Abstract: The combination of an interleukin-6 (IL-6) antagonist and an antiproliferative drug is described. In its preferred embodiment, the present invention describes the combination of an IL-6 superantagonist, particularly a superantagonist totally incapable of binding gp130 and an antiproliferative drug belonging to the glucocorticoid class (SANT-7 and dexamethasone). The combination according to the present invention has shown surprising synergism in an animal model of multiple myeloma and the ability to overcome the resistance to the antiproliferative drug developed by myeloid cells. The combination according to the present invention is useful for the preparation of a medicament for the treatment of tumours, particularly IL-6-dependent tumours.

Abstract: Synthetic polynucleotides encoding human carcinoembryonic antigen (CEA) are provided, the synthetic polynucleotides being codon-optimized for expression in a human cellular environment. The gene encoding CEA is commonly associated with the development of human carcinomas. The present invention provides compositions and methods to elicit or enhance immunity to the protein product expressed by the CEA tumor-associated antigen, wherein aberrant CEA expression is associated with a carcinoma or its development. This invention specifically provides adenoviral vector and plasmid constructs carrying codon-optimed human CEA and discloses their use in vaccines and pharmaceutical compositions for preventing and treating cancer.

Abstract: Cytokines, including muteins thereof, which are biologically inactive in humans but remain immunogenic, are used in pharmaceutical compositions to promote a neutralizing immune response against native cytokines when administered to a subject in need thereof to treat homeostatic disorders and disorders associated with an overproduction of cytokines.

Abstract: Helper dependent adenoviral vectors encoding erythropoietin (epo) provide high levels of epo to achieve a long-term therapeutically effective dosage, and allow for repeat administration to patients with disorders such as anaemia of Chronic Renal Failure (CFR), anaemias due to beta-thalassaemia, and sickle cell anaemia (SCA).

Abstract: The subject matter of the present invention are recombinant defective adenoviruses comprising a heterologous DNA sequence coding for a mutein having the activity of human Interleukin 6 (hIL-6) antagonists or superantagonist. Moreover, the invention refers to therapeutical uses thereof, in particular for preparing pharmaceutical compositions for treating and/or preventing pathologies caused by hIL-6 overproduction.

Abstract: The subject matter of the present invention are recombinant defective adenoviruses comprising a heterologous DNA sequence coding for a mutein having the activity of human Interleukin 6 (hIL-6) antagonists or superantagonist. Moreover, the invention refers to therapeutical uses thereof, in particular for preparing pharmaceutical compositions for treating and/or preventing pathologies caused by hIL-6 overproduction.

Abstract: The present invention relates to human interleukin-6 receptor antagonists which are incapable of binding to the receptor chain responsible for transduction of the signal associated with interleukin-6, namely, gp130. The present invention also relates to DNA encoding human interleukin-6 receptor antagonists.

Abstract: It is known that the ligands of the group of cytokines similar to Interleuk 6 (IL-6), that is Oncostatin M (OSM), Leukemia Inhibitory Factor (LIF), Ciliary Neurotrophic Factor (CNTF) and Interleukin 11 (IL-11), induce the formation of a receptor complex of which the membrane molecule gp 130 is a part. The present invention refers to a methodology for selecting superagonists, antagonists and superantagonists of human interleukin-6 comprising the following operations: comparing the amino acid sequence of bovine granulocyte colony stimulating factor (bG-CSF) with the sequence of said hormone; and on the basis of the above comparison, formulating a three dimensional model of said hormone, which allows the identification of residues that form the site of interaction with the specific receptor (Site 1) and those that constitute the site of interaction with gp 130 (Site 2) respectively.

Abstract: Disclosed are interleukin-6 receptor agonists. These receptor agonists were enerated by mutating amino acid positions 175, 176, 177, 181, and/or 183 of human interleukin-6.

Abstract: It is known that the ligands of the group of cytokines similar to Interleukin 6 (IL-6), that is Oncostatin M (OSM), Leukemia Inhibitory Factor (LIF), Ciliary Neurotrophic Factor (CNTF) and Interleukin 11 (IL-11), induce the formation of a receptor complex of which the membrane molecule gp 130 is a part. The present invention refers to a methodology for selecting superagonists, antagonists and superantagonists of human interleukin-6 comprising the following operations: comparing the amino acid sequence of bovine granulocyte colony stimulating factor (bG-CSF) with the sequence of said hormone; and on the basis of the above comparison, formulating a three dimensional model of said hormone, which allows the identification of residues that form the site of interaction with the specific receptor (Site 1) and those that constitute the site of interaction with gp 130 (Site 2) respectively.

Abstract: Disclosed are interleukin-6 receptor antagonists. These receptor antagonists are generated by mutating amino acid positions 31, 35, 118, 121, 175, 176 and/or 183 of human interleukin-6.

Abstract: The present invention is drawn to mutant interleukin 6, which has the amino acid arginine in position 176, replacing serine in position 176 with wild-type interleukin 6. The mutant interleukin 6 of the present invention has greater biological activity than the wild-type protein. The present invention is further drawn to methods of making mutant interleukin 6, having arginine at position 176 and methods of using the same.