Abstract: The present invention relates to improved human FVIII variants having at least one substitution in the A2 and/or C2 domain. The present invention also relates to their uses in the treatment of hemophilia A, particularly in patients with inhibitors.

Abstract: The invention relates to a recombinant human factor IX (FIX) characterized in that said factor is obtained by a preparation method comprising, or even consisting of, the steps which consist in causing the genetic material encoding the FIX to be expressed in vitro in a human hepatocyte cell line Huh7, recovering the cellular supernatant in which the FIX was secreted and, optionally, purifying the synthesized FIX.

Abstract: The present invention relates to modified nucleic acid sequences coding for coagulation factors, in particular human Factor VIII and their derivatives with improved stability, recombinant expression vectors containing such nucleic acid 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 modified DNA sequences.

Abstract: The present invention relates to improved human FVIII variants having at least one substitution in the A2 and/or C2 domain. The present invention also relates to their uses in the treatment of hemophilia A, particularly in patients with inhibitors.

Abstract: The present invention relates to modified DNA sequences coding for biologically active recombinant human factor VIII and its derivatives, recombinant expression vectors containing such DNA sequences, host cells transformed with such recombinant expression vectors, and processes for the manufacture of the recombinant human factor VIII and its derivatives. The invention also covers a transfer vector for use in human gene therapy which comprises such modified DNA sequences. The present invention relates to modified DNA sequences coding for biologically active recombinant human factor VIII and its derivatives, recombinant expression vectors containing such DNA sequences, host cells transformed with such recombinant expression vectors, and processes for the manufacture of the recombinant human factor VIII and its derivatives. The invention also covers a transfer vector for use in human gene therapy which comprises such modified DNA sequences.

Abstract: A DNA-construct has been disclosed which is suitable for a tissue-specific expression of a blood coagulation factor like Factor IX, which comprises a DNA coding for an amino acid sequence of a blood coagulation factor and a DNA coding for a promoter which is specific for the expression in hematopoietic cells.

Abstract: A modified Factor VIII cDNA is described in which the B-domain of the wild-type Factor VIII cDNA has been deleted and a truncated Factor IX intron 1 has been inserted in one or more locatons of the Factor VIII cDNA. Such modified Factor VIII cDNA may be used for a higher yield production of Factor VIII in vitro as well as in a transfervector for gene therapy.

Abstract: A modified Factor VIII cDNA is disclosed wherein the B-domain of the wild type factor cDNA has been deleted and a truncated Factor IX intron 1 has been inserted in two locations of the Factor VIII cDNA and as a promoter a cDNA is used which is suitable for the expression in hematopoietic cell lines and specifically in platelets.

Abstract: A modified factor VIII CDNA is disclosed, wherein one or more spliceable nucleotide sequences have been inserted into introns 1 and/or 13 of the wild-type factor VIII cDNA. Further, a process for the production of a biologically active recombinant human factor VIII or its derivative is disclosed, which is performed by cultivating an animal cell line comprising a recombinant expression vector containing said modified factor VIII cDNA. Moreover, a transfer vector for use in the human gene therapy is described which comprises said modified factor VIII cDNA. Finally, the use of recombinant human factor VII and its derivatives for the treatment of hemophilia is disclosed.

Abstract: A modified Factor VIII cDNA is disclosed wherein the B-domain of the wild type factor cDNA has been deleted and a truncated Factor IX intron 1 has been inserted in two locations of the Factor VIII cDNA and as a promoter a cDNA is used which is suitable for the expression in hematopoietic cell lines and specifically in platelets.

Abstract: A modified Factor VIII cDNA is described in which the B-domain of the wild-type Factor VIII cDNA has been deleted and a truncated Factor IX intron 1 has been inserted in one or more locatons of the Factor VIII cDNA. Such modified Factor VIII cDNA may be used for a higher yield production of Factor VIII in vitro as well as in a transfervector for gene therapy.

Abstract: A DNA construct is disclosed which encodes a fusion protein comprising an amino acid sequence of a blood clotting factor like Factor IX and an amino acid sequence of the cytoplasmic domain of P-Selectin. Such construct may be used for the somatic gene therapy of patients suffering from a defiency of a blood coagulation factor.

Abstract: A modified Factor VIII cDNA is described comprising deletion of the B-domain and insertion of at least one truncated Factor IX intron 1 in the Factor VIII cDNA. The modified Factor VIII cDNA may be used for the production of a high yield of Factor VIII in vitro. The modified Factor VIII cDNA may be incorporated into a vector for gene therapy.