Devices, Assemblies, and Methods for Delivering Fluid Formulations Inside the Gastrointestinal Tract - Patent application

Abstract

A delivery assembly for an ingestible device for delivering a fluid formulation into a GI tract lumen wall or surrounding tissue of a subject includes a housing, a piston, a needle, a conduit, and a valve member. The housing defines a piston chamber. The piston is movably disposed within the piston chamber. The needle is coupled to or integrally formed with the piston. The conduit is configured to direct the fluid formulation from a fluid source to the needle. The valve member has a first state and a second state. In the first state, the valve member substantially prevents flow of the fluid formulation from the conduit to the needle. In the second state, the valve member is configured to allow flow of the fluid formulation through the conduit to the needle.

Description

[Technical field]

[0001] (CROSS REFERENCE TO RELATED APPLICATIONS) This application claims the benefit of and priority to U.S. Provisional Application No. 63 / 312,352, filed February 21, 2022, the entire contents of which are incorporated herein by reference. [Background technology]

[0002] Therapeutic agents, such as drugs, can be administered to subjects (patients) by ingestion or parenteral injection (e.g., subcutaneously, intramuscularly, or intravenously) to provide a desired therapeutic effect. However, these routes of administration have several drawbacks. For example, some therapeutic agents, such as molecules with large molecular weights (macromolecules), are not suitable for delivery by ingestion due to enzymatic degradation of these molecules in the gastrointestinal (GI) tract of the subject. Other types of therapeutic agents are poorly tolerated in the GI tract and have low systemic uptake. In the case of parenteral injections, subjects may experience pain and inconvenience that significantly impact compliance and quality of life.

[0003] To address these shortcomings, ingestible devices have been proposed for orally administering solid dosage forms of therapeutic agents to the luminal wall of the GI tract or surrounding tissue.However, solid dosage forms may be limited to relatively small dosage amounts (e.g., a few milligrams).Therefore, the use of solid dosage forms may be disadvantageous for treatment regimens that require higher dosage amounts, for example, for reasons of administration frequency, convenience, or cost.

[0004] Thus, there is a need for devices that can deliver a wide range of dosages of therapeutic agents and that can address one or more of the shortcomings associated with traditional oral and parenteral administration routes. Summary of the Invention [Problem to be solved by the invention]

[0005] Embodiments of the present disclosure generally relate to devices, assemblies, and methods for delivering a fluid formulation to the GI tract (e.g., the GI luminal wall or surrounding tissues) of a subject. The devices and assemblies are configured to deliver up to about 400 microliters (μL) or more of a fluid formulation, which may include up to about 100 milligrams (mg) or more of at least one therapeutic agent. In this manner, the disclosed devices, assemblies, and methods can enable efficient delivery of a wide range of dosages of a therapeutic agent for most treatment regimens. [Means for solving the problem]

[0006] In one aspect, a delivery assembly for an ingestible device for delivering a fluid formulation to a GI tract lumen wall or surrounding tissue of a subject includes a housing, a piston, a needle, a conduit, and a valve member. The housing defines a piston chamber. The piston is movably disposed in the piston chamber. The needle is coupled to or integrally formed with the piston. The conduit is configured to direct the fluid formulation from a fluid source to the needle. The valve member has a first state and a second state. In the first state, the valve member substantially prevents flow of the fluid formulation from the conduit to the needle. In the second state, the valve member is configured to allow the fluid formulation to flow through the conduit to the needle.

[0007] In another aspect, an ingestible device for delivering a fluid formulation to a GI luminal wall or surrounding tissue of a subject includes an expandable member, a container, a fluid formulation, and a delivery assembly. The container is disposed within the expandable member. The fluid formulation is disposed in the container and includes at least one therapeutic agent. The delivery assembly is coupled to or disposed on the expandable member. The delivery assembly includes a housing, a piston, a needle, a conduit, and a valve member. The housing defines a piston chamber. The piston is movably disposed in the piston chamber. The needle is coupled to or integrally formed with the piston. The conduit is configured to direct the fluid formulation from the container to the needle. The valve member is operably coupled to the conduit and has a first state and a second state. In the first state, the valve member substantially prevents flow of the fluid formulation from the conduit to the needle. In the second state, the expandable member moves the piston relative to the housing to release the valve member from the conduit and allow the fluid formulation to flow from the container to the needle.

[0008] In another aspect, a method of delivering a fluid formulation to a GI luminal wall or surrounding tissue of a subject includes ingesting, by the subject, an ingestible device described herein. The ingestible device includes an expandable member, a container, a fluid formulation, and a delivery assembly. The container is disposed within the expandable member. The fluid formulation is disposed in the container and includes at least one therapeutic agent. The delivery assembly is coupled to and disposed on the expandable member. The delivery assembly includes a housing, a piston, a needle, a conduit, and a valve member. The housing defines a piston chamber. The piston is movably disposed in the piston chamber. The needle is coupled to or integrally formed with the piston. The conduit is configured to direct the fluid formulation from the container to the needle. The valve member is operably coupled to the conduit and has a first state and a second state. In the first state, the valve member substantially prevents flow of the fluid formulation from the conduit to the needle. In the second condition, the expandable member moves the piston relative to the housing to release the valve member from the conduit and allow the fluid formulation to flow from the container to the needle.

[0009] In another aspect, use of an ingestible device to deliver a fluid formulation to a GI luminal wall or surrounding tissue of a subject includes the subject ingesting an ingestible device described herein. The ingestible device includes an expandable member, a container, a fluid formulation, and a delivery assembly. The container is disposed within the expandable member. The fluid formulation is disposed in the container and includes at least one therapeutic agent. The delivery assembly is coupled to and disposed on the expandable member. The delivery assembly includes a housing, a piston, a needle, a conduit, and a valve member. The housing defines a piston chamber. The piston is movably disposed in the piston chamber. The needle is coupled to or integrally formed with the piston. The conduit is configured to direct the fluid formulation from the container to the needle. The valve member is operably coupled to the conduit and has a first state and a second state. In the first state, the valve member substantially prevents flow of the fluid formulation from the conduit to the needle. In the second condition, the expandable member moves the piston relative to the housing to release the valve member from the conduit and allow the fluid formulation to flow from the container to the needle.

[0010] In another aspect, a method of preparing an ingestible device for delivering a therapeutic agent to a GI tract lumen wall or surrounding tissue of a subject is provided, the method comprising loading a fluid formulation comprising a therapeutic agent into a delivery assembly described herein.

[0011] In one or more embodiments of any of the aforementioned aspects, the valve member is releasably coupled to the conduit, and the valve member is configured to release from the conduit in response to movement of the piston to allow the fluid formulation to flow through the conduit to the needle in the second state.

[0012] In one or more embodiments of any of the aforementioned aspects, at least a portion of the conduit defines a valve member, and the conduit is configured to open in response to pressure of the fluid formulation to allow the fluid formulation to flow through the conduit to the needle in the second state.

[0013] In one or more embodiments of any of the aforementioned aspects, the device further includes an ingestible enclosure, wherein the expandable member and the delivery assembly are disposed in the ingestible enclosure for delivery to the GI tract of the subject.

[0014] In one or more embodiments of any of the aforementioned aspects, the piston is configured to move in response to gas pressure generated within the expandable member to advance the needle from the housing and into the GI lumen wall while the valve member is in the first state.

[0015] In one or more embodiments of any of the preceding aspects, the container is configured to expel the fluid formulation through the conduit and to the needle in the second state in response to gas pressure applied to an exterior surface of the container.

[0016] In one or more embodiments of any of the aforementioned aspects, the container defines a volume containing up to about 400 μL of fluid.

[0017] In one or more embodiments of any of the aforementioned aspects, the container defines a volume containing between about 50 μL and about 300 μL of fluid.

[0018] In one or more embodiments of any of the preceding aspects, the valve member includes a cover coupled to the housing, the cover defining an opening and a flexible leg extending into the opening.

[0019] In one or more embodiments of any of the aforementioned aspects, the piston includes a shaft, and a portion of the conduit and a portion of the shaft each extend through the opening in the cover such that the shaft biases the flexible legs against the conduit to substantially impede flow of the fluid formulation through the conduit in a first state. In one or more embodiments, the piston moves relative to the housing to move the shaft away from the cover and unbias the flexible legs away from the conduit, thereby allowing flow of the fluid formulation to the needle in a second state.

[0020] Alternatively, in one or more embodiments of any of the aforementioned aspects, the piston includes a shaft, and at least a portion of the conduit or the shaft extends through an opening in the cover, and the clip is disposed outside the piston chamber adjacent the release feature. In one or more embodiments, the piston moves relative to the housing to move the clip toward the cover, whereby the release feature releases the clip from the conduit, thereby allowing the fluid formulation to flow to the needle in the second state.

[0021] In one or more embodiments of any of the aforementioned aspects, the valve member includes a clip releasably coupled to the conduit, the clip, in a first state, substantially preventing flow of the fluid formulation through the conduit.

[0022] In one or more embodiments of any of the aforementioned aspects, the delivery assembly further includes a cover coupled to the housing, the cover defining an opening and a release mechanism.

[0023] In one or more embodiments of any of the aforementioned aspects, the valve member includes one of a sleeve, a clip, or a band releasably coupled to the conduit such that in a first condition, a portion of the conduit is held in a temporarily kinked condition to substantially prevent flow of the fluid formulation through the conduit.

[0024] In one or more embodiments of any of the aforementioned aspects, the piston moves relative to the housing to create tension in the conduit such that the sleeve, clip, or band is released from the conduit, thereby allowing the fluid formulation to flow to the needle in a second state.

[0025] In one or more embodiments of any of the aforementioned aspects, at least a portion of the conduit defines a valve member and is formed at least in part from a thermosetting polymer that defines a temporary seal within the conduit to substantially prevent flow of the fluid formulation through the conduit in a first state. In one or more embodiments, pressure of the fluid formulation overcomes the temporary seal, thereby allowing the fluid formulation to flow through the conduit to the needle in a second state.

[0026] In one or more embodiments of any of the preceding aspects, the at least one therapeutic agent is one or more selected from an immunosuppressant, a chemotherapeutic agent, a central nervous system (CNS) drug, an antidiabetic drug, an enzyme replacement therapy (ERT) drug, an antibody, a hormone, insulin, an incretin, or a combination thereof, or an oligonucleotide.

