Abstract: The present invention relates to an immunostimulant and to the use of an immunostimulant in the form of a cross-linked muramyl dipeptide microparticle in the treatment of radiation exposure, radiation poisoning, and mitigating the toxic effects of radiotherapy.

Abstract: A method for treating a subject afflicted with an autoimmune disease with a pharmaceutical composition comprising glatiramer acetate and a pharmaceutically acceptable carrier, comprising the steps of administering a therapeutic amount of the pharmaceutical composition to the subject, determining whether the subject is a glatiramer acetate responder or a glatiramer acetate hypo-/non-responder by measuring the value of a biomarker selected from the group consisting of IL-10 concentration, IL-17 concentration, IL-18 concentration, TNF-? concentration, BDNF concentration, caspase-1 concentration, IL-10/IL-18 ratio and IL-10/IL-17 ratio in the blood of the subject, and comparing the measured value to a reference value for the biomarker to identify the subject as a glatiramer acetate responder or a glatiramer acetate hypo-/non-responder, and continuing the administration if the subject is identified as a glatiramer acetate responder, or modifying treatment of the subject if the subject is identified as a glatiramer

Abstract: Novel polypeptides and polynucleotides encoding same are provided. Also provided methods and pharmaceutical compositions which can be used to treat various disorders such as cancer, immunological-related, blood-related and skin-related disorders using the polypeptides and polynucleotides of the present invention. Also provided are methods and kits for diagnosing, determining predisposition and/or prognosis of various disorders using as diagnostic markers the novel polypeptides and polynucleotides of the present invention.

Abstract: The invention relates to methods of use of synthetic peptide amides that are ligands of the kappa opioid receptor in the treatment and prevention of kappa opioid receptor-associated diseases and conditions; and particularly to uses of these agonists in the prophylaxis, inhibition and treatment of pain, inflammation and pruritis associated with a variety of diseases, disorders and conditions. Inflammatory conditions preventable or treatable by the methods of the invention include diseases and conditions associated with elevated levels of a proinflammatory cytokines, such as TNF-?, IL-?, IL-6, MMP-1 and MMP-3.

Abstract: The present invention relates to the discovery of novel receptors for the signaling of PTH and/or fragments of PTH, and the role of cPTH in bone development. The novel PTH receptors identified are selected from the group consisting of LRP5/6, TGF?RII, BMPRII (long form and short form), ActRIIA, and ActRIIB. Specifically, the present invention provides a novel screening tool for identifying compounds that improve bone mass by affecting certain pathways that promote or downregulate bone-forming activity. This promotion of bone-forming activity could provide for treatments for bone-loss or bone density disorders and/or kidney disease. The invention further encompasses the compounds, PTH ligands, and fragments of PTH ligands described herein; pharmaceutical compositions comprising the compounds, PTH ligands, or fragments of PTH ligand; and methods of increasing bone density using the compounds, PTH ligands, or fragments of PTH ligands.

Abstract: Methods, formulations and kits are described that allow for the controlled release of octreotide, e.g., octreotide acetate, in a subject.

Abstract: Novel peptidic pth receptor agonists and methods of using the same are provided.

Abstract: Disclosed herein is an osteogenic synthetic peptide, derived from bone morphogenetic protein-7, consisting of a sequence of 15 amino acid residues. Provided are also a pharmaceutical composition and a medium composition comprising the same. Having remarkable activity related to promoting osteoblast differentiation, the osteogenic synthetic peptide is very useful in the treatment of osteoporosis, bone defects and/or osteoarthritis.

Abstract: Black bear parathyroid hormone (PTH) and functional fragments thereof are provided. Also provided are methods of using black bear PTH and functional fragments for increasing cAMP in a bone-forming cell; reducing apoptosis in a bone-forming cell; decreasing the ratio of expression levels of Bax protein to Bcl-2 protein in a bone-forming cell; increasing the expression level of one or more of a bone matrix protein, a transcriptional activator, or a transcriptional regulator in a bone-forming cell; enhancing bone mineral density, increasing bone mass, decreasing bone loss, or reducing the incidence of bone fractures, or any combination thereof, in a subject; also provided are antibodies directed against black bear parathyroid hormone (PTH) and functional fragments thereof.

Abstract: Methods and compositions for modulating bone development are described.

