Antibody design using anti-lipid antibody crystal structures

Details Antibody design using anti-lipid antibody crystal structures Antibody design using anti-lipid antibody crystal structures

C - Chemistry, Metallurgy

07

K

C07K 16/44 (2006.01) A61K 39/395 (2006.01) C07K 16/18 (2006.01) C07K 16/46 (2006.01) G01N 33/53 (2006.01) G06F 19/00 (2011.01)

Patent

CA 2745436

The present invention provides crystalline forms of an anti-lipid antibody or fragment thereof, which may further comprise a lipid ligand of said antibody and/or salts, metals, or co-factors. Methods for making such crystals and co-crystals are provided. The lipid may be a bioactive lipid, including sphingolipids such as S1P. X-ray coordinates of such a crystal are provided, as are methods of using this information in antibody design or optimization. Methods for designing a humanized antibody to a lipid are provided. These methods may be performed in silico and may be intended to enhance binding affinity of an antibody to its original target lipid, and/or to alter binding specificity. Antibodies produced by these methods are also provided.

La présente invention porte sur des formes cristallines d'un anticorps anti-lipidique ou d'un fragment de celui-ci, qui peuvent en outre comprendre un ligand de lipide dudit anticorps et/ou des sels, des métaux ou des cofacteurs. L'invention porte également sur des procédés de fabrication de tels cristaux et co-cristaux. Le lipide peut être un lipide bioactif, comprenant des sphingolipides tels que S1P. Des coordonnées de rayons X d'un tel cristal sont fournies, ainsi que des procédés d'utilisation de ces informations dans une conception ou une optimisation d'anticorps. L'invention porte également sur des procédés de conception d'un anticorps humanisé dirigé contre un lipide. Ces procédés peuvent être réalisés in silico et peuvent avoir pour but d'augmenter l'affinité de liaison d'un anticorps à son lipide cible d'origine, et/ou de modifier la spécificité de liaison. L'invention porte également sur des anticorps produits par ces procédés.

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