Claims for Patent: 6,602,503

Summary for Patent: 6,602,503

Title:	Recombinant anti-VLA-4 antibody molecules
Abstract:	The present invention disclosed recombinant anti-VLA-4 antibody molecules, including humanized recombinant anti-VLA-4 antibody molecules. These antibodies are useful in the treatment of specific and non-specific inflammation, including asthma and inflammatory bowel disease. In addition, the humanized recombinant anti-VLA-4 antibodies disclosed can be useful in methods of diagnosing and localizing sites of inflammation.
Inventor(s):	Lobb; Roy R. (Westwood, MA), Carr; Frank J. (Balmedie, GB), Tempest; Philip R. (Royston, GB)
Assignee:	Biogen, Inc. (Cambridge, MA)
Application Number:	08/454,899
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 6,602,503
Patent Claims:	1. A humanized recombinant antibody molecule, or an .alpha.4-binding fragment thereof, comprising: at least one antibody heavy chain, or an .alpha.4-binding fragment thereof, comprising non-human CDRs at positions 31-35 (CDR1), 50-65 (CDR2) and 95-102 (CDR3) (Kabat numbering) from a mouse anti-.alpha.4 antibody and having non-human residues at framework positions 27-30 (Kabat numbering), wherein said positions 27-30 have the amino acid sequence Phe 27, Asn 28, Ile 29 and Lys 30 (SEQ ID NO: 107); and at least one antibody light chain, or an .alpha.4-binding fragment thereof, comprising non-human CDRs at positions 24-34 (CDR1), 50-56 (CDR2) and 89-97 (CDR3) from a mouse anti-.alpha. 4 antibody and framework regions from the REI monoclonal antibody (SEQ ID NO: 100), wherein said REI framework regions have at least one non-human framework residue and the amino acid sequence Val 104, Glu 105 and Lys 107. 2. The humanized recombinant antibody molecule, or .alpha.4-binding fragment thereof, according to claim 1, wherein said heavy chain or .alpha.4-binding fragment thereof, comprises additional non-human residues at framework position 75 (Kabat numbering). 3. The humanized recombinant antibody molecule, or .alpha.4-binding fragment thereof, according to claim 2, wherein said heavy chain, or .alpha.4-binding fragment thereof, comprises additional non-human residues at framework position(s) 77-79 or 66-67 and 69-71 or 84-85 or 38 and 40 or 24. 4. The humanized recombinant antibody molecule, or .alpha.4-binding fragment thereof, according to claim 1, wherein said light chain, or .alpha.4-binding fragment thereof, comprises non-human residues at framework positions 60 and 67. 5. The humanized recombinant antibody molecule, or .alpha.4-binding fragment thereof, according to claim 1, which comprises two full length antibody heavy chains and two full length antibody light chains. 6. The humanized recombinant antibody molecule or .alpha.4-binding fragment thereof according to claim 1, wherein the non-human CDRs are derived from the HP1/2 murine monoclonal antibody (SEQ ID NO: 6 and SEQ ID NO: 10). 7. A DNA encoding an antibody heavy chain, or an .alpha.4-binding fragment thereof, comprising non-human CDRs at positions 31-35 (CDR1), 50-65 (CDR2) and 95-102 (CDR3) (Kabat numbering) from a mouse anti-.alpha.4 antibody and having non-human residues at framework positions 27-30 (Kabat numbering), wherein said positions 27-30 have the amino acid sequence Phe 27, Asn 28, Ile 29 and Lys 30 (SEQ ID NO: 107). 8. The DNA encoding an antibody heavy chain, or an .alpha.4-binding fragment thereof, according to claim 7, wherein said heavy chain, or .alpha.4-binding fragment thereof, comprises additional non-human residues at framework position 75 (Kabat numbering). 9. The DNA encoding an antibody heavy chain, or an .alpha.4-binding fragment thereof, according to claim 7, wherein said heavy chain, or .alpha.4-binding fragment thereof comprises additional non-human residues at framework position(s) 77-79 or 66-67 and 69-71 or 84-85 or 38 and 40 or 24. 10. A DNA encoding an antibody light chain, or an .alpha.4-binding fragment thereof, comprising non-human CDRs at positions 24-34 (CDR1), 50-56 (CDR2) and 89-97 (CDR3) from a mouse anti .alpha.4 antibody and framework regions from the REI monoclonal antibody (SEQ ID NO: 100), wherein said REI framework regions have at least one non-human framework residue and the amino acid sequence Val 104, Glu 105 and Lys 107. 11. The DNA encoding an antibody light chain, or an .alpha.4-binding fragment thereof, according to claim 10, wherein said antibody light chain is a full length antibody light chain. 12. The DNA encoding an antibody light chain, or an .alpha.4-binding fragment thereof, according to claim 10, wherein said light chain, or .alpha.4-binding fragment thereof, comprises non-human residues at framework positions 60 and 67. 13. DNA encoding an antibody light chain, or an .alpha.4-binding fragment thereof, according to claim 11, wherein said antibody light chain is a full length antibody light chain. 14. A DNA encoding an antibody molecule, or an .alpha.4-binding fragment thereof, comprising: at least one antibody heavy chain, or an .alpha.4-binding fragment thereof, comprising non-human CDRs at positions 31-35 (CDR1), 50-65 (CDR2) and 95-102 (CDR3) (Kabat numbering) from a mouse anti-.alpha.4 antibody and having non-human residues at framework positions 27-30 (Kabat numbering), wherein said positions 27-30 have the amino acid sequence Phe 27, Asn 28, Ile 29 and Lys 30 (SEQ ID NO: 107); and at least one antibody light chain, or an .alpha.4-binding fragment thereof, comprising non-human CDRs at positions 24-34 (CDR1), 50-56 (CDR2) and 89-97 (CDR3) from a mouse anti-.alpha.4 antibody and framework regions from the REI monoclonal antibody (SEQ ID NO: 100), wherein said REI framework regions have at least one non-human framework residue and the amino acid sequence Val 104, Glu 105 and Lys 107. 15. The DNA encoding an antibody molecule, or an .alpha.4-binding fragment thereof, according to claim 14, wherein said heavy chain, or .alpha.4-binding fragment thereof, comprises additional non-human residues at framework position 75 (Kabat numbering). 16. The DNA encoding an antibody molecule, or an .alpha.4-binding fragment thereof, according to claim 14, wherein said heavy chain, or .alpha.4-binding fragment thereof, comprises additional non-human residues at framework position(s) 77-79 or 66-67 and 69-71 or 84-85 or 38 and 40 or 24. 17. The DNA encoding an antibody molecule, or an .alpha.4-binding fragment thereof, according to claim 14, wherein said light chain, or .alpha.4-binding fragment thereof, comprises non-human residues at framework positions 60 and 67. 18. The DNA encoding an antibody molecule, or an .alpha.4-binding fragment thereof, according to claim 14, which antibody molecule comprises two full length antibody heavy chains and two full length antibody light chains. 19. The DNA encoding an antibody molecule, or an .alpha.4-binding fragment thereof, according to claim 14, wherein the non-human CDRs are derived from the HP1/2 murine monoclonal antibody (SEQ ID NO: 6 and SEQ ID NO: 10). 20. A vector comprising DNA encoding an antibody heavy chain, or an .alpha.4-binding fragment thereof, comprising non-human CDRs at positions 31-35 (CDR1), 50-65 (CDR2) and 95-102 (CDR3) (Kabat numbering) from a mouse anti-.alpha.4 antibody and having non-human residues at framework positions 27-30 (Kabat numbering), wherein said positions 27-30 have the amino acid sequence Phe 27, Asn 28, Ile 29 and Lys 30 (SEQ ID NO: 107). 21. The vector comprising DNA, according to claim 20, wherein said heavy chain, or .alpha.4-binding fragment thereof, comprises additional non-human residues at framework position 75 (Kabat numbering). 