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 are methods and compositions for identifying compounds having an ability to modulate expression of a morphogen, particularly OP-1, OP-1 homologues and closely related proteins, using one or more OP-1-specific, non-coding sequences and a suitable reporter gene. In preferred embodiments, the OP-1-specific non-coding DNA sequence comprises a Pax-responsive OP-1-modulating element.

Abstract: Disclosed are 1) amino acid sequence data, structural features, homologies and various other data characterizing morphogenic proteins, 2) methods of producing these proteins from natural and recombinant sources and from synthetic constructs, 3) morphogenic devices comprising these morphogenic proteins and a suitably modified tissue-specific matrix, and 4) methods of inducing non-chondrogenic tissue growth in a mammal.

Abstract: Disclosed are therapeutic treatment methods, compositions and devices for maintaining neural pathways in a mammal, including enhancing survival of neurons at risk of dying, inducing cellular repair of damaged neurons and neural pathways, and stimulating neurons to maintain their differentiated phenotype. In one embodiment, the invention provides means for stimulating CAM expression in neurons. The invention also provides means for evaluating the status of nerve tissue, including means for detecting and monitoring neuropathies in a mammal. The methods, devices and compositions include a morphogen or morphogen-stimulating agent provided to the mammal in a therapeutically effective concentration.

Abstract: Disclosed are (1) nucleic acid sequences, amino acid sequences, homologies, structural features and various other data characterizing a morphogen cell surface receptors particularly OP-1-binding cell surface receptors ALK-2, ALK-3, and ALK-6; (2) methods for producing receptor proteins, including fragments thereof, using recombinant DNA technology; (3) methods for identifying novel morphogen receptors and their encoding DNAS; (4) methods and compositions for identifying compounds capable of modulating endogenous morphogen receptor levels; and (5) methods and compositions for identifying morphogen receptor binding analogs useful in the design of morphogen agonists and antagonists for therapeutic, diagnostic and experimental uses.

Abstract: Disclosed are therapeutic treatment methods, compositions and devices for maintaining neural pathways in a mammal, including enhancing survival of neurons at risk of dying, inducing cellular repair of damaged neurons and neural pathways, and stimulating neurons to maintain their differentiated phenotype. In one embodiment, the invention provides means for stimulating CAM expression in neurons. The invention also provides means for evaluating the status of nerve tissue, including means for detecting and monitoring neuropathies in a mammal. The methods, devices and compositions include a morphogen or morphogen-stimulating agent provided to the mammal in a therapeutically effective concentration.

Abstract: The present invention is based on the discovery that a true tissue morphogen such as OP-1 provided systemically, alone in its mature dimeric form, or as part of a soluble complex, can induce new replacement tissue regeneration at a localized, permissive defect site distal to the site of administration. Specifically, systemically administered protein is sufficient to induce formation of new functional replacement tissue, sufficient to repair a local defect in a tissue, including skeletal or orthopedic tissues, liver, pancreas, lung, cardiac, renal, uterine, intestinal, gastrointestinal _____ tissue. (As used herein, “orthopedic” or “skeletal” or “joint” or “chondrogenic” tissue is understood to encompass the skeletal and skeletal joint tissues: bone, cartilage, tendon, ligament, and synovial membrane tissues.

Abstract: Disclosed are matrix materials, methods, and devices for manufacture in vivo of autogenous replacement body parts comprising plural distinct tissues. In one embodiment, the replacement body part is a skeletal joint and the new plural distinct tissues include bone and articular cartilage.

Abstract: Disclosed are therapeutic treatment methods, compositions and devices for maintaining neural pathways in a mammal, including enhancing survival of neurons at risk of dying, inducing cellular repair of damaged neurons and neural pathways, and stimulating neurons to maintain their differentiated phenotype. In one embodiment, the invention provides means for stimulating CAM expression in neurons. The invention also provides means for evaluating the status of nerve tissue, including means for detecting and monitoring neuropathies in a mammal. The methods, devices and compositions include a morphogen or morphogen-stimulating agent provided to the mammal in a therapeutically effective concentration.

Abstract: Disclosed are terminally sterilized osteogenic devices for implantation into a mammal. The devices contain a combination of a biologically active osteogenic protein and an insoluble carrier which after being combined are sterilized by exposure to ionizing radiation, for example, by exposure to gamma rays or an electron beam. The terminally sterilized devices of the invention are characterized in that they induce bone formation following implantation into a mammal. Also disclosed is a method for inducing bone formation in a mammal by implanting a terminally sterilized device of the invention into a preselected locus in a mammal. Also disclosed is a method for preparing the terminally sterilized device of the invention.

