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 mutated factor (FX) polypeptides and uses thereof for the treatment of haemophilia.

Abstract: The invention relates to an isolated monoclonal antibody that specifically binds to the D4 domain of VWF, competes for binding to VWF D4 domain with ADAMTS13 and partially inhibits ADAMTS 13-mediated degradation of VWF. More particularly, the invention relates to an isolated monoclonal antibody comprising a heavy chain wherein the variable domain comprises at least one CDR having a sequence selected from the group consisting of SEQ ID NO: 3 for H-CDR1, SEQ ID NO: 4 for H-CDR2 and SEQ ID NO: 5 for H-CDR3 and a light chain wherein the variable domain comprises at least one CDR having a sequence selected from the group consisting of SEQ ID NO: 7 for L-CDR1, SEQ ID NO: 8 for L-CDR2 and SEQ ID NO: 9 for L-CDR3. Antibodies of the invention are presented to be useful in for the prevention or the treatment of bleeding episodes, such as bleeding episodes occurring in patients with aortic stenosis or patients with ventricular assist devices (VAD).

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 a method and compositions for the treatment of haemorrhagic diseases.

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 wherein the heavy chain comprises at least one mutation selected from the group consisting of: —the mutation which consists of the substitution of the glutamic acid residue (E) at position 255 of Seq. ID No. 1 by a glutamine residue (Q), an asparagine residue (N), a serine residue (S), an alanine residue (A), or a tyrosine residue (Y); —the mutation which consists of the substitution of the glutamic acid residue (E) at position 256 of Seq. ID No. 1 by a glutamine residue (Q); and —the mutation which consists of the substitution of the glutamic acid residue (E) at position 258 of Seq. ID No.

Abstract: The invention relates to an isolated monoclonal antibody that specifically binds to the D4 domain of VWF, competes for binding to VWF D4 domain with ADAMTS13 and partially inhibits ADAMTS 13 -mediated degradation of VWF. More particularly, the invention relates to an isolated monoclonal antibody comprising a heavy chain wherein the variable domain comprises at least one CDR having a sequence selected from the group consisting of SEQ ID NO: 3 for H-CDR1, SEQ ID NO: 4 for H-CDR2 and SEQ ID NO: 5 for H-CDR3 and a light chain wherein the variable domain comprises at least one CDR having a sequence selected from the group consisting of SEQ ID NO: 7 for L-CDR1, SEQ ID NO: 8 for L-CDR2 and SEQ ID NO: 9 for L-CDR3. Antibodies of the invention are presented to be useful in for the prevention or the treatment of bleeding episodes, such as bleeding episodes occurring in patients with aortic stenosis or patients with ventricular assist devices (VAD).