IP Library › Granted Patent US 12679899
Granted Patent B2
US 12679899 · App. 18/474,134 · Granted Jul 14, 2026

Matrix metalloproteinase substrates and other cleavable moieties and methods of use thereof

Inventors: Stephen James Moore (Danville, CA); Margaret Thy Luu Nguyen (San Francisco, CA); Daniel R. Hostetter (Rocklin, CA); Olga Vasiljeva (Highlands Ranch, CO); Jeanne Grace Flandez (Benicia, CA)
Assignee: CYTOMX THERAPEUTICS, INC.
C07K16/2866C07K7/06C07K16/2863C07K16/44C07K2317/73C07K2319/50
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Quick Facts
Patent No.
US 12679899
App. No.
18/474,134
Granted
Jul 14, 2026
Kind
B2
Abstract

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.

Claims (21)

1 . A polypeptide comprising: a cleavable moiety (CM) comprising the amino acid sequence selected from the group consisting of SEQ ID NOs: 15 and 379-393, 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 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 15, 379, 380, 382, and 391-393.

3 . The polypeptide of claim 1 , wherein the CM comprises the amino acid sequence of SEQ ID NO: 15.

4 . The polypeptide of claim 1 , wherein the CM comprises the amino acid sequence of SEQ ID NO: 379.

5 . The polypeptide of claim 1 , wherein the CM comprises the amino acid sequence of SEQ ID NO: 380.

6 . The polypeptide of claim 1 , wherein the CM comprises the amino acid sequence of SEQ ID NO: 382.

7 . The polypeptide of claim 1 , wherein the CM comprises the amino acid sequence of SEQ ID NO: 391.

8 . The polypeptide of claim 1 , wherein the CM comprises the amino acid sequence of SEQ ID NO: 392.

9 . The polypeptide of claim 1 , wherein the CM comprises the amino acid sequence of SEQ ID NO: 393.

10 . The polypeptide of claim 1 , wherein the CM is cleaved by at least one matrix metalloprotease (MMP).

11 . The polypeptide of claim 1 , wherein the CM is cleaved by at least one of MMP9 or MMP14.

12 . The polypeptide of claim 1 , wherein the CM is cleaved by at least MMP14.

13 . The polypeptide of claim 1 , wherein the CM is cleaved by at least MMP9.

14 . The polypeptide of claim 1 , wherein the CM consists of the amino acid sequence of SEQ ID NO: 382.

15 . The polypeptide of claim 1 , wherein the CM consists of the amino acid sequence of SEQ ID NO: 391.

16 . The polypeptide of claim 1 , wherein the CM consists of the amino acid sequence of SEQ ID NO: 392.

17 . The polypeptide of claim 1 , wherein the CM consists of the amino acid sequence of SEQ ID NO: 393.

18 . The polypeptide of claim 1 , further comprises a linking peptide.

19 . The polypeptide of claim 18 , wherein the linking peptide is 2 to 20 amino acids in length.

20 . The polypeptide of claim 18 , 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).

21 . The polypeptide of claim 18 , 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).