Conaris Research Institute Ag

Christian-albrechts-universitat Zu Kiel

Hadasit Medical Research Services and Development Ltd.

Applied Research Systems Ars Holding N.v.

Hadasit Medical Research Services and Development Company

Baker Medical Research Institute

Angewandte Gentechnologie Systeme Gmbh

Akademia Medyczna Im. K. Marcinkowskiego

Stefan Rose-John

Eithan Galun

Dirk Seegert

Nikolaus Rahaus

Georg Wätzig

Joachim Grötzinger

Stefan Schreiber

Jonathan H Axelrod

Georg H Watzig

Jürgen Scheller

Georg Waetzig

Yael Nehemia

Stephanie Tenhumberg

Marc Ehlers

Andrzej Mackiewicz

Malte Peters

Joachim Grotzinger

Matthias Aurich

Ytzhack Marmary

Jessica Daecke

Mark Anthony Febbraio

Daniel Barkan

Georg H Wätzig

Jurgen Scheller

Jonathan Axelrod

Itzhack Marmary

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.

Treatment of obesity

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

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.

Methods for the treatment of radiation or chemotherapy-induced tissue damage

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.

Optimized nucleotide sequences encoding sgp130

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.

Methods for the treatment of renal failure

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.

PEGylated soluble GP130-dimers useful as a medicament

PEGylated soluble gp130-dimers useful as a medicament

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.

Conjugate for modifying interactions between proteins

The present invention relates to a new IL-6 mutein, a DNA sequence coding for it, its use in therapy as well as a pharmaceutical composition comprising it. It is a potent IL-6 antagonist and can be advantageously used as a medicament in the treatment of diseases in which IL-6 has a pathogenetic action, such as, for example, plasmocytoma/myeloma, osteoporosis and neoplastic and auotoimmune diseases.

IL-6 mutein and DNA encoding thereto

Genetic anticancer vaccine

A method for treating an injury of a liver of a subject with a composition featuring a pharmaceutically acceptable amount of an IL-6/sIL-6R complex, preferably Hyper-IL-6. The composition is administered to the subject such that the injury to the liver is treated.

IL-6/SIL-6R complex for promotion of liver functions

Growing community of inventors

Schellhorn, Germany

Stefan Rose-John