Anti-tlr4 antibodies and uses thereof

Abstract

Disclosed are antibodies that specifically bind Toll-like Receptor 4 (TLR-4), and to methods of using the anti-TLR4 antibodies as therapeutics and diagnostic agents.

1 - 32 . (canceled) 
     
     
         33 . A method of treating scleroderma in a subject in need thereof, comprising administering to the subject a composition comprising an antibody that binds specifically to Toll-like Receptor 4 (TLR4), wherein the antibody comprises:
 a) a heavy chain variable region comprising a complementarity determining region 1 (CDRH1) comprising the amino acid sequence of SEQ ID NO: 25;   a complementarity determining region 2 (CDRH2) comprising the amino acid sequence of SEQ ID NO: 26;   a complementarity determining region 3 (CDRH3) comprising the amino acid sequence of SEQ ID NO: 44; and   b) a light chain variable region comprising a complementarity determining region 1 (CDRL1) comprising the amino acid sequence of SEQ ID NO: 37;   a complementarity determining region 2 (CDRL2) comprising the amino acid sequence of SEQ ID NO: 38; and   a complementarity determining region 3 (CDRL3) comprising the amino acid sequence of SEQ ID NO: 39.   
     
     
         34 . The method of  claim 33 , wherein the scleroderma is systemic sclerosis (SS). 
     
     
         35 . The method of  claim 33 , wherein the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 43 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 4. 
     
     
         36 . The method of  claim 33 , wherein the antibody is a monoclonal antibody. 
     
     
         37 . The method of  claim 33 , wherein the antibody is a humanized antibody. 
     
     
         38 . The method of  claim 33 , wherein the antibody is an IgG isotype. 
     
     
         39 . The method of  claim 38 , wherein said antibody is an IgG1 isotype. 
     
     
         40 . The method of  claim 39 , wherein amino acid residues at positions 325-328 (EU numbering) of the CH2 domain of a IgG1 consist of an amino acid motif of SKAF (SEQ ID NO: 42).