Abstract: The present invention provides a co-culture system and method for assessing cellular cholesterol (Choi) efflux and uptake in vitro. The co-culture system mimics in vivo Choi efflux and uptake in the context of mammalian physiology. The methods and systems provided can be used in some embodiments to evaluate the effect of a pharmacological agent on cellular Choi efflux and uptake or for diagnostic purposes.

Abstract: The present invention relates to reconstituted high density lipoprotein (rHDL) formulations comprising an apolipoprotein, a lipid and a lyophilization stabilizer. Said formulations have reduced renal toxicity and good long-term stability, especially in lyophilized form.

Abstract: The present disclosure provides therapeutic agents for the treatment of age-related macular degeneration (AMD) and other eye disorders. One or more therapeutic agents can be used to treat any stages (including the early, intermediate and advance stages) of AMD, and any phenotypes of AMD, including geographic atrophy (including non-central GA and central GA) and neovascularization (including types 1, 2 and 3 NV). In some embodiments, the one or more therapeutic agents are or include an anti-dyslipidemic agent, an antioxidant, an anti-inflammatory agent, a complement inhibitor, a neuroprotector or an anti-angiogenic agent, or any combination thereof. In certain embodiments, the one or more therapeutic agents are or include an anti-dyslipidemic agent (e.g., an apolipoprotein mimetic or/and a statin).

Abstract: Disclosed are a human serum albumin mutant that can be linked to a physiologically active protein to increase the stability of the protein in the blood, as well as a resulting protein produced by linking with the mutant. The protein produced by linking with the mutant consists of a human serum albumin mutant comprising the amino acid sequence set forth as SEQ ID NO:3 or an amino acid sequence that, in comparison with it, lacks not more than 10 amino acid residues and/or has not more than 10 amino acid residues replaced, with the proviso that the asparagine residue occurring at position 318 and the threonine at position 320 from the N-terminus of the amino acid sequence set forth as SEQ ID NO:3 are preserved and linked by peptide bonds via a single amino acid residue (X) except proline placed between those two amino acid residues, and a physiologically active protein linked to the mutant.

Abstract: Methods and reagents for enhancing cellular uptake of a cargo molecule by covalently bonding optionally-substituted fluorenyl groups to the cargo molecules, where cellular uptake includes at least partial uptake into the cytosol. Useful fluorenylation reagents include those of formula: and salts thereof where variables are as defined. Cargo molecules include peptides and proteins. Also provided are fluorenylated cargo molecules, including fluorenylated peptides and proteins.

Abstract: Methods and compositions are provided for extending the half-life of a therapeutic agent. A modified therapeutic agent (mTA) comprises a therapeutic agent, a staple, and a half-life extending molecule. The mTAs disclosed herein may be used to treat a disease or a condition in a subject in need thereof.

Abstract: Methods and compositions are provided for extending the half-life of a therapeutic agent. A modified therapeutic agent (mTA) comprises a therapeutic agent, a staple, and a half-life extending molecule. The mTAs disclosed herein may be used to treat a disease or a condition in a subject in need thereof.

Abstract: Provided are peptides, compositions thereof, and methods for treating or preventing dyslipidemia, a cardiovascular disease, endothelial dysfunction, a macrovascular disorder, or a microvascular disorder.

Abstract: The present invention relates to reconstituted high density lipoprotein (rHDL) formulations comprising an apolipoprotein, a lipid and a lyophilization stabilizer. Said formulations have reduced renal toxicity and good long-term stability, especially in lyophilized form.

Abstract: Apolipoprotein M forms a complex with sphingosine-1-phosphate (S1P) and is the carrier of S1P in high density lipoprotein particles and mediates its endothelial protective effect. Increasing the concentration of the apoM/S1P complex by administering it, either alone or in HDL particles, can prevent or treat diseases caused by endothelial cell injury, including inflammatory diseases, sepsis, atherosclerosis and acute lung injury, ischemic heart disease, stroke, vital organ failure after ischemic stress.

Abstract: Provided are peptides, compositions thereof, and methods for treating or preventing dyslipidemia, a cardiovascular disease, endothelial dysfunction, a macrovascular disorder, or a microvascular disorder.

Abstract: Methods for treating fatty liver disease, e.g., hepatic steatosis, using peptide fragments of the C-terminal end of glucagon-like peptide-1 (GLP-1), e.g., GLP-1(28-36).

