Commercial manufacturing of gastric residence systems

Abstract

A method of manufacturing a gastric residence system includes loading a transit puck sized and shaped to hold the gastric residence system with a core and a plurality of arm components at one or more loading stations. The transit puck is configured to transit a track connecting the one or more loading stations, a component joining station, a webbing station, and an encapsulation station. At the component joining station, adjacent components are joined within the transit puck to form the gastric residence system. At the webbing station, the gastric residence system is transferred from the transit puck to a webbing puck to connect adjacent arms with a filament within the webbing puck and returned to the transit puck. At the encapsulation station, the gastric residence system is folded into a compacted configuration, bound in the compacted configuration with a sleeve, and encapsulated with a capsule.

Description

Attorney Docket No. 75056-20042.40COMMERCIAL MANUFACTURING OF GASTRIC RESIDENCE SYSTEMSCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to United States Provisional Patent Application No. 63 / 749,554, filed January 25, 2025, the disclosure of which is incorporated herein by reference in its entirety.FIELD

[0002] The present disclosure relates generally to gastric residence systems, and more specifically to systems and methods for commercial-scale manufacturing of gastric residence systems.BACKGROUND

[0003] Gastric residence systems are delivery systems for therapeutic agents which remain in the stomach for days, weeks, or even longer periods, during which time drugs or other active ingredients can elute from the systems for absorption in the gastrointestinal tract. Gastric residence systems can be administered to a patient using capsules which are swallowed or introduced into the stomach of the patient by an alternate method (e.g., via a feeding tube or a gastric tube). Upon dissolution of a capsule in the stomach, a gastric residence system may expand or unfold to a size which remains in the stomach and resists passage through the pylorus over a desired gastric residence period. Throughout the desired residence period, the system elutes one or more active ingredients (e.g., drugs) at a desired rate. At the end of the residence period, the system passes through the pylorus and is eliminated from the patient.

[0004] Existing gastric residence systems have been manufactured on a small scale. However, manufacturing gastric residence systems on a larger scale poses unique challenges. Gastric residence systems often include multiple very small components. For example, a gastric residence system may include a plurality of arms that can unfold in the stomach of a patient. Each of the arms may be made from multiple smaller components that serve different functions (e.g., active ingredient-containing components that can deliver an active ingredient to a patient, disintegrating matrix components that can help the gastric residence1ny-2823215Attorney Docket No. 75056-20042.40system break apart after a desired residence period has elapsed, and / or inert components that can help to join the other components together). The individual arm components can be extremely small (e.g., about 0.5 mm in length). Due to the small size and delicate nature of the components, aligning the components into desired positions and connecting the components to form a gastric residence system can be challenging. The components must be arranged in a particular order and joined in a way that avoids damaging or otherwise altering the properties or performance of the components. Assembling these components precisely is particularly challenging to do quickly — handling small, delicate components without damaging them typically requires very slow and deliberate effort. As a result, manufacturing gastric residence systems at a commercial scale while maintaining the quality of the gastric residence systems produced is difficult.SUMMARY

[0005] Gastric residence systems may include a plurality of small components that serve various functions. For example, as discussed above, a gastric residence system may include a core and a plurality of arms made up of various small components, including active ingredient-containing components for delivering an active ingredient to a patient, disintegrating matrix components for helping the gastric residence system break apart after a desired residence period has elapsed, and / or inert components used for joining the other components together. These components must be assembled in a precise spatial arrangement and joined in a particular manner in order to ensure the gastric residence system stays intact during administration and while in the stomach of a patient. Given this small size of these components (e.g., about 0.5 mm in length for some components), aligning and joining the components without damaging them is challenging, especially at the speed required by commercial scale manufacturing operations.

[0006] Developing a larger-scale manufacturing process is crucial for effectively commercializing gastric residence system products. Commercial gastric residence systems must be uniform and high quality so as to comply with relevant health and safety standards. The gastric residence systems also must be capable of being produced in large quantities in a relatively short period of time in order to meet patient demand. To ensure that the uniformity, quality, and quantity requirements for gastric residence system production are2ny-2823215Attorney Docket No. 75056-20042.40met, standardized systems and methods for manufacturing gastric residence systems are needed.

[0007] Provided herein are systems and methods for manufacturing gastric residence systems at a commercial scale. The systems and methods described herein include a plurality of manufacturing stations configured to perform different gastric residence system assembly operations. The various manufacturing stations can be connected by a track. The track can be transited by a transit puck in which the gastric residence system can be assembled in a piecemeal fashion at the various stations.

[0008] A method for assembling a gastric residence system includes loading a transit puck sized and shaped to hold the gastric residence system with a core and a plurality of arm components at one or more loading stations. The transit puck may include grooves into which the core and arm components can be placed. The transit puck may be configured to transit a track (e.g., an electromagnetic track) that connects the one or more loading stations, a component joining station (e.g., a laser welding station), a webbing station, and an encapsulation station. Optionally, the track may run through other manufacturing stations as well, such as cooling and rounding stations. At the component joining station, adjacent components may be joined within the transit puck to form the gastric residence system. The gastric residence system may include the core and a plurality of arms extending radially from the core in a “stellate” or asterisk shape. Optionally, the transit puck may transport the gastric residence system to a cooling station for cooling the gastric residence system and / or a rounding station for rounding or chamfering the edges or ends of the gastric residence system. At the webbing station, the gastric residence system may be transferred from the transit puck to a webbing puck. Adjacent arms may then be connected with a filament within the webbing puck. The gastric residence system may then be returned to the transit puck. The transit puck may transport the gastric residence system to an encapsulation station, which may be located on a separate track. Upon reaching the encapsulation station, the gastric residence system may be removed from the transit puck and placed into a workpiece carrier on the separate track for folding and sleeving. The gastric residence system may then be folded into a compacted configuration and bound in the compacted configuration with a sleeve. The gastric residence system may then be encapsulated with a capsule.3ny-2823215Attorney Docket No. 75056-20042.40

[0009] An exemplary method of manufacturing a gastric residence system comprises: at one or more loading stations, loading a transit puck sized and shaped to hold the gastric residence system with a core and a plurality of arm components, wherein the transit puck is configured to transit a track connecting the one or more loading stations, a component joining station, a webbing station, and an encapsulation station; at the component joining station, joining adjacent components within the transit puck to form the gastric residence system, wherein the gastric residence system may include the core and a plurality of arms extending radially from the core; at the webbing station: transferring the gastric residence system from the transit puck to a webbing puck; connecting adjacent arms with a filament within the webbing puck; and returning the gastric residence system to the transit puck; and at the encapsulation station: removing the gastric residence system from the transit puck; folding the gastric residence system into a compacted configuration; binding the gastric residence system in the compacted configuration with a sleeve; and encapsulating the gastric residence system with a capsule.

[0010] The track may be an electromagnetic track. Loading the transit puck with the core may include: with a bowl feeder, transporting a plurality of cores toward a plurality of feeding lanes; vibrating the plurality of feeding lanes such that cores having a predetermined orientation are received by a feeding lane of the plurality of feeding lanes and cores not having the predetermined orientation are returned to the bowl feeder; and with a pick and place machine: selecting a core from a feeding lane of the plurality of feeding lanes; and placing the core into the transit puck. Selecting a core from a feeding lane of the plurality of feeding lanes may include receiving the core with a vacuum head of the pick and place machine. Placing the core into the transit puck may include releasing the core from the vacuum head of the pick and place machine into the transit puck.

[0011] Loading the transit puck with a plurality of arm components may include: for at least one arm of the gastric residence system: placing a linker component adjacent to the core; placing an active ingredient-containing component adjacent to the linker component; and placing an inactive component adjacent to the active ingredient-containing component. The linker component may include at least one disintegrating matrix component. The at least one disintegrating matrix component may include a time-dependent disintegrating matrix. The at least one disintegrating matrix component may include an enteric disintegrating4ny-2823215Attorney Docket No. 75056-20042.40matrix. The linker component may include at least one inert component. The linker component may include a first inert component, a disintegrating matrix component, and a second inert component connected in that order. The first inert component, the disintegrating matrix component, and the second inert component may be connected by: heating each component to partially melt at least one surface of the respective component; and tacking the first inert component, the disintegrating matrix component, and the second inert component to one another to form the linker component. The disintegrating matrix component may be a first disintegrating matrix component, and the linker may further include a second disintegrating matrix component. The second disintegrating matrix component may be connected to the first inert component or the second inert component by: heating the second disintegrating matrix component to partially melt at least one surface of the second disintegrating matrix component; and tacking the partially melted at least one surface of the second disintegrating matrix component to the first inert component or the second inert component. One of the first disintegrating matrix component and the second disintegrating matrix component may include an enteric disintegrating matrix and the other of the first disintegrating matrix component and the second disintegrating matrix component may include a time-dependent disintegrating matrix.

[0012] The component joining station may be a laser welding station, and joining adjacent components within the transit puck may include laser welding adjacent components within the transit puck.

[0013] Laser welding adjacent components within the transit puck to form the gastric residence system may include applying downward and radial pressure to the gastric residence system while laser welding the adjacent components within the transit puck. The downward pressure may be applied by a plate sized and shaped to cover the transit puck. The plate may include glass. The plate may include fluorinated ethylene propylene. The plate may include a ceramic coating. The component joining station may be a vibrational welding station or an infrared welding station.

[0014] The method may further include cooling the gastric residence system after joining the adjacent components within the transit puck and prior to transferring the gastric residence system from the transit puck to the webbing puck. The method may further include rounding at least one comer of at least one arm of the gastric residence system prior to connecting5ny-2823215Attorney Docket No. 75056-20042.40adjacent arms of the gastric residence system with the filament. The method may further include rounding at least one comer of at least one arm of the gastric residence system after connecting adjacent arms of the gastric residence system with the filament. Rounding at least one comer of the at least one arm of the gastric residence system may include applying a heated die to the at least one comer to at least partially melt and round the at least one comer.

[0015] Connecting adjacent arms with the filament within the webbing puck may include: heating a distal end of each arm of the gastric residence system so as to partially melt the distal end of each arm; pressing the filament into the partially molten distal end of each arm; and covering the filament with the partially molten distal end of each arm to secure the filament within the distal end of each arm. Heating a distal end of each arm of the gastric residence system may include placing a heater configured to heat the distal end of each arm of the gastric residence system adjacent to the webbing puck. The heater may be a ring shape, and a cooling element may be located in a center of the ring. The cooling element may be a water-cooled tower. The water-cooled tower may be configured to cool the core and a remainder of each arm while the distal end of each arm is heated.

[0016] Folding the gastric residence system into the compacted configuration may include: transferring the gastric residence system from the transit puck to a workpiece carrier comprising an upper circular surface, wherein the plurality of arms of the gastric residence system are configured to sit flush against the upper circular surface; and applying a first force to the core of the gastric residence system, wherein applying the first force to the core causes the upper circular surface to apply a second force to the plurality of arms, causing the gastric residence system to fold. Binding the gastric residence system in the compacted configuration with the sleeve may include: positioning the sleeve underneath the gastric residence system in the compacted configuration; and pushing the gastric residence system in the compacted configuration downward into the sleeve. The sleeve may include at least one of gelatin, hydroxypropyl methylcellulose, or pullulan. The sleeve may include a capsule cap. Encapsulating the gastric residence system with the capsule may include inserting the gastric residence system bound by the sleeve into the capsule.6ny-2823215Attorney Docket No. 75056-20042.40

[0017] The method may further include determining that the encapsulated gastric residence system does not contain metal using a metal detector. The method may further include transporting the encapsulated gastric residence system to a storage facility.

[0018] An exemplary system for manufacturing a gastric residence system comprises: one or more loading stations; a component joining station; a webbing station; an encapsulation station; a track connecting the one or more loading stations, the component joining station, the webbing station, and the encapsulation station; and a transit puck configured to transit the track, wherein the transit puck is sized and shaped to hold the gastric residence system.

[0019] The one or more loading stations may include a core loading station. The core loading station may include: a plurality of feeding lanes; a bowl feeder configured to provide cores having a predetermined orientation to a feeding lane of the plurality of feeding lanes and receive cores not having the predetermined orientation; and a pick and place machine configured to select a core from a feeding lane of the plurality of feeding lanes and place the core into the transit puck. The one or more loading stations may include a linker component loading station. The linker component loading station may include: at least three vacuum nozzles, wherein a first vacuum nozzle is configured to receive a first inert component, a second vacuum nozzle is configured to receive a disintegrating matrix component, and a third vacuum nozzle is configured to receive a second inert component; a heater configured to at least partially melt at least one surface of each of the first inert component, the disintegrating matrix component, and the second inert component; a workpiece carrier configured to receive the first inert component, the disintegrating matrix component, and the second inert component, such that adjacent components attach to one another to form the linker component; and a pick and place machine configured to transfer the linker component from the workpiece carrier into the transit puck. The one or more loading stations may include an active ingredient-containing component loading station. The active ingredient-containing component loading station may include: a step feeder; and a pick and place machine configured to transfer an active ingredient-containing component from the step feeder into the transit puck. The one or more loading stations may include an inactive component loading station. The inactive component loading station may include: a step feeder; and a7ny-2823215Attorney Docket No. 75056-20042.40pick and place machine configured to transfer an inactive component from the step feeder into the transit puck.

[0020] The component joining station may be a laser welding station, and the laser welding station may include: at least one laser; at least one plate sized and shaped to cover the transit puck, wherein the at least one plate is configured to apply downward pressure to the gastric residence system during laser welding; and a plurality of radial pistons configured to apply radial pressure to the gastric residence system during laser welding.

[0021] The system may further include a cooling station. The cooling station may include at least one compressed air line configured to direct compressed air toward the gastric residence system. The system may further include a rounding station. The rounding station may include at least one heated die configured to at least partially melt at least one comer of at least one arm of the gastric residence system.

[0022] The webbing station may include: a webbing puck sized and shaped to hold the gastric residence system; a heater configured to heat a distal end of each arm of the gastric residence system when the heater is placed adjacent to the webbing puck so as to at least partially melt the distal end of each arm; a filament inserter configured to insert a portion of the filament into the partially molten distal end of each arm; and a cooling element configured to cool the core and a remainder of each arm of the gastric residence system while the distal end of each arm is heated. The filament inserter may include a first plurality of mechanical fingers configured to: hold the filament in circular shape sized to connect the distal ends of the plurality of arms; and press the filament into the partially molten distal end of each arm. The webbing station further may include a second plurality of mechanical fingers configured to cover the filament using the partially molten distal end of each arm to secure the filament within the distal end of each arm. The cooling element may include a water-cooled tower.

[0023] The encapsulation station may include: a sleeving puck comprising an upper circular surface, wherein a plurality of arms of the gastric residence system are configured to sit flush against the upper circular surface; a first plunger configured to fold the gastric residence system into a compacted configuration; a retaining element configured to hold the gastric residence system in the compacted configuration; a second plunger configured to push the gastric residence system in the compacted configuration through the upper circular8ny-2823215Attorney Docket No. 75056-20042.40surface into a sleeve; and an encapsulator configured to insert the sleeved gastric residence system into a capsule. The track may include an electromagnetic track.

[0024] An exemplary method for manufacturing a linker component of a gastric residence system comprises: receiving a first inert component with a first vacuum nozzle, a disintegrating matrix component with a second vacuum nozzle, and a second inert component with a third vacuum nozzle; exposing the first inert component, the disintegrating matrix component, and the second inert component to a heater while holding each component in its respective vacuum nozzle, such that at least one surface of each component becomes at least partially molten; and while at least one surface of each component is at least partially molten, placing the disintegrating matrix component between the first and second inert components in a workpiece carrier, such that adjacent components attach to one another to form the linker component.

[0025] At least one of the first inert component and the second inert component may include polycaprolactone. At least one of the first inert component and the second inert component further may include bismuth subcarbonate. The disintegrating matrix component may include an enteric disintegrating matrix. The enteric disintegrating matrix may include polycaprolactone. The enteric disintegrating matrix further may include hydroxypropylmethylcellulose acetate succinate (HPMCAS). The enteric disintegrating matrix further may include a poloxamer. The disintegrating matrix component may include a time-dependent disintegrating matrix. The time-dependent disintegrating matrix may include polycaprolactone. The time-dependent disintegrating matrix further may include poly(ethylene oxide). The time-dependent disintegrating matrix further may include 50 / 50 DL-Lactide / Glycolide copolymer. A length of at least one of the first inert component and the second inert component may be between 0.3-0.7 mm. A length of at least one of the first inert component and the second inert component may be 0.5 mm. A length of the disintegrating matrix component may be between 1.5-2.0 mm. A length of the disintegrating matrix component may be 1.85 mm. A length of the disintegrating matrix component may be between 0.7-1.3 mm. A length of the disintegrating matrix component may be 1.0 mm. The disintegrating matrix component may be a first disintegrating matrix component, and the method may further include: receiving a second disintegrating matrix component with a fourth vacuum nozzle; exposing the second disintegrating matrix component to the heater9ny-2823215Attorney Docket No. 75056-20042.40while holding the second disintegrating matrix component in the fourth vacuum nozzle, such that at least one surface of the second disintegrating matrix component becomes at least partially molten; and while the at least one surface of the second disintegrating matrix component is at least partially molten, placing the at least one partially molten surface of the second disintegrating matrix component adjacent to the first inert component or the second inert component in the workpiece carrier, such that the second disintegrating matrix component attaches to the first inert component or the second inert component. At least one of the first and second disintegrating matrix components may include an enteric disintegrating matrix component and the other of the first and second disintegrating matrix components may include a time-dependent disintegrating matrix. The method may further include: measuring a length of the linker component; determining that the length of the linker component matches a target length of the linker component; and providing the linker component to a system for manufacturing gastric residence systems.

[0026] An exemplary system for manufacturing a linker component of a gastric residence system comprises: at least three vacuum nozzles, wherein a first vacuum nozzle is configured to receive a first inert component, a second vacuum nozzle is configured to receive a disintegrating matrix component, and a third vacuum nozzle is configured to receive a second inert component; a heater configured to at least partially melt at least one surface of each of the first inert component, the disintegrating matrix component, and the second inert component; a workpiece carrier configured to receive the first inert component, the disintegrating matrix component, and the second inert component, such that adjacent components attach to one another to form the linker component; and a pick and place machine configured to transfer the linker component from the workpiece carrier into a transit puck.

[0027] The disintegrating matrix component may be a first disintegrating matrix component, and the system may further include a fourth vacuum nozzle configured to receive a second disintegrating matrix component. At least one of the first and second disintegrating matrix components may include an enteric disintegrating matrix component and the other of the first and second disintegrating matrix components may include a time-dependent disintegrating matrix. The system may further include an inspection station configured to: measure a length of the linker component; determine that the length of the linker component10ny-2823215Attorney Docket No. 75056-20042.40matches a target length of the linker component; and provide the linker component to a system for manufacturing gastric residence systems.

[0028] An exemplary method for connecting adjacent arms of a gastric residence system comprising a core and a plurality of arms extending radially from the core with a filament comprises: placing the gastric residence system into a webbing puck; heating a distal end of each arm of the plurality of arms so as to partially melt the distal end of each arm; pressing the filament into the partially molten distal end of each arm; and covering the filament using the partially molten distal end of each arm to secure the filament within the distal end of each arm.

[0029] Heating a distal end of each arm of the gastric residence system may include placing a heater configured to heat the distal end of each arm of the gastric residence system adjacent to the webbing puck. The heater may be a ring shape and may include a cooling element in a center of the ring. The cooling element may include a water-cooled tower. The water-cooled tower may be configured to cool the core and a remainder of each arm while the distal end of each arm is heated. The method may further include: prior to pressing the filament into the partially molten distal end of each arm, winding the filament into a circle sized and shaped to connect the distal ends of the plurality of arms. The method may further include: rounding at least one corner of the gastric residence system. Rounding at least one comer of the gastric residence system may include applying a rounding die to the at least one comer.

