Abstract: The invention relates to a pharmaceutical composition for vaginal administration of a treating agent normally associated with undesired side effects at detrimental blood levels. The composition releases the treating agent at a rate to achieve local tissue concentrations without such detrimental blood levels by using a therapeutically effective amount of the treating agent and a bioadhesive, cross-linked water swellable, but water-insoluble polycarboxylic acid polymer. Using this composition and the method of treatment provides sufficient local levels of the drug to provide therapeutic efficacy, but avoids many untoward adverse events. The invention also relates to a pharmaceutical composition for use during menses that includes a treating agent and a bioadhesive, cross-linked water swellable, but water-insoluble polycarboxylic acid polymer.

Abstract: Compositions for nucleus pulposus regeneration is provided. Such composition may comprise a scaffolding material and a pore creating agent dispersed within the scaffolding material. The pore creating agent is removed from the scaffolding material in vivo, after the composition is administered to a patient. The pore creating agent may include an active agent, such as a growth factor, which may be released as the pore creating agent is being gradually removed from the scaffolding material. In addition, removal of the pore creating agent results in a porous scaffold for cells capable of regeneration of nucleus pulposus, either existing in situ or delivered separately, to attach to for further proliferation and regeneration.

Abstract: A composition for oral delivery of a poorly absorbed drug is disclosed. The composition includes the drug, an enhancer for increasing absorption of the drug through the intestinal mucosa, a promoter, which further increases the absorption of the drug in the presence of the enhancer, and optionally a protector for protecting the drug from physical or chemical decomposition or inactivation in the gastrointestinal tract. Illustrative enhancers include sucrose fatty acid esters, and illustrative promoters include aminosugars and amino acid derivatives, such as poly(amino acids). Illustrative protectors include methylcellulose, poly(vinyl alcohol), and poly(vinyl pyrrolidone).

Abstract: Catheter injectable depot compositions are provided that include a bioerodible, biocompatible polymer, a solvent having miscibility in water of less than or equal to 7 wt. % at 25° C., in an amount effective to plasticize the polymer and form a gel therewith, a thixotropic agent, and a beneficial agent. The solvent comprises an aromatic alcohol, an ester of an aromatic acid, an aromatic ketone, or mixtures thereof. The compositions are have substantially improved the shear thinning behavior and reduced injection force, rendering the compositions readily implanted beneath a patient's body surface by injection.

Abstract: The present invention is directed to sulphated compounds comprising at least one glycosidic amine group, and polysaccharide, oligosaccharide, peptide and protein derivatives comprising such compounds, and mixtures thereof. The present invention is also directed to methods of synthesising such compounds. Such compounds may bind to a range of proteins, find application in methods of modifying, or testing for a modification in the level of a cytokine in vivo, ex vivo or in vitro, and find application in the treatment and/or prevention of inflammation, an inflammatory disorder, a proliferative disorder, an immune disorder, an angiogenesis-dependent disorder, a sensitivity disorder, an adverse endocrine reaction, a degenerative disorder, wound healing, depression, and other diseases and disorders.

Abstract: The present invention relates to therapeutic compositions and methods of treatment that contain or employ at least two of: an oligomeric proanthocyanidin; a protease inhibitor; and/or a lactoferrin. The compositions of this invention may be in various forms depending upon the disease or condition to be treated. The compositions and methods of this invention are useful to treat a patient suffering from or susceptible to gram negative bacterial infections, including those associated with cystic fibrosis, ear infections and with wounds.

Abstract: The invention provides fibronectin type III (Fn3)-based binding molecules that bind to a specific target antigen. The invention further provides bispecific Fn3-based binding molecules that bind to two or more targets simultaneously. The Fn3-based binding molecules of the invention can also be linked together to form multispecific Fn3-based binding molecules, and/or can be conjugated to a non-Fn3 moiety, such as, Human Serum Albumin (HSA), for improved half life and stability. The invention also provides methods for generating, screening and using Fn3-based binding molecules in a variety of therapeutic and diagnostic applications.

