Anti-human cd19 antibodies with high affinity

Abstract

The present invention relates to antibodies against human CD19 (anti-human CD19 antibodies), methods for their production, pharmaceutical compositions containing these antibodies, and methods of using the same.

What is claimed is: 
     
         1 . An antibody that specifically binds to human CD19 with a higher affinity than an antibody comprising a variable heavy chain comprising an amino acid sequence of SEQ ID NO:113 and a variable light chain comprising an amino acid sequence of SEQ ID NO:114. 
     
     
         2 . An antibody that specifically binds to human CD19, wherein the antibody comprises
 (a) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 43,   (b) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 44,   (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 45,   (d) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 46,   (e) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 47, and   (f) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 48.   
     
     
         3 . The antibody of  claim 1 , wherein the antibody is a monoclonal antibody. 
     
     
         4 . The antibody of  claim 1 , wherein the antibody is a humanized or chimeric antibody. 
     
     
         5 . The antibody of  claim 1 , wherein the antibody is an antibody fragment that specifically binds to human CD19. 
     
     
         6 . The antibody of  claim 1 , wherein the antibody comprises a VH domain comprising an amino acid sequence of SEQ ID NO:99 and a VL domain comprising an amino acid sequence of SEQ ID NO:100. 
     
     
         7 . The antibody of  claim 1 , which is a full length IgG1 antibody. 
     
     
         8 . The antibody of  claim 1 , which is a full length IgG1 antibody with mutations L234A, L235A and P329G (numbering according to the EU index of Kabat). 
     
     
         9 . The antibody of  claim 1 , wherein the antibody is cross reactive for human and cynomolgus CD19. 
     
     
         10 . A bispecific antibody which specifically binds to human CD19 and to a second antigen, wherein the antibody comprises
 (a) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 43,   (b) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 44,   (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 45,   (d) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 46,   (e) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 47, and   (f) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 48.   
     
     
         11 . A polynucleotide encoding the antibody of  claim 1 . 
     
     
         12 . A vector, particularly an expression vector, comprising the polynucleotide according to  claim 11 . 
     
     
         13 . A host cell comprising the vector of  claim 12 . 
     
     
         14 . A method of producing the antibody of  claim 1 , comprising the steps of (i) culturing the host cell according to  claim 13  under conditions suitable for expression of the antibody, and (ii) recovering the antibody. 
     
     
         15 . A pharmaceutical formulation comprising the antibody of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         16 . A method of treating a disease in an individual, comprising administering to the individual a therapeutically effective amount of the antibody of  claim 1 . 
     
     
         17 . The method of  claim 16 , wherein the disease is a B-cell cancer. 
     
     
         18 . The method of  claim 16 , wherein the disease is selected from the group consisting of an autoimmune disease, rheumatoid arthritis, lupus, psoriasis, and a bone disease.