[0030] An exemplary system for connecting adjacent arms of a gastric residence system comprising a core and a plurality of arms extending radially from the core with a filament comprises: a webbing puck sized and shaped to hold the gastric residence system; a heater configured to heat a distal end of each arm of the gastric residence system when the heater is placed adjacent to the webbing puck so as to at least partially melt the distal end of each arm; a filament inserter configured to insert a portion of the filament into the partially molten distal end of each arm; and a cooling element configured to cool the core and a remainder of each arm of the gastric residence system while the distal end of each arm is heated.

[0031] The heater may be a ring shape and the cooling element may be located in a center of the ring. The cooling element may include a water-cooled tower. The filament inserter may include a first plurality of mechanical fingers configured to hold the filament in11ny-2823215Attorney Docket No. 75056-20042.40circular shape sized to connect the distal ends of the plurality of arms. The first plurality of mechanical fingers may be configured to press the filament in the circular shape into the distal end of each arm. The system may further include a second plurality of mechanical fingers configured to cover the filament using the partially molten distal end of each arm to secure the filament within the distal end of each arm. The system may further include a rounding die configured to round at least one corner of the gastric residence system. The rounding die may be a heated die.

[0032] It will be appreciated that any of the variations, aspects, features, and options described in view of the systems apply equally to the methods and vice versa. It will also be clear that any one or more of the above variations, aspects, features, and options can be combined.BRIEF DESCRIPTION OF THE DRAWINGS

[0033] The invention will now be described, by way of example only, with reference to the accompanying drawings, in which:

[0034] FIG. 1 illustrates a gastric residence system, according to some embodiments.

[0035] FIG. 2 illustrates a manufacturing system for manufacturing gastric residence systems, according to some embodiments.

[0036] FIG. 3 illustrates a track of a manufacturing system, according to some embodiments.

[0037] FIG. 4 illustrates a transit puck of a manufacturing system, according to some embodiments.

[0038] FIGS. 5A-5B illustrate a core loading station of a manufacturing system, according to some embodiments.

[0039] FIGS. 6A-6C illustrate a linker component assembly portion of a linker component loading station, according to some embodiments.

[0040] FIG. 7 illustrates a linker component, according to some embodiments.

[0041] FIG. 8 illustrates an active or inactive arm component loading station of a manufacturing system, according to some embodiments.

[0042] FIG. 9 illustrates a laser welding station of a manufacturing system, according to some embodiments.12ny-2823215Attorney Docket No. 75056-20042.40

[0043] FIGS. 10A-10B illustrate a webbing station of a manufacturing system, according to some embodiments.

[0044] FIG. 11 illustrates a folding apparatus of an encapsulation station of a manufacturing system, according to some embodiments.

[0045] FIG. 12 illustrates a folded and sleeved gastric residence system, according to some embodiments.

[0046] FIG. 13 illustrates a method for manufacturing a gastric residence system, according to some embodiments.DETAILED DESCRIPTION

[0047] Described herein are commercial-scale systems and methods for manufacturing gastric residence systems. As described above, gastric residence systems can include a plurality of very small, delicate components. The individual components need to be joined in a precise way in order to ensure they do not get damaged and to ensure that the gastric residence system performs as intended (e.g., to ensure that it stays folded during administration, unfolds when in the stomach of a patient, and maintains its unfolded configuration for a predetermined gastric residence period).

[0048] Existing off-the-shelf manufacturing systems are not capable of performing the very precise operations required to arrange and join these very small components without damaging them, especially at speed. For example, a given gastric residence system may require a large number of components to be assembled (e.g., a gastric residence system may include a core and a plurality of arms, with each arm comprising disintegrating matrix components, inert components, and active ingredient-containing components). The components may need to be assembled in a particular order. The components may be very delicate (e.g., sensitive to heating). The components may also be very small - for example, as discussed above, certain pieces of the arms may be less than 0.5 mm in length.Accordingly, assembling these components in a precise manner while preserving their integrity and functionality can be challenging, especially when done quickly.

[0049] The systems and methods provided herein may remedy one or more of the aboveidentified issues. An exemplary system for manufacturing a gastric residence system includes a plurality of assembly stations, such as various component loading stations, a13ny-2823215Attorney Docket No. 75056-20042.40component joining station (e.g., a laser welding station), a webbing station, and an encapsulation station. The various stations can be connected by a track. One or more transit pucks can be configured to transit the track. Components can be assembled within the transit puck, and the transit puck can be used to transport gastric residence systems or components thereof to the various assembly stations. For instance, a transit puck may be loaded with a core and a plurality of arm components at one or more loading stations. The transit puck may continue to a component joining station, at which adjacent components may be joined (e.g., laser welded) within the transit puck to form the gastric residence system. Optionally, the transit puck may transport the gastric residence system to a cooling station to cool the gastric residence system and / or to a rounding station for rounding or chamfering edges or ends of the gastric residence system. The transit puck may continue to a webbing station, where the gastric residence system may be transferred from the transit puck to a webbing puck, and adjacent arms may be connected with a filament within the webbing puck. The gastric residence system may then be returned to the transit puck and transported to an encapsulation station. At the encapsulation station, the gastric residence system may be removed from the transit puck and placed into a workpiece carrier for folding and sleeving. The gastric residence system may then be folded into a compacted configuration and bound in the compacted configuration with a sleeve. The gastric residence system may then be encapsulated with a capsule.Definitions

[0050] As used herein, “gastric residence system” is a dosage form comprising an agent and is configured to be administered to a patient in a folded configuration. A “gastric residence dosage form” comprises a folded gastric residence system and is configured to hold the gastric residence system in a folded configuration until deployment.

[0051] An “active ingredient” is any substance intended for therapeutic, diagnostic, or nutritional use in a patient, individual, or subject. Active ingredients include, but are not limited to, drugs, nutrients, vitamins, and minerals. Active ingredients may also be referred to herein as “agents,” “active agents,” or “active pharmaceutical ingredients.”

[0052] An “elastic polymer” or “elastomer” (also referred to as a “tensile polymer”) is a polymer that is capable of being deformed by an applied force from its original shape for a14ny-2823215Attorney Docket No. 75056-20042.40period of time, and which then substantially returns to its original shape once the applied force is removed.

[0053] An “enteric disintegrating matrix component” is a component comprising an enteric polymer that is relatively resistant to the acidic pH levels encountered in the stomach but dissolve at the higher pH levels found in the duodenum. If a gastric residence system passes intact through the pylorus, the enteric polymer will dissolve, and the components linked by the enteric disintegrating matrix will break apart, allowing passage of the gastric residence system through the small and large intestines.

[0054] A “time-dependent disintegrating matrix component” is a component comprising a polymer that degrades in a time-dependent manner when a gastric residence system is deployed in the stomach. A time-dependent disintegrating matrix component is typically not affected by the normal pH variations in the stomach.

[0055] A “patient,” “individual,” or “subject” refers to a mammal, preferably a human or a domestic animal such as a dog or cat. In a most preferred embodiment, a patient, individual, or subject is a human.

[0056] The “diameter” of a particle as used herein refers to the longest dimension of a particle.

[0057] “Treating” a disease or disorder with the systems and methods disclosed herein is defined as administering one or more of the systems disclosed herein to a patient in need thereof, with or without additional agents, in order to reduce or eliminate either the disease or disorder, or one or more symptoms of the disease or disorder, or to retard the progression of the disease or disorder or of one or more symptoms of the disease or disorder, or to reduce the severity of the disease or disorder or of one or more symptoms of the disease or disorder.

[0058] As used herein, the singular forms “a,” “an,” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. It is also to be understood that the term “and / or” as used herein refers to and encompasses any and all possible combinations of one or more of the associated listed items. It is further to be understood that the terms “includes, “including,” “comprises,” and / or “comprising,” when used herein, specify the presence of stated features, integers, steps, operations, elements, components, and / or units but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, units, and / or groups thereof.15ny-2823215Attorney Docket No. 75056-20042.40

[0059] When numerical values are expressed herein using the term “about” or the term “approximately,” it is understood that both the value specified, as well as values reasonably close to the value specified, are included. For example, the description “about 50° C.” or “approximately 50° C.” includes both the disclosure of 50° C. itself, as well as values close to 50° C. Thus, the phrases “about X” or “approximately X” include a description of the value X itself. If a range is indicated, such as “approximately 50° C. to 60° C.” or “about 50° C. to 60° C.,” it is understood that both the values specified by the endpoints are included, and that values close to each endpoint or both endpoints are included for each endpoint or both endpoints; that is, “approximately 50° C. to 60° C.” (or “about 50° C. to 60° C ”) is equivalent to reciting both “50° C. to 60° C.” and “approximately 50° C. to approximately 60° C.” (or “about 50° C. to 60° C ”).

[0060] This application discloses several numerical ranges in the text and figures. The numerical ranges disclosed inherently support any range or value within the disclosed numerical ranges, including the endpoints, even though a precise range limitation is not stated verbatim in the specification because this disclosure can be practiced throughout the disclosed numerical ranges.

[0061] With respect to numerical ranges disclosed in the present description, any disclosed upper limit for a component may be combined with any disclosed lower limit for that component to provide a range (provided that the upper limit is greater than the lower limit with which it is to be combined). Each of these combinations of disclosed upper and lower limits are explicitly envisaged herein. For example, if ranges for the amount of a particular component are given as 10% to 30%, 10% to 12%, and 15% to 20%, the ranges 10% to 20% and 15% to 30% are also envisaged, whereas the combination of a 15% lower limit and a 12% upper limit is not possible and hence is not envisaged.

[0062] Unless otherwise specified, percentages of ingredients in compositions are expressed as weight percent, or weight / weight percent. It is understood that reference to relative weight percentages in a composition assumes that the combined total weight percentages of all components in the composition add up to 100. It is further understood that relative weight percentages of one or more components may be adjusted upwards or downwards such that the weight percent of the components in the composition combine to a16ny-2823215Attorney Docket No. 75056-20042.40total of 100, provided that the weight percent of any particular component does not fall outside the limits of the range specified for that component.

[0063] Some embodiments described herein are recited as “comprising” or “comprises” with respect to their various elements. In alternative embodiments, those elements can be recited with the transitional phrase “consisting essentially of’ or “consists essentially of’ as applied to those elements. In further alternative embodiments, those elements can be recited with the transitional phrase “consisting of’ or “consists of’ as applied to those elements. Thus, for example, if a composition or method is disclosed herein as comprising A and B, the alternative embodiment for that composition or method of “consisting essentially of A and B” and the alternative embodiment for that composition or method of “consisting of A and B” are also considered to have been disclosed herein. Likewise, embodiments recited as “consisting essentially of’ or “consisting of’ with respect to their various elements can also be recited as “comprising” as applied to those elements. Finally, embodiments recited as “consisting essentially of’ with respect to their various elements can also be recited as “consisting of’ as applied to those elements, and embodiments recited as “consisting of’ with respect to their various elements can also be recited as “consisting essentially of’ as applied to those elements.

[0064] When a composition or system is described as “consisting essentially of’ the listed elements, the composition or system contains the elements expressly listed, and may contain other elements which do not materially affect the condition being treated (for compositions for treating conditions), or the properties of the described system (for compositions comprising a system). However, the composition or system either does not contain any other elements which do materially affect the condition being treated other than those elements expressly listed (for compositions for treating systems) or does not contain any other elements which do materially affect the properties of the system (for compositions comprising a system); or, if the composition or system does contain extra elements other than those listed which may materially affect the condition being treated or the properties of the system, the composition or system does not contain a sufficient concentration or amount of those extra elements to materially affect the condition being treated or the properties of the system. When a method is described as “consisting essentially of’ the listed steps, the method contains the steps listed, and may contain other steps that do not materially affect the17ny-2823215Attorney Docket No. 75056-20042.40condition being treated by the method or the properties of the system produced by the method, but the method does not contain any other steps which materially affect the condition being treated or the system produced other than those steps expressly listed.

[0065] This disclosure provides several embodiments. It is contemplated that any features from any embodiment can be combined with any features from any other embodiment where possible. In this fashion, hybrid configurations of the disclosed features are within the scope of the present invention.General Principles of Gastric Residence Systems

[0066] Gastric residence systems are designed to be administered to a stomach of a patient, either by swallowing or other method of administration (e.g., feeding tube or gastric tube). Once administered, the gastric residence system remains in the stomach for a predetermined residence period (e.g., three days, seven days, two weeks, one month, etc.), referred to as a gastric residence system. During the gastric residence period, the system resists passage through the pylorus, which separates the stomach and the small intestine. The system releases an agent (e.g., an active pharmaceutical ingredient or drug) into the stomach over the gastric residence period at a controlled rate of release. While residing in the stomach, the system may not interfere with the normal passage of food or other gastric contents. Once the desired gastric residence period has elapsed, the system may pass through the pylorus and be eliminated from the patient.

[0067] To administer a gastric residence system to a patient, the gastric residence system may be folded into a configuration small enough to be swallowed or otherwise administered. In some embodiments, the folded gastric residence system is retained in a capsule and / or other container which can be swallowed by the patient or otherwise administered. In some embodiments, a capsule may comprise at least one of gelatin, hydroxypropyl methylcellulose, or pullulan.

[0068] In some embodiments, the folded gastric residence system may also be secured by a dissolvable retaining band or sleeve that can prevent premature deployment of the gastric residence system in case of a failure of the capsule or other container. A gastric residence system folded and retained in a folded configuration with a sleeve or band may be encapsulated by a capsule. In some embodiments, a sleeve or band may comprise at least one of gelatin, hydroxypropyl methylcellulose, or pullulan.18ny-2823215Attorney Docket No. 75056-20042.40

[0069] Once the capsule or other container storing the gastric residence system reaches the stomach of a patient, the capsule or container dissolve and release the folded gastric residence system. Upon release, the gastric residence system may unfold and assume an open configuration. The open configuration may be a stellate shape. The dimensions of the gastric residence system in the open configuration are, when left unaltered, suitable to prevent passage of the gastric residence system through the pylorus for the desired residence period.

[0070] While in the stomach, the gastric residence system is compatible with digestion and other normal functioning of the stomach or gastrointestinal tract. The gastric residence system does not interfere with or impede the passage of chyme (partially digested food) or other gastric contents which exit the stomach through the pylorus into the duodenum.

[0071] The gastric residence system releases an active ingredient (e.g., while in the stomach). The gastric residence system may include one or more active ingredients (e.g., active pharmaceutical ingredients). The one or more active ingredients may be mixed with one or more polymers to form one or more active ingredient-containing components. Active ingredient-containing components may be connected to one or more linker components and / or one or more elastomeric components. An active ingredient may be eluted from the active ingredient-containing components into the gastric fluid of the patient over the desired residence time of the system. Release of the active ingredient may be controlled by appropriate formulation of the active ingredient-containing components, such as by using a dispersant in the formulation of the active ingredient-containing components and / or by milling of the active ingredient to particles of a desired size prior to blending the active ingredient with a polymer and dispersant. In addition, coatings can be applied to outer surfaces of the gastric residence system. The coatings may include additional active ingredients or components that can affect the release of active ingredients or the residence period of the gastric residence system.

[0072] Once the desired residence time has elapsed, the gastric residence system passes out of the stomach. To do so, various components of the gastric residence system are designed to weaken and degrade. The specific dimensions of the system are also taken into consideration. In its intact, open configuration, the gastric residence system is designed to resist passage through the pylorus. However, some linker components of the gastric19ny-2823215Attorney Docket No. 75056-20042.40residence system are chosen such that they gradually degrade over the specified residence period in the stomach. When the linker components are sufficiently weakened by degradation, the gastric residence system loses critical resilience to compression or size reduction and can break apart into smaller pieces. The reduced-size system and any smaller pieces are designed to pass through the pylorus. The system then passes through the intestines and is eliminated from the patient. In some embodiments, a gastric residence system may be designed to weaken at specific locations such that the gastric residence system can pass through a pyloric valve intact once the residence time expires without degrading into numerous smaller pieces.Gastric Residence System Configuration

[0073] Gastric residence systems can be prepared in different configurations. A gastric residence system according to some examples of the disclosure includes one or more arms connected to a central core. An arm may be a component of a gastric residence system which helps the gastric residence system to avoid premature passage through the pyloric sphincter (e.g., by expanding or unfolding in a gastric environment). In some embodiments, at least one arm of a gastric residence system includes an active ingredient-containing component. An active ingredient-containing component may include an agent (also referred to herein as an active ingredient, an active pharmaceutical ingredient, or a therapeutic agent). The active ingredient-containing component may further include one or more polymers and / or other excipients or additives (e.g., stabilizers or dispersants).

[0074] An active ingredient-containing component of a given arm may be attached to at least one linker component, for example via laser welding, infrared welding, adhesion, or any other suitable method of attachment. In some embodiments, linker components may include one or more inert components, time dependent disintegrating matrix components, or enteric disintegrating matrix components. In some embodiments, a given arm may comprise a plurality of linker components. For example, an arm may include an enteric disintegrating matrix component and a time-dependent disintegrating matrix component.

[0075] In some embodiments, a gastric residence system may comprise multiple arms. For example, a gastric residence system may include at least two arms, at least three arms, at least four arms, at least five arms, or at least six arms. In some embodiments, one or more arms may include an active-ingredient containing component. For example, in a gastric20ny-2823215Attorney Docket No. 75056-20042.40residence system with six arms, one arm may include an active-ingredient containing component while five arms exclude an active-ingredient containing component; two arms may include an active-ingredient containing component while four arms exclude an activeingredient containing component; three arms may include an active-ingredient containing component while three arms exclude an active-ingredient containing component; four arms may include an active-ingredient containing component while two arms exclude an activeingredient containing component; five arms may include an active-ingredient containing component while one arm excludes an active-ingredient containing component; or all six arms may include an active-ingredient containing component.

[0076] In some embodiments, the one or more arms may be attached to a core. The core may be an elastomeric component, which may enable the gastric residence system to be compacted, such as by being folded or compressed, into a form suitable for administration to the stomach by swallowing a container or capsule containing the compacted system. Upon dissolution of the capsule in the stomach, the gastric residence system expands into a shape which prevents passage of the system through the pyloric sphincter of the patient for the desired residence time of the system. Thus, the elastomeric component must be capable of being stored in a compacted configuration in a capsule for a reasonable shelflife, and of expanding to its original shape, or approximately its original shape, upon release from the capsule without breaking due to torque or stress.

[0077] In some embodiments, the elastomeric component may comprise an elastomer (also referred to as an elastic polymer or a tensile polymer) overmolded onto one or more intercomponent anchors. An intercomponent anchor serves to link, or anchor, different components of the gastric residence system (e.g., the elastomeric component and an arm) together. In some embodiments, intercomponent anchors may comprise any suitable polymer that adheres or joins well to the components to be linked (e.g., polycarbonate, polyphenylsulfone, a polyphenylene ether-polystyrene blend, polyphenylene ether, polystyrene, or polyether ether ketone). In some embodiments, an intercomponent anchor may be “dumbbell” shaped, comprising relatively thicker lobes at either end of the anchor joined together by a thinner connector portion. Optionally, the intercomponent anchors can have a larger central body from which the first portion and second portion project in opposite directions from each other. The larger central body can have the dimensions of the arms of21ny-2823215Attorney Docket No. 75056-20042.40the gastric residence system, so as to form an intermediate region between the central elastomer and the remainder of the arms of the gastric residence system.

