Abstract: The invention provides a carrier-linked prodrugs, wherein the biologically active moieties comprise at least one carboxylic acid and wherein the linkage between the drug moiety and linker is in the form of an ester wherein the hydroxyl group required for ester formation is provided by the linker moiety and the carboxyl group required for ester formation is provided by the drug moiety. The hydroxyl group of the linker is sterically hindered by the presence of an alkyl or aryl group on the carbon directly bound to or adjacent to the carbon carrying the hydroxyl group (?-carbon). The steric effect of the alkyl or aryl group enables greater control of the rate of hydrolytic degradation of such carrier-linked prodrugs.

Abstract: The pharmaceutical composition includes at least one pharmaceutically acceptable carrier, and an active ingredient including an artificially synthesized peptide includes: (A) an amino acid sequence constituting a cell-penetrating peptide and (B) an amino acid sequence constituting the signal peptide in amyloid precursor protein (APP) or an N-terminal partial amino acid sequence or C-terminal partial amino acid sequence from the amino acid sequence constituting that signal peptide.

Abstract: Fusion proteins comprising a transferrin moiety and integrin binding domain and peptide libraries thereof are disclosed. The present invention includes a method of screening transferrin and integrin peptide libraries displayed in fusion proteins expressed by host cells. The fusion proteins of the present invention include transferrin fusion proteins capable of expression in yeast.

Abstract: Compositions and methods relating to soluble dimeric proteins are disclosed. The dimeric proteins comprise first and second polypeptide fusions linked via a dimerizing domain, each polypeptide fusion comprising first and second monomer domains corresponding to a cytokine or an extracellular domain of a cell-surface receptor. The monomer domains may be positioned amino terminal and carboxyl terminal to the dimerizing domain. Alternatively, the monomer domains may be positioned in tandem, either carboxyl terminal or amino terminal to the dimerizing domain. The dimeric proteins are useful in methods for therapy, diagnosis, and research.

Abstract: The present invention relates to the use of a composition including of at least a mutated antithrombin having an anticoagulant activity substantially reduced with respect to the anticoagulant activity of the non mutated antithrombin, or having no anticoagulant activity, for the preparation of a drug intended for the prevention or the treatment of pathologies associated with cellular injury, such as infection, inflammation or hypoxic injury.

Abstract: The invention provides compositions and methods for the targeted bacteriostatic and antibacterial agents and for treatment of sepsis caused by infectious diseases, such as bacterial and fungal diseases. In one aspect, the invention provides methods and compositions for decreasing the levels of LPS in the circulation of an individual, e.g., a human patient with sepsis, e.g., gram negative septic shock. In one aspect, the invention is directed to chimeric proteins comprising the MD-2 polypeptide and an opsinizing agent, e.g., antibody Fc domains, or equivalent. In one aspect, the invention is directed to chimeric proteins comprising fragments or altered form of MD-2 polypeptide and an opsinizing agent, e.g., antibody Fc domains, or equivalent. The invention also provides pharmaceutical compositions comprising the chimeric polypeptides of the invention, and methods of making and using them, including methods for ameliorating or preventing sepsis.

Abstract: The present invention relates to the use of secreted proteins from mesenchymal stem cells and other cells for the treatment of myocardial infarction. In particular, the invention provides compositions and methods based on secreted proteins from mesenchymal stem cells and the genes encoding them.

Abstract: The present invention relates to the use of Meteorin for the treatment of allodynia, hyperalgesia, spontaneous pain and phantom pain. In a preferred embodiment the disorder to be treated is allodynia, and hyperalgesia, more preferably allodynia including thermal and tactile allodynia.

Abstract: Disclosed are compositions and methods useful for targeting tumors, sites of injury and blood clots. The compositions and methods are based on peptide sequences that selectively bind to and home to tumors, sites of injury and blood clots in animals. The disclosed targeting is useful for delivering therapeutic and detectable agents to tumors, sites of injury and blood clots.

Abstract: The present invention is based on the discovery of genetic polymorphisms that are associated with rheumatoid arthritis. In particular, the present invention relates to nucleic acid molecules containing the polymorphisms, variant proteins encoded by such nucleic acid molecules, reagents for detecting the polymorphic nucleic acid molecules and proteins, and methods of using the nucleic acid and proteins as well as methods of using reagents for their detection.

