117 results about "RANKL" patented technology

The present invention relates to non-naturally occurring variant Tumor Necrosis Factor Super Family member proteins with reduced immunogenicity. More specifically, the present invention relates to variant BAFF, RANKL, TRAIL, CD40L and APRIL proteins with reduced immunogenicity.

The present invention relates to a method for predicting the risk of a subject developing a cardiovascular event comprising detecting at least one biomarker in (a sample of) the cardiovascular system from said subject, wherein said biomarker comprises at least one protein selected from the group consisting of Tumor Necrosis Factor Alpha Precursor; Lysosomal-associated Membrane Protein (1); Interleukin-5 Precursor; Interleukin-6 Precursor; C-C Motif Chemokine (2) Precursor; C-C Motif Chemokine (5) Precursor RANTES; Cathepsin L1 Precursor; Adenylate Kinase (1); Leukotriene B4 Receptor (1); Complement Factor D; Secreted Phosphoprotein (1); Small Inducible Cytokine A17 Precursor; C-X-C Motif Chemokine (10) Precursor; Tumor Necrosis Factor Ligand Superfamily Member (11)(RANKL); C-C Motif Chemokine (18) Precursor; 72 kDa Type IVCollagenase Precursor; Neutrophil Collagenase Precursor; fatty acid binding protein (4); calpain (2), (m / II) large subunit; Macrophage Migration Inhibitory Factor; Cathepsin S Precursor; Interleukin (13) Precursor; and soluble ICAM-1.

Devices and methods for stimulation of the vagus nerve to modulate (e.g., reduce, suppress, etc.) bone erosion. Methods and apparatus for modulating bone erosion may modulate levels of Receptor Activator for Nuclear Factor κB Ligand (RANKL), and / or to modulate (increase, enhance, etc.) osteoprotegerin (OPG) and / or OPG / RANKL ratio. Devices may include electrical stimulation devices that may be implanted, and may be activated to apply current for a proscribed duration, followed by a period without stimulation.

A method for constructing stable bioactive fusion proteins of the difficult to express tumor necrosis factor superfamily (TNFSF), and particularly members CD40L (CD154) and RANKL / TRANCE, with collecting, particularly pulmonary surfactant protein D (SPD) is described. Single trimers of these proteins lack the full stimulatory efficacy of the natural membrane forms of these proteins in many cases. The multimeric nature of these soluble fusion proteins enables them to engage multiple receptors on the responding cells, thereby, mimicking the effects of the membrane forms of these ligands. For CD40L-SPD, the resulting protein stimulates B cells, macrophages, and dendritic cells, indicating its potential usefulness as a vaccine adjuvant. The large size of these fusion proteins makes them less likely to diffuse into the circulation, thereby limiting their potential systemic toxicity. This property may be especially useful when these proteins are injected locally as a vaccine adjuvant or tumor immunotherapy agent to prevent them from diffusing away. In addition, these and other TNFSF-collectin fusion proteins present new possibilities for the expression of highly active, multimeric, soluble TNFSF members.

Isolated human antibodies or antigen-binding fragments thereof, which specifically bind to human RANKL and block hRANKL binding to a RANK receptor, are provided. The antibodies are useful in preventing or treating disorders and / or diseases, which are associated with RANKL / RANK interactions, including bone disorders or cancer.

The invention relates to a RANKL-TNF sample region mouse monoclonal antibody and its preparation method and use. The RANKL-TNF sample region mouse monoclonal antibody is extracted from a RANKL-TNF sample region mouse monoclonal antibody hybridoma cell strain and has the preservation number of CGMCC NO.6853. The RANKL-TNF sample region mouse monoclonal antibody and its related reagents can effectively neutralize TNF-alpha in vitro thereby inhibiting cell apoptosis caused by TNF-alpha, and neutralize RANKL in vitro thereby inhibiting osteoclast generation. The RANKL-TNF sample region mouse monoclonal antibody can effectively relieve an acute inflammation degree, improve bone mass of a mouse suffering from osteoporosis, improve a cancellous bone trabecula microstructure, and effectively improve osteoporosis symptoms.

