Abstract: An insulin analogue comprises a B-chain polypeptide incorporating a halogenated phenylalanine at position B24, B25 or B26. The halogenated phenylalanine may be ortho-monofluoro-phenylalanine, ortho-monobromo-phenylalanine, ortho-monochloro-phenylalanine, or para-monochloro-phenylalanine. The analogue may be of a mammalian insulin, such as human insulin. A nucleic acid encodes such an insulin analogue. The halogenated insulin analogues retain significant activity. A method of treating a patient comprises administering a physiologically effective amount of the insulin analogue or a physiologically acceptable salt thereof to a patient. Halogen substitution-based stabilization of insulin may enhance the treatment of diabetes mellitus in regions of the developing world lacking refrigeration.

Abstract: The present invention features a compound having the formula A-X-B, where A is peptide vector capable of enhancing transport of the compound across the blood-brain barrier or into particular cell types, X is a linker, and B is a GLP-1 agonist (e.g., exendin-4 or an exendin-4 analog). The compounds of the invention can be used to treat any disease where increased GLP-1 activity is desired, for example, metabolic diseases, such as obesity and diabetes.

Abstract: The present invention relates to nociceptin peptide mimetics that have ?-helical structures and bind to and modulate the opioid receptor-like-1 (ORL-1) receptor. The peptide mimetics are constrained cyclic nociceptin analogs which have either agonist or antagonist activity. Pharmaceutical compositions comprising the nociceptin peptide mimetics and methods of treating or preventing a disease or condition ameliorated by modulating the ORL-1 receptor are also described.

Abstract: A new compound inhibiting phosphorylation of Ser727 of STAT3, a phosphorylation inhibitor containing the new compound, an insulin resistance improving agent and a preventive or therapeutic agent for diabetes; and a screening method for at least one of the insulin resistance improving agent and the preventive or therapeutic agent for diabetes.

Abstract: This invention relates to novel analogs of pituitary adenylate cyclase-activating polypeptide (PACAP), which are agonists for the PACAP/vasoactive intestinal peptide (VIP) receptors: PAC1, VPAC1 and VPAC2 receptors. These PACAP analogs can be used as prophylactic/therapeutic agents for a wide range of medical disorders, including (but not limited to) cancer and autoimmune disease. These PACAP analogs can be coupled to suitable radionuclides and used in the localization, diagnosis and treatment of disseminated cancers and metastatic tumors, or coupled to small molecule therapeutics and used as vectors for targeted drug delivery. This invention also provides pharmaceutical compositions of one or more PACAP-like compounds of the invention either alone or in combination with one or more other prophylactic/therapeutic agents.

Abstract: The invention provides di-peptide conjugated antitumor agents, pharmaceutical compositions and methods for preparation and use thereof for treating various cancer and inflammation-related diseases and conditions. The present invention addresses the shortcomings of the existing anti-tumor and anti-inflammatory drugs, particularly in that the anti-tumor agents of the invention that selectively kill cancer cells with minimal damage to normal cells.

Abstract: Methods for reducing body weight, altering body composition, treating diabetes, reducing HbA1c and reducing average daily blood glucose by the use of exendins, exendin agonists or exendin analog agonists are provided.

Abstract: Methods and compositions relating to CDP-JAK inhibitor conjugates are described herein.

Abstract: The present invention relates to shelf stable non-aqueous pharmaceutical compositions, and to the use thereof in methods of treating diabetes and hyperglycaemia.

Abstract: Provided is a method of treating type 2 diabetes in a subject, comprising administering a polypeptide comprising thymosin, or an active fragment or variant thereof, preferably comprising or consisting of the peptide LKKTETQ (SEQ ID NO: 1).

Abstract: Amylin derivatives, pharmaceutical compositions containing such derivatives, as well as methods of treating diabetes and hyperglycaemia are disclosed.

