Abstract: A modified release composition comprising tacrolimus which is useful for the treatment or prevention of rejection reactions by transplantation of organs or tissues.

Abstract: A modified release composition comprising tacrolimus releases less than 20% w/w of the active ingredient within 0.5 hours when subjected to an in vitro dissolution test using USP Paddle method and using 0.1 N HCl as dissolution medium and has increased bioavailability by effectively reducing or even avoiding the effects of CYP3A4 metabolism. The modified composition may be coated with an enteric coating; and/or may comprise a solid dispersion or a solid solution of tacrolimus in a hydrophilic or water-miscible vehicle and one or more modifying release agents; and/or may comprise a solid dispersion or a solid solution of tacrolimus in an amphiphilic or hydrophobic vehicle and optionally one or more modifying release agents.

Abstract: Disclosed is a method of preventing the development of mucositis in a subject undergoing radiation therapy or chemotherapy for a disease in need thereof comprising administering an effective amount of a mammalian target of rapamycin (mTOR) inhibitor, such as rapamycin, to the subject. Further disclosed is a method of increasing the lifespan of a normal oral keratinocyte and/or reducing oxidative stress in a normal epithelial cell, wherein the method comprises administering an effective amount of an mTOR inhibitor to a subject undergoing radiation therapy or chemotherapy for a disease in need thereof.

Abstract: A modified release composition comprising tacrolimus which is useful for the treatment or prevention of rejection reactions by transplantation of organs or tissues.

Abstract: Described are medicaments and methods of treating or preventing metabolic bone diseases, such as Critical Illness Related Metabolic Bone Disease or of critical illness induced Osteopenia secondary to ICU Admission by sufficient autophagy inducing compound to inhibit or suppress critical illness enhanced osteoclastogenesis or increased osteoclast differentiation. The methods include administering of an autophagy activating compound to a mammal to: treat or prevent a bone degenerative disorder; slow bone deterioration; restore lost bone; maintain bone mass and/or bone quality or inhibit bone resorption in particularly by inhibiting or reducing a process by which osteoclasts break down bone and release the minerals resulting in a transfer of calcium from bone fluid to the blood. Also described are methods for administering the autophagy activating compound to treat a bone disorder of hyperresorption of bone and/or enhanced activation of osteoclasts.

Abstract: Devices and methods for reducing, eliminating, preventing, suppressing, or treating tissue responses to hemostatic devices e.g., biological sealants or vascular procedures are disclosed. The invention employs a combination of resorbable, biocompatible matrix materials and a variety of therapeutic agents, such as antiproliferatives or antibiotics, applied to a vascular puncture or incision to achieve hemostasis following diagnostic or interventional vascular catheterizations and to treat neointimal hyperplasia and stenosis. A matrix of a material such as collagen provides a reservoir of a therapeutic agent such as rapamycin (sirolimus) and its derivatives and analogs for delivery at a tissue site at risk for vasculoproliferation, infection, inflammation, fibrosis or other tissue responses.

Abstract: The present invention relates to a pharmaceutical combination comprising a phosphatidylinositol-3-kinase (PI3K) inhibitor compound which is a 2-carboxamide cycloamino urea derivative or a pharmaceutically acceptable salt thereof and at least one mammalian target of rapamycin (mTOR) inhibitor or a pharmaceutically acceptable salt thereof; a pharmaceutical composition comprising such a combination; and the uses of such a combination in the treatment proliferative diseases, more specifically of mammalian target of rapamycin (mTOR) kinase dependent diseases.

Abstract: Diseases and conditions associated with tissues of the body, including but not limited to tissues in the eye, can be effectively treated, prevented, inhibited, onset delayed, or regression caused by administering therapeutic agents to those tissues. Described herein are liquid formulations which deliver a variety of therapeutic agents, including but not limited to rapamycin, to a subject for an extended period of time; liquid formulations which form a non-dispersed mass when placed in an aqueous medium of a subject; non-dispersed mass-forming liquid formulations which form a gel or gel-like substance in an aqueous medium; liquid formulations, comprising a therapeutic agent and a plurality of polymers; and methods for delivering therapeutic agents to a subject for an extended period of time using the liquid formulations.

Abstract: An extended release oral dosage form comprising as active substance tacrolimus or a pharmaceutically active analogue thereof for a once daily immunosuppressive treatment of a patient in need thereof, preferable a kidney or liver transplant patient. The dosage form releases the active substance over an extended period of time. It also provides improved pharmacokinetic parameters due to an extended and constant in vivo release including substantial decreased peak concentrations, despite increased bioavailability, substantial extended times for maximal concentration, and higher minimal concentrations when compared with conventional immediate release dosage forms and a recent modified release tacrolimus dosage form.

