Massachusetts Institute of Technology

The Invention Science Fund I LLC

The Brigham and Women's Hospital, Inc.

Elwha LLC

Harvard College

The General Hospital Corporation

The Penn State Research Foundation

Other

Novo Nordisk A/s

The Johns Hopkins University

United States of America, As Represented by the Secretary of the Navy

University of California

US Government As Represented by the Secretary of the Army

Tsinghua University

Columbia University

Robert Samuel Langer

Lowell L Wood, Jr

Eric Leuthardt

Roderick A Hyde

Edward K Y Jung

Clarence T Tegreene

Daniel Griffith Anderson

Muriel Y Ishikawa

Omid C Farokhzad

Carlo Giovanni Traverso

Elizabeth A Sweeney

Nathan P Myhrvold

Victoria Y H Wood

Dennis James Rivet, Ii

Edward Stuart Boyden

Michael A Smith

Jeffrey Michael Karp

Daniel Hawkins

Gregory J Della Rocca

Parag Jitendra Parikh

Arturo Jose Vegas

Joshua S Shimony

Terence Myckatyn

Jordin T Kare

Leroy E Hood

Philip Andrew Eckhoff

David A Edwards

John T Santini, Jr

Ed Harlow

Joseph P Vacanti

Alexander M Klibanov

Ulrich Von Andrian

Michael John Cima

W Daniel Hillis

Abraham J Domb

William Henry Gates, Iii

Justin Scot Hanes

Robert W Lord

Norman F Sheppard, Jr

Peter L Hagelstein

Edith Mathiowitz

David M Lynn

Daniel S Kohane

Klavs F Jensen

Robert J Linhardt

Charles Whitmer

Eyal S Ron

Mark A Malamud

Royce A Levien

John D Rinaldo, Jr

Hon Wah Chin

Erez Lieberman

Cato T Laurencin

Harry R Allcock

Abraham Domb

Chung Chang Young

James C Weaver

Michael Scott Williams

Mahalaxmi Gita Bangera

Stephen L Malaska

Moses J Folkman

Andreas Lendlein

Elazer Reuven Edelman

Daniel R Deaver

Yadong Wang

Joachim B Kohn

Kam W Leong

Stephen Jack Herman

Mark R Prausnitz

Gordana Vunjak-Novakovic

Guillermo A Ameer

Alexander H Slocum, Jr

Donald Elliot Ingber

Jeffrey T Borenstein

David J Mooney

Ram Sasisekharan

Charles M Lieber

Howard Bernstein

Akin Akinc

Scott Albert Uhland

Stephen E Zale

Donald E Chickering, Iii

Ganesh Venkataraman

Jennifer H Elisseeff

George M Church

Alistair K Chan

Anthony Atala

David R Walt

Noubar Boghos Afeyan

Marc Steven Weinberg

Darrell J Irvine

Eleanor V Goodall

Douglas Adam Levinson

Christine E Schmidt

Stephen J Lippard

Paula T Hammond

Rakesh K Jain

Richard C Mulligan

Ramin Haghgooie

Hidde L Ploegh

The present application provides compositions and methods for determining a disease or condition in a subject. The method comprises contacting a body fluid with a molecule comprising a reporter thereof and the reported is cleaved by an agent in the body fluid. Diseases and conditions that can be determined by the method are also described.

Ex vivo protease activity detection for disease detection/diagnostic, staging, monitoring and treatment

Disclosed is a pharmaceutical container comprising a lumen defined in part by a wall, the wall having an interior surface facing the lumen, an outer surface, and a coating set on the interior surface comprising a pH protective layer, wherein the pH protective layer is applied using atomic layer deposition.

Pharmaceutical container with pH protective layer deposited by atomic layer deposition

Systems and methods related to reconfigurable medical devices are described. In some embodiments, a reconfigurable medical device may include a central core and a plurality of arms. The arms may be rotatably coupled to the central core such that the plurality of arms may rotate outwards away from the central core to selectively reconfigure the reconfigurable device between a retracted configuration and an expanded configuration. In an initial state, the arms may be biased outwards away from the central core into the expanded configuration. When the reconfigurable device is exposed to a temperature greater than a threshold temperature, the arms may be biased towards the central core into the retracted configuration. In some embodiments, a reconfigurable medical device may include therapeutic compound-loaded needles coupled to distal portions of the arms.

Thermally controlled reconfigurable medical devices

Self-righting articles, such as self-righting capsules for administration to a subject, are generally provided. In some embodiments, the self-righting article may be configured such that the article may orient itself relative to a surface. In some embodiments, the self-righting article may have a particular shape and/or distribution of density (or mass) which, for example, enables the self-righting behavior of the article. In some embodiments, the self-righting article may comprise a tissue interfacing component and/or a pharmaceutical agent. In some cases, upon contact of the tissue with the tissue engaging surface of the article, the self-righting article may be configured to release one or more tissue interfacing components. In some cases, the tissue interfacing component may comprise and/or be associated with the pharmaceutical agent.

Self-righting systems, methods, and related components

Products, such as devices, prostheses, and materials, whose surfaces have been modified in order to impart beneficial properties to these products are disclosed. The surface-modified products have improved biocompatibility compared to a corresponding product that lacks the modification. Following implantation in a subject, the surface-modified products induce a lower foreign-body response, compared to a corresponding unmodified product.

