Abstract: The present invention provides a new stable pharmaceutical composition of erythropoietin (EPO) that is stabilized with a combination of a poloxamer polyol and a polyhydric alcohol.

Abstract: The present invention concerns methods and compositions for making and using bioactive assemblies of defined compositions, which may have multiple functionalities and/or binding specificities. In particular embodiments, the bioactive assembly is formed using dock-and-lock (DNL) methodology, which takes advantage of the specific binding interaction between dimerization and docking domains (DDD) and anchoring domains (AD) to form the assembly. In various embodiments, one or more effectors may be attached to a DDD or AD sequence. Complementary AD or DDD sequences may be attached to an adaptor module that forms the core of the bioactive assembly, allowing formation of the assembly through the specific DDD/AD binding interactions. Such assemblies may be attached to a wide variety of effector moieties for treatment, detection and/or diagnosis of a disease, pathogen infection or other medical or veterinary condition.

Abstract: The present invention provides a method of treating or preventing the inflammatory response of ulcerative colitis or Crohn's disease in a subject comprising administering to the subject an effective amount of a substance that inhibits the binding of IL-13 to IL-13 receptors on NKT cells or delivers an effector molecule to the NKT cells.

Abstract: Peptides have been discovered which are capable of binding to and internalizing with the human transferrin receptor (hTfR). The sequences HAIYPRH (Seq. ID No. 1) and THRPPMWSPVWP (Seq. ID No. 2) are capable of binding to and internalizing with the human transferrin receptor. When these molecules were fused with other molecules, the fusion product was internalized in cells expressing hTfR. The sequences have use for targeting other peptides and proteins into cells expressing hTfR.

Abstract: Methods and compositions are provided for the diagnosis and treatment of iron misregulation diseases, including HFE polypeptides, agonists, and antagonists, and transferrin receptor agonists and antagonists.

Abstract: A drug conjugate comprising a targeting agent and an anti-cancer agent, wherein said targeting agent comprises an erythropoietin receptor ligand, is described. The drug conjugate can be used in methods of treating cancer. Also described are methods of treating cancer using the conjugate, methods of diagnosis, methods of imaging and pharmaceutical compositions.

Abstract: Elevated blood levels of the chemokine CXCL10 polypeptide are associated with respiratory illnesses (e.g. SARS, influenza and community-acquired pneumonia) and are useful in diagnosis of patients. Methods are provided for diagnosis and treatment of patients suffering from respiratory illnesses. Methods are provided for identifying inhibitors of the CXCL10:CXCR3 axis, for use in treating patients suffering from respiratory illnesses.

Abstract: The invention relates to isolated and/or recombinant nucleic acids which encode a human chemotactic cytokine designated human eotaxin, and to isolated and/or recombinant human eotaxin proteins or polypeptides, including synthetic polypeptides. The invention further relates to recombinant nucleic acid constructs, comprising a nucleic acid which encodes a human eotaxin, a portion thereof, or a variant; to host cells comprising such constructs, useful for the production of recombinant human eotaxin; and to antibodies reactive with human eotaxin, useful in in vitro methods, diagnosis and/or therapy. Also provided are methods of use of the eotaxin proteins, e.g., in the recruitment of eosinophils to a particular site or in the treatment of allergic conditions. Human eotaxins can be used to identify inhibitors (e.g., antagonists) or promoters (agonists) of human eotaxin, which can be used to selectively modulate leukocyte function, in inflammatory and autoimmune diseases, or in infections.

Abstract: The present invention relates to isolated and/or recombinant nucleic acids which encode a human chemotactic cytokine designated human eotaxin, and to proteins or polypeptides referred to herein as isolated and/or recombinant human eotaxin, including synthetic polypeptides. The invention further relates to recombinant nucleic acid constructs, comprising a nucleic acid which encodes a human eotaxin of the present invention, a portion thereof, or a variant; to host cells comprising such constructs, useful for the production of recombinant human eotaxin; and to antibodies reactive with human eotaxin, which are useful in in vitro methods, diagnostic and/or therapeutic applications. Also provided are methods of use of the proteins of the present invention, for example in the recruitment of eosinophils to a particular site or in the treatment of allergic conditions. Human eotaxins can be used in assays to identify inhibitors (e.g., antagonists) or promoters (agonists) of human eotaxin function.