Abstract: This present invention relates to pharmacologically potent and stable human fibroblast growth factor 21 (FGF21) variants, pharmaceutical compositions comprising FGF21 variants, and methods for treating type 2 diabetes, obesity, dyslipidemia, and/or metabolic syndrome using such variants.

Abstract: Provided are peptides, compositions thereof, and methods for treating or preventing dyslipidemia, a cardiovascular disease, endothelial dysfunction, a macrovascular disorder, or a microvascular disorder.

Abstract: Methods and compositions for the prevention and treatment of liver damage or disease in a subject in need thereof are provided. The methods involve providing the sulfated oxysterol 25-hydroxycholesterol-3-sulfate (25HC3S) to the subject e.g. by 1) administering 25HC3S to the subject; or 2) overexpressing, in the subject, the hydroxysterol sulfotransferase enzyme SULT2B1b, which catalyzes the sulfation of 25-hydroxycholesterol (25HC) to form 25HC3S.

Abstract: Provided herein are pharmaceutical formulations containing exendins, exendin agonists, or exendin analog agonists that are administered at therapeutic plasma concentration levels over a sustained period of time to lower total cholesterol levels; to lower LDL-cholesterol levels; to lower triglyceride levels; to treat dyslipidemia; to treat and slow the progression of atherosclerosis; and to treat, prevent, and reduce the risk of heart attacks and strokes in patients. In the pharmaceutical formulations and methods of the invention, the exendin may be exendin-4, an exendin-4 agonist, or an exendin-4 analog agonist. The pharmaceutical formulations may be polymer-based pharmaceutical formulations that may be administered once weekly. An exemplary pharmaceutical formulation comprises 5% (w/w) of exenatide, about 2% (w/w) of sucrose, and about 93% (w/w) of a poly(lactide-co-glycolide) polymer, wherein the poly(lactide-co-glycolide) polymer is in the form of microspheres encapsulating the exenatide.

Abstract: GLP-2 analogues are disclosed which comprise one of more substitutions as compared to h[Gly2]GLP-2 and which may have the property of an altered GLP-1 activity, and their medical use. The analogues are particularly useful for the prophylaxis, treatment or ameliorating of the gastro-intestinal associated side effects of diabetes.

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

Abstract: A composition which includes oxyntomodulin and polyethylene glycol polymer (PEG polymer) linked via a reversible linker such as 9-fluorenylmethoxycarbonyl (Fmoc) or 2-sulfo-9-fluorenylmethoxycarbonyl (FMS) is disclosed. Pharmaceutical compositions comprising the reverse pegylated oxyntomodulin and methods of using same are also disclosed.

Abstract: Compositions and methods for treatment of obesity and/or Type II diabetes and related metabolic disorders are provided wherein the methods and treatments comprise an effective amount of an isolated and/or purified C1q/TNF-related Protein-9 (CTRP9) or a functional portion thereof, and a pharmaceutically acceptable carrier. Methods of screening for molecules which elevate levels of CTRP9 in vivo are also provided. The present inventors provide the first in vivo evidence linking CTRP9 to regulation of fat metabolism in liver and skeletal muscle via AMPK signaling pathway, and highlight its protective metabolic function in the context of HFD-mediated metabolic insults.

Abstract: There is provided a novel series of analogues of glucose-dependent insulinotropic polypeptide compounds, pharmaceutical compositions containing said compounds, and the use of said compounds as GIP-receptor agonists or antagonists for treatment of GIP-receptor mediated conditions, such as non-insulin dependent diabetes mellitus and obesity.

Abstract: Bile acids and related compositions and methods of synthesis and use. More specifically, deoxycholic acid and related compositions, said compositions being free of all moieties of animal origin and free of pyrogenic moieties.

Abstract: The invention features compositions and methods of using a dimeric inhibitor, e.g., A1-A1, to selectively target ?2GPI in ?2GPI/antibody complexes. The compositions can be administered to subjects (e.g., a mammal, such as a human) having or likely to develop APS, or one or more symptoms of APS, in order to treat or inhibit the disease or treat or reduce its symptoms. The inhibitors of the invention include two ligand-binding A1 modules, e.g., from ApoER2, connected by a flexible linker.