[0027] The foregoing general description and the following detailed description are provided by way of example only and are intended to provide further explanation of the present disclosure as set forth in the claims, without limiting the scope of the disclosure or the claims. Other objects, advantages, and novel features will be readily apparent to those skilled in the art from the following brief description of the drawings and detailed description of the present disclosure. [Brief description of the drawings]

[0028] [Figure 1] FIG. 1 is a block diagram illustrating one embodiment of a device for delivering a fluid formulation to a subject. [Diagram 2] FIG. 2 is a cross-sectional view of one embodiment of the device of FIG. [Diagram 3] FIG. 3 is a detailed view of a portion of the device of FIG. [Figure 4] FIG. 4 is a cross-sectional view taken along line 4-4 of FIG. [Diagram 5] FIG. 5 is a cross-sectional view taken along line 5-5 of FIG. [Figure 6]FIG. 6 shows the device of FIG. 3 in a second state when it has reached a desired location within the GI tract for delivering a fluid formulation. [Figure 7] FIG. 7 is a cross-sectional view taken along line 7-7 of FIG. [Figure 8] FIG. 8 shows an embodiment of the conduit and vessel of the device of FIG. [Figure 9] FIG. 9 is a cross-sectional view of another embodiment of the device of FIG. [Figure 10] FIG. 10 shows the device of FIG. 9 in a second state when it has reached a desired location within the GI tract for delivering a fluid formulation. [Figure 11] FIG. 11 is a cross-sectional view of an alternative embodiment of the device of FIG. [Figure 12] FIG. 12 illustrates the device of FIG. 11 in a second state when it reaches a desired location within the GI tract for delivery of a fluid formulation. [Figure 13] FIG. 13 illustrates a method of delivering a fluid formulation to the interior of the GI tract using the devices and assemblies of the present disclosure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0029] Before describing the details of the devices, assemblies, and methods of the present disclosure, some conventions are provided for the convenience of the reader.

[0030] As used in this disclosure, the terms "eg," "such as," "for example," "for an example," "for another example," "example of," "by way of example," and "etc." indicate that a list of one or more non-limiting example(s) is preceded or followed, and it is to be understood that other unlisted examples are within the scope of the disclosure.

[0031] As used herein, the singular terms "a," "an," and "the" may include plural references unless the context clearly dictates otherwise. Additionally, the singular terms "a," "an," and "the" do not mean "one and only one" unless expressly stated otherwise, but rather "one or more."

[0032] As used herein, a phrase in the form "A / B" or in the form "A and / or B" means (A), (B), or (A and B), and a phrase in the form "at least one of A, B, or C" means (A), (B), (C), (A and B), (A and C), (B and C), or (A, B, and C).

[0033] The term "in one embodiment" or variations thereof (e.g., "in another embodiment" or "in one embodiment") is used herein to refer to use in one or more embodiments and does not in any way limit the scope of the disclosure to only the embodiments shown and / or described. Thus, components illustrated and / or described herein with respect to an embodiment can be omitted or used in another embodiment (e.g., another embodiment illustrated and described herein, or another embodiment within the scope of the disclosure but not illustrated and / or described herein).

[0034] As used herein, the term "component" refers to one item of a set of one or more items that collectively constitute the device, composition, or system under discussion. A component may be a solid, powder, gel, plasma, fluid, gas, or other configuration. For example, a device may include multiple solid components that are assembled together to constitute the device and may further include a fluid component disposed within the device. As another example, a composition may include a single component, or two or more components that are mixed together to make the composition. A composition may be in the form of a fluid, slurry, powder, or solid (e.g., in a compacted or combined form such as a tablet or microtablet). A device or system may include one or more compositions and / or one or more other components.

[0035] The term “design” or grammatical variations thereof (e.g., “designing” or “designed”), as used herein, refers to features that are intentionally built into a device based on, for example, estimates of tolerances (e.g., component tolerances and / or manufacturing tolerances) and estimates of the environmental conditions that are expected to be encountered (e.g., temperature, humidity, external or internal ambient pressure, external or internal mechanical pressure, stress due to external or internal mechanical pressure, or, if introduced into the body, physiology, body chemistry, biological composition). It is understood that different components, devices, compositions, or systems with identical designs may have different actual values ​​for these properties, since internal ambient pressure, external or internal mechanical pressure, stress from external or internal mechanical pressure, age or shelf life of the product, or if introduced into the body, physiology, body chemistry, biological composition of body fluids or tissues, chemical composition of body fluids or tissues, pH, species, diet, health, sex, age, ancestry, disease, or tissue damage), actual tolerances and environmental conditions before and / or after delivery may affect the properties. Design also includes pre- or post-manufacturing changes or modifications.

[0036] The term "structured" or grammatical variations thereof (e.g., "structure" or "structuring"), as used herein, refers to a component, device, composition, or system that is produced according to a concept or design, or variations or modifications thereof (whether such variations or modifications occur before, during, or after production), regardless of whether such concept or design is described in writing.

[0037] As used herein, the term "body" refers to an animal body, unless the context clearly indicates otherwise.

[0038] As used herein, the term "subject" refers to a body to which an embodiment of the present disclosure is delivered or is intended to be delivered. For example, with respect to a human, a subject may be a patient receiving treatment from a medical professional. The terms "individual," "subject," and "patient" may be used interchangeably herein and refer to any individual animalia subject (e.g., bovine, canine, feline, equine, or human). In certain embodiments, the subject, individual, or patient is a human.

[0039] The term "fluid" as used herein refers to a liquid or gas, and includes water and humidity. The term "fluidic environment" as used herein refers to an environment in which one or more fluids are present.

[0040] The term "ingest" or grammatical variations thereof (e.g., "ingesting," "ingestion," or "ingested"), as used herein, refers to taking into the stomach, whether by swallowing or by other means of deposition into the stomach (e.g., deposition into the stomach by an endoscope or via a port).

[0041] The term "degrade" or grammatical variations thereof (e.g., "degrading," "degraded," "degradable," and "degradation"), as used herein, refers to weakening, partial degradation, or complete breakdown, such as by dissolution, chemical degradation (including biodegradation), breakdown, chemical modification, mechanical degradation, or disintegration, including, but not limited to, dissolving, crumbling, deformation, withering, or shrinking. The term "non-degradable" means that in the expected environment, at least for the expected period of time, degradation is minimal or within some acceptable design rate.

[0042] The term "degradation rate" or grammatical variations thereof (e.g., "rate of degradation"), as used herein, refers to the rate at which a material breaks down. The designed degradation rate of a material in certain embodiments can be defined by the rate at which the material is expected to degrade under the conditions (e.g., physiological conditions) expected at the target delivery site. The designed degradation time for certain embodiments can refer to the designed time to complete degradation or the designed time to partial degradation sufficient to achieve the design objective (e.g., breach). Thus, for example, the designed degradation time can be component specific and / or specific to the conditions expected at the target delivery site. The designed degradation time can be short or long and can be defined in terms of an approximate time, a maximum time, or a minimum time.

[0043] As used herein, the term "substantially" is used to describe and take into account small variations that may result, for example, from manufacturing or assembly processes. For example, when used with a numerical value, the term can refer to a variation in the numerical value of ±10% or less.

[0044] As used herein, the term "lumen" refers to the interior space of a tubular structure. Examples of lumens in the body include arteries, veins, lumens within organs, etc.

[0045] The term "lumen wall" means the wall of a lumen, and includes all layers of the lumen from the inner periphery to the outer periphery. For example, with respect to a lumen in the body, it includes the mucosa, submucosa, muscularis, serosa, the outer wall of the lumen, and the blood vessels and tissues that constitute it.

[0046] As used herein, the term "gastrointestinal tract" or "GI tract" refers to the intake / excretion system of the body including, for example, the mouth, pharynx, esophagus, stomach, pylorus, small intestine, cecum, large intestine, colon, rectum, anus, and the valves or sphincters between them.

[0047] The term "GI lumen" generally refers to any lumen of the GI tract (eg, the lumen of the esophagus, stomach, small intestine, large intestine, colon), and the term "GI lumen wall" refers to the luminal wall of the GI lumen.

[0048] As used herein, the terms "comprising," "comprise," "comprises," "includes," and "including" are intended to mean that the compositions and methods include the recited elements, but do not exclude other elements.

[0049] Referring generally to the drawings, disclosed herein are embodiments of devices, assemblies, and methods for delivering a fluid formulation to the luminal wall or surrounding tissues (e.g., the peritoneum or peritoneal cavity) of a subject's GI tract. The devices are advantageously configured to substantially preserve one or more therapeutic agents in the fluid formulation within the GI lumen for delivery within the luminal wall or surrounding tissues. Delivery to the luminal wall or surrounding tissues may allow for systemic uptake of one or more therapeutic agents in the fluid formulation. Additionally, the fluid form of the formulation may allow for delivery of a wide range of dosages (e.g., up to about 100 mg or more) of one or more therapeutic agents for most treatment regimens. As described below, the disclosed devices and assemblies can deliver a variety of different types of therapeutic agents, such as macromolecules that are not typically suitable for delivery by ingestion. In this manner, the disclosed devices, assemblies, and methods can address many of the shortcomings associated with traditional oral and parenteral routes of administration.

[0050] 1 illustrates, in block diagram form, an example of a device 100 in accordance with one or more embodiments of the present disclosure. The device 100 includes an enclosure 102, an optional outer coating 104, an expandable member 106, a release 108, a reservoir 110, a fluid formulation 112, a conduit 114, a valve member 116, and a delivery assembly 118. The delivery assembly 118 includes at least a housing 120, a piston 122, and a needle 124.

[0051] According to a non-limiting example, the housing 102 (or optionally the housing 102 and / or the outer coating 104) can be degraded at a desired location within the subject's GI tract (e.g., stomach or small intestine) for delivery of the fluid formulation 112, as described in more detail below. In response to at least partial degradation of the housing 102 and / or the outer coating 104, the release means 108 is actuated to cause a chemical reaction within the expandable member 106 that results in the formation of a gas for inflating the expandable member 106, as described in more detail below. Expansion of the expandable member 106 within the GI lumen places the delivery assembly 118 in close proximity (e.g., adjacent or in contact with) the lumen wall. When the internal pressure generated by the gas within the expandable member 106 reaches a threshold value (e.g., upon full or partial expansion of the expandable member 106), the pressure moves the piston 122 relative to the housing 120 to advance the needle 124 from the housing 120 into the GI lumen wall. Internal pressure created by the gas is also applied to the container 110 before the valve member 116 is released or opened. In response to sufficient movement of the needle 124 (e.g., when the needle 124 penetrates the GI lumen wall), the valve member 116 releases from or otherwise opens the conduit 114 to allow the fluid formulation 112 to flow from the container 110, through the needle 124, and into the GI lumen wall or surrounding tissue, where one or more therapeutic agents of the fluid formulation 112 can be released into the subject's bloodstream.

[0052] In another non-limiting example, as described in further detail below, at least a portion of the conduit 114 may itself function as the valve member 116. In this embodiment, the conduit 114 / valve member 116 opens in response to a threshold pressure applied against the container 110, allowing the fluid formulation 112 to flow through the conduit 114 to the needle 124 and into the GI lumen wall or surrounding tissue.

