Modulators of epha2 and ephrina1 for the treatment of...

A - Human Necessities – 61 – K

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A61K 48/00 (2006.01) A61K 39/00 (2006.01) A61K 39/395 (2006.01)

Patent

CA 2585703

The present invention relates to methods and compositions designed for the treatment, management, prevention and/or amelioration of non-neoplastic hyperproliferative epithelial and/or endothelial cell disorders, including but not limited to disorders associated with increased deposition of extracellular matrix components (e.g., collagen, proteoglycans, tenascin and fibronectin) and/or aberrant angiogenesis. Non-limiting examples of such disorders include cirrhosis, fibrosis (e.g., fibrosis of the liver, kidney, lungs, heart, retina and other viscera), asthma, ischemia, atherosclerosis, diabetic retinopathy, retinopathy of prematurity, vascular restenosis, macular degeneration, rheumatoid arthritis, osteoarthritis, infantile hemangioma, verruca vulgaris, Kaposi's sarcoma, neurofibromatosis, recessive dystrophic epidermolysis bullosa, ankylosing spondylitis, systemic lupus, Reiter's syndrome, Sjogren's syndrome, endometriosis, preeclampsia, atherosclerosis, coronary artery disease, psoriatic arthropathy and psoriasis. The methods of the invention comprise the administration of an effective amount of one or more agents that are modulators of EphA2 and/or its endogenous ligand, EphrinAl. The invention also provides pharmaceutical compositions comprising one or more EphA2/EphrinAl Modulators of the invention either alone or in combination with one or more other agents useful for therapy for such non~neoplastic hyperproliferative epithelial and/or endothelial disorders. Diagnostic methods and methods for screening for EphA2/EphrinAl Modulators are also provided.

L'invention concerne des méthodes et des compositions pour le traitement, la gestion, la prévention et/ou l'amélioration de troubles de cellules épithéliales et/ou endothéliales non-néoplastiques hyperproliférantes, y compris mais sans se limiter à des troubles associés à un dépôt accru de composants matriciels extra-cellulaires (par ex., un collagène, des protéoglycanes, une tenascine ou une fibronectine) et/ou une angiogénèse aberrante. Des exemples non limitatifs de tels troubles comprennent la cirrhose, la fibrose (par ex., la fibrose du foie, du rein, du poumon, du coeur, de la rétine ou d'un autre viscère), l'asthme, l'ischémie, l'athérosclérose, la rétinopathie diabétique, la rétinopathie de la prématurité, la resténose vasculaire, la dégénération maculaire, la polyarthrite rhumatoïde, l'ostéoarthrite, l'hémangiome infantile, la verrue vulgaire, le sarcome de Kaposi, la neurofibromatose, l'épidermolyse bulleuse dystrophique récessive, la spondylite ankylosante, le lupus systémique, le syndrome de Reiter, le syndrome de Sjogren, l'endométriose, l'éclampsisme, l'athérosclérose, l'insuffisance coronaire, l'arthropathie psoriatique et le psoriasis. Les méthodes de l'invention consistent à administrer une quantité suffisante d'un ou de plusieurs agents que sont les modulateurs de EphA2 et/ou son ligand endogène, EphrinAl. La présente invention porte également sur des compositions pharmaceutiques contenant un ou plusieurs modulateurs de EphA2/EphrinAl selon l'invention, soit seul soit combiné avec un ou plusieurs autres agents utiles dans la thérapie de ces troubles de cellules épithéliales et/ou endothéliales non-néoplastiques hyperproliférantes. Enfin, l'invention concerne aussi des procédés de diagnostic et des méthodes pour cribler des modulateurs de EphA2/EphrinAl.

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