Baxter Aktiengesellschaft

Immuno Aktiengesellschaft

Uwe Schlokat

Johann J Eibl

Friedrich Dorner

Falko-Guenter Falkner

Bernhard Fischer

Artur Mitterer

Michele Himmelspach

Peter Turecek

Hans-Peter Schwarz

Manfred Reiter

Wolfgang Mundt

Renate Den-Bouwmeester

Michael Pfleiderer

Andreas Fisch

Barbara Plaimauer

Falko-Gunter Falkner

Sabine E Herlitschka

Nucleic acids encoding factor X analogues are provided that have a modification in the region of the natural Factor Xa activation cleavage site. The modification results in a processing site for a protease not naturally cleaving in this region of the Factor X sequence.

Nucleic acids encoding factor X analogues having a modified protease cleavage site

This invention describes a factor Xa analog which has a substitution of a minimum of one of the amino acid between Glu226 and Arg234 and possibly Ile235, relative to the amino acid numbering according to FIG., a preparation containing the activated form of the factor X analog, and a method for the production of these molecules.

Factor X analog with an improved ability to be activated

Nucleic acids encoding factor X&#x394; analogues having a deletion of amino acids Arg180 to Arg234 and a modification in the region of the amino acid sequence between Gly173 and Arg 179 are provided.

Nucleic acids encoding factor X deletion mutants and analogues thereof

The present invention comprises a furin polypeptide having a modified amino acid sequence between the middle, homo-B-domain and the transmembrane domain compared to wild-type furin which retains proteolytic activity but is secreted at lower levels in cell culture compared to wild-type furin. Additionally, the invention includes nucleic acid molecules encoding such furin polypeptides, vectors and host cells comprising said nucleic acid molecules, compositions comprising said furin polypeptide and methods for producing such compositions.

Furin polypeptides with improved characteristics

Factor X analogues having a modification in the region of the natural Factor Xa activation cleavage site, said modification representing a processing site of a protease not naturally cleaving in this region of the Factor X sequence, preparations containing the Factor X analogues according to the invention, and processes for the preparation thereof are described.

Factor X analogues with a modified protease cleavage site

Factor X&Dgr; analogues are provided, as well as pharmaceutical preparations containing such analogues and methods of preparing such analogues. The factor X&Dgr; analogues have a deletion of the amino acids Arg180 to Arg234 and a modification in the region of the amino acid sequence between Gly173 and Arg179 of the factor X amino acid sequence. Such analogues can include a processing site not normally present in factor X, thus allowing for selective conversion of the analogue to an active form. The analogues and preparations have utility in the treatment of a number of blood coagulation disorders.

Factor X deletion mutants and analogues thereof

Fusion proteins of an optionally C-terminally deleted furin derivative, or of a derivative of a furin analogue, and a heterologous sequence, methods of preparing the same and methods of recovering proproteins from proteins by using the proproteins according to the invention are described.

Fusion protein comprising a furin derivative or a derivative of a furin analogue and a heterologous sequence

The invention describes an expression plasmid containing a dicistronic transcription/translation unit, which unit comprises a sequence for a foreign protein and a sequence for a fusion protein, the fusion protein containing at least one selection marker and at least one amplification marker. Further described is a method of producing foreign proteins by using the plasmids according to the invention, as well as cell lines transformed with the plasmid according to the invention.

Expression plasmid, a fusion protein, a transfected eukaryotic cell

The invention relates to a method for isolation of highly pure von Willebrand Factor in which recombinant von Willebrand Factor (rvWF) is chromatographically purified by anion exchange chromatography on an anion exchanger of the quaternary amino type in a buffer solution comprising buffer substances and optionally salt. The buffer solutions are preferably free of stabilizers, amino acids and other additives. According to this method, highly pure recombinant vWF can be obtained, which is free from blood plasma proteins, especially free from Factor VIII, and is physiologically active. Further, the invention relates to a pharmaceutical preparation that contains rvWF, which is comprised of multimers with a high structural integrity.

Method for isolation of highly pure von willebrand factor

Prothrombin derivatives

The invention relates to a method for isolation of highly pure von Willebrand Factor in which recombinant von Willebrand Factor (rvWF) is chromatographically purified by anion exchange chromatography on an anion exchanger of the quaternary amino type in a buffer solution comprising buffer substances and optionally salt. The buffer solutions are preferably free of stabilizers, amino acids and other additives. According to this method, highly pure recombinant vWF can be obtained, which is free from blood plasma proteins, especially free from Factor VIII, and is physiologically active. Further, the invention relates to a pharmaceutical preparation that contains rvWF, which is comprised of multimers with a high structural integrity

Method for isolation of highly pure von Willebrand Factor

The invention relates to a method for isolation of highly pure von Willebrand Factor in which recombinant von Willebrand Factor (rvWF) is chromatographically purified by anion exchange chromatography on an anion exchanger of the quaternary amino type in a buffer solution comprising buffer substances and optionally salt. The buffer solutions are preferably free of stabilizers, amino acids and other additives. According to this method, highly pure recombinant rvWF can be obtained, which is free from blood plasma proteins, especially free from Factor VIII, and is physiologically active. Further, the invention relates to a pharmaceutical preparation that contains rvWF, which comprises mulitimers with a high structural integrity.

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Orth/Donau, Austria

Uwe Schlokat