Transgene S.a.

Behringwerke Aktiengesellschaft

Noechst Ag

Yves Lemoine

Tilman Achstetter

Gerard Loison

Martine Nguyen

Alain Balland

Nathalie Labat

Eric Degryse

Jean-Pierre Lecocq

Michael J Courtney

Paul Tolstoshev

Remi Gloeckler

Jean-Marc Reichhart

Denis Speck

The invention relates to a functional DNA block by means of which hirudin may be prepared from yeast, which block contains at least the sequence:

Functional DNA block and plasmid coding for hirudin, transformed yeast,

The present invention relates to an improved system for producing mature heterologous proteins, and especially hirudin, by means of yeasts comprising an expression vector containing a sequence coding for the heterologous protein. This improvement is characterized by amplification of the KEX2 gene of yeast, coding for the endoprotease yscF. The amplification is carried out either by integration of one or more copies of all or part of the KEX2 gene in the yeast genome, or by insertion of one or more copies of all or part of the KEX2 gene into the vector for expression of the heterologous protein.

Yeast strains for the production of mature heterologous proteins,

Functional block of DNA enabling to prepare hirudine from yeast, characterized in that it comprises at least:--the gene of hirudine or one of its variants (gene H); --A DNA sequence (S.sub.tr) comprising the signals providing for the transcription of the gene H by the yeast.

Vectors for the expression and secretion of hirudin by transformed yeasts

The present invention relates to variants of hirudin containing an amino acid different from the amino acid in the natural form at position 47 or 63.

Hirudin HV2 having a SN7LYS substitution, method of making, and method

The invention relates to new DNA fragments and to their application as a DNA coding fragment for a signal peptide which can be used for the secretion of proteins, said peptide including a sequence of amino-acids which show a degree of correspondence of at least 60% with the sequence of amino-acids (I) or (II), preferably with the sequence (II). The sequences (I) and (II) are as follows: (I) Arg-Phe-Ser-Thr-Thr-Leu-Ala-Thr-Ala-Ala-Thr-Ala-Leu-Phe-Phe-Thr-Ala-Ser-Gl n. (II) Arg-Phe-Ser-Thr-Thr-Leu-Ala-Thr-Ala-Ala-Thr-Ala-Leu-Phe-Phe-Thr-Ala-Ser-Gl n-Val-Ser-Ala.

Application of novel DNA fragments as a coding sequence for a signal

Yeast vector coding for heterologous gene fusions linked via KEX2

The invention relates to a new strain of Saccharomyces cerevisiae productive of a heterologous protein, and more especially of hirudin, characterized by a suppression of the proteolytic function encoded by the PRC1 gene. More specifically, this deficiency is due to a mutation or more especially to a deletion of the PRC1 structural gene.

Saccharomyces cerevisiae strain productive of a heterologous protein and

The present invention relates, in particular, to a DNA sequence corresponding to one of the following genes involved in the chain of biotin biosynthesis in bacteria: bioA gene, bioD gene, bioF, bioC and bioH gene. Vectors containing these sequences enable other microorganisms to be transformed in order to improve the production of biotin.

Growing community of inventors

Strasbourg, France

Yves Lemoine