Abstract: The present invention relates generally to a method of increasing lipid oxidation in a mammal and to agents useful for same. More particularly, the present invention relates to a method of increasing lipid oxidation in a mammal by administering a ligand which interacts with the IL-6 receptor and signals via interaction with a gp130/LIF receptor heterodimer. In a related aspect, the present invention provides a method of increasing insulin sensitivity in a mammal. The method of present invention is useful, inter alia, in the treatment and/or prophylaxis of conditions characterized by unwanted lipid accumulation (such as obesity, obesity induced-metabolic disorders, type II diabetes, dyslipidemia, glucose intolerance, insulin resistance, obstructive sleep apnea, cardiovascular disease or non-alcoholic fatty liver disease) or inadequate insulin sensitivity.

Abstract: 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.

Abstract: 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.

Abstract: The present invention relates generally to a method of increasing lipid oxidation in a mammal and to agents useful for same. More particularly, the present invention relates to a method of increasing lipid oxidation in a mammal by administering a ligand which interacts with the IL-6 receptor and signals via interaction with a gp130/LIF receptor heterodimer. In a related aspect, the present invention provides a method of increasing insulin sensitivity in a mammal. The method of present invention is useful, inter alia, in the treatment and/or prophylaxis of conditions characterised by unwanted lipid accumulation (such as obesity, obesity induced-metabolic disorders, type II diabetes, dyslipidemia, glucose intolerance, insulin resistance, obstructive sleep apnea, cardiovascular disease or non-alcoholic fatty liver disease) or inadequate insulin sensitivity.

Abstract: Described are soluble gp130 polypeptide monomers and dimers, wherein, in a preferred embodiment, at least one of the three amino acid residues Thr102 GIn113 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.

Abstract: 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.

Abstract: The present invention relates to methods for preventing or treating toxicities associated with exposure to ionizing radiation or to chemotherapy. Particularly, the present invention relates to methods for preventing or treating toxicities associated with radiation or chemotherapy comprising administering to a subject in need of such treatment polypeptide complexes comprising an IL-6 linked to a soluble IL-6 receptor, the polypeptide complexes capable of preventing or treating toxicities, particularly xerostomia.

Abstract: Described are codon optimized sgp130 encoding nucleic acid molecules as well as a method for the highly efficient recombinant production of sgp130 in mammalian cells or bacteria using a nucleic acid molecule of the invention.

Abstract: The present invention relates to methods for preventing or treating toxicities associated with exposure to ionizing radiation or to chemotherapy. Particularly, the present invention relates to methods for preventing or treating toxicities associated with radiation or chemotherapy comprising administering to a subject in need of such treatment polypeptide complexes comprising an IL-6 linked to a soluble IL-6 receptor, the polypeptide complexes capable of preventing or treating toxicities, particularly xerostomia.

Abstract: The present invention relates to methods for treating renal failure. Particularly, the present invention relates to methods for treating renal failure by administering to a subject complexes that include a member of the IL-6 family linked to a soluble receptor of the member of the IL-6 family, or isolated polynucleotides encoding same, the complexes capable of activating a gp130 mediated signaling pathway, thereby treating acute or chronic renal failure.

Abstract: 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.

Abstract: The present invention relates generally to a method of increasing lipid oxidation in a mammal and to agents useful for same. More particularly, the present invention relates to a method of increasing lipid oxidation in a mammal by administering a ligand which interacts with the IL-6 receptor and signals via interaction with a gp130/LIF receptor heterodimer. In a related aspect, the present invention provides a method of increasing insulin sensitivity in a mammal. The method of present invention is useful, inter alia, in the treatment and/or prophylaxis of conditions characterised by unwanted lipid accumulation (such as obesity, obesity induced-metabolic disorders, type II diabetes, dyslipidemia, glucose intolerance, insulin resistance, obstructive sleep apnea, cardiovascular disease or non-alcoholic fatty liver disease) or inadequate insulin sensitivity.

Abstract: The present invention relates to methods for treating renal failure. Particularly, the present invention relates to methods for treating renal failure by administering to a subject complexes that include a member of the IL-6 family linked to a soluble receptor of the member of the IL-6 family, or isolated polynucleotides encoding same, the complexes capable of activating a gp130 mediated signaling pathway, thereby treating acute or chronic renal failure.

Abstract: A polypeptide-dimer comprising two soluble gp130 molecules is described, wherein at least one of said soluble gp130 molecules is covalently linked to polyethylene glycol. Furthermore, a pharmaceutical composition containing said dimer and various medical uses are described.

Abstract: A polypeptide-dimer comprising two soluble gp130 molecules is described, wherein at least one of said soluble gp130 molecules is covalently linked to polyethylene glycol. Furthermore, a pharmaceutical composition containing said dimer and various medical uses are described.

Abstract: The present invention concerns a new designer cytokine termed H11, which is constructed by fusion of two soluble components, soluble interleukin 11 receptor (sIL-11 R) and interleukin 11 (IL-11) using their natural sequence and its use for the production of a medicament for treating or preventing a disease selected from the group consisting of a proliferative disease, a cytopathy, radiation damage, an IL-11 dependent inflammatory disorder, IL-11 dependent degenerative disorder and IL-11 dependent or mediated soft tissue disorder.

Abstract: A polypeptide-dimer comprising two soluble gp130 molecules is described, wherein at least one of said soluble gp130 molecules is covalently linked to polyethylene glycol. Furthermore, a pharmaceutical composition containing said dimer and various medical uses are described.

Abstract: Described are codon optimized sgp130 encoding nucleic acid molecules as well as a method for the highly efficient recombinant production of sgp130 in mammalian cells or bacteria using a nucleic acid molecule of the invention.

Abstract: A polypeptide-dimer comprising two soluble gp130 molecules is described, wherein at least one of said soluble gp130 molecules is covalently linked to polyethylene glycol. Furthermore, a pharmaceutical composition containing said dimer and various medical uses are described.

Abstract: The present invention concerns a conjugate comprising two polypeptides with a mutual affinity, the polypeptides being connected with each other via a linker. This invention also concerns the use of such a conjugate to influence interactions between proteins.