Abstract: Compounds, methods, uses, compositions, kits and packages for the treatment of imbalance between bone resorption and bone formation, based on uses of 4-phenyl-2-propionamidotetralin (4-P-PDOT) and analogs, derivatives, prodrugs, precursors thereof, and salts thereof, are described.

Abstract: The present invention provides novel calcium phosphate nanoparticles suitable for efficient encapsulation of biologically active molecules. The invention further provides pharmaceutical compositions comprising these nanoparticles, as well as methods of making such nanoparticles and using them as carriers for therapeutic delivery of biologically active macromolecules.

Abstract: The present invention relates to alkylglycoside-containing compositions and methods for increasing the stability, reducing the aggregation and immunogenicity, increasing the biological activity, and reducing or preventing fibrillar formation of a peptide, polypeptide, or analog thereof, for example parathyroid hormone (PTH) or PTH analogs, amylin, insulin, Peptide T or analog thereof, gastrin, gastrin releasing peptides, gastrin releasing peptide-like (GRP) proteins, epidermal growth factor or analog thereof.

Abstract: Microparticles consisting of (a) a matrix with a mixture of (a1) at least one hydrophobic, biologically degradable polymer and (a2) optionally at least one water-soluble polymer, (b) a pharmaceutical active ingredient distributed in the matrix, and (c) in addition at least one water-insoluble, surface-active substance from the group of lecithins and phospholipids, distributed in the matrix, and a three-phase emulsion process for their preparation.

Abstract: Pharmaceutical compositions for the effective oral delivery of a parathyroid hormone, PTH, as well as methods for administration of the compositions are provided. Additionally, methods for stimulating new bone formation and treating and/or preventing osteoporosis are also provided.

Abstract: The invention relates to a combined pharmaceutical preparation comprising parathyroid hormone and a bone resorption inhibitor, said preparation being adapted for (a) the administration of parathyroid hormone during a period of approximately 6 to 24 months; (b) after the administration of parathyroid hormone has been terminated, the administration of a bone resorption inhibitor during a period of approximately 12 to 36 months.

Abstract: A method for orally administering a parathyroid hormone, PTH, comprising orally co-administering to a patient in need of PTH an effective amount of a PTH and an effective amount of calcitonin. The method according to the invention allows for the oral administration of PTH without the hypercalcemia, hypercalcuria and nephrolithiasis side effects.

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

Abstract: The present invention relates to crystalline polymorphic forms of the di-sodium salt of N-(5-chlorosalicyloyl)-8-aminocaprylic acid, pharmaceutical compositions containing the same, methods of preparing the same, and methods for facilitating the delivery of active agents with the same.

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

Abstract: Various nucleic acid-based matrixes are provided, comprising nucleic acid monomers as building blocks, as well as nucleic acids encoding proteins, so as to produce novel biomaterials. The nucleic acids are used to form dendrimers that are useful as supports, vectors, carriers or delivery vehicles for a variety of compounds in biomedical and biotechnological applications. In particular, the macromolecules may be used for the delivery of drugs, genetic material, imaging components or other functional molecule to which they can be conjugated. An additional feature of the macromolecules is their ability to be targeted for certain organs, tumors, or types of tissues. Methods of utilizing such biomaterials include delivery of functional molecules to cells.

Abstract: Acid-containing oral pharmaceutical compositions are provided wherein the pharmaceutical active agents are peptide compounds (i.e., those that include a plurality of amino acids and at least one peptide bond in their molecular structures). Certain barrier layers and/or particulate coated acid are used to reduce any adverse interactions that might otherwise occur between the acid of the compositions and other components of the composition. Use of these barrier layers and/or use of particulate coated acid is believed to promote a more simultaneous release of the components of the composition than is achieved by prior art acid-protection techniques, thus enhancing, and making more consistent, the bioavailability of the active peptide compounds.

Abstract: Compositions and pharmaceutical formulations for buccally delivering parathyroid hormone comprising a) a delivery agent, b) a PTH component and, optionally, c) an antiresorptive agent are provided.

Abstract: Provided herein are compositions and methods related to promoting protection or repair of articular cartilage and/or musculoskeletal soft tissue by contacting the cartilage, tissues or cellular components thereof with a parathyroid hormone/parathyroid hormone-related protein (PTH/PTHrP) receptor agonist or releasing factor.

Abstract: Disclosed herein are diketopiperazine microparticles having a specific surface area of less than about 67 m2/g. The diketopiperazine microparticle can be fumaryl diketopiperazine and can comprise a drug such as insulin.

