Abstract: Methods and compositions for the prevention and treatment of cardiovascular disease is described. Administration of osteoprotegerin (OPG) in a pharmaceutical composition prevents and treats atherosclerosis and associated cardiovascular diseases.

Abstract: There are disclosed Interleukin-15 Receptor (IL-15R) proteins, DNAs and expression vectors encoding IL-15R, and processes for producing IL-15R as products of recombinant cell cultures.

Abstract: The present invention concerns therapeutic agents that mimic the activity of Apo-AI amphipathic helix peptide. In accordance with the present invention, the compounds of the invention comprise: a. a Apo-AI amphipathic helix peptide or Apo-AI amphipathic helix peptide-mimetic domain, preferably the amino acid sequence of SEQ ID NO: 7, or sequences derived therefrom by phage display, RNA-peptide screening, or the other techniques mentioned above; and b. a vehicle, such as a polymer (e.g., PEG or dextran) or an Fc domain, which is preferred; wherein the vehicle, preferably an Fc domain, is covalently attached to the Apo-AI amphipathic helix peptide or Apo-AL amphipathic helix peptide-mimetic domain. The vehicle and the Apo-AI amphipathic helix peptide or Apo-AI amphipathic helix peptide-mimetic domain may be linked through the N- or C-terminus of the Apo-AI amphipathic helix peptide or Apo-AI amphipathic helix peptide-mimetic domain, as described further below.

Abstract: The in vivo circulating life and/or absorption of cationic therapeutic proteins, including but not limited to basic proteins such as NT-3 and BDNF, can be increased by generating analogs that have a lower isoelectric point and, preferably, also a lower protein charge relative to the protein of native sequence.

Abstract: The present invention concerns therapeutic agents that antagonize the activity of glucagon. In accordance with the present invention, the compounds of the invention comprise: a. a glucagon antagonist domain, preferably the amino acid sequence of SEQ ID NO: 7, or sequences derived therefrom by phage display, RNA-peptide screening, or the other techniques; and b. a vehicle, such as a polymer (e.g., PEG or dextran) or an Fc domain, which is preferred; wherein the vehicle is covalently attached to the glucagon antagonist domain. The vehicle and the glucagon antagonist domain may be linked through the N- or C-terminus of the glucagon antagonist domain. The preferred vehicle is an Fc domain, and the preferred Fc domain is an IgG Fc domain.

Abstract: A mammal lacking expression of particular CD45 isoform in certain cells of the immune system is provided. The mammal may optionally contain a transgene encoding the CD45RO isoform. Also provided are methods of using these mammals.

Abstract: The present invention concerns fusion of Fc domains with biologically active peptides and a process for preparing pharmaceutical agents using biologically active peptides. In this invention, pharmacologically active compounds are prepared by a process comprising: a) selecting at least one peptide that modulates the activity of a protein of interest; and b) preparing a pharmacologic agent comprising an Fc domain covalently linked to at least one amino acid of the selected peptide. Linkage to the vehicle increases the half-life of the peptide, which otherwise would be quickly degraded in vivo. The preferred vehicle is an Fc domain. The peptide is preferably selected by phage display, E. coli display, ribosome display, RNA-peptide screening, or chemical-peptide screening.

Abstract: The present invention relates to sustained-release formulations using alginate gel beads and methods thereof.

Abstract: Selected novel substituted pyrimidinone and pyridone compounds are effective for prophylaxis and treatment of diseases, such as TNF-&agr;, IL-1&bgr;, IL-6 and/or IL-8 mediated diseases, and other maladies, such as pain and diabetes. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving inflammation, pain, diabetes and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Abstract: Selected novel urea compounds are effective for prophylaxis and treatment of diseases, such as cell proliferation or apoptosis mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving stoke, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Abstract: Disclosed are methods for improving the solubility of a protein of interest produced recombinantly by expressing the protein of interest as a fusion protein with Uracil DNA glycosylase inhibitor (UGI).

Abstract: The present invention discloses a novel secreted polypeptide, termed Osteoprotegerin, which is a member of the tumor necrosis factor receptor superfamily and is involved in the regulation of bone metabolism. Also disclosed are nucleic acids encoding Osteoprotegerin, polypeptides, recombinant vectors and host cells for expression, antibodies which bind Osteoprotegerin, and pharmaceutical compositions. The polypeptides are used to treat bone diseases characterized by increased resorption such as osteoporosis.

Abstract: Selected novel substituted pyrimidine compounds are effective for prophylaxis and treatment of diseases, such as TNF-&agr;, IL-1&bgr;, IL-6 and/or IL-8 mediated diseases, and other maladies, such as pain and diabetes. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving inflammation, pain, diabetes and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Abstract: The present invention comprises a new class of novel aryl and heteroaryl substituted fused pyrrole compounds useful for the prophylaxis and treatment of diseases or conditions, such as TNF-&agr;, IL-1&bgr;, IL-6 and/or IL-8 mediated diseases, and other maladies, such as pain and diabetes. In particular, the compounds of the invention are useful for the prophylaxis and treatment of diseases or conditions involving inflammation. Accordingly, the invention also comprises pharmaceutical compositions comprising the compounds of the invention, methods for the prophylaxis and treatment of inflammation and other maladies, such as pain and diabetes, using the compounds and compositions of the invention, and intermediates and processes useful for the preparation of compounds of the invention. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Abstract: The invention relates to the three-dimensional structure of a crystal of a kinase enzyme complexed with a ligand. The three-dimensional structure of a protein kinase-ligand complex is disclosed. The invention also relates to methods of preparing such crystals. Kinase-ligand crystal structures wherein the ligand is an inhibitor molecule are useful for providing structural information that may be integrated into drug screening and drug design processes. Thus, the invention also relates to methods of using the crystal structure of kinase enzyme-ligand complexes for identifying, designing, selecting, or testing inhibitors of kinase enzymes, such inhibitors being useful as therapeutics for the treatment or modulation of i) diseases; ii) disease symptoms; or iii) the effect of other physiological events mediated by kinases; having one or more kinase enzymes involved in their pathology.

Abstract: The present invention broadly relates to the field of protein modification, and, more specifically, the attachment of water soluble polymers to novel erythropoietin stimulating protein (NESP).

Abstract: There are provided compounds, compositions and methods of use thereof in the modulation of feeding behavior, obesity, diabetes, cancer (tumor), inflammatory disorders, depression, stress related disorders, Alzheimer's disease and other disease conditions.

Abstract: Methods and compositions for pulmonary delivery of chemically modified G-CSF, and pegylated proteins are disclosed.

Abstract: Compounds are disclosed having the general formula R1-X-R2, wherein R1 and R2 are biologically active groups, at least one of which is polypeptidic. X is a non-peptidic polymeric group. R1 and R2 may be the same or different. Preferred R1 and R2 groups are TNF inhibitors.

Abstract: The present invention relates generally to the development of pharmaceutical compositions which provide for sustained release of biologically active polypeptides. More specifically, the invention relates to the use of thermosensitive, biodegradable hydrogels, consisting of a block copolymer of poly(d,l- or l-lactic acid)(PLA) or poly(lactide-co-glycolide)(PLGA) and polyethylene glycol (PEG), for the sustained delivery of biologically active agents, such as leptin.