Abstract: The present invention is directed to polypeptide-nucleic acid conjugates. These conjugates can allow for targeted application of a therapeutic RNAi agent across the blood-brain barrier to treat, for example, a cancer, neurodegenerative disease, or lysosomal storage disorder.

Abstract: The present invention generally relates to methods for detecting, identifying, and measuring bacterial adherence to mucus and epithelial cells. In particular, the present invention provides assays for detecting and identifying the presence or absence of bacterial adherence to mucus (epithelial cells (e.g., present in the intestines), or other portion of an animal where bacteria may be present, and methods for identifying and characterizing (e.g., the efficacy of) modulators of bacterial adherence to mucus and epithelial cells, or other portion of the animal where bacteria may be present.

Abstract: Pharmaceutical compositions for treating male sub-fertility that include an agent that causes a reduction in an effect of extracellular DNA on sperm cells, are provided. The agent may be, for example, an enzyme that degrades DNA such as DNase, a substance that blocks the interaction between cell free DNA and sperm cell surface receptors, a substance that binds to DNA, a substance that inhibits endogenous sperm cell DNase, a substance that inhibits a member of a signal transduction pathway mediated by DNA binding to sperm cell surface receptors, or an agent that stimulates production of an endogenous substance that causes a reduction in an antifertility effect of cell free DNA on sperm cells. Also provided are methods for treating male sub-fertility by administering the pharmaceutical composition to a subject in need thereof.

Abstract: The present invention provides compounds and compositions that enhance the innate immune system. The present invention comprises methods of preventing, treating or ameliorating an infectious disease comprising administering said compounds to a subject. The invention also comprises methods of formulation and administration of said compounds.

Abstract: The present invention generally relates to the protection and repair of connective tissues. In particular, the present invention relates to the use of chondroitin sulfates and its derivatives in connective tissue protection and repair. The present inventors have found that unsaturated disaccharidic chondroitin sulfate can be used for the preparation of a composition to develop, protect and/or repair connective tissues. This allows it for example to treat or prevent osteoarthritis or rheumatoid arthritis, and/or the symptoms thereof as well as to treat or prevent signs of skin ageing such as the appearance of wrinkles effectively.

Abstract: Provided herein are methods and compositions for regulating airway tissue remodelling and for treating or preventing conditions associated with airway inflammation and/or airway tissue remodelling. The methods comprise normalising fibulin-1 levels in said tissue relative to normal endogenous levels. In an embodiment the methods comprise administering to a subject in need thereof an effective amount of at least one agent capable of inhibiting the expression and/or activity of fibulin-1.

Abstract: The present invention provides natural occurring, recombinant and synthetic chemokines, interleukins and cytokines in which at least one arginine residue is replaced by or modified into a cltrulline residue. The present Invention also relates to the use of said chemokines, interleukins or cytokines and pharmaceutical compositions comprising said chemokines, interleukins or cytokines as anti-inflammatory agents and as haematopoietic cell (including stem-cell, progenitor cell and leukocyte) or endothelial cell mobilizing agents. Furthermore, the present invention relates to the use of said chemokines, interleukins or cytokines to create antibodies and to use said chemokines, interleukins, cytokines and/or said antibodies as diagnostic tools and as a medicine. In addition, the present invention provides for the processes for the identification and production of the citrullinated chemokines, interleukins or cytokines of the invention.

Abstract: It is an object of the present invention to attach a biopolymer composition to a synthetic polymer substrate without the use of a toxic adhesive. The present invention provides a medical composition, wherein a synthetic polymer substrate and a composition mainly composed of a biopolymer directly adhere to each other due to dissolution of the surfaces thereof.

Abstract: The present invention relates to the use of proteins comprising at least one follistatin domain to modulate the level or activity of growth and differentiation factor-8 (GDF-8). More particularly, the invention relates to the use of proteins comprising at least one follistatin domain, excluding follistatin itself, for treating disorders that are related to modulation of the level or activity of GDF-8. The invention is useful for treating muscular diseases and disorders, particularly those in which an increase in muscle tissue would be therapeutically beneficial. The invention is also useful for treating diseases and disorders related to metabolism, adipose tissue, and bone degeneration.

