Abstract: Peptide analogs of nociceptin/orphanin FQ, compositions thereof, and their use in treatment of disorders and dysfunctions related to activation or blocking of NOP receptors are described.

Abstract: The invention provides SPARC antisense oligonucleotides and methods of their use in proliferative diseases such as cancer and hepatic fibrosis.

Abstract: The present invention relates to the use of novel compounds for the manufacture of a medicament for treatment of, inter alia, conditions associated with critical care sepsis, septic shock, hepatorenal syndrome type I, hypertension induced by endstage venal disease, severe burns, thermal injury as well as to a method for treatment of the conditions by administering the compounds. The compounds used are represented by the general formula (1), as further defined in the specification.

Abstract: The present invention discloses proteinaceous compounds that comprise at least a biologically active portion of a taipan natriuretic peptide (TNP) or a variant or derivative thereof. The invention also relates to the use of these compounds in methods for stimulating vasodilation, natriuresis, diuresis, renin-suppression, bactericidal activity, weight-loss or bone growth in a mammalian host. In specific embodiments, the compounds are useful in the treatment of congestive heart failure.

Abstract: In one aspect, the invention relates to compounds having the formula: where R1-R6, a, b, and X are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds have neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and processes and intermediates for preparing such compounds.

Abstract: The present invention relates to multimeric (e.g., dimeric, trimeric) forms of peptide vectors that are capable of crossing the blood-brain barrier (BBB) or efficiently entering particular cell types. These multimeric peptide vectors, when conjugated to agents (e.g., therapeutic agents) are capable of transporting the agents across the BBB or into particular cell types. These compounds are therefore particularly useful in the treatment of neurological diseases.

Abstract: Disclosed are peptide ligands for G-protein coupled receptors that are useful for treating disorders associated with G-protein coupled receptor activation.

Abstract: The present invention provides novel tetrahydrocarbazole compounds according to formula (I) as ligands of G-protein coupled receptors (GPCR) which are useful in the treatment and/or prophylaxis of physiological and/or pathological conditions in mammals mediated by GPCR or of physiological and/or pathological conditions which can be treated by modulation of these receptors.

Abstract: The present invention provides a compound of formula I; or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R4, R5, B, X, m and n are defined herein. The invention also relates to a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides pharmaceutical composition of compounds of the invention, and a combination of pharmacologically active agents and a compound of the invention.

Abstract: The present invention relates to pharmaceutical formulations of Aviptadil and its derivatives. The stability of the Aviptadil formulation was shown to be improved by a formulation having a defined concentration of Aviptadil prepared in a buffer having a defined pH range.

Abstract: Methods are provided for the preparation of conjugates of a variety of bioactive components, especially proteins, with water-soluble polymers (e.g., poly(ethylene glycol) and derivatives thereof), which conjugates have reduced antigenicity and immunogenicity compared to similar conjugates prepared using poly(ethylene glycol) containing a methoxyl or another alkoxyl group. The invention also provides conjugates prepared by such methods, compositions comprising such conjugates, kits containing such conjugates or compositions and methods of use of the conjugates and compositions in diagnostic and therapeutic protocols.

Abstract: A method for treating a disorder characterized by salt retention, fluid retention, and combinations thereof. A method for determining the presence of or the progression of a disorder characterized by salt retention, fluid retention, salt loss, fluid loss, and combinations thereof. An immunoassay kit for detecting a level of prouroguanylin in a sample.

Abstract: The present invention relates to peptides which are highly biologically and pharmacologically active as therapeutic drug for the treatment of diseases related to hypertension, especially in medical interventions involving dilatation and remodeling of arterial blood vessels, either in the pulmonary or in the systemic circulation. The peptides which can be used according to the invention for the treatment of said diseases comprise at least one specific highly conservative amino acid residue sequence which seem to play an important role in connection with pulmonary and arteriolar hypertension events. It could be shown that the known naturally occurring peptides “vasoactive intestinal peptide (VIP)” and “pituitary adenylate cyclase-activating polypeptide (PACAP)”, having these specific sequences are potent drugs which can be successfully used for treatment of primary pulmonary hypertension (PPH), secondary pulmonary hypertension (SPH), and hypertension of the systemic circulation.

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 cyclic peptides, comprising alternating D- and L- amino acids and wherein the peptide possesses immunomodulatory activity. The present invention also relates to pharmaceutical compositions comprising the cyclic peptides and to methods for the treatment of disease.

