Thrombin muteins as antidotes for thrombin inhibitors

US6060300A · kind A · utility

Assignee

• BASF SE

Inventors

• Martin Raditsch · Eppelheim, DE
• Thomas Friedrich · Darmstadt, DE
• Claus Bollschweiler · Heidelberg, DE
• Martin Schmidt · Frankfurt am Main, DE
• Hans Wolfgang Höffken · Ludwigshafen, DE
• Jurgen Schweden · Neustadt, DE
• Klaus Rübsamen · Neustadt, DE

Key dates

• Filing date: Aug 4, 1998
• Grant date: May 9, 2000
• Expiry date: Aug 4, 2018

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61K38/00
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

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.