Abstract: The invention relates to a compound comprising a GLP-1 receptor agonist and an amylin receptor agonist. The invention also relates to a pharmaceutical formulation, suitable for but not limited to oral administration, which comprises such a compound. The compound and pharmaceutical formulation comprising it may be used for the medical treatment of subjects with overweight, obesity and associated co-morbidities.

Abstract: The pharmaceutical compositions described herein include a suspension which comprises an admixture in solid form of a therapeutically effective amount of a therapeutic agent and at least one salt of a medium chain fatty acid and a hydrophobic medium, e.g. castor oil or glyceryl tricaprylate or a mixture thereof. The pharmaceutical compositions described herein contain medium chain fatty acid salts and are substantially free of alcohols. The pharmaceutical compositions may be encapsulated in a capsule. Methods of treating or preventing diseases by administering such compositions to affected subjects are also disclosed.

Abstract: The invention relates to a derivative of a GLP-1 analogue of a general Formula I, which derivative comprises a side chain attached to a Lys residue at position 34, 35, 36, 37, or 38 of the GLP-1 analogue, which side chain comprises a Branched linker, a 1st and a 2nd Protractor selected from C18 diacid, C20 diacid, and sulfonic acid C16, and at least one Linker element-1 incorporating ethylene glycol units. Linker element-1 may be incorporated in an optional Pre-linker, and/or in a 1st or 2nd Post-linker. The invention also relates to novel GLP-1 analogues, novel side chain intermediate products and their manufacture and use to prepare derivatives of biologically active peptides and proteins, as well as pharmaceutical compositions and medical uses of the analogues and derivatives. The derivatives have very long half-lives while maintaining a satisfactory potency, which makes them potentially suitable for once-monthly administration.

Abstract: Disclosed are pharmaceutical compositions comprising the peptide of SEQ ID No. 1, or a pharmaceutically acceptable salt or counterion thereof, methods of preparing such pharmaceutical compositions, and methods of treating diabetes and diabetes-related disorders with such pharmaceutical compositions.

Abstract: A a triple agonist having activities to all of glucagon, GLP-1, and GIP receptors is disclosed. Uses of the triple agonist are disclosed.

Abstract: Described herein are isolated monovalent antibodies or antibody fragments thereof that bind human properdin. Such antibodies are useful in methods of treatment for diseases mediated by alternative complement pathway dysregulation.

Abstract: The invention provides genetic markers of severe suicidal behavior, related compositions, computer systems, and methods.

Abstract: Described herein are compounds of Formula (I) wherein R1, R2, R3, R4, R5, R6, R7, R8 and R9 are defined herein, their use as diacylglycerol acyltransferase 2 (DGAT2) inhibitors, pharmaceutical compositions containing such inhibitors and the use of such inhibitors to treat, for example, NASH.

Abstract: Insulin dimers conjugated to peptides having at least one incretin activity are disclosed.

Abstract: The present invention relates to exendin-4 peptide analogues which selectively bind and activate the glucagon receptor and comprise a chelating moiety capable of binding a metal ion and their use, for example in PET imaging.

Abstract: The present invention relates to a method of preparing a lysine side-chain modified peptide by solid phase peptide synthesis.

Abstract: The disclosure is related to a method of treating a disorder, such as Prader Willi Syndrome (PWS), obesity or hyperphagia, in a subject using a melanocortin-4 receptor (MC4R) agonist. Also described is method of treating a subject having a deficiency in the pro-opiomelanocortin (POMC)-MC4R pathway, such as a POMC-null or a PCSK-null subject, using a MC4R agonist.

Abstract: The present invention relates to polypeptides and analogues thereof for use in the treatment of diabetes and bone disorders. Also disclosed are pharmaceutical compositions comprising the polypeptides and analogues thereof, and methods for the treatment of diabetes and bone disorders.

Abstract: Glycosylated peptides with glycosylation at or near the C-terminal domain of the peptide have an enhanced ability to cross the blood brain barrier (BBB) and/or enhanced half-lives. These glycosylated peptides may be used as drugs. For example, a PACAP peptide with a C-terminal glycosylation, e.g., in lieu of the terminal leucine, functions as a PAC1 agonist with enhanced ability to cross the BBB and with enhanced half-life. The peptides can have a pseudoproline residue with glycosylation at or near the C-terminal domain.

