Matrix metalloproteinase substrates and other cleavable moieties and methods of use thereof
The invention relates generally to polypeptides that include a cleavable moiety that is a substrate for at least one matrix metalloprotease (MMP), to activatable antibodies and other larger molecules that include the cleavable moiety that is a substrate for at least one MMP protease, and to methods of making and using these polypeptides that include a cleavable moiety that is a substrate for at least one MMP protease in a variety of therapeutic, diagnostic and prophylactic indications.
1 . A polypeptide comprising: a cleavable moiety (CM) comprising the amino acid sequence of SEQ ID NO: 14, wherein the cleavable moiety is a substrate for a protease; and an antibody or antigen binding fragment thereof (AB) that binds a target.
2 . The polypeptide of claim 1 , wherein the CM is cleaved by at least one matrix metalloprotease (MMP).
3 . The polypeptide of claim 1 , wherein the CM is cleaved by at least MMP14.
4 . The polypeptide of claim 1 , further comprises a linking peptide.
5 . The polypeptide of claim 4 , wherein the linking peptide is 2 to 20 amino acids in length.
6 . The polypeptide of claim 4 , wherein the linking peptide comprises an amino acid sequence selected from the group consisting of (GS) n , (GGS) n , (GSGGS) n (SEQ ID NO: 1), (GGGS) n (SEQ ID NO: 2), GGSG (SEQ ID NO: 3), GGSGG (SEQ ID NO: 4), GSGSG (SEQ ID NO: 5), GSGGG (SEQ ID NO: 6), GGGSG (SEQ ID NO: 7), and GSSSG (SEQ ID NO: 8).
7 . The polypeptide of claim 4 , wherein the linking peptide comprises an amino acid sequence selected from the group consisting of GSSGGSGGSGGSG (SEQ ID NO: 9), GSSGGSGGSGG (SEQ ID NO: 10), GSSGGSGGSGGS (SEQ ID NO: 11), GSSGGSGGSGGSGGGS (SEQ ID NO: 155), GSSGGSGGSG (SEQ ID NO: 156), or GSSGGSGGSGS (SEQ ID NO: 157).