Abstract: The present invention is directed to a pharmaceutical composition comprising 0.5 ng to 20 ?g desmopressin and a pharmaceutically acceptable carrier. The present invention is also directed to a pharmaceutical composition comprising desmopressin and a pharmaceutically acceptable carrier, wherein the pharmaceutical composition is effective to establish a steady plasma/serum desmopressin concentration in the range of from about 0.1 picograms desmopressin per mL plasma/serum to about 10.0 picogram desmopressin per mL plasma/serum. Articles of manufacture and methods of using the above invention are also disclosed.

Abstract: Provided is a composition comprising a peptide comprising amino acids and/or amino acid analogs comprising a continuous sequence of a sclerostin fragment comprising Tyr43 or Tyr213. Also provided is a composition comprising a peptide comprising less than about 75 amino acids and/or amino acid analogs including an amino acid or amino acid analog capable of being sulfated, where the composition is capable of inhibiting sclerostin binding to an LRP. Further provided is a composition comprising a peptide comprising less than about 75 amino acids and/or amino acid analogs including an amino acid or amino acid analog capable of being post-translationally sulfated, where the composition is capable of inhibiting binding of a protein ligand comprising a sulfation site to its binding partner.

Abstract: Methods are provided for the diagnosis and treatment of patients with increased risk of preeclampsia. The methods involve measuring levels of TGF-?3, receptors of cytokines of the TGf? family, or HIF-1?.

Abstract: The inventors have discovered that both soluble erythropoietin-binding protein and antibodies against the erythropoietin-binding protein, when they are administered to a mammal along with erythropoietin (Epo), prevent or reduce the blood pressure increase normally caused by erythropoietin, while not affecting the hematocrit increase that is the purpose of Epo treatment. The invention provides a method of treating anemia in a mammal involving: administering erythropoietin (Epo) to the mammal; and administering to the mammal an agent selected from a soluble Epo-binding protein (Epo-bp), a recognition protein that binds Epo receptor on an extracellular soluble portion of the Epo receptor, and a combination thereof. The invention also provides a method of reducing hypertension in a mammal receiving Epo, and pharmaceutical compositions containing a soluble Epo-bp and/or a recognition protein that binds Epo receptor on an extracellular soluble portion of the Epo receptor.

Abstract: The invention provides novel nucleic acids and polypeptides, referred to herein as stresscopin 1 and stresscopin 2, which preferentially activate the CRH-R2 receptor over the R1 receptor. Stresscopins, analogs and mimetics, and related CRH-R2 agonists suppress food intake and heat-induced edema; but do not induce substantial release of ACTH. Stresscopin also finds use in the recovery phase of stress responses, as an anti-inflammatory agent, as a hypotensive agent, as a cardioprotective agent, and in the treatment of psychiatric and anxiolytic disorders. Stresscopin nucleic acid compositions find use in identifying homologous or related proteins and the DNA sequences encoding such proteins; in producing compositions that modulate the expression or function of the protein; and in studying associated physiological pathways.

Abstract: The invention provides a method of inhibiting vascular hyperpermeability in an animal in need thereof. The method comprises administering an effective amount of a diketopiperazine, a prodrug of a diketopiperazine or a pharmaceutically-acceptable salt of either of them to the animal, wherein the diketopiperazine has the formula set forth in the specification. The invention also provides a method of modulating the cytoskeleton of an endothelial cell in an animal. The method comprises administering an effective amount of a diketopiperazine, a prodrug of a diketopiperazine or a pharmaceutically-acceptable salt of either of them to the animal, wherein the diketopiperazine has the formula set forth in the specification. The invention further provides a kit. The kit comprises a diketopiperazine, a prodrug of a diketopiperazine or a pharmaceutically-acceptable salt of either of them to the animal, wherein the diketopiperazine has the formula set forth in the specification.

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: The present invention relates to novel analogues of neuropeptide Y, pharmaceutical compositions containing the same, pharmaceutical formulations containing the same, and method of treating diseases or conditions mediated by neuropeptide Y-receptor binding. More particularly, the present invention relates to novel analogues of neuropeptide Y having proline substitution at position 34 and other substitution(s) as defined herein that selectively bind to the neuropeptide Y1 receptor subtype compared to the neuropeptide Y2 receptor subtype.

Abstract: Peptides that act as GC-C receptor agonists and contain at least one D-cys and are useful for the treatment of diuresis and heart disease as well as other disorders are described.

Abstract: The present invention relates to novel analogues of neuropeptide Y, pharmaceutical compositions containing the same, pharmaceutical formulations containing the same, and method of treating diseases or conditions mediated by neuropeptide Y-receptor binding. More particularly, the present invention relates to novel analogues of neuropeptide Y having at least one unnatural amino acid substitution, such as 4Hyp at position 34, that selectively bind to the neuropeptide Y1 receptor subtype compared to the neuropeptide Y2 receptor subtype.

