Massachusetts Institute of Technology

The Brigham and Women's Hospital, Inc.

Lyndra Therapeutics, Inc.

Tokitae LLC

Tyler Grant

Andrew Bellinger

Carlo Giovanni Traverso

Robert Samuel Langer

Shiyi Zhang

Angela DiCiccio

Dean Liang Glettig

Stacy Mo

Mousa Jafari

Lowell L Wood, Jr

Philip Andrew Eckhoff

Rosemary Lynn Kanasty

Erik Robert Waldemar Ryde

Colin R Gardner

Megan Bishoff

Raymond Patrick Knox

Stephen E Zale

Taylor Bensel

Robert S Langer, Jr

Nupura Bhise

Malvika Verma

Ameya R Kirtane

Jung Hoon Yang

David Altreuter

Daniel Minahan

Jacob Freake

Kristofer Kurtin

Robert Debenedictis

Carmi Mandelkern

John Klier

Douglas Sabin

Marlene Schwarz

Omar Abouzid

Sonia Holar

David C Dufour

John James Healy

Benjamin August Rothenberg Peterson

Todd William Roberts

Saumya Moorthy

Nathan Andrew Herrmann

Rosemary Kanasty

Erick Peeke

Colin Gardner

Drug delivery articles, resident articles, and retrieval systems e.g., for gram-level dosing, are generally provided. In some embodiments, the articles are configured for transesophageal administration, transesophageal retrieval, and/or gastric retention to/in a subject. In certain embodiments, the article includes dimensions configured for transesophageal administration with a gastric resident system. In some cases, the article may be configured to control drug release e.g., with zero-order drug kinetics with no potential for burst release for weeks to months. In some embodiments, the articles described herein comprise biocompatible materials and/or are safe for gastric retention. In certain embodiments, the article includes dimensions configured for transesophageal retrieval. In some cases, the articles described herein may comprise relatively large doses of drug (e.g., greater than or equal to 1 gram).

Resident articles for gram-level dosing

Compactable gastric residence systems comprising therapeutic agent formulations for sustained gastric release of therapeutic agents are disclosed, as well as methods and systems for encapsulating such gastric residence systems. The methods and systems for encapsulating the gastric residence systems can be automated from receiving a bulk of gastric residence systems, orienting, placing, compacting, securing, and encapsulating the gastric residence systems.

Encapsulation of gastric residence systems

Provided are stomach simulating devices and methods for simulating a stomach. Stomach simulating devices can comprise a bag-shaped conduit, a mechanical constrictor, and a valve. The conduit can have a body portion, a first diameter at an inlet portion, and a second diameter at an outlet portion, wherein the first diameter at the inlet portion is greater than the second diameter at the outlet portion, the body portion is located between the inlet portion and the outlet portion, and at least a portion of the conduit is curved in a direction from the inlet portion the outlet portion. The mechanical constrictor can he configured to constrict at least a portion of the body portion of the conduit. The valve can be configured to at least partially close a portion of the conduit closer to the outlet portion than the inlet portion of the conduit.

Stomach simulating device

The invention provides gastric residence systems with specifically tailored architectures and methods for making such systems. The components of the gastric residence systems can be manufactured by three-dimensional printing or by co-extrusion. The ability to construct precise architectures for the systems provides excellent control over drug release, in vivo stability, and residence time of the systems.

Materials architecture for gastric residence systems

The invention provides gastric residence systems with configurations and geometrical dimensions that allow for improved shelf life during prolonged storage, and optimal residence properties when the systems are deployed in the stomach of a patient.

Geometric configurations for gastric residence systems

Compactable gastric residence systems comprising therapeutic agent formulations for sustained gastric release of therapeutic agents are disclosed, as well as methods and systems for encapsulating such gastric residence systems. Hie methods and systems for encapsulating the gastric residence systems can be automated from receiving a bulk of gastric residence systems, orienting, placing, compacting, securing, and encapsulating the gastric residence systems.

Gastric residence systems comprising therapeutic agent formulations for sustained gastric release of therapeutic agents are disclosed, as well as methods for using such systems. The systems are characterized by use of a dispersant in the formulations, which improves the burst release characteristics and long-term release rate characteristics of the systems. Milling of therapeutic agent can also be performed to prepare agent particles of desired size.

Gastric residence systems for sustained release of therapeutic agents and methods of use thereof

Certain embodiments comprise administering a residence structure to a subject (e.g., a patient) such that the residence structure is retained at a location internal to the subject for a particular amount of time (e.g., at least about 24 hours) before being released. In certain embodiments, the structure has a modular design, combining a material configured for controlled release of therapeutic, diagnostic, and/or enhancement agents with a structural material necessary for gastric residence but configured for controlled and/or tunable degradation/dissolution to determine the time at which retention shape integrity is lost and the structure passes out of the gastric cavity. For example, in certain embodiments, the residence structure comprises a first elastic component, a second component configured to release an active substance, and, optionally, a linker. In some such embodiments, the linker may be configured to degrade.

Residence structures and related methods

Residence structures, systems, and related methods are generally provided. Certain embodiments comprise administering (e.g., orally) a residence structure to a subject (e.g., a patient) such that the residence structure is retained at a location internal to the subject for a particular amount of time (e.g., at least about 24 hours) before being released. The residence structure may be, in some cases, a gastric residence structure. In some embodiments, the structures and systems described herein comprise one or more materials configured for high levels of active substances (e.g., a therapeutic agent) loading, high active substance and/or structure stability in acidic environments, mechanical flexibility and strength in an internal orifice (e.g., gastric cavity), easy passage through the GI tract until delivery to at a desired internal orifice (e.g., gastric cavity), and/or rapid dissolution/degradation in a physiological environment (e.g., intestinal environment) and/or in response to a chemical stimulant (e.g., ingestion of a solution that induces rapid dissolution/degradation). In certain embodiments, the structure has a modular design, combining a material configured for controlled release of therapeutic, diagnostic, and/or enhancement agents with a structural material necessary for gastric residence but configured for controlled and/or tunable degradation/dissolution to determine the time at which retention shape integrity is lost and the structure passes out of the gastric cavity. For example, in certain embodiments, the residence structure comprises a first elastic component, a second component configured to release an active substance (e.g., a therapeutic agent), and, optionally, a linker. In some such embodiments, the linker may be configured to degrade such that the residence structure breaks apart and is released from the location internally of the subject after a predetermined amount of time.

Certain embodiments involve administering a residence structure to a subject (e.g., a patient) in a constrained configuration, then unconstraining the structure such that it is retained at a location internally of the subject for a period of time. The structure includes a loadable component that can carry an active substance for release internally of the subject.

Certain embodiments involve gastric residence structures which can be administered to a subject (e.g., a patient) in a configuration constrained by a retaining element, and configured to mediate a change in shape when unconstrained by the retaining element to assume a configuration in the stomach in which is retained and unable to pass through the gastric pyloric orifice of the subject under gastrointestinal physiological conditions. The residence structures can be loaded with an agent for release in the stomach.

Growing community of inventors

Arlington, MA, United States of America

Tyler Grant