New protein or peptide comprising epitope of plasminogen activator inhibitor-1, useful for screening substance for treating thromboembolic and cardiovascular diseases, cancer or related diseases

摘要

A protein or peptide (I) comprising the epitope of plasminogen activator inhibitor-1 (PAI-1) or its fragment or functional derivative, is new. A protein or peptide (I) comprising the epitope of plasminogen activator inhibitor-1 (PAI-1) having the amino acids His-Arg-Arg, Glu-Lys-Glu, Glu-Glu-Ile-Ile-Met-Asp-Arg or Glu-Asp-Arg, or their fragment or functional derivative, is new. Independent claims are also included for the following: (1) a protein or peptide (II) comprising two or more of the epitopes of (I) or its functional derivative; (2) nucleic acid (III) encoding (I) or (II); (3) an antibody (IV) specific for (I) or (II); (4) screening (M) for substances capable of inhibiting PAI-1 by incubating (I) or (II), or entire PAI-1 with a test compound in a suited buffer, tissue-type plasminogen activator (tPA) or its fragment and a monoclonal antibody specific for (I) or (II), or PAI-1 and a monoclonal antibody specific for tPA that are detectably labeled with a reporter, the unbound antibodies are washed out, the amount of reporter is measured, and the value obtained is compared to the value obtained in the absence of the test compound; (5) an antibody (V) or its fragment for use in (M) binds specifically to (I) or (II), or PAI-1, or the protein or peptide having formed a complex with tPA; (6) an antibody (VI) or its fragment for use in (M) binds specifically to tPA, tPA having formed a complex with PAI-1 or (I) or (II); (7) use of an antibody specific for (I) or specific to a different epitope of PAI-1 in (M); (8) a substance (VII) identifiable by (M) is capable of specifically inhibiting PAI-1; (9) an Fv fragment, Fab fragment, Fab' fragment, or F(ab')2 fragment of (VII); and (10) pharmaceutical composition comprising (VII).