Abstract: A therapeutic or bioeffecting film delivery system which includes nanoparticles having actives bound to or associated with the nanoparticles and which when administered allow the active to perform a therapeutic or bioeffecting function.

Abstract: Bioavailability of peptide active agents to be administered orally is enhanced by a pharmaceutical composition providing an active peptide that is amidated at a site that is not naturally amidated.

Abstract: Supplemented matrices comprising a PTH releasably incorporated therein, optionally containing a granular material, which are used to heal bone fractures, particularly bone fractures with a risk of becoming delayed unions or non-unions, are described herein. The PTH is incorporated either through covalent linkage to the matrix or through non-covalent interaction with the matrix and/or the granules. These supplemented matrices decrease the time of healing compared to autograft and or trigger healing of bone fractures which otherwise would not heal. The matrices are biocompatible, preferably biodegradable, and can be formed in vitro or in vivo, at the time of implantation. The PTH may be a part of a fusion peptide. PTH can be incorporated into the matrices with full retention of its bioactivity. PTH can be releasably incorporated in the matrix.

Abstract: The present invention provides a method for producing a controlled release microsphere with mean average size greater than 50 ?m, comprising preparing a water-in-oil (w/o) emulsion comprising an inner aqueous layer containing a pharmaceutically effective amount of a biologically active polypeptide with activity similar to parathyroid hormone, and an oil layer containing a polymer substance of poly (lactic-co-glycolic acid) (PLGA), then adding the w/o emulsion into aqueous polyvinyl alcohol (PVA) solution to form a water-in-oil-in-water (w/o/w) double emulsion and then desorbing the solvent in the oil layer. The present invention also provides a controlled release microsphere prepared by the method and use thereof.

Abstract: The present invention relates to alkylglycoside-containing compositions and methods for increasing the stability, reducing the aggregation and immunogenicity, increasing the biological activity, and reducing or preventing fibrillar formation of a peptide, polypeptide, or variant thereof, for example insulin and Peptide T or analog thereof.

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

Abstract: A method is disclosed whereby levels of calcium, phosphate and parathyroid hormone are measured in a patient. The patient is treated with a formulation comprising a compound having phosphotonin activity and thereafter measurements are made again. Dosing of the formulation is adjusted based on measurements with measuring, administering and adjusting dosing continually repeated as needed.

Abstract: Proteins are incorporated into protein or polysaccharide matrices for use in tissue repair, regeneration and/or remodeling and/or drug delivery. The proteins can be incorporated so that they are released by degradation of the matrix, by enzymatic action and/or diffusion. As demonstrated by the examples, one method is to bind heparin to the matrix by either covalent or non-covalent methods, to form a heparin-matrix. The heparin then non-covalently binds heparin-binding growth factors to the protein matrix. Alternatively, a fusion protein can be constructed which contains a crosslinking region such as a factor XIIIa substrate and the native protein sequence. Incorporation of degradable linkages between the matrix and the bioactive factors can be particularly useful when long-term drug delivery is desired, for example in the case of nerve regeneration, where it is desirable to vary the rate of drug release spatially as a function of regeneration, e.g.

Abstract: The invention relates to methods for manipulating hematopoietic stem or progenitor cells, mesenchymal stem cells, epithelial stem cells, neural stem cells and related products through activation of the PTH/PTHrP receptor in neighboring cells.

Abstract: Antibodies for a variant of intact parathyroid hormone (PTH) or its fragments which have at position 17 the amino acid serine which is phosphorylated [p(17) PTH] and methods of producing the same. The invention further includes various immunoassay methods which use the described antibody alone or in combination with other antibodies to determine the circulating levels of p(17) intact PTH (1-84) or fragments thereof in biological fluids. Such antibodies and immunoassays can be used in conjunction with other antibodies to detect all biologically active forms of hPTH present in biological fluids.

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: The invention describes compositions of peptide analogs that are active in blood or cleavable in blood to release an active peptide. The peptide analogs have a general formula: A-(Cm)x-Peptide (SEQ ID NO: 76), wherein A is hydrophobic moiety or a metal binding moiety, e.g., a chemical group or moiety containing 1) an alkyl group having 6 to 36 carbon units, 2) a nitrilotriacetic acid group, 3) an imidodiacetic acid group, or 4) a moiety of formula (ZyHisw)p (SEQ ID NO: 50), wherein Z is any amino acid residue other than histidine, His is histidine, y is an integer from 0-6; w is an integer from 1-6; and p is an integer from 1-6; wherein if A has alkyl group with 6 to 36 carbon units x is greater than 0; and Cm is a cleavable moiety consisting of glycine or alanine or lysine or arginine or N-Arginine or N-lysine, wherein x is an integer between 0-6 and N may be any amino acid or none. The peptide analogs are complexed with polymeric carrier to provide enhanced half-life.