Abstract: Disclosed are compositions and methods useful for targeting and internalizing molecules into cells of interest and for penetration by molecules of tissues of interest. The compositions and methods are based on peptide sequences, such as truncated CAR peptides, that are selectively internalized by a cell, penetrate tissue, or both. The disclosed internalization and tissue penetration is useful for delivering therapeutic and detectable agents to cells and tissues of interest.

Abstract: The invention relates to compositions comprising vasoactive intestinal peptide (VIP) or fragments thereof, and the use of such compositions in the treatment of aortic fibrosis and other associated conditions.

Abstract: The invention relates generally to compounds which are allosteric modulators (e.g., negative and positive allosteric modulators, allosteric agonists, and ago-allosteric modulators) of the G protein coupled receptor apelin, also known as the APJ receptor. The APJ receptor compounds are derived from the intracellular loops and domains of the the APJ receptor. The invention also relates to the use of these APJ receptor compounds and pharmaceutical compositions comprising the APJ receptor compounds in the treatment of diseases and conditions associated with APJ receptor modulation, such as heart diseases (e.g., hypertension and tension and heart failure, such as congestive heart failure), cancer, diabetes, stem cell trafficking, fluid homeostasis, cell proliferation, immune function, obesity, metastatic disease, and HIV infection.

Abstract: The present invention provides a process for producing a composition which is preferably a food, food intermediate, dietary supplement, feed or pet food, which comprises mixing together a peptide mixture, comprising a bioactive peptide, and a protein source having a protein quality (expressed as PER) of 2.4 or lower. The composition of the invention can be used to improve the bioavailability of bioactive peptides or used as a food, food intermediate, nutraceutical, dietary supplement, feed, or pet food.

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 relates to a heat shock protein from alfalfa and/or a hydrolysate of a heat shock protein from alfalfa in the manufacture of a food product for the prophylactic or therapeutic treatment of a chronic inflammatory disorder. Further, the invention relates to a clinical food product comprising heat shock protein from alfalfa and/or a hydrolysate of a heat shock protein from alfalfa.

Abstract: The invention provides methods for treatment of tissue factor (TF) mediated or associated diseases or processes, such as cancer, by administering at least an active fragment of an Ixolaris polypeptide to a subject. The invention further includes identification of a subject in need of such treatment, and monitoring a subject for amelioration of at least one sign or symptom of the disease. The invention also features kits.

Abstract: Methods of treatment using Fzd8 extracellular domains (ECDs), Fzd8 ECD fusion molecules, and/or antibodies that bind Fzd8 are provided. Such methods include, but are not limited to, methods of treating obesity and obesity-related conditions. Fzd8 ECDs and Fzd8 ECD fusion molecules are also provided. Polypeptide and polynucleotide sequences, vectors, host cells, and compositions comprising or encoding such molecules are provided. Methods of making and using Fzd8 ECDs, Fzd8 ECD fusion molecules, and antibodies that bind Fzd8 are also provided.

Abstract: The present invention relates to methods of reducing blood pressure in a subject by administering a plasma kallikrein inhibitor.

Abstract: The invention is directed to a pharmacologically active peptide conjugate having a reduced tendency towards enzymatic cleavage comprising a pharmacologically active peptide sequence (X) and a stabilising peptide sequence (Z) of 4-20 amino acid residues covalently bound to X.

Abstract: The present invention provides compositions and methods for treating disorders associated with epithelial tissues.

Abstract: Based on the discovery that a soluble polypeptide including a nonphosphorylatable form of the cytoplasmic domain is capable of inhibiting in a dominant negative manner, the present invention provides compositions including MT1-MMP inhibitors such as peptide inhibitors, and methods for treating diseases associated with MT1-MMP activity. Such diseases include cancer, arthritis, and heart disease, and vascular disease.

Abstract: Neuromedin U receptor agonists for use in the treatment of metabolic disorders such as obesity and diabetes are disclosed. In particular, disclosed are neuromedin U receptor agonists that comprise neuromedin S (NMS).

Abstract: Conjugates of a polymer having attached thereto an angiogenesis targeting moiety and a therapeutically active agent such as an anti-cancer agent or anti-angiogenesis agent, and processes of preparing same are disclosed. Pharmaceutical compositions containing these conjugates and uses thereof in the treatment of angiogenesis-related medical conditions such as cancer and cancer metastases are also disclosed.

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 peptide therapeutic. The compounds of the invention can be used to treat any disease for which the peptide therapeutic is useful.