[0053] The housing 102 and optional outer coating 104, if provided, are configured to allow ingestion of the device 100 and temporarily protect the contents of the device 100 from degradation within one or more portions of the GI tract of a subject. The housing 102 can take a variety of different forms and shapes, such as a swallowable capsule (e.g., a size 00 capsule, a size 000 capsule, or other size capsule) or any other structure suitable for ingestion by a subject and capable of housing or containing one or more of the components of the device 100 (e.g., at least the expandable member 106, the release means 108, the reservoir 110, the conduit 114, the valve member 116, and the delivery assembly 118, as described below). In one or more embodiments, the housing 102 includes two or more sections that are joined (e.g., press-fit) together to define the housing 102. For example, the housing 102 may be configured as a capsule that includes a first section that at least partially overlaps a second section in a press-fit arrangement to define the housing 102. The first and second portions may be removably coupled to allow for separation of the two portions. In one or more embodiments, the expandable member 106, the release means 108, the container 110, the fluid formulation 112, the conduit 114, the valve member 116, and the delivery assembly 118 are each configured to be contained within the interior of the housing 102. The release means 108 may optionally be located outside of the interior of the housing 102, such as on an exterior portion of the housing 102.

[0054] In one or more embodiments, the housing 102 can degrade under certain conditions. Additionally, different portions of the housing 102 can be configured to degrade under different conditions or at different degradation rates depending on the target site in the GI tract for delivery of the fluid formulation 112. For example, some or all of the housing 102 may be constructed of a material that degrades in water (e.g., in the presence of water in the form of humidity or moisture in the surrounding environment, such as within the body) and / or when exposed to a pH level above a certain threshold or within a certain range, such as a pH level associated with a target site in the GI tract for delivery of the fluid formulation 112.

[0055] An optional outer coating 104 optionally covers some or all of the housing 102. The outer coating 104 may include a single layer or multiple layers. The various layers may be formed of the same material or a combination of different materials. In one or more embodiments, the outer coating 104 may degrade under certain conditions, as described above with reference to the housing 102. One example of an outer coating 104 is an enteric coating, such as an enteric coating that degrades at a predetermined rate in water and / or an enteric coating that degrades when exposed to a solution having a pH level above a certain threshold or within a certain range. Another example of an outer coating 104 is a protective coating (e.g., a wax), such as a coating that protects a portion of the outer surface of the housing 102 from contact with fluids or tissues (e.g., bodily tissues or fluids).

[0056] In one or more embodiments, degradation of the housing 102 and / or outer coating 104 allows fluids (e.g., gastric or intestinal fluids) to enter the interior of the housing 102 / outer coating 104 and activate the release means 108. Alternatively, the release means 108 may be located on an exterior portion of the housing 102, and degradation of the outer coating 104 may expose the release means 108 to a surface of the housing 102 to facilitate activation of the release means 108. Alternatively, the release means 108 may be located in a portion of the housing 102 that is not exposed to the outer coating 104, and the release means 108 may be structured to degrade at a different rate than the housing 102 and / or under different conditions within the GI tract.

[0057] The housing 102 and / or the outer coating 104 may define one or more degradation regions for localized degradation of the housing 102 and / or the outer coating 104, for example, to enable controlled degradation and detachment of the housing 102. For example, the outer coating 104 may be selectively applied only to certain regions of the housing 102 (e.g., ends of the housing 102) to expose selected portions of the housing 102 (e.g., a mid-portion of the housing 102 between the ends), thereby defining regions of the housing 102 that can degrade at a faster rate and / or degrade faster than other regions of the housing 102. This controlled degradation of the housing 102 allows for more consistent detachment of the housing 102 to enable delivery of the fluid formulation 112 from the delivery assembly 118 into the GI lumen wall.

[0058] The expandable member 106 is a flexible, adjustable structure. In one or more embodiments, the expandable member 106 is configured to expand from a collapsed state (e.g., folded, rolled, flattened) to an expanded state within a desired location of the GI lumen for delivery of the fluid formulation 112. The expandable member 106 may have a variety of different shapes, sizes, and configurations for temporary storage in the housing 102 and deployment within the lumen of the subject's GI tract. The expandable member 106 may be configured as a balloon, a bellows / accordion structure, or any other structure that is adjustable from a collapsed state to an expanded state.

[0059] The expandable member 106 defines an interior volume for containing various components of the device 100. For example, the expandable member 106 can include (e.g., contain) one or more reactants that are temporarily separated from one another within the interior volume. The interior volume is configured to facilitate a chemical reaction caused by mixing the reactants together (e.g., in response to actuation of the release means 108) to form a gas that causes expansion of the expandable member 106. The expandable member 106 can further include structure for contracting the expandable member 106 upon delivery of the fluid formulation 112 to facilitate excretion of the expandable member 106 from the subject. The expandable member 106 is configured to stretch a prescribed amount without perforating upon expansion.

[0060] The expandable member 106 can be formed from one or more materials. Examples of suitable materials for the expandable member 106 include hydroxypropyl methylcellulose (HPMC), polyvinyl acetate (PVA), lactide, glycolide, lactic acid, glycolic acid, per-dioxanone, trimethylene carbonate, caprolactone, and mixtures and copolymers thereof. The expandable member 106 can include one or more layers of material. The expandable member 106 can be a monolithic structure. In other embodiments, the expandable member 106 can be composed of one or more sections that are joined together (e.g., sealed or sutured).

[0061] The release means 108 is a chemical, mechanical, electrical, electromechanical, electrochemical, chemical-mechanical, or electromechanical-chemical structure. The release means 108 is a structure that causes expansion of the expandable member 106 upon actuation of the release means 108. In one or more embodiments, the release means 108 is configured to be actuated (e.g., degrade, release, move, open) in response to conditions in the GI tract. For example, the release means 108 may be configured to degrade in water such that the release means 108 degrades upon contact with liquids in the GI tract. As another example, the release means 108 may be configured to degrade above a particular pH level or within a range of pH levels associated with a location in the GI tract (e.g., stomach pH, ​​intestinal pH). In these and other embodiments, the release means 108 may be made from a biodegradable material, such as an enteric material. Additionally or alternatively, the release means 108 may be configured as a latch, clip, cover, plug, coating, or any other structure that moves, opens, or otherwise releases in response to conditions in the GI tract. The release means 108 may be comprised of a single material or a combination of materials. In embodiments in which multiple components are included in the release means 108, the components may be co-located (e.g., coaxial) or may be physically separated from one another.

[0062] The container 110 is a flexible structure that defines an interior volume for containing the fluid formulation 112. The interior volume can contain up to about 400 μL or more of fluid, including 400 μL of fluid. For example, the interior volume can contain about 50 μL to about 300 μL of fluid, such as 50 μL, 100 μL, 150 μL, 200 μL, 250 μL, or 300 μL of fluid, or any value therebetween, or 300 μL, 350 μL, or 400 μL of fluid, or any value therebetween. The container 110 is further configured to be received within the expandable member 106. The container 110 can have any suitable shape, such as spherical, cubic, ellipsoidal, or other shape. The container 110 is further configured to expel the fluid formulation 112 from the interior volume in response to pressure applied to the exterior surface of the container 110 (e.g., pressure from a gas generated within the expandable member 106). The container 110 may be formed from or may include a flexible or pliable material to allow deformation of the container 110 (e.g., shrinking by squeezing) to expel the fluid formulation 112. Examples of suitable materials for the container 110 include flexible polymeric materials (e.g., polyethylene terephthalate (PET)), or other materials or combinations of materials. The container 110 may be formed from a single material or combinations of materials. Additionally, the container 110 may include one or more layers of materials. The container 110 may be a monolithic structure. In other embodiments, the container 110 may be comprised of multiple parts that are joined (e.g., sealed) together to define the container 110. The container 110 may include a conduit 114 integrally formed therewith for directing the fluid formulation 112 to the needle 124. In other embodiments, the conduit 114 is joined (e.g., pressed, glued) to the container 110. The container 110 may include one or more components. In embodiments in which multiple components are included in the container 110, the components may be co-located or may be physically separated from one another.

[0063] Fluid formulation 112 is a formulation that includes one or more components, where the formulation is intended for a therapeutic, diagnostic, or other biological purpose. Fluid formulation 112 is in a fluid form, such as a liquid, a slurry, a gel, a suspension (including a colloidal suspension), a gas, a powder, or any combination thereof. Fluid formulation 112 includes one or more components that include one or more therapeutic agents, such as proteins, peptides, polypeptides, antibodies, drugs (e.g., one or more selected from immunosuppressants (e.g., adalimumab), chemotherapeutic drugs, central nervous system (CNS) drugs (e.g., anti-Parkinson's drugs, anti-emetic drugs), anti-diabetic drugs (e.g., metformin), enzyme replacement therapy (ERT) drugs), hormones (e.g., parathyroid hormone (PTH), follicle stimulating hormone (FSH), and analogs thereof), and the like. ), insulin, incretins or combinations thereof (e.g., GLP-1, GLP-2, GIP, glucagon, PYY, and analogs thereof), oligonucleotides (e.g., antisense oligonucleotides (ASO), RNA interference (RNAi), aptamer RNA), DNA or SiRNA transcripts, cells, cytotoxic agents, vaccines or other prophylactic agents, nutritional supplements, vasodilators or vasoconstrictors, delivery enhancers, retardants, excipients, diagnostic agents, or cosmetic enhancements. The fluid formulation 112 may contain a therapeutically effective amount of one or more therapeutic agents, as well as appropriate amounts of other ingredients (e.g., excipients) to achieve a desired therapeutic effect in a subject.

[0064] The conduit 114 is a mechanical structure for directing the fluid formulation 112 from the container 110 to the needle 124. The conduit 114 may be coupled to the container 110 or may be integrally formed therewith. The conduit 114 may form part of the delivery assembly 118. For example, the conduit 114 may be coupled to the shaft of the piston 122 or may be integrally formed therewith. The conduit 114 is configured to direct the fluid formulation 112 from the container 110 to the delivery assembly 118 for delivery of the fluid formulation 112 into the GI lumen wall or into the surrounding tissue. At least a portion or all of the conduit 114 is flexible or deformable. The conduit 114 may be formed from one or more materials. Suitable materials for the conduit 114 include, for example, silicone (e.g., silicone tubing), thermoset polymers (e.g., polyimide tubing), or other materials or combinations of materials. In one or more embodiments, the conduit 114 is further configured to interface with a valve member 116 to selectively control the flow of the fluid formulation 112 through the conduit 114. In other embodiments, at least a portion of the conduit 114 itself may define the valve member 116 (e.g., when the conduit 114 includes a portion formed from a thermosetting polymer such as polyimide). The conduit 114 may include one or more components. In embodiments in which multiple components are included in the conduit 114, the components may be co-located or physically separated from one another.