[0078] In some embodiments, an elastomer may be overmolded onto a first portion of an intercomponent anchor (e.g., onto one lobe of a dumbbell-shaped anchor). To facilitate the attachment of the arms to the elastomeric component, an additional component may be overmolded onto a second portion of the intercomponent anchor (e.g., onto the second lobe of the dumbbell). In some embodiments, the additional component may be an inactive component (e.g., poly caprolactone). An arm may then be attached to the additional overmolded component, thus attaching the arm to the elastomeric component. In some embodiments, the elastomeric component may comprise a plurality of intercomponent anchors overmolded with elastomer, such that the elastomer holds one lobe of each of the plurality of intercomponent anchors together. An additional component may be overmolded onto the other lobe of each intercomponent anchor, such that multiple arms may be attached to the elastomeric component via the additional overmolded components.

[0079] In some embodiments, the resulting gastric residence system configuration is a stellate configuration, also known as a “star” or “asterisk” configuration, wherein the elastomeric component is in the center of the system and the arms extend radially outward from the elastomeric component.

[0080] An example of a stellate-shaped gastric residence system 100 is illustrated in FIG.1. The system 100 includes a disk-shaped core 110. The core may be an elastomeric component comprising one or more elastomers (also referred to herein as elastic polymers or tensile polymers) that allow gastric residence system 100 to be compacted, such as by being folded or compressed, into a form suitable for administration to a patient. Upon dissolution of the capsule in the stomach, the gastric residence system expands into a shape which prevents passage of the system through the pyloric sphincter of the patient for the desired residence time of the system. Thus, the core must be capable of being stored in a compacted configuration in a capsule for a reasonable shelflife, and of expanding to its original shape, or approximately its original shape, upon release from the capsule.

[0081] The shape of core 110 may be an asterisk or stellate with branches to which arms may attach. In the example shown in FIG. 1, core 110 has six branches to which six arms are attached. In some embodiments, core 110 may comprise liquid silicon rubber overmolded22ny-2823215Attorney Docket No. 75056-20042.40onto a polycarbonate component. The polycarbonate component may serve as an intercomponent anchor, in that it may extend from core 110 into one or more additional segments, serving to strengthen the connection between core 110 and the arms. In some embodiments, the polycarbonate component of core 110 may be about 7-15 mm, about 10-12 mm, or about 11.5 mm in length at its longest (e.g., from a tip of a first branch to a tip of a second branch positioned directly opposite the first branch), while the overmolded silicon rubber component of core 110 may be about 5-10 mm, about 6-9 mm, about 7-8 mm, or about 7.5 mm in length at its longest.

[0082] System 100 may include a plurality of arms connected to core 110 at a proximal end of each arm and extending radially outward. The arms may be active ingredientcontaining arms 120 or inactive arms 130. FIG. 1 shows an example in which the gastric residence system includes six arms, two of which is an active ingredient-containing arm 120 and four of which are inactive arms 130. However, it should be understood that any number of active and inactive arms can be used. For example, one arm may be an active ingredientcontaining arm while five arms are inactive arms, three arms may be active ingredientcontaining arms while three arms are inactive arms, and so on. Gastric residence systems with having more or less than six total arms are also possible, such as gastric residence systems with two, three, four, five, seven, eight, or more arms.

[0083] In some embodiments, the arms (both active ingredient-containing arms 120 and inactive arms 130) of gastric residence system 100 may have triangular cross-sections. The triangular cross-section may be an equilateral triangular cross-section. In some embodiments, when the cross-section is an equilateral triangle, the base length of the equilateral triangle may be about 2.5 -3.5 mm, about 2.9-3.3 mm, or about 3.1 mm. Arms may have other cross-sectional shapes. For example, arms may have circular cross-sections, pie-shaped cross-sections, square cross-sections, or other polygon-shaped cross-sections.

[0084] Each arm of gastric residence system 100 may include multiple components. For example, an active ingredient-containing arm 120 may include an active ingredientcontaining portion, one or more disintegrating matrix components (also referred to herein as “linker components”) to help the system break down after the desired residence period has elapsed, and one or more inactive components to facilitate connecting the various components.23ny-2823215Attorney Docket No. 75056-20042.40

[0085] Active ingredient-containing arm 120 is connected to core 110 via first inactive component 121. The first inactive component 121 may comprise polycaprolactone (PCL). In some embodiments, first inactive component 121 may be injection molded onto core 110 (e.g., onto a protruding portion of a polycarbonate component of a core comprising silicon rubber overmolded onto a polycarbonate intercomponent anchor) such that first inactive component 121 is a part of elastomeric component 110, rather than a separate component of the active ingredient-containing arm 120. In some embodiments, the radial length of first inactive component may be about 0.1-5 mm, about 0.5-3 mm, or about 1.3 mm.

[0086] First inactive component 121 may be attached to a time-dependent disintegrating matrix component 122. In some embodiments, time-dependent disintegrating matrix component 122 may comprise one or more of PCL (e.g., PCL12), poly(ethylene oxide) (e.g., PEO100K), a DL-lactide / glycolide copolymer (e.g., 50 / 50 DL-Lactide / Glycolide copolymer, acid (pDLG 5002 A)), and / or ferrosoferric oxide. In some embodiments, the radial length of time-dependent disintegrating matrix component 122 may be about 0.1-5 mm, about 0.5-3 mm, or about 1.0 mm. Time-dependent disintegrating matrix component 122 may be configured to degrade in a predictable, time-dependent manner. In some embodiments, degradation of time-dependent disintegrating matrix component 122 may not be affected by the varying pH of the gastrointestinal system.

[0087] Time-dependent disintegrating matrix component 122 may be attached to a second inactive component 123. The second inactive component 123 may comprise radiopaque PCL (rPCL), which may comprise PCL (e.g., Corbion PCI 7) and bismuth subcarbonate. In some embodiments, the radial length of second inactive component 123 may be about 0.05-3 mm, about 0.1-1.5 mm, or about 0.5 mm.

[0088] Second inactive component 123 may be attached to an enteric disintegrating matrix component 124. Enteric disintegrating matrix component 1024 may comprise one or more of PCL, an enteric polymer (e.g., hydroxypropyl methylcellulose acetate succinate MG grade, i.e., HPMCAS-MG), or poloxamer 407 (P407). In some embodiments, the radial length of enteric disintegrating matrix component 124 may be about 0.1-5 mm, about 0.5-3 mm, or about 1.85 mm. Enteric disintegrating matrix component 124 may be designed to break down gradually in a controlled manner during the residence period of the system in the stomach and break down more rapidly if the gastric residence system prematurely passes into24ny-2823215Attorney Docket No. 75056-20042.40the small intestine intact. Enteric disintegrating matrix component 124 may be relatively resistant to the acidic pH levels of the stomach but may dissolve at the higher pH levels found in the duodenum. Thus, enteric disintegrating matrix component 124 may protect against undesired passage of an intact gastric residence system into the small intestine.

[0089] Enteric disintegrating matrix component 124 may be attached to a third inactive component 125. The third inactive component 125 may have the same composition as the second inactive component 123, namely rPCL comprising PCL (e.g., Corbion PC17) and bismuth subcarbonate. In some embodiments, the radial length of third inactive component 125 may be about 0.05-3 mm, about 0.1-1.5 mm, or about 0.5 mm.

[0090] Third inactive component 125 may be attached to an active ingredient-containing component 126. In some embodiments, active ingredient-containing component 126 may include risperidone. Risperidone is used as an illustrative example, but it should be understood that any suitable active ingredient or combination of active ingredients may be used in the gastric residence systems described herein. In some embodiments, if gastric residence system 100 includes multiple active ingredient-containing arms 120, the active ingredient-containing portions of the active ingredient-containing arms may include different active ingredients. For example, a first active ingredient-containing arm 120 may include a first active ingredient, while a second active ingredient-containing arm 120 may include a second active ingredient that is different from the first active ingredient. Active ingredientcontaining component 126 may further include one or more of PCL (e.g., PCL17), copovidone (e.g., Kollidon VA64), poloxamers (e.g., P407), Vitamin E succinate, colloidal silicon dioxide, or colorants (e.g., FD&C Yellow 5 Alum lake, FD&C Blue 1 Alum lake). In some embodiments, the radial length of active ingredient-containing component 126 may be about 3-12 mm, about 5-9 mm, or about 7.3 mm.

[0091] Active ingredient-containing component 126 may be connected to a fourth inactive component 127. Optionally, in some embodiments, a portion of a filament 140 may be embedded in the fourth inactive component 127, which may connect active ingredientcontaining arm 120 to adjacent arms. The fourth inactive component 127 may comprise PCL (e.g., Corbion PCI 7). In some embodiments, the fourth inactive component 127 may further comprise one or more of copovidone (e.g., VA64), poloxamers (e.g., P407), or colorants25ny-2823215Attorney Docket No. 75056-20042.40(e.g., FD&C Blue 1 Alum lake (11-13%)). In some embodiments, the radial length of fourth inactive component 127 may be about 2-10 mm, about 4-7 mm, or about 5.8 mm.

[0092] Inactive arms 130 of gastric residence system 100 do not include an active ingredient-containing component. An inactive arm 130 may include a first inactive component 131 connected to a branch of core 110. The first inactive component 131 may comprise PCL. First inactive component 131 may have the same composition as first inactive component 121. Like first inactive component 121, first inactive component 131 may be injection molded onto a portion of core 110, such that first inactive component 131 is a part of the elastomeric component rather than a separate component of a non-drug eluting arm 130. The radial length of first inactive component 131 may be about 0.1-5 mm, about 0.5-3 mm, or about 1.3 mm.

[0093] First inactive component 131 may be attached to a time-dependent disintegrating matrix component 132. Time-dependent disintegrating matrix component 132 may have the same composition as time-dependent disintegrating matrix component 122, namely one or more of PCL (e.g., PCL12), poly(ethylene oxide) (e.g., PEO100K), a DL-lactide / glycolide copolymer (e.g., 50 / 50 DL-Lactide / Glycolide copolymer, acid (pDLG 5002A)), and / or ferrosoferric oxide. The radial length of time-dependent disintegrating matrix component 132 may be about 0.1-5 mm, about 0.5-3 mm, or about 1.0 mm.

[0094] Time-dependent disintegrating matrix component 132 may be attached to a second inactive component 133. Second inactive component 133 may have the same composition as second inactive component 123, namely PCL (e.g., Corbion PC 17) and bismuth subcarbonate. The radial length of second inactive component 133 may be about 0.05-3 mm, about 0.1-1.5 mm, or about 0.5 mm.

[0095] Second inactive component 133 may be attached to an enteric disintegrating matrix component 134. Enteric disintegrating matrix component 134 may have the same composition as enteric disintegrating matrix component 124, namely one or more of PCL, an enteric polymer (e.g., HPMCAS-MG), or a poloxamer (e.g., P407). The radial length of enteric disintegrating matrix component 134 may be about 0.1-5 mm, about 0.5-3 mm, or about 1.85 mm.

[0096] Enteric disintegrating matrix component 134 may be attached to a third inactive component 1035. Third inactive component 135 may have the same composition as third26ny-2823215Attorney Docket No. 75056-20042.40inactive component 125, namely PCL (e.g., Corbion PC 17) and bismuth subcarbonate. The radial length of third inactive component 135 may be about 0.05-3 mm, about 0.1-1.5 mm, or about 0.5 mm.

[0097] Third inactive component 135 may be attached to a fourth inactive component 1036. Fourth inactive component 136 may have the same composition as fourth inactive component 127, namely one or more of PCL (e.g., Corbion PC17), copovidone (e.g., VA64), poloxamer (e.g., P407), or colorants (e.g., FD&C Blue 1 Alum lake (11-13%)). Optionally, in some embodiments, a portion of a filament 140 may be embedded in the fourth inactive component. The radial length of fourth inactive component 136 may be about 5-20 mm, about 10-15 mm, or about 13.1 mm.

[0098] It should be understood that the composition and arrangement of the gastric residence system components described above are merely exemplary. In some embodiments, gastric residence system may include more, less, or different components than those described above with reference to FIG. 1. For example, as described further below, a gastric residence system may include only a single disintegrating matrix component instead of an enteric disintegrating matrix component and a time-dependent disintegrating matrix component.

[0099] In some embodiments, gastric residence system 100 is about 30 mm to about 60 mm from the tip of a first arm to the tip of a second arm directly opposite the first arm when unfolded. In some embodiments, system 100 is about 41 mm to about 51 mm when unfolded. In some embodiments, system 100 is about 45 mm to about 47 mm when unfolded. In some embodiments, system 100 is about 46 mm when unfolded.

[0100] Gastric residence system 100 must be able to adopt a compacted state with dimensions that enable the patient to swallow the system (or for the system to be introduced into the stomach by alternate means, such as a feeding tube or gastrostomy tube). Typically, the system is held in the compacted state by a container such as a capsule. Upon entry into the stomach, the system is then released from the container and adopts an uncompacted state, that is, an expanded conformation, with dimensions that prevent passage of the system through the pyloric sphincter, thus permitting retention of the system in the stomach.

[0101] Accordingly, the system should be capable of being placed inside a standard-sized capsule of the type commonly used in pharmacy. Standard capsule sizes used in the United27ny-2823215Attorney Docket No. 75056-20042.40States are shown in the Capsule Table below. Preferred capsule sizes are 00 and OOel (where a OOel -size capsule has the approximate length of a 000-size capsule and the approximate width of a 00-size capsule). As these are the outer dimensions of the capsule, and as dimensions will vary slightly between capsule manufacturers, the system should be capable of adopting a configuration which is about 0.5 to about 1 mm smaller than the outer diameter shown, and about 1 mm to about 2 mm shorter than the length shown in the Capsule Table.Capsule TableGastric Residence System Manufacturing

[0102] FIG. 2 illustrates an exemplary manufacturing system 200 for manufacturing gastric residence systems, such as those described above with reference to FIG. 1. The manufacturing system 200 includes a plurality of subsystems or “stations” connected by a track 202. One or more transit pucks can transit track 202 and stop at the various stations, where various components of gastric residence systems are assembled and processed. For example, manufacturing system 200 includes a plurality of loading stations 204, 206, 208, 210, and 212 at which various components of the gastric residence system are loaded into the transit puck. The components can be joined together at a component joining station (e.g., laser welding station 214) and cooled at a cooling station 216. Edges and / or ends of the arms of the resulting gastric residence system can then be rounded at rounding station 218, and the arms of the gastric residence system can be connected with a filament at webbing station 220.28ny-2823215Attorney Docket No. 75056-20042.40The webbed gastric residence system can then be folded, sleeved, and encapsulated at an encapsulation station 222.

[0103] As noted above, the stations of manufacturing system 200 may be connected by a track 202. An exemplary track is illustrated in FIG. 3. The track 302 shown in FIG. 3 mirrors the track configuration illustrated in FIG. 2. However, it should be understood that the configuration of track 302 shown in FIG. 3 is merely exemplary, and any number of suitable track configurations may be used. In some embodiments, track 302 may comprise a plurality of track segments combined together, thus allowing the configuration of track 302 to be customized. In some embodiments, track 302 may be about 10-200 m long, about 20- 150 m long, or about 50-100 m long.

[0104] As noted above, track 302 may be transited by one or more transit pucks 304. Transit pucks 304 may be removably mounted to track 302. In some embodiments, removably mounting a transit puck 304 to track 302 may include mounting transit puck 304 to a workpiece carrier attached to track 302. In some embodiments, track 302 may be an electromagnetic track, and transit pucks 304 may be configured to transit track 302 based on interactions between the electromagnetic components within track 302 and transit pucks 304. For example, a transit puck 304 may include one or more magnets (e.g., permanent magnets) configured to generate a magnetic field. Track 302 may act as a stator, and coils embedded within the track may also generate a magnetic field. The interactions between the magnetic fields of track 302 and transit pucks 304 may provide the force required to drive transit pucks 304 along track 302.

[0105] An exemplary transit puck 400 is illustrated in FIG. 4. Transit puck 400 may be formed from one or more metals such as stainless steel and / or aluminum. The puck may be plated with nickel, silver, chromium, platinum, or any other suitable material, which may increase reflectivity of the puck. The increased reflectivity may be beneficial for the laser welding processes described herein. The puck may have a substantially circular crosssection, with the top surface of the puck having a plurality of grooves 402 sized and shaped for receiving the components of a gastric residence system. For example, in FIG. 4, grooves 402 are sized and shaped to receive the components of a stellate-shaped gastric residence system, such as gastric residence system 100 of FIG. 1. Optionally, transit puck 400 may29ny-2823215Attorney Docket No. 75056-20042.40include a silicone skin covering the grooves 402, which may facilitate removal of the gastric residence system from transit puck 400.

[0106] Transit puck 400 may be at least about 25 mm in diameter, at least about 30 mm in diameter, at least about 35 mm in diameter, at least about 40 mm in diameter, at least about 45 mm in diameter, at least about 50 mm in diameter, at least about 55 mm in diameter, at least about 60 mm in diameter, at least about 65 mm in diameter, at least about 70 mm in diameter, or at least about 75 mm in diameter. In some embodiments, transit puck 400 may be less than about 80 mm in diameter, less than about 75 mm in diameter, less than about 70 mm in diameter, less than about 65 mm in diameter, less than about 60 mm in diameter, less than about 55 mm in diameter, less than about 50 mm in diameter, less than about 45 mm in diameter, less than about 40 mm in diameter, less than about 35 mm in diameter, or less than about 30 mm in diameter. Transit puck 400 may be at least about 11 mm deep, at least about 12 mm deep, at least about 13 mm deep, at least about 14 mm deep, at least about 15 mm deep, at least about 16 mm deep, at least about 17 mm deep, at least about 18 mm deep, or at least about 19 mm deep. In some embodiments, transit puck 400 may be less than about 20 mm deep, less than about 19 mm deep, less than about 18 mm deep, less than about 17 mm deep, less than about 16 mm deep, less than about 15 mm deep, less than about 14 mm deep, less than about 13 mm deep, or less than about 12 mm deep.

[0107] As described above, transit puck 400 may be mounted to a track, allowing the puck to move between gastric residence system assembly stations. In some embodiments, multiple transit pucks 400 may be mounted to a given track to enable multiple gastric residence systems to be assembled simultaneously. In some embodiments, at least 20 transit pucks, at least 30 transit pucks, at least 40 transit pucks, at least 50 transit pucks, at least 60 transit pucks, at least 70 transit pucks, at least 80 transit pucks, at least 90 transit pucks, at least 100 transit pucks, at least 125 transit pucks, at least 150 transit pucks, at least 175 transit pucks, at least 200 transit pucks, at least 300 transit pucks, at least 400 transit pucks, at least 500 transit pucks, at least 600 transit pucks, at least 700 transit pucks, at least 800 transit pucks, or at least 900 transit pucks may be mounted to a given track. In some embodiments, at most 1000 transit pucks, at most 900 transit pucks, at most 800 transit pucks, at most 700 transit pucks, at most 600 transit pucks, at most 500 transit pucks, at most 400 transit pucks, at most 300 transit pucks, at most 200 transit pucks, at most 175 transit pucks, at most 15030ny-2823215Attorney Docket No. 75056-20042.40transit pucks, at most 125 transit pucks, at most 100 transit pucks, at most 90 transit pucks, at most 80 transit pucks, at most 70 transit pucks, at most 60 transit pucks, at most 50 transit pucks, at most 40 transit pucks, or at most 30 transit pucks may be mounted to a given track.

[0108] Returning to FIG. 3, the movement of transit pucks 304 along track 302 may be controlled by a control system 306. Control system 306 may be integrated into the manufacturing system or may be a remote system. Control system 306 may include a user input (e.g., a keyboard, mouse, touch screen, etc.) by which an operator can control the movement of transit pucks 304 along track 302. For example, the operator may use control system 306 to bring a transit puck 304 to a stop at a station or to control the speed or acceleration of the transit puck 304 as it travels between stations. In some embodiments, if multiple transit pucks 304 are transiting track 302, control system 306 may be used to control each transit puck 304 independently. For example, a first transit puck 304 may be controlled to stop at a station while a second transit puck 304 further along track 302 may be simultaneously controlled to accelerate. In some embodiments, control system 306 may be configured to automatically control transit pucks 304 without manual intervention by an operator. For example, control system 306 may be configured to control each transit puck 304 to stop at each of the stations along track 302.