Abstract: The present invention provides methods of treating prediabetes, hyperglycemia, type 2 diabetes, AMIS syndrome, and obesity in a subject by administering to the patient HISS. The present invention also provides methods of diagnosing AMIS syndrome in a patient. Additionally, the present invention provides a method of shifting nutrient storage in meat-producing livestock to muscle rather than fat.

Abstract: The present invention is directed to methods and compositions for systemic delivery of minimally-soluble bioactive agents such as, but not limited to, proteins of the TGF-? superfamily. According to the invention, an exemplary bioactive agent is BMP-7 The invention further provides for minimally-invasive systemic treatment of skeletal disorders such as osteoporosis as well as minimally-invasive systemic treatment of injured or diseased non-mineralized tissues and organs such kidneys. Practice of the invention eliminates adverse side effects at the site of intravascular delivery of the bioactive agent.

Abstract: New gene therapy constructions and compositions are the subject of present invention. The gene therapy compositions consist in adeno-associated vectors which jointly express insulin (Ins) and glucokinase (Gck) genes. The new gene therapy constructions are useful for treatment of diabetes either in dogs or human beings.

Abstract: The present invention relates to novel peptides derivable from the polypeptide chaperonin 60.1 and to their use in medicine, such as for the prevention and/or treatment of inflammatory conditions.

Abstract: The present invention provides methods of preventing, treating or ameliorating diabetes by administering to a subject in need thereof a therapeutically effective amount of Dll4 antagonists that block Dll4-Notch signal pathways. As observed in a mouse model of diabetes, Dll4 antagonists exhibit protective effects on pancreatic islets, lower blood glucose levels, and block the production of auto-antibodies, including those against insulin and glutamic acid decarboxylase 65 (GAD65), via the expansion of regulatory T cells (Tregs). Thus, the present invention further provides methods of lowering the levels of blood glucose, and/or reducing or blocking the production of auto-antibodies, by administering to a subject in need thereof a therapeutically effective amount of Dll4 antagonists. Suitable Dll4 antagonists for the invention include antibodies or antibody fragments that specifically bind Dll4 and block Dll4-Notch interactions, the extracellular domain of Dll4, and the like.

Abstract: Provided are a fusion protein of Exendin-4 and its analog, the preparation method and use thereof. The fusion protein is obtained by fusing of Exendin-4 or its analog to Fc region of human IgG2 via a linking peptide, which has the better stability and prolonged serum half-life, and can be used for treating diabetes and obesity.

Abstract: The present invention is directed to novel compounds of Formula I. The compounds of the present invention are potent tyrosine kinase modulators, and are suitable for the treatment and prevention of diseases and conditions related to abnormal activities of tyrosine kinase receptors.

Abstract: The present invention provides novel peptidomimetics, of formula (I), which primarily act as glucose dependent insulin secretagogues. Furthermore, it was found that these peptidomimetics showed glucagon receptor antagonistic activity, along with the GLP-I receptor agonistic activity.

Abstract: The invention provides methods for treatment, prevention or management of obesity, obesity related disorders, diabetes mellitus, and metabolic syndrome in a subject by administering a ghrelin O-acyltransferase (GOAT) inhibitor and/or a ghrelin receptor antagonist to the subject. The invention also provides ghrelin receptor antagonists of formula (VII): A11-A12-A13-Gly-Ser-A14-Phe-Leu-A15-A16-A17-A18 (SEQ ID NO: 93), wherein each of A11, A12, and A13 is independently absent, an amino acid, or an amino protecting group; each of A15, A16, A17, and A18 is independently absent or an amino acid; and A14 is a serine conjugated with a —(O)C1-C20alky or a diaminopropionic acid conjugated with a —C(O)C1-C20alkyl group, provided that at least one of A11, A12, or A13 is present.

