Antibodies specific for proteins having polyglutamine...

C - Chemistry – Metallurgy – 07 – K

Patent

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Details

C07K 16/00 (2006.01) C07K 16/18 (2006.01)

Patent

CA 2395700

Antibodies, as well as binding fragments and mimetics thereof, that specifically bind to polyglutamine expansion containing proteins, e.g. mutant huntingtin protein, mutant androgen receptor, mutant dentatorubral- pallidoluysian atrophy gene, are provided. The subject binding agents, e.g. antibodies, fragments and mimetics thereof, etc., are characterized in that they bind to the target polyglutamine expansion containing protein in a manner that differs from the 1C2 antibody, e.g. in terms of affinity, avidity, and the like. Also provided are methods of screening compounds for polyglutamine expansion protein binding modulation activity, as well as pharmaceutical compositions of such agents. In addition, methods and devices for screening samples for the presence of polyglutamine expansion containing proteins, e.g. mutant huntingtin protein mutant androgen receptor, mutant dentatorubral- pallidoluysian atrophy gene, are provided. Finally, nucleic acids encoding the subject antibodies and methods for their expression, including in therapeutic treatment protocols, are provided.

La présente invention concerne des anticorps, ainsi que des fragments de liaison et des analogues de ceux-ci, qui sont de liaison spécifique à des protéines renfermant l'expansion de la polyglutamine, par exemple la protéine huntingtin mutante, le récepteur d'androgènes mutant, le gène d'atrophie dentatorubral-pallidolyuisien mutant. Les agents de liaison de l'invention, par exemple, les anticorps, fragments et leurs analogues, sont caractérisés en ce qu'ils se lient à la protéine contenant l'expansion de polyglutamine cible d'une manière différente de celle de l'anticorps 1C2, par exemple en ce qui concerne l'affinité, l'avidité, et autres. L'invention concerne également des procédés de criblage des composés pour l'activité de modulation des protéines d'expansion de polyglutamine. En outre, l'invention concerne des procédés et des dispositifs de criblage d'échantillons en vue de déterminer la présence de protéines contenant l'expansion de la polyglutamine, par exemple, de la protéine huntingtin mutante, le récepteur d'androgènes mutant, le gène d'atrophie dentatorubral-pallidoluysien. Enfin, l'invention concerne les acides nucléiques codant pour lesdits anticorps et les procédés pour leur expression, y compris dans les protocoles de traitement thérapeutique.

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