Abstract: Disclosed herein are improved methods of treating hyperglycemia with a combination of an ultrarapid acting insulin and insulin glargine comprising prandial administration of the ultrarapid insulin, and administration of a first dose of insulin glargine within 6 hours of waking for a day.

Abstract: Cryogranulation systems with improved dispenser assemblies are provided for use in manufacturing frozen pellets of pharmaceutical substances in a fluid medium. Methods of cryogranulating the pharmaceutical substance in the fluid medium are also provided. In particular embodiments, the dispenser assembly is used with suspensions or slurries of pharmaceutical compositions including biodegradable substances, such as proteins, peptides, and nucleic acids. In certain embodiments, the pharmaceutical substance can be adsorbed to any pharmaceutically acceptable carrier particles suitable for making pharmaceutical powders. In one embodiment, the pharmaceutical carrier can be, for example, diketopiperazine-based microparticles. The dispenser assembly improves the physical characteristics of the cryopellets formed and minimizes product loss during processing.

Abstract: Compounds which directly inhibit IRE-1? activity in vitro, prodrugs, and pharmaceutically acceptable salts thereof. Such compounds and prodrugs are useful for treating diseases associated with the unfolded protein response and can be used as single agents or in combination therapies.

Abstract: A breath-powered, dry powder inhaler, a cartridge, and a pulmonary drug delivery system are provided. The dry powder inhaler can be provided with or without a unit dose cartridge for using with the inhaler. The inhaler and/or cartridge can be provided with a drug delivery formulation comprising, for example, a diketopiperazine and an active ingredient, including, peptides and proteins such as insulin and glucagon-like peptide 1 for the treatment of diabetes and/or obesity. The dry powder inhaler is compact; can be provided in various shapes and sizes, colors, and comprises a housing, a mouthpiece, a cartridge placement area, and a mechanism for opening and closing the medicament cartridge. The device is easy to manufacture, provides a pre-metered single unit dose, it is relatively easy to use, and can be reusable or disposable.

Abstract: Kinase with inhibitory activity against kinases disposed in multiple signaling pathways and their therapeutic uses.

Abstract: Methods and apparatus are provided for determining weight percent of solids in a suspension using Raman spectroscopy. The methods can be utilized to acquire Raman spectral data from the suspension and to determine weight percent of solids in a process being carried out, for example, in a vessel, without the need to remove samples for analysis. The weight percent of the solids can be determined with a desired accuracy in a relatively short time, typically 10 minutes or less. The acquired Raman spectral data may be processed by chemometric software using, for example, a partial least squares algorithm and data pretreatment to provide a predicted value of weight percent solids. In some embodiments, the invention is used to determine the weight percent of microparticles of a diketopiperazine in an aqueous solution.

Abstract: Methods are provided for promoting the adsorption of an active agent to microparticles by modifying the structural properties of the active agent in order to facilitate favorable association to the microparticle.

Abstract: A breath-powered, dry powder inhaler, a cartridge, and a pulmonary drug delivery system are provided. The dry powder inhaler can be provided with or without a unit dose cartridge for using with the inhaler. The inhaler and/or cartridge can be provided with a drug delivery formulation comprising, for example, a diketopiperazine and an active ingredient, including, peptides and proteins such as insulin and glucagon-like peptide 1 for the treatment of diabetes and/or obesity. The dry powder inhaler is compact; can be provided in various shapes and sizes, colors, and comprises a housing, a mouthpiece, a cartridge placement area, and a mechanism for opening and closing the medicament cartridge. The device is easy to manufacture, provides a pre-metered single unit dose, it is relatively easy to use, and can be reusable or disposable.

Abstract: The disclosed embodiments detail improved methods for the synthesis of diketopiperazines from amino acids. In particular improved methods for the cyclocondensation and purification of N-protected 3,6-(aminoalkyl)-2,5-diketopiperazines from N-protected amino acids. Disclosed embodiments describe methods for the synthesis of 3,6-bis-[N-protected aminoalkyl]-2,5-diketopiperazine comprising heating a mixture of an amino acid in the presence of a catalyst in an organic solvent. The catalyst is selected from the group comprising sulfuric acid, phosphoric acid, p-toluenesulfonic acid, 1-propylphosphonic acid cyclic anhydride, tributyl phosphate, phenyl phosphonic acid and phosphorous pentoxide among others. The solvent is selected from the group comprising: dimethylacetamide, N-methyl-2-pyrrolidone, diglyme, ethyl glyme, proglyme, ethyldiglyme, m-cresol, p-cresol, o-cresol, xylenes, ethylene glycol and phenol among others.

