Patent Application
20230302264
The present disclosure generally relates to drug delivery devices and, more particularly, swallowable drug delivery devices capable of delivering drugs in the gastrointestinal tract.
In recent years there has been an increase in the development of drugs for which an injection is the preferred or required administration route. Certain such drugs are not be suitable for oral administration due to complications related to chemical breakdown of active ingredients by enzymes in the gastrointestinal tract or liver, unpredictable or slow absorption of the drug by the gastrointestinal tract, irritation to the stomach or other organs included in the gastrointestinal tract, among other issues.
Various conventional administration techniques for injectable drugs involve piercing the patient's skin with a needle and subsequently injecting, via the needle, the drug subcutaneously, intravenously, etc. Oftentimes needle insertion can be painful or uncomfortable for the patient. Additionally, certain conventional injection techniques involve a risk of exposing the needle to contaminants in, for example, the ambient environment, as well as a risk for needlestick injuries. Moreover, in cases where a conventional syringe is used to inject a drug, it may be necessary to employ the services of a medical professional, which, in turn, reduces opportunities for home- or self-administration.
The present disclosure sets forth drug delivery devices embodying advantageous alternatives to existing drug delivery devices and that may address one or more of the challenges or needs mentioned herein, as well as provide other benefits and advantages.
One aspect of the present disclosure provides a swallowable drug delivery device including a capsule and a tissue attachment member. The capsule may contain a drug and may be sized to move through at least a portion of a gastrointestinal tract of a patient. The tissue attachment member may be coupled to the capsule. In an initial state, the tissue attachment member may allow the capsule to move through the at least a portion of the gastrointestinal tract. In an activated state, the tissue attachment member may be configured to at least selectively attach the capsule to a wall of the gastrointestinal tract. The tissue attachment member may be configured to change from the initial state to the activated state in response to an in vivo condition associated with the gastrointestinal tract at a predetermined location.
Another aspect of the present disclosure provides a swallowable drug delivery device including a capsule, an adhesive, and a coating or shell. The capsule may contain a drug and may be sized to move through at least a portion of a gastrointestinal tract of a patient. The adhesive may be disposed on an exterior surface of the capsule and may be configured to at least selectively attach the capsule to a wall of the gastrointestinal tract. The coating or shell may cover at least a portion of the adhesive and may be configured to degrade to uncover the at least a portion of the adhesive in response to an in vivo condition associated with the gastrointestinal tract at a predetermined location.
An additional aspect of the present disclosure provides a system including a swallowable drug delivery device and an ex vivo device. The swallowable drug delivery deice may include a capsule and a tissue penetrating delivery member. The capsule may contain a drug and may be sized to move through at least a portion of a gastrointestinal tract of a patient. The tissue penetrating delivery member may have an interior passage in fluid communication or configured to be connected in fluid communication with the drug. The ex vivo device may be positionable adjacent to an abdomen of the patient. The ex vivo device may be configured to magnetically interact with the swallowable drug delivery device to position the swallowable drug delivery device against a wall of the gastrointestinal tract.
A further aspect of the present disclosure provides a swallowable drug delivery device including a capsule and a projectile. The capsule may be sized to move through at least a portion of a gastrointestinal tract of a patient. The projectile may contain a drug. In an initial state, the projectile may be disposed at least partially within the capsule. In an activated state, the projectile may move in a direction away from the capsule for insertion into a wall of the gastrointestinal tract.
It is believed that the disclosure will be more fully understood from the following description taken in conjunction with the accompanying drawings. Some of the drawings may have been simplified by the omission of selected elements for the purpose of more clearly showing other elements. Such omissions of elements in some drawings are not necessarily indicative of the presence or absence of particular elements in any of the exemplary embodiments, except as may be explicitly delineated in the corresponding written description. Also, none of the drawings is necessarily to scale.
