Hoechst Aktiengesellschaft

The General Hospital Corporation

Wolfgang Ulmer

Paul Habermann

Peter Crause

Dominique Tripier

Gerhard Schmid

Eugen Uhlmann

Brian Seed

Siegfried Stengelin

Joachim Engels

Michael Leineweber

Jorg Moller

The present invention relates to a process for inactivating Carboxypeptidase Y (CPY) in a hirudin-containing culture broth produced by fermenting a transformed yeast. It has been found that inactive precursors of CPY are activated at a temperature 70.degree. C. and that the active peptidases will further degrade hirudin when the two proteins are present together in a composition. The present invention overcomes the CPY activation problem by heating a broth containing hirudin and CPY to a temperature of about 80.degree.-100.degree. C. in about one minute or less.

Process for inactivating carboxypeptidase Y in hirudin-containing

The invention relates to novel synthetic isohirudins which have improved stability owing to exchange in the region of the Asp-Gly motif. This results, on the one hand, in an increase in the yield during workup and, on the other hand, in making possible pharmaceutical formulation as directly injectable solution ready for use.

Synthetic isohirudins with improved stability

Novel synthetic isohirudins with improved stability The invention relates to novel synthetic isohirudins which have improved stability owing to exchange in the region of the Asp-Gly motif. This results, on the one hand, in an increase in the yield during workup and, on the other hand, in making possible pharmaceutical formulation as directly injectable solution ready for use.

Fusion proteins are obtained in high yields if a mixed oligonucleotide is constructed which codes for the ballast constituent of the fusion protein. The oligonucleotide mixture is introduced in a vector in such a manner that it is functionally linked to a regulatory region and to the structural gene for the desired protein. Appropriate host cells are transformed with the plasmid population obtained in this manner and the clones producing a high yield of coded fusion protein are selected.

Fusion proteins, their preparation and use

Partial sequences of human-.gamma.-interferon, comprising aminoacid sequences 5 to 127, 1 to 127 and 5 to 146, having biological activity. These partial sequences can be obtained by a genetic engineering process, for which purpose the appropriate DNA sequences are chemically synthesized. The DNA sequences are incorporated in hybrid plasmids, and the latter are introduced into host organisms and their expression is induced there. The biologically active polypeptides are suitable, as is human-.gamma.-interferon, for medicaments.

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Eppstein am Taunus, Germany

Wolfgang Ulmer