The invention provides an RANKL-TNF (Receptor Activator of Nuclear Factor Kappa-B Ligand-Tumour Necrosis Factor) sample region fusion protein, and in particular relates to a fusion protein of an RANKL-TNF sample region protein and a Th2 cell epiposition segment with broad host range property. An experiment shows that an antibody produced by an RANKL-TNF sample region fusion protein immune mouse has the effect of combining RANKL with TNF-alpha, can be used for treating diseases such as rheumatoid arthritis and the like and can play effects of antagonistic bone destruction and inflammation inhibition. The RANKL-TNF sample region fusion protein disclosed by the invention can be used as a therapeutic vaccine and provides a new therapeutic approach and thinking for the diseases such as rheumatoid arthritis and the like. According to the invention, the RANKL-TNF sample region fusion protein is expressed in vitro, and therefore the method has the advantages of high expression yield, strong controllability and relatively low production cost;, and the product has good immunogenicity and is easy to realize mass production.

The invention relates to RANKL-Fc fusion protein, a preparation method and the application thereof. The RANKL-Fc fusion protein has P1-P2 or P1-L-P2 structural style; wherein, the P1 is the extracellular region fragment of PANKL protein, P2 is the Fc part of human I g C, and L is linker peptide. The fusion protein provided by the invention can be used for preparing medicines used for treating bone resorption diseases.

The invention discloses a germacrane type sesquiterpene lactone compound, and a preparation method and application thereof. The germacrane type sesquiterpene lactone compound has structural formulas shown as formulas (I) to (IV). In the formulas (I) to (IV), R1 is H or OH; R2 is OH, OMeacr, or OEt; R3 is OAng, OH, or OMeacr; R4 is OTig or OAng; and R5 is CH2OH or CHO. The germacrane sesquiterpenelactone compound provided by the invention has an obvious differentiation inhibition effect on RANKL-induced osteoclasts, the IC50 of most of the compounds is 10.0 [mu]M or below, cytotoxicity is notshown under 10 [mu]M, and the germacrane sesquiterpene lactone can be applied to preparation of drugs for treating and / or preventing osteoporosis and has a good application prospect.

The invention provides fusion protein of a human interleukin receptor C (IL-17RC). The fusion protein contains a key region where the human IL-17RC is bonded with interleukin 17A(IL-17A) and interleukin 17F(IL-17F)and a human IgG1 Fc segment. The IL-17RC-hFc fusion protein provided by the invention has the capacity of binding the IL-17A and the IL-17F, can inhibit release of inflammatory cytokines and expression of RANKL molecules irritated by the IL-17A and the IL-17F, can be used for treating IL-17 associated autoimmune diseases such as rheumatoid arthritis and the like, and exerts the effects of inhibiting inflammation and antagonizing bone destruction. The IL-17RC-hFc fusion protein can serve as a therapeutic bait receptor and provides a new therapeutic approach and thought for diseases such as rheumatoid arthritis and the like. The IL-17RC-hFc fusion protein is subjected to prokaryotic expression in vitro; and the method is high in expression quantity, high in controllability, relatively low in production cost and easy in large-scale production.

The present invention pertains to the provision of trimeric binding units which bind to trimeric cytokines. In particular there is provided a trimeric polypeptide comprising a trimerising domain and three monomers with binding members capable of binding a trimeric cytokine. Preferably , the trimeric binding units bind in a manner such that upon binding, all receptor binding sites of the trimeric cytokine are substantially blocked, and hence the potential biological activity of the trimeric cytokine is suppressed. In one aspect the invention relates to trimeric binders capable of binding to trimeric cytokines of the Tumor necrosis factor ligand superfamily, such as TNF, TRAIL, RANKL, TWEAK, APRIL and BAFF.

