EGFR binding molecules
The application relates to specific binding members which bind the human epidermal growth factor receptor (EGFR). The specific binding members preferably comprise an EGFR antigen-binding site which may be located in two or more structural loops of a CH3 domain of the specific binding member. The specific binding members are expected to find application in the treatment of cancers expressing EGFR.
1. An antibody molecule, comprising an EGFR antigen-binding site located in a CH3 domain of the antibody molecule, wherein the EGFR binding site comprises the amino acid sequences:
(i)
(SEQ ID NO: 1)
LDEGGP
and
(SEQ ID NO: 3)
SHWRWYS;
(ii)
(SEQ ID NO: 1)
LDEGGP
and
(SEQ ID NO: 8)
SYWRWVK;
or
(iii)
(SEQ ID NO: 13)
TDDGP
and
(SEQ ID NO: 14)
SYWRWYK;
and wherein the amino acid sequence set forth in SEQ ID NO: 1 or 13 is located in the AB loop of the CH3 domain and the amino acid sequence set forth in SEQ ID NO: 3, 8, or 14 is located in the EF loop of the CH3 domain.
2. The antibody molecule according to claim 1 , wherein the EGFR antigen-binding site further comprises the amino acid sequence TYG (SEQ ID NO: 2) in the CD loop of the CH3 domain.
3. The antibody molecule according to claim 2 , wherein the antibody molecule comprises the CH3 domain set forth in SEQ ID NO: 4, 9, or 15.
4. The antibody molecule according to claim 1 , wherein the antibody molecule further comprises a CH2 domain.
5. The antibody molecule according to claim 3 , wherein the antibody molecule comprises the sequence set forth in SEQ ID NO: 6, 11, or 17.
6. The antibody molecule according to claim 1 , wherein the antibody molecule comprises a CDR-based antigen-binding site.
7. The antibody molecule according to claim 1 , wherein the antibody molecule is an immunoglobulin isotype.
8. The antibody molecule according to claim 6 , wherein the CDR-based antigen-binding site binds to human HGF and comprises the complementarity determining regions (CDRs) of antibody rilotumumab set forth in SEQ ID NOs: 21-26 or the CDRs of antibody ficlatuzumab set forth in SEQ ID NOs: 31-36.
9. The antibody molecule according to claim 8 , wherein the CDR-based antigen-binding site comprises the CDRs of antibody rilotumumab set forth in SEQ ID NOs: 21-26.
10. The antibody molecule according to claim 8 , wherein the CDR-based antigen-binding site comprises the CDRs of antibody ficlatuzumab set forth in SEQ ID NOs: 31-36.
11. The antibody molecule according to claim 9 , comprising the VH and VL domains of antibody rilotumumab set forth in SEQ ID NOs: 29 and 30.
12. The antibody molecule according to claim 10 , comprising the VH and VL domains of antibody ficlatuzumab set forth in SEQ ID NOs: 39 and 40.
13. The antibody molecule according to claim 9 , comprising the heavy chain sequence set forth in any one of SEQ ID NOs: 41, 43, or 45.
14. The antibody molecule according to claim 13 , comprising the light chain sequence set forth in SEQ ID NO: 28.
15. The antibody molecule according to claim 10 , comprising the heavy chain sequence set forth in any one of SEQ ID NOs: 42, 44, or 46.
16. The antibody molecule according to claim 15 , comprising the light chain sequence set forth in SEQ ID NO: 38.
17. The antibody molecule according to claim 7 , wherein the immunoglobulin isotype is immunoglobulin G.
18. The antibody molecule according to claim 17 , wherein the immunoglobulin G is of IgG1, IgG2, IgG3, or IgG4 subclass.
19. The antibody molecule according to claim 3 , wherein the CH3 domain comprises a lysine residue (K) at the immediate C-terminus of the sequence set forth in SEQ ID NO: 4, 9, or 15.
20. A nucleic acid encoding the antibody molecule according to claim 1 .