Abstract: The present invention provides specific methods of using and administering etanercept to improve cognitive function in a human, for both the treatment and prevention of cognitive impairment, or, alternatively, to enhance cognitive function including Alzheimer's Disease, Idiopathic Dementia, and Traumatic Brain Injury. The methods of the present invention include the perispinal administration of etanercept. For the purposes of this patent “perispinal” is to be considered as referring to “perispinal extrathecal;” therefore direct intrathecal administration is excluded. Perispinal administration leads to enhanced delivery of etanercept to the brain in a therapeutically effective amount, via the vertebral venous system and/or the cerebrospinal fluid. Delivery of etanercept to the brain utilizing the methods of the present invention includes the use of the vertebral venous system to deliver etanercept to the brain via retrograde venous flow.

Abstract: In one embodiment, a composition of somatostatin analogues having the general formula: is provided wherein Z may be absent or present and when present is selected from DOTA- and DTPA-based chelators, NOTA-based chelators, carbonyl compounds, hydrazino nicotinamide, N4-chelators, desferrioxamine, NxSy-chelators, optionally complexed or labeled with a radioisotope, tyrosine for halogenation, a fluorescent dye, or biotin. The composition further provides that L may or may not be present and when present is a linker molecule, X1 is glutamic acid or a symmetric or asymmetric diamino acid containing 3 or 4 consecutive C atoms, X2 is a positively charged natural or unnatural amino acid, an arginine mimic, citrulline, or a neutral amino acid, X3 is phenylalanine, Ala-[3-(2-thienyl)], ?-naphthylalanine, or ?-naphthylalanine, X4 is an aromatic amino acid, X5 is threonine or serine, and X6 is phenylalanine, Ala-[3-(2-thienyl)], ?-naphthylalanine, or ?-naphthylalanine.

Abstract: The invention provides a novel, secreted protein that contains a region homologous to ligand binding domain of a cytokine receptor. This protein, called Frizzled-related protein (FRP), antagonizes the signaling of the Wnt family of cytokines. Extracellular signaling molecules such as the Wnt family members have essential roles as inducers of cellular proliferation, migration, differentiation, and tissue morphogenesis. As Wnt molecules are known to participate in the aberrant growth associated with neoplasia, Wnt antagonists such as FRP are valuable tools which both for understanding oncogenesis and for the design of new cancer therapies.

Abstract: A stable protein formulation containing tryptophan or a tryptophan derivative or a salt thereof as a stabilizer.

Abstract: The present invention relates to compounds capable of binding to the oncogene protein MDM2, processes for the preparation of such compounds, pharmaceutical preparations comprising such compounds, and uses of said compounds, e.g. in the therapeutic (including prophylactic) treatment of an animal or especially of the human body. The present further relates to methods of and compounds for inhibiting the growth of tumor cells which comprise the wild type p53 suppressor by interfering with the interaction between human p53 and human MDM2.

Abstract: Metallopeptides and metallopeptide combinatorial libraries specific for melanocortin receptors are provided, for use in biological, pharmaceutical and related applications. The metallopeptides and combinatorial libraries are made of peptides, peptidomimetics and peptide-like constructs, in which the peptide, peptidomimetic or construct is conformationally fixed on complexation of a metal ion-binding portion thereof with a metal ion.

Abstract: A conjugate of a toxin and a cytokine, and a fusion protein comprising a bispecific antibody that has a first specificity for a cell marker specific to a malignant cell and a second specificity for a region of IL-15?, each optionally further comprising a radionuclide, are useful therapeutic reagents for treating leukemias and lymphomas.

Abstract: A method is described comprising the combined administration of a novel composition comprising serum complement proteins with complement-fixing antibodies to induce transient disruption of myelin and/or demyelination. The antibodies specifically bind to one or more epitopes of myelin, and complement proteins. A method is also described for promoting regrowth, repair, and regeneration of neurons in a mammalian subject. The methods can be used following immediate or chronic injury.

Abstract: The present invention relates to a method for enhancing angiogenic activity to promote neovascularization comprising administering to a subject a formulation comprising a synergistically effective amount of a TWEAK agonist and an angiogenic factor.

Abstract: Described is a method for screening for alterations in exocytosis of a population of cells. The cells are sorted by a FACS machine by assaying for alterations in at least three of the properties selected from the group consisting of light scattering, fluorescent dye uptake, fluorescent dye release, annexin granule binding, surface granule enzyme activity, and the quantity of granule specific proteins. Methods for screening for bioactive agents capable of modulating exocytosis in a cell are also described. The methods provide for reduced background and increased specificity without increasing the time or steps involved in assaying for exocytosis.