Abstract: The present invention encompasses albumin fusion proteins. Nucleic acid molecules encoding the albumin fusion proteins of the invention are also encompassed by the invention, as are vectors containing these nucleic acids, host cells transformed with these nucleic acids vectors, and methods of making the albumin fusion proteins of the invention and using these nucleic acids, vectors, and/or host cells. Additionally the present invention encompasses pharmaceutical compositions comprising albumin fusion proteins and methods of treating or preventing diseases, disorders or conditions related to diabetes mellitus using albumin fusion proteins of the invention.

Abstract: Methods, compounds, pharmaceutical compositions and kits are described for treating or preventing amyloid-related disease.

Abstract: A process for preparing human relaxin-2 having the following amino acid sequence: A chain: (SEQ?ID?NO:?1) pGlu-Leu-Tyr-Ser-Ala-Leu-Ala-Asn-Lys-Cys-Cys-His- Val-Gly-Cys-Thr-Lys-Arg-Ser-Leu-Ala-Arg-Phe-Cys B chain: (SEQ?ID?NO:?2) Asp-Ser-Trp-Met-Glu-Glu-Val-Ile-Lys-Leu-Cys-Gly- Arg-Glu-Leu-Val-Arg-Ala-Gln-Ile-Ala-Ile-Cys-Gly- Met-Ser-Thr-Trp-Ser; comprising the following steps: providing the amino acids necessary for the synthesis of the A and B chains with usual protective groups, wherein the cysteines are employed as trityl-protected amino acids (L-Cys(Trt)-OH); effecting a chromatographic purification of the individual chains A and B after the solid state synthesis; followed by the simultaneous folding and combination of the individual chains A and B in ammonium hydrogencarbonate buffer at pH 7.9 to 8.4; and subsequent purification of the relaxin-2 formed.

Abstract: The present invention relates to compositions forming a low viscosity mixture of: a. 25-55 wt. % of at least one diacyl glycerol and/or at least one tocopherol; b. 25-55 wt. % of at least one phospholipid component comprising phospholipids having i. polar head groups comprising more than 50% phosphatidyl ethanolamine, and ii. two acyl chains each independently having 16 to 20 carbons wherein at least one acyl chain has at least one unsaturation in the carbon chain, and there are no more than four unsaturations over two carbon chains; c. 5-25 wt. % of at least one biocompatible, oxygen containing, low viscosity organic solvent; wherein 0.1-10 wt. % of at least one peptide active agent comprising at least one somatostatin receptor agonist is dissolved or dispersed in the low viscosity mixture; and wherein the pre-formulation forms, or is capable of forming, at least one non-lamellar liquid crystalline phase structure upon contact with an aqueous fluid.

Abstract: The present invention is directed to a method of treating a metabolic disorder or key elements of a metabolic disorder such method comprising the use of an agent(s) that increases central dopaminergic activity plus a first-phase insulin secretagouge.

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: 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: The invention provides nucleic acid molecules encoding FGF21 mutant polypeptides, FGF21 mutant polypeptides, pharmaceutical compositions comprising FGF21 mutant polypeptides, and methods for treating metabolic disorders using such nucleic acids, polypeptides, or pharmaceutical compositions.

Abstract: The present invention concerns the use of HYD1 peptides to reduce activated T-cell numbers and/or to promote bone preservation in vivo. The present invention concerns methods of treating a bone deficiency and/or an autoimmune disorder, comprising administering an effective amount of a HYD1 peptide. Another aspect of the invention concerns a pharmaceutical composition comprising a HYD1 peptide and another agent for treating a bone deficiency and/or another agent for treating an autoimmune disorder.

Abstract: The invention includes methods of neuroprotection, inducing release of neurotrophic factors, inhibiting the over-activation of innate immune cells, attenuating the toxin-induced death and/or damage of tissues, reducing inflammation, treating an inflammation-related condition, and inhibiting NADPH oxidase, that includes contacting or administering an effective amount of at least one compound of the invention that include: valproic acid, sodium butyrate, and salts thereof; opioid peptides; a peptide comprising the tripeptide GGF; and morphinans, such as naloxone, naltrexone, 3-hydroxy-morphinan and dextromethorphan.