[0065] The valve member 116 comprises a chemical, mechanical, electrical, electromechanical, electrochemical, chemical-mechanical, or electromechanical structure. The valve member 116 is configured to interface with the conduit 114 to selectively control the flow of the fluid formulation 112 from the container 110 to the delivery assembly 118. In one or more embodiments, the valve member 116 may form part of the delivery assembly 118. For example, the valve member 116 may include a cover coupled to the housing 120. The cover may include a biasing feature for interfacing with the conduit 114 to function as a pinch valve. Additionally or alternatively, the cover may include a release feature for engaging with a valve clip releasably coupled to the conduit 114. The release feature and the valve clip may cooperate to define the valve member 116. Additionally or alternatively, the conduit 114 may be held in a kinked state by the valve member 116, which may be configured as a sleeve, band, clip, or other structure releasably coupled to the conduit 114. In these embodiments, movement of the piston 122 relative to the housing 120 may disengage the valve member 116 from the conduit 114 or otherwise open the conduit 114 to allow the fluid formulation 112 to flow from the container 110 to the needle 124 for delivery into the GI lumen wall or surrounding tissue.

[0066] Additionally or alternatively, the conduit 114 may include at least a portion formed from a thermosetting polymer (e.g., polyimide) such that the conduit 114 itself can function as the valve member 116. The thermosetting polymer portion may be heated and compressed to define a temporary seal within the conduit 114 to substantially prevent the flow of the fluid formulation 112 through the conduit 114. In this embodiment, the pressure of the fluid formulation 112 may rupture the temporary seal within the conduit 114 and open the conduit 114 (partially or completely) to expel the fluid formulation 112 to allow the fluid formulation 112 to flow from the container 110 to the needle 124 for delivery into the GI lumen wall or surrounding tissue. The valve member 116 may include one or more components. In embodiments in which multiple components are included in the valve member 116, the components may be co-located or physically separated from one another.

[0067] The delivery assembly 118 may have a chemical, mechanical, electrical, electromechanical, electrochemical, chemical-mechanical, or electromechanical structure. In one or more embodiments, the delivery assembly 118 includes a housing 120, a piston 122, and a needle 124. As discussed above, the valve member 116 and the conduit 114 may also form part of the delivery assembly 118.

[0068] The housing 120 defines a piston chamber for movably receiving the piston 122. The housing 120 further includes structure for temporarily retaining the needle 124 therein. The housing 120 is configured to be coupled to and in fluid communication with the expandable member 106. In one or more embodiments, the housing 120 may include a cover that can function as part of (or define) the valve member 116.

[0069] The piston 122 is movably (e.g., slidably) disposed in the housing 120. The piston 122 may include a shaft coupled to or integrally formed with the piston 122. The conduit 114 is coupled to an end of the shaft or integrally formed with the shaft. The needle 124 is coupled to an opposing end of the shaft or integrally formed with it. The shaft may be at least partially hollow to allow for flow of the fluid formulation 112 from the conduit 114 to the needle 124.

[0070] The needle 124 is configured to penetrate into the GI lumen wall or surrounding tissue and deliver the fluid formulation 112 into the lumen wall or surrounding tissue. The needle 124 includes an opening for ejecting the fluid formulation 112. The needle 124 may be at least partially degradable or may be fully degradable such that the needle 124 can degrade within the GI lumen after delivery of the fluid formulation 112. Suitable materials for the needle 124 include, for example, polyethylene oxide (PEO), magnesium, polymeric materials, or other materials or combinations of materials. In other embodiments, the needle 124 may be substantially non-degradable or may include substantially non-degradable portions. In any embodiment, particularly in those in which the needle is substantially non-degradable, the delivery assembly 118 may include a return spring or other structure to allow retraction of the needle 124 from the GI lumen wall within the housing 120 to prevent injury to the subject.

[0071] In one or more embodiments, the delivery assembly 118 is configured such that when an internal pressure generated by the gas within the expandable member 106 reaches a threshold value, the gas pressure causes the piston 122 to move within the housing 120 to advance the needle 124 out of the housing 120 and into the GI lumen wall or surrounding tissue. When the valve member 116 is released or otherwise opened from the conduit 114 (e.g., when the needle 124 penetrates the GI lumen wall), the delivery assembly 118 is further configured to deliver the fluid formulation 112 from the needle 124 into the GI lumen wall or surrounding tissue. The device 100 can include one or more injector assemblies 118. The delivery assembly 118 can include one or more components. In embodiments in which multiple components are included in the delivery assembly 118, the components can be co-located or physically separated from one another.

[0072] One or more components of the device 100 (e.g., capsule 102, outer coating 104, expandable member 106, release means 108, reservoir 110, conduit 114, valve member 116, housing 120, piston 122, needle 124) may be formed from or otherwise include one or more biodegradable materials to facilitate degradation of such components, e.g., to allow passage through the remainder of the subject's intestinal tract following delivery of the fluid formulation 112. Examples of biodegradable materials that may be suitable for use with various components of the ingestible device 100 include, for example, hydroxypropyl methylcellulose (HPMC), polyvinyl acetate (PVA), lactide, glycolide, lactic acid, glycolic acid, per-dioxanone, trimethylene carbonate, caprolactone, and mixtures and copolymers thereof.

[0073] The above description is an overview of ingestible device 100. The following description, with reference to Figures 2-10, relates to examples of various features and aspects of device 100. These examples are intended to be illustrative of device 100, but are not intended to be limiting.

[0074] 2, a cross-sectional view of device 200 (one embodiment of device 100) is illustrated in an unfolded and / or unrolled state. Device 200 is illustrated without housing 102 and / or outer coating 104. However, it should be understood that device 200 may be folded, rolled, and / or otherwise manipulated to be disposed within housing 102 and / or outer coating 104 to enable ingestion and subsequent delivery of device 200 into the GI tract.

[0075] The device 200 includes an expandable member in the form of a balloon 202 (an embodiment of the expandable member 106), a deflation valve 212, a reactant reservoir 214 containing a first reactant 215, a release means 216 (an embodiment of the release means 108), a second reactant 217, a container 220 (an embodiment of the container 110), a fluid formulation 221 (an embodiment of the fluid formulation 112) disposed in the container 220, a conduit 226 (an embodiment of the conduit 114), and a delivery assembly 300 (an embodiment of the delivery assembly 118).

[0076] Referring again to FIG. 2, the balloon 202 includes an inflator portion 204, a deflator portion 205, a lower portion 206, and an elongated portion 210 extending between the inflator portion 204 and the deflator portion 205. The lower portion 206 extends downwardly (in the orientation shown in FIG. 2) between the inflator portion 204 and the deflator portion 205. The various portions of the balloon 202 cooperatively define an interior 202a for housing the various components of the device 200. As described below, the balloon 202 is configured to expand at a desired location within the lumen of the GI tract (e.g., stomach, intestines) in response to the formation of a gas from a chemical reaction between a first reactant 215 and a second reactant 217 within the interior 202a. In this manner, the balloon 202 can facilitate delivery of the fluid formulation 221 from the delivery assembly 300 into the GI lumen wall or into the surrounding tissue.

[0077] The balloon 202 has a size and shape to occupy a space within the GI lumen upon inflation of the balloon 202 and enable delivery of the fluid formulation 221 into the GI lumen wall. For example, upon inflation of the balloon 202, the outer periphery of the balloon 202 (e.g., the outer periphery of the lower portion 206 and the elongated portion 210) presses against the surface of the lumen wall. The pressure exerted by the balloon 202 is sufficient to temporarily hold the balloon 202 against the lumen wall for delivery of the fluid formulation 221. Depending on the inner circumference of the lumen delivery site, the lower portion 206 may remain partially folded or may fully expand when the balloon 202 is inflated. For example, if the lumen is relatively large and there are no obstacles resisting the expansion of the balloon 202, the balloon 202 will assume a fully inflated configuration with the lower portion 206 fully expanded (as shown in FIG. 2). In this manner, the balloon 202 can self-adjust to the size of the GI lumen to hold the balloon 202 in position for delivery of the fluid formulation 221, allowing the same balloon 202 to be used with a wide range of lumen sizes (e.g., different inner circumferences).

[0078] The deflation valve 212 is configured to cause deflation of the balloon 202 upon completion of delivery of the fluid formulation 221 into the GI lumen wall or surrounding tissue. In this manner, the deflation valve 212 can facilitate passage of the balloon 202 through the remainder of the GI tract and out the subject's anus. In the illustrated embodiment, the deflation valve 212 is configured as a degradable plug that temporarily covers an opening leading to the interior 202a. The degradable plug may be structured to degrade upon contact with fluids (e.g., bodily fluids) in the GI tract, thereby allowing gas contained in the interior 202a to exit through the opening. For example, the deflation valve 212 can be formed from or include an enteric material. The balloon 202 can include an optional flap 228 that can temporarily cover the deflation valve 212 to prevent premature activation (e.g., degradation) of the deflation valve 212 until the balloon 202 is inflated. For example, the flaps 228 can be temporarily held (e.g., glued, tacked, or otherwise held) in a folded position 228' about the flap fold axis 228a. Inflation of the balloon 202 can cause the flaps 228 to deploy from the folded position 228' to expose the deflation valve 212 and allow fluid within the GI tract to reach and cause the deflation valve 212 to disintegrate, thereby providing an opening for gas to escape to allow deflation.

[0079] Although the deflation valve 212 is shown disposed at the deflator portion 205, the deflation valve 212 may be disposed elsewhere on the expandable member 202 in other embodiments. Additionally, the balloon 202 may include multiple deflation valves 212. The deflation valve 212 may be configured differently than in the embodiment shown in FIG. 2. For example, in other embodiments, the deflation valve 212 may be configured as a dissolvable and / or movable cover disposed over an opening in the balloon 202. In these embodiments, dissolving and / or moving the cover away from the opening allows gas to exit the interior 202a through the opening, thereby enabling deflation.

[0080] The reactant reservoir 214 is disposed within the interior 202a and is structured to hold a first reactant 215 within the reactant reservoir 214 and temporarily prevent the first reactant 215 from contacting a second reactant 217 that is separately disposed within the interior 202a. The first reactant 215 may be, for example, citric acid. The second reactant 217 may be, for example, a carbonate such as potassium bicarbonate. In other embodiments, the first reactant 215 and the second reactant 217 may be other types of reactants (e.g., an acid and a base) that, when mixed, result in the formation of a gas sufficient to inflate the balloon 202. The second reactant 217 is shown disposed within the interior 202a of the inflator portion 204 near the first reactant 215. In other embodiments, the first reactant 215 and the second reactant 217 may be included in other regions of the balloon 202 so long as they are temporarily separated from one another.

