32 results about "PYY receptors" patented technology

The present invention relates to novel Pancreatic Polypeptide Family (“PPF”) polypeptides. The PPF polypeptides of the invention generally include at least two PPF motif, have at least 50% sequence identity to PYY (3-36) over its length and will generally retain, at least in part, a biological activity of a PP, PYY or NPY. Preferred PPF polypeptides of the invention are those having a potency in one of the assays described herein (preferably food intake, gastric emptying, pancreatic secretion, or weight reduction assays) which is greater than the potency of PP, NPY, PYY, or PYY(3-36) in that same assay. In one aspect, the PPF polypeptides of the invention include novel PYY analog polypeptides. In another aspect, the PPF polypeptides of the invention include PPF chimeric polypeptides including a fragment of a PP family polypeptide linked to a second PP family polypeptide, wherein each of the first and second fragments includes a PPF motif. Methods of using the PPF polypeptides of the invention, and pharmaceutical compositions including the PPF polypeptides of the invention are also disclosed.

Pharmaceutical compositions and methods are described comprising at least one Y2 receptor-binding peptide, such as peptide YY(PYY), Neuropeptide Y (NPY) or Pancreatic Peptide (PP) and one or more mucosal delivery-enhancing agents for enhanced nasal mucosal delivery of the peptide YY, for treating a variety of diseases and conditions in mammalian subjects, including obesity.

Methods and compositions are disclosed to treat metabolic disorders such as obesity, diabetes, and increased cardiovascular risk comprising administering a therapeutically effective amount of a PYY or a PYY agonist.

Pharmaceutical compositions comprising PYY(3-36), a cyclodextrin, and a compound selected from phosphatidylcholine or diglyceride, wherein the PYY(3-36) is present in an amount effective to alleviate one or more symptom(s) of obesity in a subject, and the cyclodextrin and the compound selected from phosphatidylcholine or diglyceride are present in an amount sufficient to enhance epithelial permeation.

The invention provides a PYY agonist derivative of the formula: (X)n-Z, wherein X is a radical 9-fluorenylmethoxy-carbonyl (Fmoc) or 2-sulfo-9-fluorenyl-methoxycarbonyl (FMS), Z is the residue of a PYY agonist linked to the radical X through an amino or hydroxyl group, and n is 1 to 3, or a pharmaceutically acceptable salt thereof, for reducing food intake and treatment of a disease, condition or disorder that can be alleviated by reduction of food intake such as obesity, hypertension, dyslipidemia, cardiovascular risk, eating disorder, insulin-resistance, or diabetes mellitus.

The present invention relates to methods of using GPR119 receptor to identify peptide YY (PYY) secretagogues and compounds useful in the treatment of conditions modulated by PYY, such as conditions modulated by stimulation of NPY Y2 receptor (Y2R). Agonists of GPR119 receptor are useful as therapeutic agents for treating or preventing a condition modulated by PYY, such as a condition modulated by stimulation of Y2R. Conditions modulated by PYY such as may be a condition modulated by stimulation of Y2R include bone-related conditions, metabolic disorders, angiogenesis-related conditions, ischemia-related conditions, convulsive disorders, malabsorptive disorders, cancers, and inflammatory disorders.

This invention relates generally to neuropeptide Y (“NPY”) Y4 receptor agonists including pancreatic polypeptide (PP), analogs thereof, and peptide fragments of PP, e.g. PP(32-36), and analogs thereof, to pharmaceutical compositions containing such Y4 receptor agonists, and to methods for treatment of mammals using the same. The NPY Y4 receptor agonists may be administered to mammals either alone or in combination with NPY Y2 receptor agonists including peptide YY (PYY) (3-36), analogs thereof, and to peptide fragments of PYY(3-36), e.g. PYY(22-36) and PYY(25-36), and analogs thereof, such as to control food intake in mammals, blood pressure, cardiovascular response, libido, circadian rhythm, hyperlipidimia, chronic pancreatitis, and nonalcoholic fatty liver disease including nonalcoholic steatohepatitis.

Analogues of the peptide PYY (1-36) are described in which the tertiary structure of the peptide is preserved and stabilised particularly to enhance binding and activation of the Y2 receptor by the use of cross links or rigid bends in the peptide to constrain conformationally the positions of the N-terminal part of the peptide sequence and amino acid 34. The analogues are useful in the control of food intake.