22. The vector comprising DNA encoding an antibody heavy chain, or an .alpha.4-binding fragment thereof, according to claim 20, wherein said heavy chain, or .alpha.4-binding fragment thereof, comprises additional non-human residues at framework position(s) 77-79 or 66-67 and 69-71 or 84-85 or 38 and 40 or 24. 23. The vector comprising DNA, according to claim 20, wherein said antibody heavy chain is a full length antibody heavy chain. 24. A vector comprising DNA encoding an antibody light chain, or an .alpha.4-binding fragment thereof, comprising non-human CDs at positions 24-34 (CDR1), 50-56 (CDR2) and 89-97 (CDR3) from a mouse anti .alpha.4 antibody and framework regions from the REI monoclonal antibody (SEQ ID NO: 100), wherein said REI framework regions have at least one non-human framework residue and the amino acid sequence Val 104, Glu 105 and Lys 107. 25. The vector comprising DNA encoding an antibody light chain, or an .alpha.4-binding fragment thereof, according to claim 24, wherein said light chain, or .alpha.4-binding fragment thereof, comprises non-human residues at framework positions 60 and 67. 26. The vector comprising DNA, according to claim 25, wherein said antibody light chain is a full length antibody light chain. 27. A vector comprising DNA encoding an antibody molecule or an .alpha.4-binding fragment thereof comprising: at least one antibody heavy chain, or an .alpha.4-binding fragment thereof, comprising non-human CDRs at positions 31-35 (CDR1), 50-65 (CDR2) and 95-102 (CDR3) (Kabat numbering) from a mouse anti-.alpha.4 antibody and having non-human residues at framework positions 27-30 (Kabat numbering), wherein said positions 27-30 have the amino acid sequence Phe 27, Asn 28, Ile 29 and Lys 30 (SEQ ID NO: 107); and at least one antibody light chain, or an .alpha.4-binding fragment thereof, comprising non-human CDRs at positions 24-34 (CDR1), 50-56 (CDR2) and 89-97 (CDR3) from a mouse anti-.alpha.4 antibody and framework regions from the REI monoclonal antibody (SEQ ID NO: 100), wherein said REI framework regions have at least one non-human framework residue and the amino acid sequence Val 104, Glu 105 and Lys 107. 28. The vector comprising DNA encoding an antibody molecule, or an .alpha.4-binding fragment thereof, according to claim 27, wherein said heavy chain, or .alpha.4-binding fragment thereof, comprises additional non-human residues at framework position 75 (Kabat numbering). 29. The vector comprising DNA encoding an antibody molecule, or an .alpha.4-binding fragment thereof, according to claim 27, wherein said heavy chain, or .alpha.4-binding fragment thereof, comprises additional non-human residues at framework position(s) 77-79 or 66-67 and 69-71 or 84-85 or 38 and 40 or 24. 30. The vector comprising DNA encoding an antibody molecule, or an .alpha.4-binding fragment thereof, according to claim 27, wherein said light chain, or .alpha.4-binding fragment thereof, comprises non-human residues at framework positions 60 and 67. 31. The vector comprising DNA encoding an antibody molecule, or an .alpha.4-binding fragment thereof, according to claim 27, which antibody molecule comprises two full length antibody heavy chains and two full length antibody light chains. 32. The vector comprising DNA encoding an antibody molecule, or an .alpha.4-binding fragment thereof, according to claim 27, wherein the non-human CDRs are derived from the HP1/2 murine monoclonal antibody (SEQ ID NO: 6 and SEQ ID NO: 10). 33. An expression vector comprising DNA encoding an antibody molecule, or an .alpha.4-binding fragment thereof, comprising: at least one antibody heavy chain, or an .alpha.4-binding fragment thereof, comprising non-human CDRs at positions 31-35 (CDR1), 50-65 (CDR2) and 95-102 (CDR3) (Kabat numbering) from a mouse anti-.alpha.4 antibody and having non-human residues at framework positions 27-30 (Kabat numbering), wherein said positions 27-30 have the amino acid sequence Phe 27, Asn 28, Ile 29 and Lys 30 (SEQ ID NO: 107); and at least one antibody light chain, or an .alpha.4-binding fragment thereof, comprising non-human CDRs at positions 24-34 (CDR1), 50-56 (CDR2) and 89-97 (CDR3) from a mouse anti-.alpha.4 antibody and framework regions from the REI monoclonal antibody (SEQ ID NO: 100), wherein said REI framework regions have at least one non-human framework residue and the amino acid sequence Val 104, Glu 105 and Lys 107. 34. The expression vector comprising DNA, according to claim 33, wherein said heavy chain, or .alpha.4-binding fragment thereof, comprises additional non-human residues at framework position 75 (Kabat numbering). 35. The expression vector comprising DNA, according to claim 33, wherein said heavy chain, or .alpha.4-binding fragment thereof, comprises additional non-human residues at framework position(s) 77-79 or 66-67 and 69-71 or 84-85 or 38 and 40 or 24. 36. The expression vector comprising DNA, according to claim 33, wherein said light chain, or .alpha.4-binding fragment thereof, comprises non-human residues at framework positions 60 and 67. 37. The expression vector comprising DNA, according to claim 33, which DNA encodes two full length antibody heavy chains and two full length antibody light chains. 38. The expression vector comprising DNA according to claim 33, wherein the non-human CDRs of the antibody molecule, or .alpha.4-binding fragment thereof, are derived from the HP1/2 murine monoclonal antibody (SEQ ID NO: 6 and SEQ ID NO: 10). 39. A host cell transformed with a first vector and a second vector, said first vector comprising DNA encoding an antibody heavy chain, or an .alpha.4-binding fragment thereof, comprising non-human CDRs at positions 31-35 (CDR1), 50-65 (CDR2) and 95-102 (CDR3) (Kabat numbering) from a mouse anti-.alpha.4 antibody and having non-human residues at framework positions 27-30 (Kabat numbering), wherein said positions 27-30 have the amino acid sequence Phe 27, Asn 28, Ile 29 and Lys 30 (SEQ ID NO: 107), and said second vector comprising DNA encoding an antibody light chain, or an .alpha.4-binding fragment thereof, comprising non-human CDRs at positions 24-34 (CDR1), 50-56 (CDR2) and 89-97 (CDR3) from a mouse anti-.alpha.4 antibody and framework regions from the REI monoclonal antibody (SEQ ID NO: 100), wherein said REI framework regions have at least one non-human framework residue and the amino acid sequence Val 104, Glu 105 and Lys 107. 40. The host cell transformed with a first and second vector, according to claim 39, wherein said heavy chain, or .alpha.4-binding fragment thereof, comprises additional non-human residues at framework position 75 (Kabat numbering). 41. The host cell transformed with a first and second vector, according to claim 39, wherein said heavy chain, or .alpha.4-binding fragment thereof, comprises additional non-human residues at framework position(s) 77-79 or 66-67 and 69-71 or 84-85 or 38 and 40 or 24. 42. The host cell transformed with a first and second vector, according to claim 39, wherein said light chain, or .alpha.4-binding fragment thereof, comprises non-human residues at framework positions 60 and 67. 43. The host cell transformed with a first and second vector, according to claim 39, which DNA encodes two full length antibody heavy chains and two full length antibody light chains. 44. The host cell transformed with a vector, according to claim 39, wherein the non-human CDRs are derived from the HP1/2 murine monoclonal antibody (SEQ ID NO: 6 and SEQ ID NO: 10). 