Soluble gp130 muteins with improved binding activity

Details Soluble gp130 muteins with improved binding activity Soluble gp130 muteins with improved binding activity

C - Chemistry, Metallurgy

07

K

C07K 14/435 (2006.01)

Patent

CA 2702982

Described are soluble gp130 polypeptide monomers and dimers, wherein, in a preferred embodiment, at least one of the three amino acid residues Thr102 Gln113 or ASn114 of the N-terminal Ig- like domain of gp130 is mutated to Tyr102, Phe113 or Leu114, respectively. These mutations, alone or in combination, specifically enhance binding of gp130 to its ligand complex of interleukin-6 and soluble interleukin-6 receptor, thus increasing the biological activity of the gp130 muteins. In a particularly preferred embodiment, all three mutations are combined in the triple mutein Thr102Tyr/Gln113Phe/Asn114Leu(T102Y/Q113F/N114L). Moreover, a pharmaceutical composition containing said monomers or dimers and various medical uses are described.

L'invention porte sur des monomères et dimères du polypeptide gp130 solubles dans lesquels, dans un mode de réalisation préféré, au moins l'un des trois résidus d'acide aminé Thr102 GIn113 ou ASn114 du domaine de type Ig N-terminal de gp130 est muté respectivement en Tyr102, Phe113 ou Leu114. Ces mutations, individuellement ou en combinaison, augmentent de façon spécifique la liaison de gp130 à son complexe de ligand d'interleukine-6 et de récepteur d'interleukine-6 soluble, augmentant ainsi l'activité biologique des mutéines gp130. Dans un mode de réalisation particulièrement préféré, ces trois mutations sont combinées dans la triple mutéine Thr102Tyr/Gln113Phe/Asn114Leu (T102Y/Q113F/N114L). De plus, l'invention concerne une composition pharmaceutique contenant lesdits monomères ou dimères et diverses utilisations médicales.

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