Abstract: A device comprising a scaffold coated with a protein having at least 83% identity to the amino acid sequence of the core protein of domain I of a mammalian perlecan, wherein at least one glycosaminoglycan is attached to the protein is described. The device may be used in vitro or in vivo to induce replication and/or differentiation of connective tissue cells and to repair tissue.

Abstract: The invention provides modified hepatitis C virus (HCV) E2 glycoproteins comprising the HCV-E2 receptor-binding domain (RBD) including the HVR1, HVR2 and igVR variable regions wherein in at least one of said variable regions at least a part of the variable region is replaced with a flexible linker sequence. The invention also provides vaccine compositions comprising the modified glycoproteins as well as methods of use thereof.

Abstract: A multiple layer microbubble drug delivery system, multiple layer microbubble drug delivery vehicle, method thereof and fabrication method are disclosed. The microfluidic drug delivery system for producing multiple layer microbubbles includes a first inlet which receives a gas and directs the gas into a central stream, a second inlet which receives a first liquid containing a drug substance and flow focuses the first liquid around the gas, a third inlet which receives a second liquid and flow focuses the second liquid around the first liquid and a fourth inlet which receives a third liquid and flow focuses the third liquid around the second liquid. The multiple layer microbubble drug delivery vehicle includes a gas core, a first liquid layer containing a drug and surrounding the gas core, a second liquid layer surrounding the first liquid layer to stabilize the first liquid layer and a plurality of particles outside the second liquid layer.

Abstract: The present invention provides methods, compositions, and systems for treating a subject at risk for, with, or suspected of having, myocardial ischemia using hepatocyte secretory factors (e.g., AGP2, BMPER, FGF21, NRG4, and/or TFF3) or using factors that promote liver cell migration to ischemic myocardial tissue (e.g., IL-6 and/or MMP-2).

Abstract: A method of producing a polyethylene glycolated (PEGylated) lactoferrin complex having a linear polyethylene glycol (PEG) or a modified product thereof covalently bonded to lactoferrin via an amide bond includes causing a reaction to occur in a reaction liquid, which contains the lactoferrin and a linear PEG derivative having a para-nitrophenol leaving group, under conditions that allow formation of an amide group between the PEG derivative and the lactoferrin. A PEGylated lactoferrin complex contains a linear PEG or a modified product thereof covalently bonded to lactoferrin via an amide bond, and a pharmaceutical composition includes a PEGlyated lactoferrin complex, a therapeutically inert base, and/or an additive.

Abstract: The invention provides a compound (which can act as an adjuvant) of Formula I or Formula (II), wherein R1 R4 R5 R6 and R7 are each independently selected from hydrogen, acetyl, hydrocarbyl, a lipid moiety and a lipid acyl moiety; R2 is a hydroxyl, a hydrocarbyl, a lipid moiety, a lipid acyl moiety; or an amino hydrocarbyl group optionally substituted with a hydrocarbyl, a lipid moiety or a lipid acyl moiety; R3 and R8 are each independently selected from acetyl, a hydrocarbyl, a lipid moiety and a lipid acyl moiety; X is a peptide chain; The above normuramylglycopeptide compounds can be located in liposomes and micelles and can function as immunomodulators, along with a desired antigen (or DNA encloding the antigen), in (e.g. DNA) vaccines.

Abstract: The invention relates to particles which exhibit a stimulable shape change and allow control of their uptake in active cells. The particles can be used as carrier systems for bioactive molecules or as diagnostic agents, and the spherical shape thereof has a size permitting uptake in a cell. Each particle assumes a temporary, non-spherical and thus non-uptakeable or only slightly uptakeable shape which can be transformed into a spherical and thus uptakeable shape by a suitable stimulus.

Abstract: This invention provides methods for modifying glycosylation patterns of glycopeptides, including recombinantly produced glycopeptides. Also provided are glycopeptide compositions in which the glycopeptides have a uniform glycosylation pattern.

