Institut National De La Sante Et De La Recherche Medicale

Université Paris—sud

Université Paris-Saclay

Université De Droit Et De La Santé De Lille 2

Université Paris Diderot-Paris 7

Inserm (Institut National De La Sante Et De La Recherche Medicale)

Centre Hospitalier Régional Universitaire De Lille

Universite Paris Xiii Paris-Nord

Centre Hospitalier Regionale Universitaire De Lille

Université De Paris

Université De Lille

Inserm

Petrus Lenting

Olivier Christophe

Cécile Denis

Cecile Denis

Sophie Susen

Antoine Rauch

Gabriel Ayme

Paulette Legendre

Marie-Christine Bouton

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).

Antibodies for the prevention or the treatment of bleeding episodes

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&#x2032;D3 domain.

Anti-VWF D'D3 single-domain antibodies fuse to clotting factors

The present invention relates to a method and compositions for the treatment of haemorrhagic diseases.

Methods of administering neutralizing anti-protease nexin-1 antibodies to treat hemophilia A

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: &#x2014;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); &#x2014;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 &#x2014;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).

Mutated factor X polypeptides and uses thereof for the treatment of haemophilia

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&#x2032;D3 domain.

Anti-VWF D'D3 single-domain antibodies and methods of use

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Le Kremlin-Bicetre, France

Petrus Lenting