Monoclonal antibodies and antibody cocktail for detection of...

A - Human Necessities – 61 – K

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A61K 39/00 (2006.01) A61K 39/395 (2006.01) A61K 39/40 (2006.01) A61K 39/42 (2006.01) A61K 49/00 (2006.01) C07K 14/47 (2006.01) C07K 16/00 (2006.01) C07K 16/18 (2006.01) C12P 21/04 (2006.01) C12P 21/08 (2006.01) G01N 33/53 (2006.01) G01N 33/543 (2006.01) G01N 33/567 (2006.01) G01N 33/68 (2006.01)

Patent

CA 2379349

Methods to detect prion or PrP-Sc protein as an indication of transmissible spongiform encephalopathies (TSEs) are described. In one aspect, the invention is directed to monoclonal antibodies that specifically bind a conserved epitope of prion proteins and use of the antibodies in immunoassays to detect PrP-Sc, in fixed or unfixed tissue, as an indication of the presence of TSE infection. In another aspect, the invention is directed to a monoclonal antibody cocktail having the monoclonal antibody in combination with a second monoclonal antibody which specifically binds to a second conserved epitope of prion proteins. One or both monoclonal antibodies of the cocktail can recognize epitopes found in all mammalian species in which a natural TSE has been reported and in a number of closely related species. Thus, the antibody cocktail provides high sensitivity, defined specificity, and broad reactivity to PrP proteins in spite of interspecies and intraspecies variation of species such as ruminant livestock, cats, mink, humans, and non-human primates.

L'invention concerne des méthodes de détection de protéines prions (PrP-Sc) indicatrices des encéphalopathies spongiformes transmissibles (TSE). Un aspect de l'invention porte sur des anticorps monoclonaux se liant spécifiquement à un épitope conservé de protéines prions, et sur l'utilisation des anticorps dans des immunoessais permettant de détecter, dans des tissus fixés ou non fixés, la PrP-Sc indicatrice de la présence d'infection TSE. Un autre aspect de l'invention concerne un cocktail d'anticorps monoclonaux, dans lequel un premier anticorps monoclonal est combiné à un second anticorps monoclonal qui se lie spécifiquement à un second épitope conservé de protéines prions. L'un des anticorps monoclonaux du cocktail, ou les deux, peuvent reconnaître des épitopes identifiés dans toutes les espèces mammifères, dans lesquelles une TSE naturelle a été signalée, et dans un grand nombre d'espèces étroitement associées. Ainsi, le cocktail d'anticorps confère aux protéines PrP une sensibilité élevée, une spécificité déterminée et une réactivité étendue, malgré des variations interspécifiques et intraspécifiques d'espèces, telles que les ruminants, les chats, les visons, l'homme et les primates non humains.

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