[0081] The reactant reservoir 214 defines an interior volume for containing the first reactant 215. The reactant reservoir 214 can take a variety of different forms and shapes, such as a balloon or other structure. The reactant reservoir 214 is in selective fluid communication with the interior 202a via a reactant conduit 218 and a release means 216. The release means 216 is coupled to the reactant conduit 218 such that upon actuation (e.g., decomposition) of the release means 216, the first reactant 215 can exit the reactant reservoir 214 through the reactant conduit 218 to the interior 202a. For example, the release means 216 can be in the form of a degradable plug that blocks the interior of the reactant conduit 218 to temporarily prevent the first reactant 215 from entering the interior 202a. For example, when fluid in the GI tract contacts the release means 216 (upon decomposition of the housing 102 and / or outer coating 104), the release means 216 then decomposes allowing the reactant conduit 218 to discharge the first reactant 215 into the interior 202a.

[0082] In other embodiments, the device 200 includes a clip, band, or other structure for holding a portion of the balloon 202 to temporarily define separate chambers within the interior 202a for separately housing the first reactant 215 and the second reactant 217, respectively. For example, a portion of the balloon 202 can be clamped or compressed with a degradable clip or band to temporarily define multiple separate chambers within the interior 202a. The multiple chambers can be substantially sealed together to substantially prevent the first reactant 215 and the second reactant 217 from mixing. The clip or band can be positioned on an outer portion of the balloon 202 such that exposure to fluids within the GI tract (e.g., upon degradation of the housing 102 and / or the outer coating 104) causes the clip or band to degrade and then be released from the balloon 202. When the clip or band or similar structure is released from the balloon 202, the separate chambers are no longer substantially sealed together, allowing the first reactant 215 to mix with the second reactant 217 within the interior 202a.

[0083] Combining the first reactant 215 with the second reactant 217 in the interior 202a causes a chemical reaction to occur that produces a gas (e.g., CO 2 ) is formed. The gas expands the balloon 202 to an inflated state within the GI lumen, causing the elongated portion 210 to substantially align with a surface of the GI lumen wall. The substantial alignment of the elongated portion 210 with the GI lumen wall advantageously helps to facilitate delivery of the fluid formulation 221 from the delivery assembly 300 into the GI lumen wall or surrounding tissue.

[0084] 2, the container 220 defines a reservoir for holding the fluid formulation 221 therein. The container 220 is configured to expel the fluid formulation 221 via a conduit 226 to the delivery assembly 300 in response to pressure applied to an exterior surface of the container 220. The container 220 is disposed within the interior 202a and is coupled (e.g., heat sealed) to the balloon 202. For example, during the assembly process of the device 200, a fill port 222 extends from the container 220 by a fill conduit 224. Fill port 222 and fill conduit 224 are configured to allow container 220 to be initially filled with a volume of fluid formulation 221 (e.g., a volume ranging from about 50 μL to about 300 μL, e.g., 50 μL, 100 μL, 150 μL, 200 μL, 250 μL, or 300 μL of fluid, or any value therebetween, or 300 μL, 350 μL, or 400 μL of volume, or any value therebetween) using, for example, a syringe or other device. Once filling of container 220 is complete, balloon 202 can be sealed (e.g., by heat sealing) along a periphery of balloon 202, including a portion of fill conduit 224. In this manner, a portion of fill conduit 224 within interior 202a is substantially sealed, preventing fluid formulation 221 from exiting container 220 through fill conduit 224. Additionally, sealing the balloon 202 along the fill conduit 224 fixes the position of the container 220 relative to the balloon 202. The portion of the fill conduit 224 that includes the fill port 222 located outside the circumference of the balloon 202 can be removed from the balloon 202 after sealing.

[0085] In the illustrated embodiment, the container 220 has a spherical shape. In other embodiments, the container 220 may have other shapes, such as a cube, an ellipsoid, or any other shape. The container 220 may be configured as a balloon or other bladder-like structure. The container 220 is formed, at least in part, from a flexible or pliable material to allow deformation (e.g., contraction by squeezing) of the container 220 to expel the fluid formulation 221 from the container 220 to the delivery assembly 300. For example, gas formed within the interior 202a results in an internal pressure that is applied against the exterior surface of the container 220. This pressure is sufficient to cause squeezing of the container 220 when the valve member 310 is released from the conduit 226, thereby expelling the fluid formulation 221 from the container 220, as will be described in more detail below with respect to Figures 3-12.

[0086] The conduit 226 is coupled to or integrally formed with the container 220. The conduit 226 is configured to direct the fluid formulation 221 to the delivery assembly 300 for delivery of the fluid formulation 221 into the GI lumen wall or into the surrounding tissue. Although the conduit 226 is illustrated in the embodiment of FIG. 2 as a substantially flexible tube (e.g., silicone tubing, polyimide tubing), it should be understood that the conduit 226 may include substantially inflexible portions in other embodiments. In the illustrated embodiment, the conduit 226 is configured to interface with a valve member in the form of a cover 310 (an embodiment of the valve member 116) to selectively control the flow of the fluid formulation 221 from the container 220 to the delivery assembly 300, as described below with respect to FIGS. 3-6.

[0087] Referring again to FIG. 2, the delivery assembly 300 is coupled to the balloon 202 and is in separate fluid communication with the interior 202a and the container 220. For example, gas pressurizing the balloon 202 can pass through one or more openings in the cover 310 to apply pressure against the piston 322 of the delivery assembly 300. When a threshold pressure is reached (e.g., upon full or partial inflation of the balloon 202), the gas moves the piston 322 and advances the needle 324 of the delivery assembly 300 into the GI lumen wall or into the surrounding tissue. The gas pressurizing the balloon 202 is also applied against the exterior surface of the container 220 to expel the fluid formulation 221 through the conduit 226 to the needle 324 and through the needle 324. However, as described below, the cover 310 is structured to interface with the conduit 226 to substantially impede flow of the fluid formulation 221 through the conduit 226 to the needle 324 until the needle 324 has traveled a sufficient distance. When the needle 324 has moved sufficiently (e.g., when the needle 324 has penetrated the GI lumen wall), the cover 310 is further configured to release the conduit 226 to allow the fluid formulation 221 to flow through the conduit 226 to the needle 324 and be delivered into the GI lumen wall or surrounding tissue.

[0088] 3, a detailed view of a portion of device 200 including a portion of balloon 202 (e.g., elongated portion 210) and a delivery assembly 300 is shown in an unactuated state. Delivery assembly 300 includes a housing 302, a release mechanism 306, an upper seal 308, a cover 310, a piston 322, a needle 324, and a shaft 326. Piston 322, needle 324, and shaft 326 may cooperate to define a piston-needle assembly 320. As described below, piston-needle assembly 320 is configured to move axially relative to housing 302 along a longitudinal axis 302ab defined by housing 302 to deliver fluid formulation 221 through the GI lumen wall.

[0089] The housing 302 is collectively defined by an upper housing portion 302a and a lower housing portion 302b. The upper housing portion 302a may be bonded (e.g., heat set, glued) to the lower housing portion 302b with a portion of the balloon 202 (e.g., a portion of the elongated portion 210) disposed therebetween. In other embodiments, the upper housing portion 302a and the lower housing portion 302b may define a one-piece structure. The upper housing portion 302a extends outwardly from the elongated portion 210 and is configured to temporarily house the needle 324 therein. The upper housing portion 302a has a substantially cylindrical shape and defines a needle chamber 302a' for housing the needle 324 therein, although other shapes are contemplated according to other embodiments. The upper housing portion 302a and the lower housing portion 302b cooperate to define a longitudinal axis 302ab. The seal 308 is coupled (e.g., glued) to the top of the upper housing portion 302a to substantially prevent fluid within the GI tract from entering the needle chamber 302a' until the needle 324 penetrates the seal 308. The seal 308 may be formed from a penetrable material (e.g., aluminum foil) to allow the needle 324 to penetrate the seal 308. In this manner, the seal 308 and the upper housing portion 302a can cooperate to define a substantially sterile environment within the needle chamber 302a' to accommodate the needle 324 prior to delivery of the fluid formulation 221 to the GI lumen wall.

[0090] The needle 324 is temporarily disposed within the needle chamber 302a'. The needle 324 includes a tapered end (e.g., a pointed end) configured to pierce the seal 308 and penetrate the GI lumen wall or surrounding tissue in response to sufficient axial movement of the piston 322. The needle 324 defines a needle channel 324a extending from an opposite end of the needle 324 to a needle opening 324b located adjacent the tapered end for ejecting the fluid formulation 221. In other embodiments, the needle 324 may include an opening at the pointed end for ejecting the fluid formulation 221. The needle 324 is coupled (e.g., press-fit) to the shaft 326 or integrally molded (e.g., insert molded) with the shaft 326. The needle 324 is at least partially or completely degradable such that the needle 324 may substantially disintegrate within the GI lumen wall (or elsewhere within the GI lumen) upon delivery of the fluid formulation 221. For example, needle 324 may be formed from or otherwise include polyethylene oxide (PEO), magnesium, or other degradable material or combination of materials.

[0091] The release mechanism 306 (e.g., actuator, trigger) is coupled (e.g., press-fit, snap-fit, glued) to or integrally formed with the lower portion of the upper housing portion 302a. The release mechanism 306 is configured to interface with the shaft 326 to prevent advancement of the needle 324 until sufficient pressure is generated by the gas in the interior 202a. For example, FIG. 4 illustrates a cross-sectional view of the release mechanism 306 taken along line 4-4 of FIG. 3. As shown in FIG. 4, the release mechanism 306 has a substantially circular cross-sectional shape and includes one or more fingers 306a extending radially inward toward the longitudinal axis 302ab. Each of the plurality of fingers 306a extends radially inward in a cantilevered manner from a circumferential end of the release mechanism 306 to a free end 306a′ located adjacent the shaft 326. Fingers 306a are configured to interface with protrusions 326d (shown in FIG. 3 ) of shaft 326 via an interference (e.g., overlap) to substantially prevent needle 324 from penetrating seal 308 until sufficient pressure is generated within interior 202a. When a threshold internal pressure is reached (e.g., upon full or partial inflation of balloon 202), protrusions 326d break the interference with fingers 306a by deflecting free end 306a′ away from shaft 326, thereby allowing shaft 326 to move axially along longitudinal axis 302ab toward upper housing portion 302a such that needle 324 penetrates seal 308 and enters the GI lumen wall.