Abstract: A method to determine the clinical outcome of breast tumour affecting a patient if treated with an antitumoural agent against breast tumour, the said method comprising the step of assaying a sample of a breast tumour from said patient for an expression level of selected genes, by contacting mRNA sequences from the cells of this breast tumour with a set of more than 3 nucleotide sequences related to human mutated PIK3CA.

Abstract: This invention relates to novel crystalline forms of tiotropium bromide, processes for preparing them, and their use in pharmaceutical formulations.

Abstract: The invention provides a method of improving one or more clinical outcomes of an individual experiencing an acute respiratory attack. The acute respiratory attack may include acute reversible bronchospasm, severe acute bronchospasm, or acute exacerbation of asthma. The method includes administering to an individual suffering from an acute respiratory attack an effective amount of bedoradrine or a pharmaceutically acceptable salt thereof in combination with a standard of care (SOC) treatment regimen.

Abstract: The invention features methods and compositions feature lapatinib and/or rapamycin for treating or preventing a cardiac condition induced by anthracycline treatment.

Abstract: Described herein are formulations comprising therapeutic agents, including but not limited to formulations comprising rapamycin, pharmaceutical formulations, unit dose forms, kits, methods of preparing formulations, and methods of using formulations. Such formulations and methods have increased stability.

Abstract: A combination of temsirolimus and trastuzumab in the treatment of cancer is provided. A combination of temsirolimus and HKI-272 is provided. A combination of a trastuzumab and a HKI-272 is also provided. Regimens and kits for treatment of metastatic breast cancer, containing trastuzumab, temsirolimus and/or HKI-272, optionally in combination with other anti-neoplastic agents, or immune modulators are described.

Abstract: Treatment of lymphangioleiomyomatosis with the MEK1/2 inhibitor CI-1040 delayed the development of primary tumors and blocked the estrogen-induced lung metastases in treated animals. Such treatment also reduced the number of circulating ELT3 cells and decreased their lung colonization after intravenous injection.

Abstract: The present invention refers to a method of treating a disease or disorder associated with the expression of at least one transgluaminase-2 and a method of identifying a candidate transglutaminase-2 inhibitor.

Abstract: The present invention is a composition composed of a therapeutic agent encapsulated in a copolymer of an N-alkylacrylamide, a vinyl monomer, and a polyethylene glycol (PEG) conjugate and a method for using the same in the treatment or prevention of a disease or condition.

Abstract: Disclosed are novel compounds and a method of treating a disease associated with aberrant leukocyte recruitment and/or activation. The method comprises administering to a subject in need an effective amount of a compound represented by: or physiologically acceptable salt thereof.

Abstract: The present invention provides compounds of Formula (I), or a pharmaceutically acceptable salt thereof, where R1, R2, R3, R4, R5, R6, A and n are as defined herein. A deuteriated derivative of the compound of Formula (I) is also provided.

Abstract: The invention provides compounds of formula I: or a salt thereof as described herein. The invention also provides pharmaceutical compositions comprising a compound of formula I, processes for preparing compounds of formula I, intermediates useful for preparing compounds of formula I and therapeutic methods for treating the proliferation of the HIV virus, treating AIDS or delaying the onset of AIDS or ARC symptoms in a mammal using compounds of formula I.

Abstract: Pancreatic Neuroendocrine Tumors (PanNETs) are a rare but clinically important form of pancreatic neoplasia. To explore the genetic basis of PanNETs, we determined the exomic sequences of ten non-familial PanNETs and then screened the most commonly mutated genes in 58 additional PanNETs. Remarkably, the most frequently mutated genes specify proteins implicated in chromatin remodeling: 44% of the tumors had somatic inactivating mutations in MEN-1, which encodes menin, a component of a histone methyltransferase complex; and 43% had mutations in genes encoding either of the two subunits of a transcription/chromatin remodeling complex consisting of DAXX (death-domain associated protein) and ATRX (alpha thalassemia/mental retardation syndrome X-linked). Clinically, mutations in the MEN1 and DAXX/ATRX genes were associated with better prognosis.

Abstract: The present invention provides a quinolone compound that inhibits the chronic progression of Parkinson's disease or protects dopamine neurons from disease etiology, thereby suppressing the progression of neurological dysfunction, so as to prolong the period of time until L-dopa is administered while also improving neuronal function; the quinolone compound of the invention is represented by Formula (1): wherein: R1 represents hydrogen or the like; R2 represents hydrogen or the like; R3 represents substituted or unsubstituted phenyl or the like; R4 represents halogen or the like; R5 represents hydrogen or the like; R6 represents hydrogen or the like; and R7 represents hydrogen or the like.

