Combinatorial interleukin-2 muteins

C - Chemistry – Metallurgy – 12 – N

Patent

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Details

C12N 15/26 (2006.01) A61K 38/20 (2006.01) A61P 35/00 (2006.01) A61P 37/02 (2006.01) C07K 14/55 (2006.01) C12N 1/21 (2006.01) C12N 5/10 (2006.01) C12N 15/63 (2006.01) C12P 21/02 (2006.01)

Patent

CA 2564614

Novel human interleukin-2 (IL-2) muteins or variants thereof, and nucleic acid molecules and variants thereof are provided. Methods for producing these muteins as well as methods for stimulating the immune system of an animal are also disclosed. In addition, the invention provides recombinant expression vectors comprising the nucleic acid molecules of this invention and host cells into which expression vectors have been introduced. Pharmaceutical compositions are included comprising a therapeutically effective amount of a human IL-2 mutein of the invention and a pharmaceutically acceptable carrier. The IL-2 muteins have lower toxicity than native IL-2 or Proleukin ® IL-2, while maintaining or enhancing NK cell-mediated effects, and can be used in pharmaceutical compositions for use in treatment of cancer, and in stimulating the immune response.

L'invention concerne de nouvelles mutéines d'interleukine 2 (IL-2) humaines ou variants de celles-ci, ainsi que des molécules d'acides nucléiques et variants de ceux-ci. Par ailleurs, l'invention concerne des procédés de production de ces mutéines ainsi que des procédés de stimulation du système immunitaire d'un animal. L'invention concerne également des vecteurs d'expression recombinants qui comprennent les molécules d'acides nucléiques de l'invention ainsi que des cellules hôtes dans lesquelles on a introduit des vecteurs d'expression. L'invention concerne en outre des compositions pharmaceutiques qui renferment une dose thérapeutiquement efficace d'une mutéine IL-2 humaine de l'invention ainsi qu'un excipient pharmaceutiquement acceptable. Les mutéines IL-2 présentent par ailleurs une plus faible toxicité par rapport à IL-2 endogène ou la IL-2Proleukin ®, tout en maintenant ou stimulant les effets exercés par les cellules NK, et elles peuvent être utilisées dans des compositions pharmaceutiques destinées au traitement du cancer, ainsi que pour stimuler la réponse immunitaire.

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