Abstract: A series of stapled BCL-2 family peptide helices were identified as able to target the survival protein MCL-I with high affinity and a subset with unprecedented selectivity. Agents and methods for selective pharmacologic neutralization of MCL-I are provided for drug discovery and therapeutic uses, including use in overcoming the apoptotic resistance of cancer and other diseases associated with impaired cell death.

Abstract: It is an object of the present invention to provide a bone regeneration agent and a bone supplementation formulation, in which a supplementation material itself is capable of promoting bone regeneration. The present invention provides a bone regeneration agent which comprises a gelatin having an amino acid sequence derived from a partial amino acid of collagen.

Abstract: Provided herein are methods for enhancing bone mineralization for bone repair or regeneration and compositions and grafts therefor. Methods for screening agents that enhance or modulate NELL-1 gene expression or NELL-1 protein production in a cell are also provided.

Abstract: Novel peptides are described which comprise an amino acid motif selected from the group consisting of “PG”, “GP”, “PI” and “IG” and having up to 10 amino acids upstream and/or downstream of the amino acid motif, wherein “P” in the motif is proline or hydroxyproline and the peptide stimulates the development, maintenance and repair of bone, cartilage and associated connective tissue. The invention further relates to pharmaceutical compositions of these peptides, as well as therapeutic and prophylactic uses of such peptides.

Abstract: Compositions and kits are provided having a peptide having an amino acid sequence that binds to eukaryotic cells and effects differentiation and support growth of the cells. Peptide-scaffold compositions containing at least one peptide or combinations of peptides are therapeutic agents for stimulating and promoting osteogenic activity and osteoinduction activity for cells. The scaffold is for example apatite, natural cancellous bone, demineralized natural cancellous bone, collagen, calcium phosphate, or hydroxyapatite.

Abstract: The present invention provides peptides and methods of their use in treating bone disorders and bone-related conditions and in treating obesity.

Abstract: Disclosed herein are heretofore undescribed preparations of highly concentrated, solubilized proteins, such as but not limited to, Bone Morphogenetic Proteins. Such protein preparations can be formulated in an aqueous carrier at protein concentrations in excess of 10 mg/ml when using the methods of manufacture taught herein. Such methods yield stable protein preparations in either solubilized or lyophilized form. The protein preparations of the present invention are particularly beneficial when administered either locally or systemically, in part, because low administration volumes can be accomplished. This is especially important for local treatment of certain anatomic locations such as, for example, the synovial fluid of a joint when treating osteoarthritis with BMP-7 or the intradiscal space when treating degenerative disc disease with BMP-7.

Abstract: The present disclosure provides variants of C-type natriuretic peptide (CNP), pharmaceutical compositions comprising CNP variants, and methods of making CNP variants. The CNP variants are useful as therapeutic agents for the treatment of diseases responsive to CNP, including but not limited to bone-related disorders, such as skeletal dysplasias (e.g., achondroplasia), and vascular smooth muscle disorders (e.g., restenosis and arteriosclerosis).

Abstract: A carrier matrix may be delivered to a target position within a patient in a minimally invasive manner by first cutting a collagen sponge sheet into a plurality of relatively small pieces. These pieces are sized so that, when wet, they are capable of flowing through a cannula and/or reduced-diameter syringe tip. The pieces are placed into a syringe and wetted, say with a morphogenic solution, and optionally mixed with a bulking material, which is similarly sized to fit through the cannula. The thoroughly mixed and wetted product forms a viscous aggregate which may then be injected into the patient at the target site.

Abstract: Provided herein are tissue protective peptides derived from or sharing consensus sequences with portions of cytokine receptor ligands, including Erythropoietin (EPO), that are generally located on or within the region of the cytokine receptor ligand that faces away from a receptor complex while the ligand is bound to the receptor. Also provide herein are fragments, chimeras, as well as peptides designed to mimic the spatial localization of key amino acid residues within the tissue protective receptor ligands, e.g., EPO; methods for treating or preventing a disease or disorder using tissue protective peptides; and methods for enhancing excitable tissue function using tissue protective peptides.

