Methods of reducing eosinophil levels

Abstract

The present invention relates to a method of reducing the numbers of eosinophils in a human subject comprising administration to a subject an IL-5R binding molecule that comprises (a) a region that specifically binds to the IL-5R and (b) an immunoglobulin Fc region. In a specific embodiment, a method of the invention reduces the number of eosinophils in blood, bone marrow, gastrointestinal tract (e g, esophagus, stomach, small intestine and colon), or lung.

1 - 102 . (canceled) 
     
     
         103 . A method of reducing the numbers of eosinophils in a human subject comprising parenterally administering to said subject between about 0.001 to about 100 mg/kg monoclonal, chimeric, humanized or human antibody that binds IL-5R and comprises an immunoglobulin Fc region comprising:
 a) reduced levels of fucose;   b) no fucose; or   c) amino acid substitution comprising the inclusion of the following amino acid sequences in the Fc region: 332E, 239D and 330L, as numbered by the EU index as set forth in Kabat.   
     
     
         104 . The method of  claim 103 , wherein said antibody specifically binds to the IL-5Rα chain. 
     
     
         105 . The method of  claim 104 , wherein the reduction of eosinophils takes place within the first 48 hours after administration. 
     
     
         106 . The method of  claim 104 , wherein the reduction of eosinophils is reversible. 
     
     
         107 . The method of  claim 104 , wherein the numbers of eosinophils are reduced to a level that is less than 50 eosinophils/mm 3 . 
     
     
         108 . The method of  claim 104 , wherein there is a post-administration reduction in absolute eosinophil count of at least about 25, at least about 50, at least about 75, at least about 100, at least about 125, at least about 150, at least about 175, at least about 200, at least about 225, at least about 250, at least about 275, at least about 300, at least about 325, at least about 350, at least about 375, at least about 400, at least about 425, at least about 450, at least about 475 or at least about 500 eosinophils/mm 3 . 
     
     
         109 . The method of  claim 104 , wherein there is a post-administration reduction in absolute eosinophil count of between and including about 50 to about 500 eosinophils/mm 3 . 
     
     
         110 . The method of  claim 104 , wherein the absolute eosinophil count post-administration is less than about 100, less than about 75, less than about 50, or less than about 25 eosinophils/mm 3 . 
     
     
         111 . The method of  claim 104 , wherein said subject's pre-administration absolute eosinophil count is between about 50 and about 500 eosinophils/mm 3 . 
     
     
         112 . The method of  claim 104 , wherein said subject's pre-administration absolute eosinophil count is about 25, about 50, about 75, about 100, about 125, about 150, about 175, about 200, about 225, about 250, about 275, about 300, about 325, about 350, about 375, about 400, about 450, about 475 or about 500 eosinophils/mm 3 . 
     
     
         113 . The method of  claim 104 , wherein said subject's post-administration absolute basophil count is reduced by at least about 5, at least about 10, at least about 15, at least about 20, at least about 25, at least about 30, at least about 35, at least about 40, at least about 45, at least about 50, at least about 55, at least about 60, at least about 65, at least about 70 basophils/mm 3 . 
     
     
         114 . The method of  claim 104 , wherein said reduction in eosinophils leads to a reduction in asthma symptoms. 
     
     
         115 . The method of  claim 104 , wherein said reduction in eosinophils leads to a reduction in COPD symptoms. 
     
     
         116 . The method of  claim 104 , with the proviso that the IL-5R binding antibody is not MEDI-563. 
     
     
         117 . An isolated anti-IL-5R antibody that binds to the same epitope as MEDI-563. 
     
     
         118 . The anti-IL-5R antibody of  claim 117 , wherein the antibody binds to an epitope comprising residues 52-67 of SEQ ID NO: 5, provided that the antibody is not MEDI-563. 
     
     
         119 . The anti-IL-5R antibody of  claim 117 , wherein the antibody binds to a first antigen comprising residues 40-67 of SEQ ID NO: 5 but does not bind to a second antigen comprising a variant of residues 40-67 of SEQ ID NO: 5 wherein the variant comprises the I61K substitution, provided that the antibody is not MEDI-563. 
     
     
         120 . The anti-IL-5R antibody of  claim 117 , wherein the antibody binds to human IL-5R alpha polypeptide comprising the amino acid sequence of SEQ ID NO:5 but does not bind to a mutant human IL-5R alpha polypeptide comprising the I61K substitution, provided that the antibody is not MEDI-563. 
     
     
         121 . The anti-IL-5R antibody of  claim 117 , wherein the antibody is a human, humanized or chimeric antibody. 
     
     
         122 . An isolated epitope of IL-5R alpha comprising amino acid residues 52-67 of SEQ ID NO: 5.