Antibody binding to fibrin, fibrinolytic protein containing antibody, and pharmaceutical formulation containing protein
AssigneeRin Institute Inc.
InventorsYasuhiro MATSUMURA, Shingo HANAOKA
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Abstract
The present invention provides a protein stable, capable of dissolving fibrin clots, excellent in production in a protein-expressing cell cultured in a serum-free medium and suppressed in the production of impurities such as a degradation product; a pharmaceutical formulation containing the protein; and methods for producing these.
Claims13
A fusion protein comprising an antibody that binds to insoluble fibrin or an antigen-binding fragment thereof and a catalytic domain of prourokinase having an amino acid sequence corresponding to a sequence of amino acids at positions 156 to 411 of prourokinase set forth in SEQ ID NO:
- 6 or 7, wherein the antibody or an antigen-binding fragment thereof and the catalytic domain of prourokinase are linked directly or via a linker to each other, wherein
- the antibody or an antigen-binding fragment thereof contains a heavy chain variable region and light chain variable region of the antibody that binds to insoluble fibrin, and
- phenylalanine of the catalytic domain corresponding to phenylalanine at position 157 of the prourokinase set forth in SEQ ID NO:
- 6 or 7 is substituted with another amino acid.
A method for producing a fusion-protein variant excellent in stability or a pharmaceutical composition containing the fusion-protein variant, wherein
- the fusion protein comprises
- an antibody that binds to insoluble fibrin or an antigen-binding fragment thereof and a catalytic domain of prourokinase having an amino acid sequence corresponding to a sequence of amino acids at positions 156 to 411 of prourokinase set forth in SEQ ID NO:
- 6 or 7, wherein the antibody or an antigen-binding fragment thereof and the catalytic domain of prourokinase are linked directly or via a linker to each other;
- the antibody or antigen-binding fragment thereof contains a heavy chain variable region and light chain variable region of the antibody that binds to insoluble fibrin;
- and
- the method comprising introducing an F157E or F157D mutation to the fusion protein, thereby imparting excellent stability compared to the fusion protein not modified.
Dependencies are inferred from the claim text.