Antibodies for inhibiting blood coagulation and methods of...

C - Chemistry – Metallurgy – 07 – K

Patent

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Details

C07K 16/46 (2006.01) A61K 39/395 (2006.01) A61P 7/02 (2006.01) A61P 29/00 (2006.01) A61P 35/00 (2006.01) C07K 16/36 (2006.01) C12N 5/16 (2006.01) C12N 15/13 (2006.01) C12P 21/08 (2006.01)

Patent

CA 2465325

The invention includes antibodies that provide superior anti-coagulant activity by binding native human TF with high affinity and specificity. Antibodies of the invention can effectively inhibit blood coagulation in vivo. Antibodies of the invention can bind native human TF, either alone or present in a TF:FVIIa complex, effectively preventing factor X or FIX binding to TF or that complex, and thereby reducing blood coagulation. Preferred antibodies of the invention specifically bind a conformational epitope predominant to native human TF, which epitope provides an unexpectedly strong antibody binding site. Also provided are humanized antibodies and fragments thereof that bind to the TF.

L'invention concerne des anticorps présentant une activité anticoagulante supérieure par liaison à un TF (facteur tissulaire) humain naturel à affinité et spécificité élevées. Les anticorps selon l'invention peuvent inhiber de manière efficace la coagulation sanguine <i>in vivo</i> et peuvent se lier à un TF humain naturel, soit seul, soit présent dans une complexe TF:FVII, empêchant de manière efficace la liaison d'un facteur X ou FIX au TF ou à ce complexe, réduisant ainsi la coagulation sanguine. Les anticorps préférés selon l'invention se lient de manière spécifique à un épitope conformationnel prédominant un TF humain naturel, ledit épitope présentant un site de liaison d'anticorps inopinément solide. L'invention concerne également des anticorps humanisés et des fragments de ceux-ci se liant au TF.

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