Antibodies to granulocyte-macrophage colony-stimulating factor

Abstract

The current invention relates to high-affinity antibodies to Granulocyte-Macrophage Colony-Stimulating Factor that have reduced immunogenicity when administered to a human to treat diseases and method of using such antibodies.

1 . An isolated anti-GM-CSF antibody, comprising:
 a V H  region that comprises a CDR1 having a sequence NYYIH (SEQ ID NO:25), a CDR2 having a sequence WINAGNGNTKYSQKFQG (SEQ ID NO:27), and a CDR3 having a sequence RQRFPYYFDY (SEQ ID NO:16); and   a V L  region.   
     
     
         2 . (canceled) 
     
     
         3 . The antibody of  claim 1 , wherein the J segment of the V H  region comprises YFDYWGQGTLVTVSS (SEQ ID NO:14). 
     
     
         4 . The antibody of  claim 1 , wherein the V-segment of the V H  region has a V-segment sequence as shown in SEQ ID NO:5. 
     
     
         5 . The antibody of  claim 1 , wherein the V H  region has the sequence of SEQ ID NO:5. 
     
     
         6 . The antibody of  claim 1 , wherein the antibody comprises a V L  region that comprises a CDR1 having a sequence 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 31) 
                 
                     
                   RASQSVGTNVA 
                 
                     
                   or 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 32) 
                 
                     
                   RASQSIGSNLA, 
                 
             
                
                
                
                
                
                
               
            
           
         
         a CDR2 having a sequence STSSRAT (SEQ ID NO:33); and a CDR3 having a sequence QQFN(K/R)SPLT (SEQ ID NO:17). 
       
     
     
         7 . The antibody of  claim 6 , wherein the V L  region comprises a V segment that has a V-segment sequence as shown in SEQ ID NO:7. 
     
     
         8 . The antibody of  claim 6 , wherein the V L  region has the sequence of SEQ ID NO:7. 
     
     
         9 . The antibody of  claim 1 , wherein the antibody is an IgG. 
     
     
         10 . A pharmaceutical composition comprising an antibody of  claim 1 . 
     
     
         11 . A method of treating a patient that has a disease in which GM-CSF is a therapeutic target, the method comprising administering an antibody of  claim 1  to the patient in a therapeutically effective amount. 
     
     
         12 . The method of  claim 11 , wherein the disease is osteopenia, rheumatoid arthritis, asthma, multiple sclerosis, psoriasis, chronic obstructive pulmonary disease, idiopathic thrombocytopenia purpura, heart failure, cardiac damage due to an ischemic event, or diabetes.