Abstract: The invention provides compositions and methods for evaluating neuromuscular function in a subject, e.g., a subject at risk for or suffering from a neuromuscular disorder.

Abstract: Methods and compounds for conferring site-specific or local immune privilege.

Abstract: The present invention provides pharmacological compounds including an effector moiety conjugated to a binding moiety that directs the effector moiety to a biological target of interest. Likewise, the present invention provides compositions, kits, and methods (e.g., therapeutic, diagnostic, and imaging) including the compounds. The compounds can be described as a protein interacting binding moiety-drug conjugate (SDC-TRAP) compounds, which include a protein interacting binding moiety and an effector moiety. For example, in certain embodiments directed to treating cancer, the SDC-TRAP can include an Hsp90 inhibitor conjugated to a cytotoxic agent as the effector moiety.

Abstract: The present invention relates to radiopharmaceutical compositions comprising the mother nuclide 224Ra, its daughter nuclide 212Pb, and a complexing agent that complexes with the daughter nuclide. The use of targeted chelate scavengers for 224Ra daughter nuclide opens up the possibility for using 224Ra based solutions for medial treatments.

Abstract: Disclosed herein are compounds, extracts, and active fractions of the plant Geum japonicum and methods for preventing or treating brain diseases or conditions, such as ischemic stroke, Alzheimer's disease, vascular dementia, mild cognitive impairment (MCI), chronic cerebral ischemia and Parkinson's disease. The compounds provided herein can be formulated into pharmaceutical compositions and medicaments that are useful in the disclosed methods. Also provided are the use of the compounds and extracts in preparing pharmaceutical formulations and medicaments.

Abstract: The invention relates to a composition and method used for injuries treatment with a surprisingly therapeutic effect. This composition comprises a population of cells derived from human umbilical cord blood which expresses one of the following markers: CD34, CD45, and CD31; a population of CD34+ derived endothelial cells; and a biomimetic gel, preferably fibrin. The method for obtaining the composition comprises the derivation of a population of endothelial cells from CD34+ cells and then a co-culture of a CD34+ cells with CD34+-derived endothelial cells within a biomimetic gel.

Abstract: A mechanism of monoamine oxidases (MAOs) driven epithelium-to-mesenchymal transition (EMT) is disclosed. Also disclosed are methods for treating cancer by inhibiting or suppressing MAOs in cancer cells. Novel MAOs inhibitors, such as small molecules, siRNA, shRNA, antisense oligonucleotides, aptamers, decoys, and pharmaceutical compositions useful for treating cancer by disrupting the workings of MAOs are provided. In particular, a class of conjugates formed by covalently conjugating near infrared dye 783, IR-780, and MHI-148 to a MAO inhibitor, such as clorgyline, with and without encapsulation it in a nanoparticle is provided. Other aspects of the invention include methods for forming the nano-conjugates, method for monitoring treatment progress in a cancer patient by monitoring the changes in MAO activity, methods for screening patients who are at risk of cancer or differentiating different forms of cancer by assaying the level and location of MAO activity.

Abstract: The present invention concerns methods and compositions for forming cytokine-antibody complexes using dock-and-lock technology. In preferred embodiments, the cytokine-MAb DNL complex comprises an IgG antibody attached to two AD (anchor domain) moieties and four cytokines, each attached to a DDD (docking and dimerization domain) moiety. The DDD moieties form dimers that bind to the AD moieties, resulting in a 2:1 ratio of DDD to AD. The cytokine-MAb complex exhibits improved pharmacokinetics, with a significantly longer serum half-life than either naked cytokine or PEGylated cytokine. The cytokine-MAb complex also exhibits significantly improved in vitro and in vivo efficacy compared to cytokine alone, antibody alone, unconjugated cytokine plus antibody or cytokine-MAb DNL complexes incorporating an irrelevant antibody. In more preferred embodiment the cytokine is G-CSF, erythropoietin or INF-?2b.

Abstract: The present invention provides agents comprising or consisting of a binding moiety with specificity for interleukin-1 receptor accessory protein (IL1RAP) for use in inducing cell death and/or inhibiting the growth and/or proliferation of cells associated with a solid tumour, wherein the cells express IL1RAP. A related aspect of the invention provides agents comprising or consisting of a binding moiety with specificity for interleukin-1 receptor accessory protein (IL1RAP) for use in detecting pathological cells associated with a solid tumor, wherein the cells express IL1RAP. Further provided are pharmacological compositions comprising the agents of the invention and methods of using the same.

