Optimized antibodies that target cd19

Abstract

The present invention describes antibodies that target CD19, wherein the antibodies comprise at least one modification relative to a parent antibody, wherein the modification alters affinity to an FcγR or alters effector function as compared to the parent antibody. Also disclosed are methods of using the antibodies of the invention.

What is claimed is: 
     
         1 . A method of treating a disease selected from the group consisting of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE or lupus), multiple sclerosis, Sjogren's syndrome, and idiopathic thrombocytopenia purpura (ITP), wherein said method comprises administering an antibody that binds CD19, said antibody comprising a heavy chain and a light chain, said heavy chain comprising a variable region having a CDR1 comprising SEQ ID NO:132, a CDR2 comprising SEQ ID NO:147, and a CDR3 comprising SEQ ID NO:116; and said light chain comprising a variable region having a CDR1 comprising SEQ ID NO:120, a CDR2 comprising SEQ ID NO:129, and a CDR3 comprising SEQ ID NO:130, wherein the heavy chain comprises an Fc domain comprising an amino acid substitution at position 5239 and/or 1332, wherein the Fc numbering is according to the EU index as in Kabat. 
     
     
         2 . The method of treating a disease or disorder selected according to  claim 1 , wherein said method comprises administering a composition comprising a plurality of glycosylated antibodies that bind CD19, said antibody comprising a heavy chain and a light chain, said heavy chain comprising a variable region having a CDR1 comprising SEQ ID NO:132, a CDR2 comprising SEQ ID NO:147, and a CDR3 comprising SEQ ID NO:116; and said light chain comprising a variable region having a CDR1 comprising SEQ ID NO:120, a CDR2 comprising SEQ ID NO:129, and a CDR3 comprising SEQ ID NO:130, wherein about 80-100% of the glycosylated antibodies in the composition comprise a mature core carbohydrate structure which lacks fucose. 
     
     
         3 . An antibody that binds CD19, said antibody comprising a heavy chain or a light chain, said heavy chain having a CDR1 comprising the amino acid sequence selected from the group consisting of SEQ ID NOs:132 and 138, a CDR2 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs:111-115 and 147, and a CDR3 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs:116-118; and said light chain having a CDR1 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs:119-128, a CDR2 comprising the amino acid sequence of SEQ ID NO:129, and a CDR3 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs:130-131. 
     
     
         4 . The antibody according to  claim 3 , wherein said heavy chain variable region comprises SEQ ID NO: 87. 
     
     
         5 . The antibody according to  claim 3 , wherein said light chain variable region comprises SEQ ID NO: 106. 
     
     
         6 . The antibody according to  claim 3 , wherein said heavy chain variable region comprises SEQ ID NO: 87 and said light chain variable region comprises SEQ ID NO: 106.