Orally deliverable and anti-toxin antibodies and methods for...

A - Human Necessities – 61 – K

Patent

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A61K 39/395 (2006.01) C07K 16/00 (2006.01)

Patent

CA 2592015

The invention provides antibodies with superior therapeutic efficacy and related methods of engineering such antibodies to increase their stability and resistance to proteases, e.g., in the digestive tract. Protease cleavage motifs are identified and subsequently modified to reduce or eliminate cleavage at that site. Methods of employing these orally deliverable antibodies as therapeutic compositions, particularly against gastrointestinal pathogens are also provided herein. In one aspect, the invention provides combinations of monoclonal antibodies, e.g., ~synthetic polyclonals~, that work synergistically to neutralize bacterial toxins, particularly enteric bacterial toxins such as Clostridium difficile toxin A.

La présente invention a trait à des anticorps présentant une efficacité thérapeutique supérieure et des procédés associés de modification génétique de tels anticorps pour accroître leur stabilité et leur résistance aux protéases, par exemple, dans le système digestif. Des motifs de clivage de protéase sont identifiés et ultérieurement modifiés pour réduire ou éliminer un clivage au niveau de ce site. L'invention a également trait à des procédés d'utilisation de ces anticorps aptes à l'administration orale en tant que compositions thérapeutiques, notamment contre des agents pathogènes gastro-intestinaux. Dans un mode de réalisation, l'invention a trait à des combinaisons d'anticorps monoclonaux, par exemple, "des anticorps polyclonaux synthétiques", qui fonctionnent en synergie pour neutraliser des toxines bactériennes, notamment des toxines bactériennes entériques telles que la toxine du Clostridium difficile A.

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