Abstract: The present invention relates to methods and pharmaceutical compositions of inducing immune tolerance by mucosal vaccination with Fc-coupled antigens. In particular, the present invention relates to a method for inducing tolerance to one antigen of interest in a subject in need thereof, comprising the mucosal administration to the subject of a therapeutically effective amount of a recombinant chimeric construct comprising a FcRn targeting moiety and an antigen-containing moiety.

Abstract: Constructs and methods for inducing immune tolerance during gestation, e.g. in utero, are provided. The constructs comprise a moiety that targets and binds to the neonatal Fc receptor (FcRn) and a moiety comprising an antigen of interest for which immune tolerance is desired. Administration of the constructs to a fetus during gestation results in immune tolerance, e.g. to antigens that otherwise elicit an unwanted immune response such as an autoimmune reaction.

Abstract: There is provided in accordance with the practice of this invention a demannosylated Factor VIII, the immunogenicity of which is substantially decreased or abolished in Human. The modified factor VIII is disclosed together with the modified amino acid sequence, changed by at least one substitution. The modified factor VIII is useful for hemophiliacs, either to avoid or prevent the action of inhibitory anti-FVIII antibodies.

Abstract: There is provided in accordance with the practice of this invention a demannosylated Factor VIII, the immunogenicity of which is substantially decreased or abolished in Human. The modified factor VIII is disclosed together with the modified amino acid sequence, changed by at least one substitution. The modified factor VIII is useful for hemophiliacs, either to avoid or prevent the action of inhibitory anti-FVIII antibodies.

Abstract: The invention relates to a compound capable of inhibiting the endocytosis of FVIII (factor VIII) by immune system cells capable of endocytosing the antigen and to the therapeutic use of such a compound for the manufacture of a medicament for use in the treatment of hemophiliacs in order to reduce the immunogenicity of FVIII and/or increase the half-life of FVIII.

Abstract: The present invention relates to a method of determining the presence of catalytic anti-Factor VIII allo-antibodies capable of degrading Factor VIII in a mammal, and of characterising the cleavage sites in said Factor VIII molecule by said catalytic anti-Factor VIII allo-antibodies. It also relates to an anti-Factor VIII allo-antibody-catalysed Factor VIII degradation inhibitor; and to a pharmaceutical composition comprising said catalytic anti-Factor VIII allo-antibodies which are capable of degrading Factor VIII and which originate from said method of determination; and further to a pharmaceutical composition comprising said anti-Factor VIII allo-antibody-catalysed Factor VIII degradation inhibitor.

Abstract: A method is disclosed of determining the presence of catalytic anti-Factor VIII allo-antibodies capable of degrading Factor VIII in a mammal, and of characterising the cleavage sites in said Factor VIII molecule by said catalytic anti-Factor VIII allo-antibodies. It also relates to an anti-Factor VIII allo-antibody-catalysed Factor VIII degradation inhibitor; and to a pharmaceutical composition comprising said catalytic anti-Factor VIII allo-antibodies which are capable of degrading Factor VIII and which originate from said method of determination; and further to a pharmaceutical composition comprising said anti-Factor VIII allo-antibody-catalysed Factor VIII degradation inhibitor.