Abstract: Provided are activated collagen scaffold materials as well as their special fused active restoration factors useful for promoting tissue repair, such as bone damage repair or nerve injury repair. The special fused active restoration factors are fusion proteins comprising a collagen-binding domain (CBD) at N-/C-terminus of cytokines, wherein the collagen-binding domain is a polypeptide consisting of 7-27 amino acid residues with a conservative sequence shown in SEQ ID NO:4 at N-terminus.

Abstract: A method to measure the volume of fluid present that relies on the pattern of light refraction as it passes though an airway surface liquid (ASL) meniscus. The method comprises allowing epithelial cells to grow on a membrane in a well so as to form a fluid meniscus about the perimeter of the well. The well is then illuminated by a light source. The illuminated cells in the well are then optically imaged by a scanner, a flat bed optical scanner, a camera, or any device capable of imaging. Microscopy may be used but is not needed, and high powered microscopy is certainly not needed. Then the imaging information from the cells in the well is used to determine a property of the meniscus in the well. Specifically, the imaging information can be analyzed to determine the dimensions, shape, and/or volume of the meniscus and the fluid in the well.

Abstract: The invention relates to the field of biomedical and pharmacological research, in particular to the area of immunology, allergies and autoimmune diseases. The inventors have shown that SWAP-70 is a higher-level regulator for STAT-6 and BCL-6, the regulator being specific for IgE production in B-cells by amplifying the effect of STAT-6 and antagonizing the effect of BCL-6. The inventors have observed no influence of SWAP-70 on the expression of other genes that are likewise regulated by STAT-6 and/or BCL-6. In summary, it can be concluded that SWAP-70 positively regulates IgE production by shifting the interaction of the two antagonists STAT-6 and BCL-6 with regulatory elements of the IgE gene in favor of the activator STAT-6. Based on said findings, the invention provides a screening method which allows for identifying novel active agents that specifically inhibit IgE production.

Abstract: An antikine antibody binds to two, three, four, five or more CC chemokines, such as RANTES/CCL5, MIP-1?/CCL3, MIP-1?/CCL4, or MCP-1/CCL2. Methods for affinity maturation and humanization of antikine antibodies as well as the production of hybridoma cell lines producing antikine antibodies by sequential immunization are also disclosed.

Abstract: The present invention also relates to a method of reducing metastases in a subject comprising administering to the subject a composition comprising a multifunctional molecule comprising a first part which is capable of binding to an antigen bearing target and a second part which is capable of binding to a cell.

Abstract: The present invention provides a method for the generation of 223Ra of pharmaceutically tolerable purity comprising i) preparing a generator mixture comprising 227Ac, 227Th and 223Ra; ii) loading said generator mixture onto a strong base anion exchange resin; iii) eluting said 223Ra from said strong base anion exchange resin using a first mineral acid in an alcoholic aqueous solution to give a first eluted 223Ra solution; iv) loading the 223Ra of the first eluted 223Ra solution onto a strong acid cation exchange resin; and v) eluting the 223Ra from said strong acid cation exchange resin using a second mineral acid in aqueous solution to provide a second eluted solution. The invention additionally provides products of corresponding purity and/or products obtained or obtainable by such a method.

Abstract: Methods are disclosed which are useful in increasing maturation of dendritic cells from CD14+ mononuclear cells, by contact with a composition comprising a fucose-containing glycoprotein fraction from Ganoderma lucidum. The extract can also be used for increasing production of a cytokine or a chemokine in a dendritic cell or CD19+ B cell. In addition, a fucose-containing glycoprotein fraction from Ganoderma lucidum can be administered to a subject identified as needing increased immunoglobulin, cytokine, or chemokine production.

Abstract: Disclosed is a highly effective macrophage phagocytosis-activating composition and/or composition promoting cytokine production in macrophages using an active component derived from natural products. A culture obtained by culturing microorganisms belonging to the genus Aureobasidium (Aureobasidium sp.) is used as the active component of the macrophage phagocytosis-activating composition and/or composition promoting cytokine production in macrophages. By means of the macrophage phagocytosis-activating composition and/or composition promoting cytokine production in macrophages, macrophage phagocytosis can be activated, and cytokine production in macrophages can be promoted. In particular, a macrophage phagocytosis-activating composition can activate the phagocytosis of cancer cells or cells damaged or destroyed by anticancer drugs.

