Abstract: This invention describes an ICE inhibitor prodrug (I) having good bioavailability. Compound I is useful for treating IL-1 mediated diseases such as rheumatoid arthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, inflammatory peritonitis, septic shock, pancreatitis, traumatic brain injury, organ transplant rejection, osteoarthritis, asthma, psoriasis, Alzheimer's disease, myocardial infarction, congestive heart failure, Huntington's disease, atherosclerosis, atopic dermatitis, leukemias and related disorders, myelodysplastic syndrome, uveitis or multiple myeloma.

Abstract: The present invention is directed to methods, kits and compositions for preventing or treating age-related conditions or metabolic disorders. The Klotho fusion polypeptides of the invention include at least a Klotho protein or an active fragment thereof. In one embodiment, the fusion polypeptide comprises a Klotho polypeptide, a FGF (such as FGF23) and (optionally) a modified Fc fragment. The Fc fragment can, for example, have decreased binding to Fc-gamma-receptor and increased serum half-life. The Klotho fusion proteins are useful in the treatment and prevention of a variety of age-related conditions and metabolic disorders. In another embodiment, the fusion polypeptide comprises a FGF (such as FGF23) and a modified Fc fragment.

Abstract: The present invention relates to potent compounds having combined antioxidant, anti-inflammatory, anti-radiation and metal chelating properties. Specifically, the present invention relates to short peptides having these properties, and to methods and uses of such short peptides in clinical and cosmetic applications.

Abstract: The invention provides glucagon analogue peptides and their use for promoting weight loss or preventing weight gain, and the treatment of obesity or excess body weight and associated conditions. The compounds may also be used to improve glycemic control and/or for the treatment of diabetes. The compounds may mediate their effect, inter alia, by having increased selectivity for the GLP-1 receptor as compared to human glucagon.

Abstract: Novel HDL mimetic polypeptides are disclosed, particularly Apo A-1 Carnivora/Sapien polypeptides. Nucleic acids coding for the Apo A-1 Carnivora/Sapien polypeptides are also disclosed, as are pharmaceutical formulations comprising the disclosed polypeptides and pharmaceutical formulations comprising the disclosed nucleic acids. Finally, methods to prevent, treat, ameliorate, and diagnose atherosclerosis and related disorders, in mammals, such as humans, are disclosed.

Abstract: The present invention provides the use of recombinant plasminogen activator inhibitor-1 (PAI-1) isoform 23 in methods of increasing plasmin activity, inhibiting angiogenic vasa vasorum, promoting plaque regression and treating atherosclerosis by administering to a subject in need of treatment an effective amount of recombinant plasminogen activator inhibitor type isoform 23 (rPAI-123). In some embodiments, rPAI-123 is set forth in SEQ ID NOs:5-8. In other embodiments, rPAI-123 is administered at a dose in the range of approximately 2.5 ?g/kg/day to 20 ?g/kg/day. In further embodiments, the effective amount achieves a ratio of rPAI-123 to PAI-1 is in the range of approximately 1:2 to 3:1.

Abstract: Disclosed herein are methods and compositions for the treatment and/or prevention of diseases or conditions comprising administration of GLP-1, and/or naturally or artificially occurring variants or analogues of GLP-1, or pharmaceutically acceptable salts thereof, alone or in combination with one or more active agents (e.g., an aromatic-cationic peptide such as D-Arg-2?6?-Dmt-Lys-Phe-NH2).

Abstract: The disclosure provides microcrystals of Y receptor agonists; microcrystalline pellets of Y receptor agonists, and microcrystalline suspensions of Y receptor agonists. Pharmaceutical compositions containing these microcrystals, microcrystalline pellets, and microcrystalline suspensions have prolonged pharmacokinetic profiles making them useful for once daily or once weekly administration.

Abstract: Embodiments described herein are directed to methods for the treatment and control of hyperlipidemia, hypercholesterolemia, dyslipidemia, and other lipid disorders, and in delaying the onset of or reducing the risk of conditions and sequelae that are associated with these diseases, including atherosclerosis and non-insulin dependent diabetes. In addition, embodiments are directed to methods of treating coronary heart disease and metabolic syndrome. Embodiments are also directed to neurotensin analogs. In embodiments, the neurotensin analogs may be capable of binding to neurotensin receptors and, upon binding, may modulate the levels of lipids in subjects.