Abstract: Provided herein are methods of preventing and treating obesity and diabetes in patients comprising administering GLP-1/glucagon agonists peptides.

Abstract: The present invention relates to a long-acting conjugate of a triple agonist having activities to all of glucagon, GLP-1, and GIP receptors and uses thereof.

Abstract: The present invention relates to a triple agonist having activities to all of glucagon, GLP-1, and GIP receptors and uses thereof.

Abstract: A composition for preventing or treating diabetes mellitus includes insulin and a GLP-1/glucagon dual agonist. The composition can inhibit the weight gain and reduce the danger of hypoglycemia due to the administration of insulin, lower the administration dose and greatly improve the compliance of drugs through a combined administration of a long-acting insulin conjugate and a long-acting GLP-1/glucagon dual agonist conjugate. In addition, the long-acting insulin conjugate and the long-acting GLP-1/glucagon dual agonist conjugate can improve the in vivo sustainability and stability because an insulin and a GLP-1/glucagon dual agonist are linked to the immunoglobulin Fc region via a non-peptidyl linker. A method for preventing or treat diabetes mellitus includes administration of the insulin and a GLP-1/glucagon dual agonist.

Abstract: The present disclosure relates to a class of engineered polypeptides having a binding affinity for albumin. In particular, the present invention relates to albumin binding polypeptides which have a high resistance to enzymatic cleavage. The disclosure provides an albumin binding polypeptide comprising an albumin binding motif, which motif consists of the amino acid sequence GVSDFYKKLI XaKAKTVEGVE ALKXbXcI (SEQ ID NO:29).

Abstract: The present invention provides a novel peptide compound having an activating action on GLP-1 receptors and GIP receptors and use of the peptide compound as a medicament. Specifically, a peptide containing a partial sequence represented by the formula (I) or a salt thereof and a medicament comprising the same are provided. P1-Tyr-Aib-Glu-Gly-Thr-alphaMePhe-Thr-Ser-Asp-Tyr-A11-A12-A13-Leu-Asp-A16-A17-Ala-Gln-A20-Glu-Phe-Val-Lys-Trp-Leu-Leu-Lys-A29 (I) wherein each symbol is as defined 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: The present invention relates to dual GLP-1/glucagon receptor agonists or optionally trigonal GLP-1/glucagon/GIP receptor agonists and their medical use, for example in the treatment of disorders of the metabolic syndrome, including diabetes and obesity, as well as for reduction of excess food intake.

Abstract: Described herein are peptide analogs of glucagon-like peptide 1 (GLP-1) that retain agonist activity, but are more resistant to proteolytic degradation than native GLP-1. In the analogs, at least one ?-amino acid found in the native GLP-1 is replaced with a ?-amino acid residue, which may or may not be cyclically constrained. Pharmaceutical compositions containing the analogs are described, as are methods to treat diabetes, and methods to make proteolytically resistant GLP-1 analogs.

Abstract: The present invention is related generally to a method for screening subjects to determine those subjects more likely to develop diabetes by quantization of insulin producing cells. The present invention is also related to the diagnosis of diabetes and related to monitor disease progression or treatment efficacy of candidate drugs.

Abstract: Provided herein are glucagon analogs which exhibit potent activity at the GIP receptor, and, as such are contemplated for use in treating diabetes and obesity. In exemplary embodiments, the glucagon analog of the present disclosures exhibit an EC50 at the GIP receptor which is within the nanomolar or picomolar range.

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: An oral combination therapy or oral composition that protects orally administered exogenous leptin from the environment of the gastrointestinal tract, allowing delivery of the exogenous leptin to the bloodstream. The oral combination therapy includes (a) leptin or a leptin functional derivative; (b) a stomach acid-neutralizing agent such as a buffer; and (c) a pancreatic protease inhibitor that protects the exogenous leptin from degradation by pancreatic enzymes; and (d) a bile acid or a bile acid analog that facilitates absorption of the exogenous leptin. The oral combination therapy or oral composition may also include at least one agent that stimulates endogenous leptin secretion; as well as at least one agent capable of promoting, enhancing or improving adherence to treatment such as a sweetener or a satiety triggering agent.

