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:
Application
Filed:
December 8, 2009
Publication date:
April 8, 2010
Applicant:
MANNKIND CORPORATION
Inventors:
John J. Stevenson, Destardi Moye-Sherman
Abstract: Methods are provided for purifying peptides and proteins by incorporating the peptide or protein into a diketopiperazine or competitive complexing agent to facilitate removal one or more impurities, from the peptide or protein. Formulations and methods also are provided for the improved transport of active agents across biological membranes, resulting for example in a rapid increase in blood agent concentration. The formulations include microparticles formed of (i) the active agent, which may be charged or neutral, and (ii) a transport enhancer that masks the charge of the agent and/or that forms hydrogen bonds with the target biological membrane in order to facilitate transport. In one embodiment, insulin is administered via the pulmonary delivery of microparticles comprising fumaryl diketopiperazine and insulin in its biologically active form. This method of delivering insulin results in a rapid increase in blood insulin concentration that is comparable to the increase resulting from intravenous delivery.
Type:
Application
Filed:
December 10, 2009
Publication date:
April 8, 2010
Applicant:
MANNKIND CORPORATION
Inventors:
Solomon S. Steiner, Rodney J. Woods, Joseph W. Sulner
Abstract: Methods are provided for purifying peptides and proteins by incorporating the peptide or protein into a diketopiperazine or competitive complexing agent to facilitate removal of one or more impurities from the peptide or protein. Formulations and methods also are provided for the improved transport of active agents across biological membranes, resulting for example in a rapid increase in blood agent concentration. The formulations include microparticles formed of (i) the active agent, which may be charged or neutral, and (ii) a transport enhancer that masks the charge of the agent and/or that forms hydrogen bonds with the target biological membrane in order to facilitate transport. In one embodiment insulin is administered via the pulmonary delivery of microparticles comprising fumaryl diketopiperazine and insulin in its biologically active form. This method of delivering insulin results in a rapid increase in blood insulin concentration that is comparable to the increase resulting from intravenous delivery.
Type:
Grant
Filed:
November 21, 2003
Date of Patent:
January 19, 2010
Assignee:
MannKind Corporation
Inventors:
Solomon S. Steiner, Rodney J. Woods, Joseph W. Sulner
Abstract: Disclosed herein are polypeptides, including epitopes, clusters, and antigens. Also disclosed are compositions that include said polypeptides and methods for their use.
Type:
Application
Filed:
August 19, 2008
Publication date:
November 19, 2009
Applicant:
Mannkind Corporation
Inventors:
John J. L. Simard, David C. Diamond, Liping Liu, Zheng Liu
Abstract: Some embodiments relate to analogs of peptides corresponding to class I MHC-restricted T cell epitopes and methods for their generation. These analogs can contain amino acid substitutions at residues that directly interact with MHC molecules, and can confer improved, modified or useful immunologic properties. Additionally, classes of analogs, in which the various substitutions comprise the non-standard residues norleucine and/or norvaline, are disclosed.
Type:
Grant
Filed:
June 16, 2006
Date of Patent:
October 20, 2009
Assignee:
MannKind Corporation
Inventors:
Liping Liu, Adrian Bot, David C. Diamond
Abstract: Compositions useful in the delivery of active agents are provided. These delivery compositions include (a) an active agent; and (b) a carrier of at least one mono-C-substituted or di-C-substituted diketopiperazine. Methods for preparing these compositions and administering these compositions are also provided.
Abstract: Disclosed herein are immunogenic compositions, methods of designing immunogenic compositions, methods of treatment using immunogenic compositions, methods of evaluating cell-mediated immunity resulting from immunogenic compositions, research models, and methods of making research models, all of which relate to targeting tumor vasculature.
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.
Type:
Application
Filed:
June 9, 2008
Publication date:
July 23, 2009
Applicant:
MANNKIND CORPORATION
Inventors:
John B. PATTERSON, David G. LONERGAN, Gary A. FLYNN, Qingping ZENG, Peter V. PALLAI
Abstract: Disclosed herein are methods and compositions for inducing an immune response against various combinations of tumor-associated antigens, which can promote effective immunologic intervention in pathogenic processes. Embodiments of the invention disclosed herein are directed to the use of effective combinations of TuAAs for the immunotherapy of patients with various types of cancer. Both immunogenic compositions for inducing an immune response to these combinations of antigens and methods for their use are disclosed.
Type:
Application
Filed:
October 16, 2008
Publication date:
June 11, 2009
Applicant:
MANNKIND CORPORATION
Inventors:
Chih-Sheng CHIANG, Adrian Ion BOT, John J.L. SIMARD, David C. DIAMOND
Abstract: Some embodiments relate to analogs of peptides corresponding to class I MHC-restricted T cell epitopes and methods for their generation. These analogs can contain amino acid substitutions at residues that directly interact with MHC molecules, and can confer improved, modified or useful immunologic properties. Additionally, classes of analogs, in which the various substitutions comprise the non-standard residues norleucine and/or norvaline, are disclosed.
Type:
Grant
Filed:
June 16, 2006
Date of Patent:
March 31, 2009
Assignee:
MannKind Corporation
Inventors:
Liping Liu, Adrian Bot, Jian Gong, David Diamond
Abstract: Some embodiments relate to analogs of peptides corresponding to class I MHC-restricted T cell epitopes and methods for their generation. These analogs can contain amino acid substitutions at residues that directly interact with MHC molecules, and can confer improved, modified or useful immunologic properties. Additionally, classes of analogs, in which the various substitutions comprise the non-standard residues norleucine and/or norvaline, are disclosed.
Type:
Grant
Filed:
June 16, 2006
Date of Patent:
March 31, 2009
Assignee:
MannKind Corporation
Inventors:
Liping Liu, Adrian Bot, David C. Diamond
Abstract: A dry powder inhaler having improved aerodynamic properties for diluting, dispersing, and metering drug particles for increasing the efficiency of pulmonary drug delivery to a patient is described. The inhaler comprises, in general, a housing having an air intake, an air flow-control/check-valve, a mixing section and a mouthpiece. A cartridge loaded with a single dose of medicament can be installed in the mixing section.
Type:
Grant
Filed:
September 4, 2003
Date of Patent:
December 16, 2008
Assignee:
MannKind Corporation
Inventors:
Solomon S. Steiner, Trent A. Poole, Per B. Fog, Roderike Pohl, Michael Crick, Robert Feldstein
Abstract: A composition is disclosed comprising glucagon-like peptide 1 (GLP-1) particles in combination with diketopiperazine (DKP) that is stable both in vitro and in vivo. The composition has utility as a pharmaceutical formulation for treating diseases such as diabetes, cancers, and obesity but is not limited to such diseases or conditions. In particularly, the composition has utility as a pharmaceutical formulation for pulmonary delivery.
Type:
Application
Filed:
April 16, 2007
Publication date:
October 23, 2008
Applicant:
MANNKIND CORPORATION
Inventors:
Mark J. Hokenson, David Brandt, Mark King, Stephanie Greene, Mary Faris, Keith Oberg, Wayman Wendell Cheatham, Cohava Gelber, Andrea Leone-Bay