HUMANIZED AFFINITY MATURED ANTI-FcRn ANTIBODIES

Abstract

Provided herein are recombinant antibodies and antigen-binding portions thereof useful for binding to FcRn and blocking binding of FcRn to IgG Fc. The FcRn-binding proteins can be used to treat a variety of disorders including autoimmune disorders.

We claim: 
     
         1 . A nucleic acid encoding an antibody or antigen-binding fragment thereof which binds to FcRn, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region and a light chain variable region and wherein each of the heavy chain and the light chain variable regions comprises a CDR1, CDR2, and CDR3; and
 wherein:   the sequence of CDR1 of the heavy chain is SEQ ID NO:2; and   the sequence of CDR2 of the heavy chain is SEQ ID NO:4; and   the sequence of CDR3 of the heavy chain is SEQ ID NO:55; and   the sequence of CDR1 of the light chain is SEQ ID NO:6; and   the sequence of CDR2 of the light chain is SEQ ID NO:8; and   the sequence of CDR3 of the light chain is SEQ ID NO:10.   
     
     
         2 . The nucleic acid of  claim 1 , wherein:
 the sequence of the heavy chain variable region comprises SEQ ID NO:56, or the sequence of the heavy chain variable region comprises a sequence that is at least 95% identical to the heavy chain variable region amino acid sequence of SEQ ID NO:56; and   the sequence of the light chain variable region comprises SEQ ID NO:22, or the sequence of the light chain variable region comprises a sequence that is at least 95% identical to the light chain variable region amino acid sequence of SEQ ID NO:22.   
     
     
         3 . The nucleic acid of  claim 2 , wherein the sequence of the heavy chain variable region of the antibody or antigen-binding fragment thereof is SEQ ID NO:56, and wherein the sequence of the light chain variable region of the antibody or antigen-binding fragment thereof is SEQ ID NO:22. 
     
     
         4 . A nucleic acid vector comprising the nucleic acid of  claim 1 . 
     
     
         5 . A prokaryotic or eukaryotic host cell comprising the nucleic acid according to  claim 1 . 
     
     
         6 . The nucleic acid of  claim 1 , wherein the antibody or antigen-binding fragment thereof has isotype IgG4. 
     
     
         7 . The nucleic acid of  claim 6 , wherein the antibody or antigen-binding fragment thereof contains a S241P modification in the heavy chain.