Activatable antibodies that bind epidermal growth factor receptor and methods thereof

A method of treating or delaying the progression of a cancer associated with aberrant expression or activity of Epidermal Growth Factor Receptor (EGFR) in a subject comprising administering to a subject in need thereof a therapeutically effective amount of an activatable antibody that in an activated state binds EGFR, wherein said activatable antibody comprises:

• (a) an antibody or an antigen binding fragment thereof (AB) that specifically binds to EGFR, wherein the AB comprises:
• (i) a heavy chain comprising:
• (1) an amino acid sequence with at least one of the following amino acid sequence features:
• (1) a glutamine residue at the position corresponding to position 88 of SEQ ID NO:
• 26, SEQ ID NO:
• 30, and SEQ ID NO:
• 34, and (2) an alanine residue at the position corresponding to position 299 of SEQ ID NO:
• 26, SEQ ID NO:
• 30, and SEQ ID NO:
• 34, and
• (2) heavy chain complementarity determining regions (HCDRs), wherein the HCDRs are the HCDRs of a heavy chain amino acid sequence selected from the group consisting of:
• SEQ ID NO:
• 26, SEQ ID NO:
• 30, and SEQ ID NO:
• 34, and
• (ii) a light chain comprising light chain complementarity determining regions (LCDRs), wherein the LCDRs are the LCDRs of light chain amino acid sequence SEQ ID NO:
• 68;
• (b) a masking moiety (MM) coupled to the AB that inhibits the binding of the AB of the activatable antibody in an uncleaved state to EGFR, wherein the MM comprises the amino acid sequence CISPRGCPDGPYVMY (SEQ ID NO:14);
• and
• (c) a cleavable moiety (CM) coupled to the AB, wherein the CM is a polypeptide that functions as a substrate for a protease and wherein the CM comprises the amino acid sequence LSGRSDNH (SEQ ID NO:
• 13),
• wherein the activatable antibody in the uncleaved state has the structural arrangement from N-terminus to C-terminus as follows:
• MM-CM-AB or AB-CM-MM.