45. A host cell transformed with a vector comprising DNA encoding an antibody molecule or an .alpha.4-binding fragment thereof comprising: at least one antibody heavy chain, or an .alpha.4-binding fragment thereof, comprising non-human CDRs at positions 31-35 (CDR1), 50-65 (CDR2) and 95-102 (CDR3) (Kabat numbering) from a mouse anti-.alpha.4 antibody and having non-human residues at framework positions 27-30 (Kabat numbering), wherein said positions 27-30 have the amino acid sequence Phe 27, Asn 28, Ile 29 and Lys 30 (SEQ ID NO: 107); and at least one antibody light chain, or an .alpha.4-binding fragment thereof, comprising non-human CDRs at positions 24-34 (CDR1), 50-56 (CDR2) and 89-97 (CDR3) from a mouse anti-.alpha.4 antibody and framework regions from the REI monoclonal antibody (SEQ ID NO: 100), wherein said REI framework regions have at least one non-human framework residue and the amino acid sequence Val 104, Glu 105 and Lys 107. 46. The host cell transformed with a vector, according to claim 45, wherein said heavy chain, or .alpha.4-binding fragment thereof, comprises additional non-human residues at framework position 75 (Kabat numbering). 47. The host cell transformed with a vector, according to claim 45, wherein said heavy chain, or .alpha.4-binding fragment thereof, comprises additional non-human residues at framework position(s) 77-79 or 66-67 and 69-71 or 84-85 or 38 and 40 or 24. 48. The host cell transformed with a vector, according to claim 45, wherein said light chain or .alpha.4-binding fragment thereof, comprises non-human residues at framework positions 60 and 67. 49. The host cell transformed with a vector, according to claim 45, in which said antibody molecule comprises two full length antibody heavy chains and two full length antibody light chains. 50. The host cell transformed with a vector, according to claim 45, wherein the non-human CDRs are derived from the HP1/2 murine monoclonal antibody (SEQ ID NO: 6 and SEQ ID NO: 10). 51. A process for the production of a humanized recombinant anti-.alpha.4 antibody, or an .alpha.4-binding fragment thereof, comprising: (a) producing a first expression vector comprising an operon having a DNA sequence encoding an antibody heavy chain, or an .alpha.4-binding fragment thereof, or light chain, or an .alpha.4-binding fragment thereof, wherein the CDRs of the variable domain are derived from a mouse anti-.alpha.4 antibody and the remaining immunoglobulin-derived parts of the antibody chain are derived from a human immunoglobulin; (b) producing a second expression vector comprising an operon having a DNA sequence encoding a complementary antibody light chain, or an .alpha.4-binding fragment thereof, or heavy chain, or an .alpha.4-binding fragment thereof, wherein the CDRs of the variable domain are derived from a mouse anti-.alpha.4 antibody and the remaining immunoglobulin-derived parts of the antibody chain are derived from a human immunoglobulin; (c) transfecting a host cell with the first and second expression vector; and (d) culturing the transfected cell line to produce the humanized recombinant anti-.alpha.4 antibody molecule, or .alpha.4-binding fragment thereof, provided that the light chain, or an .alpha.4-binding fragment thereof, comprises non-human CDRs at positions 24-34 (CDR1), 50-56 (CDR2) and 89-97 (CDR3) from a mouse anti-.alpha.4 antibody and framework regions from the REI monoclonal antibody (SEQ ID NO: 100), wherein said REI framework regions have at least one non-human framework residue and the amino acid sequence Val 104, Glu 105 and Lys 107. 52. The process for the production of a humanized recombinant anti-.alpha.4 antibody, or an .alpha.4-binding fragment thereof, according to claim 51, wherein said light chain, or .alpha.4-binding fragment thereof, comprises non-human residues at framework positions 60 and 67. 53. The process for the production of a humanized recombinant anti-.alpha.4 antibody, or an .alpha.4-binding fragment thereof, according to claim 51, wherein said antibody light chain is a full length antibody light chain. 54. A process for the production of a humanized recombinant anti-.alpha.4 antibody, or an .alpha.4-binding fragment thereof, comprising: (a) producing an expression vector comprising (i) an operon having a DNA sequence encoding an antibody heavy chain, or an .alpha.4-binding fragment thereof, or light chain, or an .alpha.4-binding fragment thereof, wherein the CDRs of the variable domain are derived from a mouse anti-.alpha.4 antibody and the remaining immunoglobulin-derived parts of the antibody chain are derived from a human immunoglobulin, and (ii) an operon having a DNA sequence encoding a complementary antibody light chain, or an .alpha.4-binding fragment thereof, or heavy chain, or an .alpha.4-binding fragment thereof, wherein the CDRs of the variable domain are derived from a mouse anti-.alpha.4 antibody and the remaining immunoglobulin-derived parts of the antibody chain are derived from a human immunoglobulin; (b) transfecting a host cell with said vector; and (c) culturing the transfected cell line to produce the humanized recombinant anti-.alpha.4 antibody molecule, or .alpha.4-binding fragment thereof, provided that the light chain, or an .alpha.4-binding fragment thereof, comprises non-human CDRs at positions 24-34 (CDR1), 50-56 (CDR2) and 89-97 (CDR3) from a mouse anti-.alpha.4 antibody and framework regions from the REI monoclonal antibody (SEQ ID NO: 100), wherein said REI framework regions have at least one non-human framework residue and the amino acid sequence Val 104, Glu 105 and Lys 107. 55. The process for the production of a humanized recombinant anti-.alpha.4 antibody, or an .alpha.4-binding fragment thereof, according to claim 54, wherein said light chain, or .alpha.4-binding fragment thereof, comprises non-human residues at framework positions 60 and 67. 56. The process for the production of a humanized recombinant anti-.alpha.4 antibody, or an .alpha.4-binding fragment thereof, according to claim 54, wherein said antibody light chain is a full length antibody light chain. 57. A process for the production of a humanized recombinant anti-.alpha.4 antibody, or an .alpha.4-binding fragment thereof, comprising: (a) producing a first expression vector comprising an operon having a DNA sequence encoding an antibody heavy chain, or an .alpha.4-binding fragment thereof, or light chain, or an .alpha.4-binding fragment thereof, wherein the CDRs of the variable domain are derived from a mouse anti-.alpha.4 antibody and the remaining immunoglobulin-derived parts of the antibody chain are derived from a human immunoglobulin; (b) producing a second expression vector comprising an operon having a DNA sequence encoding a complementary antibody light chain, or an .alpha.4-binding fragment thereof, or heavy chain, or an .alpha.4-binding fragment thereof, wherein the CDRs of the variable domain are derived from a mouse anti-.alpha.4 antibody and the remaining immunoglobulin-derived parts of the antibody chain are derived from a human immunoglobulin; (c) transfecting a host cell with the first and second expression vector; and (d) culturing the transfected cell line to produce the humanized recombinant anti-.alpha.4 antibody molecule, or an .alpha.4-binding fragment thereof, provided that the heavy chain, or an .alpha.4-binding fragment thereof, comprises non-human CDRs at positions 31-35 (CDR1), 50-65 (CDR2) and 95-102 (CDR3) (Kabat numbering) from a mouse anti-.alpha.4 antibody and having non-human residues at framework positions 27-30 (Kabat numbering), wherein said positions 27-30 have the amino acid sequence Phe 27, Asn 28, Ile 29 and Lys 30 (SEQ ID NO: 107). 