Abstract: Methods and compositions are provided for improving tissue growth and device integration in vivo. Substrates and devices coated with an ?2?1 or ?5?1 integrin-specific ligand are provided. The substrates and devices coated with an ?2?1 or ?5?1 integrin-specific ligand are shown to have greater tissue formation on the surface relative to controls, in particular greater bone formation.

Abstract: Osteogenic sponge compositions having enhanced osteoinductive properties for use in bone repair are described. The compositions include a quickly resorbable porous carrier, a more slowly resorbed mineral scaffold and an osteogenic factor, preferably a bone morphogenetic protein. The compositions enable increased osteoinductive activity while retaining a reliable scaffold for the formation of new bone at an implant site. Methods for therapeutic use of the compositions are also described.

Abstract: A cyclized peptide designated BMP Binding Peptide (BBP) is a synthetic peptide that avidly binds rhBMP-2, as do endogenous forms of BBP, and sequence conservation between species results in a variety of useful BBP compositions. BBP increases the over-all osteogenic activity of rhBMP-2, increases the rate at which rhBMP-2 induces bone formation, and BBP induces calcification alone. Compositions and substrates including BBP, and methods of using BBP are useful in therapeutic, diagnostic and clinical applications requiring calcification and osteogenesis.

Abstract: The invention pertains to methods and compositions for treating medical disorders characterized by elevated levels or abnormal expression of TNF? by administering a TNF? antagonist, such as recombinant TNFR:Fc.

Abstract: Methods are disclosed for determining progression of a condition, onset of a condition, or efficacy of treatment of a condition characterized by an adipocyte imbalance in a patient. In addition, methods are disclosed of treating diabetes, abnormal adipocyte activity, and insulin resistance using monomeric, homodimeric, and heterodimeric forms of certain C-terminal fragments of adiponectin receptor. In addition, methods of treating abnormal adipocyte activity, treating metabolic syndrome, causing insulin secretion, increasing insulin levels, inhibiting insulin degradation enzyme, treating Alzheimer's disease, treating cardiovascular disease associated with adiponectin levels, inhibiting ADAM-17 enzyme, inhibiting a protease, treating a condition associated with TNF-alpha, and treating a condition associated with HER2-neu are disclosed. Compositions, dosage forms, and kits are also disclosed.

Abstract: A cyclized peptide designated BMP Binding Peptide (BBP) is a synthetic peptide that avidly binds rhBMP-2. BBP increases the over-all osteogenic activity of rgBMP-2, increases the rate at which rhBMP-2 induces bone formation, and BBP induces calcification alone. Compositions and substrates including BBP, and methods of using BBP are useful in therapeutic, diagnostic and clinical applications requiring calcification and osteogenesis.

Abstract: An osteogenic composition is provided for implantation at or near a target tissue site beneath the skin, the osteogenic composition comprising a growth factor and a coloring agent, wherein the coloring agent imparts color to the growth factor to allow the user to see the growth factor at or near the target tissue site. In some embodiments, a method is provided for accelerating bone repair, the method comprising mixing bone morphogenic protein-2 and a coloring agent to form a mixture; applying the mixture to a surface of a porous collagen matrix, wherein the coloring agent allows the user to see bone morphogenic protein-2 distribution on or in the porous collagen matrix; and implanting the porous collagen matrix at or near a target tissue site in need of bone repair.

Abstract: One aspect of the current invention is a method of preventing and/or treating arthritis and/or preventing or treating lameness in a subject. Additionally, subject quality of life and welfare, and body condition scores are improved by utilizing methodology that administers the nucleic acid expression construct encoding a GHRH or functional biological equivalent to a subject through a parenteral route of administration. Following a single dose of nucleic acid expression vector, subjects are healthier and effects are demonstrated long term without additional administration(s) of the expression construct.

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

Abstract: A method and pharmaceutical composition for inhibiting the effect of glucocorticoids, particularly dexamethasone, which suppress growth hormone secretion, by administering ghrelin or a ghrelin analogue, for example, [Aib2, Glu3(NH-hexyl)]hGhrelin(1-28)-NH2 (SEQ ID NO:2) or other suitable ghrelin agonist, to counteract the catabolic effects of said dexamethasone and other natural glucocorticoids.

