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, oxyntomodulin and glucagon-like peptide.
Type:
Grant
Filed:
July 2, 2013
Date of Patent:
February 12, 2019
Assignee:
MannKind Corporation
Inventors:
Chad C. Smutney, P. Spencer Kinsey, Carl R. Sahi, Benoit Adamo, John M. Polidoro, Scott McLean, Dennis Overfiled, Anthony Bryant
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.
Type:
Grant
Filed:
August 15, 2016
Date of Patent:
February 5, 2019
Assignee:
MannKind Corporation
Inventors:
John J. Freeman, Adrienne Stamper, Melissa Heitmann
Abstract: Disclosed are drug delivery systems for the delivery of small molecule and macromolecular drugs. More particularly, disclosed are substituted analogs of 3,6-di(alkyl-4 aminobutyl)-2,5-diketopiperazine (which may also be referred to DKP), their use in the formulation of both small molecule and macromolecular drugs including therapeutic, prophylactic and diagnostic agents, stabilizing agents and systems for their delivery.
Abstract: Dry powder inhalable compositions and methods for using and making the compositions are disclosed for vaccinating a subject against disease. In particular, the compositions are inhalable dry powders useful for preventing and/or treating diseases caused by microorganisms, for example, microorganisms such as viral or bacterial pathogens, including, the influenza virus. In particular, the method comprises the administration of an inhalable composition comprising virus-like particles and/or specific protein/s or antigenic peptides, peptide fragments and/or derivatives thereof using a dry powder drug delivery system.
Type:
Grant
Filed:
October 25, 2013
Date of Patent:
December 25, 2018
Assignees:
MannKind Corporation, Technovax, Inc.
Inventors:
Chad C. Smutney, Andrea Leone-Bay, Jose M. Galarza, Hector Munoz, George R. Martin, Marshall L. Grant
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: 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.
Type:
Application
Filed:
August 1, 2018
Publication date:
November 29, 2018
Applicant:
MannKind Corporation
Inventors:
Edwin Amoro, Karel Vanackere, Michael A. White
Abstract: Methods are provided for drying a particle. Specifically, there is provided a spray-dried diketopiperazine-insulin particle formulation having improved aerodynamic performance and in which the active agent is more stabile and efficiently delivered as compared to that of the lyophilized diketopiperazine-insulin formulation. The dry powders have utility as pharmaceutical formulations for pulmonary delivery.
Abstract: Drug delivery systems have been developed based on the formation of diketopiperazine carboxylate salts and microparticles containing the same. The systems may further comprise a bioactive agent. Related methods for making and using the biologically active agent delivery compositions are also provided. In certain embodiments, the pharmaceutically acceptable salts described can be formed by removal of solvent by methods including distillation, evaporation, spray drying or lyophilization.
Type:
Grant
Filed:
June 9, 2017
Date of Patent:
November 20, 2018
Assignee:
MannKind Corporation
Inventors:
Andrea Leone-Bay, Destardi Moye-Sherman, Bryan R. Wilson
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.
Type:
Grant
Filed:
May 11, 2016
Date of Patent:
November 20, 2018
Assignee:
MannKind Corporation
Inventors:
Marshall Grant, Paul Menkin, Grayson W. Stowell
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.
Type:
Grant
Filed:
September 7, 2017
Date of Patent:
October 30, 2018
Assignee:
MannKind Corporation
Inventors:
John J. Stevenson, Destardi Moye-Sherman
Abstract: Disclosed embodiments relate to improved methods for the synthesis of activated fumarate intermediates and their use in chemical synthesis. Disclosed embodiments describe the synthesis of activated fumarate esters including those derived from activating groups including: 4-nitrophenyl, diphenylphophoryl azide, pivaloyl chloride, chlorosulfonyl isocyanate, p-nitrophenol, MEF, trifluoroacetyl and chlorine, for example, ethyl fumaroyl chloride and the subsequent use of the activated ester in situ. Further embodiments describe the improved synthesis of substituted aminoalkyl-diketopiperazines from unisolated and unpurified intermediates allowing for improved yields and reactor throughput.
Type:
Grant
Filed:
November 23, 2015
Date of Patent:
September 11, 2018
Assignee:
MannKind Corporation
Inventors:
Kelly Sullivan Kraft, John J. Freeman, Paul Serwinski, Vincent Pavia, Otto Phanstiel, Navneet Kaur
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.
Type:
Grant
Filed:
January 17, 2017
Date of Patent:
August 21, 2018
Assignee:
MannKind Corporation
Inventors:
Edwin Amoro, Karel Vanackere, Michael A. White
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.
Type:
Grant
Filed:
February 1, 2017
Date of Patent:
August 14, 2018
Assignee:
MannKind Corporation
Inventors:
Anders Hasager Boss, Richard Petrucci, Campbell Howard, Alfred Mann
Abstract: Reactors, reactor systems and methods for producing particles in a precipitation process are provided. The reactor includes a housing defining a reaction chamber, a stator assembly including two or more stators, a rotor assembly including two or more rotors, the rotor assembly configured for rotation about an axis of rotation relative to the stator assembly, a first inlet to supply a first reactant material to the reaction chamber at a first radial location, a second inlet to supply a second reactant material to the reaction chamber at a second radial location different from the first radial location, wherein the first and second reactant materials react to produce precipitation of particles in the reaction chamber, and an outlet to supply the particles formed in the reaction chamber.
Type:
Application
Filed:
March 7, 2018
Publication date:
July 12, 2018
Applicant:
Mannkind Corporation
Inventors:
Sanket Gandhi, Karen Moraleda, Jadwiga Jachowicz, Michael Zupon
Abstract: A method for the synthesis of N-protected 3,6-aminoalkyl-2,5-diketopiperazines is provided. The method includes obtaining a cyclic ?-N protected active amino ester and adding it to a mixture of an amine catalyst in an organic solvent.
Type:
Grant
Filed:
November 16, 2015
Date of Patent:
April 17, 2018
Assignee:
MannKind Corporation
Inventors:
John J. Freeman, Otto Phanstiel, William Elliot Bay, Kelly Sullivan Kraft