Abstract: This invention relates to methods for promoting reinnervation of auditory hair cells, specifically, by inhibiting Repulsive Guidance Molecule a (RGMa), a repulsive axonal guidance molecule that is expressed in the cochlea, or its receptor, neogenin.

Abstract: The present invention provides methods of repairing and regenerating cartilage tissue by administering into the cartilage or the area surrounding the cartilage a composition comprising a therapeutically effective amount of a morphogenic protein.

Abstract: A sustained-release drug composition consisting essentially of microparticles of hyaluronic acid having a high molecular weight or an inorganic salt thereof and a protein or peptide drug encased in said microparticles, wherein the average size of said microparticles ranges from 0.1 to 40 ?m.

Abstract: Methods and compositions are disclosed for an intra-articular injection for the treatment of osteoarthritis. The methods and compositions comprising combinations of hyaluronic acid and a bone morphogenetic protein, like rhGDF-5, can be useful for any synovial joint, including the knee, shoulder, hip, ankle, hands, spinal facet, or temporomandibular joint, both for the relief of pain and for slowing disease progression.

Abstract: This invention relates to biomaterials, said biomaterials for use in methods to control and/or induce bone growth. Particularly, the invention relates to macroporous calcium phosphate biomaterials pre-loaded with certain amounts of osteoclastic activity inhibitors for use in methods to control and/or induce bone growth in primates.

Abstract: The present invention provides novel methods of inhibiting fibrosis, as well as methods of treating or inhibiting fibrotic disorders, using BMP9 and/or BMP10 antagonists. The present invention also provides methods of assessing whether a subject has or is at risk of developing a fibrotic disorder by detecting levels of BMP9 and/or BMP10. Further provided are methods of assessing the efficacy of a treatment regimen for treating a fibrotic disorder by detecting and comparing pre-treatment levels of BMP9 and BMP10 with post-treatment levels of BMP9 and BMP10.

Abstract: Osteogenic proteins are delivered via an injectable solid rod or hardenable paste. The formulation comprises a calcium phosphate material, an osteogenic protein, and optional additives and active ingredients such as a bone resorption inhibitor. Methods of making injectable pharmaceutical compositions and methods of using the osteogenic compositions to treat bone defects are also disclosed.

Abstract: The invention relates to truncated growth factors and variants thereof. The invention also relate to methods of making and using the truncated growth factors.

Abstract: The present invention provides a method for preparing chitosan and xylan composite thereto-gelling solutions to allow regulating the conditions in which the chitosan and xylan solution will gel. The present invention also provides methods for using chitosan/xylan solutions as compositions and for using chitosan/xylan solutions in vitro and in vivo. A thermally-responsive composite hydrogel has been developed and synthesized from the natural polymers chitosan and xylan. The new material is a viscous liquid at room temperature, but turns to a solid gel at physiological temperature (37 C). Rate of gelation is controlled with addition of a salt solution. Applications are for tissue engineering and local delivery of therapeutic agents, including proteins and drugs, as wells as cells.

Abstract: Osoteogenic implants, and related compositions, methods and kits. The implants comprise a biodegradable scaffold comprising a polycaprolactone matrix and tricalcium phosphate particles within the matrix. The implants further include a formulation comprising BMP-7.

Abstract: The invention relates to truncated growth factors and variants thereof. The invention also relates to methods of making and using the truncated growth factors.

Abstract: The invention is directed to bone morphogenetic proteins that have reduced immunogenicity. In particular, the invention is directed to human BMP-7 that has been modified to reduce immunogenicity through alteration of the amino acid sequence of wild-type BMP-7.

Abstract: The present invention is directed to stabilizing Bone Morphogenetic Protein in various lyophilized formulations and compositions. The present invention comprises formulations primarily including trehalose as an excipient for lyophilized compositions and their subsequent storage and reconstitution, and can also optionally include other excipients, including buffers and surfactants.

Abstract: The present invention provides modified, highly potent bone morphogenetic proteins. In particular, the present invention relates to the observation that BMP-6 and BMP-9 are less susceptible to inhibition by Noggin that are other members of the BMP subfamily of proteins. The present invention features chimeric bone morphogenetic proteins in which the middle portion of BMP-6 or BMP-9 replaces the middle portion of another BMP subfamily protein to cause resistance to inhibition by Noggin or other Noggin-like antagonists. Other embodiments of modified BMPs, compositions and methods of use are also included.