The present disclosure generally relates to delivering drugs at various locations in the body of a patient, including at a predetermined or preferred location. Certain embodiments provide a swallowable or ingestible drug delivery device for delivering a drug within the gastrointestinal tract of the patient, including, for example, into a wall (e.g., inner wall) of the small intestine or other organ included in the gastrointestinal tract. It has been found that, in certain cases, delivering into the wall of the small intestine is advantageous due to the relative thinness of the mucosa of the small intestine as compared to other organs included in the gastrointestinal tract. In certain embodiments the swallowable device may be configured to at least selectively attach to the gastrointestinal tract at a predetermined location by passively or actively sensing an in vivo condition associated with the predetermined location. So configured, the swallowable drug delivery device may self-activate (e.g., autonomously activate) in response the in vivo condition to anchor itself and then deliver the drug at the predetermined location. Embodiments of the present disclosure may be useful for delivering drugs which are vulnerable to breakdown by enzymes and/or other degrading elements in the gastrointestinal tract and thus previously may have been limited to delivery via non-oral routes of administration such as, for example, subcutaneous and/or intravenous routes of administration. As used herein, the term “gastrointestinal tract” refers to the mouth, esophagus, stomach, small intestine, large intestine, and anus. As used herein, the term “intestinal” refers to the small intestine and the large intestine.
The capsule 102 may have a wall 114 defining an interior space containing at least the reservoir 104 and the actuator 110. The capsule 102 may be sized to pass through some or all of the gastrointestinal tract, including, for example, passing through at least the mouth, esophagus, stomach, and an entry portion of the small intestine. To facilitate sliding through the esophagus, the capsule 102 may have, at least initially, an elongated shape corresponding to a cylinder with hemispherical ends, as seen in
The capsule 102 may protect the drug payload from degradation by enzymes and other degrading elements in the gastrointestinal tract, at least during the time period between when the capsule 102 is swallowed by the patient and when the capsule 102 reaches a predetermined location within the gastrointestinal tract where delivery of the drug is intended. In some embodiments, the capsule 102 may be constructed of a material that degrades (e.g., dissolves, breaks apart into smaller pieces, etc.) when exposed to enzyme(s) and/or other degrading element(s) in the gastrointestinal tract, including, for example, after exposure to such element(s) for a predetermined amount of time (for example, 8-12 hours after the swallowable drug delivery device 100 is swallowed by the patient) and/or exposure to enzyme(s), a concentration of enzyme(s), and/or a pH unique to a particular portion of the gastrointestinal tract such as the small intestine. In some embodiments, the predetermined amount of time may be selected so that the capsule 102 does not release the drug prior to the time when the swallowable drug delivery device 100 is expected to deliver the drug at a predetermined location such as, for example, within the small intestine.
The reservoir 104 may be disposed, entirely or partially, within the capsule 102 and may be filled, entirely or partially, with a drug. The drug may be, but is not limited to, various biologicals such as peptides, peptibodies, or antibodies. More examples of the drug are described below. The drug may be in a fluid or liquid form, although the disclosure is not limited to a particular state. Some or all of the wall(s) enclosing the drug in the reservoir 104 may correspond to the wall 114 of the capsule 102. Additionally or alternatively, some or all of the wall(s) enclosing the drug in the reservoir 104 may correspond to a wall 116 of the tissue attachment member 106. In some embodiments, the wall(s) enclosing the drug in the reservoir 104 may be physically distinct from the wall 114 of the capsule 102 and/or the wall 116 of the tissue attachment member 106. In some embodiments, the wall(s) enclosing the drug in the reservoir 104 may be rigid, flexible, or some combination of rigid and flexible. In some embodiments, the reservoir 104 may be a drug storage bladder having a flexible wall which can be compressed or otherwise deformed (e.g., elastically deformed) to expel the drug from the interior of the drug storage bladder.
