Ingestible device for delivery of therapeutic agent to the gastrointestinal tract
Inventors
Shimizu, Jeffrey A. • Jones, Mitchell Lawrence • Drlik, Mark Sasha • Niknia, Iman • Muller, Nathan John • Nguyen, Tuyen • Wahl, Christopher Loren • Mudge, Edward • Salt, Nicholas Mark • Stevens, Nia Eleri • Abercrombie, Stuart Robert • Bunce, Christopher Ian • Quintana, Nelson
Assignees
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Publication Number
US-11439802-B2
Publication Date
2022-09-13
Expiration Date
Abstract
A method of treating a disease or condition in a subject in need thereof is disclosed. The method comprising: trans-epithelially administering a dispensable substance to the gastrointestinal (GI) tract of the subject by orally administering an ingestible device comprising the dispensable substance to the subject. The ingestible device is configured for trans-epithelial delivery of the dispensable substance to the GI tract of the subject and the dispensable substance comprises a pharmaceutical formulation comprising a therapeutically effective amount of a glucagon receptor agonist or a glucagon-like peptide-1 (GLP-1) receptor agonist. The ingestible device releases the dispensable substance as at least one jet to a desired location of the GI tract of the subject.
Core Innovation
The invention relates to treating a disease or condition in a subject by trans-epithelially administering a dispensable substance to the gastrointestinal (GI) tract using an orally administered ingestible device configured for trans-epithelial delivery. The ingestible device contains a pharmaceutical formulation comprising a therapeutically effective amount of a glucagon receptor agonist or a glucagon-like peptide-1 (GLP-1) receptor agonist, and releases the dispensable substance as at least one jet to a desired location in the GI tract.
The disclosed approach directly delivers the dispensable substance to the submucosa of the GI tract, where the desired location is the small intestine. The trans-epithelial delivery is characterized by jetting performance, deposition in tissue compartments including submucosa and mucosa, and systemic exposure and delivery performance metrics relative to intravenous or subcutaneous administration.
A corresponding method is provided for treating a disease or condition in a patient by trans-epithelially administering a pharmaceutical formulation via swallowing an ingestible device containing the formulation. The device releases the pharmaceutical formulation in the small intestine as one or more jets to directly deliver the pharmaceutical formulation to the submucosa of the gastrointestinal tract, with performance comparisons of systemic uptake, AUC, and Cmax relative to intravenous or subcutaneous administration.
Claims Coverage
Two independent claims are identified, both directed to treatment by swallowing an ingestible device and releasing a therapeutically effective formulation as one or more jets for direct trans-epithelial delivery to the GI submucosa in the small intestine. Across the independent claims, the core inventive features are trans-epithelial jet release from an orally swallowed ingestible device and the use of a glucagon receptor agonist or a GLP-1 receptor agonist.
Oral ingestible device delivering a jet into small intestine submucosa
Trans-epithelially administering a dispensable substance to the gastrointestinal tract by orally administering an ingestible device configured for trans-epithelial delivery, releasing the dispensable substance as at least one jet to a desired location of the GI tract, where the desired location is the small intestine and the trans-epithelial administration directly delivers the dispensable substance to the submucosa.
Glucagon receptor agonist or GLP-1 receptor agonist jet trans-epithelial treatment
Treating a disease or condition by trans-epithelial administration that delivers a pharmaceutical formulation comprising a therapeutically effective amount of a glucagon receptor agonist or a GLP-1 receptor agonist to the submucosa of the GI tract, where the disease or condition is responsive to treatment with the glucagon receptor agonist or GLP-1 receptor agonist.
Swallowed ingestible device releasing one or more jets in the small intestine
Trans-epithelially administering a pharmaceutical formulation to the gastrointestinal tract via swallowing an ingestible device containing the pharmaceutical formulation, where the ingestible device is configured for trans-epithelial delivery, and releasing the pharmaceutical formulation from the ingestible device in the small intestine as one or more jets to directly deliver the pharmaceutical formulation to the submucosa of the gastrointestinal tract.
Overall claim coverage centers on trans-epithelial jet delivery from a swallowed ingestible device into the small intestine submucosa, with the therapeutic payload comprising a glucagon receptor agonist or a GLP-1 receptor agonist for treating a disease or condition responsive to these agents.
Stated Advantages
Direct delivery of a therapeutically effective amount of a glucagon receptor agonist or a GLP-1 receptor agonist to the submucosa of the GI tract via trans-epithelial administration using jet release.
Documented Applications
Treatment of a disease or condition responsive to glucagon receptor agonists or GLP-1 receptor agonists using trans-epithelial jet delivery to the small intestine submucosa.
Comparative delivery experiments including swine insulin administered subcutaneously versus intra-jejunal jet delivery, with insulin PK/PD comparisons.
Bioavailability studies in pigs for adalimumab and dulaglutide delivered intraduodenally via a jet device across different internal pressure settings and nozzle configurations.
Ex vivo porcine jejunum submucosal delivery testing using India ink to identify pressure ranges for submucosal delivery.
Drug stability/integrity assessment for adalimumab after jet dispensing.
Mouse PK/PD/toxicity-related experiments including tofacitinib citrate in a DSS-induced colitis mouse model and intracecal antibody delivery using surrogate antibodies via intra-cecal or topical routes.
In vivo disease modeling and pharmacokinetic/pharmacodynamic assessment for jet-based intraluminal/transmucosal delivery in GI disease models, including DSS-induced colitis mice with PK/PD assessment and cytokine inhibition readouts.
Adoptive T-cell transfer chronic colitis model comparing targeted intracecal anti-TNFα and anti-IL12p40 surrogate dosing versus systemic dosing, with outcomes including disease activity index, histopathology scores, lymphocyte reductions, and reductions in inflammatory cytokines.
Pharmacokinetics and bioavailability evaluation of semaglutide after intraduodenal jet delivery in female Yorkshire pigs compared with IV and SC administration.
Pharmacokinetic evaluation of adalimumab in pigs using intraduodenal endoscopic injection needle compared with jet device routes.
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