[0109] Transit pucks 304 may travel at varying speeds as they progress along track 302. In some embodiments, a transit puck 304 may reach speeds of about 1 m / s, about 1.5 m / s, about 2 m / s, about 2.5 m / s, about 3 m / s, about 3.5 m / s, about 4 m / s, about 4.5 m / s, or about 5 m / s. In some embodiments, a transit puck 304 may travel at different speeds when transiting different portions of the track. For instance, a transit puck 304 may travel at a first speed between a core loading station and a linker component loading station and travel at a second speed different from the first speed between the linker component loading station and an active ingredient-containing component loading station. Transit pucks 304 may also accelerate and decelerate at various points along track 302. For example, a transit puck 304 may accelerate when leaving a station and decelerate when arriving at the next station.

[0110] Returning to FIG. 2, manufacturing of a gastric residence system may begin at a core loading station 204 at which cores are placed into transit pucks. The core may be the first gastric residence system component loaded into a transit puck. In some embodiments, a check may be performed to ensure that a transit puck is empty before placing the core into31ny-2823215Attorney Docket No. 75056-20042.40the puck. The check may be an automated check in which a camera captures an image of the puck, and an automated image analysis process is performed (e.g., by a processor of a computing system, such as control system 306 of FIG. 3) to verify that the puck is empty. Alternatively, the check may be a manual check in which an operator visually inspects the puck to confirm that the puck is empty.[OHl] Core loading station 204 may include a bowl feeder, a plurality of feeding lanes, and a pick and place system. The bowl feeder may be configured to feed cores into feeding lanes while the feeding lanes vibrate, which causes cores with a predetermined orientation to enter the feeding lanes while cores having different orientations are returned to the bowl feeder. The feeding lanes then transport the cores with the predetermined orientation to a pick and place system, which can place the cores into waiting transit pucks. The cores may be fully formed prior to being introduced into core loading station 204.

[0112] An exemplary core loading station is illustrated in FIGS. 5A-5B. FIG. 5A illustrates a first portion of the core loading station 500 having a bowl feeder 504 configured to feed cores 502 into feeding lanes 508. Only one feeding lane 508 is illustrated in FIG. 5A for the sake of brevity; however, it should be understood that any number of feeding lanes can be used. In some embodiments, core loading station 500 may include two, three, four, five, six, or more feeding lanes. For example, core loading station 500 may include six feeding lanes with six corresponding pick and place heads configured to place cores into six pucks simultaneously.

[0113] Bowl feeder 504 may comprise a substantially cylindrical bowl with a conveyer 506 for transporting cores 502 from the bowl into feeding lanes 508. In some embodiments, the conveyer 506 originates at the bottom of the bowl of bowl feeder 504 (e.g., at a trough 512 for holding cores) and moves upward through the bowl in a helical pattern. Conveyer 506 may terminate at feeding lanes 508, such that cores transported through bowl feeder 504 by conveyer 506 are provided to feeding lanes 508 for further processing.

[0114] Feeding lanes 508 may be vibratory feeding lanes. Feeding lanes 508 may be vibrated in order to orient cores 502 such that they can fit through channels 510 that are placed along a downstream portion of feeding lanes 508. Channels 510 may have a top 511a that extends downward so as to partially cover branches of core 502, bottom 511b that extends upward so as to partially cover branches of core 502 opposite the branches covered32ny-2823215Attorney Docket No. 75056-20042.40by top 511a, and flat backside 511c. Cores 502 may only fit through channels 510 when in a predetermined orientation. For example, cores 502 may have a defined top and bottom. In some embodiments, the bottom of the core may be substantially flat, while the top of the core may be rounded. Thus, a core may only fit within a channel 510 if the flat bottom of the core is flush against flat backside 511 c of channel 510 and the rounded top of the core is facing away from flat backside 511c, such that the rounded top of the core sits between top 511a and bottom 51 lb of channel 510.

[0115] Vibrating feeding lanes 508 may change the orientation of cores 502 such that some cores become correctly aligned with channel 510 and can continue downstream to be loaded into a transit puck. However, not all cores achieve the correct orientation. Cores that do not have the correct orientation to fit into channels 510 may fall into a trough 512.Trough 512 may collect the incorrectly oriented cores and feed them back into bowl feeder 504. Trough 512 may also be used for depositing new cores into core loading station 500. Additional cores can also be introduced into the bowl feeder to replenish cores that have been placed into pucks by depositing the additional cores directly into trough 512.

[0116] Correctly oriented cores that are successfully fed through channels 510 may continue along feeding lanes 508 to be loaded into transit pucks. In some embodiments, if a feeding lane 508 nears its capacity of correctly oriented cores (e.g., if a sensor determines that more correctly oriented cores are making it through a channel 510 than can be transferred to transit pucks in a given amount of time or if an operator observes that feeding lanes 508 are nearly full), bowl feeder 504 may be temporarily shut off such that additional cores are not provided to feeding lanes 508 until bowl feeder 504 is turned back on. Bowl feeder 504 may be turned back on when feeding lanes 508 are ready to receive more cores (e.g., when a sensor determines that less than a certain number of correctly oriented cores are sitting in feeding lanes 508 or when an operator manually turns bowl feeder 504 back on).

[0117] FIG. 5B shows a second portion of core loading station 500 that includes a pick and place system 514 configured to pick cores out of feeding lanes 508 and place them into waiting transit pucks 516. FIG. 5B shows only one pick and place system 514 for the sake of brevity, but it should be understood that core loading station 500 may include multiple pick and place systems. In some embodiments, each feeding lane 508 may have its own33ny-2823215Attorney Docket No. 75056-20042.40corresponding pick and place system 514. Thus, in some embodiments, core loading station may include two, three, four, five, six, or more pick and place systems 514.

[0118] Pick and place system 514 may include a vacuum head. The vacuum head may pick up a core 502 from a feeding lane 508 using suction and transport the core to a waiting transit puck 516, into which the vacuum head may release the core. In some embodiments, if an empty transit puck 516 has not yet arrived at core loading station 500, the pick and place system 514 may hold a core 502 in the vacuum head until the transit puck arrives.

[0119] Returning to FIG. 2, once a transit puck has been loaded with a core, the transit puck can continue along track 202 to a linker component loading station 206. In some embodiments, linker component loading station may be configured to first manufacture a linker component and then load the linker component into a transit puck. In some embodiments, manufacturing system 200 may include multiple linker component loading stations 206, such that multiple linker components can be manufactured and loaded into transit pucks simultaneously. For example, FIG. 2 shows a manufacturing system having two linker component loading stations 206.

[0120] As discussed above with reference to FIG. 1, a gastric residence system may include one or more disintegrating matrix components configured to help the gastric residence system break down after the desired residence period has elapsed, allowing the gastric residence system to pass through the pylorus. However, the disintegrating matrix components may be extremely small. For example, as described above with reference to FIG. 1, the radial length of an enteric disintegrating matrix component may be approximately 1.85 mm, and the radial length of a time-dependent disintegrating matrix component may be approximately 1 mm. Handling components of this size can be challenging, especially at the speeds required for commercial manufacturing. Furthermore, disintegrating matrix components may be sandwiched in between inert components that facilitate joining of adjacent components (e.g., laser welding of adjacent components). The inert components may be even smaller (e.g., approximately 0.5 mm in radial length) and thus even more challenging to handle. Accordingly, loading disintegrating matrix components and their associated inert components into a transit puck directly may be challenging and error-prone.

[0121] To facilitate loading of these components into a transit puck, the components may be pre-assembled into a unified linker component at linker component loading station 206.34ny-2823215Attorney Docket No. 75056-20042.40The linker component loading station may include a linker component assembly portion at which the linker components can be assembled and a pick and place system, similar to the system described above with reference to FIG. 5B, which can transfer assembled linker components into a transit puck.

[0122] FIGS. 6A-6C illustrate an exemplary linker component assembly portion 600 of a linker component loading station. Linker component assembly portion 600 may include a rod feeder 602 configured to feed a rod 604 comprising a linker component material toward a vacuum nozzle 610 and a blade 606 configured to cut a linker component piece 608 from rod 604. Only one rod, rod feeder, vacuum nozzle, and blade are illustrated in FIG. 6A for the sake of brevity. However, it should be understood that linker component assembly portion 600 includes a plurality of rods, feeders, vacuum nozzles, and blades. For example, a linker component assembled by linker component assembly portion 600 may include a disintegrating matrix component sandwiched by two inert components. Thus, linker component assembly portion 600 may include three sets of rods, feeders, vacuum nozzles, and blades, where each set corresponds to a linker component piece. In another example, a linker component assembled by linker component assembly portion may include two disintegrating matrix components (e.g., an enteric disintegrating matrix component and a time-dependent disintegrating matrix component) and two inert components, and linker component assembly portion 600 may include four sets of rods, feeders, vacuum nozzles, and blades.

[0123] Accordingly, in some embodiments, rod 604 may be a disintegrating matrix component or an inert component. Rod 604 may be fed in the direction of blade 606 and vacuum nozzle 610 by rod feeder 602. In some embodiments, rod feeder 602 may comprise a mechanical “finger” configured to push a pre-existing rod toward blade 606 and vacuum nozzle 610.

[0124] Rod feeder 602 may feed rod 604 toward vacuum nozzle 610. When rod 604 contacts vacuum nozzle 610, a blade 606 may descend to cut a linker component piece 608 from rod 604. The geometry of blade 606 may depend on the type of linker component piece being cut. For instance, a blade with a straight edge may be used to cut some linker component pieces, while a blade with a curved edge may be used to cut other linker component pieces. The vacuum nozzle 610 may serve as a hard stop for the rod. Thus, the35ny-2823215Attorney Docket No. 75056-20042.40length of vacuum nozzle 610 may be used to control the length of a linker component piece 608. For example, in FIG. 6 A, using a shorter vacuum nozzle 610 while keeping blade 606 in the same location results in a longer linker component piece 608, while using a longer vacuum nozzle 610 while keeping blade 606 in the same location results in a shorter linker component piece 608. Accordingly, different vacuum nozzles 610 may be used when cutting different types of linker component pieces having different lengths (e.g., a first vacuum nozzle having a first length may be used when cutting an inert component, and a second vacuum nozzle having a second length may be used when cutting a disintegrating matrix component). In some embodiments, linker component assembly portion 600 may produce linker component pieces with a length tolerance of less than about ±0.15 mm.

[0125] Once linker component piece 608 has been cut, it may be held by vacuum nozzle 610. Vacuum nozzle 610 may be turned on (i.e., may begin providing suction) before linker component piece 608 is cut or while linker component piece 608 is being cut. Vacuum nozzle 610 may then transport the cut linker component piece 608 to a heat source and eventually to a workpiece carrier in which a linker component can be assembled. To assemble a linker component, various linker component pieces 608 may be tacked together using heat. For example, a linker component piece 608 may be heated enough to partially melt at least a portion of at least one surface of the linker component piece, and the partially molten surface can be tacked to a portion of another linker component piece. Heat tacking of linker component pieces 608 may create a relatively weak bond between the pieces. The bond may be enough to keep the pieces together while loading them into a transit puck, which may be beneficial because it allows manufacturing system 200 to handle a larger unified linker component rather than a plurality of very small individual linker component pieces. However, the linker component pieces may need to be joined together more permanently later in the gastric residence system manufacturing process to provide the gastric residence system with the necessary structural integrity (e.g., by laser welding the pieces together at laser welding station 212 of FIG. 2).

[0126] In some embodiments, vacuum nozzle 610 may rotate to expose a linker component piece 608 to heat. For example, as shown in FIG. 6B, vacuum nozzle 610 may rotate such that linker component piece 608 is exposed to a heater 612. Heater 612 may be a conductive heater, a convective heater, a micro wave heater, a ceramic heater, a laser heater,36ny-2823215Attorney Docket No. 75056-20042.40an infrared heater, an induction heater, an ultrasonic heater, or any other suitable type of heater.

[0127] After linker component piece 608 has been exposed to heater 612 for a sufficient amount of time to at least partially melt a surface of the piece, vacuum nozzle 610 may rotate such that it is positioned above a workpiece carrier 614. Workpiece carrier 614 may include grooves 616 that are sized and shaped to receive linker component pieces. Workpiece carrier 614 may be similar to the transit puck used in gastric residence manufacturing system 200, except with grooves sized and shaped to receive only pieces of a linker component rather than grooves sized and shaped to receive the components of an entire gastric residence system. Like the transit puck, workpiece carrier 614 may be configured to move along a track 618 that connects various portions of the linker component loading station (e.g., one or more linker component assembly portions 600 and / or one or more inspection stations).Track 618 may be similar to the track used in gastric residence manufacturing system 200.

[0128] Once the workpiece carrier 614 is positioned underneath vacuum nozzle 610, the suction of vacuum nozzle 610 may be turned off in order to deposit linker component piece 608 into a predetermined location within a groove 616 of workpiece carrier 614. Once linker component piece 608 has been deposited, workpiece carrier 614 can move along track 618 to receive another linker component piece from a different vacuum nozzle. The new linker component piece can be deposited adjacent to the existing linker component piece such that a molten surface of at least one of the linker component pieces can be used to tack the two pieces together.

[0129] FIG. 7 illustrates an exemplary heat tacked linker component 700. Linker component 700 includes a time-dependent disintegrating matrix component 702, a first inert component 704, an enteric disintegrating matrix component 706, and a second inert component 708. It should be understood that FIG. 7 is only one example of a linker component, and other linker component configurations can be used. For example, a linker component may include only a time-dependent disintegrating matrix component between two or more inert components or only an enteric disintegrating matrix component between two or more inert components. Alternatively, a linker component may include a combination timedependent and enteric disintegrating matrix component between two or more inert components.37ny-2823215Attorney Docket No. 75056-20042.40

[0130] Once a linker component has been assembled, the linker component may optionally be transported to one or more inspection stations by the workpiece carrier prior to being loaded into the main gastric residence system manufacturing system 200. An inspection station may include a probe that is configured to measure the length of the linker component. The measured length of the linker component may be compared to a target length. If the linker component is within an acceptable range of the target length, the workpiece carrier may transport the linker component to a loading portion of the linker component loading station.

[0131] The loading portion may include one or more feeding lanes and one or more corresponding pick and place heads configured to transfer linker components from the feeding lane(s) to transit pucks of the main gastric residence manufacturing system. The feeding lanes and pick and place heads may be similar to the vibratory feeding lanes and pick and place heads used in the core loading station, as discussed above with reference to FIGS.5A-5B. The loading portion may be configured to load a single transit puck with multiple linker components. For example, a transit puck configured to hold a gastric residence system having six arms may receive six linker components at the linker component loading station (one linker component corresponding to each arm). The pick and place heads may be configured to rotate while holding the linker components such that linker components can be deposited into each of the arm grooves, which are located 60-degrees relative to one another.

[0132] Returning to FIG. 2, once a transit puck has been loaded with the requisite number of linker components, the transit puck can continue along track 202 to active ingredient-containing component loading station 208 and inactive component loading stations 210 and 212. Each of stations 208, 210, and 212 may include similar equipment but may be configured to load the transit puck with different types of arm components. In the example of FIG. 2, station 208 is an active ingredient-containing component loading station, and stations 210 and 212 are inactive component loading stations. However, it should be understood that alternative configurations may be used, and active ingredient-containing components and inactive components may be loaded at any one or more of stations 208, 210, and 212.

[0133] Active ingredient-containing component loading station 208 may be configured to load active ingredient-containing components into one or more arms of the gastric residence38ny-2823215Attorney Docket No. 75056-20042.40system. The active ingredient-containing components may be formed (e.g., extruded, injection molded, and / or overcoated) and cut to the desired size prior to being provided to active ingredient-containing component loading station 208. In some embodiments, active ingredient-containing components may also be coated with a release rate-modulating coating prior to being provided to station 208. Manufacturing system 200 may include one or more active ingredient-containing component loading stations 208. Only one such station is illustrated in FIG. 2, but it should be understood that any other suitable number of active ingredient-containing component loading stations 208 can be used, such as two, three, four, five, six, or more active ingredient-containing component loading stations.

[0134] Inactive component loading station 210 may be configured to load inactive components onto the arms that received active ingredient-containing components at station 208. Manufacturing system 200 may include one or more inactive component loading stations 210. One such station is illustrated in FIG. 2, but it should be understood that any other suitable number of inactive component loading stations 210 can be used, such as two, three, four, five, six, or more active ingredient-containing component loading stations.

[0135] Inactive component loading station 212 may be configured to load inactive components onto the arms that did not receive active ingredient-containing components at station 208. Thus, the inactive components fed at station 212 may have a greater length than the inactive components fed at station 210. For example, the inactive components fed at station 210 may correspond to inactive tips 127 of FIG. 1, while the inactive components fed at station 212 may correspond to inactive tips 136 of FIG. 1.

[0136] FIG. 8 illustrates an exemplary active or inactive component loading station. The station 800 may include a step feeder 802 configured to feed a plurality of arm components 804 into a feeding lane 810. Only one step feeder and feeding lane are illustrated in FIG. 8 for the sake of brevity; however, it should be understood that any number of step feeders and / or feeding lanes can be used in parallel (e.g., two, three, four, five, six, or more).

[0137] Step feeder 802 may include a moving tray 806 and a trough 808. Moving tray 806 may be configured to feed arm components 804 from trough 808 to feeding lanes 810. Moving tray 806 may be lowered into trough 808 to receive arm components 804. Once loaded with arm components 804, moving tray 806 may move upward toward feeding lanes 810 and deposit the arm components into the feeding lanes. Feeding lanes 810 may be39ny-2823215Attorney Docket No. 75056-20042.40vibratory feeding lanes, similar to those described above with reference to FIGS. 5A-5B. If an arm component 804 does not have a predetermined orientation when it reaches a channel 812 in feeding lane 810 that is sized and shaped to receive components in the predetermined orientation, the component may fall out of feeding lane 810 and into trough 808 below.

[0138] Components that fit through channel 812 may continue along feeding lane 810 to a pick and place head 814. Pick and place head 814 may include a vacuum nozzle configured to pick up components 804 using suction and transport the components to a rotating component placement system 816. Because the arms of a stellate shaped gastric residence system are distributed around the circumference of the core (e.g., in a six arm stellate, the arms are angled 60-degrees relative to one another), some components must be rotated in order to fit into the grooves in the transit puck. Accordingly, pick and place head 814 may release a component 804 into a slot in rotating component placement system 816, which can then rotate the component before depositing it into the proper location in a transit puck 818 that is transiting track 820. In some embodiments, a second pick and place head (not pictured in FIG. 8) may be used to transfer rotated components from rotating component placement system 816 into transit puck 818.

[0139] The placement of various arm components within the grooves of transit puck 818 and the amount by which each component needs to be rotated may be determined by a control system. For example, a control system such as system 306 of FIG. 3 may monitor each transit puck that is transiting the track of the manufacturing system. For each transit puck, the control system may determine whether the transit puck has received the necessary components and which components, if any, are still needed and the orientation in which they need to be placed into the transit puck. For example, the control system may be programmed to produce gastric residence systems with two active ingredient-containing arms; thus, only two arms should receive active ingredient-containing components from station 208 and the shorter inactive tips from station 210, while four arms should receive the longer inactive tips from station 212. Based on a pre-determined arrangement of the active ingredient-containing arms and the inactive arms, the control system may determine how much each component should be rotated in order to be placed in the correct grooves.