Abstract: The present invention provides methods of achieving directed evolution of viruses by in vivo screening or “panning” to identify viruses comprising scrambled AAV capsids having characteristics of interest, e.g., tropism profile and/or neutralization profile (e.g., ability to evade neutralizing antibodies). The invention also provides scrambled AAV capsids and virus particles comprising the same.

Abstract: According to the embodiments described herein, a series of biological materials for treatment/therapy of DMD and/or BMD through the recovery of sarcolemmal nNOS is provided. The biological material comprises the complete dystrophin repeats R16 and R17 or certain domains, sections, or fragments of the dystrophin repeats R16 and R17. In some aspects, such domains, sections, or fragments may be selected from sequence motifs including dystrophin R17 ?1 helix, ?2 and ?3 helices of both R16 and R17, or a combination thereof.

Abstract: The present invention provides methods of using PILR? agonists, or PILR? antagonists, to treat immune disorders, such as autoimmune and inflammatory disorders, including CNS, joint and gut inflammation.

Abstract: Methods and compositions are provided for the therapeutic use of Wnt proteins, for enhancing bone growth and regeneration, including repair following injury, osseointegration of implants, and the like. In some embodiments of the invention, the compositions are administered locally, e.g. by injection at the site of an injury. For certain conditions it is desirable to provide Wnt activity for short periods of time, and an effective dose will be administered over a defined, short period of time.

Abstract: The present invention relates to a method for the treatment of vascular dysfunction, reducing ischemic pain and/or treatment of a vascular disease comprising administering a therapeutically effective amount of Annexin A5 or a functional analogue or variant thereof to a patient in need of such treatment. The vascular dysfunction, ischemic pain and/or vascular disease may be associated with impaired endothelium mediated vasodilatation, a reduced eNOS activity, and/or a reduced NO bioavailability. The patient may be suffering from a disease selected from angina pectoris, ischemic heart disease, peripheral artery disease, systolic hypertension, migraine, type 2 diabetes and erectile dysfunction.

Abstract: Nanoparticle delivery systems for use in targeting biologically active agents to the central nervous system comprise a composition comprising (a) a nanoparticle comprising: (i) a core comprising a metal and/or a semiconductor; and (ii) a corona comprising a plurality of ligands covalently linked to the core, wherein said ligands comprise a carbohydrate, insulin and/or a glutathione; and (b) the at least one agent to be delivered to the CNS. Methods of treatment and diagnosing CNS disorders utilising the nanoparticle delivery systems and related screening methods are also disclosed.

Abstract: The composition includes either an isolated protein complex including MCM8 and MCM9 proteins, or nucleic acid molecules coding for the proteins that constitute the complex, or compounds inhibiting the formation and/or the stability, or the activity of the complex, for its use for enhancing or reducing animal, preferably mammal, fertility.

Abstract: A novel use of a neuropeptide for treating brain injury in a subject in need thereof is provided. The present invention also provides various amenable routes of administering urocortin, that is, via injection intracerebroventricularly and intraperitoneally, and via intravenous bolus administration.

Abstract: The invention relates to methods of promoting the expression of pro-angiogenic factors and decreasing the expression of anti-angiogenic and fibrotic factors in a cell, as well as the treatment of cardiomyopathy and wounds.

Abstract: The present invention relates to binding proteins specific for Vascular Endothelial Growth Factor A (VEGF-A), in particular to recombinant binding proteins comprising a polyethylene glycol moiety and a binding domain, which inhibits VEGF-Axxx (wherein xxx denotes the amino acid length of the VEGF-A mature protein) binding to Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2). Examples of such recombinant binding proteins are proteins which comprise an ankyrin repeat domain with the desired binding specificity, and a polyethylene glycol moiety. The binding proteins are useful in the treatment of cancer and other pathological conditions, e.g. eye diseases such as age-related macular degeneration.

