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: 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 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: 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: 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: 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 invention comprises novel compounds that are effective in the prophylaxis and treatment of diseases, such as integrin receptors mediated diseases, in particular, diseases or conditions mediated by integrin receptors, such as &agr;v&bgr;3, &agr;v&bgr;5, &agr;v&bgr;6 and the like. The invention encompasses novel compounds, pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of such diseases and disorders. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Abstract: The in vivo circulating life and/or absorption of Neurophic Factor-3 (NT-3) is increased by generating certain substitution analogs of the native protein sequence that result in a lower isoelectric point and charge in relation to NT-3 of native sequence.

Abstract: Selected novel substituted pyridine 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, 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: The present invention relates to glial cell line-derived neurotophic factor (GDNF), a potent neurotrophin that exhibits a broad spectrum of biological activities on a variety of cell types from both the central and peripheral nervous systems. The present invention involves the cloning and characterization of a high affinity receptor for GDNF. This molecule has been named GDNF receptor (GDNFR) since it is the first known component of a receptor system. Nucleic acid and amino acid sequences are described for GDNFR protein products. A hydrophobic domain with the features of a signal peptide is found at the amino terminus, while a second hydrophobic domain at the carboxy terminus is involved in the linkage of the receptor to the cell membrane. The lack of a transmembrane domain and cytoplasmic region indicates that GDNFR requires one or more accessory molecules in order to mediate transmembrane signaling.

Abstract: A method is provided for the localized intravascular administration of a fibrinolytic metalloproteinase to a human subject in amounts that are both safe and effective to lyse an occluding fibrin-containing blood clot, while also avoiding the neutralizing effects of &agr;2-macroglobulin in the circulating blood.

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 present invention relates to sustained-release formulations using biodegradable alginate delayed gels or particles and methods thereof.

Abstract: The present invention broadly relates to chemical modification of biologically active proteins or analogs thereof. More specifically, the present invention describes novel methods for site-specific chemical modification of various proteins, and resultant compositions having improved biocompatibility and bioactivity.

Abstract: The present invention relates generally to the chemical modification of biologically active agents. More, specifically, the invention relates to a novel approach to engineer, through mutagenesis and site-directed chemical conjugation, specific, well-defined dualPEGylated-protein bioconjugates, consisting of two polyethylene glycol (PEG) macromolecules chemically conjugated to the protein at two specifically defined amino acid residues. The described dualPEGylated-protein bioconjugates show substantially improved bioefficacy and biocompatibility.

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 OPG, and pharmaceutical compositions. The polypeptides are used to treat bone diseases characterized by increased resorption such as osteoporosis.

Abstract: Disclosed are nucleotide sequences encoding a novel polypeptide termed LSIRF. Also disclosed are methods of preparing the polypeptide and uses thereof.

Abstract: An improved flow field-flow fractionation (flow FFF) process has been developed which permits the high-resolution separation of analytes without stopping or reversing the axial flow, introducing additional axial flow streams, or further splitting the axial flow stream. The improved procedure speeds up, streamlines, and simplifies the apparatus and the procedure without unduly concentrating the sample, permits the use of flow-sensitive detection technologies in a manner which has previously been difficult or impossible, and avoids the artifactual aggregation which is known to result from other relaxation procedures. The process also permits the calculation of the channel width w without reference to system or void peaks in the fractogram. These capabilities render the improved flow FFF procedure more accurate as well as more practical, and permit automated flow FFF separations to be routinely performed on commercially-available HPLC systems with only minor modifications.