Three-dimensional model of a complex between a fc epsilon...

C - Chemistry – Metallurgy – 12 – N

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C12N 15/12 (2006.01) A61K 38/17 (2006.01) C07C 15/38 (2006.01) C07K 14/00 (2006.01) C07K 16/06 (2006.01) G01N 33/53 (2006.01) G01N 33/68 (2006.01)

Patent

CA 2403739

The present invention includes three-dimensional models of complexes between antibody receptor proteins, such as Fc.epsilon.RI.alpha. proteins, and antibodies, such as Fc-C.epsilon.3/C.epsilon.4 regions of IgE antibodies, as well as methods to produce such models. The present invention also includes muteins having increased stability and/or antibody binding activity, as well as methods to produce such muteins, preferably using information derived from three-dimensional models of the present invention. Also included are nucleic acid sequences encoding muteins of the present invention and use of those sequences to produce such muteins. Also included is the use of the model to identify compounds that inhibit the binding of an antibody receptor protein to an antibody. The present invention also includes uses of such muteins and inhibitory compounds, for example, in methods to diagnose and protect animals from allergy and other abnormal immune response.

La présente invention concerne, d'une part des modèles tridimensionnels de complexes entre des protéines réceptrices d'anticorps telles que les protéines Fc.epsilon.RI.alpha., et des anticorps, tels que les régions Fc-C.epsilon.3/C.epsilon.4 des anticorps IgE, et des procédés de production de tels models. L'invention concerne également des mutéines à stabilité accrue et/ou à activité accrue de liaison aux anticorps, ainsi que des procédés de production de telles mutéines, de préférence en utilisant de l'information déduite des modèles tridimensionnels de l'invention. L'invention concerne aussi, d'une part des séquences d'acide nucléique codant les mutéines de l'invention et l'utilisation de ces séquences pour produire de telles mutéines, et d'autre part l'utilisation de ce modèle pour identifier des composés inhibiteurs de la liaison d'une protéine réceptrice d'anticorps avec un anticorps. L'invention concerne enfin des utilisations de telles mutéines et composés inhibiteurs notamment pour des procédés visant au diagnostic, et à la protection d'animaux contre des allergies et d'autres réponses immunitaires anormales.

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