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 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: Ligands which bind to the eck receptor are disclosed. More particularly, polypeptides which bind specifically to the eck receptor (eck receptor binding proteins or EBPs) and DNA sequences encoding said polypeptides are disclosed. Methods of treatment using eck receptor ligands and soluble eck receptor and disclosed, as are pharmaceutical compositions containing same. A rapid and sensitive method for the detection of receptor binding activity in crude samples is provided.

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: Disclosed are nucleic acids encoding novel proteins, designated kd312. Also disclosed are amino acid sequences for kd312 polypeptides, methods for preparing kd312 polypeptides, and other related aspects.

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 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 pH/thermosensitive biodegradable hydrogels, consisting of a A-B di block or A-B-A tri block copolymer of poly(d,l- or l-lactic acid) (PLA) or poly(lactide-co-glycolide) (PLGA) (block A) and polyethylene glycol (PEG) (block B), with ionizable functional groups on one or both ends of the polymer chains, for the sustained delivery of biologically active agents.

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: 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.

Abstract: A novel neurotrophic factor referred to as glial derived neurotrophic factor (GDNF) has been identified and isolated from serum free growth conditioned medium of B49 glioblastoma cells. Rat and human genes encoding GDNF have been cloned and sequenced. A gene encoding GDNF has been subcloned into a vector, and the vector has been used to transform a host cell in order to produce biologically active GDNF in a recombinant DNA process.

Abstract: A novel polypeptide, osteoprotegerin binding protein, involved in osteolcast maturation has been identified based upon its affinity for osteoprotegerin. Nucleic acid sequences encoding the polypeptide, or a fragment, analog or derivative thereof, vectors and host cells for production, methods of preparing osteoprotegerin binding protein, and binding assays are also described. Compositions and methods for the treatment of bone diseases such as osteoporosis, bone loss due to arthritis or metastasis, hypercalcemia, and Paget's disease are also provided. Receptors for osteoprotegerin binding proteins are also described. The receptors, and agonists and antagonists thereof, may be used to treat bone diseases.

Abstract: The invention relates to methods for treating or preventing acute and/or septic shock. The method comprises administering to patients in need thereof therapeutically effective amounts of a TNF binding protein and a Fas antigen. In a preferred embodiment, the TNF binding protein is sTNFR-I or sTNFR-II. The invention also relates to pharmaceutical compositions containing a TNF binding protein and a Fas antigen useful in such methods.

Abstract: The present invention provides peptides related to agouti signaling protein and agouti related protein which are useful in modulating the activity of the melanocortin 3 and melanocortin 4 receptors. Also provided are methods of preparing the peptides, as well as nucleic acid molecules encoding the peptides.

Abstract: A protein which exhibits a therapeutic effect on inflammation and is useful for treating IL-1-mediated inflammatory diseases, particularly diseases of the joint.