Recombinant antibodies against vascular endothelial growth...

C - Chemistry – Metallurgy – 07 – K

Patent

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C07K 16/22 (2006.01)

Patent

CA 2667594

The invention relates to recombinant antibody-related polypeptide molecules which specifically recognise human vascular endothelial growth factor-A (VEGF-A) and interfere with the in vivo proangiogenic and in vitro stimulatory effects thereof. The aforementioned recombinant polypeptide molecules can affect the proliferation of in vitro human endothelial cells, subcutaneous angiogenesis in mice, induced by matrigel plugs containing VEGF-A, and the growth of human tumours transplanted to nude mice. Some of these molecules prevent choroid neovascularisation in a non-human primate experimental model. Said molecules can be used for passive immunotherapy of pathological entities having a course that is associated with an increase in vasculature, such as age-related macular degeneration (moist type), cancer and the metastasis thereof, neovascular glaucomas, diabetic and neonatal retinopathy, acute and chronic inflammatory processes, infectious diseases, autoimmune diseases, organ transplant rejection, hemangiomas and angiofibromas among others.

L'invention concerne des molécules peptidiques de recombinaison associées à des anticorps, qui reconnaissent de manière spécifique le facteur de croissance de l'endothélium vasculaire A (VEGF-A) humain, et interfèrent avec ses effets stimulateurs in vitro et pro-angiogéniques in vivo. Lesdites molécules polypeptidiques de recombinaison peuvent affecter la prolifération de cellules endothéliales humaines in vitro, l'angiogenèse sous-cutanée chez les souris, induite par des bouchons de matrigel contenant le VEGF-A, et la croissance de tumeurs humaines transplantées chez des souris nues. Certaines de ces molécules préviennent la néovascularisation choroïdienne dans un modèle expérimental chez les primates non humains. Ces molécules peuvent être utilisées dans l'immunothérapie passive d'entités pathologiques dont le développement est associé à l'augmentation du système vasculaire, telles que la dégénération maculaire associées à l'âge (variante humide), le cancer et ses métastases, les glaucomes néovasculaires, la rétinopathie diabétique et du nouveau-né, les processus inflammatoires aigus et chroniques, les maladies infectieuses, les maladies auto-immunes, le rejet de greffes d'organes, les hémangiomes et les angiofibromes, entres autres.

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