Anti-MCAM antibodies and associated methods of use
Described herein are anti-MCAM antibodies and antigen binding fragments thereof that are capable of inhibiting the interaction between MCAM and its ligand, a protein comprising a laminin α-4 chain. These anti-MCAM antibodies and antigen binding fragments thereof may be useful for, for example, treating inflammatory conditions characterized by the infiltration of MCAM-expressing cells into a site of inflammation in the body.
1. The isolated anti-MCAM antibody, or antigen binding fragment thereof, wherein said antibody or antigen binding fragment thereof comprises three light chain hypervariable regions (HVR-L1, HVR-L2, and HVR-L3) and three heavy chain hypervariable regions (HVR-H1, HVR-H2, and HVR-H3), wherein:
(a) HVR-L1 comprises the amino acid sequence of SEQ ID NO:73, HVR-L2 comprises the amino acid sequence of SEQ ID NO:74, HVR-L3 comprises the amino acid sequence of SEQ ID NO:75, HVR-H1 comprises the amino acid sequence of SEQ ID NO:78, HVR-H2 comprises the amino acid sequence of SEQ ID NO:79, and HVR-H3 comprises the amino acid sequence of SEQ ID NO:80;
(b) HVR-L1 comprises the amino acid sequence of SEQ ID NO:73, HVR-L2 comprises the amino acid sequence of SEQ ID NO:74, HVR-L3 comprises the amino acid sequence of SEQ ID NO:75, HVR-H1 comprises the amino acid sequence of SEQ ID NO:141, HVR-H2 comprises the amino acid sequence of SEQ ID NO:79, and HVR-H3 comprises the amino acid sequence of SEQ ID NO:80;
(c) HVR-L1 comprises the amino acid sequence of SEQ ID NO:73, HVR-L2 comprises the amino acid sequence of SEQ ID NO:74, HVR-L3 comprises the amino acid sequence of SEQ ID NO:75, HVR-H1 comprises the amino acid sequence of SEQ ID NO:139, HVR-H2 comprises the amino acid sequence of SEQ ID NO:79, and HVR-H3 comprises the amino acid sequence of SEQ ID NO:80; or
(d) HVR-L1 comprises the amino acid sequence of SEQ ID NO:73, HVR-L2 comprises the amino acid sequence of SEQ ID NO:74, HVR-L3 comprises the amino acid sequence of SEQ ID NO:75, HVR-H1 comprises the amino acid sequence of SEQ ID NO:140, HVR-H2 comprises the amino acid sequence of SEQ ID NO:79, and HVR-H3 comprises the amino acid sequence of SEQ ID NO:80.
2. The isolated anti-MCAM antibody, or antigen binding fragment thereof, of claim 1 , wherein HVR-L1 comprises the amino acid sequence of SEQ ID NO:73, HVR-L2 comprises the amino acid sequence of SEQ ID NO:74, HVR-L3 comprises the amino acid sequence of SEQ ID NO:75, HVR-H1 comprises the amino acid sequence of SEQ ID NO:141, HVR-H2 comprises the amino acid sequence of SEQ ID NO:79, and HVR-H3 comprises the amino acid sequence of SEQ ID NO:80.
3. The isolated anti-MCAM antibody, or antigen binding fragment thereof, of claim 2 , wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:119.
4. The isolated anti-MCAM antibody, or antibody binding fragment thereof, of claim 2 , wherein the antibody further comprises a heavy chain framework region 1 (FR1) comprising the amino acid sequence of SEQ ID NO:133.
5. The isolated anti-MCAM antibody, or antibody binding fragment thereof, of claim 2 , wherein the antibody further comprises a heavy chain framework region 2 (FR2) comprising the amino acid sequence of SEQ ID NO:134.
6. The isolated anti-MCAM antibody, or antibody binding fragment thereof, of claim 2 , wherein the antibody further comprises a heavy chain framework region 3 (FR3) comprising the amino acid sequence of SEQ ID NO:135.
7. The isolated anti-MCAM antibody, or antibody binding fragment thereof, of claim 2 , wherein the antibody further comprises a light chain framework region 1 (FR1) comprising the amino acid sequence of SEQ ID NO:147.
8. The isolated anti-MCAM antibody, or antibody binding fragment thereof, of claim 2 , wherein the antibody further comprises a light chain framework region 2 (FR2) comprising the amino acid sequence of SEQ ID NO:148.
9. The isolated anti-MCAM antibody, or antibody binding fragment thereof, of claim 2 , wherein the antibody further comprises a light chain framework region 3 (FR3) comprising the amino acid sequence of SEQ ID NO:149.
10. The isolated anti-MCAM antibody, or antigen binding fragment thereof, of claim 2 , wherein the light chain variable region comprises the amino acid sequence of SEQ ID NO:123.
11. The isolated anti-MCAM antibody, or antigen binding fragment thereof, of claim 10 , wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:119.
12. The isolated anti-MCAM antibody, or antigen binding fragment thereof, of claim 2 , which is a chimeric or humanized antibody.
13. The isolated anti-MCAM antibody, or antigen binding fragment thereof, of claim 2 , which is an IgG1 antibody.
14. The isolated anti-MCAM antibody, or antigen binding fragment thereof, of claim 2 , which is produced in bacteria or CHO cells.
15. A pharmaceutical composition comprising an anti-MCAM antibody, or antigen binding fragment thereof, according to claim 1 .
16. A pharmaceutical composition comprising an anti-MCAM antibody, or antigen binding fragment thereof, according to claim 2 .
17. A pharmaceutical composition comprising an anti-MCAM antibody, or antigen binding fragment thereof, according to claim 10 .
18. A pharmaceutical composition comprising an anti-MCAM antibody, or antigen binding fragment thereof, according to claim 5 .
19. A pharmaceutical composition comprising an anti-MCAM antibody, or antigen binding fragment thereof, according to claim 6 .
20. A pharmaceutical composition comprising an anti-MCAM antibody, or antigen binding fragment thereof, according to claim 7 .
21. A pharmaceutical composition comprising an anti-MCAM antibody, or antigen binding fragment thereof, according to claim 8 .
22. A pharmaceutical composition comprising an anti-MCAM antibody, or antigen binding fragment thereof, according to claim 9 .