EFGR antibodies comprising modular recognition domains
Antibodies containing one or more modular recognition domains (MRDs) that can be used to target the antibodies to specific sites are described. The use of antibodies containing one or more modular recognition domains to treat disease, and methods of making antibodies containing one or more modular recognition domains are also described.
1. A complex comprising an antibody and at least one modular recognition domain (MRD), wherein the antibody binds to EGFR and the MRD competitively inhibits binding of angiopoietin-2 (Ang2) to a polypeptide consisting of the amino acid sequence of SEQ ID NO:8 or SEQ ID NO:21.
2. The complex of claim 1 , wherein the EGFR is human.
3. The complex of claim 1 , wherein the antibody is chimeric, humanized, or human.
4. The complex of claim 3 , wherein the antibody is humanized.
5. The complex of claim 1 , wherein the antibody binds to the same epitope as cetuximab.
6. The complex of claim 1 , wherein the antibody competitively inhibits cetuximab binding to EGFR.
7. The complex of claim 1 , wherein the antibody is cetuximab.
8. The complex of claim 1 , wherein the antibody binds to the same epitope as panitumumab.
9. The complex of claim 8 , wherein the antibody competitively inhibits panitumumab binding to EGFR.
10. The complex of claim 9 , wherein the antibody is panitumumab.
11. The complex of claim 1 , wherein the MRD is located on a terminus selected from the group consisting of (a) the N-terminus of the antibody heavy chain, (b) the N-terminus of the antibody light chain, (c) the C-terminus of the antibody heavy chain, and (d) the C-terminus of the antibody light chain.
12. The complex of claim 11 , wherein a first MRD is located on (c) the C-terminus of the antibody heavy chain and a second MRD is located on (d) the C-terminus of the antibody light chain.
13. The complex of claim 11 , wherein the antibody and the MRD are operably linked through a linker peptide.
14. The complex of claim 13 , wherein the linker comprises a sequence selected from the group consisting of: SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:19.
15. The complex of claim 1 , wherein the Ang2-binding MRD consists of the amino acid sequence of SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:21, SEQ ID NO:23, SEO ID NO:24, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:33, or SEQ ID NO:34.
16. The complex of claim 15 , wherein the Ang2-binding MRD consists of the amino acid sequence of SEQ ID NO:8.
17. The complex of claim 15 , wherein the MRD is located on a terminus selected from the group consisting of (a) the N-terminus of the antibody heavy chain, (b) the N-terminus of the antibody light chain, (c) the C-terminus of the antibody heavy chain, and (d) the C-terminus of the antibody light chain.
18. The complex of claim 17 , wherein the antibody and the MRD are operably linked through a linker peptide.
19. The complex of claim 18 , wherein the linker comprises a sequence selected from the group consisting of: SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:19.
20. The complex of claim 1 , wherein the complex further comprises an MRD that binds to insulin-like growth factor-1 receptor (IGF-1R), wherein the IGF-1R-binding MRD consists of a sequence selected from the group consisting of SEQ ID NO:14, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, and SEQ ID NO:58.
21. The complex of claim 20 , wherein the IGF-1R-binding MRD consists of the amino acid sequence of SEQ ID NO:14.
22. The complex of claim 20 , wherein the complex further comprises an MRD that binds to insulin-like growth factor-1 receptor (IGF-1R), wherein the IGF-1R-binding MRD competitively inhibits binding to IGF-1R to a polypeptide consisting of the amino acid sequence of SEQ ID NO:14.
23. The complex of claim 22 , wherein the IGF-1R-binding MRD is located on a terminus selected from the group consisting of (a) the N-terminus of the antibody heavy chain, (b) the N-terminus of the antibody light chain, (c) the C-terminus of the antibody heavy chain, and (d) the C-terminus of the antibody light chain.
24. The complex of claim 23 , wherein the antibody and the IGF-1R-binding MRD are operably linked through a linker peptide.
25. The complex of claim 24 , wherein the linker comprises a sequence selected from the group consisting of: SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:19.
26. The complex of claim 23 , wherein the Ang2-binding MRD is located on the C-terminus of the antibody heavy chain and the IGF-1R-binding MRD is located on a terminus selected from the group consisting of (a) the N-terminus of the antibody heavy chain, (b) the N-terminus of the antibody light chain, (c) the C-terminus of the antibody heavy chain, and (d) the C-terminus of the antibody light chain.
27. The complex of claim 23 , wherein the Ang2-binding MRD is located on the N-terminus of the antibody heavy chain and the IGF-1R-binding MRD is located on a terminus selected from the group consisting of (a) the N-terminus of the antibody heavy chain, (b) the N-terminus of the antibody light chain, (c) the C-terminus of the antibody heavy chain, and (d) the C-terminus of the antibody light chain.
28. The complex of claim 23 , wherein the Ang2-binding MRD is located on the C-terminus of the antibody light chain and the IGF-1R-binding MRD is located on a terminus selected from the group consisting of (a) the N-terminus of the antibody heavy chain, (b) the N-terminus of the antibody light chain, (c) the C-terminus of the antibody heavy chain, and (d) the C-terminus of the antibody light chain.
29. The complex of claim 23 , wherein the Ang2-binding MRD is located on the N-terminus of the antibody light chain and the IGF-1R-binding MRD is located on a terminus selected from the group consisting of (a) the N-terminus of the antibody heavy chain, (b) the N-terminus of the antibody light chain, (c) the C-terminus of the antibody heavy chain, and (d) the C-terminus of the antibody light chain.
30. The complex of claim 23 , wherein the antibody and (a) the Ang2-binding MRD, or (b) the Ang2-binding MRD and the IGF-1R-binding MRD are operably linked through a linker peptide.
31. The complex of claim 30 , wherein the linker comprises a sequence selected from the group consisting of: SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:19.
32. The complex of claim 1 , wherein the antibody and the MRD bind their targets simultaneously.
33. The complex of claim 20 , wherein the antibody, the Ang2-binding MRD, and the IGF-1R binding MRD bind their targets simultaneously.
34. The complex of claim 1 , wherein the complex exhibits ADCC activity.
35. A pharmaceutical composition comprising the complex of claim 1 .
36. A method for inhibiting the growth of a cell expressing EGFR comprising contacting the cell with the complex of claim 1 .
37. A method for inhibiting angiogenesis in a patient comprising administering to said patient a therapeutically effective amount of the complex of claim 1 .