Abstract: Formulations and methods for weight loss and body contouring are disclosed. An illustrative formulation comprises human chorionic gonadotrophin (hCG) and resveratrol. An illustrative method for weight loss and body contouring comprises administering hCG and resveratrol sublingually.

Abstract: A combination comprising at least a first insulin-like compound and a second insulin-like compound for treating a condition or a disease in a subject in need thereof where administration of insulin would be of benefit to said subject is described.

Abstract: Modified glucagon peptides are disclosed having enhanced potency at the glucagon receptor relative to native glucagon. Further modification of the glucagon peptides by forming lactam bridges or the substitution of the terminal carboxylic acid with an amide group produces peptides exhibiting glucagon/GLP-1 receptor co-agonist activity. The solubility and stability of these high potency glucagon analogs can be further improved by modification of the polypeptides by pegylation, substitution of carboxy terminal amino acids, or the addition of a carboxy terminal peptide selected from the group consisting of SEQ ID NO: 26 (GPSSGAPPPS), SEQ ID NO: 27 (KRNRNNIA) and SEQ ID NO: 28 (KRNR).

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: A unique combination of weight loss modalities that produce 20-40 pounds of weigh loss in a six week treatment period. Treatment includes a meal plan chosen to provide adequate protein and nutrition during dieting and to assist metabolism of toxins created from the release of stored fat, high amounts of fiber to assist in collecting toxins and fat in the elimination system and to encourage peristaltic action in the bowel, a bowel toner to further increase peristaltic action in the bowel, stimulating liver functions of fat and toxins. The weight loss portion of the treatment is limited to six week segments, and added to the plurality of modalities comprising the invention, to further support the body during weight loss. By supporting the body during weight loss, his invention(s) avoids the “plateau” routinely experienced by existing weight loss systems, when the metabolism slows to avoid further damage from ultra-low calories, medications, bariatric surgeries, and other stressful programs.

Abstract: Peptide analogues of PYY, compositions comprising said analogues and methods of using said analogues for the treatment and prevention of metabolic disorders, for example disorders of energy metabolism such as diabetes and obesity, and for a reduction in appetite, reduction in food intake or reduction of calorie intake in a subject.

Abstract: The present invention relates to osmotic delivery devices, formulations, and methods for delivery of two or more beneficial agents. In one aspect, the present invention provides osmotic delivery devices useful for substantially concurrent administration of two or more beneficial agents. In another aspect, the present invention provides beneficial agent formulations for use in the osmotic delivery devices. The formulations include formulations wherein beneficial agents are soluble in the vehicle, suspension formulations comprising particle formulations of one or more beneficial agent, and combinations thereof. Further, methods for treatment of a variety of diseases or conditions using two or more beneficial agents are disclosed, wherein the methods are preferably practiced using the osmotic delivery devices and/or formulations of the invention.

Abstract: The invention provides methods for treating diabetes or obesity, as well as methods for inducing weight loss, preventing weight gain, or controlling weight in a patient in need thereof. The methods comprise administering to the patient at least one effective dose of a GLP-1 receptor agonist, or a regimen of GLP-1 receptor agonist comprising a plurality of substantially evenly spaced doses. The effective dose or regimen does not induce substantial nausea or appetite suppression in the patient.

Abstract: The invention provides materials and methods for the treatment of obesity and excess weight, diabetes, and other associated metabolic disorders. 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: The present invention relates to compositions and methods for enhancing the growth of infants. Particularly, the present invention discloses the use of insulin for promoting the growth of low birth weight infants, including preterm infants and small for gestational age (SGA) infants over the expected rate.

Abstract: The invention provides materials and methods for promoting weight loss or preventing weight gain, and in the treatment of diabetes, metabolic syndrome and associated disorders. 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: The invention relates to pharmaceutical compositions comprising a first type of granules and a second type of granules, wherein said first type of granules comprises a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and no GLP-1 peptide, and wherein said second type of granules comprises a GLP-1 peptide and no salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid, as well as the intermediate granules, processes for the preparation of the granules and compositions, and use thereof in medicine.