[0092] 3, lower housing portion 302b extends into interior 202a and defines a piston chamber 302b' for movably receiving piston 322. Piston 322 is disposed within piston chamber 302b' and is movably (e.g., slidably) coupled to an inner surface of lower housing portion 302b that defines piston chamber 302b'. Piston 322 may include one or more seals for interacting with an inner surface of lower housing portion 302b to form a substantially fluid-tight seal within at least a portion of piston chamber 302b'.

[0093] The shaft 326 is coupled (e.g., press-fit, glued) to the piston 322 or integrally formed (e.g., insert molded) therewith. In the illustrated embodiment, the shaft 326 is configured as a substantially cylindrical member having a generally elongated configuration, although other shapes and configurations are contemplated in other embodiments. The shaft 326 extends from a first end 326a to a second end 326b. The first end 326a is coupled (e.g., press-fit, glued, insert molded) to the needle 324 or integrally formed therewith. The second end 326b is coupled (e.g., via a hose barb, clamp) to the conduit 226 or integrally formed therewith. The piston 322 is disposed between the first end 326a and the second end 326b. The shaft 326 further defines an inner shaft channel 326c for directing the fluid formulation 221 from the conduit 226 to the needle channel 324a. As shown in FIG. 3, the shaft channel 326c extends the entire length of the shaft 326. In other embodiments, the shaft channel 326c extends a portion of the length of the shaft 326. In the position shown in FIG. 3, the protrusion 326d is located on the shaft 326 outside the upper housing portion 302a and below (e.g., adjacent) the release mechanism 306. As described above, the protrusion 326d interfaces with the multiple fingers 306a of the release mechanism 306 and substantially prevents advancement of the needle 324 through the seal 308 until the internal pressure provided by the gas in the interior 202a reaches a threshold pressure. For example, the threshold pressure can be associated with a fully inflated state of the balloon 202 to ensure substantial alignment of the elongated portion 210 with the GI lumen wall prior to advancing the needle 324 into the lumen wall.

[0094] The cover 310 is coupled (e.g., press-fit, snap-fit, glued) to or integrally formed with the lower housing portion 302b. In the illustrated embodiment, the cover 310 interfaces with the conduit 226 and includes a biasing feature that functions as a pinch valve to selectively control the flow of the fluid formulation 221 to the needle 324. The cover 310 is further configured such that gas pressurizing the balloon 202 exerts pressure against a surface of the piston 322, thereby moving the piston 322 within the piston chamber 302b' and advancing the needle 324 through the seal 308. For example, FIG. 5 illustrates a cross-section of the cover 310 taken along line 5-5 of FIG. 3. As shown in FIG. 5, the cover 310 has a generally circular cross-sectional shape, although other shapes and configurations are contemplated in other embodiments. The cover 310 includes a first opening 310a and a second opening 310b. The cover 310 further includes a first leg 310c and a second leg 310d that each extend into the first opening 310a. The first leg 310c and the second leg 310d are flexible members that are configured to flex within the first opening 310a between a biased position (e.g., a first state) shown in FIGS. 3-5 and an unbiased position (e.g., a second state) shown in FIGS. 6-7 to selectively control the flow of the fluid formulation 221 through the conduit 226 to the needle 324. It is worth noting that the first leg 310c functions as a biasing feature to control the flow of fluid through the conduit 226, whereas the second leg 310d is an optional feature that may help ensure axial alignment of the shaft 326 with respect to the longitudinal axis 302ab, as described below.

[0095] As shown in FIG. 5, the first leg 310c has a generally arcuate shape and extends from the upper left side of the cover 310 to the center right side within the first opening 310a. The first leg 310c terminates at a free end defined by the first leg 310c' within the first opening 310a. The second leg 310d is a mirror image of the first leg 310c. The second leg 310d has a generally arcuate shape and extends from the lower right side of the cover 310 to the center left side within the first opening 310a. The second leg 310d terminates at a free end defined by the second leg 310d' within the first opening 310a adjacent to the first leg 310c'. The first leg 310c and the second leg 310d are each laterally offset in opposite directions from the longitudinal axis 302ab by the shaft 326 in a first state shown in Figure 5. The cover 310 includes an optional recess 310e disposed adjacent the first leg 310c' for engaging a portion of the conduit 226. The recess 310e may help maintain the position of the conduit 226 relative to the first leg 310c'.

[0096] 5, a portion of the shaft 326 extends through the first opening 310a between the first leg 310c' and the second leg 310d' along the longitudinal axis 302ab such that the first leg 310c and the second leg 310d are laterally biased in opposite directions from the longitudinal axis 302ab by the shaft 326. The first leg 310c' and the second leg 310d' may provide a biasing force to opposite sides of the shaft 326 to help maintain the axial position (along the longitudinal axis 302ab) of the shaft 326 relative to the cover 310. The conduit 226 extends through the first opening 310a between the recess 310e and the opposite side of the first leg 310c'. 3-5, the first leg 310c' is biased by the shaft 326 relative to the conduit 226 such that the conduit 226 is locally constricted (e.g., pinched) by the first leg 310c', substantially impeding the flow of the fluid formulation 221 through the conduit 226 towards the needle 324. In other words, the first leg 310c' effectively functions as a pinch valve to control the flow of the fluid formulation 221 through the conduit 226.

[0097] As described below with respect to Figures 6 and 7, which show the first leg 310c in the second state, sufficient movement of the piston-needle assembly 320 causes the first leg 310c' to move laterally away from the conduit 226 to an unbiased (relaxed) position such that the conduit 226 is no longer pinched by the first leg 310c'. Furthermore, the spacing between the first leg 310c' and the second leg 310d' in the unbiased position allows substantially unimpeded movement of the third conduit portion 226c through the first opening 310a, thereby allowing axial movement of the piston-needle assembly 320. In this manner, the fluid formulation 221 can flow through the conduit 226 and the shaft 326 to the needle 324 for delivery into the lumen wall in the second state.

[0098] 3 and 5, the conduit 226 includes a first conduit portion 226a extending from the container 220 to the cover 310, a second conduit portion 226b extending into the second housing portion 302b, and a third conduit portion 226c extending from the cover 310 to the shaft 326. The second conduit portion 226b passes from the first conduit portion 226a through the first opening 310a at least partially around the shaft 326 in the second housing portion 302b, through the second opening 310b, and into the third conduit portion 226c. The third conduit portion 226c is configured to move with the piston-needle assembly 320 along the longitudinal axis 302ab.

[0099] To aid in the assembly and routing of the conduit 226 through the cover 310, the conduit 226 may include one or more positioning or stop means disposed on its exterior surface. For example, FIG. 8 illustrates an embodiment of the conduit 226 designated as conduit 226'. The conduit 226' includes one or more protrusions 227' disposed between one or more of the conduit sections 226a', 226b', and 226c'. The protrusions 227' are configured to engage a portion of the cover 310 to act as guides for assembling the conduit 226' to the cover 310 and to maintain the position (e.g., length) of the conduit section relative to the cover 310 during operation of the device 200. The protrusions 227' may be, for example, a sleeve or band (e.g., a silicone band) like structure disposed around a portion of the conduit 226'.

[0100] In addition to providing a path through the conduit 226, the first opening 310a and / or the second opening 310b of the cover 310 further provide a fluid path for gas (produced by the reaction of the first reactant 215 and the second reactant 217) from the interior 202a to apply pressure to the surface of the piston 322. When the gas pressure reaches a threshold value, the pressure causes the piston 322 to move axially within the piston chamber 304c, advancing the needle 324 into the GI lumen wall or into the surrounding tissue. For example, referring to FIGS. 6-7, the device 200 is illustrated in a second state, where the balloon 202 may be in a fully inflated state and the elongated portion 210 is substantially aligned with the GI lumen wall when the gas (from the reaction of the first reactant 215 and the second reactant 217) in the interior 202a reaches a threshold pressure. Gas (indicated in FIG. 6 by unidirectional arrow 330) pressurizing balloon 202 is applied against the surface of piston 322 through first opening 310a and / or second opening 310b, causing protrusion 326d to break interference with release mechanism 306. As a result, piston 322 is moved axially within piston chamber 304c along longitudinal axis 302ab toward first housing portion 302a such that needle 324 advances through seal 308 and into the GI lumen wall.

[0101] 6-7, gas pressure within interior 202a (indicated by unidirectional arrow 330 in FIG. 6) is also applied against the exterior surface of container 220. However, first leg 310c remains biased against conduit 226 (indicated by dashed line 310c' in FIG. 7) by shaft 326 during part of the axial movement of needle 324, thereby substantially impeding flow of fluid formulation 221 through conduit 226 until needle 324 has traveled a sufficient distance. For example, the portion of the shaft 326 that extends through the first opening 310a to bias the first leg 310c and the second leg 310d (as shown by dashed line 310d'') can have a length that corresponds to a desired amount of axial movement (e.g., a desired penetration depth) of the needle 324; as shown in FIG. 6, once the needle 324 has moved a sufficient distance, the shaft 326 moves axially away from the first leg 310c to move the first leg 310c away from the conduit 226, thereby allowing flow of the fluid formulation 221 from the container 220 through the conduit 226 to the needle 324. In this manner, the device 200 can allow sufficient penetration of the needle 324 into or around the GI lumen wall prior to delivery of the fluid formulation 221, which can help ensure delivery of substantially all of the fluid formulation 221 at a desired location (e.g., depth) within the subject. In other words, the device 200 allows for the discharge of the fluid formulation 221 through the GI luminal wall in a sequential manner, thereby substantially avoiding discharge of the fluid formulation 221 into the luminal environment.

[0102] 6-7, by releasing shaft 326 from first leg 310c and placing first leg 310c' in an unbiased position away from conduit 226, gas pressure within interior 202a (indicated by unidirectional arrow 330) applied to container 220 can expel fluid formulation 221 through conduit 226, shaft channel 326c, needle channel 324a, and needle opening 324b into the GI lumen wall or surrounding tissue. In this manner, device 200 can enable delivery of one or more therapeutic agents contained in fluid formulation 221 to the bloodstream of a subject for systemic delivery.

[0103] Once delivery of the fluid formulation 221 is complete, the needle 324 may then dissolve within the GI lumen wall or other area within the GI lumen along with one or more additional components of the device 200 (e.g., the housing 302, the shaft 326, the piston 322, the cover 310). In embodiments in which the needle 324 is substantially non-dissolvable, the device 200 includes a return spring or other biasing feature to retract the needle 324 within the housing 302 after delivery of the fluid formulation 221 is complete. In any of these embodiments, the deflation valve 212 releases a substantial amount of gas contained within the interior 202a to substantially deflate the balloon 202 and thereafter permit the device 200 to pass through the remainder of the GI tract and out the subject's anus.

