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: Compositions and methods relating to epitopes of sclerostin protein, and sclerostin binding agents, such as antibodies capable of binding to sclerostin, are provided.

Abstract: A G-CSF solution formulation which is substantially free from proteins as a stabilizer but which contains at least one amino acid or a salt thereof as a stabilizer.

Abstract: Polypeptides of the neuregulin (NRG) heparin binding domain (N-HBD) and nucleic acids coding therefor are disclosed. In particular, fusion polypeptides are produced that comprise, as a targeting structure, a N-HBD polypeptide, fragment, homologue or functional derivative and a protein to be targeted. This is fused to a polypeptide or peptide being targeted (P<SUB>trg</SUB>) to cell surfaces rich in heparan sulfate proteoglycans to either activate or inhibit interactions at tyrosine kinase receptors. A preferred fusion polypeptide comprises an N-HBD, a spacer and the extracellular domain of erbB4, one of several receptors signaled by NRG, which is potent NRG antagonist. Such products are used to treat diseases or conditions where either agonism or antagonism at tyrosine kinase receptors has beneficial effects, including cancer and a multitude of diseases of the nervous system.

Abstract: An IL-1? binding molecule, in particular an antibody to human IL-1?, especially a human antibody to human IL-1? is provided, wherein the CDRs of the heavy and light chains have amino acid sequences as defined, for use in the treatment of an IL-1 mediated disease or disorder, e.g. osteoarthritis, osteoporosis and other inflammatory arthritides.

Abstract: A composition comprising a synthetic growth factor analogue comprising a non-growth factor heparin binding region, a linker and a sequence that binds specifically to a cell surface receptor and an osteoconductive material where the synthetic growth factor analogue is attached to and can be released from the osteoconductive material and is an amplifier/co-activator of osteoinduction.

Abstract: The present invention provides for isolated polypeptides capable of binding ErbB-4.

Abstract: A transgenic non-human animal of the species selected from the group consisting of avian, bovine, ovine and porcine having a transgene which results in disrupting the production of and/or activity of growth differentiation factor-11 (GDF-11) chromosomally integrated into the germ cells of the animal is provided. Also provided are methods for making such animals, and methods of treating animals, including humans, with antibodies or antisense directed to GDF-11. The animals so treated are characterized by increased muscle tissue and bone tissue.

Abstract: The present invention encompasses IL-18 binding proteins, particularly antibodies that bind human interleukin-18 (hIL-18). Specifically, the invention relates to antibodies that are entirely human antibodies. Preferred antibodies have high affinity for hIL-18 and/or that neutralize hIL-18 activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Method of making and method of using the antibodies of the invention are also provided. The antibodies, or antibody portions, of the invention are useful for detecting hIL-18 and for inhibiting hIL-18 activity, e.g., in a human subject suffering from a disorder in which hIL-18 activity is detrimental.

Abstract: Methods and compositions for inhibiting FGF signaling are described. Methods of the invention include contacting an FGF-responsive cell with exogenous heparan sulfate 6-O endosulfatase (Sulf1) in an amount effective to modify endogenous heparan sulfate, thereby inhibiting FGF signaling. Methods of the invention also include contacting an FGF-responsive cell with an exogenous Sulf1-modified compound, the exogenous Sulf1-modified compound being characterized by the ability to reduce binding of FGF2 or FGF4 to FGFR1. Compositions comprising exogenous Sulf1-modified compounds are also provided for use in conjunction with methods of the present invention.

Abstract: This invention is generally in the field of methods for diagnosis, treatment and prevention of various disorders involving the Slit2 mediated angiogenesis.

Abstract: Methods for enhancing or stimulating hematopoiesis including the step of administering Interleukin-12 (IL-12) to yield hematopoietic recovery in a mammal in need. Preferred methods include the step of administering IL-12 as an adjuvant therapy to alleviate the hematopoietic toxicities associated with one or more treatment regimens used to combat a disease state. Other methods include administering IL-12 to ameliorate various hematopoietic deficiencies. Still other methods are directed to uses of IL-12 for in-vivo proliferation of hematopoietic repopulating cells, hematopoietic progenitor cells and hematopoietic stem cells. Other disclosed methods are directed to uses of Il-12 for bone marrow preservation or recovery.

Abstract: The present invention is directed to methods for the treatment of adenocarcinomas that are characterized by the overexpression of a particular oncogene, Pim-1. The procedure involves administering a therapeutically effective amount of interleukin-10 that has been coupled to a carrier that increases its circulating plasma half-life.

Abstract: The present invention relates to new arginine substituted peptides designed based on the sequence of human lactoferrin and to use thereof, in particular for treatment and/or prevention of infections, inflammations, tumours, pain, wounds and/or scars.

Abstract: A novel P-selectin ligand glycoprotein is disclosed, comprising the amino acid sequence set forth in SEQ ID NO:2 or by the amino acid sequence set forth in SEQ ID NO:4. DNA sequences encoding the P-selectin ligand protein are also disclosed, along with vectors, host cells, and methods of making the P-selectin ligand protein. Pharmaceutical compositions containing the P-selectin ligand protein and methods of treating inflammatory disease states characterized by P-selectin- and E-selectin-mediated intercellular adhesion are also disclosed.

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: The invention provides methods for diagnosis or prognosis of cardiovascular disease involving the detection of an elevated amount of MIC-1 in a test body sample. The invention also provides methods for treatment of cardiovascular disease and other chronic inflammatory disease.

Abstract: The Rho family of GTPases regulates axon growth and regeneration. Inactivation of Rho with C3, a toxin from Clostridium botulinum, can stimulate regeneration and sprouting of injured axons. The present invention provides novel chimeric C3-like Rho antagonists. These new antagonists are a significant improvement over C3 compounds because they are 3-4 orders of magnitude more potent to stimulate axon growth on inhibitory substrates than recombinant C3. The invention further provides methods of treating a disease of the eye by administering the compounds of the invention.

Abstract: The present invention relates to diagnosing abnormal cell proliferation in biological samples and screening for drugs which inhibit, reduce or abolish cell growth, especially tumorigenic cell growth, by detecting a phosphovariant isoform of a guanine nucleotide exchange factor biomarker, such as the novel GEF-H1S.

Abstract: The present invention discloses the use of active dendritic cells (DCs) releasing interleukin 12 (IL-12) which are loaded with an antigen against a specific pathogen or a specific tumor and, due to the treatment with lipopolysaccharide (LPS) and interferon-gamma (IFN-?), release IL-12, for the preparation of a medicament for treating a patient having an infection with said specific pathogen or for treating a patient having said specific tumor.