Monoclonal antibodies that bind to hgm-csf and medical compositions comprising same

Abstract

Disclosed herein are anti-hGM-CSF monoclonal antibodies and antigen-binding fragments of such antibodies, with improved neutralizing capacity to hGM-CSF activity. Pharmaceutical compositions comprising such an antibody or antigen-binding fragment are also provided. The present invention is useful for the treatment of various diseases that are associated with aberrant expression of hGM-CSF.

1 - 95 . (canceled) 
     
     
         96 . A method for treatment of a disease or disorder associated with over-expression of hGM-CSF in a subject, comprising administering to the subject a therapeutically effective amount of an isolated anti-hGM-CSF monoclonal antibody or antigen-binding fragment thereof comprising
 (a) a heavy chain comprising a VH-CDR1-containing sequence, a VH-CDR2-containing sequence, and a VH-CDR3-containing sequence, wherein:
 (i) the VH-CDR1-containing sequence is SYGMH (SEQ ID NO: 4), 
 (ii) the VH-CDR2-containing sequence is LTYHHGNRKFYADSVRG (SEQ ID NO: 5), and 
 (iii) the VH-CDR3-containing sequence is ESMGAINDN (SEQ ID NO: 6); and 
   (b) a light chain comprising a VL-CDR1-containing sequence, a VL-CDR2-containing sequence, and a VL-CDR3-containing sequence, wherein:
 (i) the VL-CDR1-containing sequence is IGNNNNIGSHAVG (SEQ ID NO: 7), 
 (ii) the VL-CDR2-containing sequence is GRSPPS (SEQ ID NO: 8), and 
 (iii) the VL-CDR3-containing sequence is STWDSSLSAVV (SEQ ID NO: 9), wherein the antibody or antigen-binding fragment thereof binds hGM-CSF and is capable of neutralizing hGM-CSF activity, thereby treating the disease or disorder. 
   
     
     
         97 . The method as claimed in  claim 96 , wherein the antibody or antigen-binding fragment is administered to the subject at a dose not exceeding 500 mg. 
     
     
         98 . The method as claimed in  claim 96 , wherein the disease or disorder is selected from the group consisting of chronic obstructive pulmonary disease (COPD), asthma, bronchial asthma, paediatric asthma, severe asthma, acute asthma attacks, cystic fibrosis, interstitial lung disease, rhinitis, arthritis and related arthropathies, rheumatoid arthritis, psoriasis, myeloid leukemia, and multiple sclerosis. 
     
     
         99 . The method as claimed in  claim 98 , wherein the antibody or antigen-binding fragment is administered to the subject at a dose not exceeding 500 mg. 
     
     
         100 . A method for treatment of a disease or disorder associated with over-expression of hGM-CSF in a subject, comprising administering to the subject a therapeutically effective amount of an isolated anti-hGM-CSF monoclonal antibody or antigen-binding fragment thereof comprising a heavy chain variable region having a heavy chain variable region sequence and a light chain variable region having a light chain variable region sequence, wherein the heavy chain variable region sequence is SEQ ID NO: 348, and wherein the light chain variable region sequence is SEQ ID NO: 365, wherein the antibody or antigen-binding fragment thereof binds hGM-CSF and is capable of neutralizing hGM-CSF activity, thereby treating the disease or disorder. 
     
     
         101 . A method for treatment of a disease or disorder associated with over-expression of hGM-CSF in a subject, comprising administering to the subject a therapeutically effective amount of an isolated anti-hGM-CSF monoclonal antibody or antigen-binding fragment thereof comprising a heavy chain variable region having a heavy chain variable region sequence and a light chain variable region having a light chain variable region sequence, wherein the heavy chain variable region sequence is SEQ ID NO: 361, and wherein the light chain variable region sequence is SEQ ID NO: 365, wherein the antibody or antigen-binding fragment thereof binds hGM-CSF and is capable of neutralizing hGM-CSF activity, thereby treating the disease or disorder. 
     
     
         102 . A method for treatment of a disease or disorder associated with over-expression of hGM-CSF in a subject, comprising administering to the subject a therapeutically effective amount of an isolated anti-hGM-CSF monoclonal antibody comprising a heavy chain having a heavy chain sequence and a light chain having a light chain sequence, wherein the heavy chain sequence is SEQ ID NO: 46, and wherein the light chain sequence is SEQ ID NO: 36, wherein the antibody binds hGM-CSF and is capable of neutralizing hGM-CSF activity, thereby treating the disease or disorder. 
     
     
         103 . A method for treatment of a disease or disorder associated with over-expression of hGM-CSF in a subject, comprising administering to the subject a therapeutically effective amount of an isolated anti-hGM-CSF monoclonal antibody comprising a heavy chain having a heavy chain sequence and a light chain having a light chain sequence, wherein the heavy chain sequence is SEQ ID NO: 51, and wherein the light chain sequence is SEQ ID NO: 36, wherein the antibody binds hGM-CSF and is capable of neutralizing hGM-CSF activity, thereby treating the disease or disorder.