Csl Behring Gmbh

Aventis Behring Gmbh

Hans-Arnold Stoehr

Juergen Roemisch

Annette Feussner

Wiegand Lang

Gudrun Muth-Naumann

Thomas Weimer

Margret Becker

Claudia Nerlich

Bernd Knoblauch

Stefan Schulte

Sabine Zollner

Rolf Spirig

Johann Willeit

Michael Moses

Stefan Kiechl

Christian Josef Wiedermann

Volker Doersam

Wilfried Wormsbaecher

Harald Stauss

Klaus T Preissner

Christian Kannemaier

Fumie Nakazawa

The invention relates to compositions comprising an isolated sugar for use in the treatment of von Willebrand disease and/or hemophilia A, wherein the sugar is an accessible sugar residue derived from ABO(H) blood group antigen.

Sugar compositions for treating hemophilia A and/or Von Willebrand disease

Sugar compositions for treating hemophilia A and/or von Willebrand disease

The present application relates to procedures for the determination of the activity of the protease which activates factor VII, also known as factor VII activating protease or FSAP. The application also relates to a method of detecting whether an individual has increased or lowered activity in the protease which activates factor VII compared to at least one standard sample, wherein the increased or lowered activity indicates an increased risk for disease or cardiovascular complications.

Procedure for the determination of the activity of the protease which activates factor VII from protein solutions

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 stabilized protein preparation is described which contains no antithrombin III and is protected against loss of activity during pasteurization by the addition of stabilizers which comprise one or more saccharides as a mixture with more than 0.5 mol/l of one or more amino acids chosen from the group arginine, lysine, histidine, phenylalanine, tryptophan, tyrosine, aspartic acid and its salts or glutamic acid and its salts. Glycine and/or glutamine can also be additionally added to each of these amino acids. A process for the viral inactivation or viral depletion of a protein preparation of this type which contains the abovementioned stabilizers and is subjected to pasteurization or viral depletion by filtration, centrifugation or treatment with detergents or bactericidal or virucidal agents is also described.

Stabilized protein preparation and process for its preparation

A process for the preparation of a pure form of protein, wherein the protein is protease activating blood clotting factor VII, the proenzyme for the protease, or a mixture of both the-protease and the proenzyme, is described. The protein is obtained from biological fluids or through genetic engineering and is isolated by anion- and/or cation-exchange chromatography at a pH below the isoelectric point of the protein to be isolated, or by a combination of anion- or cation-exchange chromatography with a chromatography process and/or fractional precipitation at pH between 2.5 and 9.0.

Process for the preparation in pure form of the protease activating blood clotting factor VII, its proenzyme or a mixture of both proteins by means of ion-exchange chromatography

A process for the preparation in pure form of the protease activating blood clotting factor VII and/or its proenzyme by the use of a chromatography separation processes and/or fractional precipitation is described. The process used may include adsorption on calcium phosphate/hydroxyapatite, a hydrophobic matrix, a chelate matrix, a matrix on which heparin or a substance related to heparin, such as heparin sulfate or dextran sulfate, is immobilized, or a matrix that is coated with an immobilized monoclonal or polyclonal antibody directed against the protein to be isolated, or F(ab) or F(ab) fragments of antibodies directed against the protein to be isolated. A pharmaceutical preparation and a reagent are described which contain the said protease and/or its proenzyme.

Process for the preparation in pure form of the protease activating blood clotting VII, its proenzyme or a mixture of both proteins by means of affinity chromatography

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Wetter, Germany

Hans-Arnold Stoehr