[0104] 9-10, a delivery assembly 400 (one embodiment of the delivery assembly 118) according to another embodiment is illustrated. For efficiency, identical reference numerals refer to the same components between the embodiments. In this embodiment, the delivery assembly 400 includes a cover 410 including a release mechanism 410c for interfacing with a separate valve member in the form of a clip 432 (an embodiment of the valve member 116) releasably coupled to the conduit 226. The release mechanism 410c and the clip 432 may cooperatively define the valve member of this embodiment. For example, as shown in FIG. 9, the cover 410 is coupled to or integrally formed with the lower housing portion 302b. The cover 410 defines one or more openings 410a for providing a fluid path between the interior 202a and the piston 322. The release mechanism 410c has a tapered (e.g., conical) structure extending outwardly from the outer surface of the cover 310. The release mechanism 410c further defines a conduit opening 410c' through the cover 310 for a portion of the conduit 226 and / or shaft 326 to extend therethrough. Thus, the release mechanism 410c substantially surrounds a portion of the conduit 226.

[0105] The clip 432 is releasably coupled to the conduit 226 adjacent the release mechanism 410c. The clip 432 is coupled to the conduit 226 such that the conduit 226 is locally clamped by the clip 432 to substantially prevent flow of the fluid formulation 221 through the conduit 226. The clip 432 may be configured as a C-clip, spring clip, claw clip, clamp, or other structure capable of being releasably coupled to the conduit 226 in a similar manner. As described below, the release mechanism 410c is configured to engage the clip 432 in response to sufficient axial movement of the piston-needle assembly 320 to release the clip 432 from the conduit 226 and allow the fluid formulation 221 to flow to the needle 324.

[0106] The clip 432 may be positioned a sufficient distance from the release mechanism 410c on the conduit 226 to allow sufficient penetration of the needle 324 into the lumen wall prior to release of the clip 432 by the release mechanism 410c. For example, the distance between the release mechanism 410c and the clip 432 in the first state shown in FIG. 9 may correspond to a desired penetration depth of the needle 324. In this manner, the delivery assembly 400 can penetrate the needle 324 to a desired location (e.g., depth) within the GI lumen wall or surrounding tissue prior to delivering the fluid formulation 221.

[0107] 10, the delivery assembly 400 is shown in a second state in which the fully inflated state of the balloon 202 can be caused when the gas within the interior 202a reaches a threshold pressure, thereby causing the elongated portion 210 to be substantially aligned with the GI lumen wall. Gas (represented by one-way arrow 330) pressurizing the balloon 202 is applied through the opening 410a in the cover 410 against the surface of the piston 322, causing the protrusion 326d to break interference with the release mechanism 306. As a result, the piston 322 is moved axially along the longitudinal axis 302ab within the piston chamber 304c toward the first housing portion 302a such that the needle 324 is advanced through the seal 308 and into the GI lumen wall or surrounding tissue.

[0108] Gas pressure within the interior 202a (indicated by unidirectional arrow 330) is also applied against the exterior surface of the container 220. However, the conduit 226 remains clamped by the clip 432 during a portion of the axial movement of the piston-needle assembly 320 to substantially prevent flow of the fluid formulation 221 through the conduit 226 until the needle 324 has moved a sufficient distance. For example, as described above, the distance between the release mechanism 410c and the clip 432 in the first state shown in FIG. 9 may correspond to a desired amount of axial movement of the needle 324 (e.g., a desired penetration depth). As shown in FIG. 10, when the needle 324 has moved a sufficient distance, the conduit 226 and clip 432 are moved axially toward the release mechanism 410b, which engages the clip 432 and releases the clip 432 from the conduit 226 (e.g., by spreading the clip 432 outward, away from the conduit 226), thereby allowing the flow of the fluid formulation 221 from the container 220, through the conduit 226 and to the needle 324.

[0109] 11-12, a delivery assembly 500 (one embodiment of the delivery assembly 118) is illustrated according to another embodiment. For efficiency, identical reference numerals will refer to like components between embodiments. In this embodiment, the delivery assembly 500 includes a valve member in the form of a sleeve 532 (an embodiment of the valve member 116) releasably coupled to the conduit 226. The sleeve 532 is coupled to the conduit 226 such that a portion of the conduit 226 is held in a kinked state to temporarily prevent flow of the fluid formulation 221 therethrough. In this embodiment, the delivery assembly 500 is shown without a cover, however, it should be understood that the delivery assembly 500 may include a cover in other embodiments.

[0110] The sleeve 532 is releasably coupled around a portion of the conduit 226 to hold the conduit 226 in a kinked state to locally constrict the conduit 226 to substantially prevent flow of the fluid formulation 221 through the conduit 226. The sleeve 532 may be configured as a flexible tube, band, clip, or any other structure that can be releasably coupled to the conduit 226 in a similar manner. As described below, the conduit 226 has a length such that when tension is applied to the conduit 226 in response to sufficient axial movement of the piston-needle assembly 320, the sleeve 532 is released from the conduit 226 and the conduit 226 is unkinked, thereby allowing the fluid formulation 221 to flow through the conduit 226 to the needle 324.

[0111] The conduit 226 may have a length that allows the needle 324 to penetrate sufficiently into the lumen wall or surrounding tissue before the sleeve 532 is released. For example, the length of the conduit 226 may be such that there is not enough tension in the conduit 226 to release the sleeve 532 until the needle 324 has traveled a sufficient axial distance, which may correspond to a desired penetration depth of the needle 324. In this manner, the delivery assembly 400 may allow the needle 324 to penetrate to a desired location (e.g., depth) within the GI lumen wall or surrounding tissue before delivering the fluid formulation 221.

[0112] 12, a second condition of the delivery assembly 500 is shown in which the gas within the interior 202a reaches a threshold pressure, causing the balloon 202 to be fully inflated, with the elongated portion 210 substantially aligned with the GI lumen wall. Gas (indicated by one-way arrow 330) pressurizing the balloon 202 is applied against the surface of the piston 322 via the lower housing portion 302b, causing the protrusion 326d to break interference with the release mechanism 306. As a result, the piston 322 moves axially along the longitudinal axis 302ab within the piston chamber 304c toward the first housing portion 302a such that the needle 324 advances through the seal 308 and into the GI lumen wall.

[0113] Gas pressure within interior 202a (indicated by unidirectional arrow 330) is also applied against the exterior surface of container 220. However, conduit 226 remains constricted by sleeve 532 during a portion of the axial travel of piston-needle assembly 320 to substantially prevent flow of fluid formulation 221 through conduit 226 until needle 324 has moved a sufficient distance. For example, as discussed above, the length of conduit 226 is such that there is not sufficient tension in conduit 226 to release sleeve 532 until needle 324 has moved a sufficient axial distance (e.g., a desired penetration depth). As shown in FIG. 12, when needle 324 has moved a sufficient distance, conduit 226 is under sufficient tension to release sleeve 532 from conduit 226 such that conduit 226 can unkink to allow flow of fluid formulation 221 from container 220 through conduit 226 to needle 324.

[0114] Additionally or alternatively, the conduit 226 may be formed from or otherwise include at least a portion made from a thermosetting polymer, such as polyimide (e.g., a polyimide tube / sheet). For example, prior to assembly of the balloon 202, a portion (or all) of the conduit 226 including the thermosetting polymer may be heated and compressed (e.g., with a mold) to form a temporary seal within the conduit 226 that substantially prevents the flow of the fluid formulation 221 therethrough in the first state of the device. In this embodiment, the cover 310 / 410, clip 432, and / or sleeve 532 may be omitted entirely, and the conduit 226 itself may function as a valve member (one embodiment of the valve member 116). In the second state, when the gas pressure within interior 202a applied to container 220 reaches a threshold associated with delivery of fluid formulation 221 (e.g., when needle 324 penetrates the GI lumen wall), the fluid pressure of fluid formulation 221 within container 220 breaks the temporary seal in conduit 226, opening conduit 226 and allowing fluid formulation 221 to flow through conduit 226 and needle 324 for delivery into the GI lumen wall or surrounding tissue.

[0115] 13, a method 600 of delivering a fluid formulation 112 to a subject's GI tract using the device 100 is shown. In a first step, the subject ingests the device 100 (e.g., by swallowing the device 100) (step 601), which results in the housing 102 and / or the outer coating 104 being at least partially (or completely) degraded when the device 100 reaches a desired location in the GI tract for delivery of the fluid formulation 112 (step 602). As a result, the delivery assembly 118 is positioned adjacent to the GI lumen wall (step 604). When the gas pressure in the expandable member 106 reaches a threshold value, the piston 122 moves relative to the housing 120, advancing the needle 124 into the GI lumen wall or into the surrounding tissue (step 605). Upon sufficient axial movement of the needle 124, the valve member 116 is released from or opens the conduit 114 (step 606). In this manner, device 100 can release one or more therapeutic agents contained in fluid formulation 112 into the subject's bloodstream for systemic delivery.

[0116] The foregoing description of various embodiments has been presented for purposes of illustration and description. It is not intended to limit the invention to the precise form disclosed. Many modifications, variations, and improvements will be apparent to those skilled in the art. For example, the device embodiments can be sized and otherwise adapted for various pediatric and neonatal applications, as well as various veterinary applications. Additionally, those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, numerous equivalents to the specific devices and methods described herein. Such equivalents are deemed to be within the scope of the present disclosure.

[0117] Although the present disclosure has been described and illustrated with reference to specific embodiments thereof, these descriptions and illustrations are not intended to limit the present disclosure. It can be clearly understood that various changes can be made within the embodiments and equivalent components can be substituted without departing from the true spirit and scope of the present disclosure as defined by the appended claims. Also, components, properties, or acts from one embodiment can be easily recombined or substituted with one or more components, properties, or acts from other embodiments to form numerous additional embodiments within the scope of the present invention. Furthermore, a component illustrated or described as being combined with other components can exist as a single component in various embodiments. Furthermore, when a component, property, component, feature, step, etc. is positively described, the embodiment of the present invention specifically contemplates excluding that component, value, property, component, feature, step, etc. The illustrations are not necessarily drawn to scale. There may be a distinction between the artistic depictions in the present disclosure and the actual device due to variables in the manufacturing process, etc. There may be other embodiments of the present disclosure that are not specifically illustrated. The present specification and drawings are considered to be illustrative and not restrictive. Modifications may be made to adapt a particular situation, material, composition of matter, method, or process to the objective, spirit, and scope of the present disclosure. All such modifications are intended to be within the scope of the claims appended hereto. Although the methods disclosed herein have been described with reference to certain operations performed in a particular order, it will be understood that these operations can be combined, further divided, or reordered to form equivalent methods without departing from the teachings of the present disclosure. Thus, unless specifically indicated herein, the order and grouping of operations are not limitations of the present disclosure.