58. The process for the production of a humanized recombinant anti-.alpha.4 antibody, or an .alpha.4-binding fragment thereof, according to claim 57, wherein said heavy chain, or .alpha.4-binding fragment thereof, comprises additional non-human residues at framework position 75 (Kabat numbering). 59. The process for the production of a humanized recombinant anti-.alpha.4 antibody, or an .alpha.4-binding fragment thereof, according to claim 57, wherein said heavy chain, or .alpha.4-binding fragment thereof, comprises additional non-human residues at framework position(s) 77-79 or 66-67 and 69-71 or 84-85 or 38 and 40 or 24. 60. The process for the production of a humanized recombinant anti-.alpha.4 antibody, or an .alpha.4-binding fragment thereof, according to claim 57, wherein said antibody heavy chain is a full length antibody heavy chain. 61. A process for the production of a humanized recombinant anti-.alpha.4 antibody, or an .alpha.4-binding fragment thereof, comprising: (a) producing an expression vector comprising (i) an operon having a DNA sequence encoding an antibody heavy chain, or an .alpha.4-binding fragment thereof, or light chain, or an .alpha.4-binding fragment thereof, wherein the CDRs of the variable domain are derived from a mouse anti-.alpha.4 antibody and the remaining immunoglobulin-derived parts of the antibody chain are derived from a human immunoglobulin, and (ii) an operon having a DNA sequence encoding a complementary antibody light chain, or an .alpha.4-binding fragment thereof, or heavy chain, or an .alpha.4-binding fragment thereof, wherein the CDRs of the variable domain are derived from a mouse anti-.alpha.4 antibody and the remaining immunoglobulin-derived parts of the antibody chain are derived from a human immunoglobulin; (b) transfecting a host cell with said vector; and (c) culturing the transfected cell line to produce the humanized recombinant anti-.alpha.4 antibody molecule, or an .alpha.4-binding fragment thereof, provided that the heavy chain, or an .alpha.4-binding fragment thereof, comprises non-human CDRs at positions 31-35 (CDR1), 50-65 (CDR2) and 95-102 (CDR3) (Kabat numbering) from a mouse anti-.alpha.4 antibody and having non-human residues at framework positions 27-30 (Kabat numbering), wherein said positions 27-30 have the amino acid sequence Phe 27, Asn 28, Ile 29 and Lys 30 (SEQ ID NO: 107). 62. The process for the production of a humanized recombinant anti-.alpha.4 antibody, or an .alpha.4-binding fragment thereof, according to claim 61, wherein said heavy chain, or .alpha.4-binding fragment thereof, comprises additional non-human residues at framework position 75 (Kabat numbering). 63. The process for the production of a humanized recombinant anti-.alpha.4 antibody, or an .alpha.4-binding fragment thereof, according to claim 61, wherein said heavy chain, or .alpha.4-binding fragment thereof, comprises additional non-human residues at framework position(s) 77-79 or 66-67 and 69-71 or 84-85 or 38 and 40 or 24. 64. The process for the production of a humanized recombinant anti-.alpha.4 antibody, or an .alpha.4-binding fragment thereof, according to claim 61, wherein said antibody heavy chain is a full length antibody heavy chain. 65. A process for the production of a humanized recombinant anti-.alpha.4 antibody, or an .alpha.4-binding fragment thereof, comprising: (a) producing a first expression vector comprising an operon having a DNA sequence encoding an antibody heavy chain, or an .alpha.4-binding fragment thereof, or light chain, or an .alpha.4-binding fragment thereof, wherein the CDRs of the variable domain are derived from a mouse anti-.alpha.4 antibody and the remaining immunoglobulin-derived parts of the antibody chain are derived from a human immunoglobulin; (b) producing a second expression vector comprising an operon having a DNA sequence encoding a complementary antibody light chain, or an .alpha.4-binding fragment thereof, or heavy chain, or an .alpha.4-binding fragment thereof, wherein the CDRs of the variable domain are derived from a mouse anti-.alpha.4 antibody and the remaining immunoglobulin-derived parts of the antibody chain are derived from a human immunoglobulin; (c) transfecting a host cell with the first and second vector; and (d) culturing the transfected cell line to produce the humanized recombinant anti-.alpha.4-antibody molecule or an .alpha.4-binding fragment thereof, provided that (i) the heavy chain, or an .alpha.4-binding fragment thereof, comprises non-human CDRs at positions 31-35 (CDR1), 50-65 (CDR2) and 95-102 (CDR3) (Kabat numbering) from a mouse anti-.alpha.4 antibody and having non-human residues at framework positions 27-30 (Kabat numbering), wherein said positions 27-30 have the amino acid sequence Phe 27, Asn 28, Ile 29 and Lys 30 (SEQ ID NO: 107); and (ii) the light chain, or an .alpha.4-binding fragment thereof, comprises non-human CDRs at positions 24-34 (CDR1), 50-56 (CDR2) and 89-97 (CDR3) from a mouse anti-.alpha.4 antibody and framework regions from the REI monoclonal antibody (SEQ ID NO: 100), wherein said REI framework regions have at least one non-human framework residue and the amino acid sequence Val 104, Glu 105 and Lys 107. 66. The process for the production of a humanized recombinant anti-.alpha.4 antibody, or an .alpha.4-binding fragment thereof, according to claim 65, wherein said heavy chain, or .alpha.4-binding fragment thereof, comprises additional non-human residues at framework position 75 (Kabat numbering). 67. The process for the production of a humanized recombinant anti-.alpha.4 antibody, or an .alpha.4-binding fragment thereof, according to claim 65, wherein said heavy chain, or .alpha.4-binding fragment thereof, comprises additional non-human residues at framework position(s) 77-79 or 66-67 and 69-71 or 84-85 or 38 and 40 or 24. 68. The process for the production of a humanized recombinant anti-.alpha.4 antibody, or an .alpha.4-binding fragment thereof, according to claim 65, wherein said light chain, or .alpha.4-binding fragment thereof, comprises non-human residues at framework positions 60 and 67. 69. The process for the production of a humanized recombinant anti-.alpha.4 antibody, or an .alpha.4-binding fragment thereof, according to claim 65, which said humanized recombinant anti-.alpha.4 antibody, or .alpha.4-binding fragment thereof, comprises two full length antibody heavy chains and two full length antibody light chains. 70. The process for the production of a humanized recombinant anti-.alpha.4 antibody, or an .alpha.4-binding fragment thereof, according to claim 65, wherein the non-human CDRs are derived from the HP1/2 murine monoclonal antibody (SEQ ID NO: 6 and SEQ ID NO: 10). 