Abstract: The present invention relates to novel drug depot implant designs for optimal delivery of therapeutic agents to subjects. The invention provides a method for alleviating pain associated with neuromuscular or skeletal injury or inflammation by targeted delivery of one or more therapeutic agents to inhibit the inflammatory response which ultimately causes acute or chronic pain. Controlled and directed delivery can be provided by drug depot implants, comprising therapeutic agents, specifically designed to deliver the therapeutic agent to the desired location by facilitating their implantation, minimizing their migration from the desired tissue location, and without disrupting normal joint and soft tissue movement.

Abstract: This invention provides a method of promoting bone healing by locally administering a vanadium-based insulin mimetic agent to a patient in need thereof. The invention also provides a new use of insulin-mimetic vanadium compounds for manufacture of medicaments for accelerating bone-healing processes. In addition, the invention also encompasses a bone injury treatment kit suitable for localized administration of insulin-mimetic vanadium compounds or compositions thereof to a patient in need of such treatment.

Abstract: Methods and compositions are disclosed for an intra-articular injection for the treatment of osteoarthritis. The methods and compositions comprising combinations of hyaluronic acid and a bone morphogenetic protein, like rhGDF-5, can be useful for any synovial joint, including the knee, shoulder, hip, ankle, hands, spinal facet, or temporomandibular joint, both for the relief of pain and for slowing disease progression.

Abstract: The present invention provides formulations of cysteine knot proteins, including TGF-? superfamily proteins and bone morphogenic proteins that are pH stabilized. In particular, the present invention relates to the observation that certain buffers enhance the stability of cysteine knot proteins, including TGF-? superfamily proteins and bone morphogenic proteins. In particular, disclosed herein are liquid and lyophilized formulations prepared with a glycylglycine and tartaric acid buffers to stabilize the pH of the formulation.

Abstract: The present invention relates to pharmaceutical compositions for a combination therapy with a cytokine antagonist and a corticosteroid. By means of the combination therapy diseases such as osteoarthritis, tendon injuries and/or degenerative spinal diseases can be treated.

Abstract: Small molecule compounds and methods for stem cell differentiation are provided herein. An example of a class of compounds that may be used to practice the methods disclosed herein is represented by enantiomerically pure isomers of compounds of Formula I: or a chirally pure stereoisomer, pharmaceutically acceptable salt, or solvate thereof, wherein R1, R2, R3, R4, R5, R5?, R6, R6?, R7, R7? are as described herein.

Abstract: Disclosed herein are improved osteogenic devices and methods of use thereof for repair of bone and cartilage defects. The devices and methods promote accelerated formation of repair tissue with enhanced stability using less osteogenic protein than devices in the art. Defects susceptible to repair with the instant invention include, but are not limited to: critical size defects, non-critical size defects, non-union fractures, fractures, osteochondral defects, subchondral defects, and detects resulting from degenerative diseases such as osteochondritis dessicans.

Abstract: The present invention is directed to sustained release formulations of biologic agents which permit persistent bioavailability. Preferred biologic agents include bone morphogenetic proteins. Diseases susceptible to amelioration and/or treatment with the formulations of the present invention include skeletal tissue diseases such as, but not limited to, osteoarthritis and other osteochondral diseases. The sustained release formulations of the present invention are especially suitable for treatment of minimally-vascularized or non-vascularized tissue sites such as, but not limited to, intrajoint, interarticular, or intraminiscal sites.

Abstract: Provided are novel methods and compositions for the diagnosis, prognosis and treatment of leiomyomas, in particular uterine leiomyoma (UL). In addition, methods of identifying anti-tumor agents are described. Furthermore, novel methods and compositions are provided for the treatment of diseases characterized by an aberrant growth of mesenchymal stem cells and their descendants and for the treatment of obesity are disclosed.

Abstract: Provided herein is tumor suppression composition and methods of making and using the same.

