Therapeutic application of kazal-type serine protease...

A - Human Necessities – 61 – K

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A61K 38/57 (2006.01) A61P 7/02 (2006.01) C07K 14/81 (2006.01)

Patent

CA 2678001

The subject of the present invention is, in the most general aspect, the therapeutic application of the Kazal-type serine protease inhibitor lnfestin or domains thereof or modified Kazal-type serine protease inhibitors based on lnfestin homologs, which prevent the formation and/or stabilization of three-dimensional arterial or venous thrombi by interfering with proteins involved in activation of the so-called intrinsic coagulation pathway. In particular the present invention relates to the use of said Kazal-type serine protease inhibitors or fragments thereof or modified Kazal-type serine protease inhibitors, in the treatment or prophylaxis of a condition or disorder related to arterial thrombus formation, i. e. stroke or myocardial infarction, inflammation, complement activation, fibrinolysis, angiogenesis and/or diseases linked to pathological kinin formation such as hypotonic shock, edema including hereditary angioedema, bacterial infections, arthritis, pancreatitis, or articular gout, Disseminated Intravasal Coagulation (DIC) and sepsis.

La présente invention concerne, par son aspect le plus général, l'application thérapeutique d'Infestine qui est une inhibitrice de sérine protéase de type Kazal, de certains de ses domaines, ou d'inhibiteurs de sérine protéase de type Kazal modifiés à base d'homologues d'Infestine. Ces inhibiteurs préviennent la formation et/ou la stabilisation des caillots de thrombose artériels ou veineux tridimensionnels par interférence avec des protéines impliquées dans l'activation de ce qu'il est convenu d'appeler le chemin de coagulation intrinsèque. L'invention concerne plus particulièrement l'utilisation de tels inhibiteurs de sérine protéase de type Kazal, de certains de leurs fragments, ou d'inhibiteurs de sérine protéase de type Kazal modifiés, pour le traitement ou la prévention d'un état ou d'un trouble en relation avec la formation du caillot de thrombose artériel, et notamment l'accident vasculaire cérébral ou l'infarctus du myocarde, l'inflammation, l'activation du complément, la fibrinolyse, l'angiogenèse et/ou des affections en lien avec la formation pathologique de kinine telles que le choc hypotonique, l'AEdème, y-compris l'AEdème de Quincke héréditaire, les infections bactériennes, l'arthrite, la pancréatite, ou la goutte articulaire, la DIC (Disseminated Intravasal Coagulation) et la sepsie.

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