The present invention provides an inhibitor of an autoimmune response to a periodontal bacterial enzymatic degradation product of keratin in gingival epithelium in a mammal having a periodontal bacterium in the oral cavity, containing a substance having affinity to the keratin or a degradation product thereof and / or a substance having affinity to an autoantibody to the degradation product, an agent for the prophylaxis and / or treatment of a periodontal disease and / or a complication thereof; a RANKL expression inhibitor containing a substance having affinity to the keratin or a degradation product thereof; and a method of diagnosing a periodontal disease including detecting the keratin or a degradation product thereof and / or an autoantibody thereto.

Novel methods and drug products for treating inflammatory joint diseases such as rheumatoid arthritis and associated arthritides are disclosed. The methods and products employ various serum markers of bone and cartilage metabolism or destruction, including cartilage oligomer matrix protein (COMP) and Receptor activator of NFB ligand (RANKL), as biomarkers to assess the effect of IL-17A antagonists on joint destruction in inflammatory joint diseases.

The invention discloses an application of nitidine chloride in resisting osteoporosis and in preventing and treating bone loss diseases caused by osteoclasts; the inventor, through researches, discovers that the nitidine chloride can inhibit the formation of the osteoclasts and a bone absorption function in a dose-dependent mode for the first time; it discovers that the nitidine chloride, by intervening RANKL-activated NF-kB and NFAT signaling pathways, can develop an effect of inhibiting the osteoclasts; and by establishing an ovariectomized osteoporosis mouse model, it further provides the effect of the nitidine chloride on the osteoclasts. The nitidine chloride can be used as an ideal medicine for preventing and treating the bone loss diseases caused by the osteoclasts in the future.

The present invention relates to fully humanized antibodies, specifically to a fully human anti-RANKL antibody, a nucleic acid molecule encoding the antibody, and a composition containing the antibody. The present invention further relates to uses of the antibody in preparation of drugs for prevention and treatment of bone loss related diseases, especially osteoporosis, arthritis osteolysis damage or tumor bone metastasis and other diseases. According to the present invention, the antibody is specifically bound with human RANKL and blocks the activity of the human RANKL while the potential immunesuppression of the human RANKL on human body is reduced, the antibody has good stability, and the defect of the non-uniformity (heterogeneity) of the IgG2 antibody production on the batch quality identification is avoided.

The invention discloses a bone-marrow-derived osteoclast culturing method, belonging to the technical field of cell culturing, comprising the steps of: subjecting an extracted bone marrow to treatmentby a separation solution to obtain monocytes, washing, adding a complete culture medium and macrophage colony stimulating factor (M-CSF) to the obtained monocytes, inoculating into a 96-pore plate, and adding a culture medium containing RANKL and M-CSF for culturing on a second day, wherein the complete culture medium is prepared by adding fetal bovine serum and double antibodies into an MEM Alpha basic medium. The bone-marrow-derived osteoclast culturing method has the characteristics of shortened culturing time and reduced culturing cost, so that the monocytes (osteoclast precursor cells) which can be differentiated into osteoclasts and obtained by bone marrow separation have higher purity, the cultured osteoclasts have comparative or even better effect, and the osteoclasts have a widerrange at the respect of enzyme activity and quantity, for providing a finer, more rapid and convenient culture method for screening drugs.

Flt3-ligand can be used to generate large numbers of dendritic cells from hematopoietic progenitor and stem cells. Flt3-ligand can be used to augment immune responses in vivo, and expand dendritic cells ex vivo. Such dendritic cells can then be used to present tumor, viral or other antigens to naive T cells, can be useful as vaccine adjuvants. When flt3-L is used and / or administered in combination with other reactive agents, e.g. CD40 binding proteins, 4-1BBL or antibodies reactive with 4-1BB, CD30 ligand antagonists, RANKL, and / or interferon alpha the combination further enhances immune responses and the effectiveness of vaccine adjuvants.