Abstract: The disclosure provides one-component, injectable, sustained release formulations which comprise microspheres containing active pharmaceutical ingredients (e.g., exenatide), wherein the microspheres are suspended in a non-aqueous carrier. The non-aqueous carrier can be an oil, a fractionated oil, triglycerides, diglycerides, monoglycerides, propylene glycol fatty acid diesters, and the like. The formulations offer distinct advantages of long shelf life for the stability and potency of the formulation and sustained release of active pharmaceutical ingredients to reduce the frequency of medication dosing and to increase patient compliance.

Abstract: The present invention relates to substituted quinazolines of formula (I) wherein X and Y are defined as in claim 1, the tautomers, stereoisomers, mixtures and salts thereof, which have valuable pharmacological properties, particularly an inhibitory effect on the activity of the enzyme dipeptidylpeptidase-IV(DPP-IV).

Abstract: This invention relates to novel compositions comprising analogs of glucagon, wherein the analog comprises an ?-amino acid and at least one ?-amino acid. Administration of the compositions may be used for effecting treatment or prevention of a plurality of disease states caused by dysfunctional biochemical or biological pathways, including diabetes and other metabolic disorders. The compositions and methods of this invention are particularly useful to identify novel therapeutic modulators of in-vivo receptor activity with extended half-lives and relevant bioactivity as compared to the naturally translated polypeptides upon which the analogs are derived.

Abstract: Described herein are melanocortin analogs having enhanced activity and transport.

Abstract: Provided is a glucagon-like peptide-1 (GLP-1) analog shown as the following formula, wherein X is selected from glycine and glycinamide. The GLP-1 analog has a non-proteogenic amino acid residue in position 8 relative to the sequence GLP-1, and is acylated with a moiety comprising two acidic groups to the lysine residue in position 26. The GLP-1 analog is resistant to dipeptidyl peptidase IV so as to have an extended half-life in vivo. Also provided is a use of the GLP-1 analog in conquering blood sugar.

Abstract: Novel modified exendins and exendin agonists having an exendin or exendin agonist linked to one or more polyethylene glycol polymers, for example, and related formulations and dosages and methods of administration thereof are provided. These modified exendins and exendin agonists, compositions and methods are useful in treating diabetes and conditions that would be benefited by lowering plasma glucose or delaying and/or slowing gastric emptying or inhibiting food intake.

Abstract: The invention relates to granules and pharmaceutical compositions comprising a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and a lubricant obtained by mixing hereof for more than 5 minutes prior to granulation as well as processes for their preparation and use thereof in medicine.

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 invention relates to peptides and peptide derivatives based on the naturally occurring peptide xenin. The invention provides a peptide of SEQ ID No. 1 or an analogue thereof which is able to stimulate insulin secretion and which has no more than 7 amino acid substitutions or deletions as compared to the native sequence, the peptide having one or more lysine residues substituted with a lipophilic substituent of 840 carbon atoms, optionally via a spacer. The present invention also provides a peptide of SEQ ID No. 1 or an analogue thereof which is able to stimulate insulin secretion and which has no more than 7 amino acid substitutions or deletions as compared to the native sequence and in which one or more of Lys4, Lys8, Arg11, Lys13, Phe17, Lys20, or Arg21 have been replaced with another amino acid which increases resistance of the peptide to enzymatic degradation. Further provided are molecules and formulations comprising these peptides and therapeutic uses of these peptides.

Abstract: Compounds of the invention are novel peptide analogues of oxyntomodulin (oxm) in which one or more amino acids of the oxm sequence have been changed. Changing amino acids 15-24 of oxm to either amino acids 968-977 of the ?-latrotoxin peptide (and variations thereof) or amino acids 15-24 of exendin-4 (and variations thereof), or combinations of sequences from these sources, and/or changing amino acids 27-33 of oxm to amino acids 27-33 of exendin-4, and/or the addition of amino acids to the C-terminus of the peptide, results in a series of analogues of oxm that demonstrate the oxm like activity of reducing food intake, and with certain embodiments a greater ability to decrease food intake.

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.