Biological products

Abstract

There is disclosed antibody molecules containing at least one CDR derived from a mouse monoclonal antibody having specificity for human CD22. There is also disclosed a CDR grafted antibody wherein at least one of the CDRs is a modified CDR. Further disclosed are DNA sequences encoding the chains of the antibody molecules, vectors, transformed host cells and uses of the antibody molecules in the treatment of diseases mediated by cells expressing CD22.

1 - 4 . (canceled)  
     
     
         5 . The antibody molecule of  claim 58 , which is a CDR-grafted antibody molecule.  
     
     
         6 . The antibody molecule of  claim 5 , wherein the variable domain comprises human acceptor framework regions and non-human donor CDRs.  
     
     
         7 . The antibody molecule of claims  6  or  47 , wherein the human acceptor framework regions of the variable domain of the heavy chain are based on a human sub-group I consensus sequence and comprise donor residues at positions 1, 28, 48, 71 and 93 that correspond to the residues at those positions in SEQ ID NO:8.  
     
     
         8 . The antibody molecule of  claim 7 , additionally comprising donor residues at positions 67 and 69 that correspond to the residues at those positions in SEQ ID NO:8.  
     
     
         9 . The antibody molecule of claims  6  or  47 , wherein the human acceptor framework regions of the variable domain of the light chain are based on a human sub-group I consensus sequence and comprise donor residues at positions 2, 4, 37, 38, 45 and 60 that correspond to the residues at those positions in SEQ ID NO:7.  
     
     
         10 . The antibody molecule of  claim 9 , additionally comprising a donor residue at position 3 that corresponds to the residue at that position in SEQ ID NO:7.  
     
     
         11 . An antibody molecule having specificity for human CD22, comprising a heavy chain according to  claim 7 , and a light chain according to  claim 9 .  
     
     
         12 - 18 . (canceled)  
     
     
         19 . A variant of the antibody molecule of any one of claims  58 ,  5  to  6 , and  46  to  47 , which has an improved affinity for CD22 as compared to the murine monoclonal antibody from which it was derived.  
     
     
         20 . The variant of  claim 19  which is obtained by an affinity maturation protocol.  
     
     
         21 - 22 . (canceled)  
     
     
         23 . An antibody molecule having specificity for human CD22 comprising a hybrid CDR comprising a truncated donor CDR sequence wherein the missing portion of the donor CDR is replaced by a different sequence and forms a functional CDR.  
     
     
         24 . The antibody molecule of  claim 23 , wherein the different sequence is from the antibody from which the framework regions of the antibody molecule are derived.  
     
     
         25 . The antibody molecule of  claim 24 , wherein the different sequence is derived from a germline antibody having consensus framework regions.  
     
     
         26 . The antibody molecule of any one of  claims 23  to  25 , wherein CDR-H2 of the heavy chain is hybrid in the antibody molecule.  
     
     
         27 . The antibody molecule of any one of  claims 23  to  25 , wherein the truncation of the donor CDR is from 1 to 8 amino acids.  
     
     
         28 . The antibody molecule of  claim 27 , wherein the truncation is from 4 to 6 amino acids.  
     
     
         29 . The antibody molecule of any one of  claims 23  to  25 , wherein the truncation is made at the C-terminus of the CDR.  
     
     
         30 - 39 . (canceled)  
     
     
         40 . A composition comprising the antibody molecule of any one of claims  58 ,  4  to  6 ,  23  to  25 , and  46  to  47 .  
     
     
         41 . The composition according to  claim 40 , comprising a pharmaceutically acceptable excipient, diluent or carrier.  
     
     
         42 . The composition according to  claim 40 , additionally comprising anti-T cell, anti-IFNγ or anti-LPS antibodies, or a non-antibody ingredients.  
     
     
         43 - 45 . (canceled)  
     
     
         46 . The antibody molecule of  claim 58  which is a CDR-grafted antibody molecule.  
     
     
         47 . The antibody molecule of  claim 46 , wherein the variable domain comprises human acceptor framework regions and non-human donor CDRs.  
     
     
         48 - 57 . (canceled)  
     
     
         58 . An antibody molecule having specificity for human CD22 comprising a heavy chain wherein the variable domain comprises SEQ ID NO:1 for CDR-H1; SEQ ID NO: 2 or SEQ ID NO:13 or SEQ ID NO:15 or SEQ ID NO:16 or residues 50-65 of SEQ ID NO: 27 for CDR-H2; SEQ ID NO:3 for CDR-H3; SEQ ID NO:4 for CDR-L1; SEQ ID NO:5 for CDR-L2; and SEQ ID NO:6 for CDR-L3.  
     
     
         59 . The antibody molecule according to claim  57  having residues 50-65 of SEQ ID NO:27 for CDR-H2.