Abstract: Derivatives of purine, 3H-imidazo[4,5-b]pyrimidine and 1H-imidazo[4,5-d]pyrazine of Formula I that inhibit the activity of the diacylglycerol acyltransferase 2 (DGAT2) and their uses in the treatment of diseases linked thereto in animals are described herein.

Abstract: The present invention provides a family of non-naturally occurring polypeptides having cholesterol efflux activity that parallels that of full-length apolipoproteins (e.g., Apo AI and Apo E), and having high selectivity for ABAC1 that parallels that of full-length apolipoproteins. The invention also provides compositions comprising such polypeptides, methods of identifying, screening and synthesizing such polypeptides, and methods of treating, preventing or diagnosing diseases and disorders associated with dyslipidemia, hypercholesterolemia and inflammation.

Abstract: This invention comprises a sterically stabilized liposome carrier encapsulating a selected drug for the aerosol delivery of the drug effectual in the treatment of a mammal, a composition containing the sterically stabilized liposome carrier and a drug effective for the treatment a mammal as an aerosol and a method of treatment using the composition. The composition provides effective treatment for the longer of a period of time at least twice as long as the drug alone or up to at least one week.

Abstract: The method provides methods and compositions for treating metabolic disorders such as impaired glucose tolerance, elevated blood glucose, insulin resistance, dyslipidaemia, obesity, and fatty liver.

Abstract: Nanostructures, compositions and methods for treating cancers and other conditions are provided. In some cases, the nanostructures and/or compositions may be used to treat cancers or other diseases or conditions at least in part by controlling cholesterol metabolism in cells. The nanostructures and compositions may be used, for example, to control cholesterol influx and/or efflux in cells. In some cases, the nanostructures or compositions may be used to kill the cells. Examples of cancer cells that may be affected by the nanostructures and compositions described herein include those having scavenger receptor type B-I (SR-B1), B-cell lymphoma cells, non-Hodgkin's lymphoma cells, melanoma cells and/or others. In some embodiments, the nanostructures may be mimics of natural high-density lipoprotein (HDL).

Abstract: A substrate mimicking intercellular lipids in stratum corneum consisting of a substrate and a lipid membrane formed on the substrate, wherein the lipid membrane is formed from ceramide, palmitic acid and cholesterol, and the ceramide, palmitic acid and cholesterol are present at a mass ratio of 20-70%:10-60%:20-40% (ceramide:palmitic acid:cholesterol).

Abstract: Reversible pegylated drugs are provided by derivatization of free functional groups of the drug selected from amino, hydroxyl, mercapto, phosphate and/or carboxyl with groups sensitive to mild basic conditions such as 9-fluorenylmethoxycarbonyl (Fmoc) or 2-sulfo-9-fluorenylmethoxycarbonyl (FMS), to which group a PEG moiety is attached. In these pegylated drugs, the PEG moiety and the drug residue are not linked directly to each other, but rather both residues are linked to different positions of the scaffold Fmoc or FMS structure that is highly sensitive to bases and is removable under physiological conditions. The drugs are preferably drugs containing an amino group, most preferably peptides and proteins of low or medium molecular weight. Similar molecules are provided wherein a protein carrier or another polymer carrier replaces the PEG moiety.

Abstract: Disclosed herein are peptides and peptide analogs with multiple amphipathic ?-helical domains that promote lipid efflux from cells via an ABCA1-dependent pathway, as well as peptides that activate lipoprotein lipase, and compositions comprising such peptides or combinations thereof. Also provided herein are methods of using multi-domain amphipathic ?-helical peptides or peptide analogs to treat or inhibit dyslipidemic disorders. Methods for identifying non-cytotoxic peptides that promote ABCA1-dependent lipid efflux from cells and activate lipoprotein lipase within cells are also disclosed herein.

Abstract: The invention relates to derivatives of GLP-1 like peptides which are C-terminally extended analogues of native GLP-1. The derivatives comprise two side chains, one at a position corresponding to position 42, and one at a position corresponding to position 18, 23, 27, 31, 36, or 38, wherein both positions are when compared to GLP-1(7-37). The side chains comprise a C19, C20, or C22 diacid protracting moiety and optionally a linker. The invention also relates to intermediate products in the form of novel GLP-1 analogues incorporated in the derivatives of the invention, as well as pharmaceutical compositions and medical uses of the derivatives. The derivatives have very long half-lives while maintaining a satisfactory potency, which makes them potentially suitable for once-monthly administration.

