Use of tight junction antagonists in the treatment of acute lung injury and acute respiratory distress syndrome
Inventors
Paterson, Blake • Ward, Peter • Fasano, Alessio
Assignees
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Publication Number
US-10723763-B2
Publication Date
2020-07-28
Expiration Date
Abstract
The present application provides compositions and methods for treating acute lung injury and acute respiratory distress syndrome. The methods include administering one or more tight junction antagonists to the lung of a subject in need thereof.
Core Innovation
The disclosed subject matter describes compositions and methods for treating acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Treatment is achieved by administering to the lung a tight junction antagonist, exemplified as peptides having amino acid sequences provided as SEQ ID NOs:1-24.
A specific peptide tight junction antagonist is exemplified as GGVLVQPG (SEQ ID NO:15). The disclosure also references a tight junction antagonist derived from zonula occludens toxin (ZOT), including an active domain of ZOT (ΔG), and interaction with a ZOT receptor, in relation to endothelial barrier integrity and lung permeability.
The disclosure further describes formulation and delivery approaches for the antagonist in pulmonary delivery formats, including pulmonary delivery and pharmaceutical aerosol dosage forms. Example embodiments reference intravenous (IV) and intratracheal (IT) administration and dose effects, and compare delivery routes in an immune-complex (IC) lung injury model.
The disclosure additionally describes optional co-therapy with additional therapeutic agents, including agents such as aminosalicylates and corticosteroids, and outlines that immune-complex lung injury can be used with relevant components such as bovine serum albumin (BSA) and anti-BSA antibodies. Referenced results in FIGS. 2-3 address lung permeability effects associated with SEQ ID NO:15.
Claims Coverage
The relevant independent claim set includes 1 independent claim. The independent claim covers an ALI/ARDS treatment method by administering a pharmaceutical composition containing a peptide tight junction antagonist with the specific amino acid sequence GGVLVQPG (SEQ ID NO:15), directed to a human subject in need thereof.
Peptide tight junction antagonist for ALI/ARDS treatment
A method for treating acute respiratory distress syndrome or acute lung injury by administering to a human subject in need thereof a composition comprising a peptide tight junction antagonist, wherein the tight junction antagonist is a peptide having the amino acid sequence GGVLVQPG (SEQ ID NO:15).
Overall claim coverage is grounded in administering a peptide tight junction antagonist with the specific sequence GGVLVQPG (SEQ ID NO:15) to treat acute respiratory distress syndrome or acute lung injury, with dependent claim variations narrowing formulation/delivery and optional adjunct therapy categories.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treatment of acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) by administering a peptide tight junction antagonist to the lung.
Use of an immune-complex (IC) lung injury model in which lung permeability effects are assessed for the peptide GGVLVQPG (SEQ ID NO:15) (results referenced in FIGS. 2-3).
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