Abstract: Described herein are peptide compositions of a prominin-1, which have regenerative activity. As such the peptides are useful when regeneration is needed, for example, to enhance angiogenesis, increase VEGF binding to endothelial cells, promote vasodilation, enhance cell migration, enhance cell proliferation, stimulate neuronal growth, prevent neurodegeneration, and/or promote neuroregeneration.

Abstract: Compression resistant matrices and methods are provided that have elongated particles embedded therein. The compression resistant matrices provide improved stability and mechanical strength and resists shifting, extrusion and rotation after implantation. In some embodiments, the matrices provided reduce or prevent surface compression of the implantable matrix which will cause unwanted increased amounts of growth factor (e.g., bone morphogenic protein) to leak from the matrix.

Abstract: The invention relates to the use of agonists of integrin alpha for promoting osteoblast differentiation of mesenchymal stem cells. These agonists are useful in particular for enhancing osteogenesis in the treatments of diseases associated with bone loss or insufficient bone formation.

Abstract: The present invention provides variant activin IIB soluble receptor polypeptides and proteins capable of binding and inhibiting the activities of activin A, myostatin, or GDF-11. The present invention also provides polynucleotides, vectors and host cells capable of producing the variant polypeptides and proteins. Compositions and methods for treating muscle-wasting and other diseases and disorders are also provided.

Abstract: The present invention relates to the use of Yersinia outer protein M (YopM), a YopM fragment, or a YopM variant, which is capable of autopenetrating the cell membrane and of integrating into the cell cytosol without the requirement of additional factors for delivering a cargo molecule across the membrane to the cytosol of a cell. The present invention also relates to a pharmaceutical composition comprising YopM, a YopM fragment, or a YopM variant being capable of autopenetrating the cell membrane and of integrating into the cell cytosol without the requirement of additional factors for the regulation of inflammatory reactions of the immune system and the treatment of diseases caused by autoimmunity of the host. The present invention further relates to a YopM fragment or variant, which is capable of autopenetrating the cell membrane and of integrating into the cell cytosol without the requirements of additional factors as well as such proteins or YopM linked to a cargo molecule.

Abstract: Novel parathyroid hormone peptide (PTH) and parathyroid hormone related peptide (PTHrP) or derivatives thereof which are biologically active are disclosed, as are pharmaceutical compositions containing such peptides, and synthetic and recombinant methods for producing such peptides. Also disclosed are methods for treating mammalian conditions characterized by decreases in bone mass using therapeutically effective pharmaceutical compositions containing such peptides. Also disclosed are methods for screening candidate compounds of the invention for antagonistic or agonistic effects on parathyroid hormone receptor action. Also disclosed are diagnostic and therapeutic methods of such compounds.

Abstract: Disclosed are peptide ligands for G-protein coupled receptors that are useful for treating disorders associated with G-protein coupled receptor activation.

Abstract: The invention provides cyclo[{4-(NH2—C2H4—NH—CO—O—)Pro}-Phg-DTrp-Lys-Tyr(4-Benzyl)-Phe], optionally in protected form, or a pharmaceutically acceptable salt or complex thereof, which has interesting pharmaceutical properties.

Abstract: The present invention provides screening methods for GPCRs based on the discovery that the affinity of a receptor agonist for a GPCR (such as the parathyroid hormone receptor) when not bound to a G-protein is correlated with the length of time over which the agonist is effective, independently of its pharmacokinetic properties. The invention also provides PTH- and PTHrP-derived polypeptides.

Abstract: Compositions are provided comprising a family of peptides having binding specificity for bone, and their use to produce coating compositions. The coating compositions are used to deliver a pharmaceutically active agent to bone, and are used in methods related to bone implants, bone repair, and bone-related diseases.

Abstract: A composition for the induction of bone growth is disclosed. The composition includes a substrate, bone growth protein, and sources of calcium and phosphate. The composition is acidic which promotes high activity of the bone growth protein. The calcium and phosphate sources can be provided as an acidic calcium phosphate salt. Also disclosed are methods of the making the composition and methods of using it.

Abstract: The invention provides disintegrin variants, and more specifically to disintegrin variants which are selective ?v?3 integrin antagonists for treatment and prevention of ?v?3 integrin-associated diseases. The present invention also relates to pegylated proteins, including proteins comprising a disintegrin variant having an RGD motif variant 48ARLDDL53. The invention also relates to the use of the polypeptides of the invention for the treatment and prevention of ?v?3 integrin-associated diseases.

Abstract: The isolation and identification of glycosaminoglycans capable of binding to proteins having a heparin-binding domain is disclosed, as well as the use of the glycosaminoglycans isolated in the growth and/or development of tissue.

