Anti-tissue factor antibodies and compositions with enhanced...

C - Chemistry – Metallurgy – 12 – N

Patent

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C12N 15/13 (2006.01) A01K 67/027 (2006.01) A61K 39/395 (2006.01) A61K 47/48 (2006.01) A61P 35/00 (2006.01) C07K 16/28 (2006.01) C07K 16/36 (2006.01) C07K 16/42 (2006.01) C12N 5/10 (2006.01) C07K 14/745 (2006.01)

Patent

CA 2685698

Variants of antibodies to human tissue factor are optimized for the capability to elicit effector functions produced by immune effector cells while maintaining the ability to neutralize the biological functions of tissue factor, such as the prevention of blood clotting via the extrinsic pathway, and are produced by mutations of the Fc-region of the antibody. The variants comprise A33 OY, A3301, and I332E where the I332E variant may optionally further comprise a second substitution selected from A33OI (in the case of the first substitution being I332E), V264I, and S239D. The variants may further be optimized for the capability to elicit effector functions produced by immune effector cells by production of the antibody variants under conditions that produce effector function enhancing glycosylation of the Fc-region.

Selon la présente invention, des variantes d'anticorps du facteur tissulaire humain sont optimisées pour leur capacité à provoquer des fonctions d'effecteur au moyen de cellules effectrices de l'immunité tout en conservant la capacité à neutraliser les fonctions biologiques du facteur tissulaire, telle la prévention de formations de caillots par une voie extrinsèque, et sont produites par les mutations de la région Fc de l'anticorps. Parmi les variantes, on trouve l'A33 OY, l'A3301 et l'I332E où la variante I332E peut éventuellement comprendre une seconde substitution sélectionnée à partir de l'A33OI (si la première substitution implique l'I332E), V264I, et S239D. Les variantes peuvent aussi être optimisées pour leur capacité à provoquer des fonctions d'effecteur obtenues à partir de cellules effectrices de l'immunité par la production de variantes d'anticorps dans des conditions qui génèrent une fonction d'effecteur augmentant la glycosylation de la région Fc.

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