Abstract: The invention relates to polypeptides comprising an amino acid sequence which is an analogue of human amylin, pharmaceutical compositions comprising these polypeptides, and these polypeptides for use as medicaments.

Abstract: The invention relates to polypeptides comprising an amino acid sequence which is an analogue of pramlintide, pharmaceutical compositions comprising these polypeptides, and these polypeptides for use as medicaments.

Abstract: A method of selecting a semaphorin for treating cancer in a subject is disclosed. The method comprises determining an expression of a semaphorin receptor on tumor cells of a tumor sample of the subject wherein an amount of the semaphorin receptor is indicative of the semaphorin suitable for treating the cancer in the subject. Methods of treating angiogenesis, kits for treating cancer and pharmaceutical compositions comprising semaphorins are also disclosed.

Abstract: The invention provides a peptide comprising or consisting of SEQ ID NO: 1 and variants thereof, particularly comprising of consisting of the sequence FTY, nucleic acids encoding said peptides and pharmaceutical and nutraceutical compositions comprising said peptide(s) and/or nucleic acids. Also provided is the use of such a peptide in therapy and in vitro methods of ACE-inhibition.

Abstract: Anti-angiogenic agents or polypeptides comprising an amino acid segment substantially similar to domain one of CD2 wherein the polypeptide has a ?-sheet formed by two segments. Methods of using such agents and polypeptide are also included.

Abstract: Disclosed herein are methods for treating a vascular inflammatory disorder or endothelial cell disorder using inhibitor compounds that inhibit the expression or biological activity of Tie-1, Tie-1 endodomain, thrombin, VEGFR2, VEGFR2 endodomain, EphA2, and any of the cytokines or kinases that are upregulated by activation of Tie-1 or thrombin, as provided herein. Also disclosed are the use of combinations of inhibitor compounds or the use of an eNOS activator compound in combination with any one or more of the inhibitor compounds. Also disclosed are methods for inhibiting the pro-coagulant activity of thrombin using a Tie-1 or Tie-1 endodomain inhibitor compound or an EphA2 inhibitor compound. Methods for diagnosing and monitoring vascular inflammatory disorders or endothelial cell disorders that include the measurement of any of the polypeptides or nucleic acid molecules of the invention are also disclosed.

Abstract: The present invention relates generally to tissue differentiation factor (TDF) analogs. More specifically, the invention relates to structure-based methods and compositions useful in designing, identifying, and producing molecules which act as functional modulators of TDF-like receptors. The invention further relates to methods of detecting, preventing, and treating TDF-associated disorders.

Abstract: The present invention relates to compositions and methods for the reduction of atherosclerotic plaques and the decrease in the level of total serum cholesterol, triglycerides, serum LDL cholesterol, and serum HDL cholesterol. The present invention also relates to methods for the diagnosis, prevention and treatment of atherosclerosis and mycoplasma associated diseases, cardiotoxicity related to cancer treatment, and Chagas disease related cardiomyopathies.

Abstract: Treatments employing the matricellular protein thrombospondin-1 (TSP-I) and related compositions are disclosed for stabilizing atherosclerotic plaque and decreasing occurrence of plaque rupture events leading to, for example, myocardial infarction, stroke, and acute limb ischemia. Various peptides, including certain synthetic peptides, related to TSP-I are also disclosed. Such peptides have utility in stabilizing plaque in various contexts, including the disease states mentioned above. Some of these peptides include one or more sequences related to active sites of TSP-I for regulating, e.g., TGF-ss1 and MMP-9 activity. Experimental data show that a representative peptide provides a beneficial effect with systemic injection of the peptide.

Abstract: Provided is a rapamycin formulation using a recombinant high-density lipoprotein including apolipoprotein mutant, the rapamycin formulation in which solubility of rapamycin and medical use, such as aging suppression and arteriosclerosis suppression, are improved by using recombinant high-density lipoprotein including apolipoprotein A-I and its mutant V156K.

