Patent ID: 6133011
Filing Date: 2000-10-17
Classification: A61K,A61P,C07K,C12N

Abstract:
A chimeric protein with fibrinolytic and thrombin-inhibiting properties comprising a plasminogen-activating amino acid sequence which is linked at its C-terminal end to an amino acid sequence of the formula ISer-X.sub.1 -X.sub.2 -X.sub.3 -X.sub.4 -X.sub.5 -Pro-Arg-Pro-Y.sub.1 -Y.sub.2 -Y.sub.3 -Y.sub.4 -Asn-Pro-Z (I)(SEQ ID NO: 1),whereinX.sub.1 represents Pro or Leu;X.sub.2 represents Gly, Val or Pro;X.sub.3 represents Lys, Val, Arg, Gly or Glu;X.sub.4 represents Ala, Val, Gly, Leu or Ile;X.sub.5 represents Gly, Phe, Trp, Tyr or Val;Y.sub.1 represents Phe;Y.sub.2 represents Leu;Y.sub.3 represents Leu;Y.sub.4 represents Arg, andZ represents at least one amino acid sequence selected from the group consisting of:Gly-Asp-Z.sub.1 -Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu-Gln (II)(SEQ ID NO: 2),wherein Z.sub.1 represents Phe or Tyr,Asn-Asp-Lys-Tyr-Glu-Pro-Phe-Glu-Glu-Tyr-Leu-Gln (III)(SEQ ID NO: 3),Ser-Asp-Phe-Glu-Glu-Phe-Ser-Leu-Asp-Asp-Ile-Glu-Gln (IV)(SEQ ID NO: 4), andSer-Glu-Phe-Glu-Glu-Phe-Glu-Ile-Asp-Glu-Glu-Glu-Lys (V)(SEQ ID NO: 5),said plasminogen-activating sequence being selected from the group consisting of:the unaltered amino acid sequence of prourokinase,modified prourokinase amino acid sequences having a serine protease domain exhibiting at least 95% sequence identity to the serine protease domain of the unaltered amino acid sequence of prourokinase,the unaltered amino acid sequence of urokinase,modified urokinase amino acid sequences having a serine protease domain exhibiting at least 95% sequence identity to the serine protease domain of the unaltered amino acid sequence of urokinase,the unaltered amino acid sequence of tissue plasminogen activator (t-PA), andmodified t-PA amino acid sequences having a serine protease domain exhibiting at least 95% sequence identity to the serine protease domain of the unaltered amino acid sequence of t-