Abstract: The present invention provides for an isolated nucleic acid molecule encoding a member of the TIE ligand family. The present invention also provides for an isolated nucleic acid molecule encoding TIE ligand-3 or TIE ligand-4. In addition, the invention provides for a receptorbody which specifically binds TIE ligand-3 or TIE ligand-4. The invention also provides an antibody which specifically binds TIE ligand-3 or TIE ligand-4. The invention further provides for an antagonist of TIE. The invention also provides for therapeutic compositions as well as a method of blocking blood vessel growth, a method of promoting neovascularization, a method of promoting the growth or differentiation of a cell expressing the TIE receptor, a method of blocking the growth or differentiation of a cell expressing the TIE receptor and a method of attenuating or preventing tumor growth in a human.

Abstract: The present invention provides for an isolated nucleic acid molecule encoding a member of the TIE ligand family. The present invention also provides for an isolated nucleic acid molecule encoding TIE ligand-3 or TIE ligand-4. In addition, the invention provides for a receptorbody which specifically binds TIE ligand-3 or TIE ligand-4. The invention also provides an antibody which specifically binds TIE ligand-3 or TIE ligand-4. The invention further provides for an antagonist of TIE. The invention also provides for therapeutic compositions as well as a method of blocking blood vessel growth, a method of promoting neovascularization, a method of promoting the growth or differentiation of a cell expressing the TIE receptor, a method of blocking the growth or differentiation of a cell expressing the TIE receptor and a method of attenuating or preventing tumor growth in a human.

Abstract: The invention relates to molecules for treatment and diagnosis of tumors and malignancies, comprising a tumor seeking biomolecule, which is coupled to an intercalating moiety, which is capable of complexing a metal, which metal is preferably a radioactive metal, to the use of these molecules and to therapeutic and diagnostic compositions containing them.

Abstract: Provided are cytokines and methods of modulating activity of the immune system using cytokine agonists and antagonists. Also provided are methods of treatment of immune and proliferative disorders.

Abstract: A diagnostic agent for pancreatic exocrine function comprising an amino acid or a peptide containing at least one 13C or 14C atom, or a pharmaceutically acceptable salt thereof other than Bz-Tyr-13C-PABA is provided.

Abstract: New and improved compounds for use in radiodiagnostic imaging or radiotherapy having the formula M-N—O—P-G, wherein M is the metal chelator (in the form complexed with a metal radionuclide or not), N—O—P is the linker, and G is the GRP receptor targeting peptide. Methods for imaging a patient and/or providing radiotherapy to a patient using the compounds of the invention are also provided. A method for preparing a diagnostic imaging agent from the compound is further provided. A method for preparing a radiotherapeutic agent is further provided.

Abstract: The subject invention relates to the use of ascorbic acid and derivatives thereof in stabilizing radiolabeled proteins and peptides against oxidation loss of radiolabel and autoradiolysis. Ascorbic acid is added after radiolabeling, including any required incubation period, but prior to patient administration.

Abstract: The invention features compounds of the general formula:

Abstract: Methods for the in vivo monitoring and measuring of proteins by constructing them as chimeric polypeptides are disclosed. Through the use of the chimeric polypeptides, such methods can be used to screen and identify compounds and events that affect the presence or absence of the proteins in the cell.

Abstract: Modified proteins, modified interferons &agr;'s and &bgr;'s, phosphorylated modified proteins and DNA sequences encoding the above, applications and uses thereof. Modified phosphorylated Hu-IFN-&agr;-like proteins are provided which carry an identifiable label such as a radio-label. Corresponding phosphorylatable Hu-IFN-&agr;-like proteins which contain a putative phosphorylation site. DNA sequences which encode a Hu-IFN-&agr;-like protein and contain a sequence encoding a putative phosphorylatable site. Appropriate expression vectors are used to transform compatible host cells of various microorganisms, such as E. coli. Numerous uses for the phosphorylated proteins are disclosed.

Abstract: Diagnostic methods comprise measuring specifically the level of at least one iso-eosinophilic cationic protein (iso-ECP) in a sample from an individual to be diagnosed, and comparing the measured level of the iso-ECP with a predetermined level of the iso-ECP. The iso-ECP is cytotoxic and the cytotoxicity of the iso-ECP is not capable of neutralization by the monoclonal antibodies EG1 and EG2. Anti-iso-ECP antibody which may be used in the diagnostic methods specifically binds to a cytotoxic isoform of ECP having an epitope which is unique for the native form of the cytotoxic iso-ECP.