The invention provides a constructing object for expressing receptor activator of nuclear factor kappa B ligand (RANKL)-HBaAg recombinant protein and a preparation method thereof. The constructing object comprises 1 to 15 expression boxes, wherein each expression box comprises an initiating signal element alternative oxidase (AOX) (a), RANKL-HBsAg recombinant protein coding sequences (b) and a termination signal element AOX (TT). The invention also provides yeast cells, virus-like particles and a purpose of the particles, wherein the yeast cells comprise the constructing object, the virus-like particles are generated by the yeast cells and comprise the RANKL-HBsAg recombinant protein. The yeast cells constructed in the invention can be used for generating a large amount of RANKL-HBsAg recombinant protein, so the RANKL-HBsAg recombinant protein is used for treating or preventing diseases or symptoms such as osteoporosis and the like relative to RANK / RANKL / osteoprotegerin (OPG) systems.

The invention discloses a mouse RANKL (Receptor Activator of Nuclear Factor Kappa B Ligand) mutant as well as establishment, expression and application of an expression carrier of the mutant, provides the mouse RANKL mutant, an establishment method of the expression carrier of the mouse RANKL mutant, and a preparation method for transfecting the expression carrier of the mouse RANKL mutant into a cell, and further provides a cell and an expression system for expressing the expression carrier of the mouse RANKL mutant. The problem in the prior art that the mouse RANKL cannot be conveniently and efficiently studied is solved.

The invention discloses application of 2-bromopalmitate (2-BP) in preparation of drugs for prevention and treatment of bone loss related diseases, and belongs to the technical field of medicine. The invention, for the first time, clearly defines that 2-BP can inhibit osteoclast differentiation process of BMMs stimulated by RANKL through various experimental techniques, including tartrate resistantacid phosphatase staining, phalloidin fluorescence staining, bone lamella bone resorption function evaluation, reverse transcription real-time fluorescence quantitative PCR, Western blot, etc. In addition, the invention clearly states that 2-BP also has effects in inhibiting osteoclast differentiation and activation in vivo, and 2-BP can significantly alleviate the pathological process of massivebone loss caused by estrogen deficiency through the establishment of a mouse model of ovariectomy-induced osteoporosis, thus providing experimental data basis in vivo for the role of 2-BP in the prevention and treatment of bone loss related diseases.

The invention discloses an application of a cyclic polypeptide CST-14 in preparation of a drug for treating osteoporosis. The CST-14 can be directly combined with a key receptor RANK in an osteoporosis process to antagonize an osteoclast induction function caused by RANKL and to play a protective role in the osteoporosis. An in vitro cell experiment result shows that the CST-14 can antagonize an osteoclast differentiation process caused by an osteoporosis key molecule RANKL. Meanwhile, an animal model shows that the CST-14 can inhibit the occurrence of the osteoporosis and improve disease conditions, does not have obvious toxic and side effects after long-term use, can be applied to the field of osteoporosis treatment and has broad application value and market prospect.

The present invention provides an osteogenesis enhancer comprising a molecule capable of acting on RANKL that enhances differentiation, proliferation, maturation, or calcification of osteoblasts or cells capable of differentiating into osteoblasts. A pharmaceutical composition for treatment or prevention of bone metabolism diseases associated with osteopenia, which comprising, as an active ingredient, a compound that acts on RANKL located on osteoblasts or cells capable of differentiating into osteoblasts and promotes differentiation, proliferation, maturation, or calcification of osteoblasts or cells capable of differentiating into osteoblasts is provided.

The invention discloses a new application of aurantiamide alcohol ester as an MMP-9 inhibitor. Under the condition that the aurantiamide alcohol ester has no cytotoxicity to osteoclast precursor cellsRAW 264.7, the capability of differentiation of RAW 264.7 cells induced by RANKL into osteoclasts is remarkably inhibited, and a certain concentration dependence is shown; follow-up research finds that the aurantiamide alcohol ester significantly reduces the expression of MMP-9 in the osteoclast formation process, thereby inhibiting osteoclast differentiation and formation. The invention discloses the application of the aurantiamide alcohol ester in preventing and treating osteolytic diseases, wherein the aurantiamide alcohol ester can be used for preventing and treating osteolytic diseases including bone destruction, osteoporosis and the like together with a medicine prepared from a conventional medicinal carrier. The invention provides a new medicine for preventing and treating osteoporosis, and has a great clinical application value.

