Abstract: 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.

Abstract: The present invention relates to pharmaceutical formulations comprising the C1 esterase inhibitor (“C1-INH”), exhibiting a higher stability for prolonged storage and a reduced kinematic viscosity for ameliorated use in treating or preventing disorders related to kinin formation.

Abstract: 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.

Abstract: The invention relates to factor VIII compositions and their use.

Abstract: The present invention relates to pharmaceutical preparations comprising two-chain Factor VIII that are essentially free of Factor VIII-Light Chains (FVIII-LCs) which are not associated with Factor VIII-Heavy Chains (FVIII-HCs) having higher purity and which are less immunogenic. The invention also relates to methods to test the suitability of a pharmaceutical Factor VIII preparation and to methods to reduce in pharmaceutical Factor VIII preparations the amount of FVIII-HCs which are not associated with FVIII-LCs and/or of FVIII-LCs which are not associated with FVIII-HCs.

Abstract: The present disclosure relates to a method for increasing the stability of a Factor VIII molecule after purification, lyophilization and reconstitution, comprising preventing proteolytic cleavage of the Factor VIII molecule into a first fragment comprising essentially the A1 domain and the A2 domain and a second fragment comprising essentially the A3 domain, the C1 domain and the C2 domain throughout manufacturing the Factor VIII molecule. The disclosure further pertains to a method for improving the bioavailability of Factor VIII after intravenous and non-intravenous injection.

Abstract: The present invention relates to pharmaceutical preparations comprising Factor VIII, a sulfated glycosaminoglycan and a hyaluronidase for the non-intravenous administration in the therapy and prophylactic treatment of bleeding disorders. The invention further relates to the combined use of a Factor VIII, a sulfated glycosaminoglycan and a hyaluronidase for the treatment and prevention of bleeding disorders, and to a method for increasing the bioavailability after non-intravenous administration of Factor VIII by co-administration of a sulfated glycosaminoglycan and a hyaluronidase.

Abstract: The present invention relates to a method for increasing the stability of a Factor VIII molecule after purification, lyophilization and reconstitution, comprising preventing proteolytic cleavage of the Factor VIII molecule into a first fragment comprising essentially the A1 domain and the A2 domain and a second fragment comprising essentially the A3 domain, the C1 domain and the C2 domain throughout manufacturing of the Factor VIII molecule. The invention further pertains to a method for improving the bioavailability of Factor VIII after intravenous and non-intravenous injection.

Abstract: The present invention relates to pharmaceutical preparations comprising one or more Factor VIII and a sulfated glycosaminoglycan for increasing the bioavailability of Factor VIII upon non-intravenous administration. The invention further relates to the combined use of Factor VIII and a sulfated glycosaminoglycan for the treatment and prevention of bleeding disorders, whereby the bioavailability of Factor VIII is increased, and to a method for increasing the bioavailability after non-intravenous administration of Factor VIII by coadminstration of a sulfated glycosaminoglycan.

Abstract: 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.

Abstract: 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.

Abstract: The invention relates to therapeutic fusion proteins in which a coagulation factor is fused to a half-life enhancing polypeptide, and in which both are connected by a linker peptide that is proteolytically cleavable. The cleavage of such linkers liberates the coagulation factor from activity-compromising steric hindrance caused by the half-life enhancing polypeptide and thereby allows the generation of fusion proteins may show relatively high molar specific activity when tested in coagulation-related assays. Furthermore, the fact that the linker is cleavable can enhance the rates of inactivation and/or elimination after proteolytic cleavage of the peptide linker compared to the rates measured for corresponding therapeutic fusion proteins linked by the non-cleavable linker having the amino acid sequence GGGGGGV.

Abstract: The present invention relates to pharmaceutical preparations comprising Factor VIII, a sulfated glycosaminoglycan and a hyaluronidase for the non-intravenous administration in the therapy and prophylactic treatment of bleeding disorders. The invention further relates to the combined use of a Factor VIII, a sulfated glycosaminoglycan and a hyaluronidase for the treatment and prevention of bleeding disorders, and to a method for increasing the bioavailability after non-intravenous administration of Factor VIII by co-adminstration of a sulfated glycosaminoglycan and a hyaluronidase.

Abstract: The present invention relates to pharmaceutical preparations comprising one or more Factor VIII and a sulfated glycosaminoglycan for increasing the bioavailability of Factor VIII upon non-intravenous administration. The invention further relates to the combined use of Factor VIII and a sulfated glycosaminoglycan for the treatment and prevention of bleeding disorders, whereby the bioavailability of Factor VIII is increased, and to a method for increasing the bioavailability after non-intravenous administration of Factor VIII by coadminstration of a sulfated glycosaminoglycan.

Abstract: The present invention relates to nucleic acid sequences coding for modified coagulation factors, preferably coagulation factor VIII, and their derivatives; recombinant expression vectors containing such nucleic acid sequences; host cells transformed with such recombinant expression vectors; and recombinant polypeptides and derivatives coded for by said nucleic acid sequences, whereby said recombinant polypeptides and derivatives have biological activities and prolonged in vivo half-lives compared to the unmodified wild-type proteins. The invention also relates to corresponding sequences that result in improved in vitro stability. 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 nucleic acid sequences.

Abstract: The present invention relates to a method for increasing the stability of a Factor VIII molecule after purification, lyophilization and reconstitution, comprising preventing proteolytic cleavage of the Factor VIII molecule into a first fragment comprising essentially the A1 domain and the A2 domain and a second fragment comprising essentially the A3 domain, the C1 domain and the C2 domain throughout manufacturing of the Factor VIII molecule. The invention further pertains to a method for improving the bioavailability of Factor VIII after intravenous and non-intravenous injection.

Abstract: The present invention relates to the field of modified therapeutic polypeptides with increased in vivo recovery compared to their non-modified parent polypeptide. For example, the invention relates to fusions of therapeutic polypeptides with recovery enhancing polypeptides connected directly or optionally connected by a linker peptide.

Abstract: The present invention relates to nucleic acid sequences coding for modified coagulation factors, preferably coagulation factor VIII, and their derivatives; recombinant expression vectors containing such nucleic acid sequences; host cells transformed with such recombinant expression vectors; and recombinant polypeptides and derivatives coded for by said nucleic acid sequences, whereby said recombinant polypeptides and derivatives have biological activities and prolonged in vivo half-lives compared to the unmodified wild-type proteins. The invention also relates to corresponding sequences that result in improved in vitro stability. 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 nucleic acid sequences.

Abstract: 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.

Abstract: The present invention relates to the field of modified therapeutic polypeptides with increased in vivo recovery compared to their non-modified parent polypeptide. For example, the invention relates to fusions of therapeutic polypeptides with recovery enhancing polypeptides connected directly or optionally connected by a linker peptide.