[0140] Once all components have been loaded into the transit puck, the components may be joined together at a component joining station, such as laser welding station 214. The40ny-2823215Attorney Docket No. 75056-20042.40exemplary system of FIG. 2 includes a laser welding station, but it should be understood that the component joining station may use any other suitable techniques for joining gastric residence system components within a transit puck, such as vibrational welding, heat welding, or infrared welding.

[0141] In some embodiments, a quality check may be performed prior to laser welding. For example, a component check may be performed to ensure that all of the necessary components were loaded into the transit puck. The component check may be a camera check in which a camera positioned between the last loading station and the welding station captures one or more images that are automatically analyzed to determine whether each arm component is present and in the correct location. Alternatively, the component check may be a sensor check in which a sensor is used to determine whether the length of the arms matches a target length or a manual check in which an operator visually observes the presence and placement of the arm components. If the quality check determines that the arm components are present and placed correctly, the transit puck can continue to laser welding station 214. If the quality check determines that one or more arm components are missing and / or are in the incorrect position, the transit puck may continue through the remaining stations without being processed and eventually be disposed of at a defective gastric residence system disposal station at the end of the manufacturing process.

[0142] Laser welding station 214 may include one or more lasers configured to laser weld adjacent components within the transit puck together to form a gastric residence system. An exemplary laser welding station 900 is illustrated in FIG. 9. Only one laser is illustrated for the sake of brevity; however, it should be understood that a laser welding station may include a plurality of lasers configured to laser weld multiple gastric residence systems simultaneously. For example, a laser welding station may include two, three, four, five, six, eight, ten, twelve, fifteen, twenty, thirty, forty, fifty, sixty, seventy, eighty, ninety, one hundred, or more lasers.

[0143] Laser welding station 900 includes a laser 902 that is positioned over a portion of the track 904 transited by transit puck 906. Laser 902 may be a near infrared laser. In some embodiments, the wavelength of light emitted by laser 902 may be about 1000-3000 nm, about 1500-2500 nm, about 1800-2000 nm, or about 1940 nm. The beam emitted by laser 902 may have a diameter or spot size of about 0.5-5 mm, about 0.75-4 mm, or about 1-3 mm.41ny-2823215Attorney Docket No. 75056-20042.40Laser 902 may be directed at the interfaces between adjacent components within transit puck 906 in order to join the adjacent components and form a gastric residence system.

[0144] To laser weld the components of the gastric residence system, transit puck 906 may move along track 904 into a housing that comprises laser 902. A plate 908 may then descend to cover the top surface of transit puck 906 in order to hold the gastric residence system components 910 in place during welding. Plate 908 may help to mitigate flashing during welding as well as prevent the flow of molten materials out of the transit puck. Plate 908 may comprise fluorinated ethylene propylene (FEP). In some embodiments, plate 908 may be a glass plate coated with FEP. In some embodiments, plate 908 may be coated with a nonstick ceramic coating instead of FEP. The length and width of plate 908 may match the length and width of the top of transit puck 906. For example, if transit puck 906 has a circular cross-section, as shown in FIG. 9, the diameter of plate 908 may match the diameter of transit puck 906. In some embodiments, plate 908 may be at least about 0.025 in thick, at least about 0.027 in thick, at least about 0.029 in thick, at least about 0.031 in thick, or at least about 0.033 in thick. In some embodiments, plate 908 may be less than about 0.035 in thick, less than about 0.033 in thick, less than about 0.031 in thick, less than about 0.029 in thick, or less than about 0.027 in thick.

[0145] Plate 908 may provide a downward force to the gastric residence system components 910 during laser welding in order to prevent the flow of molten components. Plate 908 may be connected to a vertical piston 914 configured to provide the downward force. In some embodiments, vertical piston 914 may be connected to a plurality of plates (e.g., two, three, four, or more plates) in order to provide a downward force to the plurality of plates simultaneously. The downward force applied during welding may be about 100-5000 N, about 150-3000 N, or about 200-2800 N. In some embodiments, the downward force applied during welding may be at least about 100 N, at least about 200 N, or at least about 250 N. In some embodiments, the downward force applied during welding may be less than about 5000 N, less than about 4000 N, less than about 3000 N, or less than about 2800 N.

[0146] Laser welding station 900 may further include a plurality of radial pistons 912 configured to engage the tips of the arms of the gastric residence system during laser welding. Radial pistons 912 may descend from above transit puck 906 and stop parallel to the gastric residence system. Radial pistons 912 may provide a radial force to each arm to42ny-2823215Attorney Docket No. 75056-20042.40prevent the arm from expanding radially (i.e., to prevent molten components from seeping radially outward) during laser welding. In some embodiments, the radial force applied by each radial piston 912 may be about 5-200 N, about 8-100 N, or about 10-50 N. In some embodiments, the radial force applied by each radial piston 912 may be at least about 5 N, at least about 8 N, or at least about 10 N. In some embodiments, the radial force applied by each radial piston 912 may be less than about 200 N, less than about 100 N, or less than about 50 N. In some embodiments, radial pistons 912 may have a hard stop in order to prevent the pistons from deforming the arms of the gastric residence system.

[0147] In some embodiments, the radial force and downward force may be applied in a stepwise manner in order to prevent gastric residence system components 910 from becoming dislodged from transit puck 906 and to prevent deformation of the gastric residence system components 910 prior to welding. For example, a relatively low downward force (e.g., about 20 PSI) may be applied first. A relatively high radial force (e.g., about 65 PSI) may then be applied by the radial pistons. Subsequently, a larger downward force (e.g., about 80 PSI) may be applied. The radial force may then be decreased (e.g., to about 15 PSI), at which point the welding process may begin.

[0148] During laser welding, the laser beam may be moved along a repetitive path, such as a circular path. For example, the laser beam may be moved along a circular path which is symmetrical about the core of the gastric residence system and may trace the same interface on each arm of the gastric residence system, such that corresponding interfaces on different arms are heated as the laser beam moves along the circular path. A laser beam may be configured to follow multiple repetitive paths in order to laser weld a given system, wherein each repetitive path corresponds to a different set of interfaces to be welded. In some embodiments, the laser beam may be configured to follow at least one repetitive path, at least two repetitive paths, at least three repetitive paths, at least four repetitive paths, at least five repetitive paths, or at least six repetitive paths for a given gastric residence system. In some embodiments, repetitive paths may be welded in order moving radially outward from the center of the system (e.g., the first repetitive path may weld the interfaces closest to the core, while subsequent repetitive paths weld the interfaces further from the core).

[0149] In some embodiments, the laser beam may make multiple passes around a given repetitive path in order to ensure a complete weld (i.e., to ensure that the laser beam melts the43ny-2823215Attorney Docket No. 75056-20042.40entire interface between the welded components) before moving on to another repetitive path. In some embodiments, the laser beam may make about 10-2000 passes around a given path, about 25-1500 passes around a given path, or about 40-1300 passes around a given path. In some embodiments, the laser beam may make at least about 10 passes around a given path, at least about 25 passes around a given path, or at least about 40 passes around a given path. In some embodiments, the laser beam may make less than about 2000 passes around a given path, less than about 1500 passes around a given path, or less than about 1300 passes around a given path. In some embodiments, the laser beam may follow a given path for about 1-90 seconds, about 1-60 seconds, about 1-30 seconds, about 1-15 seconds, or about 1-10 seconds. In some embodiments, the laser beam may follow a given path for at least about 1 second, at least about 2 seconds, at least about 3 seconds, at least about 4 seconds, at least about 5 seconds, at least about 10 seconds, at least about 15 seconds, at least about 20 seconds, at least about 30 seconds, at least about 45 seconds, at least about 60 seconds, or at least about 75 seconds. In some embodiments, the laser beam may follow a given path for at most about 90 seconds, at most about 75 seconds, at most about 60 seconds, at most about 45 seconds, at most about 30 seconds, at most about 20 seconds, at most about 15 seconds, at most about 10 seconds, at most about 5 seconds, at most about 4 seconds, at most about 3 seconds, or at most about 2 seconds. .

[0150] Once the laser beam finishes welding a given path, the gastric residence system may be allowed to cool in place before welding a subsequent path. In some embodiments, the gastric residence system may be allowed to cool for about 1-120 seconds, about 5-90 seconds, about 8-60 seconds before starting to weld the next path. In some embodiments, the gastric residence system may be allowed to cool for at least about 1 second, at least about 5 seconds, at least about 8 seconds, at least about 10 seconds, at least about 15 seconds, at least about 20 seconds, at least about 30 seconds, at least about 45 seconds, at least about 60 seconds, at least about 75 seconds, at least about 90 seconds, or at least about 105 seconds before starting to weld the next path. In some embodiments, the gastric residence system may be allowed to cool for less than about 120 seconds, less than about 105 seconds, less than about 90 seconds, less than about 75 seconds, less than about 60 seconds, less than about 45 seconds, less than about 30 seconds, less than about 20 seconds, less than about 15 seconds, less than about 10 seconds, less than about 8 seconds, or less than about 5 seconds44ny-2823215Attorney Docket No. 75056-20042.40before starting to weld the next path. In some embodiments, the settings of the laser may be varied for different paths. For example, the energy and / or power of the laser required to laser weld an active ingredient-containing component to a linker component may differ from the energy and / or power required to laser weld a linker component to a core.

[0151] In some embodiments, one or more interfaces of the gastric residence system may be welded individually instead of following a repetitive path around the gastric residence system. For example, some arms of the gastric residence system may include active ingredient-containing components, while other arms do not. As such, interfaces on active ingredient-containing arms may not have corresponding interfaces on the other arms. Thus, certain interfaces on the active ingredient-containing arms may be welded separately.

[0152] In some embodiments, the laser beam may have a Gaussian energy profile in which the highest concentration of energy is in the center of the beam, and the concentration of energy decreases radially outward. Alternatively, the laser beam may have a flat top or “top hat” energy profile. For a beam with a top hat energy profile, the concentration of the energy is flat and uniform across the width of the beam, with sharp edges where the energy concentration drops rapidly to zero. In some embodiments, other laser beam profiles may be used, such as a diffraction energy profile or a reverse-Gaussian energy profile.

[0153] The power and energy of the laser may be varied based on the composition of the components being welded. For example, the power and energy used to laser weld a linker component to an active ingredient-containing component may differ from the power and energy used to laser weld a linker component to a core. In some embodiments, the power of the laser may be about 10-1200 W, about 20-1000 W, or about 30-800 W. In some embodiments, the power of the laser may be at least about 10 W, at least about 20 W, or at least about 30 W. In some embodiments, the power of the laser may be less than about 1200 W, less than about 1000 W, or less than about 800 W. In some embodiments, the energy of the laser may be about 10-750 J, about 30-500 J, or about 40-450 J. In some embodiments, the energy of the laser may be at least about 10 J, at least about 30 J, or at least about 40 J. In some embodiments, the energy of the laser may be less than about 750 J, less than about 500 J, or less than about 450 J.

[0154] In some embodiments, the speed of the laser may be varied depending on the amount of energy desired to be applied to a particular interface. For example, if a certain45ny-2823215Attorney Docket No. 75056-20042.40interface requires more energy to weld, the power of the laser can be kept constant while decreasing the speed, thus increasing the amount of time the laser is incident on any given point. In some embodiments, the speed of the laser may be about 500-5000 mm / s, about 700-4500 mm / s, or about 900-4000 mm / s. In some embodiments, the speed of the laser may be at least about 500 mm / s, at least about 700 mm / s, at least about 1000 mm / s, at least about 2000 mm / s, at least about 3000 mm / s, at least about 3500 mm / s, at least about 4000 mm / s, or at least about 5000 mm / s. In some embodiments, the speed of the laser may be less than about 5000 mm / s, less than about 4000 mm / s, 3500 mm / s, less than about 3000 mm / s, less than about 2000 mm / s, less than about 1000 mm / s, less than about 700 mm / s, or less than about 500 mm / s.

[0155] In some embodiments, to avoid burning the components to be welded, the laser beam may be “wobbled” about the interface(s) to be welded. When a beam is wobbled, the beam does not exactly follow the seam between the components to be welded but rather moves in a regular or irregular pattern around the seam. Thus, wobbling a beam may effectively increase the diameter of the beam. In some embodiments, the wobble radius of a wobbled beam may be about 0.5-10 mm, about 0.7-5 mm, or about 1-3 mm. In some embodiments, the wobble radius of a wobbled beam may be at least about 0.5 mm, at least about 0.7 mm, or at least about 1 mm. In some embodiments, the wobble radius of a wobbled beam may be less than about 10 mm, less than about 5 mm, or less than about 3 mm. Wobbling may be used for beams having any energy profile, including a Gaussian energy profile or a top hat energy profile.

[0156] In some embodiments, laser welding a given gastric residence system takes about 1-180 seconds from the time the gastric residence system enters the laser welding station to the time the gastric residence system exits the laser welding system. In some embodiments, laser welding a given gastric residence system takes at least about 1 second, at least about 3 seconds, at least about 5 seconds, at least about 10 seconds, at least about 20 seconds, at least about 30 seconds, at least about 45 seconds, at least about 60 seconds, at least about 75 seconds, at least about 90 seconds, at least about 105 seconds, at least about 120 seconds, at least about 135 seconds, at least about 150 seconds, at least about 165 seconds, or at least about 180 seconds. In some embodiments, laser welding a given gastric residence system takes at most about 180 seconds, at most about 165 seconds, at most about 150 seconds, at46ny-2823215Attorney Docket No. 75056-20042.40most about 135 seconds, at most about 120 seconds, at most about 105 seconds, at most about 90 seconds, at most about 75 seconds, at most about 60 seconds, at most about 45 seconds, at most about 30 seconds, at most about 20 seconds, at most about 10 seconds, at most about 10 seconds, at most about 5 seconds, or at most about 1 seconds. In some embodiments, the gastric residence system is irradiated with a laser for only a portion of the total time in the laser welding station. For example, a gastric residence system may be irradiated with a laser for a total of about 1-30 seconds, about 2-20 seconds, about 5-15 seconds, or about 6-8 seconds. In some embodiments, the gastric residence system may be irradiated with a laser for at least about 1 second, at least about 2 seconds, at least about 3 seconds, at least about 4 seconds, at least about 5 seconds, at least about 6 seconds, at least about 7 seconds, at least about 8 seconds, at least about 9 seconds, at least about 10 seconds, at least about 15 seconds, at least about 20 seconds, or at least about 25 seconds. In some embodiments, the gastric residence system may be irradiated with a laser for at most about 30 seconds, at most about 25 seconds, at most about 20 seconds, at most about 15 seconds, at most about 10 seconds, at most about 9 seconds, at most about 8 seconds, at most about 7 seconds, at most about 6 seconds, at most about 5 seconds, at most about 4 seconds, at most about 3 seconds, or at most about 2 seconds.

[0157] Once gastric residence system components 910 have been laser welded, radial pistons 912 may disengage the tips of the gastric residence system arms and retract back into the housing of laser welding station 900. Plate 908 may also retract to allow transit puck 906 to continue along track 904 to the next station.

[0158] Once plate 908 and radial pistons 912 have been removed, transit puck 906 can continue along track 904 to the next station. In some embodiments, prior to moving to the next station, a quality check may be performed. The quality check may be a camera check in which a camera positioned at an exit from the laser welding station captures one or more images that are automatically analyzed to determine whether the gastric residence system components appear to have been sufficiently laser welded together (e.g., if there is visible evidence of melting at the interfaces between components). Alternatively, the component check may be a manual check in which an operator visually observes the welds between the gastric residence system components. If the quality check determines that the gastric residence system components have been sufficiently laser welded, the transit puck can47ny-2823215Attorney Docket No. 75056-20042.40continue along the track to the next station. If the quality check determines that the laser welding failed to sufficiently join the gastric residence system components, the transit puck may continue through the remaining stations without being processed and eventually be disposed of at a defective gastric residence system disposal station at the end of the manufacturing process.

[0159] Returning to FIG. 2, the transit puck may optionally continue along track 202 to a cooling station 216. Cooling station 216 may provide active cooling to ensure that the gastric residence system is rigid enough to be removed from the transit puck for further processing (i.e., that the gastric residence system is fully cooled and there are no molten pieces). In some embodiments, cooling station 216 may include one or more compressed air lines configured to blow compressed air at the gastric residence system within the transit puck.

[0160] The transit puck may optionally continue to a rounding station 218. Rounding station 218 may include a pick and place head that is configured to remove the gastric residence system from the transit puck and place it into a rounding nest. A rounding or chamfering die may then be applied to the tips of the arms of the gastric residence system. In some embodiments, the rounding or chamfering die may be heated. The heat may partially melt the tips of the arms. The heat, combined with pressure applied by the rounding or chamfering die, may cause the tips of the arms to become rounded or chamfered. Once all of the tips of the arms have been rounded or chamfered, the pick and place head may remove the gastric residence system from the rounding nest and place the gastric residence system back into the transit puck.

[0161] Although cooling station 216 is illustrated in the example of FIG. 2 as being placed before rounding station 218 along track 202, it should be understood that the placements of cooling station 216 and rounding station 218 may be switched. If rounding station 218 is placed before cooling station 216 along track 202, the transit puck may be configured to bypass rounding station 218 to enter cooling station 216 and subsequently return to rounding station 218 after cooling.

[0162] The transit puck may continue along track 202 to a webbing station 220. As discussed above with reference to FIG. 1, a filament (also referred to herein as “webbing”) may be used to connect adjacent arms of a gastric residence system. The filament or48ny-2823215Attorney Docket No. 75056-20042.40webbing may prevent the gastric residence system from prematurely passing through the pylorus.

[0163] An exemplary webbing station 1000 is illustrated in FIGS. 10A-10B. As shown in FIG. 10A, webbing station 1000 may include a webbing puck 1002 that is sized and shaped to hold a gastric residence system 1004. In some embodiments, a pick and place head (not shown in FIG. 10A) may be used to remove gastric residence system 1004 from a transit puck transiting the track of the main gastric residence system assembly line and place gastric residence system 1004 into webbing puck 1002. Like the transit puck, webbing puck 1002 may be a substantially cylindrical metal element with grooves sized and shaped to hold a gastric residence system. Webbing puck 1002 may further include slots 1006 on either side each arm groove near the distal ends of the arms. Slots 1006 may be sized and shaped to receive a filament, such that when a filament is inserted into the distal ends of the arms of the gastric residence system, the filament can be pressed downward within slots 1006.

[0164] Webbing station 1000 may further include a heater 1008. Heater 1008 may be configured to heat the distal ends of the arms of the gastric residence system, such that a filament can be inserted into the distal ends of the arms while they are in a partially molten state. In some embodiments, the heater may be a laser heater, an infrared heater, a ceramic heater, a micro wave heater, an induction heater, an ultrasonic heater, a convective heater, and / or a conductive heater. Optionally, a lens may be used to focus the heat emitted from the heater. The heater may be heated to about 500-1500°C, about 700-1000°C, or about 800°C. Heater 1008 may be placed adjacent to but not touching gastric residence system 1004, so as to avoid burning or otherwise damaging gastric residence system 1008.

[0165] In some embodiments, heater 1008 may be a ring-shaped heater, as shown in FIG.10 A. The ring may be sized and shaped such that heater 1008 is adjacent to only the distal ends of the arms of gastric residence system 1004, which may prevent the rest of gastric residence system 1004 from melting or being otherwise damaged by the heat. In some embodiments, webbing station 1000 may further include a cooling element. In some embodiments, the cooling element may be a water-cooled tower 1010 that fits in the center of heater 1008. Water-cooled tower 1010 may help prevent the core and proximal ends of the arms of gastric residence system 1004 from being melted by heater 1008. Water-cooled tower 1010 also ensures that webbing puck 1002 does not become too hot and thus heat the49ny-2823215Attorney Docket No. 75056-20042.40core and proximal ends of the arms of gastric residence system 1004. Alternatively, the cooling element may be a cooled air or cooled gas curtain.

