Biological materials related to c-Met
The present invention relates to biological materials related to c-Met possibly in combination with VEGF and/or EGFR, and more in particular to polypeptides, nucleic acids encoding such polypeptides; to methods for preparing such polypeptides; to host cells expressing or capable of expressing such polypeptides; to compositions and in particular to pharmaceutical compositions that comprise such polypeptides, for prophylactic, therapeutic or diagnostic purposes. Methods and kits for assessing the responsiveness of a patient to c-Met therapy are also described and provided.
1. A polypeptide comprising a first immunoglobulin single variable domain (ISVD) that can displace HGF from human c-Met (SEQ ID NO: 1) and having more than 95% sequence identity with SEQ ID NO: 102, where the C-terminus of the first ISVD is linked by a peptide linker to the N-terminus of a second ISVD that binds human serum albumin selected from the group consisting of A1b11 (SEQ ID NO: 5) and A1b23 (SEQ ID NO: 101).
2. The polypeptide of claim 1 where the first ISVD and the second ISVD are linked by the linker peptide 9GS (SEQ ID NO: 15).
3. The polypeptide of claim 1 where the second ISVD is SEQ ID NO: 5.
4. The polypeptide of claim 1 where the second ISVD is SEQ ID NO: 101.
5. The polypeptide of claim 1 where the first ISVD is SEQ ID NO: 102.
6. The polypeptide of claim 1 comprising SEQ ID NO: 188.
7. A pharmaceutical composition comprising the polypeptide of any one of claims 1 - 6 and a pharmaceutically acceptable excipient.
8. A polypeptide that can displace HGF from human c-Met (SEQ ID NO: 1) comprising a polypeptide having more than 90% sequence identity with SEQ ID NOS: 7-10, 104, 106, 113, 142-150, or 188.
9. A polypeptide that can displace HGF from human c-Met (SEQ ID NO: 1) comprising a polypeptide selected from the group consisting of SEQ ID NOS: 7-10, 104, 106, 113, 142-150, and 188.
10. A pharmaceutical composition comprising the polypeptide of claim 8 or claim 9 and a pharmaceutically acceptable excipient.
11. The polypeptide of claim 9 comprising SEQ ID NO: 7.
12. The polypeptide of claim 9 comprising SEQ ID NO: 8.
13. The polypeptide of claim 9 comprising SEQ ID NO: 9.
14. The polypeptide of claim 9 comprising SEQ ID NO: 10.
15. The polypeptide of claim 9 comprising SEQ ID NO: 104.
16. The polypeptide of claim 9 comprising SEQ ID NO: 106.
17. The polypeptide of claim 9 comprising SEQ ID NO: 113.
18. The polypeptide of claim 9 comprising SEQ ID NO: 142.
19. The polypeptide of claim 9 comprising SEQ ID NO: 143.
20. The polypeptide of claim 9 comprising SEQ ID NO: 144.
21. The polypeptide of claim 9 comprising SEQ ID NO: 145.
22. The polypeptide of claim 9 comprising SEQ ID NO: 146.
23. The polypeptide of claim 9 comprising SEQ ID NO: 147.
24. The polypeptide of claim 9 comprising SEQ ID NO: 148.
25. The polypeptide of claim 9 comprising SEQ ID NO: 149.
26. The polypeptide of claim 9 comprising SEQ ID NO: 150.