Antibodies that bind MMP-14
View Patent ↗Proteins that bind to matrix metalloproteinase 14 and methods of using such proteins are described.
1. An isolated protein comprising a heavy chain (HC) immunoglobulin variable domain sequence and a light chain (LC) immunoglobulin variable domain sequence, wherein the HC and the LC immunoglobulin variable domain sequences form an antigen binding site that binds to a human membrane-type-matrix metalloproteinase 14 (MMP-14) and wherein the HC immunoglobulin variable domain comprises HC complementarity determining region (CDR) 1, CDR2, and CDR3, wherein the HC CDR1 sequence comprises residues 31-35 of SEQ ID NO:156, the HC CDR2 sequence comprises residues 50-66 of SEQ ID NO:156, and the HC CDR3 sequence comprises residues 99-104 of SEQ ID NO:156; and the LC immunoglobulin variable domain comprises LC CDR1, CDR2, and CDR3, wherein the LC CDR1 sequence comprises residues 25-35 of SEQ ID NO:157, the LC CDR2 sequence comprises residues 51-57 of SEQ ID NO:157, and the LC CDR3 sequence comprises residues 90-99 of SEQ ID NO:157.
2. The protein of claim 1 , wherein the protein inhibits human MMP-14 enzymatic activity.
3. The protein of claim 1 , wherein the HC and LC variable domain sequences are components of the same polypeptide chain.
4. The protein of claim 1 , wherein the protein comprises a human antibody framework region.
5. A pharmaceutical composition comprising the protein of claim 1 and a pharmaceutically acceptable carrier.
6. The protein of claim 1 , wherein the protein is a primate antibody.
7. The protein of claim 1 , wherein the protein comprises a primate antibody framework region.
8. The protein of claim 1 , wherein the protein is a humanized antibody.
9. The protein of claim 1 , wherein the HC immunoglobulin variable domain sequence comprises a sequence that has less than 10 conservative mutations in the framework regions relative to SEQ ID NO:156.
10. The protein of claim 1 , wherein the HC immunoglobulin variable domain sequence comprises SEQ ID NO:156.
11. The protein of claim 1 , wherein the LC immunoglobulin variable domain sequence comprises a sequence that has less than 10 conservative mutations in the framework regions relative to SEQ ID NO:157.
12. The protein of claim 1 , wherein the LC immunoglobulin variable domain sequence comprises SEQ ID NO:157.
13. The protein of claim 1 , wherein the HC immunoglobulin variable domain sequence comprises a sequence that has less than 10 conservative mutations in the framework regions relative to SEQ ID NO:156 and the LC immunoglobulin variable domain sequence comprises a sequence that is has less than 10 conservative mutations in the framework regions relative to SEQ ID NO:157.
14. The protein of claim 1 , wherein the HC immunoglobulin variable domain sequence comprises SEQ ID NO:156 and the LC immunoglobulin variable domain sequence comprises SEQ ID NO:157.
15. The protein of claim 1 , wherein the protein comprises a sequence that is at least 90% identical to residues 20 to 464 of SEQ ID NO:182 in the framework regions.
16. The protein of claim 1 , wherein the protein comprises residues 20 to 464 of SEQ ID NO:182.
17. The protein of claim 1 , wherein the protein comprises a sequence that is at least 90% identical to residues 20 to 234 of SEQ ID NO:181 in the framework regions.
18. The protein of claim 1 , wherein the protein comprises residues 20 to 234 of SEQ ID NO:181.
19. The protein of claim 1 , wherein the protein comprises a sequence that is at least 90% identical to residues 20 to 464 of SEQ ID NO:182 in the framework regions and a sequence that is at least 90% identical to residues 20 to 234 of SEQ ID NO:181 in the framework regions.
20. The protein of claim 1 , wherein the protein comprises residues 20 to 464 of SEQ ID NO:182 and residues 20 to 234 of SEQ ID NO:181.
21. A pharmaceutical composition comprising the protein of claim 14 and a pharmaceutically acceptable carrier.
22. A pharmaceutical composition comprising the protein of claim 20 and a pharmaceutically acceptable carrier.
23. The protein of claim 1 , wherein the protein binds to human MMP-14.
24. The protein of claim 1 , wherein the protein comprises a sequence that has less than 10 conservative mutations in the framework regions relative to residues 20 to 464 of SEQ ID NO:182.
25. The protein of claim 1 , wherein the protein comprises a sequence that has less than 10 conservative mutations in the framework regions relative to residues 20 to 234 of SEQ ID NO:181.
26. The protein of claim 1 , wherein the protein comprises a sequence that has less than 10 conservative mutations in the framework regions relative to residues 20 to 464 of SEQ ID NO:182 and a sequence that that has less than 10 conservative mutations in the framework regions relative to residues 20 to 234 of SEQ ID NO:181.
27. The protein of claim 1 , wherein the protein comprises a sequence that has less than 5 conservative mutations in the framework regions relative to residues 20 to 464 of SEQ ID NO:182.
28. The protein of claim 1 , wherein the protein comprises a sequence that has less than 5 conservative mutations in the framework regions relative to residues 20 to 234 of SEQ ID NO:181.
29. The protein of claim 1 , wherein the protein comprises a sequence that has less than 5 conservative mutations in the framework regions relative to residues 20 to 464 of SEQ ID NO:182 and a sequence that that has less than 5 conservative mutations in the framework regions relative to residues 20 to 234 of SEQ ID NO:181.
30. The protein of claim 1 , wherein the HC immunoglobulin variable domain sequence comprises a sequence that has less than 5 conservative mutations in the framework regions relative to SEQ ID NO:156.
31. The protein of claim 1 , wherein the LC immunoglobulin variable domain sequence comprises a sequence that has less than 5 conservative mutations in the framework regions relative to SEQ ID NO:157.
32. The protein of claim 1 , wherein the HC immunoglobulin variable domain sequence comprises a sequence that has less than 5 conservative mutations in the framework regions relative to SEQ ID NO:156 and the LC immunoglobulin variable domain sequence comprises a sequence that is has less than 5 conservative mutations in the framework regions relative to SEQ ID NO:157.