Humanized antibodies against leukocyte adhesion molecule VLA-4

A humanized immunoglobulin comprising a humanized heavy chain and a humanized light chain:

• (1) the humanized light chain comprising three complementarity determining regions (CDR1, CDR2 and CDR3) having amino acid sequences from the corresponding complementarity determining regions of the mouse 21-6 immunoglobulin light chain variable domain designated SEQ. ID. No. 2, and a variable region framework from a human kappa light chain variable region framework sequence provided that at least one position selected from a first group consisting of L45, L49, L58 and L69 (Kabat numbering convention) is occupied by the same amino acid residue present in the equivalent position of the mouse 21-6 immunoglobulin light chain variable region framework;
• and
• (2) the humanized heavy chain comprising three complementarity determining regions (CDR1, CDR2 and CDR3) having amino acid sequences from the corresponding complementarity determining regions of the mouse 21-6 immunoglobulin heavy chain variable domain designated SEQ. ID. No. 4, and a variable region framework from a human heavy chain variable region framework sequence provided that at least one position selected from a second group consisting of H27, H28, H29, H30, H44, H71 (Kabat numbering convention) is occupied by the same amino acid residue present in the equivalent position of the mouse 21-6 immunoglobulin heavy chain variable region framework;
• wherein the humanized immunoglobulin specifically binds to alpha-4 integrin with a binding affinity having a lower limit of about 10.sup.7 M.sup.-1 and an upper limit of about five-times the binding affinity of the mouse 21-6 immunoglobulin wherein the 21-6 immunoglobulin has the light chain with a variable domain designated SEQ ID NO:
• 2 and IgG1 heavy chain with a variable domain designated SEQ ID NO:
• 4.