 , wherein, said antibody further comprises in the Fc region amino acid substitution S228P. 
     
     
         10 . The antibody of  claim 1 , wherein said antibody comprises at least one complementarity determining region (CDR) selected from Table 2. 
     
     
         11 - 13 . (canceled) 
     
     
         14 . The antibody of  claim 1 , wherein said antibody comprises:
 a. a human heavy chain variable region CDR1 comprising SEQ ID NO: 21;   b. a human heavy chain variable region CDR2 comprising SEQ ID NO: 22;   c. a human heavy chain variable region CDR3 comprising SEQ ID NO: 23;   d. a human light chain variable region CDR1 comprising SEQ ID NO: 24;   e. a human light chain variable region CDR2 comprising SEQ ID NO: 25; and   f. a human light chain variable region CDR3 comprising SEQ ID NO: 26.   
     
     
         15 . The antibody of  claim 1 , wherein, said antibody comprises:
 a. a human heavy chain variable region comprising the amino acid sequence of SEQ ID No: 38; and   b. a human light chain variable region comprising the amino acid sequence of SEQ ID No: 40.   
     
     
         16 - 17 . (canceled) 
     
     
         18 . The antibody of  claim 1 , wherein, said antibody comprises:
 a. a human heavy chain variable region comprising the amino acid sequence of SEQ ID No: 28; and   b. a human light chain variable region comprising the amino acid sequence of SEQ ID No: 30.   
     
     
         19 . The antibody of  claim 1 , wherein, said antibody comprises the light chain constant region sequence of SEQ ID No: 41. 
     
     
         20 . The antibody  claim 1 , wherein, said antibody comprises the heavy chain constant region of SEQ ID No: 42. 
     
     
         21 . The antibody of  claim 1 , wherein, said antibody comprises the light chain constant region having the amino acid sequence of SEQ ID No:41 and the heavy chain constant region having the amino acid sequence of SEQ ID No: 42. 
     
     
         22 . The antibody of  claim 21 , wherein, said antibody comprises a heavy chain amino acid sequence comprising allelic variation, wherein said allelic variation is at least one or more positions selected from the group consisting of 214, 221, 356, 358 as defined by the EU index numbering system. 
     
     
         23 . (canceled) 
     
     
         24 . An isolated nucleic acid comprising a polynucleotide encoding the antibody of of  claim 1 . 
     
     
         25 - 26 . (canceled) 
     
     
         27 . A host cell comprising or transformed with a vector, wherein said vector comprises the polynucleotide of  claim 24  operably linked to a promoter. 
     
     
         28 - 29 . (canceled) 
     
     
         30 . A pharmaceutical composition comprising the antibody of  claim 1 , and a pharmaceutically acceptable excipient. 
     
     
         31 . A method of treating a condition or a disease associated with an immune disorder, comprising administering to a subject in need thereof an effective amount of the composition of  claim 30 . 
     
     
         32 - 35 . (canceled) 
     
     
         36 . The method of  claim 31 , wherein said disease or disorder is systemic lupus erythematosus. 
     
     
         37 - 60 . (canceled) 
     
     
         61 . A method of making the antibody of  claim 1 . 
     
     
         62 - 67 . (canceled)