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: Methods of using colony stimulating factor receptor (CSF1R) extracellular domain (ECD) fusion molecules for treating osteolytic bone loss, cancer metastasis, cancer metastasis-induced osteolytic bone loss, and tumor growth are provided. CSF1R ECD fusion molecules, polynucleotides encoding CSF1R ECD fusion molecules, and methods of making CSF1R ECD fusion molecules are also provided.

Abstract: Apoptosis inducing factor (“AIF”) contains a PAR-binding motif (“PBM”) that binds to Poly(ADP-ribose) (“PAR”). Binding of PAR to AIF via the PBM is required for AIF release from the mitochondria to occur, and that this PAR-related release is a key step in the programmed cell death process known as parthanatos, both in vitro and in vivo. Preventing or disrupting this release can inhibit parthanatos and thus be the basis for treatments for patients suffering from diseases or medical conditions during which parthanatos commonly occurs, including Parkinson's disease or diabetes, or patients who have had and are recovering from heart attack, stroke and other ischemia reperfusion-related injuries. Alternatively, agents could be identified that enhance the release of AIF, thereby promoting parthanatos and serving as potential anti-tumor chemotherapeutic agents.

Abstract: The disclosure provides methods of treating X-linked hypophosphatemia, related bone demineralization and renal phosphate wasting disorders in a mammalian subject.

Abstract: Disclosed are compositions of matter having an amino acid sequence of SEQ ID NO:4, or a pharmaceutically acceptable salt thereof, including embodiments comprising a toxin peptide analog related to ShK, HmK, and AETX-K and pharmaceutical compositions or medicaments containing them along with a pharmaceutically acceptable carrier. Some embodiments include a half-life extending moiety. Also disclosed are a method of preventing or mitigating a relapse of a symptom of multiple sclerosis and a method of treating an autoimmune disorder using the compositions.

Abstract: The present invention relates to a transforming growth factor-beta (TGF-?)-mimicking peptide containing a particular amino acid sequence and a composition for preventing or treating TGF-?-effective disorders or conditions using the same. The peptide of the present invention may be much higher stability than natural-occurring TGF-? and improve drawbacks caused by high molecular weight of natural-occurring TGF-?. The peptide of this invention can be advantageously applied to treatment or improvement of TGF-?-effective disorders or conditions and have excellent efficacies on skin whitening and wrinkle improvement.

Abstract: Methods and compositions are provided for the therapeutic use of Wnt proteins, for enhancing bone growth and regeneration, including repair following injury, osseointegration of implants, and the like. In some embodiments of the invention, the compositions are administered locally, e.g. by injection at the site of an injury. For certain conditions it is desirable to provide Wnt activity for short periods of time, and an effective dose will be administered over a defined, short period of time.

Abstract: A bone graft or biocomposite for treating osseous defects and neogenesis of bone which is a composite of a biodegradable polymer and granules of beta-tricalciumphosphate, further comprising as active ingredient and embedded in the biodegradable polymer a physiologically effective amount of underglycosylated recombinant human BSP as a muti-dental clathrate with a basic organic compound which simulataneously is active as a plasticizer for the biodegradable polymer. The biocomposite is moldable and shapeable, hardens rapidly in situ when placed by surgery or prosthetic dentistry and which furthers osseous repair and the healing of damage or diseased tissues and lesions.

Abstract: Novel compounds which may be for treatment, prevention or alleviation of a condition associated with bone loss or low bone density or to inhibit osteoclast differentiation and stimulation, bone resorption, or loosening of a prosthetic device.

Abstract: This invention relates, in part, to unique and newly identified genetic polynucleotides involved in the process of bone remodeling; variants and derivatives of the polynucleotides and corresponding polypeptides; uses of the polynucleotides, polypeptides, variants and derivatives; and methods and compositions for the amelioration of symptoms caused by bone remodeling disorders. Disclosed in particular are, the isolation and identification of polynucleotides, polypeptides, variants and derivatives involved in osteoclast activity, validation of the identified polynucleotides for their potential as therapeutic targets and use of the polynucleotides, polypeptides, variants and derivatives for the amelioration of disease states and research purposes.

