Use of tight junction antagonists to treat inflammatory bowel disease
Inventors
Paterson, Blake • Tamiz, Amir • Pandey, Niranjan
Assignees
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Publication Number
US-8796203-B2
Publication Date
2014-08-05
Expiration Date
Abstract
The present invention provides materials and methods for the treatment of inflammatory bowel disease (e.g., Crohn's disease and ulcerative colitis). Materials of the invention may include compositions comprising one or more tight junction antagonists and optionally one or more therapeutic agents. Methods of the invention may comprise treating a subject in need thereof with a composition comprising one or more tight junction antagonists and, optionally one or more therapeutic agents.
Core Innovation
The invention relates to methods for treating inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, in a patient by administering a peptide having the amino acid sequence GGVLVQPG (SEQ ID NO:15). The peptide is administered to the colon of a patient having IBD to prevent or reduce tight junction opening associated with IBD. Tight junction antagonists are described as preventing or reducing tight junction opening, including through a zonulin receptor and Zonula occludens toxin (ZOT)/zonulin-related mechanism.
A peptide-based tight junction antagonist approach is described in which peptide antagonists include peptides containing SEQ ID NO:15 (GGVLVQPG) and other SEQ ID variants. The disclosed treatment approach is further linked to intestinal permeability and colitis progression, including the use of assays and inflammatory readouts to evaluate effects on intestinal permeability. The document also discusses peptides in relation to preventing or reducing changes associated with zonulin and intestinal permeability.
The document further describes compositions for administration in a delayed/enteric manner that are stable in gastric fluid and unstable in intestinal fluid, supporting delivery to the colon. The delayed release composition is described as delivering the peptide to the colon, and the compositions are described as optionally co-formulated with therapeutic agents including aminosalicylates, corticosteroids, immunomodulators, antibiotics, and biologics. A study rationale is described using an IL-10 knockout mouse model to evaluate AT-1001 effects on intestinal permeability and colitis progression, with figures indicating reduced permeability and inflammation at multiple timepoints.
Claims Coverage
The provided excerpt contains two independent claims. Together, they cover (i) colon administration of the peptide GGVLVQPG (SEQ ID NO:15) for IBD and (ii) a chronic IBD regimen with delayed release to the colon and a specified per-day schedule over a plurality of days.
Colon administration of a specific peptide for IBD
Administering a peptide having the amino acid sequence GGVLVQPG (SEQ ID NO:15) to the colon of a patient having IBD.
Chronic dosing with delayed release to the colon
Administering, one or more times per day for a plurality of days, a peptide having the amino acid sequence GGVLVQPG (SEQ ID NO:15) in a delayed release composition to the colon of a chronic IBD patient in need thereof.
Across the independent claims, the core claim coverage is centered on administering the peptide GGVLVQPG (SEQ ID NO:15) to the colon, with the chronic IBD claim additionally requiring one or more administrations per day over a plurality of days and delivery by a delayed release composition to the colon.
Stated Advantages
Reduced intestinal permeability and reduced colonic inflammation are indicated in the disclosed AT-1001 evaluation results.
Documented Applications
Treating inflammatory bowel disease (Crohn’s disease and ulcerative colitis) by administering tight junction antagonists/peptide antagonists to the colon.
Evaluating an AT-1001 effect on intestinal permeability and colitis progression using an IL-10 knockout mouse study, including permeability and inflammatory readouts.
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