Abstract: Vitamin K-dependent Protein S (PS) is a natural anticoagulant acting as a non-enzymatic cofactor for both activated protein C (APC) and tissue factor pathway inhibitor (TFPI). The inventors identify an anti-PS nanobody that very surprisingly enhances the APC-cofactor activity of PS through unknown mechanisms. Very interestingly, this nanobody exerts an antithrombotic effect in injured mesenteric microvessels of mice. As a consequence, it10 constitutes a novel class of antithrombotic agents that could be used for the treatment of acute microthrombosis in pathological states such as sepsis, COVID-19, distal microvascular thrombosis induced by stroke, or sickle-cell disease. Thus, the present invention relates to isolated single-domain antibodies (sdAb) directed against protein S (PS) and polypeptides comprising thereof.

Abstract: The present invention relates to a peptide comprising the amino acid sequence QGLIGDIALPRWGALWGDSV (SEQ ID NO: 1). Inventors have tested in wild-type mice a single domain antibody directed against VWF and tagged with an albumin-binding peptide. After giving a single dose intravenously (50 microgram/mouse), VWF levels were increased 8-15 fold for at least 7 days, knowing that the half-life of VWF is about 2-3 hours in a mouse. Moreover, intravenous administration of VWF together with a sdAb fused to an albumin-binding peptide resulted in detectable levels of VWF at 48 and 72 hours after injection, whereas no VWF could be detected when injected in the absence of such sdAb fused to an albumin-binding peptide. Thus, these results show a very long-lasting effect of this new approach.

Abstract: The present invention relates to mutated factor (FX) polypeptides and uses thereof for the treatment of haemophilia. In particular, the present invention relates to a mutated factor X (FX) polypeptide which comprises a heavy chain wherein at least one amino acid residue at position 401 or 408 is mutated.

Abstract: The present invention relates to mutated factor (FX) polypeptides and uses thereof for the treatment of haemophilia. In particular, the present invention relates to a mutated factor X (FX) polypeptide which comprises a heavy chain wherein at least one amino acid residue at position 401 or 408 is mutated.

Abstract: The present invention relates to mutated factor (FX) polypeptides and uses thereof for the treatment of haemophilia. In particular, the present invention relates to a mutated factor X (FX) polypeptide which comprises a heavy chain wherein at least one amino acid residue at position 441 and/or 448 of SEQ ID NO: 1 is mutated.

Abstract: The present invention relates to isolated single-domain antibodies (sdAb) directed against Antithrombin (AT) to prolong the half-life of the proteins. Inventors have generated isolated single domain antibodies (sdAbs) directed against antithrombin. They observed that in amidolytic assays, sdAbs are incapable of blocking the inhibitory antithrombin activity towards thrombin and factor Xa in the presence of heparin. The different combinations of sdAb were able to block the inhibitory antithrombin activity towards thrombin and factor Xa in mice. Thus, the inventors propose to use different combinations of sdAb to block the inhibitory function of antithrombin in order to promote thrombin generation and thus treat haemophilia and other conditions that are associated with bleeding.

Abstract: The present invention relates to mutated factor (FX) polypeptides and uses thereof for the treatment of haemophilia. In particular, the present invention relates to a mutated factor X (FX) polypeptide which comprises a heavy chain wherein at least one amino acid residue at position 401 or 408 is mutated.

Abstract: The invention relates to a method for distinguishing between different states or forms of diseases and disorders characterized by thrombocytopenia and/or by spontaneous interaction between Von Willebrand Factor (vWF) and platelets, and/or to predict the progression of such a disease or disorder, said method comprising the steps of providing at least one biological sample obtained from a patient suffering from, or suspected to suffer from, at least one disease or disorder characterized by thrombocytopenia and/or by spontaneous interaction between Von Willebrand Factor (vWF) and platelets and of determining the amount of activated vWF in said biological sample, in which the amount of activated vWF in the sample is representative for the different states or forms of the disease or disorder.