C - Chemistry – Metallurgy – 12 – N
Patent
C - Chemistry, Metallurgy
12
N
C12N 15/62 (2006.01) A61K 31/7088 (2006.01) A61K 38/19 (2006.01) A61K 38/20 (2006.01) A61K 39/00 (2006.01) A61K 48/00 (2006.01) C07K 14/525 (2006.01) C07K 14/54 (2006.01) C07K 16/24 (2006.01) C07K 19/00 (2006.01) C12N 15/24 (2006.01) C12N 15/28 (2006.01) C12P 21/02 (2006.01)
Patent
CA 2467052
The present invention relates to novel immunogenic variants of multimeric proteins such as immunogenic variants of interleukin 5 (IL5) and tumour necrosis factor alpha (TNF, TNF.alpha.). The variants are, besides from being immunogenic in the autologous host, also highly similar to the native 3D structure of the proteins from which they are derived. Certain variants are monomeric mimics of the multimers, where peptide linkers (inert or T helper epitope containing) ensure a spatial organisation of the monomomer units that facilitate correct folding. A subset of variants are monomer TNF.alpha. variants that exhibit a superior capability of assembling into multimers with a high structural similarity to the native protein. Also disclosed are methods of treatment and production of the variants as well as DNA fragments, vectors, and host cells.
L'invention concerne des variants immunogènes de protéines multimères tels que des variants immunogènes d'interleukine 5 (IL5) et du facteur alpha de nécrose tumorale (TNF, TNF.alpha.). Ces variants, outre leur effet immunogène chez l'hôte autologue, possèdent une structure 3D très similaire à celle, native, des protéines desquelles ils sont dérivés. Certains variants sont des mimétiques monomères des multimères, dans lesquels des lieurs peptidiques (inertes ou contenant un épitope de lymphocyte T auxiliaire) assurent l'organisation spatiale des unités monomères facilitant ainsi un repliement correct. Un sous-ensemble de variants est constitué de variants de TNF.alpha. monomère qui montrent un possibilité supérieure d'assemblage en multimères avec une similarité structurale élevée à la protéine native. L'invention concerne aussi des méthodes de traitement et des procédés de production de ces variants, ainsi que des fragments d'ADN, des vecteurs et des cellules hôtes.
Bratt Tomas
Klysner Steen
Mouritsen Soren
Nielsen Finn Stausholm
Voldborg Bjorn
Pharmexa A/s
Sim & Mcburney
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