Abstract: The present invention relates to a method for suppressing neuroendocrine disease. The therapy employs use of a non-cytotoxic protease, which is targeted to a neuroendocrine tumour cell, preferably via a somatostatin or cortistatin receptor, a GHRH receptor, a ghrelin receptor, a bombesin receptor, a urotensin receptor a melanin-concentrating hormone receptor 1; a KiSS-1 receptor or a prolactin-releasing peptide receptor. When so delivered, the protease is internalised and inhibits secretion from said tumour cell. The present invention also relates to polypeptides and nucleic acids for use in said methods.

Abstract: The present invention relates to treatment of disease by inhibition of cellular secretory processes, to agents and compositions therefor, and to manufacture of those agents and compositions. The present invention relates particularly, to treatment of disease dependent upon the exocytotic activity of endocrine cells, exocrine cells, inflammatory cells, cells of the immune system, cells of the cardiovascular system and bone cells.

Abstract: A novel class or family of TGF-? binding proteins is disclosed. Also disclosed are assays for selecting molecules for increasing bone mineralization and methods for utilizing such molecules.

Abstract: The present invention relates to a bone cement precursor system that is presented in the form of two shelf-stable pastes which have been terminally sterilized and are held in separate containers during product transport and storage. When the product is used during surgery, these pastes inject to a site of application through a static mixing device by the action of applied injection force. When the two pastes are mixed, they start to react to each other while injecting out. The resulting composition is highly biocompatible, osteoconductive, injectable, rapid setting and bioresorbable, and is useful in connection with bone repair procedures, for example, in the craniomaxillofacial, trauma and orthopedic areas.

Abstract: The invention relates to covalent conjugates between endoperoxides and small peptides and organic compounds that bind to molecular cavities on the transferrin or lactoferrin receptor, and the use of compositions comprising these conjugates to treat cancer, hyperproliferative disorders, inflammatory diseases, and infections.

Abstract: An implantable screw for maintaining space during bone grafting procedures is provided, where the screw has a highly-polished contoured head having a region adapted to support soft tissue, a threaded shaft and a tip adapted to penetrate bone tissue. Also provided, a device combining multiple implantable screws in series in order to increase the available space to grow new bone and a method for implanting the implantable screw. The implantable screws provided may be used in conjunction with bone graft materials and are removable once a desired amount of new bone is generated.

Abstract: Liquid formulations of bone morphogenetic proteins are provided for prolonged use at elevated temperatures. More specifically, the invention relates to liquid formulations comprising rhGDF-5, trehalose, and one or more biocompatible excipients that provide stability to the protein for at least 30 days at temperatures up to body temperature.

Abstract: The present invention relates to methods of increasing bone formation in patient suffering from a wasting disorder by orally or intranasally administering a pharmaceutically effective amount of a leptin peptide and a pharmaceutically acceptable carrier, wherein the leptin peptide increases serum osteocalcin levels.

Abstract: There are provided Idbf (inhibitor of Dvl and Bone formation) which is a novel Dvl-binding protein that binds to Dvl to inhibit signal transduction carried out through the Wnt/?-catenin signaling pathway, a gene for coding for the same, the use thereof, and the use of an inhibitor of the Idbf. The Idbf was known to be expressed by activation of the Wnt/?-catenin signaling pathway and bind to Dvl to block signal transduction carried out through the Wnt/?-catenin signaling pathway. Therefore, the Idbf can be used in development of medicines for inhibiting the signal transduction carried out through the Wnt/?-catenin signaling pathway, and an Idbf inhibitor can be used in preparation of medicines for activating the signal transduction carried out through the Wnt/?-catenin signaling pathway.

Abstract: Disclosed is a mixture of: a bone/cartilage formation promoting agent containing sulfated galactosaminoglycan having greater than or equal to 0.6 numbers of ester sulfate groups on average per constituent monosaccharide or a salt thereof as an active ingredient; a factor having a bone/cartilage formation promoting action; or a bone filler (BMP, TGF-?, FGF, IGF, insulin, PDGF, HGF, midkine, pleiotrophin, collagen, gelatin, proteoglycan, fibronectin, osteocalcin, osteopontin, osteonectin, bone sialoprotein, hydroxyapatite, dicalcium phosphate anhydride, dicalcium phosphate dehydrate, ?-tricalcium phosphate, amorphous calcium phosphate, octacalcium phosphate, ?-tricalcium phosphate, PLLA, PLGA, titanium, decalcified bone, autogeneous bone, or the like).

