Human antithrombin variants

Details Human antithrombin variants Human antithrombin variants

C - Chemistry, Metallurgy

12

N

C12N 15/15 (2006.01) A61K 38/57 (2006.01) C07K 14/81 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2375224

Human antithrombin variants showing a high protease inhibitory activity even in the absence of heparin wherein at least one of the amino acids at positions 78, 278, 378 and 380 in the amino acid sequence of natural human antithrombin is substituted by another amino acid. Preferable examples thereof are human antithrombin variants wherein the amino acid at position 78 is substituted by Phe; the amino acid at position 278 is substituted by Ala, Arg, Asn, Gly, His, Tyr or Val; the amino acid at position 378 is substituted by Lys, Asn or Val; and/or the amino acid at position 380 is substituted by Ala, Asp, Gly, His, Ile, Leu, Asn, Pro, Arg, Thr, Tyr or Val.

L'invention concerne des variants d'antithrombine humaine présentant une forte activité d'inhibition de la protéase même en l'absence d'héparine dans lesquels au moins un des acides aminés dans les positions 78, 278, 378, et 380, dans la séquence d'acides aminés de l'antithrombine humaine naturelle, est substitué par un autre acide aminé. Les exemples préférés desdits variants sont des variants d'antithrombine humaine dans lesquels l'acide aminé en position 78 est substitué par Phe; l'acide aminé en position 278 est substitué par Ala, Arg, Asn, Gly, His, Tyr ou Val; l'acide aminé en position 378 est substitué par Lys, Asn ou Val; et/ou l'acide aminé en position 380 est substitué par Ala, Asp, Gly, His, Ile, Leu, Asn, Pro, Arg, Thr, Tyr ou Val.

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