Method for down-regulating il5 activity

C - Chemistry – Metallurgy – 12 – N

Patent

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C12N 15/24 (2006.01) A61K 31/70 (2006.01) A61K 39/00 (2006.01) A61K 39/08 (2006.01) A61K 39/385 (2006.01) A61K 39/39 (2006.01) A61K 48/00 (2006.01) A61P 37/00 (2006.01) C07K 14/54 (2006.01) C12N 1/19 (2006.01) C12N 1/21 (2006.01) C12N 5/10 (2006.01) C12N 15/70 (2006.01) C12N 15/86 (2006.01) G01N 33/68 (2006.01)

Patent

CA 2370391

The present invention relates to improvements in therapy and prevention of conditions characterized by an elevated level of eosinophil leukocytes, i.e. conditions such as asthma and other chronic allergic diseases. A method is provided for down-regulating interleukin 5 (IL5) by enabling the production of antibodies against IL5 thereby reducing the level of activity of eosinophils. The invention also provides for methods of producing modified IL5 useful in this method as well as for the modified IL5 as such. Also encompassed by the present invention are nucleic acid fragments encoding modified IL5 as well as vectors incorporating these nucleic acid fragments and host cells and cell lines transformed therewith. The invention also provides for a method for the identification of IL5 analogues which are useful in the method of the invention as well as for compositions comprising modified IL5 or comprising nucleic acids encoding the IL5 analogues. The preferred embodiment of the present invention entails the use of variants of IL5, where foreign T helper epitopes are introduced so as to induce production of cross-reactive antibodies capable of binding to autologous IL5.

L'invention concerne des améliorations relatives à la thérapie et à la prévention d'états caractérisés par un niveau élevé de leucocytes eosinophiles, à savoir des affections comme l'asthme et autres maladies allergiques chroniques. L'invention concerne un procédé de régulation négative de l'IL-5 qui consiste à lancer la production d'anticorps vis-à-vis de l'IL-5, ce qui permet de réduire le niveau d'activité des eosinophiles. L'invention concerne en outre des procédés permettant de produire une IL-5 modifiée utile aux fins du procédé décrit et utile en tant que telle. L'invention concerne en outre des fragments d'acide nucléique codant l'IL-5 modifiée, et des vecteurs renfermant ces fragments, ainsi que des cellules hôtes et des lignées cellulaires transformées par lesdits fragments. L'invention concerne par ailleurs un procédé d'identification d'analogues de l'IL-5 qui sont utiles aux fins du procédé décrit, et des compositions renfermant l'IL-5 modifiée ou renfermant des acides nucléiques qui codent les analogues en question. En mode de réalisation préféré, on utilise des variants de l'IL-5, moyennant quoi des épitopes T auxiliaires étrangers sont introduits afin d'induire la production d'anticorps à activité croisée capables de se lier à l'IL-5 autologue.

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