Abstract: Methods of treating, preventing or ameliorating one or more symptoms of hepatitis C in a subject comprising the step of administering at least one HCV protease inhibitor in combination with food are provided. Also provided are methods of increasing bioavailability of an HCV protease inhibitor and methods of increasing serum levels of an HCV protease inhibitor in a subject. All methods comprise adminstering at least one HCV protease inhibitor in combination with food, the at least one HCV protease inhibitor selected from the group consisting of compounds of Formulae I-XXVI, described herein. Administration of compounds of the present invention in combination with food provides improved bioavailability and increased peak serum levels of the compounds as compared to administration without food.

Abstract: Methods and compositions are described to regenerate cartilage in a partial thickness defect or area of reduced volume of articular cartilage comprising an infiltration suppressor agent and a columnar growth promoting agent.

Abstract: The present invention features compositions and related methods for treating IBS and other gastrointestinal disorders and conditions (e.g., gastrointestinal motility disorders, functional gastrointestinal disorders, gastroesophageal reflux disease (GERD), Crohn's disease, ulcerative colitis, Inflammatory bowel disease, functional heartburn, dyspepsia (including functional dyspepsia or nonulcer dyspepsia), gastroparesis, chronic intestinal pseudo-obstruction (or colonic pseudo-obstruction), and disorders and conditions associated with constipation, e.g., constipation associated with use of opiate pain killers, post-surgical constipation (post-operative ileus), and constipation associated with neuropathic disorders as well as other conditions and disorders using peptides and other agents that activate the guanylate cyclase C (GC-C) receptor.

Abstract: The invention provides a method of modifying a phosphomonoester moiety of a target compound. The method can include the steps of (a) providing a target compound having an electrophilic moiety and a phosphomonoester moiety; (b) contacting the target compound with a first carbodiimide compound under conditions for preferential addition of the first carbodiimide compound to the electrophilic moiety over the phosphomonoester moiety, thereby forming an electrophile-protected target compound; and (c) contacting the electrophile-protected target compound with a second carbodiimide compound and a nucleophilic compound under conditions for addition of the nucleophilic compound to the phosphomonoester.

Abstract: The invention relates to a dipeptide conjugate having general formula I, AA2-AA1-NH2, wherein A represent the radical corresponding to a monocarboxylic acid with general formula II, HOOC—R, in which: R represents a linear or branched aliphatic radical at C1-C24, which is optionally substituted by a hydroxyl group and which can comprise one or more unsaturations, preferably between 1 and 6 unsaturations, and/or which can comprise a phenyl group or lipoic acid or the reduced form thereof, dihydrolipoic acid or N-lipoyllysine; and AA1 and AA2 represent identical or different amino acids which are selected from the group containing Ala, Asn, Cys, Gln, Gly, Ile, Leu, Met, Phe, Pro, Ser, Thr, Trp, Tyr, Val, Asp, Glu, Arg, His, Lys, Orn, Dap, Dab, the corresponding homo-amino acids and the corresponding beta-amino acids in the form of enantiomers or diastereoisomers and mixtures thereof, including racemic mixtures.

Abstract: Interaction between MUC1 and ?-catenin can be interrupted using polypeptides or antibodies that specifically bind to the binding site on MUC1. Interruption provides the beneficial effect of inhibiting, reducing, and/or retarding invasiveness and metastasis. Fusion polypeptides and antibodies are provided to achieve a therapeutic effect.

Abstract: Sustained delivery formulations comprising a water-insoluble complex of a peptide and a plurality of ligands are disclosed. The formulations of the invention allow for loading of high concentrations of peptide in a small volume and for delivery of a pharmaceutically active peptide for prolonged periods, e.g., one month, after administration of the complex. The complexes of the invention can be milled or crushed to a fine powder. In powdered form, the complexes form stable aqueous suspensions and dispersions, suitable for injection. Methods of making the complexes of the invention, and methods of these complexes are also disclosed.

Abstract: The present invention features compositions and related methods for treating IBS and other gastrointestinal disorders and conditions (e.g., gastrointestinal motility disorders, functional gastrointestinal disorders, gastroesophageal reflux disease (GERD), Crohn's disease, ulcerative colitis, Inflammatory bowel disease, functional heartburn, dyspepsia (including functional dyspepsia or nonulcer dyspepsia), gastroparesis, chronic intestinal pseudo-obstruction (or colonic pseudo-obstruction), and disorders and conditions associated with constipation, e.g., constipation associated with use of opiate pain killers, post-surgical constipation, and constipation associated with neuropathic disorders as well as other conditions and disorders using peptides and other agents that activate the guanylate cyclase C (GC-C) receptor.

Abstract: Pharmaceutical agents, compositions containing the same and methods for their use for enhancing the bioavailability and pharmacological efficacy of therapeutic peptides. The pharmaceutical agents have the formula Carrier-Linker-Peptide Wherein Peptide is a therapeutically active peptide species having the formula aan wherein n is the number of amino acid residues in the peptide and n is 2 to 40, Carrier is benzoyl, phenylacetyl, cinnamoyl, 3-OH-cinnamoyl, 3,4-OH-cinnamoyl, 3,4-dimethoxycinnamoyl, 3,4-methylenedioxycinnamoyl, 3-methoxycinnamoyl, 3,4-diethoxy-cinnamoyl, 3,4,5-trimethoxy-cinnamoyl, t-butoxycarbonyl, benzyloxycarbonyl, pivaloyl, N-9-fluorenylmethoxycarbonyl, fumaroyl and derivatives thereof and Linker is a C6 to C16 lipidic chain or a derivative thereof, an 8-amino-3,6-dioxaoctanoic acid or polymeric derivative thereof, pseudo peptide, or peptide mimic. Methods of use of compositions having the formula Carrier-Peptide wherein Carrier and Peptide are as just defined are also disclosed.