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: Methods and compositions are disclosed for an intra-articular injection for the treatment of osteoarthritis. The methods and compositions comprising combinations of hyaluronic acid and a bone morphogenetic protein, like rhGDF-5, can be useful for any synovial joint, including the knee, shoulder, hip, ankle, hands, spinal facet, or temporomandibular joint, both for the relief of pain and for slowing disease progression.

Abstract: The disclosure relates to compounds and compositions for forming bone and methods related thereto. In one embodiment, the disclosure relates to a composition comprising a compound disclosed herein, such as 2,4-diamino-1,3,5-triazine derivatives or salts thereof, for use in bone growth processes. In a typical embodiment, a bone graft composition is implanted in a subject at a site of desired bone growth or enhancement.

Abstract: The present invention is directed to methods of treating or preventing the development of obesity by administering compounds that stabilize mast cells. In addition, it includes pharmaceutical compositions which have both a mast cell stabilizer and instructions regarding the use of the stabilizer in treating or preventing obesity.

Abstract: The present invention is directed to novel drug delivery devices and pharmaceutical compositions containing growth and differentiation factor proteins. Said devices and compositions are specifically designed to accelerate tissue regeneration and wound healing processes of mammalian tissues. The invention is especially useful for the supportive therapy of diabetic wounds and ulcers.

Abstract: The present invention provides a method of increasing neural stem cell numbers or neurogenesis by using a pheromone, a luteinizing hormone (LH) and/or a human chorionic gonadotrophin (hCG). The method can be practiced in vivo to obtain more neural stem cells in situ, which can in turn produce more neurons or glial cells to compensate for lost or dysfunctional neural cells. The method can also be practiced in vitro to produce a large number of neural stem cells in culture. The cultured stem cells can be used, for example, for transplantation treatment of patients or animals suffering from or suspected of having neurodegenerative diseases or conditions.

Abstract: The present invention is directed to stabilizing Bone Morphogenetic Protein in various lyophilized formulations and compositions. The present invention comprises formulations primarily including trehalose as an excipient for lyophilized compositions and their subsequent storage and reconstitution, and can also optionally include other excipients, including buffers and surfactants.

Abstract: In certain aspects, the present invention provides compositions and methods for promoting bone growth and increasing bone density and strength. In certain embodiments, the present invention provides ALK3 polypeptides, including ALK3-Fc fusion proteins.

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 present invention relates to a pharmaceutical composition for promoting arteriogenesis, and preparation method and applications of the same, wherein said pharmaceutical composition comprises an effective amount of a drug, and a peptide hydrogel, and it forms a microenvironment for autologous cell recruitment and tissue regeneration.

Abstract: A cyclized peptide designated BMP Binding Peptide (BBP) is a synthetic peptide that avidly binds rhBMP-2. BBP increases the overall 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 relates to truncated growth factors and variants thereof. The invention also relates to methods of making and using the truncated growth factors.

Abstract: The present invention relates to the clinical application of BBP, alone or in combination with other growth factors, for use in bone healing applications, such as spinal surgery. Additional applications include use in orthopedic implantable prostheses and implantation into other surgical sites (e.g., surgical reconstruction, regional osteopenia, etc.) where bone is desired.

Abstract: Disclosed are phospholipid based compositions and implant devices, as well as methods and kits that include such compositions or components thereof. In particular, the present compositions include a polymer component such as a poloxamer or PEG component and a phospholipid component, such as a Phosal. The present compositions may include at least one additional component, such as granules, powder and/or particulates. The present compositions may further include one or more bone graft materials and/or active ingredients. The compositions may be used on their own or incorporated on or in a surgical implant.

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 liquid composition in an osmotic drug delivery system and a dosage form in an osmotic drug delivery system is disclosed comprising an amphiphilic molecule, a non-aqueous liquid solvent, and a pharmaceutically active agent.

Abstract: The present invention is directed to sustained release formulations of biologic agents which permit persistent bioavailability. Preferred biologic agents include bone morphogenetic proteins. Diseases susceptible to amelioration and/or treatment with the formulations of the present invention include skeletal tissue diseases such as, but not limited to, osteoarthritis and other osteochondral diseases. The sustained release formulations of the present invention are especially suitable for treatment of minimally-vascularized or non-vascularized tissue sites such as, but not limited to, intra joint, interarticular, or intraminiscal sites.

