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1. WO2022002880 - ANTI-PROTEIN S SINGLE-DOMAIN ANTIBODIES AND POLYPEPTIDES COMPRISING THEREOF

Publication Number WO/2022/002880
Publication Date 06.01.2022
International Application No. PCT/EP2021/067746
International Filing Date 28.06.2021
IPC
C07K 16/36 2006.1
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
16Immunoglobulins, e.g. monoclonal or polyclonal antibodies
18against material from animals or humans
36against blood coagulation factors
C07K 16/38 2006.1
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
16Immunoglobulins, e.g. monoclonal or polyclonal antibodies
38against protease inhibitors of peptide structure
A61P 7/02 2006.1
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
7Drugs for disorders of the blood or the extracellular fluid
02Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
A61K 39/395 2006.1
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
39Medicinal preparations containing antigens or antibodies
395Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
Applicants
  • INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) [FR]/[FR]
  • ASSISTANCE PUBLIQUE-HÔPITAUX DE PARIS (APHP) [FR]/[FR]
  • UNIVERSITÉ PARIS-SACLAY [FR]/[FR]
Inventors
  • SALLER, François
  • DENIS, Cécile
  • BORGEL, Delphine
  • ADAM, Frédéric
  • CHRISTOPHE, Olivier
  • LENTING, Peter
Agents
  • INSERM TRANSFERT
Priority Data
20305723.729.06.2020EP
Publication Language English (en)
Filing Language English (EN)
Designated States
Title
(EN) ANTI-PROTEIN S SINGLE-DOMAIN ANTIBODIES AND POLYPEPTIDES COMPRISING THEREOF
(FR) ANTICORPS À DOMAINE UNIQUE ANTI-PROTÉINE S ET POLYPEPTIDES LES COMPRENANT
Abstract
(EN) 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.
(FR) La protéine S (PS) dépendante de la vitamine K est un anticoagulant naturel qui agit en tant que cofacteur non enzymatique pour la protéine C activée (APC) et l'inhibiteur de la voie du facteur tissulaire (TFPI). Les inventeurs identifient un nanocorps anti-PS qui améliore de manière très surprenante l'activité du cofacteur APC de la PS par l'intermédiaire de mécanismes inconnus. De manière très intéressante, ce nanocorps exerce un effet antithrombotique dans des microvaisseaux mésentériques lésés de souris. Par conséquent, il constitue une nouvelle classe d'agents antithrombotiques qui pourraient être utilisés pour le traitement de la microthrombose aiguë dans des états pathologiques tels que la sepsie, COVID-19, la thrombose microvasculaire distale induite par un accident vasculaire cérébral, ou la drépanocytose. Ainsi, la présente invention concerne des anticorps isolés à domaine unique (sdAb) dirigés contre la protéine S (PS) et des polypeptides les comprenant.
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