Abstract: A bone repair material is described that is of putty-like consistency, particularly useful for repairing dental bony defects such as those caused by bone loss resulting from moderate or severe periodontitis, augmenting of bony defects of the alveolar ridge, filling tooth extraction sites, or sinus elevation grafting. The repair material includes a porous, resorbable particulate that is bone-derived or derived from bone-like hydroxyapatite or synthetic hydroxyapatite; and, a resorbable carrier, such as high molecular weight polysaccharides, such as hyaluronic acid. A high concentration of particulate in the putty enhances bone repair and requires a high concentration of carrier to retain the putty at the defect site. For a particulate density of about 1.2 g/cc such as PEPGEN P-15® Bone Graft, a preferred formulation comprises about 55% percent by weight of the putty suspended in a hyaluronic acid gel of about 1.

Abstract: Osteoconductive bone graft materials are provided. These compositions contain injectable cements and demineralized bone matrix fibers. The combination of these materials enables the filling of a bone void while balancing strength and resorption.

Abstract: The present invention concerns improved osteoinductive materials comprising matrix materials and morphogenetic proteins, wherein depending on the subject matter the proteins may be dimeric or monomeric proteins. The osteoinductive materials according to the present invention have improved properties. The invention further concerns methods for producing the respective improved osteoinductive materials.

Abstract: A porous, self-sustaining body useful as a scaffold for bone grafting is provided. The scaffold comprises a carbonaceous matrix comprising a continuous phase having a surface and defining a plurality of open spaces throughout the matrix. The internal and external surfaces of the matrix are coated with a layer or film selected from the group consisting of osteogenic materials, therapeutic agents, and combinations thereof. The porous body comprises organic materials and is substantially free of metals. Methods of making and using the porous self-sustaining body are also provided, along with kits for facilitating the same.

Abstract: The present invention provides binding agents comprising peptides capable of binding myostatin and inhibiting its activity. In one embodiment the binding agent comprises at least one myostatin-binding peptide attached directly or indirectly to at least one vehicle such as a polymer or an Fc domain. The binding agents of the present invention produced increased lean muscle mass when administered to animals and decreased fat to muscle ratios. Therapeutic compositions containing the binding agents of the present invention are useful for treating muscle-wasting disorders and metabolic disorders including diabetes and obesity.

Abstract: Disclosed are antagonists of IL-17A and IL-17F. The antagonists are based on soluble IL-17RA and IL-17RC fusion proteins, including hybrid soluble receptors comprising portions of both IL-17RC and IL-17RA (“IL-17RC/IL-17RA”). Such antagonists serve to block, inhibit, reduce, antagonize or neutralize the activity of IL-17F, IL-17A, or both IL-17A and IL-17F. Also disclosed are methods of using such antagonists for treating disease, particularly inflammatory diseases mediated at least in part by IL-17A and/or IL-17F.

Abstract: Described are osteogenic implants that include a first implant material covered at least in part by a second implant material carrying an osteogenic protein such as a bone morphogenic protein. The first implant material can comprise a mineral and provide an inner scaffolding portion for supporting bone ingrowth, and the second implant material can comprise a collagen or other sponge carrier covering the first implant material and having a liquid osteogenic protein formulation imbibed therein. Related implant materials and methods of preparation and use constitute additional aspects of the invention.

Abstract: The present invention provides a storage-stable composition containing a parathyroid hormone-related protein (PTHrP) analogue and methods of using a PTHrP analogue and the PTHrP compositions described herein to treat osteoporosis, to increase bone mass or to increase bone quality. The composition is storage stable, in sterile form, and in general may be stored at room temperature for at least several weeks to allow convenient parenteral administration to human patients.

Abstract: A carrier matrix may be delivered to a target position within a patient in a minimally invasive manner by first cutting a collagen sponge sheet into a plurality of relatively small pieces. These pieces are sized so that, when wet, they are capable of flowing through a cannula and/or reduced-diameter syringe tip. The pieces are placed into a syringe and wetted, say with a morphogenic solution, and optionally mixed with a bulking material, which is similarly sized to fit through the cannula. The thoroughly mixed and wetted product forms a viscous aggregate which may then be injected into the patient at the target site.

