Abstract: A therapeutic composition is described that can be used for treating or prevention of diseases association with modulation of activity of human IL-1?. In certain aspects, the disclosed composition is based on engineering of a heterodimeric protein assembly that is capable of binding to human IL-1? and attenuating its function. The heterodimeric protein assembly comprises extracellular portions of human IL1-R1 and of human IL-1RAcP, or their functional fragments. Each, the IL1-R1 portion and the IL-1RAcP portion, is fused to a distinct mutant of Fc portion of the human Ig Gamma-1. The two distinct Fc mutants in the heterodimeric protein assembly are engineered as to favor the heteromeric dimer formation between the two Fc mutants over any homomeric assembly. The therapeutic composition has been formulated for administration into humans and animals.

Abstract: A therapeutic composition is described that can be used for treating or prevention of diseases association with modulation of activity of human IL-1?. In certain aspects, the disclosed invention is based, on engineering of a heterodimeric protein assembly that is capable of binding to human IL-1? and attenuating its function. The heterodimeric protein assembly comprises extracellular portions of human IL1-R1 and of human IL-1RAcP, or their functional fragments. Each, the IL1-R1 portion and the IL-1RAcP portion, is fused to a distinct mutant of Fc portion of the human Ig Gamma-1. The two distinct Fc mutants in the heterodimeric protein assembly are engineered as to favor the heteromeric dimer formation between the two Fc mutants over any homomeric assembly. The therapeutic composition has been formulated for administration into humans and animals.

Abstract: Fully human anti-PD-L1 antibodies and their corresponding applications. Fully human antibodies capable of specifically binding to human PD-L1 were obtained by employing a yeast display library-based screening technique and also by affinity maturation to further improve their affinity for PD-L1. The fully human anti-PD-L1 antibodies show good specificity, affinity and stability. They are capable of enhancing T cell activity by binding to activated T cells, while significantly inhibiting tumor growth, and can be used in the diagnosis and treatment of PD-L1-related cancers and other associated diseases.

Abstract: A therapeutic composition is described that can be used for treating or prevention of diseases association with modulation of activity of human IL-1?. In certain aspects, the disclosed invention is based, on engineering of a heterodimeric protein assembly that is capable of binding to human IL-1? and attenuating its function. The heterodimeric protein assembly comprises extracellular portions of human IL1-R1 and of human IL-1RAcP, or their functional fragments. Each, the IL1-R1 portion and the IL-1RAcP portion, is fused to a distinct mutant of Fc portion of the human Ig Gamma-1. The two distinct Fc mutants in the heterodimeric protein assembly are engineered as to favor the heteromeric dimer formation between the two Fc mutants over any homomeric assembly. The therapeutic composition has been formulated for administration into humans and animals.

Abstract: A pharmaceutical composition is described that can be used for treating or prevention of diseases association with bone resorption, particularly of a metastatic carcinoma. In certain aspects, the composition is based on a polypeptide which includes the leading 215 amino acids of the human osteoprotegerin followed by the Fc portion of the human IgG1 protein. Pharmaceutical formulations are provided that are suitable for administering the pharmaceutical composition into primates via subcutaneous and intravenous routes.

Abstract: The invention relates to the novel substituted 3-arylsulfonyl-pyrazolo[1,5-a]pyrimidines of the general formula 1, pharmaceutically acceptable salts and/or hydrates thereof, serotonin 5-HT6 receptor antagonists and pharmaceutical compositions, and also to method for prophylaxis and treatment of various diseases of central nervous system at humans and warm-blooded animals pathogenesis of which is associated with serotonin 5-HT6 receptors, in particular, Alzheimer's disease, Parkinson's disease, Huntington's disease, schizophrenia, and other neurodegenerative diseases, cognitive disorders and obesity.

Abstract: The invention relates to antagonists of serotonin 5-HT6 receptors simultaneously regulating homeostasis of Ca+2 ions in cells, representing substituted 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles of the general formula 1, pharmaceutically acceptable salts and/or hydrate thereof. In the general formula 1: R1 represents amino group substituent selected from optionally substituted C1-C5 alkyl; R2i is one or more substituents selected from hydrogen, halogen, C1-C3 alkyl, CF3, OCF3; Ar is phenyl optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, substituted amino group, or CF3; or optionally substituted aromatic 6-membered heterocycle comprising 1-2 nitrogen atoms in the cycle; W represents ethylene group —CH2—CH2—, ethenyl group —CH?CH—, or ethynyl group —C?C—. The invention also relates to the novel compounds selected from the compounds of the general formula 1, methods for their preparation, pharmaceutical compositions and methods of their use.

Abstract: The invention relates to novel heterocyclic compounds and to the use thereof, to pharmaceutical compositions containing said chemical compounds as an active ingredient and to the use thereof for producing medicinal preparations for the human being and warm-blood animals for treating diseases caused by the aberrant activity of an Hedgehog (Hh)-signal system, in particular oncological diseases. The invention also relates to the use of the above-mentioned compounds in the form of ‘molecular pharmacological tools’ for examining (in vitro and in vivo) the biochemical features of the Hh-signal system, in particular, the interaction of Hh protein and transmembrane proteins, namely, suppressor Patched (Ptc) and protooncogenic proteins.

Abstract: The invention relates to the use of INSP035 for treatment and/or prevention of fibrotic diseases, in particular of scleroderma.

Abstract: The invention relates to the novel substituted 3-arylsulfonyl-pyrazolo[1,5-a]pyrimidines of the general formula 1, pharmaceutically acceptable salts and/or hydrates thereof, serotonin 5-HT6 receptor antagonists and pharmaceutical compositions, and also to method for prophylaxis and treatment of various diseases of central nervous system at humans and warm-blooded animals pathogenesis of which is associated with serotonin 5-HT6 receptors, in particular, Alzheimer's disease, Parkinson's disease, Huntington's disease, schizophrenia, and other neurodegenerative diseases, cognitive disorders and obesity.

Abstract: The invention relates to antagonists of serotonin 5-HT6 receptors simultaneously regulating homeostasis of Ca+2 ions in cells, representing substituted 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles of the general formula 1, pharmaceutically acceptable salts and/or hydrate thereof. In the general formula 1: R1 represents amino group substituent selected from optionally substituted C1-C5 alkyl; R2, is one or more substituents selected from hydrogen, halogen, C1-C3 alkyl, CF3, OCF3; Ar is phenyl optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, substituted amino group, or CF3; or optionally substituted aromatic 6-membered heterocycle comprising 1-2 nitrogen atoms in the cycle; W represents ethylene group —CH2—CH2—, ethenyl group —CH?CH—, or ethynyl group —C?C—. The invention also relates to the novel compounds selected from the compounds of the general formula 1, methods for their preparation, pharmaceutical compositions and methods of their use.

Abstract: This invention relates to a novel protein (INSP002), herein identified as a secreted protein that is a member of the Dan family of the cystine-knot fold cytokine superfamily and to the use of this protein and nucleic acid sequences from the encoding genes in the diagnosis, prevention and treatment of disease.

Abstract: The invention relates to the use of INSP035 for treatment and/or prevention of fibrotic diseases, in particular of scleroderma.

Abstract: Highly specific hammerhead ribozymes are provided that human target estrogen receptor mRNA. These ribozymes, designated RZ1 through RZ7 provide predictable mRNA cleavage products. Methods for inhibiting estrogen-dependent tumor growth, such as that characteristic of breast cancer, are also provided employing these ribozymes. One or both of the ribozymes may be used together or separately with equal efficiency. The ribozymes possess a sequence region with a catalytic core that provides the attributed catalytic activity to these ribozymes.