Humanised antibodies

Abstract

CDR-grafted antibody heavy and light chains comprise acceptor framework and donor antigen binding regions, the heavy chains comprising donor residues at at least one of positions ( 6, 23 ) and/or ( 24, 48 ) and/or ( 49, 71 ) and/or ( 73, 75 ) and/or ( 76 ) and/or ( 78 ) and ( 88 ) and/or ( 91 ). The CDR-grafted light chains comprise donor residues at at least one of positions ( 1 ) and/or ( 3 ) and ( 46 ) and/or ( 47 ) or at at least one of positions ( 46,48, 58 ) and ( 71 ). The CDR-grafted antibodies arc preferably humanised antibodies, having non human, e.g. rodent, donor and human acceptor frameworks, and may be used for in vivo therapy and diagnosis. A generally applicable protocol is disclosed for obtaining CDR-grafted antibodies

1 - 23 . (canceled)  
     
     
         24 . A humanized immunoglobulin having complementarity determining regions (CDRs) from a donor immunoglobulin and heavy and light chain variable region frameworks from human acceptor immunoglobulin heavy and light chain frameworks, which humanized immunoglobulin specifically binds to an antigen with a binding affinity of at least 10 8  M −1 , wherein said humanized immunoglobulin comprises amino acids from the donor immunoglobulin framework outside both the Kabat CDRs and the structural loop CDRs of the variable regions, wherein the donor amino acids replace corresponding amino acids in the acceptor immunoglobulin heavy or light chain frameworks, and each of said donor amino acids is adjacent a CDR in the donor immunoglobulin sequence.  
     
     
         25 . A method of producing the humanized immunoglobulin of  claim 24  comprising providing a cell containing first and second polynucleotides encoding said variable regions and expressing the polynucleotides in said cell to produce the immunoglobulin.  
     
     
         26 . A method of producing a pharmaceutical composition comprising combining the humanized immunoglobulin of  claim 24  with a pharmaceutically acceptable carrier.  
     
     
         27 . A humanized immunoglobulin having complementarity determining regions (CDRs) from a donor immunoglobulin and heavy and light chain variable region frameworks from human acceptor immunoglobulin heavy and light chain frameworks, which humanized immunoglobulin specifically binds to an antigen with a binding affinity similar to that of the donor immunoglobulin, wherein the sequence of the humanized immunoglobulin heavy chain variable region framework has at least 74 residues identical to an acceptor human immunoglobulin heavy chain variable region amino acid sequence using Kabat numbering.  
     
     
         28 . A method of producing the humanized immunoglobulin of  claim 27  comprising providing a cell containing first and second polynucleotides encoding said variable regions and expressing the polynucleotides in said cell to produce the immunoglobulin.  
     
     
         29 . A method of producing a pharmaceutical composition comprising combining the humanized immunoglobulin of  claim 27  with a pharmaceutically acceptable carrier.  
     
     
         30 - 32 . (canceled)