Matrix metalloprotease-cleavable and serine protease-cleavable substrates and methods of use thereof
The invention relates generally to polypeptides that include at least a first cleavable moiety (CM1) that is a substrate for at least one matrix metalloprotease (MMP) and at least a second cleavable moiety (CM2) that is a substrate for at least one serine protease (SP), to activatable antibodies and other larger molecules that include these polypeptides that include at least a CM1 that is a substrate for at least one MMP protease and at least a CM2 that is a substrate for at least one SP protease, and to methods of making and using these polypeptides that include at least a CM1 that is a substrate for at least one MMP protease and at least a CM2 that is a substrate for at least one SP protease in a variety of therapeutic, diagnostic and prophylactic indications.
1. An isolated polypeptide comprising a CM1-CM2 substrate comprising a first cleavable moiety (CM1) that is a substrate for a matrix metalloprotease (MMP) and a second cleavable moiety (CM2) that is a substrate for a serine protease (SP), wherein the CM1-CM2 substrate comprises the amino acid sequence
selected from the group consisting of SEQ ID NOs: 483-490 and 555.
2. The isolated polypeptide of claim 1 , wherein the CM1-CM2 substrate comprises the amino acid sequence of SEQ ID NO: 483.
3. The isolated polypeptide of claim 1 , wherein the CM1-CM2 substrate comprises the amino acid sequence of SEQ ID NO: 484.
4. The isolated polypeptide of claim 1 , wherein the CM1-CM2 substrate comprises the amino acid sequence of SEQ ID NO: 485.
5. The isolated polypeptide of claim 1 , wherein the CM1-CM2 substrate comprises the amino acid sequence of SEQ ID NO: 486.
6. The isolated polypeptide of claim 1 , wherein the CM1-CM2 substrate comprises the amino acid sequence of SEQ ID NO: 487.
7. The isolated polypeptide of claim 1 , wherein the CM1-CM2 substrate comprises the amino acid sequence of SEQ ID NO: 488.
8. The isolated polypeptide of claim 1 , wherein the CM1-CM2 substrate comprises the amino acid sequence of SEQ ID NO: 489.
9. The isolated polypeptide of claim 1 , wherein the CM1-CM2 substrate comprises the amino acid sequence of SEQ ID NO: 490.
10. The isolated polypeptide of claim 1 , wherein the CM1-CM2 substrate comprises the amino acid sequence of SEQ ID NO: 555.