Abstract: A controlled release composition containing a physiologically active substance in high content, suppressing the initial excess release, and achieving a stable release speed over a long period of time is provided. A controlled release composition comprising (1) a physiologically active substance or salt thereof in an amount of about 14% (w/w) to about 24% (w/w) based on the total composition weight, (2) hydroxynaphthoic acid selected from the group consisting of 3-hydroxy-2-naphthoic acid and 1-hydroxy-2-naphthoic acid or salt thereof, and (3) a lactic acid polymer or salt thereof having a weight-average molecular weight of 15000 to 50000 in which the content of polymers having molecular weights of 5000 or less is about 5% by weight or less, wherein the molar ratio of said hydroxynaphthoic acid or salt thereof to said physiologically active substance or salt thereof is from 3:4 to 4:3.

Abstract: This document provides methods and materials for treating pain. For example, this document provides methods that involve administering a neurotensin receptor (NTR) agonist and an opioid receptor agonist to a mammal (e.g., a human). Compositions containing an NTR agonist in combination with an opioid receptor agonist also are provided.

Abstract: Calcitonin drug-oligomer conjugates that include a calcitonin drug coupled to an oligomer including a single polyalkylene glycol moiety consisting of between 4 and 10 polyalkylene glycol subunits are disclosed. Pharmaceutical compositions including such conjugates and methods of treating bone disorders by administering such conjugates are also disclosed.

Abstract: A complex of an echinocandin compound with a carbohydrate is described having improved thermal stability and water solubility. A process for making the echinocandin/carbohydrate complex is also described as well as the use of the complex in pharmaceutical formulations and treatments of fungal infections.

Abstract: The invention relates to a tripeptide conjugate having general formula I, A-AA1-AA2-AA3-NH2, wherein A represents the radical corresponding to a monocarboxylic acid with general formula II, HOOC—R, in which: R represents a linear or branched aliphatic radical at C1-C24, which is optionally substituted by a hydroxyl group and which can comprise one or more unsaturations, preferably between 1 and 6 unsaturations, lipoic acid or the reduced form thereof, dihydrolipoic acid, N-lipoyllysine, or phenylbutyric acid; and AA1, AA2 and AA3, which may be identical or different, represent independently of each other an amino acid selected from His, Phe, Ala, Arg, Lys, Orn, Trp, Nap, Tpi and Tic, on the condition that at least one of AA1, AA2 or AA3 represent Phe, preferably Dphe in the form of enantiomers or diastereoisomers and mixtures thereof, including racemic mixtures.

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 normalized. 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: A new and improved method for extending the half life of pharmaceutical compounds for use in diagnostic imaging or therapy uses a novel linker to attach a diagnostic or therapeutic moiety to a targeting peptide or another diagnostic or therapeutic moiety. The resulting compound may have the general formula M-N-O-P-Q, wherein M is the diagnostic or therapeutic moiety, N-O-P is the linker of the present invention, and Q is the targeting peptide. In another embodiment the compounds may have the formula M-N-O-P-M, wherein M is independently a diagnostic or therapeutic moiety and N-O-P is the linker of the invention. Methods for imaging or treating a patient using the compounds of the invention are also provided. Methods and kits for preparing a diagnostic imaging agent from the compound are further provided. Methods for radiotherapy of a patient using the compounds are further provided, as are methods for preparing a radiotherapeutic agent from the compounds.

Abstract: Smac mimetics that inhibit IAPs.

Abstract: The invention describes a pharmaceutical composition to combat multiple-drug-resistant bacteria in non-ocular infective conditions. Compositions comprising glycopeptides, in particular vancomycin, and cephalosporins, in particular ceftriaxone, are disclosed. Such compositions are found to be useful for parenteral administration for hospitalized patients with serious infections. Specifically, this invention also discloses a pharmaceutical composition further including an excipient such as CVMC agent and is available in dry powder form for reconstitution before injection with a suitable solvent. The pharmaceutical compositions of this invention have been found normally to enhance resistance to precipitation in solutions to be administered parenterally. The invention also gives details of the dosage forms stored in sealed containers to be reconstituted before use.

Abstract: The present invention relates to the identification of a gene, now designated negevin (ngvn), that is involved in the genetic disease Bardet Biedl Syndrome (BBS), which is characterized by such diverse symptoms as obesity, diabetes, hypertension, mental retardation, renal cancer and other abnormalities, retinopathy and hypogonadism. The human NGVN protein disclosed herein is 731 amino acids in length and is coded for by a gene spanning 17 exons. Homologs have been identified in mouse, rat, zebrafish. Methods of use for the gene, for example in diagnosis and therapy of BBS and in drug screening, also are described.

Abstract: The invention features a method of administering one or more therapeutic agents to a patient and delivering said agent or agents continuously over an extended period of time, said method comprising: obtaining a pharmaceutical composition including a peptide carrier, one or more therapeutic agents, and up to 30 percent, by weight, of a pharmaceutically acceptable, soluble, monomeric carrier; and parenterally administering said pharmaceutical composition to a subject by injection, wherein said composition automatically forms a gel after interaction with the patient's bodily fluids and releases said peptide carrier and said agent or agents continuously within the patient over an extended period.