Method of Treatment Using Humanized Anti-CD11a Antibodies

Abstract

Humanized anti-CD11 a antibodies and various uses therefor are disclosed. The humanized anti-CD11 a antibody may bind specifically to human CD11 a 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 erythematosus 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 . 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. 
     
     
         8 . The method of  claim 7 , wherein the humanized anti-CD11a antibody has all human kappa I consensus light chain framework residues. 
     
     
         9 . The method of  claim 7 , wherein the humanized anti-CD11a antibody has human V H  subgroup III consensus heavy chain framework residue 93H. 
     
     
         10 . The method of  claim 7 , 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. 
     
     
         11 . The method of  claim 7 , wherein the humanized anti-CD11a antibody is a full length antibody. 
     
     
         12 . The method of  claim 11 , wherein the humanized anti-CD11a antibody is a human IgG. 
     
     
         13 . A method of treating dermatitis 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. 
     
     
         14 . The method of  claim 13 , wherein the humanized anti-CD11a antibody has all human kappa I consensus light chain framework residues. 
     
     
         15 . The method of  claim 13 , wherein the humanized anti-CD11a antibody has human V H  subgroup III consensus heavy chain framework residue 93H. 
     
     
         16 . The method of  claim 13 , 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. 
     
     
         17 . The method of  claim 13 , wherein the humanized anti-CD11a antibody is a full length antibody. 
     
     
         18 . The method of  claim 17 , wherein the humanized anti-CD11a antibody is a human IgG. 
     
     
         19 . A method of treating Crohn's disease and ulcerative colitis 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. 
     
     
         20 . The method of  claim 19 , wherein the humanized anti-CD11a antibody has all human kappa I consensus light chain framework residues. 
     
     
         21 . The method of  claim 19 , wherein the humanized anti-CD11a antibody has human V H  subgroup III consensus heavy chain framework residue 93H. 
     
     
         22 . The method of  claim 19 , 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. 
     
     
         23 . The method of  claim 19 , wherein the humanized anti-CD11a antibody is a full length antibody. 
     
     
         24 . The method of  claim 19 , wherein the humanized anti-CD11a antibody is a human IgG. 
     
     
         25 . A method of treating graft versus host disease or host versus graft disease in an allogeneic transplantation in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a humanized anti-CD11a antibody in conjunction with an immunosuppressive agent, 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. 
     
     
         26 . The method of  claim 25 , wherein the allogeneic transplantation is a kidney transplant. 
     
     
         27 . The method of one of  claim 25  or  26 , wherein the immunosuppressive agent is a steroid. 
     
     
         28 . The method of  claim 27 , wherein the steroid is a glucocorticosteroid. 
     
     
         29 . The method of  claim 28 , wherein the glucocorticosteroid is selected from the group consisting of prednisone, methylprednisolone and dexamethasone. 
     
     
         30 . The method of  claim 25 , wherein the immunosuppressive agent is azathioprine. 
     
     
         31 . The method of one of  claim 25  or  26 , wherein the immunosuppressive agent is cyclosporine A. 
     
     
         32 . The method of one of  claim 25  or  26 , wherein the immunosuppressive agent is rapamycin. 
     
     
         33 . The method of one of  claim 25  or  26 , wherein the immunosuppressive agent is administered before, after or simultaneously with the humanized anti-CD11a antibody.