A novel use of PYY or a PYY agonist is disclosed for treating a bowel condition such as inflammatory bowel disease (e.g. ulcerative colitis and Crohn's disease), bowel atrophy, loss of bowel mucosa and loss of bowel mucosal function. The novel use is based on the discovery and demonstration that administration of PYY or a PYY agonist to an animal can protect the colon from injury induced by a hapten known to induce colitis.

Y receptor agonists other than PYY 3-36, which are selective for the Y2 receptor over the Y1 and Y4 receptors, and their use in the treatment of conditions responsive to activation of Y2 receptors, are disclosed. Broadly, a Y2-selective agonist is one which (a) is a PP-fold peptide or PP-fold peptide mimic selected from PYY, NPY, PYY mimics and NPY mimics which have a C-terminal Y2 receptor-recognition amino acid sequence and have various modifications relative to the natural peptides or (b) a PP-fold peptide or PP-fold peptide mimic selected from PP and PP-mimics which have a C-terminal Y2 receptor-recognition amino acid sequence and which have various modifications relative to the natural peptide or (c) comprise a C-terminal Y2 receptor-recognition amino acid sequence fused at its N-terminus to an amphiphilic amino acid sequence domain comprising at least one alpha helical turn adjacent the N-terminus of the said Y2 receptor-recognition sequence, said turn being constrained in a helical configuration by a covalent intramolecular link, and (ii), in the case where the agonist has an N-terminal structure analogous to NPY or PYY, having one or more of the modifications listed in (a) above and, in the case where the agonist has an N-terminal structure analogous to PP, having one or more of the modifications listed in (b) above.

The invention provides analogs of PYY. The invention also provides compositions and methods useful for controlling biological activities such as cell proliferation, nutrient transport, lipolysis, and intestinal water and electrolyte secretion.

Compositions containing a therapeutic peptide covalently linked to Vitamin B12 at the 5′-hydroxyl group of the ribose moiety of α-ligand are described. The length of the linkage is optimized so that the biological activity of both the Vitamin B12 and the therapeutic peptide is maintained. Therapeutic peptides for conjugation with vitamin B12 include insulin, PYY, NPY and GLP-1. Attachment to Vitamin B12 provides uptake of the therapeutic peptide from the digestive tract and longer residence time.

Disclosed is a method for refolding a protein or peptide that does not contain essential disulfides and that contains at least one free cysteine residue. Also disclosed are polymer IFN-γ conjugates that have been created by the chemical coupling of polymers such as polyethylene glycol moieties to IFN-γ, particularly via a free cysteine in the protein. Also disclosed are analogs of bioactive peptides that may be used to create longer acting versions of the peptides, including analogs of glucagon, glucagon-like peptide-1 (GLP-1), GLP-2, Gastric inhibitory peptide (GIP), PYY, exendin, ghrelin, gastrin, amylin, and oxyntomodulin.

The present invention relates to a PYY or PP peptide derivative or analogue thereof derivatised with one or more serum albumin binding side chains comprising a dis-tal tetrazole or carboxylic acid group. Moreover, the invention relates to compositions hereof and methods of treatment of conditions responsive to Y receptor modulation.

Disclosed is a method for refolding a protein or peptide that does not contain essential disulfides and that contains at least one free cysteine residue. Also disclosed are polymer IFN-γ conjugates that have been created by the chemical coupling of polymers such as polyethylene glycol moieties to IFN-γ, particularly via a free cysteine in the protein. Also disclosed are analogs of bioactive peptides that may be used to create longer acting versions of the peptides, including analogs of glucagon, glucagon-like peptide-1 (GLP-1), GLP-2, Gastric inhibitory peptide (GIP), PYY, exendin, ghrelin, gastrin, amylin, and oxyntomodulin.

The present invention relates to compounds of formula (1); variants or derivatives thereof, or salts or solvates thereof. The present invention also relates to the use of such compounds to control appetite, feeding, food intake, energy expenditure and calorie intake, particularly in the treatment of obesity.

The present invention provides transgenic animals having a reduced level of expression of peptide YY (PYY) and drug screening platforms using the transgenic animals for identifying agonists and antagonists of PYY. The present invention further provides monoclonal antibodies that bind specifically to full-length PYY[1-36] or the processed form thereof i.e., PYY[3-36] and to diagnostic and drug screening platforms using the monoclonal antibodies. The invention has particular utility for the diagnosis of a predisposition or risk of a subject becoming obese, developing one or more pathologies associated with obesity, or developing a disease / disorder of bone tissue.