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: An apolipoprotein formulation is provided at a fixed dosage that is efficacious in the prophylactic and/or therapeutic treatment of diseases or conditions including, but not limited to cardiovascular disease, acute coronary syndrome, atherosclerosis, unstable angina pectoris, and myocardial infarction. More particularly, the fixed dosage apolipoprotein formulation displays relatively reduced inter-patient variability compared to weight-adjusted dosages. Typically, the apolipoprotein formulation is a reconstituted high density lipoprotein formulation comprising ApoA1, one or more lipids such as phosphatidylcholine, sphingomyelin and/or phosphatidylglycerol and, optionally, a detergent such as cholate at a level that does not induce liver toxicity.

Abstract: Disclosed is the novel myokine known as myonectin (CTRP15), an isolated nucleic acid encoding the myonectin (CTRP15) gene, and the amino acid sequence encoding the myonectin (CTRP15) protein. Methods of isolation of the nucleic acid, protein, polypeptides and methods of making antibodies to the myonectin (CTRP15) protein are provided. The use of myonectin (CTRP15) in the modulation of lipid and/or glucose metabolism, suppressing the expression of autophagy genes, inhibiting LC3 lipidation and autophagosome-dependent p62 degradation, and activating the Akt/mTOR pathway is also provided.

Abstract: The invention relates to protracted Glucagon-Like Peptide-1 (GLP-1) derivatives and therapeutic uses thereof. The GLP-1 derivative of the invention comprises a modified GLP-1(7-37) sequence having a total of 2-12 amino acid modifications, including Glu22 and Arg26, and being derivatised with an albumin binding residue or pegylated in position 18, 20, 23, 30, 31, 34, 36, 37, or 39. These compounds are useful in the treatment or prevention of diabetes type 2 and related diseases. The compounds are potent, stable, have long half-lives, a high affinity of binding to albumin, and/or a high affinity of binding to the extracellular domain of the GLP-1 receptor (GLP-1R), all of which is of potential relevance for the overall aim of achieving long-acting, stable and active GLP-1 derivatives with a potential for once weekly administration.

Abstract: The present invention relates to compositions and methods for treating diseases associated with dyslipidemia, including hypercholesterolemia, hypertriglyceridemia, steatohepatitis, atherosclerosis, obesity, hyperglycemia, metabolic syndrome, and related aspects of and conditions associated with metabolic syndrome. The compositions and methods disclosed herein are useful for regulating the lipid balance (lipid homeostasis) in a subject. Compositions and methods including a Nuclear Transport Modifier may be administered to a subject to modulate the transport of transcription factors, mediated by nuclear import adaptors, into the nucleus of a cell resulting in a decrease in cholesterol and triglyceride levels in the blood and liver, a decrease in atherosclerotic lesion size, a decrease in body weight and in hyperglycemia, a reduction of fatty liver inflammation, and an improvement in liver function.

Abstract: Therapeutic peptides having guanylyl cyclase C agonist activity are disclosed. The therapeutic peptides are analogues of the E. coli STa peptide with non-natural amino acid, isosteric or D-amino acid substituents. The therapeutic peptides are useful in the treatment of chronic ideopathic constipation, inflammatory bowel disease, and other diseases. Pharmaceutical compositions comprising the therapeutic peptides are also disclosed.

Abstract: New Lactococcus lactis strains, NRRL B-50571 and NRRL B-50572, and a bacterial preparation containing the same, have the ability to produce bioactive peptides that reduce blood pressure, lower LDL-cholesterol (bad cholesterol) and present antioxidant properties for better cardiovascular health. These biologically active peptides may be produced within the food for the production of a food product, such as a functional food, or they may be produced from protein sources and subsequently added to a food as part of the formulation or as part of a food supplement or a pharmaceutical preparation.

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: Nanoparticles include a core and one or more targeting moieties, as well as one or more contrast agents or one or more therapeutic agents. The contrast agents or therapeutic agents may be contained or embedded within the core. If the nanoparticle includes therapeutic agents, the agents are preferably released from the core at a desired rate. The core may be biodegradable and may release the agents as the core is degraded or eroded. The targeting moieties preferably extend outwardly from the core so that they are available for interaction with cellular components, which interactions will target the nanoparticles to the appropriate cells, such as apoptotic cells; organelles, such as mitochondria; or the like. The targeting moieties may be tethered to the core or components that interact with the core.