Abstract: The invention relates to novel molecules that can modulate one of the mechanisms leading to the massive deposition of cholesterol in the cardiomyocytes and/or in the smooth muscle cells of the vascular wall, during acute myocardial infarction or other clinical situations involving ischaemia. The invention also shows that the blockage of LRP1 by means of certain agents, including a recombinant expression vector, an RNAi, an antibody, a siRNA etc., prevents the overaccumulation of esterified cholesterol in the cardiomyocytes and/or in the smooth muscle cells of the vascular wall exposed to ischaemia. The invention also relates to the use of said molecules in the treatment and/or prevention of the changes in the metabolism of calcium and cardiac remodeling associated with ischaemia.

Abstract: The present invention relates to the use of chaperonin 10 to modulate the function of antigen presenting cells. More particularly the invention resides in the modulation of cell surface expression of MHC molecules such as HLA.

Abstract: The present invention relates to a method for suppressing neuroendocrine disease. The therapy employs use of a non-cytotoxic protease, which is targeted to a neuroendocrine tumor cell, preferably via a somatostatin or cortistatin receptor, a GHRH receptor, a ghrelin receptor, a bombesin receptor, a urotensin receptor a melanin-concentrating hormone receptor 1; a KiSS-1 receptor or a prolactin-releasing peptide receptor. When so delivered, the protease is internalized and inhibits secretion from said tumor cell. The present invention also relates to polypeptides and nucleic acids for use in said methods.

Abstract: The invention relates to optimized adhesins and nanoparticles to which said adhesins are bound. The invention furthermore relates to providing said nanoparticles by way of in vivo contrast agents, in particular for the diagnosis of bowel cancer.

Abstract: The invention relates to IHG-1 (induced by high glucose-1) a novel gene which encodes a protein that amplifies fibrotic responses in in vitro and in vivo models of fibrotic disorders and in human diabetic nephropathy. In particular the invention relates to modifications of the IHG-1 structure which are potential fibrosuppressant biotherapeutics and modify cellular invasiveness. The invention also relates to a method of screening a therapeutic agent for suitability for the treatment of fibrotic disease comprising testing a candidate therapeutic agent for the ability to reduce the expression of IHG-1 levels in a model system.

Abstract: A method may include administering botulinum toxin to a tissue of a patient and administering a neuropeptide of the CRF family to the tissue of the patient. In some examples, the botulinum toxin is periodically administered to the tissue of the patient and/or the neuropeptide of the CRF family is periodically administered to the tissue of the patient. The periods with which the botulinum toxin and the neuropeptide of the CRF family are administered may be the same or may be different. In some examples, the botulinum toxin and the neuropeptide of the CRF family are administered to the tissue at substantially the same time, while in other embodiments, the botulinum toxin and the neuropeptide of the CRF family are administered to the tissue at different times.

Abstract: Compositions and methods for preventing or ameliorating tissue damage caused by an inflammatory disorder or pathogenic infections are described. In one aspect, a method for preventing or ameliorating tissue damage caused by an inflammatory disorder or pathogenic infection comprises administering to a subject a therapeutically effective amount of a neuregulin. In another aspect, the composition comprises one or more active agents that: (a) increase expression or activity of a neuregulin; (b) inhibit the expression or activity of CXCL10, STAT3 or HEME; or (c) both (a) and (b).

Abstract: The present invention relates to treatment of mucus hypersecretion, to compositions therefore and manufacture of those compositions. The present invention relates particularly, though not exclusively, to the treatment of chronic bronchitis in chronic obstructive pulmonary disease (COPD), asthma and other clinical conditions involving COPD.

Abstract: The invention provides T cell receptors (TCRs) having antigenic specificity for a cancer antigen, e.g., tyrosinase. Also provided are related polypeptides, proteins, nucleic acids, recombinant expression vectors, isolated host cells, populations of cells, and pharmaceutical compositions. The invention further provides a method of detecting the presence of cancer in a host and a method of treating or preventing cancer in a host using the inventive TCRs or related materials.