Abstract: The disclosure relates to antibodies to the preferentially expressed antigen in melanoma (PRAME), and the synovial sarcoma X breakpoint 2 (SSX-2) antigens, methods of use, and diagnostic kits thereof. In exemplary embodiments, the disclosure relates to monoclonal antibodies to specific epitopes of the PRAME and SSX-2 antigens and methods of using such antibodies.

Abstract: A pulmonary drug delivery system is disclosed, including a breath-powered, dry powder inhaler, and a cartridge for delivering a dry powder formulation. The inhaler and cartridge can be provided with a drug delivery formulation.

Abstract: Methods and apparatus are provided for determining weight percent of solids in a suspension using Raman spectroscopy. The methods can be utilized to acquire Raman spectral data from the suspension and to determine weight percent of solids in a process being carried out, for example, in a vessel, without the need to remove samples for analysis. The weight percent of the solids can be determined with a desired accuracy in a relatively short time, typically 10 minutes or less. The acquired Raman spectral data may be processed by chemometric software using, for example, a partial least squares algorithm and data pretreatment to provide a predicted value of weight percent solids. In some embodiments, the invention is used to determine the weight percent of microparticles of a diketopiperazine in an aqueous solution.

Abstract: An insufflation apparatus and methods for using same are disclosed. The apparatus is equipped with an interactive system for administering reproducible intratracheal aerosols in a consistent automated manner. The insufflation system is useful, in particular for use with experimental animals, including mice and rats and also for treating small animals via the pulmonary route in veterinary medicinal practice.

Abstract: Disclosed herein are diketopiperazine microparticles having high capacity for adsorbing a drug or active agent. In particular, the diketopiperazine microparticle are formed using fumaryl diketopiperazine and can comprise a drug in large doses for the treatment of disease or disorders by pulmonary delivery via oral inhalation.

Abstract: Described herein are interactive apparatus and methods for sensing and measuring real-time characteristic patterns of a subject's use of a dry powder inhalation system. The devices can be used in a wired or wireless communication mode to communicate with a display to assess the subject's usage of the inhalation system, to evaluate the performance of the inhalation system and/or to detect the characteristics profile of a dry powder formulation emitted from the inhalation system in use.

Abstract: A pulmonary drug delivery system is disclosed, including a breath-powered, dry powder inhaler, and a cartridge for delivering a dry powder formulation. The inhaler and cartridge can be provided with a drug delivery formulation comprising, for example, a diketopiperazine and an active ingredient, including, small organic molecules, peptides and proteins, including, insulin and glucagon-like peptide 1 for the treatment of disease and disorders, for example, endocrine disease such as diabetes and/or obesity.

Abstract: Provided is a method for the synthesis of N-protected bis-3,6-[4-aminobutyl]-2,5-diketopiperazine including the step of heating a solution of ?-amino protected lysine in the presence of a catalyst selected from the group consisting of sulfuric acid, phosphoric acid, and phosphorus pentoxide.

Abstract: The present disclosure relates to an improved device and methods for adapting to a laser diffraction apparatus used for measuring particle size distribution and density of the plume of a powder composition emitted from a dry powder inhaler.

Abstract: A breath-powered, dry powder inhaler, a cartridge, and a pulmonary drug delivery system are provided. The dry powder inhaler can be provided with or without a unit dose cartridge for using with the inhaler. The inhaler and/or cartridge can be provided with a drug delivery formulation comprising, for example, a diketopiperazine and an active ingredient, including, peptides and proteins such as insulin and glucagon-like peptide 1 for the treatment of diabetes and/or obesity. The dry powder inhaler is compact; can be provided in various shapes and sizes, colors, and comprises a housing, a mouthpiece, a cartridge placement area, and a mechanism for opening and closing the medicament cartridge. The device is easy to manufacture, provides a pre-metered single unit dose, it is relatively easy to use, and can be reusable or disposable.