71. A process for the production of a humanized recombinant anti-.alpha.4 antibody, or an .alpha.4-binding fragment thereof, comprising: (a) producing an expression vector comprising (i) an operon having a DNA sequence encoding an antibody heavy chain, or an .alpha.4-binding fragment thereof, or light chain, or an .alpha.4-binding fragment thereof, wherein the CDRs of the variable domain are derived from a mouse anti-.alpha.4 antibody and the remaining immunoglobulin-derived parts of the antibody chain are derived from a human immunoglobulin, and (ii) an operon having a DNA sequence encoding a complementary antibody light chain, or an .alpha.4-binding fragment thereof, or heavy chain, or an .alpha.4-binding fragment thereof, wherein the CDRs of the variable domain are derived from a mouse anti-.alpha.4 antibody and the remaining immunoglobulin-derived parts of the antibody chain are derived from a human immunoglobulin; (b) transfecting a host cell with said vector; and (c) culturing the transfected cell line to produce the humanized recombinant anti-.alpha.4 antibody molecule or an .alpha.4-binding fragment thereof, provided that (i) the heavy chain, or an .alpha.4-binding fragment thereof, comprises non-human CDRs at positions 31-35 (CDR1), 50-65 (CDR2) and 95-102 (CDR3) (Kabat numbering) from a mouse anti-.alpha.4 antibody and having non-human residues at framework positions 27-30 (Kabat numbering), wherein said positions 27-30 have the amino acid sequence Phe 27, Asn 28, Ile 29 and Lys 30 (SEQ ID NO: 107); and (ii) the light chain, or an .alpha.4-binding fragment thereof, comprises non-human CDRs at positions 24-34 (CDR1), 50-56 (CDR2) and 89-97 (CDR3) from a mouse anti-.alpha.4 antibody and framework regions from the REI monoclonal antibody (SEQ ID NO: 100), wherein said REI framework regions have at least one non-human framework residue and the amino acid sequence Val 104, Glu 105 and Lys 107. 72. The process for the production of a humanized recombinant anti-.alpha.4 antibody, or an .alpha.4-binding fragment thereof, according to claim 71, wherein said heavy chain, or .alpha.4-binding fragment thereof, comprises additional non-human residues at framework position 75 (Kabat numbering). 73. The process for the production of a humanized recombinant anti-.alpha.4 antibody, or an .alpha.4-binding fragment thereof, according to claim 71, wherein said heavy chain, or .alpha.4-binding fragment thereof, comprises additional non-human residues at framework position(s) 77-79 or 66-67 and 69-71 or 84-85 or 38 and 40 or 24. 74. The process for the production of a humanized recombinant anti-.alpha.4 antibody, or an .alpha.4-binding fragment thereof, according to claim 71, wherein said light chain, or .alpha.4-binding fragment thereof, comprises non-human residues at framework positions 60 and 67. 75. The process for the production of a humanized recombinant anti-.alpha.4 antibody, or an .alpha.4-binding fragment thereof, according to claim 71, in which said humanized recombinant anti-.alpha.4 antibody comprises two full length antibody heavy chains and two full length antibody light chains. 76. The process for the production of a humanized recombinant anti-.alpha.4 antibody, or an .alpha.4-binding fragment thereof, according to claim 71, wherein the non-human CDRs are derived from the HP1/2 murine monoclonal antibody (SEQ ID NO: 6 and SEQ ID NO: 10). 77. A therapeutic composition comprising an antibody molecule, or an .alpha.4-binding fragment thereof, having one or both of: an antibody heavy chain, or an .alpha.4-binding fragment thereof, comprising non-human CDRs at positions 31-35 (CDR1), 50-65 (CDR2) and 95-102 (CDR3) (Kabat numbering) from a mouse anti-.alpha.4 antibody and having non-human residues at framework positions 27-30 (Kabat numbering), wherein said positions 27-30 have the amino acid sequence Phe 27, Asn 28, Ile 29 and Lys 30 (SEQ ID NO: 107); and an antibody light chain, or an .alpha.4-binding fragment thereof, comprising non-human CDRs at positions 24-34 (CDR1), 50-56 (CDR2) and 89-97 (CDR3) from a mouse anti-.alpha.4 antibody and framework regions from the REI monoclonal antibody (SEQ ID NO: 100), wherein said REI framework regions have at least one non-human framework residue and the amino acid sequence Val 104, Glu 105 and Lys 107, in combination with a pharmaceutically acceptable diluent, excipient or carrier. 78. The therapeutic composition, according to claim 77, wherein said heavy chain, or .alpha.4-binding fragment thereof, comprises additional non-human residues at framework position 75 (Kabat numbering). 79. The therapeutic composition comprising an antibody molecule, according to claim 77, wherein said heavy chain, or .alpha.4-binding fragment thereof, comprises additional non-human residues at framework position(s) 77-79 or 66-67 and 69-71 or 84-85 or 38 and 40 or 24. 80. The therapeutic composition according to claim 77, wherein said light chain, or .alpha.4-binding fragment thereof, comprises non-human residues at framework positions 60 and 67. 81. The therapeutic composition according to claim 77, in which the antibody molecule comprises two full length antibody heavy chains and two full length antibody light chains. 82. The therapeutic composition comprising an antibody molecule, or an .alpha.4-binding fragment thereof according to claim 77, wherein the non-human CDRs of the antibody molecule, or an .alpha.4-binding fragment thereof, are derived from the HP1/2 murine monoclonal antibody (SEQ ID NO: 6 and SEQ ID NO: 10). 83. A diagnostic composition comprising an antibody molecule, or an .alpha.4-binding fragment thereof, having in a detectably labeled form one or both of: an antibody heavy chain, or an .alpha.4-binding fragment thereof, comprising non-human CDRs at positions 31-35 (CDR1), 50-65 (CDR2) and 95-102 (CDR3) (Kabat numbering) from a mouse anti-.alpha.4 antibody and having non-human residues at framework positions 27-30 (Kabat numbering), wherein said positions 27-30 have the amino acid sequence Phe 27, Asn 28, Ile 29 and Lys 30 (SEQ ID NO: 107), and an antibody light chain, or an .alpha.4-binding fragment thereof, comprising non-human CDRs at positions 24-34 (CDR1), 50-56 (CDR2) and 89-97 (CDR3) from a mouse anti-.alpha.4 antibody and framework regions from the REI monoclonal antibody (SEQ ID NO: 100), wherein said REI framework regions have at least one non-human framework residue and the amino acid sequence Val 104, Glu 105 and Lys 107. 84. The diagnostic composition, according to claim 83, wherein said heavy chain, or .alpha.4-binding fragment thereof, comprises additional noon-human residues at framework position 75 (Kabat numbering). 85. The diagnostic composition comprising an antibody molecule, or an .alpha.4-binding fragment thereof, according to claim 83, wherein said heavy chain, or .alpha.4-binding fragment thereof, comprises additional non-human residues at framework position(s) 77-79 or 66-67 and 69-71 or 84-85 or 38 and 40 or 24. 86. The diagnostic composition comprising an antibody molecule, or an .alpha.4-binding fragment thereof, according to claim 83, wherein said light chain, or .alpha.4-binding fragment thereof comprises non-human residues at framework positions 60 and 67. 87. The diagnostic composition, according to claim 83, in which the antibody molecule comprises two full length antibody heavy chains and two full length antibody light chains. 88. The diagnostic composition, according to claim 83, wherein the non-human CDRs of said antibody molecule, or an .alpha.4-binding fragment thereof, are derived from the HP1/2 murine monoclonal antibody (SEQ ID NO: 6 and SEQ ID NO: 10). 