Claims

1. 1. A delivery assembly for an ingestible device for delivering a fluid formulation into a GI tract lumen wall or surrounding tissue of a subject, comprising: a housing defining a piston chamber; a piston movably disposed within the piston chamber; a needle coupled to or integrally formed with said piston; a conduit configured to direct the fluid formulation from a fluid source to the needle; a valve member having a first state and a second state; In the first condition, the valve member substantially prevents flow of the fluid formulation from the conduit to the needle; A delivery assembly, wherein in the second condition, the valve member is configured to allow the fluid formulation to flow through the conduit to the needle.

2. 2. The delivery assembly of claim 1, wherein the valve member is releasably coupled to the conduit, the valve member being configured to release from the conduit in response to movement of the piston to allow the fluid formulation to flow through the conduit to the needle in the second state.

3. 2. The delivery assembly of claim 1, wherein at least a portion of the conduit defines the valve member, the conduit configured to open in response to pressure of the fluid formulation to allow the fluid formulation to flow through the conduit to the needle in the second state.

4. The delivery assembly of claim 1 , wherein the delivery assembly is a structure coupled to and disposed within an expandable member.

5. The delivery assembly of claim 1 , wherein the delivery assembly is configured to be contained in an ingestible housing for delivery to the GI tract of the subject.

6. 2. The delivery assembly of claim 1, wherein the piston is configured to move in response to gas pressure applied to an outer surface of the piston to advance the needle from the housing and into the GI lumen wall while the valve member is in the first state.

7. The delivery assembly of claim 1 , wherein the valve member includes a cover coupled to the housing, the cover defining an opening and a flexible leg extending into the opening.

8. 8. The delivery assembly of claim 7, wherein the piston includes a shaft, a portion of the conduit and a portion of the shaft each extending through the opening in the cover, the shaft biasing the flexible legs against the conduit to substantially prevent flow of the fluid formulation through the conduit in the first state.

9. 9. The delivery assembly of claim 8, wherein the piston moves relative to the housing to move the shaft away from the cover and unbias the flexible legs away from the conduit, thereby allowing the fluid formulation to flow to the needle in the second state.

10. The delivery assembly of claim 1 , wherein the valve member includes a clip releasably coupled to the conduit, the clip substantially preventing flow of the fluid formulation through the conduit in the first state.

11. The delivery assembly of claim 10 , further comprising a cover coupled to the housing, the cover defining an opening and a release mechanism.

12. 12. The delivery assembly of claim 11, wherein the piston includes a shaft, a portion of at least one of the conduit or the shaft extends through the opening in the cover, and the clip is positioned outside the piston chamber adjacent the release mechanism.

13. 13. The delivery assembly of claim 12, wherein the piston moves relative to the housing to move the clip towards the cover and the release mechanism releases the clip from the conduit, thereby allowing the fluid formulation to flow to the needle in the second state.

14. 2. The delivery assembly of claim 1, wherein the valve member comprises one of a sleeve, a clip, or a band releasably coupled to the conduit such that in the first state a portion of the conduit is held in a temporarily kinked state to substantially prevent flow of the fluid formulation through the conduit.

15. 15. The delivery assembly of claim 14, wherein the piston moves relative to the housing to cause tension in the conduit such that the sleeve, clip or band is released from the conduit, thereby allowing the fluid formulation to flow to the needle in the second state.

16. 2. The delivery assembly of claim 1, wherein at least a portion of the conduit defines the valve member, at least a portion of which is formed from a thermosetting polymer that defines a temporary seal within the conduit to substantially prevent flow of the fluid formulation through the conduit in the first condition.

17. 17. The delivery assembly of claim 16, wherein pressure of the fluid formulation ruptures the temporary seal, thereby allowing the fluid formulation to flow through the conduit to the needle in the second state.

18. 1. An ingestible device for delivering a fluid formulation into a GI tract lumen wall or surrounding tissue of a subject, comprising: An expandable member; a container disposed within the expandable member; a fluid formulation disposed within the container, the fluid formulation including at least one therapeutic agent; coupled to the expandable member and disposed within the expandable member; a housing defining a piston chamber; a piston movably disposed within the piston chamber; a needle coupled to or integrally formed with said piston; a conduit configured to direct the fluid formulation from the container to a needle; a delivery assembly comprising a valve member operably coupled to the conduit, the valve member having a first state and a second state, In the first condition, the valve member substantially prevents flow of the fluid formulation from the conduit to the needle; An ingestible device, wherein in the second condition, the expandable member moves the piston relative to the housing, releasing the valve member from the conduit and allowing the fluid formulation to flow from the container to the needle.

19. 20. The device of claim 18, wherein the valve member is releasably coupled to the conduit, the valve member being configured to release from the conduit in response to movement of the piston to allow the fluid formulation to flow through the conduit to the needle in the second state.

20. 20. The device of claim 18, wherein at least a portion of the conduit defines the valve member, the conduit being configured to open in response to pressure of the fluid formulation to allow the fluid formulation to flow through the conduit to the needle in the second state.

21. 20. The device of claim 18, further comprising an ingestible housing, the expandable member and the delivery assembly disposed within the ingestible housing.

22. 20. The device of claim 18, wherein the piston is configured to move in response to gas pressure generated within the expandable member to advance the needle from the housing and into the GI lumen wall while the valve member is in the first condition.

23. 23. The device of claim 22, wherein the container is configured to expel the fluid formulation through the conduit and to the needle in the second state in response to gas pressure applied to an exterior surface of the container.

24. 20. The device of claim 18, wherein the container defines a volume containing up to about 400 μL of fluid.

25. 20. The device of claim 18, wherein the container defines a volume containing about 50 μL to about 300 μL of fluid.

26. 20. The device of claim 18, wherein the valve member includes a cover coupled to the housing, the cover defining an opening and a flexible leg extending into the opening.

27. 27. The device of claim 26, wherein the piston includes a shaft, a portion of the conduit and a portion of the shaft each extending through the opening in the cover, and the shaft biases the flexible legs against the conduit to substantially prevent flow of the fluid formulation through the conduit in the first state.

28. 28. The device of claim 27, wherein the piston moves relative to the housing to move the shaft away from the cover and unbias the flexible legs away from the conduit, thereby allowing the fluid formulation to flow to the needle in the second state.

29. 20. The device of claim 18, wherein the valve member includes a clip releasably coupled to the conduit, the clip substantially preventing flow of the fluid formulation through the conduit in the first condition.

30. 30. The device of claim 29, further comprising a cover coupled to the housing, the cover defining an opening and a release mechanism.

31. 31. The device of claim 30, wherein the piston includes a shaft, a portion of at least one of the conduit or the shaft extending through the opening in the cover, and the clip is positioned outside the piston chamber adjacent the release mechanism.

32. 32. The device of claim 31, wherein the piston moves relative to the housing to move the clip towards the cover and the release mechanism releases the clip from the conduit, thereby allowing the fluid formulation to flow to the needle in the second state.

33. 20. The device of claim 18, wherein the valve member comprises one of a sleeve, a clip, or a band releasably coupled to the conduit such that in the first condition a portion of the conduit is held in a temporarily kinked condition to substantially prevent flow of the fluid formulation through the conduit.

34. 34. The device of claim 33, wherein the piston moves relative to the housing to cause tension in the conduit such that the sleeve, clip, or band is released from the conduit, thereby allowing the fluid formulation to flow to the needle in the second state.

35. 20. The device of claim 18, wherein at least a portion of the conduit defines the valve member, at least a portion of which is formed from a thermosetting polymer that defines a temporary seal within the conduit to substantially prevent flow of the fluid formulation through the conduit in the first condition.

36. 36. The device of claim 35, wherein the pressure of the fluid formulation ruptures the temporary seal, thereby allowing the fluid formulation to flow through the conduit to the needle in the second state.

37. 20. The device of claim 18, wherein the at least one therapeutic agent is one or more selected from an immunosuppressant, a chemotherapeutic agent, a central nervous system (CNS) drug, an antidiabetic drug, an enzyme replacement therapy (ERT) drug, an antibody, a hormone, insulin, an incretin or a combination thereof, or an oligonucleotide.

38. A method of delivering the fluid formulation into the GI tract lumen wall or into the surrounding tissue of a subject in need thereof, comprising the subject ingesting the ingestible device of any one of claims 18 to 37.

39. 38. Use of an ingestible device according to any one of claims 18 to 37 for delivery of said fluid formulation into the GI tract lumen wall or into the surrounding tissue of said subject in need thereof.

40. 20. A method of preparing an ingestible device for delivering a therapeutic agent into the GI tract lumen wall or into the surrounding tissue of the subject, comprising loading the fluid formulation comprising the therapeutic agent into a delivery assembly described in any one of claims 1 to 17.

41. 1. A delivery assembly for use in an ingestible device for delivering a fluid formulation to the GI tract of a subject, comprising: a housing defining a piston chamber; a piston movably disposed within the piston chamber; a needle coupled to or integrally formed with said piston; a conduit configured to direct the fluid formulation from a fluid source to the needle; a valve member configured to, in a first state, substantially prevent flow of the fluid formulation from the conduit to the needle, and to, in a second state, allow flow of the fluid formulation through the conduit to the needle.

42. 1. A device for delivering a fluid formulation to the gastrointestinal tract of a subject, comprising: An expandable member; a container disposed within the expandable member and containing a fluid formulation; a housing coupled to the expandable member and defining a piston chamber; a piston movably disposed within the piston chamber; a needle coupled to or integrally formed with said piston; a conduit configured to direct the fluid formulation from the container to the needle; a valve member operably coupled to the conduit; In a first state, the valve member substantially prevents flow of the fluid formulation from the conduit to the needle; In a second state, the expandable member moves the piston relative to the piston chamber to release the valve member from the conduit and allow the fluid formulation to flow from the container to the needle.

43. 1. A method for delivering a fluid formulation to the GI tract of a subject, comprising: An expandable member; a container disposed within the expandable member and containing a fluid formulation; a housing coupled to the expandable member and defining a piston chamber; a piston movably disposed within the piston chamber; a needle coupled to or integrally formed with said piston; a conduit configured to direct the fluid formulation from the container to the needle; a valve member operably coupled to the conduit; and gas pressure generated within the expandable member expands the expandable member within the lumen of the GI tract to position a delivery assembly adjacent to a wall of the GI lumen; moving the piston relative to the housing to advance the needle into the GI lumen wall or into surrounding tissue when the gas pressure reaches a threshold value; the valve member being released from the conduit to allow flow of the fluid formulation from the container to the needle upon sufficient axial movement of the needle; applying the gas pressure to the container to expel the fluid formulation from the container, through the conduit and the needle, and into the GI lumen wall or into the surrounding tissue.

Images