Abstract: Provided are activated collagen scaffold materials as well as their special fused active restoration factors useful for promoting tissue repair, such as bone damage repair or nerve injury repair. The special fused active restoration factors are fusion proteins comprising a collagen-binding domain (CBD) at N-/C-terminus of cytokines, wherein the collagen-binding domain is a polypeptide consisting of 7-27 amino acid residues with a conservative sequence shown in SEQ ID NO:1 at N-terminus.

Abstract: The present invention relates to a method for the in vivo, ex vivo, or in vitro determination of physical or chemical parameters of diagnostic interest by use of a slow tumbling paramagnetic agent that is responsive to changes of said physical or chemical parameter through changes in the R2p/R1p ratio allowing the determination of the said parameter in a manner that is independent on the actual agent concentration.

Abstract: The invention provides compositions, methods, and kits for increasing transport of GDNF across the blood brain barrier while allowing its activity to remain substantially intact. The GDNF is transported across the blood brain barrier via one or more endogenous receptor-mediated transport systems.

Abstract: Tin-117m somatoostatin analogues or antagonist are used to treat tumors and symptoms associated with these tumors which express somatostatin receptors, such as gastroenteropancreatic neuroendocrine tumors. The tin-117m somatostatin receptor binding compounds can be administered at a dosage which is effectively apoptotic and not necrotic. Also, if desired, it can be administered at a dose that is necrotic and/or induces necrosis, but only to cells within 290 microns of the tin-117m atom. A novel somatostatin analogue is also disclosed, as well as novel methods to produce the tin labeled analogues and antagonists.

Abstract: The present disclosure provides, inter alia, formulation compositions comprising modified nucleic acid molecules which may encode a protein, a protein precursor, or a partially or fully processed form of the protein or a protein precursor. The formulation composition may further include a modified nucleic acid molecule and a delivery agent. The present invention further provides nucleic acids useful for encoding polypeptides capable of modulating a cell's function and/or activity.

Abstract: The present invention provides a new stable pharmaceutical composition of erythropoietin (EPO) that is stabilized with PVP.

Abstract: A method for purifying serum amyloid P protein from fresh unfrozen plasma, includes recalcifying the fresh unfrozen plasma and separation by phenyl-type hydrophobic interaction chromatography. The serum amyloid P protein is also obtainable by the method and the use thereof for therapeutic treatment purposes. A method for determining amyloid deposits in a tissue or organ of a subject is also provided.

Abstract: The present invention relates to a method of producing a hydroxyalkyl starch derivative comprising reacting hydroxyalkyl starch of formula (I) at its reducing end which is not oxidized prior to said reaction, with a compound of formula (II) R?NH—R? (II) wherein R1-R2 and R3 are independently hydrogen or a linear or branched hydroxyalkyl group, and wherein either R? or R? or R? and R? comprise at least one functional group X capable of being reacted with at least one other compound prior to or after the reaction of (I) and (II), as well as to the hydroxyalkyl starch derivative as such, obtainable by said method, and to a pharmaceutical composition comprising said hydroxyalkyl starch derivative.

Abstract: A modular platform is provided for rapid preparation of various water-soluble prosthetic groups capable to efficiently introduce 18F into proteins with 18F labelling reagents.

Abstract: A composition having a bispecific antibody which binds a stem cell specific antigen and a tissue, differentiated cell or condition associated antigen and an agent that enhances expression of the tissue, differentiated cell or condition associated antigen, is provided. Also provided are methods of using the bispecific antibodies and/or agents to enhance cell therapy.

Abstract: Methods for treating mammals with cancer using molecules that have an IL-21 functional activity are described. The molecules having IL-21 functional activities include polypeptides that have homology to the human IL-21 polypeptide sequence and proteins fused to a polypeptide with IL-21 functional activity. The molecules can be used as a monotherapy or in combination with other known cancer therapeutics.

Abstract: An antikine antibody binds to two, three, four, five or more CC chemokines, such as RANTES/CCL5, MIP-1?/CCL3, MIP-1?/CCL4, or MCP-1/CCL2. Methods for affinity maturation and humanization of antikine antibodies as well as the production of hybridoma cell lines producing antikine antibodies by sequential immunization are also disclosed.

Abstract: The present invention provides compositions and methods for augmenting vaccine immunogenicity using mucin-immunoglobulin fusion proteins.