Abstract: The invention provides human signal peptide-containing proteins (HSPP) and polynucleotides which identify and encode HSPP. The invention also provides expression vectors, host cells, antibodies, agonists, and antagonists. The invention also provides methods for diagnosing, treating, or preventing disorders associated with expression of HSPP.

Abstract: A method for the treatment of cardiovascular disease or disorder in a subject in need thereof, the method comprising the steps of administering an ApoA1 mimetic that is capable of promoting cholesterol efflux from lipid loaded cells in the subject, wherein the ApoA1 mimetic has an amino acid sequence that includes at least a portion of the amino acid sequence of ApoA1 or a mimetic of ApoA1 that contains at least one tryptophan, at least one tryptophan from the ApoA1 or mimetic of the ApoA1 being substituted with an oxidant resistant amino acid in the amino acid sequence of the ApoA1 mimetic.

Abstract: The invention relates to a biodegradable microparticle having a diameter between 0.2 and 3.5 micrometer and comprising a pharmaceutically effective amount of at least one small heat-shock protein that induces IL-10 production in macrophages, said small heat-shock protein comprising an amino acid sequence identity of at least 50% to any of the sequences listed as SEQ ID NOs: 1 and 12-26.

Abstract: The invention relates to melanocortin receptor-specific cyclic peptides of Formula (I) or a pharmaceutically acceptable salt thereof, where R1, R2, R3, R4a, R4b, R4c, R5, x and y are as defined in the specification. These compounds are particularly useful in the treatments of energy homeostasis and metabolism related (e.g. diabetes), food intake related and/or energy balance and body weight related diseases, disorders and/or conditions, including obesity, overweight and diseases, disorders and/or conditions associated with obesity and/or overweight, such as type 2 diabetes and metabolic syndrome.

Abstract: Herein is reported a shortened tetranectin-apolipoprotein A-I fusion protein and a lipid particle comprising the shortened tetranectin-apolipoprotein A-I fusion protein as well as uses thereof.

Abstract: The invention provides methods for treating an obstructed biological conduit that include administering to the conduit an agent that can degrade extracellular matrix of obstructing tissue. Particular methods include delivery of an enzyme or a mixture of several enzymes to the area or region of obstruction wherein the enzyme(s) have the capability to degrade extracellular matrix components within the obstruction thereby restoring the normal flow of transported fluid through the conduit. The invention also includes prophylactically dilating a section of conduit to minimize the risk of obstruction formation. The invention further includes methods for prolonging patency of hemodialysis access.

Abstract: Peptides are provided that are capable of inhibiting cell activation mediated by a Toll-like receptor (TLR) selected from TLR 1, 2, 4 or 6, said peptide comprising a sequence consisting of, or found within, the sequence of the transmembrane domain of a TLR selected from TLR 1, 2, 4 or 6 and optionally cytoplasmic and extracellular regions flanking the transmembrane domain. These peptides as well as pharmaceutical composition comprising them are useful for the treatment of TLR-mediated disease.

Abstract: The present invention provides methods and compositions for treating inflammation and inflammatory disorders in a subject, by administering an effective amount of KSHV-Orf63 and/or active peptides and/or fragments thereof.

Abstract: The present invention provides a method for treating a human patient with a pathology by administering to the subject an effective amount of an agent selected from the group of: native full-length CCN3 proteins; analog CCN3 full-length proteins with native cysteine residues substituted by a replacement amino acid; CCNp native peptide fragments having from about 12 to about 20 amino acids; analog CCNp peptide fragments with native cysteine residues substituted with a replacement amino acid; and combinations thereof.

Abstract: The present invention relates to novel chimeric molecules of ficolin-associated polypeptides, such as fusion polypeptides for the use in the treatment of conditions associated with inflammation, apoptosis, autoimmunity, coagulation, thrombotic or coagulopathic related diseases. The present invention further relates to nucleic acid molecules encoding such fusion polypeptides, vectors and host cells used in the production of the fusion polypeptides.

Abstract: Site-specific modifications of proteins at their N-termini are provided. In particular, a chemical modification of proteins at their N-termini via a transamination reaction to form homogeneous adducts such as, the corresponding oxime derivatives is provided. Methods of making and using the adducts in radio-labelling, molecular imaging applications, and treatment of disorders such as cancer, Crohn's disease, arthritis, atherothrombosis and plaque rupture are also provided.