Abstract: Oligonucleotides directed against the Mcl-1 gene are developed for modulating the expression of Mcl-1 protein. The compositions comprise oligonucleotides, particularly antisense oligonucleotides, targeted to nucleic acids encoding Mcl-1. Methods of using these compounds for modulation of Mcl-1 expression and for the treatment of diseases associated with over expression of Mcl-1 are provided. Examples of such diseases include cancer and systemic mastocytosis.

Abstract: Polypeptides are susceptible to denaturation or enzymatic degradation in the blood, liver or kidney. Due to the low stability of some polypeptides, it has been required to administer polypeptide drugs in a sustained frequency to a subject in order to maintain an effective plasma concentration of the active substance. Furthermore, pharmaceutical compositions of therapeutic peptides preferably have a shelf-life of several years in order to be suitable for common use. However, peptide compositions are inherently unstable due to sensitivity towards chemical and physical degradation. In part, the invention provides SAP variant proteins, compositions, pharmaceutical preparations and formulations having a prolonged in vivo half-life, prolonged shelf-life, or rather increased in vitro stability, or increased manufacturing efficiency compared to human SAP. Advantages of increased plasma half-life include, but are not limited to, reducing the amount and/or frequency of dosing.

Abstract: A composition for treating damaged tissue and promoting healthy tissue growth, healing and tissue regeneration, wherein said composition comprises an extracellular matrix compound, a surface-active lipid, one or more enantioinerically pure L-amino acids or glycine, a hydrophilic surfactant with a high HLB, as well as vitamins, minerals or trace elements. Not only does it maintain good health, but the components are non-intrusive, bio-safe, non-coalescent and can mimic normally occurring stem-cells within a body. When applied to diseased tissues, the subject compositions can stimulate, facilitate, and accelerate protein synthesis for the regeneration of diseased organs and tissues. The healing efficacy of these tissue components gives us further appreciation of the protective action of human tissue over and above and other than the immune protective system or perhaps an integral component part of the immune system.

Abstract: Described herein are compositions and methods for use in targeted drug delivery using cell receptor binding drug delivery conjugates containing hydrophilic spacer linkers for use in imaging, diagnosing, and/or treating diseases and disease states caused by pathogenic cell populations.

Abstract: Gene expression profiling in multiple myeloma patients identifies genes that distinguish between patients with subsequent early death or long survival after treatment. Poor survival is linked to over-expression of genes such as ASPM, OPN3 and CKS1B which are located in chromosome 1q. Given the frequent amplification of 1q in many cancers, it is possible that these genes can be used as powerful prognostic markers and therapeutic targets for multiple myeloma and other cancer.

Abstract: Isolated polypeptides are disclosed comprising an amino acid sequence encoding a monomer of a fibrous polypeptide attached to a heterologous polysaccharide binding domain. Composites comprising same, methods of generating same and uses thereof are all disclosed.

Abstract: Medical foods containing glycomacroprotein and additional supplemented amounts of arginine, leucine, and optionally other amino acids, such as tyrosine, are disclosed. The medical foods can be used to provide the complete protein requirements for patients having metabolic disorders such as phenylketonuria.

Abstract: One aspect of the present invention relates to the surprising discovery that modification of a glycan structure on a human SAP polypeptide can increase the biological activity of the SAP polypeptide relative to a corresponding sample of wild-type SAP isolated from human serum. The disclosure provides both variant human SAP polypeptides and methods for making the same. In particular, the present invention provides methods and compositions for in vitro and in vivo addition, deletion, or modification of sugar residues to produce SAP polypeptides, such as a human SAP polypeptide, having a desired glycosylation pattern.

Abstract: An agent for thermally stabilizing lactoferrin, which comprises a nucleic acid as an active ingredient, can be added to lactoferrin to impart thermal stability to lactoferrin. Thermally stabilized lactoferrin can be heat-sterilized at a pH value around a neutral pH value while keeping its activity.

