Expression of the cysteine protease legumain in vascular and...

C - Chemistry – Metallurgy – 12 – N

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Details

C12N 9/64 (2006.01) A61K 39/395 (2006.01) A61P 9/00 (2006.01) C07K 16/14 (2006.01) C12P 29/00 (2006.01)

Patent

CA 2652895

The present invention provides isolated and purified polynucleotides, polypeptides, and antibodies related to mammalian (e.g., mouse and human) legumain and the novel legumain splice variant, ZB-I. The invention further relates to the use of these isolated and purified polynucleotides, polypeptides, and antibodies, as well as other legumain and ZB-I agonists and antagonists, in modulating legumain and/or ZB-I activity, expression, and/or secretion in a cell or cell population, e.g., monocytes, macrophages, foam cells, vascular endothelial cells, kidney proximal tubule cells, arterial endothelial cells, sites of inflammatory cell invasion into a vessel intima, and neointimal lesional areas of an artery. The invention also provides legumain and ZB-I antagonists, e.g., antagonistic small molecules, antibodies and antibody fragments to legumain and ZB-I, legumain and ZB-I inhibitory polypeptides, and legumain and ZB-I inhibitory polynucleotides. The present invention is also directed to novel methods for diagnosing, prognosing, monitoring, treating, ameliorating and/or preventing vascular disorders / diseases and inflammatory disorders / diseases.

La présente invention concerne des polynucléotides, des polypeptides et des anticorps isolés et purifiés, associés à la légumaïne d'un mammifère (p. ex. d'une souris ou d'un être humain), et le nouveau variant d'épissage de la légumaïne, le ZB-I. L'invention concerne également l'utilisation de ces polynucléotides, polypeptides et anticorps isolés et purifiés ainsi que d'autres agonistes et antagonistes de la légumaïne et du ZB-I, dans la modulation de l'activité, de l'expression et/ou de la sécrétion de la légumaïne et/ou du ZB-I dans une cellule ou une population cellulaire, p. ex. des monocytes, des macrophages, cellules spumeuses, des cellules endothéliales vasculaires, des cellules tubulaires proximales du rein, des cellules endothéliales artérielles, des sites d'invasion de l'intima d'un vaisseau par des cellules inflammatoires et des zones lésionnelles néointimales d'une artère. L'invention concerne également des antagonistes, p. ex des petites molécules antagonistes, de la légumaïne et du ZB-I, des anticorps et fragments d'anticorps contre la légumaïne et le ZB-I, des polypeptides inhibiteurs de la légumaïne et du ZB-I ainsi que des polynucléotides inhibiteurs de la légumaïne et du ZB-I. L'invention se rapporte en outre à de nouvelles méthodes de diagnostic, de pronostic, de surveillance, de traitement, d'amélioration et/ou de prévention de troubles / maladies vasculaires et de troubles / maladies inflammatoires.

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