Csl Behring Gmbh

Aventis Behring Gmbh

Zlb Behring Gmbh

Wiegand Lang

Thomas Weimer

Annette Feussner

Juergen Roemisch

Hans-Arnold Stoehr

Gudrun Muth-Naumann

Claudia Nerlich

Margret Becker

Bernd Knoblauch

Stefan Schulte

Ulrich Kronthaler

Hubert Metzner

J&uuml;rgen R&ouml;misch

Holger Lind

Johann Willeit

Stefan Kiechl

Christian Josef Wiedermann

Volker Doersam

Joachim R&ouml;der

Uwe Liebing

Klaus T Preissner

Wilfried Wormsbächer

Wilfried Wormsbaecher

Christian Kannemaier

Fumie Nakazawa

Wilfried Wormsbacher

The present invention relates to modified nucleic acid sequences coding for coagulation factor VIII (FVIII) and for von Willebrand factor (VWF) as well as complexes thereof and their derivatives, recombinant expression vectors containing such nucleic acid sequences, host cells transformed with such recombinant expression vectors, recombinant polypeptides and derivatives coded for by said nucleic acid sequences which recombinant polypeptides and derivatives do have biological activities together with prolonged in vivo half-life and/or improved in vivo recovery compared to the unmodified wild-type protein. The invention also relates to corresponding FVIII sequences that result in improved expression yield. The present invention further relates to processes for the manufacture of such recombinant proteins and their derivatives. The invention also relates to a transfer vector for use in human gene therapy, which comprises such modified nucleic acid sequences.

Factor VIII, von Willebrand factor or complexes thereof with prolonged in vivo half-life

The present invention relates to the fields of Factor VII (FVII) and Factor VIIa (FVIIa) albumin linked polypeptides. More specifically, the invention relates to cDNA sequences coding for human Factor VII and Factor VIIa and derivatives genetically fused to a cDNA coding for human serum albumin which may be linked by oligonucleotides which code for intervening peptidic linkers such encoded derivatives exhibiting improved stability and extended functional plasma half-life, recombinant expression vectors containing such cDNA sequences, host cells transformed with such recombinant expression vectors, recombinant polypeptides and derivatives which do have biological activities of the unmodified wild type protein but having improved stability and prolonged shelf-life and processes for the manufacture of such recombinant proteins and their derivatives. The invention also covers a transfer vector for use in human gene therapy, which comprises such modified DNA sequences.

Modified coagulation factor VIIa with extended half-life

Factor VIII, von willebrand factor or complexes thereof with prolonged in vivo half-life

Mutants of the DNA sequence coding for the protease (FSAP) which activates blood clotting factor VII and single-chain plasminogen activators, the mutants comprising a G/C base exchange at nucleotide position 1177 and/or a G/A base exchange at nucleotide position 1601, are described. The corresponding protease has a Glu/Gln exchange at amino acid position 393 and/or a Gly/Glu exchange at amino acid position 534. Diagnostic methods which are used for detecting FSAP in body fluids or tissue cells and also for identifying patients with genetic heterozygous or homozygous FSAP expression are also described. In addition, antibodies against FSAP and its mutants are disclosed and diagnostic methods which can be used to detect antibodies against FSAP and its mutants are specified.

Mutants of the factor VII-activating protease and detection methods using specific antibodies

A monoclonal antibody which inhibits the blood clotting factor VII-activating protease and its proenzyme and a blood clotting factor VII-activating protease, stabilized by the addition of said monoclonal antibody, and its proenzyme are described. A suitable monoclonal antibody is produced by hybridoma cell line DSM ACC 2533. The application of the inhibitory, monoclonal antibody in the stabilization of blood clotting preparations and in preparations for reducing the coagulability of the blood is disclosed.

Inhibitory monoclonal antibody against blood clotting factor VII-activating protease

An arterial thrombosis risk factor comprising one or more of the identified mutants of coagulation factor VII activating protease (FSAP) is described. In addition, diagnostic determination methods for detecting these mutants which are identified as risk factors are described.

Marburg I mutant of factor VII activating protease (FSAP) as risk factor for arterial thrombosis and methods of detecting FSAP and FSAP mutations

A novel arterial thrombosis risk factor comprising one or more of the identified mutants of coagulation factor VII-activating protease (FSAP) is described. In addition, diagnostic determination methods for detecting these mutants which are identified as risk factors are described.

Marburg I mutant of factor VII activating protease (FSAP) as risk factor for arterial thrombosis

A monoclonal antibody has been developed which only specifically binds activated factor VII, and not factor VII, and which does not bind to an activated factor VII which is complexed with antithrombin III. This monoclonal antibody is isolated from the hybridoma cell line DSM ACC 2332. It can be used for qualitatively and quantitatively detecting factor VIIa in body fluids, blood coagulation preparations or the intermediate stages in the production of these preparations, on cell surfaces or in tissues, and can also be used as a humanized monoclonal antibody in therapeutic preparations.

Monoclonal antibody which is specific for activated coagulation factor VII, and its use

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Cölbe, Germany

Wiegand Lang