Abstract: Osteogenic sponge compositions having enhanced osteoinductive properties for use in bone repair are described. The compositions include a quickly resorbable porous carrier, a more slowly resorbed mineral scaffold and an osteogenic factor, preferably a bone morphogenetic protein. The compositions enable increased osteoinductive activity while retaining a reliable scaffold for the formation of new bone at an implant site. Methods for therapeutic use of the compositions are also described.

Abstract: Recombinant NELL peptides and methods of preparing the same are disclosed.

Abstract: The present invention relates to amino acid sequences that are directed against/and or that can specifically bind Interleukin-6 Receptor (IL-6R) with improved affinity and/or avidity, and/or that have an improved efficacy and/or potency, and which are capable of (partially, or preferably totally) blocking the IL-6/IL-6R interaction and/or inhibit signalization through IL-6, 1L-6R and/or the IL-6/IL-6R complex. The invention further relates to compounds or constructs, and in particular proteins and polypeptides, that comprise or essentially consist of one or more such amino acid sequences.

Abstract: The present invention is related to novel parathyroid hormone polypeptide derivatives, and to pharmaceutical composition containing the polypeptides, as well as synthetic and recombinant methods for producing the polypeptides. Also disclosed are methods for treating mammalian conditions characterized by decreases in bone mass using therapeutically effective pharmaceutical compositions containing the polypeptides of the present invention. The present invention further provides diagnostic and therapeutic methods using the polypeptide derivatives.

Abstract: The present invention provides a polypeptide having a biological activity of the Chemotaxis Inhibitory Protein of Staphylococcus aureus (‘CHIPS’), the polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 2, or a fragment or variant thereof having a biological activity of CHIPS, wherein the fragment or variant retains amino acid substitutions K40E, D42V, N77H, K100R, K105R, N111 K and/or G112A relative to the wildtype CHIPS protein of SEQ ID NO:1. In one embodiment, polypeptide consists of the amino acid sequence of SEQ ID NO: 2. Related aspects of the invention provide pharmaceutical compositions comprising a polypeptide of the invention, together with methods or making and using the same.

Abstract: Provided is a composition comprising a peptide comprising amino acids and/or amino acid analogs comprising a continuous sequence of a sclerostin fragment comprising Tyr43 or Tyr213. Also provided is a composition comprising a peptide comprising less than about 75 amino acids and/or amino acid analogs including an amino acid or amino acid analog capable of being sulfated, where the composition is capable of inhibiting sclerostin binding to an LRP. Further provided is a composition comprising a peptide comprising less than about 75 amino acids and/or amino acid analogs including an amino acid or amino acid analog capable of being post-translationally sulfated, where the composition is capable of inhibiting binding of a protein ligand comprising a sulfation site to its binding partner.

Abstract: The present invention relates to a method for extracting organic molecules and/or organic minerals from a limestone material, including placing said limestone material in contact with a solution including at least one organic solvent, water and at least one acid, as well as to the organic molecules and/or organic minerals produced by the method. The products produced by the method can be used, for example, in therapeutic and non-therapeutic fields, in particular the agri-food, cosmetic and medical fields.

Abstract: This application generally relates to an isoform Nell-1 peptide, compositions thereof, and methods of using the same.

Abstract: The present invention relates to a pharmaceutical composition for preventing/treating conditions associated with PAR-2. The present invention also relates to a method for preventing/treating the condition using the pharmaceutical composition and use for manufacturing the pharmaceutical composition.

Abstract: In certain aspects, the present invention provides compositions and methods for promoting bone growth and increasing bone density.

Abstract: The invention relates to melanocortin receptor-specific cyclic peptides of Formula (I) or a pharmaceutically acceptable salt thereof, where R1, R2, R3, R4a, R4b, R4c, R5, x and y are as defined in the specification. These compounds are particularly useful in the treatments of energy homeostasis and metabolism related (e.g. diabetes), food intake related and/or energy balance and body weight related diseases, disorders and/or conditions, including obesity, overweight and diseases, disorders and/or conditions associated with obesity and/or overweight, such as type 2 diabetes and metabolic syndrome.