89. A method for treating inflammation associated with a VCAM-1/VLA-4 adhesion pathway in a mammalian subject which comprises providing to a subject in need of such treatment an amount of an anti-inflammatory agent sufficient to suppress the inflammation, wherein the anti-inflammatory agent comprises an antibody, or an .alpha.4-binding fragment thereof, having one or both of: an antibody heavy chain, or an .alpha.4-binding fragment thereof, comprising non-human CDRs at positions 31-35 (CDR1), 50-65 (CDR2) and 95-102 (CDR3) (Kabat numbering) from a mouse anti-.alpha.4 antibody and having non-human residues at framework positions 27-30 (Kabat numbering), wherein said positions 27-30 have the amino acid sequence Phe 27, Asn 28, Ile 29 and Lys 30 (SEQ ID NO: 107); and an antibody light chain, or an .alpha.4-binding fragment thereof, comprising non-human CDRs at positions 24-34 (CDR1), 50-56 (CDR2) and 89-97 (CDR3) from a mouse anti-.alpha.4 antibody and framework regions from the REI monoclonal antibody (SEQ ID NO: 100), wherein said REI framework regions have at least one non-human framework residue and the amino acid sequence Val 104, Glu 105 and Lys 107. 90. The method for treating inflammation associated with a VCAM-1/VLA-4 adhesion pathway in a mammalian subject which comprises providing to a subject in need of such treatment an amount of an anti-inflammatory agent sufficient to suppress the inflammation, wherein the anti-inflammatory agent is an antibody, or an .alpha.4-binding fragment thereof, according to claim 89, wherein said heavy chain, or .alpha.4-binding fragment thereof, comprises additional non-human residues at framework position 75 (Kabat numbering). 91. The method for treating inflammation associated with a VCAM-1/VLA-4 adhesion pathway in a mammalian subject which comprises providing to a subject in need of such treatment an amount of an anti-inflammatory agent sufficient to suppress the inflammation, wherein the anti-inflammatory agent is an antibody, or an .alpha.4-binding fragment thereof, according to claim 89, wherein said heavy chain, or .alpha.4-binding fragment thereof, comprises additional non-human residues at framework position(s) 77-79 or 66-67 and 69-71 or 84-85 or 38 and 40 or 24. 92. The method for treating inflammation associated with a VCAM-1/VLA-4 adhesion pathway in a mammalian subject which comprises providing to a subject in need of such treatment an amount of an anti-inflammatory agent sufficient to suppress the inflammation, wherein the anti-inflammatory agent is an antibody, or an .alpha.4-binding fragment thereof, according to claim 89, wherein said light chain, or .alpha.4-binding fragment thereof, comprises non-human residues at framework positions 60 and 67. 93. The method for treating inflammation associated with a VCAM-1/VLA-4 adhesion pathway in a mammalian subject which comprises providing to a subject in need of such treatment an amount of an anti-inflammatory agent sufficient to suppress the inflammation, wherein the anti-inflammatory agent is an antibody, or an .alpha.4-binding fragment thereof, according to claim 89, in which the antibody comprises two full length antibody heavy chains and two full length antibody light chains. 94. The method for treating inflammation associated with a VCAM-1/VLA-4 adhesion pathway in a mammalian subject which comprises providing to a subject in need of such treatment an amount of an anti-inflammatory agent sufficient to suppress the inflammation, wherein the anti-inflammatory agent is an antibody, or an .alpha.4-binding fragment thereof, according to claim 89, wherein the non-human CDRs of the antibody or .alpha.4-binding fragment thereof, are derived from the HP1/2 murine monoclonal antibody (SEQ ID NO: 6 and SEQ ID NO: 10). 95. A humanized recombinant anti-.alpha.4 antibody molecule, or .alpha.4-binding fragment thereof, which comprises a humanized heavy chain, or an .alpha.4-binding fragment thereof, comprising a variable heavy chain region selected from the group consisting of: SEQ ID NO: 43, SEQ ID NO: 47, SEQ ID NO: 51, and SEQ ID NO: 55, in combination with a humanized light chain, or an .alpha.4-binding fragment thereof, comprising a light chain variable region selected from the group consisting of: SEQ ID NO: 31, SEQ ID NO: 63, and SEQ ID NO: 67. 96. The humanized recombinant anti-.alpha.4 antibody molecule, or .alpha.4-binding fragment thereof, according to claim 95, which comprises two full length antibody heavy chains and two full length antibody light chains. 97. A DNA encoding a humanized recombinant anti-.alpha.4 antibody molecule or .alpha.4-binding fragment thereof, comprising DNA encoding: a humanized heavy chain, or an .alpha.4-binding fragment thereof, comprising a variable heavy chain region selected from the group consisting of: SEQ ID NO: 43, SEQ ID NO: 47, SEQ ID NO: 51, and SEQ ID NO: 55, and a humanized light chain, or an .alpha.4-binding fragment thereof, comprising a light chain variable region selected from the group consisting of: SEQ ID NO: 31, SEQ ID NO: 63, and SEQ ID NO: 67. 98. The DNA encoding a humanized recombinant anti-.alpha.4 antibody molecule or .alpha.4-binding fragment thereof, according to claim 97, which humanized recombinant anti-.alpha.4 antibody molecule comprises two full length antibody heavy chains and two full length antibody light chains. 99. A vector comprising DNA encoding a humanized heavy chain, or an .alpha.4-binding fragment thereof, comprising a variable heavy chain region selected from the group consisting of: SEQ ID NO: 43, SEQ ID NO: 47, SEQ ID NO: 51, and SEQ ID NO: 55, and a humanized light chain, or an .alpha.4-binding fragment thereof, comprising a light chain variable region selected from the group consisting of: SEQ ID NO: 31, SEQ ID NO: 63, and SEQ ID NO: 67. 100. The vector comprising DNA according to claim 99, which comprises DNA encoding two full length antibody heavy chains and two full length antibody light chains. 101. An expression vector comprising DNA encoding a humanized antibody molecule, or .alpha.4-binding fragment thereof, wherein the humanized recombinant anti-.alpha.4 antibody molecule, or .alpha.4-binding fragment thereof, comprises a humanized heavy chain, or an .alpha.4-binding fragment thereof, comprising a variable heavy chain region selected from the group consisting of: SEQ ID NO: 43, SEQ ID NO: 47, SEQ ID NO: 51, and SEQ ID NO: 55, and a humanized light chain, or an .alpha.4-binding fragment thereof, comprising a light chain variable region selected from the group consisting of: SEQ ID NO: 31, SEQ ID NO: 63, and SEQ ID NO: 67. 102. The expression vector comprising DNA, according to claim 101, in which said a humanized antibody molecule comprises two full length antibody heavy chains and two full length antibody light chains. 103. A host cell transformed with a vector comprising DNA encoding a humanized recombinant anti-.alpha.4 antibody molecule, or .alpha.4-binding fragment thereof, comprising a humanized heavy chain, or an .alpha.4-binding fragment thereof, comprising a variable heavy chain region selected from the group consisting of: SEQ ID NO: 43, SEQ ID NO: 47, SEQ ID NO: 51, and SEQ ID NO: 55, and a humanized light chain, or an .alpha.4-binding fragment thereof, comprising a light chain variable region selected from the group consisting of: SEQ ID NO: 31, SEQ ID NO: 63, and SEQ ID NO: 67. 104. The host cell transformed with a vector comprising DNA encoding a humanized recombinant anti-.alpha.4 antibody molecule, or .alpha.4-binding fragment thereof, according to claim 103, in which said humanized recombinant anti-.alpha.4 antibody molecule comprises two full length antibody heavy chains and two full length antibody light chains. 