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 . A specific binding member which binds to human epidermal growth factor receptor (EGFR), the specific binding member comprising an EGFR antigen-binding site located in a CH3 domain of the specific binding member, wherein the EGFR antigen-binding site comprises the amino acid sequences:
(i) LDEGGP (SEQ ID NO: 1) and SHWRWYS (SEQ ID NO: 3);
(ii) LDEGGP (SEQ ID NO: 1) and SYWRWVK (SEQ ID NO: 8); or
(iii) TDDGP (SEQ ID NO: 13) and SYWRWYK (SEQ ID NO: 14); 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 .- 3 . (canceled)
4 . A specific binding member 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.
5 .- 7 . (canceled)
8 . A specific binding member according to claim 4 , wherein the CH3 domain is a human IgG1 CH3 domain.
9 . A specific binding member according to claim 8 , wherein the specific binding member comprises the CH3 domain set forth in SEQ ID NO: 4, 9, or 15.
10 . A specific binding member according to claim 1 , wherein the specific binding member further comprises a CH2 domain.
11 . (canceled)
12 . A specific binding member according to claim 10 , wherein the specific binding member comprises the CH2 domain of human IgG1.
13 . A specific binding member according to claim 10 , wherein the CH2 domain has the sequence set forth in SEQ ID NO: 19.
14 . A specific binding member according to claim 9 , wherein the specific binding member comprises the sequence set forth in SEQ ID NO: 6, 11, or 17.
15 . A specific binding member according to claim 10 , wherein the specific binding member comprises an immunoglobulin hinge region, or part thereof, at the N-terminus of the CH2 domain.
16 . (canceled)
17 . A specific binding member according to claim 15 , wherein the hinge region, or part thereof, is a human IgG1 hinge region, or part thereof.
18 . A specific binding member according to claim 17 , wherein the hinge region or part thereof has the sequence set forth in 49, or the sequence set forth in SEQ ID NO: 48 or a fragment thereof.
19 . A specific binding member according to claim 1 , wherein the specific binding member further comprises a CH2 domain and an immunoglobulin hinge region, or part thereof, at the N-terminus of the CH2 domain, and wherein the immunoglobulin hinge region, or part thereof, allows two CH2-CH3 domain sequences to associate and form a dimer.
20 . A specific binding member according to claim 19 , wherein the specific binding member further comprises a CDR-based antigen-binding site.
21 . A specific binding member according to claim 19 , wherein the specific binding member is an antibody molecule.
22 . (canceled)
23 . A specific binding member according to claim 21 , wherein the antibody molecule is a human IgG1 molecule.
24 .- 38 . (canceled)
39 . A specific binding member according to claim 1 , wherein the specific binding member is conjugated to an immune system modulator, cytotoxic molecule, radioisotope, or detectable label.
40 . (canceled)
41 . A nucleic acid encoding a specific binding member according to claim 1 .
42 . (canceled)
43 . A recombinant host cell comprising the nucleic acid of claim 41 .
44 . A method of producing a specific binding member according to claim 1 , comprising culturing the recombinant host cell comprising a nucleic acid encoding the specific binding member under conditions for production of the specific binding member.
45 . (canceled)
46 . A pharmaceutical composition comprising a specific binding member according to claim 1 and a pharmaceutically acceptable excipient.
47 .- 51 . (canceled)
52 . A method of treating cancer in a patient, wherein cells of said cancer express EGFR, and wherein the method comprises administering to the patient a therapeutically effective amount of a specific binding member according to claim 1 .
53 .- 56 . (canceled)