Abstract: Processes for the preparation, prepared solutions, and the use of radium-223 for the treatment of calcified tumors, bone tumors, treatment of bones, bone surfaces and soft tissues is described.

Abstract: This invention provides mutant human interleukin 13 molecules showing varying specificity for the restricted (IL4 independent) IL13 receptor. The mutant hIL13 molecules include those made by substituting the amino acid residues that occur in the alpha-helix regions of native hIL13 with various other amino acid residues. Some of the mutants retain the ability to bind and cause signaling through IL13 receptors, while other mutants do not.

Abstract: The invention pertains to methods for labeling antigen presenting cells, by contacting the antigen presenting cells with a labeled verotoxin. The invention also pertains to methods for determining the ability of an antigen presenting cell to stimulate an immune response.

Abstract: Described are peptides and peptide mimetics that bind to and activate the thrombopoietin receptor. Such peptides and peptide mimetics are useful in methods for treating hematological disorders and particularly, thrombocytopenia resulting from chemotherapy, radiation therapy, or bone marrow transfusions as well as in diagnostic methods employing labeled peptides and peptide mimetics.

Abstract: The present invention provides novel agents for specifically targeting and detecting or treating focal sites of infection or inflammation in a subject.

Abstract: Methods for preventing or treating vascular hemorrhaging such as that incident to thrombolytic therapy, or characteristic of Alzheimer's and related diseases are provided. Such methods provide improved thrombolytic therapy to individuals who receive such therapy, and permit the diagnosis and treatment of diseases, such as Alzheimer's Disease, that are characterized by the deposition of amyloid deposits.

Abstract: An immunoassay method including reacting a sample from a patient with a bispecific antibody, wherein the bispecific antibody includes one antibody specific for a compound to be detected and a second antibody specific for a compound foreign to said patient sample, and subsequently reacting the patient sample with a polymer probe, wherein the polymer probe includes a compound recognized by the second antibody in the bispecific antibody complex and further includes at least two detectable signals; the bispecific antibody; and the polymer probe of the immunoassay method are disclosed.

Abstract: The present invention relates to a radiolabeled non-steroidal compound having the formula: 1

Abstract: Hek ligand (hek-L) polypeptides as well as DNA sequences, vectors and transformed host cells useful in providing hek-L polypeptides. The hek-L polypeptides bind to a cell surface receptor (hek) that is a member of the receptor tyrosine kinase family. Hek is expressed on cells that include certain tumor cell lines. The hek-L polypeptides also bind a distinct receptor tyrosine kinase known elk.

Abstract: The present invention relates to a conjugator system comprising liposomes with ionophores, and with chelator solution and alpha-particle emitting radionuclide(s) located inside of the liposome. Furthermore, a the method for the preparation of this type of radioactive liposomes is described, as well as use of the system and a kit for preparing the system.

Abstract: The invention relates to a method of detecting and localizing malignant tumors and their metastases in tissues, which in healthy condition and in non-neoplastic conditions of chronic inflammation do not contain substantial quantities of neurotensin-receptors, in the body of a human being, which comprises: (i) administering to said being a composition comprising, in a quantity sufficient for external imaging, a radiolabelled peptide selected from the group consisting of neurotensin (NT), NT-receptor agonists. NT-receptor antagonists, NT analogues and NT derivatives; and thereupon (ii) subjecting said being to external imaging, by radioactive scanning or by magnetic resonance imaging, to determine the targeted sites in the body of said being. The invention further relates to a method for the therapeutic treatment of said malignant tumors by administration of the above-defined peptide, labelled for this purpose, and to the differential-diagnostic assessment and detection of a specific tumor type (i.e.

Abstract: Hek ligand (hek-L) polypeptides as well as DNA sequences, vectors and transformed host cells useful in providing hek-L polypeptides. The hek-L polypeptides bind to a cell surface receptor (hek) that is a member of the receptor tyrosine kinase family. Hek is expressed on cells that include certain tumor cell lines. The hek-L polypeptides also bind a distinct receptor tyrosine kinase known elk.

Abstract: The invention relates to the use of TNF antagonists for producing drugs for the treatment of disorders characterized by elevated serum levels of interleukin-6.