Egfr binding molecules

Abstract

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)