Thrombin muteins as antidotes for thrombin inhibitors

Details Thrombin muteins as antidotes for thrombin inhibitors Thrombin muteins as antidotes for thrombin inhibitors

C - Chemistry, Metallurgy

12

N

C12N 15/57 (2006.01) A61K 38/48 (2006.01) C12N 9/74 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2245546

The invention concerns thrombin muteins which have the following differences in their sequences as compared with natural thrombin: (a) the exchange of a Gly after Ala, the Gly being in the sequence environment Tyr-Gly-Phe and having position 558 in natural human thrombin (SEQ ID No. 14); (b) at least one exchange or deletion of the following radicals: (b1) His, located in the sequence environment Ala-His-Cys and having position 363 in natural human thrombin (SEQ ID No. 14); (b2) Asp, located in the sequence environment Arg- Asp-Ile and having position 419 in natural human thrombin (SEQ ID No. 14); (b3) Ser, located in the sequence environment Asp-Ser-Gly and having position 525 in natural human thrombin (SEQ ID No. 14). The invention further concerns the use of these muteins as antidotes.

L'invention concerne des mutéines de thrombine qui présentent, comparativement à la thrombine naturelle, les différences séquentielles suivantes: (a) substitution d'un Gly après Ala, ledit Gly se trouvant dans l'environnement séquentiel Tyr-Gly-Phe et ayant la position 558 dans la thrombine humaine naturelle (SEQ ID n·14); (b) au moins une substitution ou une délétion des radicaux suivants: (b1) His qui se situe dans l'environnement séquentiel Ala-His-Cys et a la position 363 dans la thrombine humaine naturelle (SEQ ID n·14); (b2) Asp qui se situe dans l'environnement séquentiel Arg-Asp-Ile et a la position 419 dans la thrombine humaine naturelle (SEQ ID n·14); (b3) Ser qui se situe dans l'environnement séquentiel Asp-Ser-Gly et a la position 525 dans la thrombine humaine naturelle (SEQ ID n·14). L'invention concerne par ailleurs leur utilisation comme antidote.

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