Abstract: The present invention concerns methods and compositions for forming cytokine-antibody complexes using dock-and-lock technology. In preferred embodiments, the cytokine-MAb DNL complex comprises an IgG antibody attached to two AD (anchor domain) moieties and four cytokines, each attached to a DDD (docking and dimerization domain) moiety. The DDD moieties form dimers that bind to the AD moieties, resulting in a 2:1 ratio of DDD to AD. The cytokine-MAb complex exhibits improved pharmacokinetics, with a significantly longer serum half-life than either naked cytokine or PEGylated cytokine. The cytokine-MAb complex also exhibits significantly improved in vitro and in vivo efficacy compared to cytokine alone, antibody alone, unconjugated cytokine plus antibody or cytokine-MAb DNL complexes incorporating an irrelevant antibody. In more preferred embodiment the cytokine is G-CSF, erythropoietin or INF-?2b.

Abstract: The present invention concerns methods and compositions for forming PEGylated complexes of defined stoichiometry and structure. In preferred embodiments, the PEGylated complex is formed using dock-and-lock technology, by attaching a target agent to a DDD sequence and attaching a PEG moiety to an AD sequence and allowing the DDD sequence to bind to the AD sequence in a 2:1 stoichiometry, to form PEGylated complexes with two target agents and one PEG moiety. In alternative embodiments, the target agent may be attached to the AD sequence and the PEG to the DDD sequence to form PEGylated complexes with two PEG moieties and one target agent. In more preferred embodiments, the target agent may comprise any peptide or protein of physiologic or therapeutic activity. The PEGylated complexes exhibit a significantly slower rate of clearance when injected into a subject and are of use for treatment of a wide variety of diseases.

Abstract: The Invention relates to conjugates of formula (III) or (IIIa), or a salt thereof, their use as radiopharmaceuticals, processes for their preparation, and synthetic intermediates used in such processes.

Abstract: Disclosed are methods of imaging a site in a heart of a subject to detect cardiovascular disease that involve stressing a subject, administering to the stressed subject an effective amount of a radionuclide-labeled chelator-glucose analog conjugate, and imaging the heart of the subject by detecting a signal generated by the conjugate in the heart of the subject. Also disclosed are methods of imaging a peripheral blood vessel in a subject by using a detectable amount of a radionuclide-labeled chelator-glucose analog conjugate. Also disclosed are methods of distinguishing a false positive nuclear cardiology scan from a true positive nuclear cardiology scan, methods of diagnosing congestive heart failure or cardiac ischemia that involve imaging a subject that has been administered a radionuclide-labeled chelator-glucose analog conjugate, and methods to distinguish viable from nonviable myocardium.

Abstract: A method for stimulating the immune response to a vaccine applied to a mammalian subject includes the step of administering to the subject an effective amount of EtxB or a molecule having substantially equivalent activity, free from whole toxin and not linked to an antigen.

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: This invention is drawn to methods of using peptide-based antagonists of TGF-beta to facilitate the healing of cutaneous wounds that includes burns, lacerations and scrapes. The administration of peptide TGF-beta antagonists to wounds results in reduced scarring, wound contraction and deposition of extracellular matrix components, and increased rates of reepithelialization during wound healing.

Abstract: The present invention concerns methods and compositions for stably tethered structures of defined compositions, which may have multiple functionalities and/or binding specificities. Preferred embodiments concern hexameric stably tethered structures comprising one or more IgG antibody fragments and which may be monospecific or bispecific. The disclosed methods and compositions provide a facile and general way to obtain stably tethered structures of virtually any functionality and/or binding specificity. The stably tethered structures may be administered to subjects for diagnostic and/or therapeutic use, for example for treatment of cancer or autoimmune disease. The stably tethered structures may bind to and/or be conjugated to a variety of known effectors, such as drugs, enzymes, radionuclides, therapeutic agents and/or diagnostic agents.

Abstract: The present invention relates to peptide compounds that are agonists of the erythropoietin receptor (EPO-R). The invention also relates to therapeutic methods using such peptide compounds to treat disorders associated with insufficient or defective red blood cell production. Pharmaceutical compositions, which comprise the peptide compounds of the invention, are also provided.

Abstract: The present invention provides humanized, chimeric and human anti-CD74 antibodies, CD74 antibody fusion proteins, immunoconjugates, vaccines and bispecific that bind to CD74, the major histocompatibility complex (MHC) class-II invariant chain, Ii, which is useful for the treatment and diagnosis of B-cell disorders, such as B-cell malignancies, other malignancies in which the cells are reactive with CD74, and autoimmune diseases, and methods of treatment and diagnosis.

Abstract: A compound for delivering a non-cytotoxic therapeutic moiety into nerve cells, the compound having the general formula: B-L-TM where: B is a binding agent capable of selectively binding to a nerve cell surface receptor and mediating absorption of the compound by the nerve cell; TM is a therapeutic moiety which has a non-cytotoxic therapeutic effect when absorbed by a nerve cell; and L is a linker coupling B to TM.