The invention relates to methods and compositions for inhibiting the trimerization of ligands belonging to the TNF superfamily. In particular, the invention relates to inhibiting RANKL trimerization. Accordingly, the methods and compositions provided herein can be used to treat disorders associated with increased RANK signalling, in particular those related to bone loss. Novel compounds that inhibit trimerization of ligands belonging to the TNF superfamily are also provided.

This invention provides a method for administration of an effective amount of RANKL-binding molecules that act on prechondrocytes and / or mesenchymal stem cells, accelerate cartilage differentiation, proliferation, and maturation of such cells, enhance chondrocyte differentiation, and induce chondrocyte proliferation to induce chondrocyte proliferation and differentiation or increase cartilage matrix production and a pharmaceutical composition used for inducing chondrocyte proliferation and differentiation or increasing cartilage matrix production. The pharmaceutical composition used for treatment or prevention of a chondropathies comprises, as an active ingredient, a compound that acts on prechondrocytes and / or mesenchymal stem cells and induces at least one of the following: (a) acceleration of prechondrocyte and / or mesenchymal stem cell differentiation; (b) acceleration of prechondrocyte and / or mesenchymal stem cell proliferation; (c) acceleration of prechondrocyte and / or mesenchymal stem cell maturation; (d) enhancement of chondrocyte differentiation; (e) chondrocyte proliferation; and (f) increased production of the cartilage matrix.

The invention discloses application of kavain in preparing drug for treating osteoporosis. Impact of kavain on osteoclast differentiation, osteoclast absorption and osteoblast differentiaon is evaluated through tartrate-resistant acid phosphatase dyeing, immunofluorescence, reverse transcription-polymerase chain reaction and immunoblotting analysis. Results show that kavain inhibits RANKL inducedosteoclast by blocking NFAT and MAPK passages mediated by calcium while NF-kB is unaffected; kavain also inhibits bone resorption o osteoclast and has no obvious impact on differentiation and proliferation of osteoblast. In addition, kavain can inhibit formation of osteoclast to bone loss of ovariectomized mice. Data display that osteoclast of kavain which is a natural compound has specific effect, which shows that kavain has potential value in treating osteoporosis diseases.

The invention provides an antibody pair for detecting RANKL content in serum and application thereof. According to the invention, RANKL antigen is divided into two sequences of N end (SEQ ID NO: 2) and C end (SEQ ID NO: 3), and the two sequences are respectively used for immunizing mice to screen antibody pairs anti AntiRANKL_N and anti AntiRANKL_C with high specificity and high sensitivity. The antibody pair can effectively determine RANKL content in serum, and is convenient for diagnosis and treatment of osteoporosis.

The invention discloses an application of an isoindolone compound in preparation of a medicine for preventing and treating osteolytic diseases. The isoindolone compound has a structure as shown in a formula (I) which is described in the specification. The isoindolone compound can remarkably inhibit the differentiation capacity of bone marrow-derived macrophages BMMs induced by RANKL to osteoclastsand the bone resorption capacity of the osteoclasts, and is concentration-dependent; a subsequent mechanism research finds that the isoindolone compound inhibits expression of a transcription factorNFATc1 by inhibiting activation of RANKL-induced MAPK and PI3K / AKT signal transduction pathways, so that expression of osteoclast related genes is reduced, and the capacity of inhibiting osteoclast differentiation and bone resorption is exerted. Besides, the isoindolone compound does not influence differentiation of osteoblasts, application of the isoindolone compound in prevention and treatment of osteolytic diseases is disclosed, and the isoindolone compound can be used for preventing and treating the osteolytic diseases together with a pharmaceutical composition prepared from a conventionalmedicinal carrier.

The invention discloses an application of a substituted guanidyl-containing derivative in preparation of an osteoclast differentiation inhibitor. The substituted guanidyl-containing derivative has a direct and remarkable inhibition effect on RANKL-induced osteoclast differentiation and bone resorption activity, so that the substituted guanidyl-containing derivative can be used as an osteoclast differentiation inhibitor drug for treating diseases treated by an osteoclast differentiation inhibitor.