Abstract: Potent compounds having combined antioxidant, anti-inflammatory, anti-radiation and metal chelating properties are described. Short peptides having these properties, and methods and uses of such short peptides in clinical and cosmetic applications are described.

Abstract: The present invention provides novel compounds of the Formula (I), pharmaceutical compositions comprising such compounds and methods for using such compounds as tools for biological studies or as agents or drugs for therapies such as metabolic syndrome, obesity, type II diabetes, fibrosis and cardiovascular diseases, whether they are used alone or in combination with other treatment modalities.

Abstract: Methods are disclosed for determining progression of a condition, onset of a condition, or efficacy of treatment of a condition characterized by an adipocyte imbalance in a patient. In addition, methods are disclosed of treating diabetes, abnormal adipocyte activity, and insulin resistance using monomeric, homodimeric, and heterodimeric forms of certain C-terminal fragments of adiponectin receptor. In addition, methods of treating abnormal adipocyte activity, treating metabolic syndrome, causing insulin secretion, increasing insulin levels, inhibiting insulin degradation enzyme, treating Alzheimer's disease, treating cardiovascular disease associated with adiponectin levels, inhibiting ADAM-17 enzyme, inhibiting a protease, treating a condition associated with TNF-alpha, and treating a condition associated with HER2-neu are disclosed. Compositions, dosage forms, and kits are also disclosed.

Abstract: It has been found that high amounts of aspartate equivalents in combination with vitamin B12 and/or biotin, especially in relative absence of glutamate equivalents, improve the metabolism of ketobodies and/or lactate in a mammal's body, especially in diseased or traumatic conditions. As a result, levels of ketobodies and lactate can be decreased and unphysicologically high acidity normalised. Thus, it is an object of the invention to provide an enteral nutritional or a pharmaceutical composition for the treatment and/or prevention of disturbed ketone and lactate metabolism, i.e. elevated concentrations of ketone bodies, lactate and/or other organic acids and/or insufficient pH homeostasis, especially elevated concentrations of ketone bodies and/or lactate, in a mammal's blood, wherein the composition comprises high amounts of aspartate equivalents in combination with vitamin B12 and/or biotin, preferably in relative absence of glutamate equivalents.

Abstract: The present invention relates to fibronectin-based scaffold domain proteins that bind to myostatin. The invention also relates to the use of these proteins in therapeutic applications to treat muscular dystrophy, cachexia, sarcopenia, osteoarthritis, osteoporosis, diabetes, obesity, COPD, chronic kidney disease, heart failure, myocardial infarction, and fibrosis. The invention further relates to cells comprising such proteins, polynucleotides encoding such proteins or fragments thereof, and to vectors comprising the polynucleotides encoding the proteins.

Abstract: The present invention is related to insulin derivatives having a side chain attached either to the ?-amino group of the N-terminal amino acid residue of B chain or to an ?-amino group of a Lys residue present in the B chain of the parent insulin molecule via an amide bond which side chain comprises one or more residues of ethyleneglycol, propyleneglycol and/or butyleneglycol containing independently at each termini a group selected from —NH2 and —COOH; a fatty diacid moiety with 4 to 22 carbon atoms, at least one free carboxylic acid group or a group which is negatively charged at neutral pH; and possible linkers which link the individual components in the side chain together via amide or ether bonds, said linkers optionally comprising a free carboxylic acid group.

Abstract: Type-1 diabetes (T1 D) results from the autoimmune recognition of insulin producing ?-cells within the pancreatic islet. The present application discloses a new protein, islet homeostasis protein (IHoP), that has a role in glucagon synthesizing-cell functions, and in post-onset T1 D islet differential expression of IHoP. Methods of delaying the onset of diabetes are disclosed, as well as compositions including an iHoP modulating agent. Also disclosed are methods of screening for iHoP modulating agents.

