91 results about "RANKL Protein" 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 is related to the fields of molecular biology, virology, immunology and medicine. The invention provides a composition comprising an ordered and repetitive antigen or antigenic determinant array, and in particular a RANKL protein, RANKL fragment or RANKL peptide-VLP-array. More specifically, the invention provides a composition comprising a virus-like particle and at least one RANKL protein, RANKL fragment or RANKL peptide bound thereto. The invention also provides a process for producing the conjugates and the ordered and repetitive arrays, respectively. The compositions of the invention are useful in the production of vaccines for the treatment of bone diseases and as a pharmaccine to prevent or cure bone diseases and to efficiently induce immune responses, in particular antibody responses. Furthermore, the compositions of the invention are particularly useful to efficiently induce self-specific immune responses within the indicated context.

The present invention provides a RANK (receptor activator of NF-κB) inhibitor consisted of a TRAF-6 (TNF receptor-associated factor-6) binding domain attached to a leader sequence. The peptide inhibitor inhibits RANKL (RANK ligand)-mediated osteoclast differentiation, thus indicating that targeted disruption of interaction between RANK and TRAF6 may prove useful as a therapeutic for metabolic bone disorders, leukemia, arthritis, and metastatic cancer of the bone.

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.

A novel method for detection of an inflammatory disease and a novel composition for prevention or treatment of an inflammatory disease are provided. The method for detection of an inflammatory disease comprises using RANKL and / or OPG as a marker in a biological sample. The composition for prevention or treatment of an inflammatory disease comprises RANKL and / or M-CSF as an active ingredient.

Described are methods and compositions for inhibiting the trimerization of ligands belonging to the TNF superfamily, in particular, inhibiting RANKL trimerization. Accordingly, the methods and compositions provided herein can be used to treat disorders associated with increased RANK signaling, in particular those related to bone loss. Compounds that inhibit trimerization of ligands belonging to the TNF superfamily are also described.

The present invention has for its object to provide a method which comprises using edible and safe food components as active ingredients and promotes the OPG production promoting effect, RANKL expression inhibiting effect and osteoclast differentiation inhibiting effect, which take part in the prevention of bone resorption, and a composition like that. The present invention provides a method for promoting the bone resorption inhibitory effect such as the OPG production promoting effect, RANKL expression inhibiting effect and osteoclast differentiation inhibiting effect by using a composition containing extracts from plants belonging to the genus Platycodon, plants belonging to the genus Origanum, plants belonging to the genus Thymus, plants belonging to the genus Zanthoxylum, plants belonging to the genus Arctium, plants belonging to the genus Camellia, plants belonging to the genus Persea, plants belonging to the genus Stevia, plants belonging to the genus Pimpinella, plants belonging to the genus Matricaria, plants belonging to the genus Malva, plants belonging to the genus Ilex, and / or plants belonging to the genus Ptychopetalum, and a composition like that.

The invention discloses antibodies that bind high specificity to human RANKL (Receptor Activator for Nuclear Factor kappa B Ligand), wherein, the antibodies are used for the treatment of bone erosion caused by astogeny, hormonotherapy, postmenopausal osteoporosis, bone metastasis, and inflammation. The invention also discloses DNA sequences and supposed amino acid sequences of the antibodies.

Inhibitors of bone calcium resorption are administered to allow high doses of vitamin D compounds or mimetics to be given with the intent of treating non-calcium related diseases such as cancer, psoriasis, and autoimmune disease without the dangers of calcification of kidney, heart, and aorta. Inhibitors of bone calcium resorption include the bis-phosphonates, OPG (osteoprotegerin) or the soluble RANKL (receptor activator of NF-κB ligand) receptor known as sRANK (soluble RANK which is the protein expressed by the NF-κB gene), and function to block the availability of calcium from bone thereby preventing hypercalcemia and the resulting calcification of soft tissues. Thus, high doses of 1α,25-dihydroxyvitamin D3 (1,25-(OH)2D3), its analogs, prodrugs, or mimetics can be utilized with minimal risk to a patient. Specifically, alendronate is shown to block the bone calcium mobilization activity of both 1,25-(OH)2D3 and its very potent analog, 2-methylene -19-nor-(20S)-1α,25-dihydroxyvitamin D3.

Provided here are methods of inhibiting RANKL-induced osteoclastogenesis in patients suffering from specific types of cancer.

The invention provides specific binding members (e.g., antibodies or antigen-binding fragments thereof) which bind to RANKL originating from multiple species. An epitope recognized by the specific binding members can be selected from surface exposed loop domains that bind to and activate its cognate receptor, RANK (Receptor Activator of NFkB), on the surface of osteoclast precursors and other cell types. The invention provides peptides for generating such anti-RANKL antibodies, including murine sequences, other non-human sequences and cross-reactive peptides. The specific binding members are useful in the diagnosis and treatment of lytic bone diseases, including osteoporosis, rheumatoid arthritis, bone metastasis and hypercalcemia of malignancy, glucocorticoid-induced bone loss, a periodontal disease or condition, a cancer and Juvenile Paget's Disease. The binding members can also be used in therapy in combination with chemotherapeutics or anti-cancer agents and / or with other antibodies or antigen-binding fragments thereof.

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.

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.

Use of an anti-IL-20 antibody, either alone or in combination with an anti-RANKL antibody, for treating breast cancer and inhibiting cancer-associated bone loss.

