Christian-albrechts-universitat Zu Kiel

Conaris Research Institute Ag

Jürgen Scheller

Stefan Rose-John

Joachim Grötzinger

Georg Wätzig

Matthias Aurich

Stephanie Tenhumberg

Georg H Wätzig

Nucleic acid molecule selected from the group consisting of (a) a nucleic acid molecule having a nucleotide sequence shown in SEQ ID: NO 1, (b) a nucleic acid molecule which encodes a peptide having an amino acid sequence shown in SEQ ID: NO 2, (c) a nucleic acid molecule whose complementary strand hybridizes to a nucleic acid molecule according to (a) or (b) and which codes for a peptide which binds to ciliary neurotrophic factor receptor (CNTFR), the peptide binding with lower affinity than ciliary neurotrophic factor to the interleukin-6 receptor (IL-6R), (d) a nucleic acid molecule whose nucleotide sequence differs from the nucleotide sequence of a nucleic acid molecule according to (c) due to the degenerated genetic code, the codon at positions 82-84 of the nucleic acid molecule according to (a) coding for a non-positively charged amino acid, and the peptide at position 28 shown in SEQ ID: NO 2 having a non-positively charged amino acid residue.

Ciliary neurotrophic factor variants

Described are soluble gp130 polypeptide monomers and dimers, wherein, in a preferred embodiment, at least one of the three amino acid residues ThrGlnor Asnof the N-terminal Ig-like domain of gp130 is mutated to Tyr, Pheor Leu, 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.

Soluble GP130 muteins with improved binding activity

Growing community of inventors

Neuss, Germany

Jürgen Scheller