Metalloproteinase binding proteins
View Patent ↗Proteins that bind to matrix metalloproteinase 14 and methods of using such proteins are described.
1. A protein conjugate comprising a heavy chain (HC) immunoglobulin variable domain sequence and a light chain (LC) immunoglobulin variable domain sequence coupled to an agent, 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 conjugate of claim 1 , wherein the agent is an anti-cancer agent.
3. The protein conjugate of claim 2 , wherein the anticancer agent is selected from the group consisting of a cytotoxic drug, a cytotoxic enzyme and a radioisotope.
4. The protein conjugate of claim 3 , wherein the cytotoxic drug is cytotoxic drug of plant origin, fungal origin or bacterial origin.
5. The protein conjugate of claim 1 , wherein the agent is a toxin short range radiation emitter.
6. The protein conjugate of claim 5 , wherein the toxin short range radiation emitter is an α-emitter.
7. The protein conjugate of claim 3 , wherein the radioisotope is a β-emitter.
8. The protein conjugate of claim 3 , wherein the radioisotope is a γ-emitter.
9. The protein conjugate of claim 3 , wherein the radioisotope is selected from 212 Bi, 213 Bi, 211 At and 186 Re.
10. The protein conjugate of claim 3 , wherein the radioisotope is selected from 131 I, 90 Y and 177 Lu.
11. The protein conjugate of claim 1 , wherein the protein comprises a human antibody framework region.
12. The protein conjugate of claim 1 , wherein the protein is a primate antibody.
13. The protein conjugate of claim 1 , wherein the protein comprises a primate antibody framework region.
14. The protein conjugate of claim 13 , wherein the protein is a humanized antibody.
15. The protein conjugate 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.
16. The protein conjugate of claim 1 , wherein the HC immunoglobulin variable domain sequence comprises SEQ ID NO:156.
17. The protein conjugate 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.
18. The protein conjugate of claim 1 , wherein the LC immunoglobulin variable domain sequence comprises SEQ ID NO:157.
19. The protein conjugate 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.
20. The protein conjugate 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.
21. The protein conjugate 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.
22. The protein conjugate of claim 1 , wherein the protein comprises residues 20 to 464 of SEQ ID NO:182.
23. The protein conjugate 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.
24. The protein conjugate of claim 1 , wherein the protein comprises residues 20 to 234 of SEQ ID NO:181.
25. The protein conjugate 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.
26. The protein conjugate 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.
27. A pharmaceutical composition comprising the protein conjugate of claim 1 and a pharmaceutically acceptable carrier.