Abstract: The present invention relates to fibronectin based scaffold domain proteins that bind PCSK9. The invention also relates to the use of the innovative proteins in therapeutic applications to treat atherosclerosis, hypercholesterolemia and other cholesterol related diseases. The invention further relates to cells comprising such proteins, polynucleotides encoding such proteins or fragments thereof, and to vectors comprising the polynucleotides encoding the innovative protein.

Abstract: The present invention relates to a compound of the Formula (I)): or pharmaceutically acceptable salt thereof, wherein the symbols are as defined in the specification; a pharmaceutical composition comprising the same, a method for treating or preventing viral infections, inflammation, dry eye, central nervous disorders, cardiovascular diseases, cancer, obesity, diabetes, muscular dystrophy, and hair loss.

Abstract: The invention is directed to a pharmaceutical composition containing at least one FGF-21 (fibroblast growth factor 21) compound, at least one GLP-1R (glucagon-like peptide-1 receptor) agonist and optionally at least one anti-diabetic drug and/or at least one DPP-4 (dipeptidyl peptidase-4) inhibitor for the treatment of at least one metabolic syndrome and/or atherosclerosis, in particular diabetes, dyslipidemia, obesity and/or adipositas.

Abstract: The invention relates to polypeptides of amino acid sequence SEQ ID NO: 1 according to formula (1), the use thereof for producing a medicament, and medicaments for the treatment of diseases related to monocyte recruitment.

Abstract: The present invention relates to methods for preventing or treating of metabolic disorders and related conditions, such as in certain patient groups.

Abstract: The invention provides a synthetic polypeptide of Formula I?: or an amide, an ester or a salt thereof, wherein X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12 and X13 are defined herein. The polypeptides are agonist of the APJ receptor. The invention also relates to a method for manufacturing the polypeptides of the invention, and its therapeutic uses such as treatment or prevention of acute decompensated heart failure (ADHF), chronic heart failure, pulmonary hypertension, atrial fibrillation, Brugada syndrome, ventricular tachycardia, atherosclerosis, hypertension, restenosis, ischemic cardiovascular diseases, cardiomyopathy, cardiac fibrosis, arrhythmia, water retention, diabetes (including gestational diabetes), obesity, peripheral arterial disease, cerebrovascular accidents, transient ischemic attacks, traumatic brain injuries, amyotrophic lateral sclerosis, burn injuries (including sunburn) and preeclampsia.

Abstract: A reconstituted high density lipoprotein formulation having relatively low toxicity comprises an apolipoprotein such as ApoAI or fragment thereof, a lipid and a detergent at a level which is about 5-50% of that which would normally cause liver toxicity upon administration to a human. The lipid is optimally phosphatidylcholine at about 30-50 g/L and the molar ratio of apolipoprotein:lipid is optimally in the range 1:40 to 1:75. The formulation is useful for treating diseases or conditions such as cardiovascular disease, hypercholesterolaemia and hypocholesterolaemia inclusive of acute coronary syndrome (ACS), atherosclerosis and myocardial infarction.

Abstract: The present invention is directed to various uses of fibronectin binding proteins or polypeptides for treating and preventing fibrosis and fibrosis related conditions. The fibronectin binding proteins and polypeptides are also useful for treating conditions associated with vascular remodeling and cardiac dysfunction.

Abstract: Leptin, leptin analogs, and leptin derivatives are used to treat patients with lipoatrophy. Leptin is effective against conditions of lipoatrophy for both genetic and acquired forms of the disease. A therapeutically effective amount of leptin can be administered in a variety of ways, including subcutaneously and using gene therapy methods. Methods of the present invention contemplate administration of leptin, leptin analogs, and leptin derivatives to patients having a leptin level of approximately 4 ng/ml or less before treatment.

Abstract: Compositions and methods for modulating the deposition of elastin by administering compositions including insulin receptor agonists are described herein.

Abstract: An extract for preventing or treating thrombotic diseases, particularly, an extract of at least one of leeches and earthworms having a molecular weight of no more than 5,800 daltons is provided, wherein the extract includes 15% to 38% amino acid, 40% to 60% saccharide and 0.3% to 1% hypoxanthine. Processes for preparation, pharmaceutical compositions and uses thereof are also provided. Compared to conventional arts, the extract has safety greatly improved and drug actions maintained and even improved.

