Treatment for inflammatory bowel disease with α4-specific antibodies
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 method for treating inflammatory bowel disease (IBD) in a subject, the method comprising administering to the subject an anti-α4 antibody, or an α4-binding fragment thereof, wherein the antibody has one or both of:
a humanized antibody heavy chain comprising non-human CDRs from a mouse anti-α4 antibody and having non-human residues at framework positions 77–79 or 66–67 and 69–71 or 84–85 or 38 and 40; and
a humanized antibody light chain comprising non-human CDRs from a mouse anti-α4 antibody and having non-human residues at framework positions 60 and 67.
2. The method of claim 1 , wherein said heavy chain comprises additional non-human residues at framework position 75 (Kabat numbering).
3. The method of claim 1 , wherein the antibody comprises both of the humanized heavy chain and the humanized light chain.
4. The method of claim 1 , wherein the antibody comprises two full length antibody heavy chains and two full length antibody light chains.
5. The method of claim 1 , wherein the non-human CDR of the humanized heavy chain is derived from the HP1/2 murine monoclonal antibody (SEQ ID NO:6).
6. The method of claim 1 , wherein the non-human CDR of the humanized light chain is derived from the HP1/2 murine monoclonal antibody (SEQ ID NO:10).
7. The method of claim 1 , wherein the non-human CDRs of the humanized heavy chain and humanized light chain are derived from the HP1/2 murine monoclonal antibody (SEQ ID NO:6 and SEQ ID NO:10).
8. A method for treating inflammatory bowel disease (IBD) in a subject, the method comprising administering to the subject an anti-α4 antibody, or α4-binding fragment thereof, wherein the antibody comprises a humanized heavy chain 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 and SEQ ID NO: 55, and a humanized light chain 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.
9. The method of claim 8 , in which said antibody comprises two full-length antibody heavy chains and two full length antibody light chains.
10. A method for treating inflammatory bowel disease (IBD) in a subject the method comprising administering to the subject an anti-α4 antibody, or α4-binding fragment thereof, wherein the antibody comprises a humanized heavy chain comprising a variable heavy chain region of V H -AS (SEQ ID NO: 55), and a humanized light chain comprising a light chain variable region of VK2-SVMDY (SEQ ID NO: 63).
11. The method of claim 10 , wherein said antibody comprises two full length antibody heavy chains and two full length antibody light chains.