Abstract: The invention relates to truncated GLP-1 analogues, in particular a GLP-1 analogue which is a modified GLP-1(7-35) (SEQ ID No 1) having: i) a total of 2, 3, 4, 5 6, 7, 8, or 9 amino acid substitutions as compared to GLP-1(7-35), including a) a Glu residue at a position equivalent to position 22 of GLP-1(7-35), and b) an Arg residue at a position equivalent to position 26 of GLP-1(7-35); as well as derivatives thereof, and therapeutic uses and compositions. These analogues and derivatives are highly potent, have a good binding affinity to the GLP-1 receptor, also to the extracellular domain of the GLP-1 receptor, which is of potential relevance achieving long-acting, stable GLP-1 compounds with a potential for once weekly administration.

Abstract: A method including introducing into a blood stream a delipidated high density lipoprotein (HDL) and a bioactive agent. A composition including a delipidated high density lipoprotein (HDL) and an auxiliary agent in a form suitable for delivery into a blood vessel. A composition including Apo A1 comprising a hydrophobic ligand suitable to interact with cell surface binding sites. A composition including Apo A1 and an agent selected to one of increase the ATP-binding cassette protein 1 (ABCA1) transporter expression in macrophages and protect ABCA1 from thiol-mediated degradation.

Abstract: The present invention provides a family of non-naturally occurring polypeptides having cholesterol efflux activity that parallels that of full-length apolipoproteins (e.g., Apo AI and Apo E), and having high selectivity for ABCA1 that parallels that of full-length apolipoproteins. Further, the peptides of the invention have little or no toxicity when administered at therapeutic and higher doses. The invention also provides compositions comprising such polypeptides, methods of identifying, screening and synthesizing such polypeptides, and methods of treating, preventing or diagnosing diseases and disorders associated with dyslipidemia, hypercholesterolemia and inflammation.

Abstract: This invention provides novel guanylate cyclase C (GC-C) agonists and their therapeutic use. The agonists may be used either alone or in combination with one or more additional agents.

Abstract: This invention provides novel peptides and methods to prevent, control, and treat an inflammation, cancer and other disorders, particularly of the gastrointestinal tract and the lung by administering at least one agonist of guanalyte cyclase receptor either alone or in combination with a compound selected from i) 5-aminosalicyclic acid (5-ASA) or a derivative or a pharmaceutically acceptable salt thereof; ii) mercaptopurine; or iii) an anti-TNF therapy.

Abstract: Disclosed herein are peptides or peptide analogs with multiple amphipathic ?-helical domains that promote lipid efflux from cells via an ABCA1-dependent pathway. Also provided herein are methods of using multi-domain amphipathic ?-helical peptides or peptide analogs to treat or inhibit dyslipidemic disorders. Methods for identifying non-cytotoxic peptides that promote ABCA1-dependent lipid efflux from cells are also disclosed herein.

Abstract: Compounds are provided having inter alia good duration of action, high potency and/or convenient dosing regimens including once weekly administration. The compounds are engineered polypeptides which incorporate an albumin binding domain in combination with one or more biologically active polypeptides. Also provided are pharmaceutical compositions and methods of treatment for diseases and disorders including lipodystrophy, dyslipidemia, hyperlipidemia, overweight, obesity, hypothalamic amenorrhea, Alzheimer's disease, leptin deficiency, fatty liver disease or diabetes (including type I and type II). Additional diseases and disorders which can be treated by the compounds and methods described herein include nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD), metabolic syndrome X and Huntington's Disease.

Abstract: An agent for suppressing elevation of a blood triglyceride concentration, comprising a polyglutamic acid as an active ingredient.

Abstract: Provided herein are amylin-calcitonin peptide conjugates having enhanced duration of biological activity, and methods of use thereof. The amylin-calcitonin peptide conjugates include duration enhancing moieties, such as water soluble polymers and long chain aliphatic groups, bound to the amylin-calcitonin peptide. Methods of use are provided for treatment of an eating disorder, insulin resistance, obesity, overweight, abnormal postprandial hyperglycemia, Type I diabetes, Type II diabetes, gestational diabetes, metabolic syndrome, dumping syndrome, hypertension, dyslipidemia, cardiovascular disease, hyperlipidemia, sleep apnea, cancer, pulmonary hypertension, cholescystitis or osteoarthritis.