[0166] Once the distal ends of the arms of gastric residence system 1004 have been partially melted, webbing puck 1002 may move to a second portion of webbing station 1000 and come to a stop underneath a wound filament 1012. Filament 1012 may be wound into a circle that is sized to connect the distal ends of adjacent arms of gastric residence system 1004.

[0167] In some embodiments, filament 1012 may be wound around a plurality of mechanical fingers 1014, as shown in FIG. 10B. A first clamp (not pictured) may be configured to hold a first end of filament 1012 and provide the first end to a mechanical finger 1014. The first end may be attached to the mechanical finger 1014, for example by hooking the filament on a protrusion of the finger. Once the first end of the filament is secured to mechanical finger 1014, the first clamp can retract, and the plurality of mechanical fingers 1014 may begin to rotate. The mechanical fingers may rotate 360-degrees, such that the filament forms a complete circle around the plurality of mechanical fingers 1014. The second end of filament 1012 may be held by a second clamp (also not pictured), which may be pulled toward the mechanical fingers 1014 as filament 1012 is wound. Once filament 1012 has formed a complete circle, the second clamp may release filament 1012 and retract.

[0168] Once filament 1012 has been wound, filament 1012 may be pressed down into the molten distal ends of gastric residence system 1004, such as by lowering mechanical fingers 1014 (also referred to herein as a “filament inserter”). Filament 1012 may be inserted within slots 1006 of webbing puck 1002. Once filament 1012 has been placed within the molten distal ends, a separate, second plurality of mechanical fingers (not pictured) may be dragged across the exposed surfaces of the arms of gastric residence system 1004. Dragging the second plurality of mechanical fingers across the surfaces of the arms may spread the partially molten distal end of each arm over the filament, thus covering the filament with polymer so as to secure the filament within the distal end of each arm. In some embodiments, the first plurality of mechanical fingers 1014 may be used to spread the partially molten distal end of each arm over the filament instead of using a separate, second plurality of mechanical fingers. Once the filament has been secured within the distal end of each arm, the second set of mechanical fingers may then retract, and gastric residence system50ny-2823215Attorney Docket No. 75056-20042.401004 may be returned to a transit puck on the main gastric residence system assembly line (e.g., using a pick and place head). In some embodiments, gastric residence system 1004 may be returned to the same transit puck that provided gastric residence system 1004 to webbing station 1000. In some embodiments, gastric residence system 1004 may be returned to a different empty transit puck.

[0169] Optionally, webbing station 1000 may further include a rounding or chamfering die, such that rounding or chamfering of the tips of the gastric residence system arms can be performed at webbing station 1000 rather than at a separate rounding station. For example, once the filament has been inserted into the gastric residence system as described above, the gastric residence system may be exposed to a rounding or chamfering die while in the webbing puck. The rounding or chamfering die may be a room temperature rounding or chamfering die. The rounding or chamfering die may be applied to the tips of the gastric residence system arms immediately following filament insertion, such that residual heat in the arms provided by the heater used in the webbing process may at least partially melt the tips of the arms to facilitate rounding or chamfering.

[0170] It should be understood that a webbing station of a manufacturing system (e.g., webbing station 220) may include a plurality of webbing stations 1000, such that multiple gastric residence systems may be webbed simultaneously. In some embodiments, webbing station 220 includes at least about 2, 3, 4, 5, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, or 100 individual webbing stations 1000.

[0171] Returning to FIG. 2, the transit puck may continue along track 202 to an encapsulation station 222. At encapsulation station 222, the gastric residence may be removed from the transit puck, folded, inserted into a sleeve, and inserted into a capsule. Optionally, a quality check may be performed between webbing station 220 and encapsulation station 222. The quality check may be a camera check in which a camera positioned at an exit from the webbing station captures one or more images that are automatically analyzed to determine whether the filament has been completely embedded within each arm of the gastric residence system. Alternatively, the component check may be a manual check in which an operator visually observes the placement of the filament. If the quality check determines that the filament has been inserted satisfactorily, the transit puck can continue along track 202 to encapsulation station 222. If the quality check determines51ny-2823215Attorney Docket No. 75056-20042.40that the filament has not been sufficiently embedded within the arms, the transit puck may continue past encapsulation station 222 with the gastric residence system inside to deliver the gastric residence system to a defective gastric residence system disposal station.

[0172] As discussed above, encapsulation station 222 may fold, sleeve, and encapsulate a gastric residence system. When a transit puck reaches encapsulation station 222, the gastric residence system may be removed from the transit puck (e.g., using a pick and place head) and placed onto a workpiece carrier on a separate track for folding and sleeving. The transit puck may then continue along track 202 until it reaches the beginning of the assembly line, at which point the gastric residence system assembly process can start anew.

[0173] An exemplary folding and sleeving portion 1100 of an encapsulation station is illustrated in FIG. 11. As shown in FIG. 11, the folding and sleeving portion 1100 of the encapsulation station may include a workpiece carrier 1102 (also referred to herein as a “sleeving puck” or a “folding and sleeving puck”). Workpiece carrier 1102 may be substantially hollow, with a wider upper circular surface on which the arms of a gastric residence system 1104 can rest and a narrower lower circular surface. Workpiece carrier 1102 may travel along an upper track 1106 throughout the encapsulation station (e.g., from folding and sleeving portion 1100 of the station to an encapsulation portion of the station).

[0174] A sleeve 1110 may travel along a lower track 1108 that is parallel to upper track 1106. Sleeve 1110 may be positioned directly underneath the center of gastric residence system 1104 within a sleeve carrier 1112, such that gastric residence system 1104 can be pushed through workpiece carrier 1102 and into sleeve 1110. In some embodiments, sleeve 1110 may be one half of a capsule. The sleeve may be the cap portion of the capsule. The capsule may be a size 0EL, a size 0 capsule, or any other appropriately sized capsule. In other embodiments, sleeve 1110 may be a band or other retainer configured to hold gastric residence system 1104 in a folded configuration.

[0175] Gastric residence system 1104 may be folded and inserted into sleeve 1110 using a series of plungers 1114 and 1116 and a retaining element 1118. A first plunger 1114 may descend to apply a force to the central core of gastric residence system 1104. The force applied by first plunger 1114 may cause the upper circular surface of workpiece carrier 1102 to apply a force to the arms of gastric residence system 1104. The forces may cause the arms to fold inward toward one another. First plunger 1114 may continue to press downward on52ny-2823215Attorney Docket No. 75056-20042.40the core of gastric residence system 1104 until the gastric residence system is in a folded configuration with the core at one end and the distal ends of the arms at an opposite end. The arms may fold around first plunger 1114. When gastric residence system 1104 is folded or nearly folded, a retaining element 1118 may descend to surround the distal ends of the arms of gastric residence system 1104 and hold the gastric residence system in the folded or nearly folded configuration. Retaining element 1118 may have a roughly conical shape and may surround at least a portion of first plunger 1114 and second plunger 1116. With retaining element 1118 holding gastric residence system 1104 in the folded or nearly folded configuration, first plunger 1114 may retract, such that first plunger 1114 is no longer between the arms of the folded gastric residence system 1104. In some embodiments, first plunger 1114 may retract into second plunger 1116. Once first plunger 1114 has retracted, a second plunger 1116 that surrounds first plunger 1114 and has a larger diameter than first plunger 1114 may descend to push downward on the ends of the arms of gastric residence system 1104. The downward force provided by second plunger 1116 may push the folded gastric residence system through retaining element 1118, through workpiece carrier 1102, and into sleeve 1110. Alternatively, the folded gastric residence system 1104 may be held in place, and sleeve 1110 may be pushed onto the folded gastric residence system 1104. An example of a folded, sleeved gastric residence system 1200 is illustrated in FIG. 12.

[0176] The folded and sleeved gastric residence system may then be transported to an encapsulation portion of the encapsulation station. In some embodiments, compressed air may be used to transport the folded, sleeved gastric residence system through a tube connecting the folding and sleeving portion of the encapsulation station to the encapsulation portion of the encapsulation station. In some embodiments, the tube may also orient the folded, sleeved gastric residence system such that the gastric residence system may be inserted arms-first into the body of a capsule at the encapsulation portion of the encapsulation station.

[0177] At the encapsulation portion of the encapsulation station, the folded, sleeved gastric residence system may be inserted into a capsule. In some embodiments, the capsule may be a size 00EL capsule. The encapsulation portion of the encapsulation station may include a bulk hopper configured to store assembled capsules with a cap portion and a body portion. Assembled capsules from the hopper may be placed into a capsule receiving53ny-2823215Attorney Docket No. 75056-20042.40platform comprising openings sized and shaped to receive assembled capsules. The assembled capsules may be arranged in a consistent orientation within the openings of the capsule receiving platform, such that the body portion of the capsule is on the bottom, and the cap portion of the capsule is on top. The oriented capsules may then be separated by removing the cap portions.

[0178] A folded, sleeved gastric residence system may be received from a folding and sleeving portion of the encapsulation station (e.g., folding and sleeving portion 1100). In some embodiments, the folded, sleeved gastric residence system may be received via a tube, as discussed above. In some embodiments, multiple folded, sleeved gastric residence systems may be encapsulated simultaneously. For example, at least two, three, four, or more folded, sleeved gastric residence systems may be a received at the encapsulation portion of the encapsulation station simultaneously via multiple tubes.

[0179] The folded, sleeved gastric residence system may be received from the folding and sleeving portion of the encapsulation station in an orientation in which the ends of the arms are facing downward, and the core is facing up. The folded, sleeved gastric residence system may be received at a gastric residence system receiving platform including a plurality of openings sized and shaped to receive folded, sleeved gastric residence systems. The gastric residence system receiving platform may rotate and / or translate so as to align the folded, sleeved gastric residence system with the body portion of a separated capsule situated in an opening of a capsule receiving platform. At least one pushing rod may then be used to push the folded, sleeved gastric residence system into the body portion of the capsule, armside first. The cap portion of the capsule may then be placed onto the body portion of the capsule.

[0180] Optionally, a quality check may be performed following encapsulation and prior to transporting the encapsulated gastric residence system to bulk storage or further processing. In some embodiments, the quality check may be a capsule height check in which the height of the capsule is measured with a physical probe and compared to a known height range for the capsule size used. If the height of the capsule is within an acceptable range, the capsule may continue to bulk storage and / or further processing. If the height of the capsule is outside of the acceptable range, the encapsulated gastric residence system may be rejected and discarded. In some embodiments, the quality check may include a capsule weight check54ny-2823215Attorney Docket No. 75056-20042.40in which the weight of the capsule is measured and compared to an expected weight range for an encapsulated gastric residence system. If the weight of the capsule is within an acceptable range, the encapsulated gastric residence may continue to bulk storage and / or further processing. If the weight of the capsule is outside of the acceptable range, the encapsulated gastric residence system may be rejected and discarded.

[0181] In some embodiments, the encapsulated gastric residence system may be transported to bulk storage. Optionally, the encapsulated gastric residence system may be fed through a metal detector prior to providing the encapsulated gastric residence system to bulk storage to confirm the absence of metal. In some embodiments, the gastric residence system may be transported to another location for further processing. For example, the capsule may be covered with a coating (e.g., to seal the capsule).

[0182] In some embodiments, manufacturing system 200 may be configured to produce at least 5 gastric residence systems per minute, at least 10 gastric residence systems per minute, at least 20 gastric residence systems per minute, at least 30 gastric residence systems per minute, at least 50 gastric residence systems per minute, at least 75 gastric residence systems per minute, at least 100 gastric residence systems per minute, at least 200 gastric residence systems per minute, at least 300 gastric residence systems per minute, at least 400 gastric residence systems per minute, at least 500 gastric residence systems per minute, at least 600 gastric residence systems per minute, at least 700 gastric residence systems per minute, at least 800 gastric residence systems per minute, or at least 900 gastric residence systems per minute. In some embodiments, manufacturing system 200 may be configured to produce at most 1000 gastric residence systems per minute, at most 900 gastric residence systems per minute, at most 800 gastric residence systems per minute, at most 700 gastric residence systems per minute, at most 600 gastric residence systems per minute, at most 500 gastric residence systems per minute, at most 400 gastric residence systems per minute, at most 300 gastric residence systems per minute, at most 200 gastric residence systems per minute, at most 100 gastric residence systems per minute, at most 75 gastric residence systems per minute, at most 50 gastric residence systems per minute, at most 30 gastric residence systems per minute, at most 20 gastric residence systems per minute, or at most 10 gastric residence systems per minute.55ny-2823215Attorney Docket No. 75056-20042.40

[0183] FIG. 13 illustrates an exemplary method 1300 for manufacturing agastric residence system, according to some embodiments. Method 1300 may be performed by a manufacturing system such as system 200 of FIG. 2.

[0184] At step 1302, a transit puck sized and shaped to hold a gastric residence system may be loaded with a core and a plurality of arm components. The transit puck may transit a track connecting a plurality of stations on a manufacturing line. The core and plurality of arm components may be loaded into the transit puck at one or more loading stations, such as core loading station 204, linker component loading station 206, and active and inactive loading stations 208, 210, and 212 described above with reference to FIG. 2. As described above with reference to FIG. 1, the core may be an elastomeric component, and the plurality of arm components may include one or more linker components, active ingredient-containing components, and / or inert components.

[0185] At step 1304, adjacent components may be joined within the transit puck to form the gastric residence system. The transit puck may be transported to a separate component joining station to undergo component joining. In some embodiments, the component joining station may be a laser welding station for laser welding adjacent components (e.g., laser welding station 214 of FIG. 2). Laser welding may be used to join adjacent components without damaging or significantly altering the function of the components. In some embodiments, the transit puck containing the core and arm components may transit into a laser welding housing. Once inside of the housing, a plate may descend from above the transit puck to cover the gastric residence system components and provide downward pressure during laser welding. Radial pistons may also descend to engage the tips of the arms of the gastric residence system to prevent molten components of the system from flowing out of the transit puck during laser welding. A laser (e.g., a near infrared laser) may then be applied to the gastric residence system, so as to laser weld the seams between adjacent gastric residence system components. In other embodiments, adjacent components may be joined using techniques other than laser welding, such as vibrational welding, heat welding, or infrared welding.

[0186] Optionally, the gastric residence system may be cooled following component joining. For example, the component joining station may be a laser welding station, and the gastric residence system may be cooled in order to ensure the welds have solidified. The56ny-2823215Attorney Docket No. 75056-20042.40gastric residence system may be cooled within the component joining station or at a separate cooling station (e.g., cooling station 216 of FIG. 2).

[0187] Optionally, tips of the gastric residence system arms may also be rounded following component joining. For example, the gastric residence system may be transported to a rounding station (e.g., rounding station 218 of FIG. 2) in the transit puck. The gastric residence system may be removed from the transit puck and placed into a rounding nest, where a heated rounding or chamfering die may be used to round or chamfer the edges and / or ends of the gastric residence system arms. The gastric residence system may then be placed back into the transit puck, and the transit puck can continue to transit the manufacturing line.

[0188] At step 1306, the gastric residence system may be transferred from the transit puck to a webbing puck. The webbing puck may be located at a webbing station, such as webbing station 220 of FIG. 2. The gastric residence system may be transferred into the webbing puck by a pick and place head located at the webbing station. In some embodiments, the webbing puck may have grooves sized and shaped to receive the gastric residence system and slots located near the distal end of each arm that are configured to receive a filament for connecting the distal ends of the arms.

[0189] At step 1308, adjacent arms may be connected with a filament within the webbing puck. In some embodiments, a filament wound into a circle sized and shaped to connect the distal ends of the arms of the gastric residence system may be pressed into the distal ends of the arms when they are in a partially molten state. The filament may be inserted by a first plurality of mechanical fingers (e.g., filament inserter 1014 of FIG. 10B) that is configured to hold the filament in the wound position and press the filament into the partially molten distal ends of the arms of the gastric residence system. A second plurality of mechanical fingers may be used to cover the filament with the partially molten distal ends.

[0190] At step 1310, the gastric residence system may be returned to the transit puck. In some embodiments, the gastric residence system may be returned to the transit puck using a pick and place head (e.g., the same pick and place head that was used to transfer the gastric residence system from the transit puck to the webbing puck). Once the gastric residence system has been returned to the transit puck, the transit puck may continue to the next station on the manufacturing line.57ny-2823215Attorney Docket No. 75056-20042.40

[0191] At step 1312, the gastric residence system may be removed from the transit puck at an encapsulation station (e.g., encapsulation station 222 of FIG. 2). The encapsulation station may be configured to fold the gastric residence system, insert the gastric residence system into a sleeve, and insert the sleeved gastric residence system into a capsule. In some embodiments, the gastric residence system may be removed from the transit puck by a pick and place head of the encapsulation station and placed onto a workpiece carrier that is configured to transit the encapsulation station.

[0192] At step 1314, the gastric residence system may be folded into a compacted configuration. The gastric residence system may be folded into a compacted configuration in which the arms of the gastric residence system fold toward each other until the distal ends of the arms meet. The gastric residence system may be folded using at least one plunger configured to press downward on the core of the gastric residence system, thus causing the arms to fold inward toward the plunger.

[0193] At step 1316, the gastric residence system may be bound in the compacted configuration with a sleeve. The sleeve may be half of a capsule, a band, or another retainer configured to at least partially surround a folded gastric residence system. In some embodiments, the gastric residence system may be bound with a sleeve by pushing the folded gastric residence system into a sleeve positioned beneath the workpiece carrier with the plunger, as described above with reference to FIG. 11. In some embodiments, a second plunger may be used to press down on the arms of the folded gastric residence system while a retaining element holds the gastric residence system in the folded configuration in order to fully insert the folded gastric residence system into the sleeve.

[0194] At step 1318, the gastric residence system may be encapsulated with a capsule. The folded and sleeved gastric residence system may be transported to an encapsulation portion of the encapsulation station, for example by using compressed air to push the folded and sleeved gastric residence system through tubing connecting the folding and sleeving portion of the encapsulation station and the encapsulation portion of the encapsulation station.

[0195] Following encapsulation, the gastric residence system may be transported to a storage facility. For example, the encapsulated gastric residence system may be put through a metal detector, and, if no metal is detected, the encapsulated gastric residence system may58ny-2823215Attorney Docket No. 75056-20042.40be collected and stored. Optionally, the encapsulated gastric residence system may undergo further processing once removed from the manufacturing system. For instance, a coating may be applied to the capsule. Alternatively, the capsule may undergo quality testing or be packaged for transportation (e.g., to a hospital, pharmacy, etc.).Exemplary Embodiments

[0196] Embodiment 1. A method of manufacturing a gastric residence system comprising: at one or more loading stations, loading a transit puck sized and shaped to hold the gastric residence system with a core and a plurality of arm components, wherein the transit puck is configured to transit a track connecting the one or more loading stations, a component joining station, a webbing station, and an encapsulation station; at the component joining station, joining adjacent components within the transit puck to form the gastric residence system, wherein the gastric residence system comprises the core and a plurality of arms extending radially from the core; at the webbing station: transferring the gastric residence system from the transit puck to a webbing puck; connecting adjacent arms with a filament within the webbing puck; and returning the gastric residence system to the transit puck; and at the encapsulation station: removing the gastric residence system from the transit puck; folding the gastric residence system into a compacted configuration; binding the gastric residence system in the compacted configuration with a sleeve; and encapsulating the gastric residence system with a capsule.

[0197] Embodiment 2. The method of embodiment 1, wherein the track is an electromagnetic track.

[0198] Embodiment 3. The method of embodiment 1 or 2, wherein loading the transit puck with the core comprises: with a bowl feeder, transporting a plurality of cores toward a plurality of feeding lanes; vibrating the plurality of feeding lanes such that cores having a predetermined orientation are received by a feeding lane of the plurality of feeding lanes and cores not having the predetermined orientation are returned to the bowl feeder; and with a pick and place machine: selecting a core from a feeding lane of the plurality of feeding lanes; and placing the core into the transit puck.