Abstract: IL4/IL13-binding proteins comprise binding domains, which inhibit IL4/IL13 binding to IL4Ralpha and common gamma chain complexes (Type 1) and inhibit IL4 binding to IL4Ralpha and IL13Ralpha1 complexes (Type 2), and IL13 binding to IL13Ralpha1 and/or IL13Ralpha2, are useful in the treatment of cancer, inflammatory, and other pathological conditions, such as allergic or fibrotic conditions, especially pulmonary conditions.

Abstract: The invention provides a L19 source as a medicament, preferably for preventing or treating an inflammatory disorder in an individual.

Abstract: The present invention comprises the use of sickle cells or sickle cell precursors loaded with a therapeutic agent that localize in tumors and induce a tumoricidal response.

Abstract: Disclosed are compounds of Formula 1, N-oxides, and salts thereof, wherein X is O or S; Y is O or S; A is O, S, NR3e or C(R3c)?C(R3d); Z is a direct bond, O, S(O)n, NR6, C(R7)2O, OC(R7)2, C(?X1), C(?X1)E, EC(?X1), C(?NOR8) or C(?NN(R6)2); a is 1, 2 or 3; and R1, R2, R3a-R3e, R4, R5, R6, R7, R8, X1 and E are as defined in the disclosure. Also disclosed are compositions containing the compounds of Formula 1 and methods for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound or a composition of the invention.

Abstract: An isolated protein selected from the group consisting of (i) proteins comprising an amino acid sequence having at least 70% identity to the C-terminal domain of lung surfactant protein C precursor (CTproSP-C, “CTC”) from a mammal; and (ii) proteins comprising an amino acid sequence having at least 70% identity to the Brichos domain of CTproSP-C from a mammal, is disclosed for treatment of Alzheimer's disease in a mammal, including man.

Abstract: An isolated protein is provided for use in treatment of a condition selected from the group consisting of Alzheimer's disease, familial Danish dementia and familial British dementia in a mammal, including man. The isolated protein is selected from the group consisting of proteins comprising an amino acid sequence having at least 70% identity to residues 90-236 of Bri2 from human; and proteins comprising an amino acid sequence having at least 70% identity to any one of the Brichos domains of Bri2 from human, chimpanzee, bovine, pig, mouse and rat.

Abstract: This document provides methods and materials for providing teeth with a white appearance. For example, methods and materials for contacting teeth with one or more fluorescence emitting polypeptides (e.g., a blue fluorescent protein (BFP)) to provide the teeth with a whiter appearance are provided.

Abstract: The subject of the present invention is the use, in particular the cosmetic and/or therapeutic use, of the apolipoprotein D, of polypeptides derived from this protein or of analogues thereof, of a nucleic sequence encoding such a polypeptide or of an agent modulating the activity or of the expression of such a polypeptide, in particular for stimulating terminal epithelial differentiation. The invention also relates to the use of the protein apolipoprotein D, of polypeptides derived from this protein or of analogues thereof, or of a nucleic sequence encoding such a polypeptide as a marker for evaluating the state of the epidermis.

Abstract: The present invention provides soluble CTLA4 mutant molecules which bind with greater avidity to the CD80 and/or CD86 antigen than wild type CTLA4 or non-mutated CTLA4Ig. The soluble CTLA4 molecules have a first amino acid sequence comprising the extracellular domain of CTLA4, where certain amino acid residues within the S25-R33 region and M97-G107 region are mutated. The mutant molecules of the invention may also include a second amino acid sequence which increases the solubility of the mutant molecule.

Abstract: Disclosed are variant RTEF-1 polypeptides having an RTEF-1 amino acid sequence with one or more internal deletions, wherein the polypeptides reduce VEGF promoter activity. Some of the RTEF-1 polypeptides include an amino acid sequence that is at least 80% identical to the contiguous amino acids of 1) amino acids 24 to 47 of SEQ ID NO:15 and 2) each of SEQ ID NOs:16 and 17, but does not comprise the contiguous amino acids of SEQ ID NOs:8, 9, 11, or 12. Also disclosed are nucleic acids encoding the variant RTEF-1 polypeptides of the present invention. Pharmaceutical compositions that include the polypeptides and nucleic acids of the present invention are also disclosed. Methods of inducing cell contact inhibition, regulating organ size, and reducing intracellular YAP activity are also set forth, as well as methods of treating hyperproliferative diseases such as cancer using the pharmaceutical compositions of the present invention.