Abstract: Candidate compounds for use in neuro-protection and repair in neurological disorders involving Tau dysfunction (including Alzheimer's disease) are identified from a direct interaction between proteins FKBP52 and Tau. The method for screening a drug for the prevention and treatment of neurological disorders involving Tau dysfunction includes determining the ability of a candidate compound, to modulate binding between a Tau polypeptide and a FKBP52 polypeptide, and selecting positively the candidate compound that modulates binding.

Abstract: Disclosed are uses of dihydroquinolinone derivatives for combating ectoparasites on non-human animals. Example ectoparasites include, for example, representatives of the order acarina, including ticks and mites. Also disclosed are compositions containing dihydroquinolinone derivatives.

Abstract: A medicament tablet containing paracetamol (acetaminophen) as the (or an) active ingredient, and an encapsulated flavorant. The tablet may be swallowed in tablet form or may be dissolved or dispersed in water to form a palatable drink.

Abstract: Methods of treating a head and neck cancer are disclosed.

Abstract: The present invention provides isolated or substantially purified polypeptides, nucleic acids, and virus-like particles (VLPs) derived from a Merkel cell carcinoma virus (MCV), which is a newly-discovered virus. The invention further provides monoclonal antibody molecules that bind to MCV polypeptides. The invention further provides diagnostic, prophylactic, and therapeutic methods relating to the identification, prevention, and treatment of MCV-related diseases.

Abstract: The invention refers to TFEB phosphorylation inhibitors. Such molecules have a therapeutic applicability in all disorders that need induction of the cell authophagic/lysosomal system, such as lysosomal storage disorders, neurodegenerative diseases, hepatic diseases, muscle diseases and metabolic diseases.

Abstract: The present application teaches a coating having a biologically compatible compound conjugated to, or blended with, a polymer, wherein the polymer includes at least one olefin-derived unit and at least one unit derived from a vinyl alcohol, an allyl alcohol, or derivatives thereof.

Abstract: The invention relates to a stable pharmaceutical composition comprising comprising a solid dispersion of tacrolimus in a vehicle further comprising a stabilizing agent capable of providing a pH below 7 in the composition, as measured after re-dispersion in water, and preventing or reducing the formation upon storage of major degradation products of tacrolimus, in particular the 8-epitacrolimus.

Abstract: Methods and compositions are provided for modulating pancreatic islet ?-cell development. Aspects of the methods include promoting ?-cell development by providing agents that promote calcineurin/N FAT signaling, and inhibiting ?-cell development by providing agents that inhibit calcineurin/NFAT signaling. These methods find a number of uses, including, for example, in the treatment of diabetes and human islet diseases. In addition, reagents, devices and kits thereof that find use in practicing the subject methods are provided.

Abstract: The present invention relates to the identification and diagnostic use of biomarkers in primary colorectal cancer tumors whose activation level are predictive of the likelihood of the onset of metastatic disease. These biomarkers may be used to determine the suitability of a patient for aggressive and/or targeted treatments. Kits and compositions of the invention are also provided.

Abstract: This invention provides compounds, compositions and methods for treating a cognitive disorder or memory disorder in animals that result from aging or other neurodegenerative condition. In particular, compounds of this invention can stimulate neural cell growth, increased amounts of cells containing a key enzyme needed for production of the cholinergic neurotransmitter, and can improve memory and cognitive function in animals who have experienced a loss of memory or cognitive function.

Abstract: The present invention relates to non-psychoactive derivatives of tetrahydrocannabinol, which are useful in treating interstitial cystitis and relieving symptoms thereof. The invention uses (6aR,10aR)-?8-tetrahydrocannabinol-11-oic acids (hereinafter referred to as (6aR,10aR)-?8-THC-11-oic acid), as well as pharmaceutical compositions containing the (6aR,10aR)-?8-THC-11-oic acids, for treatment of interstitial cystitis in a mammal. The invention further covers methods of formulating and administering the compounds and pharmaceutical compositions as therapeutic agents in the treatment of interstitial cystitis, with particularly preferred administration routes being oral and via intravesicular instillation.

Abstract: An ophthalmic formulation having an effective amount of a parasympathomimetic agent comprising pilocarpine, or a pharmaceutically acceptable salt thereof, and one or more ?1 adrenergic agonists or antagonists is disclosed. The ophthalmic formulation may enable treatment of conditions adversely affecting the visual acuity of a patient, including presbyopia. A method of using the disclosed ophthalmic formulation to treat or ameliorate symptoms of presbyopia is also disclosed.

Abstract: The present invention provides thienopyridine compounds, compositions thereof, and methods of using the same.

Abstract: A method of inhibiting phosphorylation of the tau protein and/or a TLR4-mediated immune response is disclosed. The method contemplates administering to cells in recognized need thereof such as cells of the central nervous system an effective amount of a of a compound or a pharmaceutically acceptable salt thereof that binds to a pentapeptide of filamin A (FLNA) of SEQ ID NO: 1, and contains at least four of the six pharmacophores of FIGS. 35-40.

