SPECIFIC BINDING PROTEINS AND USES THEREOF
First Claim
1. An isolated antibody capable of binding EGFR on tumors containing amplifications of the EGFR gene, wherein cells of said tumors contain multiple copies of the EGFR gene, and on tumors that express the truncated version of the EGFR receptor de2-7, wherein said antibody does not bind to the de2-7 EGFR junctional peptide consisting of the amino acid sequence of SEQ ID NO:
- 13, wherein said antibody binds to an epitope within the sequence of residues 287-302 (SEQ ID NO;
14) of human wild-type EGFR, and wherein said antibody does not comprise a heavy chain variable region sequence having the amino acid sequence set forth in SEQ ID NO;
2 and does not comprise a light chain variable region sequence having the amino acid sequence set forth in SEQ ID NO;
4.
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Accused Products
Abstract
The present invention relates to specific binding members, particularly antibodies and fragments thereof, which bind to amplified epidermal growth factor receptor (EGFR) and to the de2-7 EGFR truncation of the EGFR. In particular, the epitope recognized by the specific binding members, particularly antibodies and fragments thereof, is enhanced or evident upon aberrant post-translational modification. These specific binding members are useful in the diagnosis and treatment of cancer. The binding members of the present invention may also be used in therapy in combination with chemotherapeutics or anti-cancer agents and/or with other antibodies or fragments thereof.
75 Citations
86 Claims
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1. An isolated antibody capable of binding EGFR on tumors containing amplifications of the EGFR gene, wherein cells of said tumors contain multiple copies of the EGFR gene, and on tumors that express the truncated version of the EGFR receptor de2-7, wherein said antibody does not bind to the de2-7 EGFR junctional peptide consisting of the amino acid sequence of SEQ ID NO:
- 13, wherein said antibody binds to an epitope within the sequence of residues 287-302 (SEQ ID NO;
14) of human wild-type EGFR, and wherein said antibody does not comprise a heavy chain variable region sequence having the amino acid sequence set forth in SEQ ID NO;
2 and does not comprise a light chain variable region sequence having the amino acid sequence set forth in SEQ ID NO;
4. - View Dependent Claims (3, 4, 5, 8, 9, 14, 15, 16, 17, 18)
- 13, wherein said antibody binds to an epitope within the sequence of residues 287-302 (SEQ ID NO;
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40. An isolated antibody capable of binding EGFR on tumors containing amplifications of the EGFR gene, wherein cells of said tumors contain multiple copies of the EGFR gene, and on tumors that express the truncated version of the EGFR receptor de2-7, wherein said antibody comprises a heavy chain and a light chain, said heavy chain having an amino acid sequence that is substantially homologous to the amino acid sequence set forth in SEQ ID NO:
- 129, and said light chain having an amino acid sequence that is substantially homologous to the amino acid sequence set forth in SEQ ID NO;
134. - View Dependent Claims (41)
- 129, and said light chain having an amino acid sequence that is substantially homologous to the amino acid sequence set forth in SEQ ID NO;
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42. An isolated antibody capable of binding EGFR on tumors containing amplifications of the EGFR gene, wherein cells of said tumors contain multiple copies of the EGFR gene, and on tumors that express the truncated version of the EGFR receptor de2-7, wherein said antibody comprises a heavy chain and a light chain, wherein the variable region of said heavy chain comprises polypeptide binding domain regions having amino acid sequences highly homologous to the amino acid sequences set forth in SEQ ID NOS:
- 130, 131, and 132, and wherein the variable region of said light chain comprises polypeptide binding domain regions having amino acid sequences highly homologous to the amino acid sequences set forth in SEQ ID NOS;
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- 130, 131, and 132, and wherein the variable region of said light chain comprises polypeptide binding domain regions having amino acid sequences highly homologous to the amino acid sequences set forth in SEQ ID NOS;
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49. An isolated antibody capable of binding EGFR on tumors containing amplifications of the EGFR gene, wherein cells of said tumors contain multiple copies of the EGFR gene, and on tumors that express the truncated version of the EGFR receptor de2-7, wherein said antibody does not bind to the de2-7 EGFR junctional peptide consisting of the amino acid sequence of SEQ ID NO:
- 13, wherein said antibody binds to an epitope within the sequence of residues 287-302 (SEO ID NO;
14) of human wild-type EGFR,said antibody comprising a light chain and a heavy chain, wherein the variable region of said light chain comprises a first polypeptide binding domain region having an amino acid sequence corresponding to the amino acid sequence set forth in Formula I; - View Dependent Claims (50, 51, 52, 53, 54, 55, 56, 57, 58)
- 13, wherein said antibody binds to an epitope within the sequence of residues 287-302 (SEO ID NO;
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82. An isolated antibody capable of binding EGFR on tumors containing amplifications of the EGFR gene, wherein cells of said tumors contain multiple copies of the EGFR gene, and on tumors that express the truncated version of the EGFR receptor de2-7, wherein said antibody does not bind to the de2-7 EGFR junctional peptide consisting of the amino acid sequence of SEQ ID NO:
- 13, wherein said antibody binds to an epitope within the sequence of residues 273-501 of human wild-type EGFR,
said antibody comprising a light chain and a heavy chain, wherein the variable region of said light chain comprises a first polypeptide binding domain region having the amino acid sequence HSSQDINSNIG (SEQ ID NO;
18);
a second polypeptide binding domain region having the amino acid sequence HGTNLDD (SEQ ID NO;
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a third polypeptide binding domain region having the amino acid sequence VQYAQFPWT (SEQ ID NO;
20),wherein the variable region of said heavy chain comprises a first polypeptide binding domain region having the amino acid sequence SDFAWN (SEQ ID NO;
15);
a second polypeptide binding domain region having an amino acid sequence corresponding to the amino acid sequence set forth in Formula IX; - View Dependent Claims (83, 84, 85, 86)
- 13, wherein said antibody binds to an epitope within the sequence of residues 273-501 of human wild-type EGFR,
Specification