Institut National De La Sante Et De La Recherche Medicale

Vanderbilt University

Katholieke Universiteit Leuven

Université De Caen Basse Normandie

Centre Hospitalier Unviersitaire De Caen

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

Paul Declerck

Denis Vivien

Douglas E Vaughan

Marina Rubio

Mesut Eren

Nick Geukens

Simon De Meyer

Ann Gils

Tine Wyseure

Disclosed herein is a bispecific inhibitor for use in treating thrombotic disorders, such as acute thrombotic disorders like stroke and thromboembolism. The bispecific inhibitor is based on monoclonal antibodies targeting TAFI and PAI-1, and shows efficacy in the presence or the absence of plasminogen activators such as tissue-type plasminogen activator (tPA).

Dual targeting of TAFI and PAI-1

A method of testing a candidate composition for PAI-1 inhibition activity is disclosed. The method includes the steps of obtaining a transgenic non-human warm blooded vertebrate animal having incorporated into its genome a PAI-1 gene encoding a biologically active PAI-1 polypeptide, the PAI-1 gene being present in the genome in a copy number effective to confer over-expression in the transgenic non-human animal of the PAI-1 polypeptide; administering the composition to the transgenic non-human animal; and observing the transgenic non-human animal for determination of a change in the transgenic non-human animal indicative of inhibition of the activity of PAI-1. A transgenic non-human animal useful in such a method is also disclosed, as is a PAI-1 transgene construct encoding a biologically active PAI-1 polypeptide useful for preparing the transgenic non-human animal.

Therapeutic methods employing PAI-1 inhibitors and transgenic non-human animal for screening candidate PAI-1 inhibitors

Growing community of inventors

Leuven, Belgium

Paul Declerck