To provide antibodies that mimic desirable characteristics of
small molecule prodrugs in the field of
antibody-based therapeutics.SOLUTION: Antibodies, activatable antibodies (AA), bispecific antibodies, and bispecific activatable antibodies (BAA) are provided. Methods for making and using these antibodies, AAs, bispecific antibodies, and BAAs are also provided. In one aspect, an activatable
antibody (AA) is provided, comprising: a) an
antibody or
antigen-binding fragment (AB) thereof that specifically binds to the epsilon chain of CD3 (CD3ε); b) a masking
moiety (MM) coupled to the AB, the MM reducing or inhibiting binding of the AB to the CD3ε when the AA is in an uncleaved state, and the MM comprising a specific
amino acid sequence; and c) a cleavable
moiety (CM) coupled to the AB, the CM being a polypeptide that functions as a substrate for a
protease.SELECTED DRAWING: Figure 17