Csl Behring Gmbh

Csl Behring Lengnau Ag

Aventis Behring Gmbh

Csl Limited

Csl Innovation Pty Ltd.

Thomas Weimer

Stefan Schulte

Wiegand Lang

Sabine Pestel

Hubert Metzner

Annette Feussner

Juergen Roemisch

Hans-Arnold Stoehr

Gudrun Muth-Naumann

Claudia Nerlich

Margret Becker

Ulrich Kronthaler

Bernd Knoblauch

Hans-Peter Hauser

Kay Hofmann

Matthias Pelzing

Hans-Wilhelm Beltz

Uwe Kalina

Albrecht Groener

Holger Lind

Christian Josef Wiedermann

Stefan Kiechl

Johann Willeit

Volker Doersam

Gerhard Dickneite

Eugene Maraskovsky

Dieter Bernhardt

Stefan Schmidbauer

Wilfried Wormsbacher

Uwe Liebing

Steve Dower

Michael Moses

Wilfried Wormsbächer

Wilfried Wormsbaecher

Huy Huynh

Marco Hofmann

Anne Verhagen

Elmar Raquet

Philipp Claar

The invention pertains to a recombinant polypeptide comprising a truncated von Willebrand Factor (VWF) for use in the treatment or prophylaxis of a blood coagulation disorder, said treatment or prophylaxis comprising administering the recombinant polypeptide and a Factor VIII protein (FVIII) extravascular to a subject having a blood coagulation disorder, wherein said recombinant polypeptide is capable of binding to said FVIII, and wherein the molar ratio of the recombinant polypeptide to be administered to the FVIII to be administered is higher than 50.

Truncated von Willebrand factor polypeptides for extravascular administration in the treatment or prophylaxis of a blood coagulation disorder

The invention pertains to a polypeptide comprising a truncated von Willebrand Factor (VWF) and a half-life extending moiety, for use in the treatment of a blood coagulation disorder, said treatment comprising administering the polypeptide to a subject having a blood coagulation disorder and having endogenous Factor VIII (FVIII), wherein the activity level of endogenous FVIII in said subject before treatment with said polypeptide is reduced relative to the activity level of FVIII in normal human plasma (NHP) provided that the activity level of endogenous FVIII in said subject is at least 0.5% of the activity level of endogenous FVIII in normal human plasma (NHP), wherein the polypeptide is capable of binding to endogenous FVIII and wherein the endogenous FVIII level is increased following administration of said polypeptide.

Truncated von Willebrand Factor polypeptides for treating hemophilia

The present invention provides modified von Willebrand Factor molecules, methods for their preparation and uses thereof. The invention further provides pharmaceutical compositions for treating coagulation disorders.

Methods for preparing modified von Willebrand Factor

The invention relates to a modified VWF molecule for use in the treatment of a blood coagulation disorder.

Modified von Willebrand factor having improved half-life

The present invention relates to a recombinant polypeptide comprising a truncated von Willebrand Factor (VWF) capable of binding to blood coagulation Factor VIII (FVIII) for use in reducing the immunogenicity of Factor VIII (FVIII) wherein said recombinant polypeptide and a blood coagulation Factor VIII (FVIII) protein are co-administered to a subject suffering from a 10 blood coagulation disorder. The invention further relates to pharmaceutical compositions and kits for said use.

Modulation of FVIII immunogenicity by truncated VWF

Methods for preparing modified von Willebrand factor

The invention relates to a polypeptide comprising a truncated von Willebrand Factor (VWF) for use in the treatment of a blood coagulation disorder, wherein the polypeptide carries a half-life extending moiety and is administered in molar excess over Factor VIII and/or endogenous VWF.

Truncated von Willebrand factor polypeptides for treating hemophilia

The present invention relates to a covalent complex of von Willebrand Factor (VWF) and Factor VIII, wherein the complex is modified such that it has an extended half-life in vivo. The invention further relates to a method of producing the complex, as well as the therapeutic or prophylactic use of the complex for treating or preventing bleeding events.

Covalent complex of von Willebrand Factor and factor VIII, compositions, and uses relating thereto

The present invention relates to a polypeptide comprising a modified von Willebrand Factor (VWF) having a higher Factor VIII binding affinity than non-modified VWF, its pharmaceutical use and method of its preparation.

Von willebrand factor variants having improved factor VIII binding affinity

The present invention relates to modified cDNA sequences coding for factor X polypeptides, in particular human factor X and its derivatives which can bypass the need for either factor VIIIa/factor IXa or factor VIIa/tissue factor for activation. The invention relates further to recombinant expression vectors containing such modified 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 altered activation properties, 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.

Coagulation factor X polypeptides with modified activation properties

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 modified cDNA sequences coding for human Factor X and their derivatives with improved stability and modified activation sequences, recombinant expression vectors containing such cDNA sequences, and host cells transformed with such recombinant expression vectors. The invention also relates to recombinant factor X polypeptides and derivatives which have biological activities of the unmodified wild type protein but with improved stability 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.

The present invention relates to modified cDNA sequences coding for vitamin K-dependent polypeptides, in particular human Factor VII, human Factor VIIa, human Factor IX and human protein C and their derivatives with improved stability and extended 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 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 vitamin K dependent polypeptides

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

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Gladenbach, Germany

Thomas Weimer