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

Abstract: The present invention concerns methods and compositions for making and using bioactive assemblies of defined compositions, which may have multiple functionalities and/or binding specificities. In particular embodiments, the bioactive assembly is formed using dock-and-lock (DNL) methodology, which takes advantage of the specific binding interaction between dimerization and docking domains (DDD) and anchoring domains (AD) to form the assembly. In various embodiments, one or more effectors may be attached to a DDD or AD sequence. Complementary AD or DDD sequences may be attached to an adaptor module that forms the core of the bioactive assembly, allowing formation of the assembly through the specific DDD/AD binding interactions. Such assemblies may be attached to a wide variety of effector moieties for treatment, detection and/or diagnosis of a disease, pathogen infection or other medical or veterinary condition.

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: Disclosed are compositions and methods for modulating the ?-arrestin pathway selectively over the G protein pathway of a G protein couple receptor, such as parathyroid hormone receptor.

Abstract: The invention relates to methods and compositions for improving wound healing and in particular for preventing scar formation and thus loss of function that can occur in injured tissues during the natural wound healing process. Particularly, although by no means exclusively, the invention relates to the healing of chronic wounds such as diabetic ulcers.

Abstract: Currently there is no treatment for hematopoietic syndrome following radiation exposure. Exposed persons are presently treated with blood transfusions, growth factors such as G-CSF to promote neutrophil recovery. Present methods are targeted towards the bone marrow microenvironment, aiding in repair and regeneration with a decrease in the severity or possibly, complete avoidance of morbidity and mortality associated with the hematopoietic syndrome. Methods are useful for treatment of mass casualties following a radiation disaster.

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: [Object] To provide a medicine that is extremely useful for preventing and/or treating and/or limiting exacerbation of human knee osteoarthritis. [Means of Achievement] A medicine characterized in comprising a parathyroid hormone (PTH) or a PTH derivative as an active ingredient for preventing and/or treating and/or limiting exacerbation of human knee osteoarthritis.

Abstract: Disclosed are drug delivery systems for the delivery of small molecule and macromolecular drugs. More particularly, disclosed are substituted analogs of 3,6-di(alkyl-4 aminobutyl)-2,5-diketopiperazine (which may also be referred to DKP), their use in the formulation of both small molecule and macromolecular drugs including therapeutic, prophylactic and diagnostic agents, stabilizing agents and systems for their delivery.

Abstract: The invention provides a pharmaceutical composition for oral drug delivery comprising a solid dosage form containing an effective amount of a therapeutic agent, a permeation enhancer and a pharmaceutically acceptable excipient and a bioadhesive layer containing a bioadhesive polymer, and optionally comprising an impermeable or semi-permeable layer having an opening capable of directing a unidirectional release of the therapeutic agent and the permeation enhancer from the solid dosage form. Methods of making and using the present pharmaceutical composition are also provided.

Abstract: A transmembrane fusion protein including ubiquitin or a ubiquitin-like protein, a membrane translocation sequence linked to the C-terminus of the ubiquitin or ubiquitin-like protein, and a biologically active molecule linked to the C-terminus of the membrane translocation sequence is disclosed herein. A polynucleotide encoding the transmembrane fusion protein, a recombinant expression vector including the polynucleotide sequence, a cell transformed by the recombinant expression vector, and a method of delivering the biologically active molecule into a cell using the transmembrane fusion protein are also disclosed.

Abstract: The invention features a method of administering one or more therapeutic agents to a patient and delivering said agent or agents continuously over an extended period of time, said method comprising: obtaining a pharmaceutical composition including a peptide carrier, one or more therapeutic agents, and up to 30 percent, by weight, of a pharmaceutically acceptable, soluble, monomeric carrier; and parenterally administering said pharmaceutical composition to a subject by injection, wherein said composition automatically forms a gel after interaction with the patient's bodily fluids and releases said peptide carrier and said agent or agents continuously within the patient over an extended period.

Abstract: A system and method for producing a scaffold coated and/or impregnated with at least one bioactive agent. This is accomplished by culturing at least one cell in the same medium as a scaffold, but without physical contact between the at least one cell and the scaffold. The system includes a container having a surface defining an interior compartment. A medium is disposed within the interior compartment. At least one cell is disposed within the medium, the at least one cell being capable of producing at least one bioactive agent. Further, a scaffold is disposed within the medium. The scaffold is physically separated from the at least one cell such that there is no contact between the scaffold and the at least one cell. Thus, as the at least one cell produces at least one bioactive agent, such as a growth factor, the at least one bioactive agent enters the medium, and contacts and coats and/or impregnates the scaffold.