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.

Chimeric molecules comprising receptor activator of NF-κB ligand (RANKL) antibodies and parathyroid hormone / parathyroid hormone-related protein (PTH / PTHrP) peptides are described. Compositions and methods for the treatment of bone diseases are also described.

The invention relates to a humanized antibody targeted to RANKL (Receptor Activator Of Nuclear Factor Kappa B Ligand) and TNF-alpha (Tumor Necrosis Factor) and an application of the humanized antibody. The antibody provided by the invention is obtained by carrying out humanized modification on a region V of a murine monoclonal antibody aiming at RANKL-TNF sample region epitope through a CDR (Complementarity Determining Region) replacement technology. The invention further provides an expression vector for expressing the humanized antibody targeted to RANKL and TNF-alpha and a construction method of the expression vector. The humanized antibody provided by the invention can effectively neutralize TNF-alpha in vitro, inhibit apoptosis caused by TNF-alpha, neutralize RANKL and inhibit generation of osteoclast and meanwhile can antagonize inflammations caused by TNF-alpha and bone destructive effect caused by RANKL. The humanized antibody provides a base for research on novel biological preparations for treating rheumatoid arthritis.

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 invention relates to a preparation method for nacre protein N16 and the application of the nacre protein N16 in preparation of drugs for prevention or treatment of orthopedic diseases such as osteoporosis and fracture. The nacre protein N16 is expressed in bacteria by using the method of genetic recombination, and a separation and purification scheme of the nacre protein N16 is established. The experiments of cells and animals prove that the nacre protein N16 can inhibit receptor activator of nuclear factor kappa B ligand (RANKL) from inducing the proliferation and the differentiation of osteoclast precursors RAW 264.7 cells, promotes the differentiation and the maturation of precursor osteoblast MC3T3-E1 cells, enhances the mineralization function of osteoblasts, treat the osteoporosis caused by ovariectomizing, and can be used in the preparation of drugs used for the prevention or the treatment of orthopedic diseases such as the osteoporosis and the fracture.

Chimeric molecules comprising receptor activator of NF-κB ligand (RANKL) antibodies and parathyroid hormone / parathyroid hormone-related protein (PTH / PTHrP) peptides are described. Compositions and methods for the treatment of bone diseases are also described.

The invention relates to 'a preparation method of OPG-HSP70 fusion protein and an application thereof', pertaining to the new technology field of biological medicaments. The preparation method provides an OPG-HSP70 fusion protein (osteoprotegerin-heat shock protein 70) medicament. According to the most significant pathological features of the rheumatoid arthritis (RA) i.e. the arthrosynovitis with cartilage and bone destruction, the medicament uses the osteoprotegerin as the decoy receptor to combine with the receptor activator of nuclear factor-kB ligand (RANKL) of the nuclear factor kB expressed by osteoblast and other cells, and to interrupt the combination between the RANKL and the RANK expressed by the osteoclast so as to inhibit the bone resorption involved by the osteoclast; and the medicament uses the protective polypeptide segments of the heat shock protein (HSP) to inhibit the inflammatory arthritis. The method contains the DNA sequence which encodes the fusion protein, the method for generating the fusing protein by the recombinant technology, the biological activity of the fusion protein and the like.

The invention provides a method for detecting the biological activity of RANKL (receptor activator for nuclear factor-KB ligands) targeted therapy medicines. The method includes steps of firstly, constructing transcription factor NF-kB (nuclear factor-kB) binding sequences, cloning the NF-kB binding sequences into luciferase reporter gene carriers, and guiding luciferase reporter gene transcription by the aid of the NF-kB binding sequences used as components of starters so as to obtain plasmids with the NF-kB binding sequences and luciferase reporter genes; secondly, transfecting cells by theplasmids with the NF-kB binding sequences and the luciferase reporter genes; thirdly, vaccinating the cells, adding RANKL and the RANKL targeted therapy medicines into the cells and then culturing thecells; fourthly, lysing the cells, adding luciferase substrates into the cells and detecting the fluorescence intensity so as to determine the biological activity of the RANKL targeted therapy medicines. The method has the advantage that the biological activity of the denosumab RANKL targeted therapy medicines can be accurately, easily, feasibly and quickly detected by the aid of the method.

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.

Disclosed is a bone formation enhancing agent comprising an RANKL-acting molecule which can enhance the differentiation, maturation or calcification of an osteoblast or a cell capable of being differentiated into an osteoblast. Specifically disclosed is a pharmaceutical composition for the treatment or prevention of a metabolic bone disease accompanied by the decrease in bone mass, which comprises, as an active ingredient, a compound which can act on an RANKL located on an osteoblast or a cell capable of being differentiated into an osteoblast to accelerate the differentiation, proliferation,maturation or calcification of the osteoblast or the cell capable of being differentiated into an osteoblast.

The invention provides a method for purifying and expressing RANK extracellular area protein, and also provides a method for preparing RANK / RANKL compound crystals, a three-dimensional crystal structure of the RANK / RANKL compound, and applications of the crystal in the medical field.

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 present invention relates to novel, soluble, recombinant variants RANKL (Receptor Activator of Nuclear Factor—κB Ligand) proteins, which may be expressed solubly in E. coli, variants that act as RANKL antagonists, and methods for generating the same.

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 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.

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.