Abstract: Heparan sulphate HS/BMP2 is disclosed, together with the use of HS/BMP2 in the repair and regeneration of bone tissue.

Abstract: The invention relates to a composition comprising an aqueous admixture of ceramic particles, polysaccharide, a therapeutic agent and, optionally, a polymer, and methods of using the same. The present invention provides a flowable bone void filler for use in medical situations where bone regeneration is desired. In an exemplary embodiment the bone void filler comprises a polysaccharide, a ceramic material and a polymer that exhibits thermosetting properties such that it exists as a viscous liquid at room temperatures and as a gel at about body temperature. In another exemplary embodiment the bone void filler comprises a polysaccharide, a ceramic material, a polymer that exhibits thermosetting properties such that it exists as a viscous liquid at room temperature and as a gel at about body temperatures, and a therapeutic agent.

Abstract: The present invention provides methods for the treatment, and pharmaceuticals for use in the treatment, of mammalian subjects in, or at risk of chronic renal failure, or at risk of a need for renal replacement therapy. The methods involve the administration of certain proteins of, or based upon, the osteogenic protein/bone morphogenetic protein (OP/BMP) family within the TGF-? superfamily of proteins.

Abstract: Disclosed herein are improved osteogenic devices and methods of use thereof for repair of bone and cartilage defects. The devices and methods promote accelerated formation of repair tissue with enhanced stability using less osteogenic protein than devices in the art. Defects susceptible to repair with the instant invention include, but are not limited to: critical size defects, non-critical size defects, non-union fractures, fractures, osteochondral defects, subchondral defects, and defects resulting from degenerative diseases such as osteochondritis dessicans.

Abstract: The present invention relates to trans-capsularly administering into a diseased joint a high specificity antagonist selected from the group consisting of: i) an inhibitor of a pro-inflammatory interleukin; ii) an inhibitor of TNF-? synthesis; iii) an inhibitor of membrane-bound TNF-?; iv) an inhibitor of a natural receptor of TNF-?; v) an inhibitor of NO synthase, vi) an inhibitor of PLA2 enzyme; vii) an anti-proliferative agent; viii) an anti-oxidant; ix) an apoptosis inhibitor selected from the group consisting of EPO mimetic peptides, EPO mimetibodies, IGF-I, IGF-II, and caspase inhibitors, and x) an inhibitor of MMPs; and xi) an inhibitor of p38 kinase.

Abstract: This invention relates to the production and use of pharmaceutical growth factor compositions with novel characteristics, e.g., improved solubility and controlled release characteristics under physiological conditions. Compositions of one or more precursor proteins of growth factors of the GDF family provoke morphogenic effects, such as growth, differentiation, protection and regeneration of a variety of tissues and organs, e.g., bone, cartilage, tendons, ligaments, nerves and skin. These compositions can be advantageously used for the healing of tissue-destructive injuries and for the prevention or therapy of degenerative disorders.

Abstract: A bio-remodable augmentation device including an implantable member configured for maintaining space in a bone defect. The implantable member is formed from a bio-remodable composite having structural properties so as to aid in the generation of new bone tissue and eventually be reabsorbed in the newly formed bone tissue. This structural and bio-remodable implant reduces, if not eliminates, the need to remove the implantable member from the patient once new bone tissue is formed. A kit including the implantable devices and bone growth material is disclosed. Methods of use are also disclosed.

Abstract: Provided herein are methods and devices for inducing the formation of functional replacement nonarticular cartilage tissues and ligament tissues. These methods and devices involve the use of osteogenic proteins, and are useful in repairing defects in the larynx, trachea, interarticular menisci, intervertebral discs, ear, nose, ribs and other fibrocartilaginous tissues in a mammal.

Abstract: Disclosed herein are improved osteogenic devices and methods of use thereof for repair of bone and cartilage defects. The devices and methods promote accelerated formation of repair tissue with enhanced stability using less osteogenic protein than devices in the art. Defects susceptible to repair with the instant invention include, but are not limited to: critical size defects, non-critical size defects, non-union fractures, fractures, osteochondral defects, subchondral defects, and defects resulting from degenerative diseases such as osteochondritis dessicans.