Recombinant anti-VLA4 antibody molecules
View Patent ↗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.
1. A vector comprising DNA encoding a humanized heavy chain, or an α4-binding fragment thereof, comprising a variable heavy chain region consisting of SEQ ID NO:39, and a humanized light chain, or an α4-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.
2. The vector of claim 1 , wherein the humanized light chain, or the α4-binding fragment thereof, comprises a light chain variable region consisting of SEQ ID NO: 31.
3. The vector of claim 1 , wherein the humanized light chain, or the α4-binding fragment thereof, comprises a light chain variable region consisting of SEQ ID NO: 63.
4. The vector of claim 1 , wherein the humanized light chain, or the α4-binding fragment thereof, comprises a light chain variable region consisting of SEQ ID NO: 67.
5. An expression vector comprising DNA encoding a humanized recombinant anti-α4 antibody molecule, or an α4-binding fragment thereof, wherein the humanized recombinant anti-α4 antibody molecule, or an α4-binding fragment thereof, comprises a humanized heavy chain, or an α4-binding fragment thereof, comprising a variable heavy chain region consisting of SEQ ID NO:39, and a humanized light chain, or an α4-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.
6. The expression vector of claim 5 wherein the humanized light chain, or the α4-binding fragment thereof, comprises a light chain variable region consisting of SEQ ID NO: 31.
7. The expression vector of claim 5 wherein the humanized light chain, or the α4-binding fragment thereof, comprises a light chain variable region consisting of SEQ ID NO: 63.
8. The expression vector of claim 5 wherein the humanized light chain, or the α4-binding fragment thereof, comprises a light chain variable region consisting of SEQ ID NO: 67.
9. A host cell transformed with a vector comprising DNA encoding a humanized recombinant anti-α4 antibody molecule, or an α4-binding fragment thereof, wherein the humanized recombinant anti-α4 antibody molecule, or an α4-binding fragment thereof, comprises a humanized heavy chain, or an α4-binding fragment thereof, comprising a variable heavy chain region consisting of SEQ ID NO:39, and a humanized light chain, or an α4-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.
10. The host cell of claim 9 wherein the humanized light chain, or the α4-binding fragment thereof, comprises a light chain variable region consisting of SEQ ID NO: 31.
11. The host cell of claim 9 wherein the humanized light chain, or the α4-binding fragment thereof, comprises a light chain variable region consisting of SEQ ID NO: 63.
12. The host cell of claim 9 wherein the humanized light chain, or the α4-binding fragment thereof, comprises a light chain variable region consisting of SEQ ID NO: 67.
13. A host cell transformed with an expression vector comprising DNA encoding an antibody molecule, or an α4-binding fragment thereof, comprising a humanized heavy chain, or an α4-binding fragment thereof, comprising a variable heavy chain region consisting of SEQ ID NO:39, and a humanized light chain, or an α4-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.
14. The host cell of claim 13 wherein the humanized light chain, or the α4-binding fragment thereof, comprises a light chain variable region consisting of SEQ ID NO: 31.
15. The host cell of claim 13 wherein the humanized light chain, or the α4-binding fragment thereof, comprises a light chain variable region consisting of SEQ ID NO: 63.
16. The host cell of claim 13 wherein the humanized light chain, or the α4-binding fragment thereof, comprises a light chain variable region consisting of SEQ ID NO: 67.
17. A therapeutic composition comprising an antibody molecule, or an α4-binding fragment thereof, comprising a humanized heavy chain, or an α4-binding fragment thereof, comprising a variable heavy chain region consisting of SEQ ID NO:39, and a humanized light chain, or an α4-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.
18. The therapeutic composition of claim 17 wherein the humanized light chain, or the α4-binding fragment thereof, comprises a light chain variable region consisting of SEQ ID NO: 31.
19. The therapeutic composition of claim 17 wherein the humanized light chain, or the α4-binding fragment thereof, comprises a light chain variable region consisting of SEQ ID NO: 63.
20. The therapeutic composition of claim 17 wherein the humanized light chain, or the α4-binding fragment thereof, comprises a light chain variable region consisting of SEQ ID NO: 67.
21. A diagnostic composition comprising an antibody molecule, or an α4-binding fragment thereof, which comprises a humanized heavy chain, or an α4-binding fragment thereof, comprising a variable heavy chain region consisting of SEQ ID NO:39, and a humanized light chain, or an α4-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.
22. The diagnostic composition of claim 21 wherein the humanized light chain, or the α4-binding fragment thereof, comprises a light chain variable region consisting of SEQ ID NO: 31.
23. The diagnostic composition of claim 21 wherein the humanized light chain, or the α4-binding fragment thereof, comprises a light chain variable region consisting of SEQ ID NO: 63.
24. The diagnostic composition of claim 21 wherein the humanized light chain, or the α4-binding fragment thereof, comprises a light chain variable region consisting of SEQ ID NO: 67.
25. 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 an α4-binding fragment thereof, which comprises a humanized heavy chain, or an α4-binding fragment thereof, comprising a variable heavy chain region consisting of SEQ ID NO:39, and a humanized light chain, or an α4-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.
26. The method of claim 25 wherein the humanized light chain, or the α4-binding fragment thereof, comprises a light chain variable region consisting of SEQ ID NO: 31.
27. The method of claim 25 wherein the humanized light chain, or the α4-binding fragment thereof, comprises a light chain variable region consisting of SEQ ID NO: 63.
28. The method of claim 25 wherein the humanized light chain, or the α4-binding fragment thereof, comprises a light chain variable region consisting of SEQ ID NO: 67.