ACTIVATABLE ANTIBODIES THAT BIND EPIDERMAL GROWTH FACTOR RECEPTOR AND METHODS OF USE THEREOF

摘要

The invention relates generally to variant activatable antibodies that include a masking moiety (MM), a cleavable moiety (CM), and an antibody (AB) that specifically binds to epidermal growth factor receptor (EGFR), and to methods of making and using these variant anti-EGFR activatable antibodies in a variety of therapeutic, diagnostic and prophylactic indications.

主权项

1. An activatable antibody that in an activated state binds Epidermal Growth Factor Receptor (EGFR) comprising:
an antibody or an antigen binding fragment thereof (AB) that specifically binds to EGFR, wherein the AB comprises (i) a heavy chain amino acid sequence selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 34 and SEQ ID NO: 36 and a light chain amino acid sequence comprising the amino acid sequence of SEQ ID NO: 32; wherein the light chain amino acid sequence is coupled to a spacer sequence and a masking moiety (MM) via a cleavable moiety (CM) to produce a masked light chain, wherein the masked light chain comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, and SEQ ID NO: 12, wherein the MM inhibits the binding of the AB of the activatable antibody in an uncleaved state to EGFR; wherein the CM is a polypeptide that functions as a substrate for a protease; and wherein the activatable antibody in the uncleaved state has the structural arrangement from N-terminus to C-terminus as follows: Spacer Sequence-MM-Linking Peptide 1 (LP1)-CM-Linking Peptide 2 (LP2)-AB or AB-LP2-CM-LP1-MM-Spacer Sequence.