Abstract: Conjugates of an active substance and hydroxyalkyl starch (HAS) are provided herein. The active substance and the HAS are linked by a chemical moiety having a structure according to formula (I) wherein Y is O or S, and X is SH or (F). The conjugate has a structure according to formula (IV) wherein HAS? is a residue of HAS or a derivative thereof linked to the thioester group, and AS? is a residue of the active substance or derivative thereof linked to the alpha-X beta-amino group; or a structure according to formula (V) wherein HAS? is a residue of HAS or derivative thereof linked to the alpha-X beta-amino group, and AS? is a residue of the active substance or derivative thereof linked to the thioester group, and wherein the group —(C?Y) is derived from the thioester group —(C?Y)—S—R? and the group HN—CH—CH2—X is derived from the alpha-X beta amino group.

Abstract: The use of substance that inhibits a pro-inflammatory cytokine, such as TNF or IL-1, for the production of a pharmaceutical composition for improving wound healing is disclosed. Also, a method for improving wound healing wherein a therapeutically effective amount of a substance that inhibits a pro-inflammatory cytokine is administered to a patient in need of said treatment is disclosed.

Abstract: Described are soluble gp130 polypeptide monomers and dimers, wherein, in a preferred embodiment, at least one of the three amino acid residues Thr102 Gln113 or Asn114 of the N-terminal Ig-like domain of gp130 is mutated to Tyr102, Phe113 or Leu114, respectively. These mutations, alone or in combination, specifically enhance binding of gp130 to its ligand complex of interleukin-6 and soluble interleukin-6 receptor, thus increasing the biological activity of the gp130 muteins. In a particularly preferred embodiment, all three mutations are combined in the triple mutein Thr102Tyr/Gln113Phe/Asn114Leu (T102Y/Q113F/N114L). Moreover, a pharmaceutical composition containing said monomers or dimers and various medical uses are described.

Abstract: The present invention provides modulators of TNF, particularly peptides and their derivatives, particularly GEP peptides, which antagonize TNF and TNF-mediated responses, activity or signaling. The invention provides methods of antagonizing TNF and the modulation of TNF-mediated diseases or responses, including inflammatory diseases and conditions. Compositions of GEP peptides, including in combination with other inflammatory mediators, are provided. Methods of treatment, alleviation, or prevention of TNF-mediated diseases and inflammatory conditions, including rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, psoriasis, inflammatory bowel diseases, Chrohn's disease, ulcerative colitis, uveitis, inflammatory lung diseases, chronic obstructive pulmonary disease, are provided.

Abstract: The present invention provides a method of treating or preventing inflammation in a subject comprising administering to the subject an effective amount of a muramyl dipeptide (MDP).

Abstract: The invention relates to neublastin neurotrophic factor polypeptides, nucleic acids encoding neublastin polypeptides, and antibodies that bind specifically to neublastin polypeptides, as well as methods of making and methods of using the same.

Abstract: The invention provides therapeutic devices comprising a polymeric anti-inflammatory agent that biodegrades to release anti-inflammatory agents. The therapeutic devices are useful for repair and regeneration of a variety of injured tissues.

Abstract: This invention relates to a novel protein mixture and the use thereof in the preparation of a food product intended for oral or enteral nutrition. This protein mixture, based on caseinate, pea proteins and milk serum proteins has very high protein quality indices (protein efficiency index) and a good digestibility, thus the ease of conversion of said protein mixture is very good when compared to that of superior-quality highly-digestible proteins per excellence.

Abstract: The current invention provides polypeptides and polypeptide conjugates that include an exogenous N-linked glycosylation sequence. The N-linked glycosylation sequence is preferably a substrate for an oligosaccharyltransferase (e.g., bacterial PgIB), which can catalyze the transfer of a glycosyl moiety from a lipid-bound glycosyl donor molecule (e.g., a lipid-pyrophosphate-linked glycosyl moiety) to an asparagine (N) residue of the glycosylation sequence. In one example, the asparagine residue is part of an exogenous N-linked glycosylation sequence of the invention. The invention further provides methods of making the polypeptide conjugates that include contacting a polypeptide having an N-linked glycosylation sequence of the invention and a lipid-pyrophosphate-linked glycosyl moiety (or phospholipid-linked glycosyl moiety) in the presence of an oligosaccharyltransferase under conditions sufficient for the enzyme to transfer the glycosyl moiety to an asparagine residue of the N-linked glycosylation sequence.