Abstract: The present invention relates to compositions comprising biologically active proteins linked to extended recombinant polypeptide (XTEN), isolated nucleic acids encoding the compositions and vectors and host cells containing the same, and methods of using such compositions in treatment of glucose-related diseases, metabolic diseases, coagulation disorders, and growth hormone-related disorders and conditions.

Abstract: Work described herein provides, in one embodiment, a method for increasing proliferation or replication of pancreatic beta cells in a subject in need thereof, comprising administering to said subject an effective amount of an agent that increases the level or activity of hepatocellular carcinoma-associated protein TD26 (TD26), thereby increasing proliferation or replication of pancreatic beta cells. Such an agent may function by, for example, increasing the level of active TD26 in the subject or by increasing the functional activity of TD26 in the subject.

Abstract: The present invention relates to the finding that certain DPP-4 inhibitors are particularly suitable for treating and/or preventing metabolic diseases, particularly diabetes, in patients for whom metformin therapy is inappropriate due to intolerability or contraindication against metformin.

Abstract: The present invention relates to fibronectin-based scaffold domain proteins that bind to myostatin. The invention also relates to the use of these proteins in therapeutic applications to treat muscular dystrophy, cachexia, sarcopenia, osteoarthritis, osteoporosis, diabetes, obesity, COPD, chronic kidney disease, heart failure, myocardial infarction, and fibrosis. The invention further relates to cells comprising such proteins, polynucleotides encoding such proteins or fragments thereof, and to vectors comprising the polynucleotides encoding the proteins.

Abstract: The present invention is related to insulin derivatives containing additional disulfide bonds and methods of making such.

Abstract: Methods of inhibiting fibroblast growth factor mediated activation of fibroblast growth factor receptors for the treatment of chronic kidney disease, diabetes, and cardiac diseases are enclosed. Pharmaceutical compositions for the treatment of such diseases using the methods are also disclosed as are methods of determining whether a subject would benefit from the methods of treatment and pharmaceutical compositions.

Abstract: MOTS3 is a novel polypeptide. Methods of treating diseases such as diabetes, obesity, fatty liver, and cancer using MOTS3 and pharmaceutical compositions thereof are disclosed herein.

Abstract: A process for the production of pramlintide, a 37-mer peptide, is provided. The synthesis provides a high yield synthesis of the peptide in relatively pure form. Further purification can be achieved by preparative HPLC.

Abstract: The invention relates to a pharmaceutical composition comprising 1.a and/or 1.b according to claim 1 in combination with at least one second therapeutic agent 2 which is suitable in the treatment or prevention of one or more conditions selected from type 1 diabetes mellitus, type 2 diabetes mellitus, impaired glucose tolerance and hyperglycemia. In addition the present invention relates to methods for preventing or treating of metabolic disorders and related conditions.

Abstract: The present invention relates to new biphenyl-3-carboxylic acid modulators of beta-3-adrenoceptor activity, pharmaceutical compositions thereof, and methods of use thereof.

Abstract: The present invention provides novel peptidomimetics, of formula (I), which primarily act as glucose dependent insulin secretagogues. Furthermore, it was found that these peptidomimetics showed glucagon receptor antagonistic activity, along with the GLP-1 receptor agonistic activity.

Abstract: This application relates to methods of predicting susceptibility or likelihood of a clinically-relevant mannose-binding lectin (MBL)-deficient subject to develop a cardiovascular disease and/or cardiodiabetes. The methods include measuring MBL mass or concentration and, optionally, measuring MBL activity, at least one other biomarker and/or genotyping of MBL gene and its promoters; combining the information obtained into a calculated MBL-inclusive index score that involves mathematical transformation; and assigning a risk of cardiadiabetic status and clinical endpoints based on the determination and comparison of the MBL inclusive index to reference values from a population.

Abstract: The invention provides ultra-small peptide inhibitors that are capable of preventing amyloid formation/amyloidosis.