Abstract: The present invention relates to methods and compositions for the treatment, management, or prevention of multiple myeloma and/or renal dysfunction in mammals. The methods of the invention comprise the administration of an effective amount of one or more pituitary adenylate cyclase activating polypeptide (“PACAP”) compounds, which includes PACAP, vasoactive intestinal peptide (“VIP”), their agonists, analogs, fragments, or derivatives, having one or more PACAP activities. The invention also provides pharmaceutical compositions comprising one or more PACAP compounds of the invention either alone or in combination with one or more other prophylactic/therapeutic agents useful in therapy for the treatment, management, or prevention of multiple myeloma and/or renal dysfunction.

Abstract: Low levels of antibodies reactive with oxidised Cardiolipin (oxCL) in mammals are related to an increased risk of developing cardiovascular diseases, auto-immune diseases or inflammatory conditions. High levels can have a protective function and in general there is a negative association between manifestations of these conditions and antibodies against oxCL. Thus, based on their relations methods of monitoring, determining and diagnosing as well as methods of immunisation and therapy of these diseases and conditions are provided.

Abstract: The present invention relates to modulators of the interaction between Epstein-Barr Virus induced receptor-2 (EBi2) and cholest-5-ene-3b,7b,25-triol (7, 25-dihydroxycholesterol) (“7,25DHC”) and/or cholest-5-ene-3b, 7b-diol (7-hydroxycholesterol) (“7HC”). The modulator maybe a small chemical molecule, antibody or other therapeutic protein. Methods of medical treatment and methods of identifying modulators are also described.

Abstract: The present invention relates to peptides having one or more stable, internally constrained ?-helices, and that include a sequence that mimics at least a portion of the C-terminal transactivation domain of HIF-1?. Also disclosed are pharmaceutical compositions containing these peptides and methods of using these peptides, for example to reduce gene transcription, treat or prevent disorders mediated by interaction of HIF-1? with CREB-binding protein and/or p300, reduce or prevent angiogenesis in a tissue, induce apoptosis, decrease cell survival and/or proliferation, and identify potential ligands of CREB-binding protein and/or p300.

Abstract: This invention relates to potent selective agonists of the EP4 subtype of prostaglandin E2 receptors, their use or a formulation thereof in the treatment of glaucoma and other conditions, which are related to elevated intraocular pressure in the eye of a patient. This invention further relates to the use of the compounds of this invention for mediating the bone modeling and remodeling processes of the osteoblasts and osteoclasts.

Abstract: The present invention relates to the use of novel compounds for the manufacture of a medicament for treatment of inter alia conditions associated with critical care as well as to a method for treatment of said conditions, wherein said compounds are administered. The compounds utilised are represented by the general formula (I), as further defined in the specification.

Abstract: The invention provides interfering RNA molecule-ligand conjugates useful as a delivery system for delivering interfering RNA molecules to a cell in vitro or in vivo. The conjugates comprise a ligand that can bind to a low density lipoprotein receptor (LDLR) or LDLR family member. Therapeutic uses for the conjugates are also provided.

Abstract: The present invention relates to a (poly)peptide or a peptidomimetic thereof having the biological activity of Conkunitzin-S1, wherein said (poly)peptide is selected from (a) a polypeptide comprising or having the amino acid sequence of SEQ ID NO: 1; (b) a polypeptide having at least 85% sequence identity to SEQ ID NO:1; or (c) a fragment of a) or b); wherein said (poly)peptide or peptidomimetic specifically modulates the activity of a channel having the activity of a Kv1.7 containing channel, for the treatment or prevention of metabolic diseases or conditions, or secondary diseases or conditions related to said metabolic diseases or conditions. The present invention furthermore relates to a method of screening for (poly)peptides derived from Conkunitzin-S1 suitable for specifically modulating the activity of a channel having the activity of a Kv1.

Abstract: The present invention provides methods of treating or preventing disorders or conditions associated with enterostatin deficiency by administering to a subject in need thereof an effective amount of enterostatin. The present invention also provides methods of selecting a subject for therapy with enterostatin. Exemplary disorders or conditions associated with enterostatin deficiency include overweight, obesity, metabolic disorders, hypertension, lipid related disorders, and type II diabetes.

Abstract: Methods for increasing urine flow are disclosed, comprising administration of an effective amount of GLP-1, an exendin, or an exendin or GLP-1 agonist. Methods for increasing urinary sodium excretion and decreasing urinary potassium concentration are also disclosed. The methods are useful for treating conditions or disorders associated with toxic hypervolemia, such as renal failure, congestive heart failure, nephrotic syndrome, cirrhosis, pulmonary edema, and hypertension. The present invention also relates to methods for inducing an inotropic response comprising administration of an effective amount of GLP-1, an exendin, or an exendin or GLP-1 agonist. These methods are useful for treating conditions or disorders that can be alleviated by an increase in cardiac contractility such as congestive heart failure. Pharmaceutical compositions for use in the methods of the invention are also disclosed.