Abstract: Alpha 1-antitrypsin compositions and treatment methods using such compositions for treating a variety of pulmonary diseases are provided. The compositions generally contain AAT, a stabilizing carbohydrate such as trehalose, a surfactant such as Polysorbate 80 and an antioxidant to stabilize AAT for use as a therapeutic. The formulations can be prepared as both liquids and solids and administered by nebulization of the liquid formulation or by conversion of dry powder formulation into an aerosol.

Abstract: Compositions provided by mixing a biotin-containing component and an avidin-containing component are useful as an adhesive or sealant for medical/surgical uses.

Abstract: A method of administering an aerosolized anti-infective, such as a glycopeptide, to the respiratory system of a patient. A ratio of an amount of the glycopeptide, such as vancomycin, delivered to the pulmonary system of the patient in a 24 hour period to a minimum inhibitory amount for the target organ for the same period is about 2 or more. A system to introduce aerosolized medicament to a patient may include a humidifier coupled to an inspiratory limb of a ventilator circuit wye, where the humidifier supplies heated and humidified air to the patient, and an endotracheal tube having a proximal end coupled to a distal end of the ventilator circuit wye. The system may also include a nebulizer coupled to the endotracheal tube, where the nebulizer generates the aerosolized medicament.

Abstract: The invention relates to a biocompatible metastable intermediate material for controlling the mobility of at least one biologically active substance. An example of the invention is a hydrogel formed by cross-linked sodium hyaluronate treated with an oxidizing agent so as to open sugar rings and form aldehyde groups. The gel according to the invention is sterilized, e.g. by autoclaving.

Abstract: The present invention is directed to a pharmaceutical composition, and methods of use thereof, comprising at least one agent which target multiple adenosine receptors (AR) simultaneously in a stoichiometric relationship (i.e. each AR receptor is targeted to an equal extent). Aspects of the present invention relate to pharmaceutical compositions, and uses thereof, comprising at least one agent which co-activates an A1-adenosine receptor (A1-AR) and an A2A-adenosine receptor (A2A-AR) or a combination of at least one agent which activates an A1-AR and at least one agent which activates an A2A-AR, where both the A1-AR and A2A-AR are activated in a stoichiometric relationship such that the level of biological activation of A1-AR is approximately the same level of biological activation of A2A-AR.

Abstract: Drugs are formulated as oral dosage forms for controlled release in which the release rate limiting portion is a shell surrounding the drug-containing core. The shell releases drug from the core by permitting diffusion of the drug from the core. The shell also motes gastric retention of the dosage form by swelling upon imbibition of gastric fluid to size that is retained in the stomach during the postprandial or fed mode.

Abstract: The main drawback in the use of most nucleoside anticancer agents originates from their hydrophilic nature, of which property requires a high and frequent dosage for an intravenous administration. Unlike other nucleoside anti-tumor agents, troxacitabine appears to predominantly enter tumor cells by passive diffusion rather then by using nucleoside transporters, although this may be model dependent. Accordingly, in the present work, a small library of twenty troxacitabine prodrugs has been synthesized using a parallel approach in order to evaluate the relationship between the lipophilicity of the prodrugs and their antitumor activity. Biological evaluation of the prodrugs on two non-small cell lung cancer cell lines (A549 and SW1573) and in pancreatic cell lines clearly showed better antitumor activity than that of troxacitabine, with IC50 values in the nanomolar range.

Abstract: The invention provides quinoxalines of the general formula I which are used as medicaments preferably for treating tumour disorders, in particular in cases of drug resistance to other active compounds and in cases of metastasic carcinoma. The possible applications are not limited to tumour disorders.