Il-2 selective agonists and antagonists

Details Il-2 selective agonists and antagonists Il-2 selective agonists and antagonists

C - Chemistry, Metallurgy

12

N

C12N 15/26 (2006.01) A61K 38/20 (2006.01) C07K 14/55 (2006.01) G01N 33/50 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2327349

The invention is directed to a polypeptide comprising a human IL-2 mutein numbered in accordance with wild-type IL-2 wherein said human IL-2 is substituted at at least one of positions 20, 88 or 126, whereby said mutein preferentially activates T cells over NK cells. D20H and I, N88G, I, and R, in particular have a relative T cell- differential activity much greater than native IL-2, with predicted associated reduced in vivo toxicity. The invention also includes polynucleotides coding for the muteins of the invention, vectors containing the polynucleotides, transformed host cells, pharmaceutical compositions comprising the muteins, and therapeutic methods of treatment.

L'invention concerne un polypeptide comprenant une mutéine de l'IL-2 humaine numérotée d'après l'IL-2 de type sauvage, ladite IL-2 humaine étant substituée à au moins une des positions 20, 88 ou 126. Cette mutéine active les cellules T de préférence aux cellules NK. D20H et I, N88G, I et R, en particulier, présentent une activité relative de différenciation des cellules T beaucoup plus importante que celle de l'IL-2 native, avec réduction de la toxicité in vivo connexe prédite. L'invention concerne également des polynucléotides codant pour les mutéines de l'invention, des vecteurs contenant ces polynucléotides, des cellules hôtes transformées, des compositions pharmaceutiques comprenant lesdites mutéines, et des méthodes thérapeutiques.

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