Abstract: The present invention relates to pharmaceutical compositions for inhalation comprising a therapeutically effective dose of clofazimine wherein the clofazimine is provided in the form of a suspension, and processes for their preparation. Furthermore, the present invention provides pharmaceutical combinations comprising clofazimine in the form of an aerosol for pulmonary inhalation. The combinations and compositions provided by the present invention may be used in the treatment and/or prophylaxis of pulmonary infections caused by mycobacteria and other gram-positive bacteria, and of pulmonary fungal infections.
Type:
Grant
Filed:
February 22, 2021
Date of Patent:
October 24, 2023
Assignee:
MANNKIND CORP.
Inventors:
Thomas Hofmann, Stefan Ufer, Kevin Stapleton
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:
December 7, 2020
Date of Patent:
October 25, 2022
Assignee:
MANNKIND, CORP.
Inventors:
Kelly Sullivan Kraft, John J. Freeman, Paul Serwinski, Vincent Pavia, Otto Phanstiel, Navneet Kaur
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:
May 4, 2020
Date of Patent:
September 13, 2022
Assignee:
MANNKIND, CORP.
Inventors:
John J. Freeman, Adrienne Stamper, Melissa Heitmann
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:
December 22, 2020
Date of Patent:
May 31, 2022
Assignee:
MANNKIND CORP.
Inventors:
John J. Freeman, Otto Phanstiel, William Elliot Bay, Kelly Sullivan Kraft
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:
March 2, 2020
Date of Patent:
December 22, 2020
Assignee:
MannKind, Corp.
Inventors:
John J. Freeman, Otto Phanstiel, William Elliot Bay, Kelly Sullivan Kraft
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:
September 10, 2018
Date of Patent:
December 8, 2020
Assignee:
MANNKIND, CORP.
Inventors:
Kelly Sullivan Kraft, John J. Freeman, Paul Serwinski, Vincent Pavia, Otto Phanstiel, Navneet Kaur
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 am inoalkyl]-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:
February 4, 2019
Date of Patent:
May 5, 2020
Assignee:
MANNKIND, CORP.
Inventors:
John J. Freeman, Adrienne Stamper, Melissa Heitmann
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:
April 16, 2018
Date of Patent:
March 3, 2020
Assignee:
MANNKIND, CORP.
Inventors:
John J. Freeman, Otto Phanstiel, William Elliot Bay, Kelly Sullivan Kraft
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:
Application
Filed:
March 14, 2014
Publication date:
September 25, 2014
Applicant:
Mannkind Corp.
Inventors:
John J. Freeman, Otto Phanstiel, William Elliot Bay, Kelly Sullivan Kraft
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, diphenylphosphoryl 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:
Application
Filed:
March 15, 2013
Publication date:
October 31, 2013
Applicant:
MANNKIND CORP
Inventors:
Kelly Sullivan Kraft, John J. Freeman, Paul Serwinski, Vinnie Pavia, Otto Phanstiel, IV, Navneet Kaur