Abstract: Polypeptide growth factors, methods of making them, polynucleotides encoding them, antibodies to them, and methods of using them are disclosed. The polypeptides comprise an amino acid segment that is at least 70% identical to residues 52-179 of SEQ ID NO:2 or residues 258-370 of SEQ ID NO:2. Multimers of the polypeptides are also disclosed. The polypeptides, multimeric proteins, and polynucleotides can be used in the study and regulation of cell and tissue development, as components of cell culture media, and as diagnostic agents.

Abstract: Compositions containing apoaequorin and methods for their use in treating symptoms and disorders related to calcium imbalances associated with, for example, sleep quality, energy quality, mood quality, memory quality or pain are provided by the present invention.

Abstract: The present invention relates to a fish protein hydrolysate having a biological activity of interest, in particular an effect on the stimulation and maintenance of bone. The fish protein hydrolysate is characterized in that it is obtained by enzymatic hydrolysis of at least one protein source selected from the fish species Micromesistius poutassou, Clupea harengus, Scomber scombrus, Sardina pilchardus, Trisopterus esmarki, Trachurus spp, Gadus morhua, Pollachius virens, Melanogrammus aeglefinus and Coryphaenoides rupestris, and the species of fish belonging to the order Siluriformes, said enzymatic hydrolysis being carried out by means of an endopeptidase enzyme derived from Bacillus subtilis. The protein hydrolysate according to the invention makes it possible to maintain the bone mass or to stimulate bone growth through stimulation of osteoblast cell growth and inhibition of osteoclast cell growth.

Abstract: Compositions and methods are provided for promoting bone growth. An implantable bone graft material is provided comprising a resorbable ceramic and a resorbable polymer, wherein the polymer comprises a covalently attached BMP binding peptide. In addition, an implantable bone graft material is provided consisting essentially of a resorbable ?-TCP and a resorbable polymer, wherein the ?-TCP has a total porosity of about 50% or greater and wherein the ?-TCP has a particle size ranging from about 100 micron to about 300 micron. The implantable bone graft materials are useful for promoting bone growth in a subject.

Abstract: The present invention relates to compositions and methods for use in osteodistraction procedures. In one embodiment, a method of stimulating osteogenesis during and/or following bone distraction comprises providing a composition comprising a PDGF solution disposed in a biocompatible matrix and applying the composition to at least one site of bone distraction.

Abstract: Implant articles with improved osseointegrating properties, osteogenic implant materials, and process of inducing differentiation of mesenchymal stem cells, proliferation of osteoblast and attachment of cells to implant surface, comprising the step of impregnating the surface with a solution containing osteoactive bone sialoprotein, recombinant human bone sialoprotein, recombinant His-Myc-Ek-BSP or substantive fragments thereof that have not been in contact with serum containing complement factor H or any other BSP processing material.

Abstract: Disclosed are pharmaceutical compositions containing, as active ingredients, a mixture of a corticosteroid and a kinin B2 receptor antagonist. Said compositions have proved particularly effective, especially in the treatment of inflammatory disorders such as asthma, ophthalmic or dermatological disorders and, above all, as regards the joints, arthritis.

Abstract: This invention relates to novel protein transduction domains (PTDs) derived from secretory leukocyte protease inhibitor (SLPI). SLPI-derived PTDs are able to deliver cargo moieties in vivo and in vitro into the cytoplasm and nucleus of a host cell. The invention also relates to a transduction complex comprising one or more SLPI-derived PTDs linked or fused to one or more cargo moieties, which may comprise, for example, proteins, nucleic acids, lipids, carbohydrates, small molecules and other chemical compounds. The invention also relates to the manufacture of SLPI-derived PTDs, complexes comprising them; compositions comprising SLPI-derived PTDs or complexes; and utilization of SLPI-derived PTDs or complexes comprising them for therapeutic, diagnostic and research methods involving delivery of heterologous molecules across cellular membranes, and especially, across nuclear membranes.

Abstract: The invention refers to the use of the PAT nonapeptide which is a thymuline analog in the treatment of autoimmune diseases, in particular of rheumatoid arthritis and intestinal bowel diseases (IBD) such as the Crohn's disease.