Abstract: The present invention refers to protein kinase inhibitors and more specifically to inhibitors of the protein kinase c-Jun amino terminal kinase. Additionally, the present invention provides JNK inhibitor sequences, chimeric peptides, nucleic acids encoding same as well as pharmaceutical compositions for treating pathophysiologies associated with JNK signaling.

Abstract: Streptavidin(SA)-4-1BBL and TLR agonists such as monophosphoryl lipid A (MPL) exhibit surprising synergy as adjuvants, inducing immune responses against weak antigens. Accordingly, there are provided adjuvant compositions comprising 4-1BBL and a toll-like receptor (TLR) agonist, such as MPL, methods of inducing an immune response against an antigen in a subject, comprising administering to the subject (a) the antigen, (b) a TLR agonist and, (c) 4-1BBL, and methods of treating a tumor or a cancer in a subject, comprising administering to the subject (a) an antigen associated with the tumor or cancer, (b) a TLR agonist, and (c) 4-1BBL.

Abstract: The invention provides compositions and method for delivering a therapeutic or diagnostic agent to a disease site in a mammal, the method comprising administering to the mammal a therapeutically or diagnostically effective amount of a pharmaceutical composition, wherein the pharmaceutical composition comprises the therapeutic or diagnostic agent coupled to a Procaspase 8 polypeptide and a pharmaceutically acceptable carrier.

Abstract: An active biological substance is disclosed for use in abnormal cellular and viral membrane physiologies in human and mammal organisms. The active substance has diagnostic and/or therapeutic properties and contains or consists of at least one component selected from the group of substances including: histones, covalently modified histones, histone-like polypeptides, biologically active histone sequences and histone-like polypeptides as agents for stopping the supply to solid tumors over their blood vessels, for killing cells infected by virus and for killing tumour cells with disturbed lipid asymmetry.

Abstract: The present invention relates to therapeutic uses of soluble alpha-Klotho.

Abstract: A chemoembolic agent is disclosed that includes an injectable, recombinantly synthesized silk-elastin like protein copolymer and one or more chemotherapeutic agents. Upon injection, the chemoembolic agent blocks the tumor vasculature, including the capillary bed, and may optionally release chemotherapeutic agents. The chemoembolic agent may be used to treat cancer, including hepatocellular carcinoma.

Abstract: [Problem] The topic of the present invention is the elucidation of the biological function of CTRP6 and its application. [Solution] A pharmaceutical composition containing CTRP6 for the prevention or treatment of autoimmune disease. Ideally, a pharmaceutical composition for the prevention or treatment of inflammation associated with autoimmune disease, for example, rheumatoid arthritis or type 1 diabetes, is provided.

Abstract: Described are compositions and methods useful for modulating the immune system of a subject. Also included are diagnostic methods for monitoring an immunologic condition. In particular the invention relates to antagonists of interferon proteins and associated methods of use as well as methods to develop neutralizing antibodies against IFN antagonists to treat viral infections.

Abstract: The present invention relates to the diagnosis of neurological disorders, more specifically to the diagnosis of multiple sclerosis. A biomarker panel is provided which can be used to detect if a subject has multiple sclerosis. Also described are methods of identification of such biomarkers.

Abstract: In certain aspects, the present invention provides BMP10 propeptides for use in treating a variety of disorders including heart disorders and other disorders associated with unwanted activity of the mature BMP10 polypeptide. The present invention also provides methods of screening compounds that modulate activity of BMP10.

Abstract: Provided are soluble neutral active Hyaluronidase Glycoproteins (sHASEGP's), methods of manufacture, and their use to facilitate administration of other molecules or to alleviate glycosaminoglycan associated pathologies. Minimally active polypeptide domains of the soluble, neutral active sHASEGP domains are described that include asparagine-linked sugar moieties required for a functional neutral active hyaluronidase domain. Included are modified amino-terminal leader peptides that enhance secretion of sHASEGP. Sialated and pegylated forms of the sHASEGPs also are provided. Methods of treatment by administering sHASEGPs and modified forms thereof also are provided.