Abstract: The present invention provides a multimeric form of a Tie 2 binding peptide monomer, wherein the multimeric form has Tie 2 agonist activity. The multimeric form, preferably a tetramer, stimulates angiogenesis and promotes wound healing. The present invention also features pharmaceutical compositions comprising the multimeric Tie 2 agonists, including those suitable for topical or systemic administration. Methods of using the multimeric Tie 2 agonists of the invention for stimulating angiogenesis and for promoting healing of wounds, such as diabetic ulcers or skin grafts, are also provided.

Abstract: The present disclosure provides methods and uses of Slit proteins and nucleic acids for inhibiting platelet coagulation and related disorders. Further provided is a vascular device coated with Slit protein or a cell expressing a Slit protein.

Abstract: Compounds of the formula I wherein R2a and R2b are independently H, halo, C1-C4alkyl, C1-C4haloalkyl or C1-C4alkoxy, or R2a and R2b together with the carbon atom to which they are attached form a C3-C6cycloalkyl; R3 is a C5-C10 alkyl, optionally substituted with 1-3 substituents independently selected from halo, C1-C4haloalkyl, C1-C4alkoxy, C1-C4haloalkoxy; or R3 is a C2-C4alkyl chain with at least 2 chloro or 3 fluoro substituents; or R3 is C3-C7cycloalkylmethyl, optionally substituted with 1-3 substituents independently selected from C1-C4alkyl, halo, C1-C4haloalkyl, C1-C4alkoxy, C1-C4haloalkoxy; R4 is C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy, C1-C6haloalkoxy, C1-C6alkylamino, C1-C6dialkylamino or; R4 is Het or Carbocyclyl, either of which is optionally substituted with 1-3 substituents R4 is Het, carbocyclyl, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy or C1-C6haloalkoxy; n is 1, 2 or 3; for the use in the prophylaxis or treatment of a disorder characterised by inappropriate expression or activation of cath

Abstract: Embodiments described herein are directed to methods for the treatment and control of hyperlipidemia, hypercholesterolemia, dyslipidemia, and other lipid disorders, and in delaying the onset of or reducing the risk of conditions and sequelae that are associated with these diseases, including atherosclerosis and non-insulin dependent diabetes. In addition, embodiments are directed to methods of treating coronary heart disease and metabolic syndrome. Embodiments are also directed to neurotensin analogs. In embodiments, the neurotensin analogs may be capable of binding to neurotensin receptors and, upon binding, may modulate the levels of lipids in subjects.

Abstract: Ligand-specific HVEM variants, compositions comprising such variants, and methods of treating inflammatory diseases comprising administering such variants, are provided.

Abstract: The present invention relates to antibodies raised against fragments of apolipoprotein B, in particular defined peptides thereof, for immunization or therapeutic treatment of mammals, including humans, against ischemic cardiovascular diseases, using one or more of the antibodies.

Abstract: The invention provides materials and methods for promoting weight loss or preventing weight gain and for treating diabetes and associated metabolic disorders. In particular, the invention provides novel glucagon analogue peptide compounds effective in such methods. The compounds may mediate their effect by having, for example, increased selectivity for the GLP-1 receptor compared to human glucagon.

Abstract: The invention provides materials and methods for promoting weight loss or preventing weight gain without affecting glycemic control. In particular, the invention provides novel glucagon analogue peptides effective in such methods. The peptides may mediate their effect by having increased selectivity for the GLP-1 receptor as compared to human glucagon.

Abstract: This invention discloses isolated short peptides comprising the amino acid sequence Cys-Glu-Phe-His (CEFH; SEQ ID NOS: 1 and 15) and analogs thereof as well as compositions comprising CEFH peptides and analogs thereof. The CEFH peptides disclosed herein are effective in mediating the denitration of 3-nitrotyrosines (3-NT) in cellular proteins thereby preventing tissue damage associated with excess nitric oxide (NO) and its reactive species. The CEFH peptides disclosed herein are useful in the treatment of ischemia/reperfusion (I/R) injury and other disorders.