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 invention relates to isolated single-domain antibodies (sdAb) directed against von Willebrand Factor (VWF) D?D3 domain and chimeric polypeptides comprising thereof such as blood clotting factors and their uses in therapy such as in the prevention and treatment of hemostatic disorders.

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 invention relates to isolated single-domain antibodies (sdAb) directed against von Willebrand Factor (VWF) D?D3 domain and chimeric polypeptides comprising thereof such as blood clotting factors and their uses in therapy such as in the prevention and treatment of hemostatic disorders. The invention also relates to a method of extending or increasing half-life of a therapeutic polypeptide comprising a step of adding to the polypeptide sequence of said therapeutic polypeptide at least one sdAb directed against VWF D?D3 domain.

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 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.

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 isolated single-domain antibodies (sdAb) directed against von Willebrand Factor (VWF) D?D3 domain and chimeric polypeptides comprising thereof such as blood clotting factors and their uses in therapy such as in the prevention and treatment of hemostatic disorders. The invention also relates to a method of extending or increasing half-life of a therapeutic polypeptide comprising a step of adding to the polypeptide sequence of said therapeutic polypeptide at least one sdAb directed against VWF D?D3 domain.

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. 1 by a glutamine residue (Q).

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 invention relates to isolated single-domain antibodies (sdAb) directed against von Willebrand Factor (VWF) D?D3 domain and chimeric polypeptides comprising thereof such as blood clotting factors and their uses in therapy such as in the prevention and treatment of hemostatic disorders. The invention also rotates to a method of extending or increasing half-life of a therapeutic polypeptide comprising a step of adding to the polypeptide sequence of said therapeutic polypeptide at least one sdAb directed against VWF D?D3 domain.

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 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 invention relates to isolated single-domain antibodies (sdAb) directed against von Willebrand Factor (VWF) D?D3 domain and chimeric polypeptides comprising thereof such as blood clotting factors and their uses in therapy such as in the prevention and treatment of hemostatic disorders. The invention also rotates to a method of extending or increasing half-life of a therapeutic polypeptide comprising a step of adding to the polypeptide sequence of said therapeutic polypeptide at least one sdAb directed against VWF D?D3 domain.

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 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.