[0199] Embodiment 4. The method of embodiment 3, wherein selecting a core from a feeding lane of the plurality of feeding lanes comprises receiving the core with a vacuum head of the pick and place machine.59ny-2823215Attorney Docket No. 75056-20042.40

[0200] Embodiment 5. The method of embodiment 4, wherein placing the core into the transit puck comprises releasing the core from the vacuum head of the pick and place machine into the transit puck.

[0201] Embodiment 6. The method of any one of embodiments 1-5, wherein loading the transit puck with a plurality of arm components comprises: for at least one arm of the gastric residence system: placing a linker component adjacent to the core; placing an active ingredient-containing component adjacent to the linker component; and placing an inactive component adjacent to the active ingredient-containing component.

[0202] Embodiment 7. The method of embodiment 6, wherein the linker component comprises at least one disintegrating matrix component.

[0203] Embodiment 8. The method of embodiment 7, wherein the at least one disintegrating matrix component comprises a time-dependent disintegrating matrix.

[0204] Embodiment 9. The method of embodiment 7 or 8, wherein the at least one disintegrating matrix component comprises an enteric disintegrating matrix.

[0205] Embodiment 10. The method of any one of embodiments 6-9, wherein the linker component comprises at least one inert component.

[0206] Embodiment 11. The method of any one of embodiments 6-10, wherein the linker component comprises a first inert component, a disintegrating matrix component, and a second inert component connected in that order.

[0207] Embodiment 12. The method of embodiment 11, wherein the first inert component, the disintegrating matrix component, and the second inert component are connected by: heating each component to partially melt at least one surface of the respective component; and tacking the first inert component, the disintegrating matrix component, and the second inert component to one another to form the linker component.

[0208] Embodiment 13. The method of any one of embodiments 7-12, wherein the disintegrating matrix component is a first disintegrating matrix component, and wherein the linker further comprises a second disintegrating matrix component.

[0209] Embodiment 14. The method of embodiment 13, wherein the second disintegrating matrix component is connected to the first inert component or the second inert component by: heating the second disintegrating matrix component to partially melt at least one surface of the second disintegrating matrix component; and tacking the partially melted60ny-2823215Attorney Docket No. 75056-20042.40at least one surface of the second disintegrating matrix component to the first inert component or the second inert component.

[0210] Embodiment 15. The method of embodiment 13 or 14, wherein one of the first disintegrating matrix component and the second disintegrating matrix component comprises an enteric disintegrating matrix and the other of the first disintegrating matrix component and the second disintegrating matrix component comprises a time-dependent disintegrating matrix.

[0211] Embodiment 16. The method of any one of embodiments 1-15, wherein the component joining station is a laser welding station, and joining adjacent components within the transit puck comprises laser welding adjacent components within the transit puck.

[0212] Embodiment 17. The method of embodiment 16, wherein laser welding adjacent components within the transit puck to form the gastric residence system comprises applying downward and radial pressure to the gastric residence system while laser welding the adjacent components within the transit puck.

[0213] Embodiment 18. The method of embodiment 17, wherein the downward pressure is applied by a plate sized and shaped to cover the transit puck.

[0214] Embodiment 19. The method of embodiment 18, wherein the plate comprises glass.

[0215] Embodiment 20. The method of embodiment 18 or 19, wherein the plate comprises fluorinated ethylene propylene.

[0216] Embodiment 21. The method of any one of embodiments 18-20, wherein the plate comprises a ceramic coating.

[0217] Embodiment 22. The method of any one of embodiments 1-15, wherein the component joining station is a vibrational welding station or an infrared welding station.

[0218] Embodiment 23. The method of any one of embodiments 1-22, further comprising cooling the gastric residence system after joining the adjacent components within the transit puck and prior to transferring the gastric residence system from the transit puck to the webbing puck.

[0219] Embodiment 24. The method of any one of embodiments 1-23, further comprising rounding at least one comer of at least one arm of the gastric residence system prior to connecting adjacent arms of the gastric residence system with the filament.61ny-2823215Attorney Docket No. 75056-20042.40

[0220] Embodiment 25. The method of any one of embodiments 1-23, further comprising rounding at least one comer of at least one arm of the gastric residence system after connecting adjacent arms of the gastric residence system with the filament.

[0221] Embodiment 26. The method of embodiment 24 or 25, wherein rounding at least one comer of the at least one arm of the gastric residence system comprises applying a heated die to the at least one comer to at least partially melt and round the at least one comer.

[0222] Embodiment 27. The method of any one of embodiments 1-26, wherein connecting adjacent arms with the filament within the webbing puck comprises: heating a distal end of each arm of the gastric residence system so as to partially melt the distal end of each arm; pressing the filament into the partially molten distal end of each arm; and covering the filament with the partially molten distal end of each arm to secure the filament within the distal end of each arm.

[0223] Embodiment 28. The method of embodiment 27, wherein heating a distal end of each arm of the gastric residence system comprises placing a heater configured to heat the distal end of each arm of the gastric residence system adjacent to the webbing puck.

[0224] Embodiment 29. The method of embodiment 28, wherein the heater is a ring shape, and a cooling element is located in a center of the ring.

[0225] Embodiment 30. The method of embodiment 29, wherein the cooling element is a water-cooled tower.

[0226] Embodiment 31. The method of embodiment 30, wherein the water-cooled tower is configured to cool the core and a remainder of each arm while the distal end of each arm is heated.

[0227] Embodiment 32. The method of any one of embodiments 1-31, wherein folding the gastric residence system into the compacted configuration comprises: transferring the gastric residence system from the transit puck to a workpiece carrier comprising an upper circular surface, wherein the plurality of arms of the gastric residence system are configured to sit flush against the upper circular surface; and applying a first force to the core of the gastric residence system, wherein applying the first force to the core causes the upper circular surface to apply a second force to the plurality of arms, causing the gastric residence system to fold.62ny-2823215Attorney Docket No. 75056-20042.40

[0228] Embodiment 33. The method of any one of embodiments 1-32, wherein binding the gastric residence system in the compacted configuration with the sleeve comprises: positioning the sleeve underneath the gastric residence system in the compacted configuration; and pushing the gastric residence system in the compacted configuration downward into the sleeve.

[0229] Embodiment 34. The method of any one of embodiments 1-33, wherein the sleeve comprises at least one of gelatin, hydroxypropyl methylcellulose, or pullulan.

[0230] Embodiment 35. The method of any one of embodiments 1-34, wherein the sleeve comprises a capsule cap.

[0231] Embodiment 36. The method of any one of embodiments 1-35, wherein encapsulating the gastric residence system with the capsule comprises inserting the gastric residence system bound by the sleeve into the capsule.

[0232] Embodiment 37. The method of any one of embodiments 1-36, further comprising determining that the encapsulated gastric residence system does not contain metal using a metal detector.

[0233] Embodiment 38. The method of any one of embodiments 1-37, further comprising transporting the encapsulated gastric residence system to a storage facility.

[0234] Embodiment 39. A system for manufacturing a gastric residence system, comprising: one or more loading stations; a component joining station; a webbing station; an encapsulation station; a track connecting the one or more loading stations, the component joining station, the webbing station, and the encapsulation station; and a transit puck configured to transit the track, wherein the transit puck is sized and shaped to hold the gastric residence system.

[0235] Embodiment 40. The system of embodiment 39, wherein the one or more loading stations comprise a core loading station.

[0236] Embodiment 41. The system of embodiment 40, wherein the core loading station comprises: a plurality of feeding lanes; a bowl feeder configured to provide cores having a predetermined orientation to a feeding lane of the plurality of feeding lanes and receive cores not having the predetermined orientation; and a pick and place machine configured to select a core from a feeding lane of the plurality of feeding lanes and place the core into the transit puck.63ny-2823215Attorney Docket No. 75056-20042.40

[0237] Embodiment 42. The system of any one of embodiments 39-41, wherein the one or more loading stations comprise a linker component loading station.

[0238] Embodiment 43. The system of embodiment 42, wherein the linker component loading station comprises: at least three vacuum nozzles, wherein a first vacuum nozzle is configured to receive a first inert component, a second vacuum nozzle is configured to receive a disintegrating matrix component, and a third vacuum nozzle is configured to receive a second inert component; a heater configured to at least partially melt at least one surface of each of the first inert component, the disintegrating matrix component, and the second inert component; a workpiece carrier configured to receive the first inert component, the disintegrating matrix component, and the second inert component, such that adjacent components attach to one another to form the linker component; and a pick and place machine configured to transfer the linker component from the workpiece carrier into the transit puck.

[0239] Embodiment 44. The system of any one of embodiments 39-43, wherein the one or more loading stations comprise an active ingredient-containing component loading station.

[0240] Embodiment 45. The system of embodiment 44, wherein the active ingredientcontaining component loading station comprises: a step feeder; and a pick and place machine configured to transfer an active ingredient-containing component from the step feeder into the transit puck.

[0241] Embodiment 46. The system of any one of embodiments 39-45, wherein the one or more loading stations comprise an inactive component loading station.

[0242] Embodiment 47. The system of embodiment 46, wherein the inactive component loading station comprises: a step feeder; and a pick and place machine configured to transfer an inactive component from the step feeder into the transit puck.

[0243] Embodiment 48. The system of any one of embodiments 39-47, wherein the component joining station is a laser welding station, the laser welding station comprising: at least one laser; at least one plate sized and shaped to cover the transit puck, wherein the at least one plate is configured to apply downward pressure to the gastric residence system during laser welding; and a plurality of radial pistons configured to apply radial pressure to the gastric residence system during laser welding.64ny-2823215Attorney Docket No. 75056-20042.40

[0244] Embodiment 49. The system of any one of embodiments 39-48, further comprising a cooling station.

[0245] Embodiment 50. The system of embodiment 49, wherein the cooling station comprises at least one compressed air line configured to direct compressed air toward the gastric residence system.

[0246] Embodiment 51. The system of any one of embodiments 39-50, further comprising a rounding station.

[0247] Embodiment 52. The system of embodiment 51, wherein the rounding station comprises at least one heated die configured to at least partially melt at least one comer of at least one arm of the gastric residence system.

[0248] Embodiment 53. The system of any one of embodiments 39-52, wherein the webbing station comprises: a webbing puck sized and shaped to hold the gastric residence system; a heater configured to heat a distal end of each arm of the gastric residence system when the heater is placed adjacent to the webbing puck so as to at least partially melt the distal end of each arm; a filament inserter configured to insert a portion of the filament into the partially molten distal end of each arm; and a cooling element configured to cool the core and a remainder of each arm of the gastric residence system while the distal end of each arm is heated.

[0249] Embodiment 54. The system of embodiment 53, wherein the filament inserter comprises a first plurality of mechanical fingers configured to: hold the filament in circular shape sized to connect the distal ends of the plurality of arms; and press the filament into the partially molten distal end of each arm.

[0250] Embodiment 55. The system of embodiment 54, wherein the webbing station further comprises a second plurality of mechanical fingers configured to cover the filament using the partially molten distal end of each arm to secure the filament within the distal end of each arm.

[0251] Embodiment 56. The system of any one of embodiments 53-55, wherein the cooling element comprises a water-cooled tower.

[0252] Embodiment 57. The system of any one of embodiments 39-56, wherein the encapsulation station comprises: a sleeving puck comprising an upper circular surface, wherein a plurality of arms of the gastric residence system are configured to sit flush against65ny-2823215Attorney Docket No. 75056-20042.40the upper circular surface; a first plunger configured to fold the gastric residence system into a compacted configuration; a retaining element configured to hold the gastric residence system in the compacted configuration; a second plunger configured to push the gastric residence system in the compacted configuration through the upper circular surface into a sleeve; and an encapsulator configured to insert the sleeved gastric residence system into a capsule.

[0253] Embodiment 58. The system of any one of embodiments 39-57, wherein the track comprises an electromagnetic track.

[0254] Embodiment 59. A method for manufacturing a linker component of a gastric residence system, comprising: receiving a first inert component with a first vacuum nozzle, a disintegrating matrix component with a second vacuum nozzle, and a second inert component with a third vacuum nozzle; exposing the first inert component, the disintegrating matrix component, and the second inert component to a heater while holding each component in its respective vacuum nozzle, such that at least one surface of each component becomes at least partially molten; and while at least one surface of each component is at least partially molten, placing the disintegrating matrix component between the first and second inert components in a workpiece carrier, such that adjacent components attach to one another to form the linker component.

[0255] Embodiment 60. The method of embodiment 59, wherein at least one of the first inert component and the second inert component comprises polycaprolactone.

[0256] Embodiment 61. The method of embodiment 60, wherein at least one of the first inert component and the second inert component further comprises bismuth subcarbonate.

[0257] Embodiment 62. The method of any one of embodiments 59-61, wherein the disintegrating matrix component comprises an enteric disintegrating matrix.

[0258] Embodiment 63. The method of embodiment 62, wherein the enteric disintegrating matrix comprises polycaprolactone.

[0259] Embodiment 64. The method of embodiment 63, wherein the enteric disintegrating matrix further comprises hydroxypropylmethylcellulose acetate succinate (HPMCAS).

[0260] Embodiment 65. The method of embodiment 63 or 64, wherein the enteric disintegrating matrix further comprises a poloxamer.66ny-2823215Attorney Docket No. 75056-20042.40

[0261] Embodiment 66. The method of any one of embodiments 59-61, wherein the disintegrating matrix component comprises a time-dependent disintegrating matrix.

[0262] Embodiment 67. The method of embodiment 66, wherein the time-dependent disintegrating matrix comprises polycaprolactone.

[0263] Embodiment 68. The method of embodiment 67, wherein the time-dependent disintegrating matrix further comprises poly(ethylene oxide).

[0264] Embodiment 69. The method of embodiment 67 or 68, wherein the timedependent disintegrating matrix further comprises 50 / 50 DL-Lactide / Glycolide copolymer.

[0265] Embodiment 70. The method of any one of embodiments 59-69, wherein a length of at least one of the first inert component and the second inert component is between 0.3-0.7 mm.

[0266] Embodiment 71. The method of embodiment any one of embodiments 59-69, wherein a length of at least one of the first inert component and the second inert component is 0.5 mm.

[0267] Embodiment 72. The method of any one of embodiments 59-71, wherein a length of the disintegrating matrix component is between 1.5-2.0 mm.

[0268] Embodiment 73. The method of any one of embodiments 59-71, wherein a length of the disintegrating matrix component is 1.85 mm.

[0269] Embodiment 74. The method of any one of embodiments 59-71, wherein a length of the disintegrating matrix component is between 0.7-1.3 mm.

[0270] Embodiment 75. The method of any one of embodiments 59-71, wherein a length of the disintegrating matrix component is 1.0 mm.

[0271] Embodiment 76. The method of any one of embodiments 59-75, wherein the disintegrating matrix component is a first disintegrating matrix component, further comprising: receiving a second disintegrating matrix component with a fourth vacuum nozzle; exposing the second disintegrating matrix component to the heater while holding the second disintegrating matrix component in the fourth vacuum nozzle, such that at least one surface of the second disintegrating matrix component becomes at least partially molten; and while the at least one surface of the second disintegrating matrix component is at least partially molten, placing the at least one partially molten surface of the second disintegrating matrix component adjacent to the first inert component or the second inert component in the67ny-2823215Attorney Docket No. 75056-20042.40workpiece carrier, such that the second disintegrating matrix component attaches to the first inert component or the second inert component.

[0272] Embodiment 77. The method of embodiment 76, wherein at least one of the first and second disintegrating matrix components comprises an enteric disintegrating matrix component and the other of the first and second disintegrating matrix components comprises a time-dependent disintegrating matrix.

[0273] Embodiment 78. The method of any one of embodiments 59-77, further comprising: measuring a length of the linker component; determining that the length of the linker component matches a target length of the linker component; and providing the linker component to a system for manufacturing gastric residence systems.

[0274] Embodiment 79. A system for manufacturing a linker component of a gastric residence system, comprising: at least three vacuum nozzles, wherein a first vacuum nozzle is configured to receive a first inert component, a second vacuum nozzle is configured to receive a disintegrating matrix component, and a third vacuum nozzle is configured to receive a second inert component; a heater configured to at least partially melt at least one surface of each of the first inert component, the disintegrating matrix component, and the second inert component; a workpiece carrier configured to receive the first inert component, the disintegrating matrix component, and the second inert component, such that adjacent components attach to one another to form the linker component; and a pick and place machine configured to transfer the linker component from the workpiece carrier into a transit puck.

[0275] Embodiment 80. The system of embodiment 79, wherein the disintegrating matrix component is a first disintegrating matrix component, the system further comprising a fourth vacuum nozzle configured to receive a second disintegrating matrix component.

[0276] Embodiment 81. The system of embodiment 80, wherein at least one of the first and second disintegrating matrix components comprises an enteric disintegrating matrix component and the other of the first and second disintegrating matrix components comprises a time-dependent disintegrating matrix.

[0277] Embodiment 82. The system of any one of embodiments 79-81, further comprising an inspection station configured to: measure a length of the linker component; determine that the length of the linker component matches a target length of the linker68ny-2823215Attorney Docket No. 75056-20042.40component; and provide the linker component to a system for manufacturing gastric residence systems.

[0278] Embodiment 83. A method for connecting adjacent arms of a gastric residence system comprising a core and a plurality of arms extending radially from the core with a filament, comprising: placing the gastric residence system into a webbing puck; heating a distal end of each arm of the plurality of arms so as to partially melt the distal end of each arm; pressing the filament into the partially molten distal end of each arm; and covering the filament using the partially molten distal end of each arm to secure the filament within the distal end of each arm.

[0279] Embodiment 84. The method of embodiment 83, wherein heating a distal end of each arm of the gastric residence system comprises placing a heater configured to heat the distal end of each arm of the gastric residence system adjacent to the webbing puck.

[0280] Embodiment 85. The method of embodiment 84, wherein the heater is a ring shape and comprises a cooling element in a center of the ring.

[0281] Embodiment 86. The method of embodiment 85, wherein the cooling element comprises a water-cooled tower.

[0282] Embodiment 87. The method of embodiment 86, wherein the water-cooled tower is configured to cool the core and a remainder of each arm while the distal end of each arm is heated.

[0283] Embodiment 88. The method of any one of embodiments 83-87, further comprising: prior to pressing the filament into the partially molten distal end of each arm, winding the filament into a circle sized and shaped to connect the distal ends of the plurality of arms.

[0284] Embodiment 89. The method of any one of embodiments 83-88, further comprising: rounding at least one comer of the gastric residence system.

[0285] Embodiment 90. The method of embodiment 89, wherein rounding at least one comer of the gastric residence system comprises applying a rounding die to the at least one comer.

[0286] Embodiment 91. A system for connecting adjacent arms of a gastric residence system comprising a core and a plurality of arms extending radially from the core with a filament, comprising: a webbing puck sized and shaped to hold the gastric residence system;69ny-2823215Attorney Docket No. 75056-20042.40a heater configured to heat a distal end of each arm of the gastric residence system when the heater is placed adjacent to the webbing puck so as to at least partially melt the distal end of each arm; a filament inserter configured to insert a portion of the filament into the partially molten distal end of each arm; and a cooling element configured to cool the core and a remainder of each arm of the gastric residence system while the distal end of each arm is heated.

[0287] Embodiment 92. The system of embodiment 91, wherein the heater is a ring shape and the cooling element is located in a center of the ring.

[0288] Embodiment 93. The system of embodiment 92, wherein the cooling element comprises a water-cooled tower.

[0289] Embodiment 94. The system of any one of embodiments 91-93, wherein the filament inserter comprises a first plurality of mechanical fingers configured to hold the filament in circular shape sized to connect the distal ends of the plurality of arms.

