Ciba-geigy Corporation

Ucp Gen-pharma Ag

Novartis Corporation

Manfred Liersch

Markus G Grutter

Hans Rink

Bernd Meyhack

Walter Marki

Dirk Heinz

Peter Sieber

Hans Fritz

Werner Rittel

Sefik Alkan

Jakob Nuesch

Francois Meyer

Walter M&auml;rki

Ursula Seem&uuml;ller

The invention relates to DNA sequences which code an eglin, expression plasmids containing such DNA sequences, hosts transformed with such expression plasmids, novel eglin compounds produced from such transformed hosts, monoclonal antibodies against eglins, hybridoma cells which produce such antibodies, and test kits for immunoassays containing such antibodies, and furthermore the processes for their preparation and a process for the preparation of eglins with the aid of the transformed hosts. The eglins which can be prepared according to the invention have useful pharmacological properties.

Process for preparing recombinant eglin, protease inhibitor

The invention relates to DNA sequences that code for the amino acid sequence of the thrombin inhibitor hirudin, hybrid vectors containing such DNA sequences, host cells transformed with such hybrid vectors, novel polypeptides with thrombin-inhibiting activity produced from such transformed host cells, processes for the manufacture of these DNA sequences, hybrid vectors and transformed host cells, and processes for the manufacture of these thrombin-inhibitors using the transformed host cells. The hirudin compounds that can be produced according to the invention have valuable pharmacological properties.

Process for the manufacture of thrombin inhibitors

DNA encoding novel eglin mutants that differ from the natural eglins B and C by the replacement of amino acids in the region of the active center (amino acid 45) by other amino acids are provided. The mutants, which are produced by recombinant genetic engineering, have valuable pharmacological properties.

Genes encoding eglin C mutants

Novel elgin mutants that differ from the natural eglins B and C by the replacement of one, two or three amino acids in the region of the active center (amino acids 45 and 46, Leu-Asp) by other amino acids are provided. The mutants, which can be produced by recombinant genetic engineering, have valuable pharmacological properties.

Modified eglin proteins

In compounds of formula ##SPC1## Wherein R represents a lower alkyl radical and R.sub.1 the acyl radical of a carboxylic acid the acylamino group is deacylated to the amino group when the compounds are treated with microorganisms possessing acylase activity or with extracts containing acylase or with the acylases themselves in aqueous medium. The isolation of the amino compounds so formed is carried out in known manner.

Process for the manufacture of 7-amino-cephalosporanic acid-type

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Riehen, Switzerland

Manfred Liersch