Abstract: The loss of the SOST gene product sclerostin leads to sclerosteosis characterized by high bone mass (HBM). In this report, we found that sclerostin could antagonize canonical Wnt signaling in human embryonic kidney A293 cells and mouse osteoblastic MC3T3 cells. This sclerostin-mediated antagonism could be reversed by over-expression of Wnt coreceptor LRP5. In addition, we found that sclerostin bound to LRP5 as well as LRP6 and identified the first two YWTD-EGF repeat domains of LRP5 as being responsible for the binding. Although these two repeat domains are required for transducing canonical Wnt signals, canonical Wnt did not appear to compete with sclerostin for binding to LRP5. Examination of the expression of sclerostin and Wnt7b, an autocrine canonical Wnt, during primary calvarial osteoblast differentiation revealed that sclerostin is expressed at the late stages of osteoblast differentiation coinciding with the expression of osteogenic marker osteocalcin and trailing after the expression of Wnt7b.

Abstract: The present invention relates to the design and composition of a depot implant for optimal delivery of growth factors to treat bone avascular necrosis, in that such depot implant is constructed to be in a cylinder (rod) or sphere shape and have a natural or synthetic polymer scaffold with or without impregnated calcium phosphate particles. The density of the depot is higher than a typical BMP sponge carrier to facilitate its implantation and slower release of the growth factor. The scaffold is such that it has adequate porosity and pore size to facilitate growth factor seeding and diffusion throughout the whole of the bone structure resulting in increased new blood vessel growth and density in the avascular necrotic bone. In addition, the shape of the depot implant allows for delivery through a cannula or large bore needle.

Abstract: Materials and methods for treating tissue defects in human or animal tissues using implantable cells are described. Further, culture techniques and factors for enhancing these procedures, and cell survival and adaptation are described. Many of the tissue defects may be treated with autologous cells, while applications involving non-autologous cells or stem cells are also described.

Abstract: The present invention relates to peptides and polypeptides having the sequence SAVTFAVCAL or variants thereof, capable of binding to Calcineurin and/or to NS5A-TP2 and to their use in therapy, as well as to nucleic acid sequences and vectors encoding these peptides and polypeptides, and to cells comprising said polypeptides, nucleic acid sequences or vectors. The invention further relates to the use of the peptides, polypeptides or their derivatives to bring about phenotypic changes in mammalian cells, particularly to up-regulate calcineurin activity. The invention finally relates to a method for intracellular identification of substances which bind to calcineurin and which modulate the physiological effects of calcineurin.

Abstract: The present invention relates to reindeer bone formation inducing protein called bone morphogenetic protein (BMP), such as BMP-6, containing a heparin binding site and nucleotide molecules encoding the proteins and host cells expressing the proteins. The present invention relates also to the use of the bone morphogenetic protein for treating disorders related to bone and cartilage formation. The present invention further relates to osteogenic devices and pharmaceutical compositions containing the protein.

Abstract: The present invention relates to a method for producing a three-dimensional macroporous filament construct comprising interconnected microporous filaments showing a suitable surface roughness and microporosity. The method comprises the steps of: a) preparing a suspension comprising particles of a predetermined material, a liquid solvent, one or more binders and optionally one or more dispersants, b) depositing said suspension in the form of filaments in a predetermined three-dimensional pattern, preferably in a non-solvent environment, thereby creating a three-dimensional filament-based porous structure, c) inducing phase inversion, whereby said filaments are transformed from a liquid to a solid state, by exposing said filaments during the deposition of the filaments with a non-solvent vapour and to a liquid non-solvent, d) thermally treating the structure of step d) by calcining and sintering said structure.

Abstract: The present invention relates to the use of a protein selected from one or more of casein, ovalbumin, whey protein and soy protein for the reduction of dental erosion caused by exposure to acidic compositions having a pH in the range 2.0 to 5.0.

Abstract: The present invention relates to a bone graft material and a scaffold for tissue engineering applications, which have an osteogenesis-promoting peptide immobilized on the surface. More particularly, the invention relates to a bone graft material and a scaffold for tissue engineering applications, which have a cell adhesion-inducing peptide and/or tissue growth factor-derived peptide immobilized on the surface. By the osteogenesis-promoting peptide immobilized on the surface, the inventive bone graft material and scaffold for tissue engineering applications can promote the transition, proliferation and differentiation of cells associated with regeneration, and eventually maximize the regeneration of tissue. Moreover, the peptide immobilized on the surface has low molecular weight, indicating a reduced risk of immune responses upon its application in the body, and can be present in a stable form within the body, thus showing lasting effects.