[0290] Embodiment 95. The system of embodiment 94, wherein the first plurality of mechanical fingers are configured to press the filament in the circular shape into the distal end of each arm.

[0291] Embodiment 96. The system of embodiment 95, further comprising a second plurality of mechanical fingers configured to cover the filament using the partially molten distal end of each arm to secure the filament within the distal end of each arm.

[0292] Embodiment 97. The system of any one of embodiments 92-96, further comprising a rounding die configured to round at least one comer of the gastric residence system.

[0293] Embodiment 98. The system of embodiment 97, wherein the rounding die is a heated die.

[0294] Although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity of understanding, it is apparent to those skilled in the art that certain changes and modifications will be practiced. Therefore, the description and examples should not be construed as limiting the scope of the invention.70ny-2823215

Claims

1. Attorney Docket No. 75056-20042.40CLAIMS1. A method of manufacturing a gastric residence system comprising:at one or more loading stations, loading a transit puck sized and shaped to hold the gastric residence system with a core and a plurality of arm components, wherein the transit puck is configured to transit a track connecting the one or more loading stations, a component joining station, a webbing station, and an encapsulation station;at the component joining station, joining adjacent components within the transit puck to form the gastric residence system, wherein the gastric residence system comprises the core and a plurality of arms extending radially from the core;at the webbing station:transferring the gastric residence system from the transit puck to a webbing puck;connecting adjacent arms with a filament within the webbing puck; and returning the gastric residence system to the transit puck; andat the encapsulation station:removing the gastric residence system from the transit puck;folding the gastric residence system into a compacted configuration; binding the gastric residence system in the compacted configuration with a sleeve; andencapsulating the gastric residence system with a capsule.

2. The method of claim 1, wherein the track is an electromagnetic track.

3. The method of claim 1 or 2, wherein loading the transit puck with the core comprises:with a bowl feeder, transporting a plurality of cores toward a plurality of feeding lanes;vibrating the plurality of feeding lanes such that cores having a predetermined orientation are received by a feeding lane of the plurality of feeding lanes and cores not having the predetermined orientation are returned to the bowl feeder; andwith a pick and place machine:selecting a core from a feeding lane of the plurality of feeding lanes; and placing the core into the transit puck.71ny-2823215Attorney Docket No. 75056-20042.

404. The method of claim 3, wherein selecting a core from a feeding lane of the plurality of feeding lanes comprises receiving the core with a vacuum head of the pick and place machine.

5. The method of claim 4, wherein placing the core into the transit puck comprises releasing the core from the vacuum head of the pick and place machine into the transit puck.

6. The method of any one of claims 1-5, wherein loading the transit puck with a plurality of arm components comprises:for at least one arm of the gastric residence system:placing a linker component adjacent to the core;placing an active ingredient-containing component adjacent to the linker component; andplacing an inactive component adjacent to the active ingredient-containing component.

7. The method of claim 6, wherein the linker component comprises at least one disintegrating matrix component.

8. The method of claim 7, wherein the at least one disintegrating matrix component comprises a time-dependent disintegrating matrix.

9. The method of claim 7 or 8, wherein the at least one disintegrating matrix component comprises an enteric disintegrating matrix.

10. The method of any one of claims 6-9, wherein the linker component comprises at least one inert component.

11. The method of any one of claims 6-10, wherein the linker component comprises a first inert component, a disintegrating matrix component, and a second inert component connected in that order.

12. The method of claim 11, wherein the first inert component, the disintegrating matrix component, and the second inert component are connected by:heating each component to partially melt at least one surface of the respective component; and72ny-2823215Attorney Docket No. 75056-20042.40tacking the first inert component, the disintegrating matrix component, and the second inert component to one another to form the linker component.

13. The method of any one of claims 7-12, wherein the disintegrating matrix component is a first disintegrating matrix component, and wherein the linker further comprises a second disintegrating matrix component.

14. The method of claim 13, wherein the second disintegrating matrix component is connected to the first inert component or the second inert component by:heating the second disintegrating matrix component to partially melt at least one surface of the second disintegrating matrix component; andtacking the partially melted at least one surface of the second disintegrating matrix component to the first inert component or the second inert component.

15. The method of claim 13 or 14, wherein one of the first disintegrating matrix component and the second disintegrating matrix component comprises an enteric disintegrating matrix and the other of the first disintegrating matrix component and the second disintegrating matrix component comprises a time-dependent disintegrating matrix.

16. The method of any one of claims 1-15, wherein the component joining station is a laser welding station, and joining adjacent components within the transit puck comprises laser welding adjacent components within the transit puck.

17. The method of claim 16, wherein laser welding adjacent components within the transit puck to form the gastric residence system comprises applying downward and radial pressure to the gastric residence system while laser welding the adjacent components within the transit puck.

18. The method of claim 17, wherein the downward pressure is applied by a plate sized and shaped to cover the transit puck.

19. The method of claim 18, wherein the plate comprises glass.

20. The method of claim 18 or 19, wherein the plate comprises fluorinated ethylene propylene.

21. The method of any one of claims 18-20, wherein the plate comprises a ceramic coating.73ny-2823215Attorney Docket No. 75056-20042.4022. The method of any one of claims 1-15, wherein the component joining station is a vibrational welding station or an infrared welding station.

23. The method of any one of claims 1-22, further comprising cooling the gastric residence system after joining the adjacent components within the transit puck and prior to transferring the gastric residence system from the transit puck to the webbing puck.

24. The method of any one of claims 1-23, further comprising rounding at least one comer of at least one arm of the gastric residence system prior to connecting adjacent arms of the gastric residence system with the filament.

25. The method of any one of claims 1-23, further comprising rounding at least one comer of at least one arm of the gastric residence system after connecting adjacent arms of the gastric residence system with the filament.

26. The method of claim 24 or 25, wherein rounding at least one comer of the at least one arm of the gastric residence system comprises applying a heated die to the at least one comer to at least partially melt and round the at least one comer.

27. The method of any one of claims 1-26, wherein connecting adjacent arms with the filament within the webbing puck comprises:heating a distal end of each arm of the gastric residence system so as to partially melt the distal end of each arm;pressing the filament into the partially molten distal end of each arm; and covering the filament with the partially molten distal end of each arm to secure the filament within the distal end of each arm.

28. The method of claim 27, wherein heating a distal end of each arm of the gastric residence system comprises placing a heater configured to heat the distal end of each arm of the gastric residence system adjacent to the webbing puck.

29. The method of claim 28, wherein the heater is a ring shape, and a cooling element is located in a center of the ring.

30. The method of claim 29, wherein the cooling element is a water-cooled tower.74ny-2823215Attorney Docket No. 75056-20042.4031. The method of claim 30, wherein the water-cooled tower is configured to cool the core and a remainder of each arm while the distal end of each arm is heated.

32. The method of any one of claims 1-31, wherein folding the gastric residence system into the compacted configuration comprises:transferring the gastric residence system from the transit puck to a workpiece carrier comprising an upper circular surface, wherein the plurality of arms of the gastric residence system are configured to sit flush against the upper circular surface; and applying a first force to the core of the gastric residence system, wherein applying the first force to the core causes the upper circular surface to apply a second force to the plurality of arms, causing the gastric residence system to fold.

33. The method of any one of claims 1-32, wherein binding the gastric residence system in the compacted configuration with the sleeve comprises:positioning the sleeve underneath the gastric residence system in the compacted configuration; andpushing the gastric residence system in the compacted configuration downward into the sleeve.

34. The method of any one of claims 1-33, wherein the sleeve comprises at least one of gelatin, hydroxypropyl methylcellulose, or pullulan.

35. The method of any one of claims 1-34, wherein the sleeve comprises a capsule cap.

36. The method of any one of claims 1-35, wherein encapsulating the gastric residence system with the capsule comprises inserting the gastric residence system bound by the sleeve into the capsule.

37. The method of any one of claims 1-36, further comprising determining that the encapsulated gastric residence system does not contain metal using a metal detector.

38. The method of any one of claims 1-37, further comprising transporting the encapsulated gastric residence system to a storage facility.

39. A system for manufacturing a gastric residence system, comprising:one or more loading stations;75ny-2823215Attorney Docket No. 75056-20042.40a component joining station;a webbing station;an encapsulation station;a track connecting the one or more loading stations, the component joining station, the webbing station, and the encapsulation station; anda transit puck configured to transit the track, wherein the transit puck is sized and shaped to hold the gastric residence system.

40. The system of claim 39, wherein the one or more loading stations comprise a core loading station.

41. The system of claim 40, wherein the core loading station comprises:a plurality of feeding lanes;a bowl feeder configured to provide cores having a predetermined orientation to a feeding lane of the plurality of feeding lanes and receive cores not having the predetermined orientation; anda pick and place machine configured to select a core from a feeding lane of the plurality of feeding lanes and place the core into the transit puck.

42. The system of any one of claims 39-41, wherein the one or more loading stations comprise a linker component loading station.

43. The system of claim 42, wherein the linker component loading station comprises:at least three vacuum nozzles, wherein a first vacuum nozzle is configured to receive a first inert component, a second vacuum nozzle is configured to receive a disintegrating matrix component, and a third vacuum nozzle is configured to receive a second inert component;a heater configured to at least partially melt at least one surface of each of the first inert component, the disintegrating matrix component, and the second inert component;a workpiece carrier configured to receive the first inert component, the disintegrating matrix component, and the second inert component, such that adjacent components attach to one another to form the linker component; anda pick and place machine configured to transfer the linker component from the workpiece carrier into the transit puck.76ny-2823215Attorney Docket No. 75056-20042.4044. The system of any one of claims 39-43, wherein the one or more loading stations comprise an active ingredient-containing component loading station.

45. The system of claim 44, wherein the active ingredient-containing component loading station comprises:a step feeder; anda pick and place machine configured to transfer an active ingredient-containing component from the step feeder into the transit puck.

46. The system of any one of claims 39-45, wherein the one or more loading stations comprise an inactive component loading station.

47. The system of claim 46, wherein the inactive component loading station comprises:a step feeder; anda pick and place machine configured to transfer an inactive component from the step feeder into the transit puck.

48. The system of any one of claims 39-47, wherein the component joining station is a laser welding station, the laser welding station comprising:at least one laser;at least one plate sized and shaped to cover the transit puck, wherein the at least one plate is configured to apply downward pressure to the gastric residence system during laser welding; anda plurality of radial pistons configured to apply radial pressure to the gastric residence system during laser welding.

49. The system of any one of claims 39-48, further comprising a cooling station.

50. The system of claim 49, wherein the cooling station comprises at least one compressed air line configured to direct compressed air toward the gastric residence system.

51. The system of any one of claims 39-50, further comprising a rounding station.

52. The system of claim 51, wherein the rounding station comprises at least one heated die configured to at least partially melt at least one comer of at least one arm of the gastric residence system.77ny-2823215Attorney Docket No. 75056-20042.4053. The system of any one of claims 39-52, wherein the webbing station comprises:a webbing puck sized and shaped to hold the gastric residence system;a heater configured to heat a distal end of each arm of the gastric residence system when the heater is placed adjacent to the webbing puck so as to at least partially melt the distal end of each arm;a filament inserter configured to insert a portion of the filament into the partially molten distal end of each arm; anda cooling element configured to cool the core and a remainder of each arm of the gastric residence system while the distal end of each arm is heated.

54. The system of claim 53, wherein the filament inserter comprises a first plurality of mechanical fingers configured to:hold the filament in circular shape sized to connect the distal ends of the plurality of arms; andpress the filament into the partially molten distal end of each arm.

55. The system of claim 54, wherein the webbing station further comprises a second plurality of mechanical fingers configured to cover the filament using the partially molten distal end of each arm to secure the filament within the distal end of each arm.

56. The system of any one of claims 53-55, wherein the cooling element comprises a water- cooled tower.

57. The system of any one of claims 39-56, wherein the encapsulation station comprises:a sleeving puck comprising an upper circular surface, wherein a plurality of arms of the gastric residence system are configured to sit flush against the upper circular surface;a first plunger configured to fold the gastric residence system into a compacted configuration;a retaining element configured to hold the gastric residence system in the compacted configuration;a second plunger configured to push the gastric residence system in the compacted configuration through the upper circular surface into a sleeve; and78ny-2823215Attorney Docket No. 75056-20042.40an encapsulator configured to insert the sleeved gastric residence system into a capsule.

58. The system of any one of claims 39-57, wherein the track comprises an electromagnetic track.

59. A method for manufacturing a linker component of a gastric residence system, comprising:receiving a first inert component with a first vacuum nozzle, a disintegrating matrix component with a second vacuum nozzle, and a second inert component with a third vacuum nozzle;exposing the first inert component, the disintegrating matrix component, and the second inert component to a heater while holding each component in its respective vacuum nozzle, such that at least one surface of each component becomes at least partially molten; andwhile at least one surface of each component is at least partially molten, placing the disintegrating matrix component between the first and second inert components in a workpiece carrier, such that adjacent components attach to one another to form the linker component.

60. The method of claim 59, wherein at least one of the first inert component and the second inert component comprises polycaprolactone.

61. The method of claim 60, wherein at least one of the first inert component and the second inert component further comprises bismuth subcarbonate.

62. The method of any one of claims 59-61, wherein the disintegrating matrix component comprises an enteric disintegrating matrix.

63. The method of claim 62, wherein the enteric disintegrating matrix comprises polycaprolactone.

64. The method of claim 63, wherein the enteric disintegrating matrix further comprises hydroxypropylmethylcellulose acetate succinate (HPMCAS).79ny-2823215Attorney Docket No. 75056-20042.4065. The method of claim 63 or 64, wherein the enteric disintegrating matrix further comprises a poloxamer.

66. The method of any one of claims 59-61, wherein the disintegrating matrix component comprises a time-dependent disintegrating matrix.

67. The method of claim 66, wherein the time-dependent disintegrating matrix comprises polycaprolactone.

68. The method of claim 67, wherein the time-dependent disintegrating matrix further comprises poly(ethylene oxide).

69. The method of claim 67 or 68, wherein the time-dependent disintegrating matrix further comprises 50 / 50 DL-Lactide / Glycolide copolymer.

70. The method of any one of claims 59-69, wherein a length of at least one of the first inert component and the second inert component is between 0.3-0.7 mm.

71. The method of claim any one of claims 59-69, wherein a length of at least one of the first inert component and the second inert component is 0.5 mm.

72. The method of any one of claims 59-71, wherein a length of the disintegrating matrix component is between 1.5 -2.0 mm.

73. The method of any one of claims 59-71, wherein a length of the disintegrating matrix component is 1.85 mm.

74. The method of any one of claims 59-71, wherein a length of the disintegrating matrix component is between 0.7-1.3 mm.

75. The method of any one of claims 59-71, wherein a length of the disintegrating matrix component is 1.0 mm.

76. The method of any one of claims 59-75, wherein the disintegrating matrix component is a first disintegrating matrix component, further comprising:receiving a second disintegrating matrix component with a fourth vacuum nozzle; exposing the second disintegrating matrix component to the heater while holding the second disintegrating matrix component in the fourth vacuum nozzle, such that at80ny-2823215Attorney Docket No. 75056-20042.40least one surface of the second disintegrating matrix component becomes at least partially molten; andwhile the at least one surface of the second disintegrating matrix component is at least partially molten, placing the at least one partially molten surface of the second disintegrating matrix component adjacent to the first inert component or the second inert component in the workpiece carrier, such that the second disintegrating matrix component attaches to the first inert component or the second inert component.

77. The method of claim 76, wherein at least one of the first and second disintegrating matrix components comprises an enteric disintegrating matrix component and the other of the first and second disintegrating matrix components comprises a time-dependent disintegrating matrix.

78. The method of any one of claims 59-77, further comprising:measuring a length of the linker component;determining that the length of the linker component matches a target length of the linker component; andproviding the linker component to a system for manufacturing gastric residence systems.

79. A system for manufacturing a linker component of a gastric residence system, comprising:at least three vacuum nozzles, wherein a first vacuum nozzle is configured to receive a first inert component, a second vacuum nozzle is configured to receive a disintegrating matrix component, and a third vacuum nozzle is configured to receive a second inert component;a heater configured to at least partially melt at least one surface of each of the first inert component, the disintegrating matrix component, and the second inert component;a workpiece carrier configured to receive the first inert component, the disintegrating matrix component, and the second inert component, such that adjacent components attach to one another to form the linker component; anda pick and place machine configured to transfer the linker component from the workpiece carrier into a transit puck.81ny-2823215Attorney Docket No. 75056-20042.4080. The system of claim 79, wherein the disintegrating matrix component is a first disintegrating matrix component, the system further comprising a fourth vacuum nozzle configured to receive a second disintegrating matrix component.

81. The system of claim 80, wherein at least one of the first and second disintegrating matrix components comprises an enteric disintegrating matrix component and the other of the first and second disintegrating matrix components comprises a time-dependent disintegrating matrix.

82. The system of any one of claims 79-81, further comprising an inspection station configured to:measure a length of the linker component;determine that the length of the linker component matches a target length of the linker component; andprovide the linker component to a system for manufacturing gastric residence systems.

83. A method for connecting adjacent arms of a gastric residence system comprising a core and a plurality of arms extending radially from the core with a filament, comprising: placing the gastric residence system into a webbing puck;heating a distal end of each arm of the plurality of arms so as to partially melt the distal end of each arm;pressing the filament into the partially molten distal end of each arm; and covering the filament using the partially molten distal end of each arm to secure the filament within the distal end of each arm.

84. The method of claim 83, wherein heating a distal end of each arm of the gastric residence system comprises placing a heater configured to heat the distal end of each arm of the gastric residence system adjacent to the webbing puck.

85. The method of claim 84, wherein the heater is a ring shape and comprises a cooling element in a center of the ring.

86. The method of claim 85, wherein the cooling element comprises a water-cooled tower.82ny-2823215Attorney Docket No. 75056-20042.4087. The method of claim 86, wherein the water-cooled tower is configured to cool the core and a remainder of each arm while the distal end of each arm is heated.

88. The method of any one of claims 83-87, further comprising:prior to pressing the filament into the partially molten distal end of each arm, winding the filament into a circle sized and shaped to connect the distal ends of the plurality of arms.

89. The method of any one of claims 83-88, further comprising:rounding at least one comer of the gastric residence system.

90. The method of claim 89, wherein rounding at least one comer of the gastric residence system comprises applying a rounding die to the at least one comer.

91. A system for connecting adjacent arms of a gastric residence system comprising a core and a plurality of arms extending radially from the core with a filament, comprising: a webbing puck sized and shaped to hold the gastric residence system;a heater configured to heat a distal end of each arm of the gastric residence system when the heater is placed adjacent to the webbing puck so as to at least partially melt the distal end of each arm;a filament inserter configured to insert a portion of the filament into the partially molten distal end of each arm; anda cooling element configured to cool the core and a remainder of each arm of the gastric residence system while the distal end of each arm is heated.

92. The system of claim 91, wherein the heater is a ring shape and the cooling element is located in a center of the ring.

93. The system of claim 92, wherein the cooling element comprises a water-cooled tower.

94. The system of any one of claims 91-93, wherein the filament inserter comprises a first plurality of mechanical fingers configured to hold the filament in circular shape sized to connect the distal ends of the plurality of arms.

95. The system of claim 94, wherein the first plurality of mechanical fingers are configured to press the filament in the circular shape into the distal end of each arm.83ny-2823215Attorney Docket No. 75056-20042.4096. The system of claim 95, further comprising a second plurality of mechanical fingers configured to cover the filament using the partially molten distal end of each arm to secure the filament within the distal end of each arm.

97. The system of any one of claims 92-96, further comprising a rounding die configured to round at least one comer of the gastric residence system.

98. The system of claim 97, wherein the rounding die is a heated die.84ny-2823215

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