Abstract: The present invention relates to a method of producing a hydroxyalkyl starch derivative comprising reacting hydroxyalkyl starch of formula (I) at its reducing end which is not oxidized prior to said reaction, with a compound of formula (II) R?NH—R? (II) wherein R1-R2 and R3 are independently hydrogen or a linear or branched hydroxyalkyl group, and wherein either R? or R? or R? and R? comprise at least one functional group X capable of being reacted with at least one other compound prior to or after the reaction of (I) and (II), as well as to the hydroxyalkyl starch derivative as such, obtainable by said method, and to a pharmaceutical composition comprising said hydroxyalkyl starch derivative.

Abstract: A modular platform is provided for rapid preparation of various water-soluble prosthetic groups capable to efficiently introduce 18F into proteins with 18F labelling reagents.

Abstract: A method for the treatment of a chronic inflammatory condition in a patient which comprises administration to the patient of an agent which blocks or inhibits IL-3 signalling events in the patient.

Abstract: Methods for the detection and measurement of tagged (labeled) biologically active materials in a sample are described. The tagged biologically active materials are detected using an atomic mass or optical spectrometer having a source of atoms or atomic ions. Element-labeled biologically active materials, comprising antibodies, antibody Fab? fragments, antigens, aptamers, protein complexes, growth factors, hormones, receptors and other biologically active materials attached to a stable elemental tag, can be used in specific binding assays and measured by elemental spectroscopic detection. Also described are methods for the determination of metals in samples of interest using specific antibodies to isolate the target metals and elemental spectroscopy for detection and quantitation. Kits are provided comprising reagents to detect and measure labeled biologically active materials or labeled competition analytes.

Abstract: The present invention relates to an active targeted water-solubility macromolecule polymer, conjugate with interferon and pharmaceutical composition comprising the conjugate. The targeted agent includes, for example, glucose, galatose and the like, as well as their derivates. The conjugate of the present invention is well in water-solubility and have long physiological cycle half-life period, and have specific recognition to pathology organize, improved and increased medication effect of interferon to Hepatitis B, Hepatitis C etc. infectivity sickness and cancer, infect complication etc.

Abstract: Methods for the detection and measurement of tagged (labeled) biologically active materials in a sample are described. The tagged biologically active materials are detected using an atomic mass or optical spectrometer having a source of atoms or atomic ions. Element-labeled biologically active materials, comprising antibodies, antibody Fab? fragments, antigens, aptamers, protein complexes, growth factors, hormones, receptors and other biologically active materials attached to a stable elemental tag, can be used in specific binding assays and measured by elemental spectroscopic detection. Also described are methods for the determination of metals in samples of interest using specific antibodies to isolate the target metals and elemental spectroscopy for detection and quantitation. Kits are provided comprising reagents to detect and measure labeled biologically active materials or labeled competition analytes.

Abstract: The present invention relates to a chelating agent of the general formula: (I), wherein m is 0 or 1; X is NR4 or S; Y is SR5, NHR5 or P(R5)2; R1 and R3 are the same or different and are selected from H, alkyl or aryl; R2 is H, COOH, NHR6 or (CH2)nCOOR6; R4 is H, alkyl, aryl, (CH2)nCOOR6 or (CH2)nOR6; R5 is H, alkyl, aryl, (CH2)nCOOR6 or (CH2)nOR6, R6 is H, alkyl or aryl; n is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; and when R1?R3?CH3, R2, R4 and R5 are not all three H. The invention further relates to a method and kit for the preparation of radiolabeled biomolecules while using the chelating agent.

Abstract: A method for delivering a biologic to a human with Alzheimer's-related dementia, comprising administering the biologic parenterally into the perispinal space of the human without direct intrathecal injection, and thereafter positioning the human's head below the horizontal. The method further includes delivering a TNF antagonist to the brain of a human for treating mild cognitive impairment, Alzheimer's related dementia, or vascular dementia, comprising administering the TNF antagonist golimumab parenterally into the perispinal space of the human without direct intrathecal injection, and thereafter positioning the human in a Trendelenburg position, for delivery of the golimumab to the brain via the human's vertebral venous system.

Abstract: In one embodiment, a method for treating a cancerous disease is provided which includes characterizing a disease by an overexpression of one or more somatostatin receptors, and exposing the one or more somatostatin receptors to a pharmaceutical composition comprising a somatostatin analogue which binds to the one or more somatostatin receptors.