Abstract: The present invention provides methods for the treatment, and pharmaceuticals for use in the treatment, of mammalian subjects at risk chronic renal failure, or at risk of a need for renal replacement therapy. The methods involve the administration of certain morphogens, inducers of those morphogens, or agonists of the corresponding morphogen receptors, or implantation of renal cells induced with those morphogens. The morphogens useful in the invention include osteogenic protein-1 (OP-1) and other members of the OP-1 subfamily of the TGF-&bgr; superfamily of growth factors.

Abstract: Disclosed are (1) nucleic acid sequences, amino acid sequences, homologies, structural features and various other data characterizing a morphogen cell surface receptors particularly OP-1-binding cell surface receptors; (2) methods for producing receptor proteins, including fragments thereof, using recombinant DNA technology; (3) methods for identifying novel morphogen receptors and their encoding DNAs; (4) methods and compositions for identifying compounds capable of modulating endogenous morphogen receptor levels; and (5) methods and compositions for identifying morphogen receptor binding analogs useful in the design of morphogen agonists and antagonists for therapeutic, diagnostic and experimental uses.

Abstract: Disclosed are terminally sterilized osteogenic devices for implantation into a mammal. The devices contain a combination of a biologically active osteogenic protein and an insoluble carrier which after being combined are sterilized by exposure to ionizing radiation, for example, by exposure to gamma rays or an electron beam. The terminally sterilized devices of the invention are characterized in that they induce bone formation following implantation into a mammal. Also disclosed is a method for inducing bone formation in a mammal by implanting a terminally sterilized device of the invention into a preselected locus in a mammal. Also disclosed is a method for preparing the terminally sterilized device of the invention.

Abstract: The invention relates to a method of treatment for a mammal in need of chemonucleolysis. The method comprising the administration of an effective proteoglycan cleaving amount of a proteoglycan-degrading enzyme and an effective amount of a growth factor effective in promoting the synthesis of a matrix component. The proteoglycan-degrading enzyme is preferably chondroitinase. The growth factor is preferably osteogenic protein. The proteoglycan-degrading enzyme and the growth factor are preferably administered simultaneously.

Abstract: Disclosed are terminally sterilized osteogenic devices for implantation into a mammal. The devices contain a combination of a biologically active osteogenic protein and an insoluble carrier which after being combined are sterilized by exposure to ionizing radiation, for example, by exposure to gamma rays or an electron beam. The terminally sterilized devices of the invention are characterized in that they induce bone formation following implantation into a mammal. Also disclosed is a method for inducing bone formation in a mammal by implanting a terminally sterilized device of the invention into a preselected locus in a mammal. Also disclosed is a method for preparing the terminally sterilized device of the invention.

Abstract: Disclosed are therapeutic treatment methods, compositions and devices for maintaining neural pathways in a mammal, including enhancing survival of neurons at risk of dying, inducing cellular repair of damaged neurons and neural pathways, and stimulating neurons to maintain their differentiated phenotype. In one embodiment, the invention provides means for stimulating CAM expression in neurons. The invention also provides means for evaluating the status of nerve tissue, including means for detecting and monitoring neuropathies in a mammal. The methods, devices and compositions include a morphogen or morphogen-stimulating agent provided to the mammal in a therapeutically effective concentration.

Abstract: The invention disclosed herein provides methods and compositions for the computer-assisted design of morphogen analogs. Practice of the invention is enabled by the use of at least a portion of the atomic co-ordinates defining the three-dimensional structure of human osteogenic protein-1 (hOP-1) as a starting point in the design of the morphogen analogs. In addition, the invention provides methods for producing morphogen analogs of interest, and methods for testing whether the resulting analogs mimic or agonize human OP-1-like biological activity. The invention also provides a family of morphogen analogs produced by such methods.

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: The invention disclosed herein provides methods and compositions for the computer-assisted design of morphogen analogs. Practice of the invention is enabled by the use of at least a portion of the atomic co-ordinates defining the three-dimensional structure of human osteogenic protein-1 (hOP-1) as a starting point in the design of the morphogen analogs. In addition, the invention provides methods for producing morphogen analogs of interest, and methods for testing whether the resulting analogs mimic or agonize human OP-1-like biological activity. The invention also provides a family of morphogen analogs produced by such methods.

Abstract: Disclosed are matrix materials, methods, and devices for manufacture in vivo of autogenous replacement body parts comprising plural distinct tissues. In one embodiment, the replacement body part is a skeletal joint and the new plural distinct tissues include bone and articular cartilage.