105. A host cell transformed with an expression vector comprising DNA encoding an antibody molecule, or .alpha.4-binding fragment thereof, comprising a humanized heavy chain, or an .alpha.4-binding fragment thereof, comprising a variable heavy chain region selected from the group consisting of: SEQ ID NO: 43, SEQ ID NO: 47, SEQ ID NO: 51, and SEQ ID NO: 55, and a humanized light chain, or an .alpha.4-binding fragment thereof, comprising a light chain variable region selected from the group consisting of: SEQ ID NO: 31, SEQ ID NO: 63, and SEQ ID NO: 67. 106. The host cell transformed with a vector comprising DNA encoding a humanized recombinant anti-.alpha.4 antibody molecule, or .alpha.4-binding fragment thereof, according to claim 105, in which said humanized recombinant anti-.alpha.4 antibody molecule comprises two full length antibody heavy chains and two full length antibody light chains. 107. A humanized recombinant anti-.alpha.4 antibody molecule, or .alpha.4-binding fragment thereof, which comprises a humanized heavy chain, or an .alpha.4-binding fragment thereof, comprising a variable heavy chain region of V.sub.H -AS (SEQ ID NO: 55), in combination with a humanized light chain, or an .alpha.4-binding fragment thereof, comprising a light chain variable region of VK2-SVMDY (SEQ ID NO: 63). 108. The humanized recombinant anti-.alpha.4 antibody molecule, or .alpha.4-binding fragment thereof, according to claim 107, which comprises two full length antibody heavy chains and two full length antibody light chains. 109. A therapeutic composition comprising, in combination with a pharmaceutically acceptable diluent, excipient or carrier, an antibody molecule, or .alpha.4-binding fragment thereof, which comprises a humanized heavy chain, or an .alpha.4-binding fragment thereof, comprising a variable heavy chain region selected from the group consisting of: SEQ ID NO: 43, SEQ ID NO: 47, SEQ ID NO: 51, and SEQ ID NO: 55, and a humanized light chain, or an .alpha.4-binding fragment thereof, comprising a light chain variable region selected from the group consisting of SEQ ID NO: 31, SEQ ID NO: 63, and SEQ ID NO: 67. 110. The therapeutic composition according to claim 109, in which said antibody molecule comprises two full length antibody heavy chains and two full length antibody light chains. 111. A therapeutic composition comprising an antibody molecule, or .alpha.4-binding fragment thereof, which comprises a humanized heavy chain, or an .alpha.4-binding fragment thereof, comprising a variable heavy chain region of V.sub.H -AS (SEQ ID NO: 55), and a humanized light chain, or an .alpha.4-binding fragment thereof, comprising a light chain variable region of VK2-SVMDY (SEQ ID NO: 63), in combination with a pharmaceutically acceptable diluent, excipient or carrier. 112. The therapeutic composition according to claim 111, in which said antibody comprises two full length antibody heavy chains and two full length antibody light chains. 113. A diagnostic composition comprising an antibody molecule, or .alpha.4-binding fragment thereof, which comprises a humanized heavy chain, or an .alpha.4-binding fragment thereof, comprising a variable heavy chain region selected from the group consisting of: SEQ ID NO: 43, SEQ ID NO: 47, SEQ ID NO: 51 and SEQ ID NO: 55, and a humanized light chain, or an .alpha.4-binding fragment thereof, comprising a light chain variable region selected from the group consisting of SEQ ID NO: 31, SEQ ID NO: 63, and SEQ ID NO: 67, in a detectably labeled form. 114. The diagnostic composition, according to claim 113, in which said antibody molecule comprises two full length antibody heavy chains and two full length antibody light chains. 115. A diagnostic composition comprising an antibody molecule, or .alpha.4-binding fragment thereof, which comprises a humanized heavy chain, or an .alpha.4-binding fragment thereof comprising a variable heavy chain region of V.sub.H -AS (SEQ ID NO: 55), and a humanized light chain, or an .alpha.4-binding fragment thereof, comprising a light chain variable region of VK2-SVMDY (SEQ ID NO: 63), in a detectably labeled form. 116. The diagnostic composition comprising an antibody molecule, or .alpha.4-binding fragment thereof, which comprises a humanized heavy chain, or an .alpha.4-binding fragment thereof, according to claim 115, in which said antibody molecule comprises two full length antibody heavy chains and two full length antibody light chains. 117. A method for treating inflammation associated with a VCAM-1/VLA-4 adhesion pathway in a mammalian subject, the method comprising providing to a subject in need of such treatment an amount of an anti-inflammatory agent sufficient to suppress the inflammation, wherein the anti-inflammatory agent comprises an antibody, or .alpha.4-binding fragment thereof, which comprises a humanized heavy chain, or an .alpha.4-binding fragment thereof, comprising a variable heavy chain region selected from the group consisting of: SEQ ID NO: 43, SEQ ID NO: 47, SEQ ID NO: 51 and SEQ ID NO: 55, and a humanized light chain, or an .alpha.4-binding fragment thereof, comprising a light chain variable region selected from the group consisting of SEQ ID NO: 31, SEQ ID NO: 63 and SEQ ID NO: 67. 118. The method for treating inflammation according to claim 117, in which said antibody comprises two full length antibody heavy chains and two full length antibody light chains. 119. A method for treating inflammation associated with a VCAM-1/VLA-4 adhesion pathway in a mammalian subject the method comprising providing to a subject in need of such treatment an amount of an anti-inflammatory agent sufficient to suppress the inflammation, wherein the anti-inflammatory agent comprises an antibody molecule, or .alpha.4-binding fragment thereof, which comprises a humanized heavy chain, or an .alpha.4-binding fragment thereof, comprising a variable heavy chain region of V.sub.H -AS (SEQ ID NO: 55), and a humanized light chain, or an .alpha.4-binding fragment thereof, comprising a light chain variable region of VK2-SVMDY (SEQ ID NO: 63). 120. The method for treating inflammation, according to claim 119, in which said antibody comprises two full length antibody heavy chains and two full length antibody light chains. 121. A humanized recombinant anti-.alpha.4 antibody molecule produced by the NSO cell line having accession number ATCC CRL 11175. 122. A composition comprising a humanized anti-.alpha.4 antibody molecule, or an .alpha.4-binding fragment thereof which comprises a humanized heavy chain, or an .alpha.4-binding fragment thereof, comprising a variable heavy chain region selected from the group consisting of SEQ ID NO: 39, SEQ ID NO: 43, SEQ ID NO: 47, SEQ ID NO: 51, SEQ ID NO: 55, in combination with a humanized light chain, or an .alpha.4-binding fragment thereof, comprising a light chain variable region selected from the group consisting of SEQ ID NO: 31, SEQ ID NO: 63, and SEQ ID NO: 67 in combination with a pharmaceutically acceptable diluent, excipient or carrier. 123. The composition according to claim 122, in which the humanized anti-.alpha.4 antibody comprises two full length antibody heavy chains and two full length antibody light chains. 124. A composition comprising an antibody molecule, or an .alpha.4-binding fragment thereof, comprising a humanized recombinant anti-.alpha.4 antibody molecule which comprises a humanized heavy chain, or an .alpha.4-binding fragment thereof, comprising a variable heavy chain region of SEQ ID NO: 55, in combination with a humanized light chain, or an .alpha.4-binding fragment thereof, comprising a light chain variable region of SEQ ID NO: 63 in combination with a pharmaceutically acceptable diluent, excipient or carrier. 