Materials with improved biocompatibility

Articles and methods for delivering a therapeutic agent to a subject are described. These articles and methods may be useful, in some cases, for the delivery of therapeutic agents to the colon of a subject. In some embodiments, an article is configured to release a secretion inducing agent e.g., to stimulate the release of intestinal fluids. The article, in some embodiments, comprises a therapeutic agent such that the stimulated release of intestinal fluid increases the amount of therapeutic agent available for absorption by the colon. For example, in some embodiments, the articles and methods described herein advantageously promote increased absorption of therapeutic agents in subjects as compared to traditionally administered therapeutic agents without additional components such as a secretion inducing agent. In some embodiments, articles and methods described herein may increase the motility of the colon of a subject. The increase in contractions and movement of fluidic in the colon caused by increase motility may advantageously facilitate the dissolution or absorption of the therapeutic agent.

Articles and methods for administration of therapeutic agents

Drug delivery articles, resident articles, and retrieval systems e.g., for gram-level dosing, are generally provided. In some embodiments, the residence articles are configured for transesophageal administration, transesophageal retrieval, and/or gastric retention to/in a subject. In certain embodiments, the residence article includes dimensions configured for transesophageal administration with a gastric resident system. In some cases, the residence 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 residence articles described herein comprise biocompatible materials and/or are safe for gastric retention. In certain embodiments, the residence article includes dimensions configured for transesophageal retrieval. In some cases, the residence articles described herein may comprise relatively large doses of drug (e.g., greater than or equal to 1 gram).

Gastroretentive articles for alcohol sensing

Gene editing can be performed by introducing gene-editing components into a cell by mechanical cell disruption. Related apparatus, systems, techniques, and articles are also described.

Gene editing through microfluidic delivery

A drug delivery device for administration to a subject is provided. In some embodiments, the drug delivery device includes a reservoir containing an active pharmaceutical ingredient and a potential energy source. The drug delivery device also includes a trigger operatively associated with the potential energy source, where the trigger is configured to actuate at a predetermined location within the subject. The drug delivery device also includes a rupturable membrane disposed along a flow path extending between the reservoir and an outlet, where the membrane is configured to rupture when the trigger is actuated. Once the trigger is actuated, the potential energy from the potential energy source may be released to expel the active pharmaceutical ingredient in a jet through the outlet.

Drug delivery device

Covalently modified alginate polymers, possessing enhanced biocompatibility and tailored physiochemical properties, as well as methods of making and use thereof, are disclosed herein. The covalently modified alginates are useful as a matrix for coating of any material where reduced fibrosis is desired, such as encapsulated cells for transplantation and medical devices implanted or used in the body.

Modified alginates for anti-fibrotic materials and applications

Components with relatively high loading of active pharmaceutical ingredients (e.g., drugs), are generally provided. In some embodiments, the component (e.g., a tissue interfacing component) comprises a solid therapeutic agent (e.g., a solid API) and a supporting material (e.g., a binder such as a polymer) such that the solid therapeutic agent is present in the component in an amount of greater than or equal to 10 wt % versus the total weight of the tissue interfacing component. Such tissue-interfacing components may be useful for delivery of API doses e.g., to a subject. Advantageously, in some embodiments, the reduction of volume required to deliver the required API dose as compared to a liquid formulation permits the creation of solid needle delivery systems for a wide variety of drugs in a variety of places/tissues (e.g., tongue, GI mucosal tissue, skin) and/or reduces and/or eliminates the application of an external force in order to inject a drug solution through the small opening in the needle. In some cases, a physiologically relevant dose may be present in a single tissue interfacing component (e.g., having a relatively high API loading).

Components with high API loading

Self-righting articles, such as self-righting capsules for administration to a subject, are generally provided. In some embodiments, the self-righting article may be configured such that the article may orient itself relative to a surface (e.g., a surface of a tissue of a subject). The self-righting articles described herein may comprise one 5 or more tissue engaging surfaces configured to engage (e.g., interface with, inject into, anchor) with a surface (e.g., a surface of a tissue of a subject). In some embodiments, the self-righting article may have a particular shape and/or distribution of density (or mass) which, for example, enables the self-righting behavior of the article. In certain embodiments, the self-righting article a tissue 10 interfacing components. In some embodiments, each tissue-interfacing component may comprise an electrically-conductive portion configured for electrical communication with tissue and an insulative portion configured to not be in electrical communication with tissue.

Systems for electrical stimulation

Self-righting articles, such as self-righting capsules for administration to a subject, are generally provided. In some embodiments, the self-righting article may be configured such that the article may orient itself relative to a surface (e.g., a surface of a tissue of a subject). The self-righting articles described herein may comprise one or more tissue engaging surfaces configured to engage (e.g., interface with, inject into, anchor) with a surface (e.g., a surface of a tissue of a subject). In some embodiments, the self-righting article may have a particular shape and/or distribution of density (or mass) which, for example, enables the self-righting behavior of the article. In some embodiments, the self-righting article may comprise a tissue interfacing component and/or a pharmaceutical agent (e.g., for delivery of the active pharmaceutical agent to a location internal of the subject). In some cases, upon contact of the tissue with the tissue engaging surface of the article, the self-righting article may be configured to release one or more tissue interfacing components. In some cases, the tissue interfacing component is associated with a self-actuating component. For example, the self-righting article may comprise a self-actuating component configured, upon exposure to a fluid, to release the tissue interfacing component from the self-righting article. In some cases, the tissue interfacing component may comprise and/or be associated with the pharmaceutical agent (e.g., for delivery to a location internal to a subject).

Self-righting systems and related components and methods

Methods and compositions for determining multiplex interactions between drugs and drug transporters using an intestinal tissue explant are provided.

Ex vivo system for determining multiple drug-drug transporter interactions and methods of use thereof

Growing community of inventors

Newton, MA, United States of America

Robert Samuel Langer