Granted Patent B2

US 12,509,507 · App. 17/915,905 · Granted Dec 30, 2025

Inventors: Yasuhiro Matsumura (Chiba, JP); Shingo Hanaoka (Chiba, JP); Shinji Saijo (Chiba, JP)

Assignees: NATIONAL CANCER CENTER; RIN INSTITUTE INC.

C07K16/18A61P9/10C12N9/6462A61K38/00C07K2317/565C07K2319/50

Abstract

Claims (11)

1 . A fusion protein comprising an antibody that binds to insoluble fibrin or an antigen-binding fragment thereof and a prourokinase mutant comprising a catalytic domain of prourokinase, wherein the antibody or the antigen-binding fragment thereof and the prourokinase mutant are linked directly or via a linker to each other, wherein the insoluble fibrin antibody or the antigen-binding fragment thereof comprises:

a heavy chain variable region comprising a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO:11, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO:12, and a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO:13; and

a light chain variable region comprising a light chain CDR1 comprising the amino acid sequence of SEQ ID NO:14, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO:15, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO:16.

2 . The fusion protein according to claim 1 , wherein the linker is a non-cleavable linker.

3 . The fusion protein according to claim 1 , wherein the linker is a peptide linker.

4 . The fusion protein according to claim 1 , wherein the prourokinase mutant further comprises a kringle domain, wherein the kringle domain and the catalytic domain of the prourokinase mutant are linked to each other in the order: kringle domain, catalytic domain.

5 . The fusion protein according to claim 4 , wherein the prourokinase mutant further comprises an EGF-like domain, wherein the EGF-like domain, the kringle domain, and the catalytic domain of the prourokinase mutant are linked to each other in the order: EGF-like domain, kringle domain, and catalytic domain.

6 . The fusion protein according to claim 1 , wherein the catalytic domain is of a prourokinase mutant comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO:2.

7 . A pharmaceutical composition comprising the fusion protein according to claim 1 .

8 . A method for dissolving a fibrin clot in a subject, the method comprising administering the pharmaceutical composition according to claim 7 to the subject.

9 . The method of claim 8 , wherein the subject has a disease selected from cerebrovascular disorder and myocardial infarction.

Assignments (2)

Priority Claims (1)

Continuity (1)

References Cited (14)