Abstract: Methods for promoting osteogenesis to accelerate or enhance bone fracture healing, treat bone defects, and enhance bone formation are disclosed. The methods rely on in vivo or ex vivo modulation of an arachidonic acid metabolic or signaling pathway in general, and, in particular, utilize 5-lipoxygenase inhibitors, leukotriene A4 hydrolase inhibitors, and/or leukotriene B4 receptor antagonists. These molecules can be delivered alone or in combination with one or more agents that inhibit bone resorption, regulate calcium resorption from bone, enhance bone accumulation, enhance bone formation, induce bone formation, impair growth of microorganisms, reduce inflammation, and/or reduce pain.

Abstract: A composition and method for treating a bone condition of an animal. The compostion includes nanoparticles; a targeted moiety covalently bonded to an outer surface of each nanoparticle; and osteoblast stimulating molecules encapsulated within each nanoparticle. The method for treating a bone condition includes introducing the composition into the animal.

Abstract: The present invention provides a storage-stable composition containing a parathyroid hormone-related protein (PTHrP) and methods of using a PTHrP 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: 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: An effective liquid preparation achieves high bioavailability (BA) of physiologically active peptides or proteins, including ghrelins, that are administered as drugs. Also provided is a method for improving the BA of physiologically active peptides or proteins, including ghrelins, that are subcutaneously injected in aqueous solutions. The liquid preparation contains: a physiologically active peptide or protein, such as ghrelins, as an active ingredient; an acid solution including one or a combination of two or more selected form the group consisting of acetic acid, lactic acid, phosphoric acid, glycine, citric acid, hydrochloric acid, propionic acid, butyric acid, benzoic acid and salts thereof; an alcohol; and a polar organic liquid including one or a combination of two or more selected from the group consisting of N-methyl-2-pyrrolidone, dimethylformamide, dimethylsulfoxide and methylparaben.

Abstract: The invention relates to a combined pharmaceutical preparation comprising parathyroid hormone and a bone resorption inhibitor, said preparation being adapted for (a) the administration of parathyroid hormone during a period of approximately 6 to 24 months; (b) after the administration of parathyroid hormone has been terminated, the administration of a bone resorption inhibitor during a period of approximately 12 to 36 months.

Abstract: A cosmetic or pharmaceutical composition includes a peptide parathyroid hormone fragment, derivatives thereof, salts thereof, and combinations thereof, where the peptide fragment conforms to the structure R1-NH-AA-R2 where R1 is selected from the group consisting of —H, a linear or branched, saturated or unsaturated acyl group having from 1 to 24 carbon atoms optionally functionalized with an —OH, —SH, —COOH or —CONH2 group, or a sterol group which is bonded by a functional group with the peptide; where R2 is —OH, —OH functionalized by a linear or branched, saturated or unsaturated alkyl group having from 1 to 24 carbon atoms, or a sterol group; and where AA corresponds completely or partially to the sequence of amino acids according to SEQ ID No. 1 corresponding to the PTH (28 to 34) region.

Abstract: The present invention provides for pharmaceutically acceptable compositions for peptidyl drugs, method of making thereof, and methods of use thereof. Compositions are disclosed comprising a pharmaceutically effective amount of a peptidyl drug and a bioavailability enhancer in an amount sufficient to increase the bioavailability of the peptidyl drug.

Abstract: Compounds having activity for lowering parathyroid hormone levels are described. In one embodiment, the compounds are comprised of a contiguous sequence of subunits, X1-X2-X3-X4-X5-X6-X7, wherein the X1 subunit comprises a thiol-containing moiety and the distribution of charge on the X2-X7 subunits provides the desired activity. Methods of using the compounds for treating hyperparathyroidism, bone disease and/or hypercalcemic disorders are also described, and in particular, methods for lowering plasma PTH and serum calcium are provided. The compounds can be used to treat subjects having, for example: primary, secondary or tertiary hyperparathyroidism; hypercalcemia of malignancy; metastatic bone disease; or osteoporosis.

Abstract: The invention provides for methods and compositions for treatment of pain via craniofacial mucosal administration of an analgesic compound (e.g. a non-opioid analgesic peptide, an NOP agonist or N/OFQ). Intranasal administration of certain analgesic peptides such as N/OFQ results in global analgesic effects.