Abstract: There is provided compounds of formula I, wherein X1 to X4, R1 to R4, Y1, Y2 and L are as defined in the description, and pharmaceutically-acceptable salts thereof, which may be useful in the treatment and/or prophylaxis of autoimmune diseases, inflammatory (e.g. chronic inflammatory) diseases and/or other diseases that may benefit from production of ROS (reactive oxygen species) by a NADPH oxidase complex.

Abstract: The present invention provides MDM2 inhibitor compounds of Formula I, wherein the variables are defined above, which compounds are useful as therapeutic agents, particularly for the treatment of cancers. The present invention also relates to pharmaceutical compositions that contain an MDM2 inhibitor.

Abstract: Described herein are formulations comprising therapeutic agents, including but not limited to formulations comprising rapamycin, pharmaceutical formulations, unit dose forms, kits, methods of preparing formulations, and methods of using formulations. Such formulations and methods have increased stability.

Abstract: The present invention is directed to polymeric compositions comprising a biodegradable copolymer that possesses shape-memory properties and implantable devices (e.g., drug-delivery stents) formed of materials (e.g., a coating) containing such compositions. The polymeric compositions can also contain at least one non-fouling moiety, at least additional biocompatible polymer, at least one biobeneficial material, at least one bioactive agent, or a combination thereof. The polymeric compositions are formulated to possess good mechanical, physical and biological properties. Moreover, implantable devices formed of materials comprising such compositions can be delivered to the treatment site in a conveniently compressed size and then can expand to dimensions appropriate for their medical functions.

Abstract: This invention relates to a semisolid ophthalmic composition, in particular an ointment, comprising (1) an ophthalmic drug, e.g. a staurosporine derivative, (2) an ointment base and (3) an agent for dispersing and/or dissolving said drug in the ointment base, selected from a poly(ethylene-glycol), a polyethoxylated castor oil, an alcohol having 12 to 20 carbon atoms and a mixture of two or more of said components.

Abstract: Medical devices, and in particular implantable medical devices, may be coated with any number of biocompatible materials. Therapeutic drugs, agents or compounds may be mixed with the biocompatible materials and affixed to at least a portion of the medical device. These therapeutic drugs, agents or compounds may also further reduce a biological organism's reaction to the introduction of the medical device to the organism. In addition, these therapeutic drugs, agents and/or compounds may be utilized to promote healing, including the formation of blood clots. Also, the devices may be modified to promote endothelialization. Various materials and coating methodologies may be utilized to maintain the drugs, agents or compounds on the medical device until delivered and positioned. In addition, various polymer combinations may be utilized to control the elution rates of the therapeutic drugs, agents and/or compounds from the implantable medical devices.

Abstract: Compounds of Formula I: in which R1, R2, R3, R4 and R10 have the meanings given in the specification, are receptor tyrosine inhibitors useful in the treatment of diseases mediated by PIM-1 and/or PIM-2 and/or PIM-3 kinases.

Abstract: Novel cromolyn analogs useful as imaging agents for detecting atherosclerotic plaques and for treating atherosclerosis and Alzheimer's Disease, and methods of making the cromolyn analogs, are disclosed. The cromolyn analogs have the general formula (I), or formula (II); wherein X is OH, C1-C6 alkoxyl, 18F, or 19F; Y and Z are independently selected from a C1-C6 alkyl, CpC6 alkoxyl, halogen, un-substituted or C1-C6 substituted amine, 18F, 19F, or H; and n is 1, 2, or 3; and wherein for structure (I), if n are both 1 and Y and Z are both H, X is not OH.

Abstract: The present disclosure generally relates to therapeutic nanoparticles. Exemplary nanoparticles disclosed herein may include about 1 to about 20 weight percent of a mTOR inhibitor; and about 70 to about 99 weight percent biocompatible polymer.

Abstract: Compositions, products and methods including silicone based excipients are provided. The compositions, products and methods of the present invention are particularly useful for the treatment of ophthalmic diseases.

Abstract: Provided herein are methods, kits, and pharmaceutical compositions that include a PI3 kinase inhibitor for treating lupus, a fibrotic condition, or inflammatory myopathies and other conditions (e.g., skin conditions).

Abstract: The present invention relates to the field of hematopoietic stem cells. More specifically, the present invention provides methods and composition useful for peripheral blood stem cell mobilization. In one embodiment, a method of treating an organ transplant recipient comprises administering to the recipient a low dose of Tacrolimus in an amount sufficient to mobilize stem cells to the peripheral blood of the recipient. In a specific embodiment, the low dose of Tacrolimus is in the range of about 0.05 mg/kg to about 0.5 mg/kg.