Method of treatment using humanized anti-CD11a antibodies

Abstract

Humanized anti-CD11a antibodies and various uses therefor are disclosed. The humanized anti-CD11a antibody may bind specifically to human CD11a I-domain, have an IC50(nM) value of no more than about 1 nM for preventing adhesion of Jurkat cells to normal human epidermal keratinocytes expressing ICAM-1, and/or an IC50 (nM) value of no more than about 1 nM in the mixed lymphocyte response assay.

1 . A method of treating systemic lupus erythmatosus in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a humanized anti-CD11a antibody which binds specifically to human CD11a I-domain, said antibody containing a heavy chain variable region comprising the amino acid sequence of (a) CDR1 (SEQ ID NO:10), CDR2 (SEQ ID NO:11) and CDR3 (SEQ ID NO:12) or (b) SEQ ID NO:5, and a light chain variable region comprising the amino acid sequence of (a) CDR1 (SEQ ID NO: 13), CDR2 (SEQ ID NO:14) and CDR3 (SEQ ID NO:15) or (b) SEQ ID NO:2.  
     
     
         2 . The method of  claim 1 , wherein the humanized anti-CD11a antibody has all human kappa I consensus light chain framework residues.  
     
     
         3 . The method of  claim 1 , wherein the humanized anti-CD11a antibody has human V H  subgroup III consensus heavy chain framework residue 93H.  
     
     
         4 . The method of  claim 1 , wherein the humanized anti-CD11a antibody has a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:5 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:2.  
     
     
         5 . The method of  claim 1 , wherein the humanized anti-CD11a antibody is a full length antibody.  
     
     
         6 . The method of  claim 5 , wherein the humanized anti-CD11a antibody is a human IgG.  
     
     
         7 . The method of  claim 1 , wherein the humanized anti-CD11a antibody is bound to a cytotoxic agent.  
     
     
         8 . A method of treating multiple sclerosis in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a humanized anti-CD11a antibody which binds specifically to human CD11a I-domain, said antibody containing a heavy chain variable region comprising the amino acid sequence of (a) CDR1 (SEQ ID NO:10), CDR2 (SEQ ID NO:11) and CDR3 (SEQ ID NO:12) or (b) SEQ ID NO:5, and a light chain variable region comprising the amino acid sequence of (a) CDR1 (SEQ ID NO: 13), CDR2 (SEQ ID NO:14) and CDR3 (SEQ ID NO:15) or (b) SEQ ID NO:2.  
     
     
         9 . The method of  claim 8 , wherein the humanized anti-CD11a antibody has all human kappa I consensus light chain framework residues.  
     
     
         10 . The method of  claim 8 , wherein the humanized anti-CD11a antibody has human V H  subgroup III consensus heavy chain framework residue 93H.  
     
     
         11 . The method of  claim 8 , wherein the humanized anti-CD11a antibody has a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:5 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:2.  
     
     
         12 . The method of  claim 8 , wherein the humanized anti-CD11a antibody is a full length antibody.  
     
     
         13 . The method of  claim 12 , wherein the humanized anti-CD11a antibody is a human IgG.  
     
     
         14 . The method of  claim 8 , wherein the humanized anti-CD11a antibody is bound to a cytotoxic agent.