The present invention provides transgenic animals having a reduced level of expression of peptide YY (PYY) and drug screening platforms using the transgenic animals for identifying agonists and antagonists of PYY. The present invention further provides monoclonal antibodies that bind specifically to full-length PYY[1-36] or the processed form thereof i.e., PYY[3-36] and to diagnostic and drug screening platforms using the monoclonal antibodies. The invention has particular utility for the diagnosis of a predisposition or risk of a subject becoming obese, developing one or more pathologies associated with obesity, or developing a disease / disorder of bone tissue.

Drug fusions and conjugates that contain an incretin therapeutic or diagnostic agent that is fused or conjugated to an antigen-binding fragment of an antibody that binds serum albumin. The conjugates and fusion have a longer in vivo half life in comparison with the unconjugated or unfused therapeutic or diagnostic agent.

Pharmaceutical compositions and methods are described comprising at least one Y2 receptor-binding peptide, such as peptide YY (PYY), Neuropeptide Y (NPY) or Pancreatic Peptide (PP) wherein the formulations have increased resistance to microbial contamination and is comprised of a Y2 receptor-binding peptide, water, a cyclodextrin and sodium benzoate.

A method for treating obesity, inducing weight-loss, or inducing satiety in a mammal comprising administering intranasally to the mammal a therapeutically effective amount of a pharmaceutical composition comprising PYY(3-36), a phosphatidylcholine or diglyceride, and a cyclodextrin, wherein the phosphatidylcholine or diglyceride and the cyclodextrin are present in an amount sufficient to enhance epithelial permeation.

A pharmaceutical device comprising a composition comprising an aqueous solution of PYY(3-36), a cyclodextrin, and a compound selected from phosphatidylcholine or diglyceride, wherein the cyclodextrin and the compound selected from phosphatidylcholine or diglyceride are present in an amount sufficient to enhance epithelial permeation, and wherein the composition is present in a container; and an actuator fluidly connected to the container, wherein the actuator has a tip which defines a passage through which the solution is ejected to produce a spray of the solution.

The invention relates to PYY compounds with the amino acid modifications 7Lys, 30Trp, and 31Leu, and in addition to these, 22Ile and / or 28Tyr, and derivatives thereof. The compounds of the invention are selective Y2 receptor agonists. The invention also relates to pharmaceutical compositions comprising such PYY compounds and pharmaceutically acceptable excipients, as well as the medical use of the PYY compounds.

The invention relates to PYY compounds with the amino acid modifications 7Lys, 30Trp, and 31Leu, and in addition to these, 22Ile and / or 28Tyr, and derivatives thereof. The compounds of the invention are selective Y2 receptor agonists. The invention also relates to pharmaceutical compositions comprising such PYY compounds and pharmaceutically acceptable excipients, as well as the medical use of the PYY compounds.

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.

Disclosed is a method for the detection of colon cancer by a blood test for elevated levels of peptide YY (PYY), a hormone which is produced in the gut, secreted into blood and transported into the brain where it regulates appetite. Other body fluids can also be evaluated in the same way. The use of PYY measurement as part of the periodic medical examination together with other screening tests such as fecal hemoccult and carcinoembryonic antigen could substantially improve the possibility of diagnosis of colon cancer at an early stage when surgery is likely to be curative.

What is described is an aqueous Y2 receptor-binding peptide formulation for enhanced intranasal delivery of a Y2 receptor-binding peptide, comprising said Y2 receptor-binding peptide, a buffer salt, and having a pH between about 3.0 and about 6.0, wherein said buffer salt comprises a net single ionogenic moiety with a pKa within two pH units of the pH of the formulation.

The present invention relates to methods of using GPR119 receptor to identify peptide YY (PYY) secretagogues and compounds useful in the treatment of conditions modulated by PYY, such as conditions modulated by stimulation of NPY Y2 receptor (Y2R). Agonists of GPR119 receptor are useful as therapeutic agents for treating or preventing a condition modulated by PYY, such as a condition modulated by stimulation of Y2R. Conditions modulated by PYY such as may be a condition modulated by stimulation of Y2R include bone-related conditions, metabolic disorders, angiogenesis-related conditions, ischemia-related conditions, convulsive disorders, malabsorptive disorders, cancers, and inflammatory disorders.