125. The composition, according to claim 124, in which the antibody molecule comprises two full length antibody heavy chains and two full length antibody light chains. 126. A method for treating inflammation associated with a VCAM-1/VLA-4 adhesion pathway in a mammalian subject, the method comprising providing to a subject in need of such treatment an amount of an anti-inflammatory agent sufficient to suppress the inflammation, wherein the anti-inflammatory agent comprises a humanized recombinant anti-.alpha.4 antibody molecule, or an .alpha.4-binding fragment thereof, which comprises a humanized heavy chain, or an .alpha.4-binding fragment thereof, comprising a variable heavy chain region selected from the group consisting of SEQ ID NO: 39, SEQ ID NO: 43, SEQ ID NO: 47, SEQ ID NO: 51, SEQ ID NO: 55, in combination with a humanized light chain, or an .alpha.4-binding fragment thereof, comprising a light chain variable region selected from the group consisting of SEQ ID NO: 31, SEQ ID NO: 63, and SEQ ID NO: 67 in combination with a pharmaceutically acceptable diluent, excipient or carrier. 127. The method for treating inflammation, according to claim 126, in which the humanized recombinant anti-.alpha.4 antibody molecule comprises two full length antibody heavy chains and two full length antibody light chains. 128. A method for treating inflammation associated with a VCAM-1/VLA-4 adhesion pathway in a mammalian subject, the method comprising providing to a subject in need of such treatment an amount of an anti-inflammatory agent sufficient to suppress the inflammation, wherein the anti-inflammatory agent comprises a humanized recombinant anti-.alpha.4 antibody molecule, or an .alpha.4-binding fragment thereof, which comprises a humanized heavy chain, or an .alpha.4-binding fragment thereof, comprising a variable heavy chain region of SEQ ID NO: 55, in combination with a humanized light chain, or an .alpha.4-binding fragment thereof, comprising a light chain variable region of SEQ ID NO: 63 in combination with a pharmaceutically acceptable diluent, excipient or carrier. 129. The method for treating inflammation, according to claim 128, in which the humanized recombinant anti-.alpha.4 antibody molecule comprises two full length antibody heavy chains and two full length antibody light chains. 130. The humanized recombinant antibody molecule, or an .alpha.4-binding fragment thereof, according to claim 1, wherein the nonhuman CDRs of the heavy chain are derived from the HP1/2 murine monoclonal antibody (SEQ ID NO: 6 and SEQ ID NO: 10). 131. The humanized recombinant antibody molecule, or .alpha.4-binding fragment thereof, according to claim 1, wherein the non-human CDRs of the light chain are derived from the HP1/2 murine monoclonal antibody (SEQ ID NO: 6 and SEQ ID NO: 10). 132. The humanized recombinant antibody molecule, or an .alpha.4-binding fragment thereof, according to claim 1, wherein the CDR1 is derived from the HP1/2 murine monoclonal antibody (SEQ ID NO: 6 and SEQ ID NO: 10). 133. The humanized recombinant antibody molecule, or an .alpha.4-binding fragment thereof, according to claim 1, wherein the CDR2 is derived from the HP1/2 murine monoclonal antibody (SEQ ID NO: 6 and SEQ ID NO: 10). 134. The humanized recombinant antibody molecule, or an .alpha.4-binding fragment thereof, according to claim 1, wherein the CDR3 is derived from the HP1/2 murine monoclonal antibody (SEQ ID NO: 6 and SEQ ID NO: 10). 135. The humanized recombinant antibody molecule, or an .alpha.4-binding fragment thereof, according to claim 1, wherein the CDR1 is derived from the HP1/2 murine monoclonal antibody (SEQ ID NO: 10). 136. The humanized recombinant antibody molecule, or an .alpha.4-binding fragment thereof according to claim 1, wherein the CDR2 is derived from the HP1/2 murine monoclonal antibody (SEQ ID NO: 10). 137. The humanized recombinant antibody molecule, or an .alpha.4-binding fragment thereof, according to claim 1, wherein the CDR3 is derived from the HP1/2 murine monoclonal antibody (SEQ ID NO: 10). 138. The humanized recombinant antibody molecule, or an .alpha.4-binding fragment thereof, according to claim 1, which has a binding affinity, as defined by half maximal binding constant, from about 20% to about 100% of the binding affinity of the HP1/2 murine monoclonal antibody (SEQ ID NO: 6 and SEQ ID NO: 10). 139. A humanized recombinant anti-.alpha.4 antibody molecule, or .alpha.4-binding fragment thereof, comprising: at least one antibody heavy chain, or an .alpha.4-binding fragment thereof, comprising three non-human CDRs from the HP1/2 murine monoclonal antibody (SEQ ID NO: 6 and SEQ ID NO: 10); and at least one antibody light chain, or an .alpha.4-binding fragment thereof, comprising three non-human CDRs from the HP1/2 murine monoclonal antibody (SEQ ID NO: 6 and SEQ ID NO: 10); wherein said humanized antibody has a binding affinity, as defined by half maximal binding constant, from about 20% to about 100% of the binding affinity of the HP1/2 murine monoclonal antibody. 140. A therapeutic composition comprising an antibody molecule or an .alpha.4-binding fragment thereof, comprising: at least one antibody heavy chain, or an .alpha.4-binding fragment thereof, comprising non-human CDRs at positions 31-35 (CDR1), 50-65 (CDR2) and 95-102 (CDR3) (Kabat numbering) from a mouse anti-.alpha.4 antibody and having non-human residues at framework positions 27-30 (Kabat numbering), wherein said positions 27-30 have the amino acid sequence Phe 27, Asn 28, Ile 29 and Lys 30 (SEQ ID NO: 107); and at least one antibody light chain, or an .alpha.4-binding fragment thereof, comprising non-human CDRs at positions 24-34 (CDR1), 50-56 (CDR2) and 89-97 (CDR3) from a mouse anti-.alpha.4 antibody and framework regions from the REI monoclonal antibody (SEQ ID NO: 100), wherein said REI framework regions have at least one non-human framework residue and the amino acid sequence Val 104, Glu 105 and Lys 107, in combination with a pharmaceutically acceptable diluent, excipient or carrier. 141. The therapeutic composition, according to claim 140, wherein said heavy chain, or .alpha.4-binding fragment thereof comprises additional non-human residues at framework position 75 (Kabat numbering). 142. The therapeutic composition, according to claim 140, wherein said heavy chain, or .alpha.4-binding fragment thereof, comprises additional non-human residues at framework position(s) 77-79 or 66-67 and 69-71 or 84-85 or 38 and 40 or 24. 143. The therapeutic composition, according to claim 140, wherein said light chain, or .alpha.4-binding fragment thereof, comprises non-human residues at framework positions 60 and 67. 144. The therapeutic composition according to claim 140, in which the antibody molecule comprises two full length antibody heavy chains and two full length antibody light chains. 145. The therapeutic composition according to claim 140, wherein the non-human CDRs are derived from the HP1/2 murine monoclonal antibody (SEQ ID NO: 6 and SEQ ID NO: 10). 146. The recombinant antibody molecule, or an .alpha.4-binding fragment thereof, of claim 1, wherein the .alpha.4-binding fragment is an Fab fragment.

Details for Patent 6,602,503

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	AVASTIN	bevacizumab	Injection	125085	02/26/2004		2020-08-05
Biogen Inc.	TYSABRI	natalizumab	Injection	125104	11/23/2004		2020-08-05

International Patent Family for US Patent 6,602,503

Country	Patent Number	Estimated Expiration
Austria	182625
Australia	5993694
Australia	688751
Canada	2153692
Germany	69419721