The tissue penetrating delivery member 108 may be configured to deliver the drug from the reservoir 104 into an inner wall 118 of the gastrointestinal tract including, for example, into an inner wall of the small intestine. In some embodiments, the tissue penetrating delivery member 108 may be configured to deliver the drug directly into the mucosa or submucosa, including, for example, directly into and/or immediately adjacent to arteries, veins, and/or capillaries in the mucosa or submucosa. In some embodiments, the tissue penetrating delivery member 108 may be configured to deliver the drug at a depth beneath the surface of the inner wall 118 of the gastrointestinal tract in a range between approximately (e.g., ±10%) 150-250 μm, or at a depth beneath the surface of the inner wall 118 of the gastrointestinal tract in a range between approximately (e.g., ±10) 100-300 μm, or at a depth beneath the surface of the inner wall 118 of the gastrointestinal tract that is greater than approximately (e.g., ±10%) 100 μm, or at a depth beneath the surface of the inner wall 118 of the gastrointestinal tract that is greater than approximately (e.g., ±10%) 150 μm, or at a depth beneath the surface of the inner wall 118 of the gastrointestinal tract that is greater than approximately (e.g., ±10%) 200 μm. In embodiments where the preferred location for drug delivery is the small intestine, having a tissue penetrating delivery member 108 that is configured to deliver the drug at a depth beneath the surface of the inner wall of the small intestine in a range between approximately (e.g., ±10%) 150-250 μm may allow the tissue penetrating delivery member 108 to deliver the drug directly into or immediately adjacent to arteries, veins, and/or capillaries in the mucosa or submucosa.
In some embodiments, the tissue penetrating delivery member 108 may include a wall that defines an interior passage between a first end and a second end of the tissue penetrating delivery member 108. The wall may have a tapered region at the first end which, in some embodiments, may result in the first end having a point. Variously herein the first end of the tissue penetrating delivery member 108 is referred to as the pointed end of the tissue penetrating delivery member 108. One or more openings may be formed in the wall at the first end of the tissue penetrating delivery member 108 and may communicate with the interior passage of the tissue penetrating delivery member 108. The interior passage of the tissue penetrating delivery member 108 may, via the second end of the tissue penetrating delivery member 108, be connected in fluid communication or configured to be connected in fluid communication with the drug in the reservoir 104. During drug delivery, the drug may move out of the reservoir 104, then through the interior passage of the tissue penetrating delivery member 108, then out of the tissue penetrating delivery member 108 via the one or more openings in the first end of the tissue penetrating delivery member 108, and then directly into the inner wall 118 of the gastrointestinal tract.
The tissue penetrating delivery member 108 may take various forms depending on, for example, a preferred rate at which the drug is absorbed by the patient's tissue, a viscosity of the drug, a thickness of the inner wall of the gastrointestinal tract at the delivery location, among other factors. In some embodiments, the tissue penetrating delivery member 108 may be configured as one or more microneedles, one or more needles, one or more nozzles, or any combination thereof. The tissue penetrating delivery member 108 may be made of a relatively rigid material such as metal and/or certain polymers. Furthermore, in some embodiments, the material used to construct the tissue penetrating delivery member 108 may degrade (e.g., dissolve, break apart into smaller pieces, etc.) when exposed to enzyme(s) and/or other degrading element(s) in the gastrointestinal tract, including, for example, after exposure to such element(s) for a predetermined amount of time (for example, 8-12 hours after the swallowable drug delivery device 100 is swallowed by the patient) and/or exposure to enzyme(s), a concentration of enzyme(s), and/or a pH unique to a particular portion of the gastrointestinal tract such as the small intestine. A single tissue penetrating deliver member 108 may be included as seen in
The tissue penetrating delivery member 108 may be coupled to the wall 114 of the capsule 102 with the first end of the tissue penetrating delivery member 108 extending outwardly from the wall 114 of the capsule 102, as illustrated in
In some embodiments, the tissue penetrating delivery member 108 may be fixed (i.e., immoveable) relative to the wall 114 of the capsule 102 and/or the wall 116 of the tissue attachment member 106. In alternative embodiments, the tissue penetrating delivery member 108 may be moveable relative to the wall 114 of the capsule 102 and/or the wall 116 of the tissue attachment member 106. In such alternative embodiments, the tissue penetrating delivery member 108 may be actuated to move from an initial position, where the first end of the tissue penetrating delivery member 108 is disposed within the capsule 102 or the tissue attachment member 106, to a delivery position, where the first end of the tissue penetrating delivery member 108 is disposed through the wall 114 of the capsule 102 or the wall 116 of the tissue attachment member 106 for insertion into the inner wall 118 of the gastrointestinal tract.
In some embodiments, the tissue penetrating delivery member 108 may be omitted. In certain such embodiments, the wall 114 of the capsule 102 and/or the wall 116 of the tissue attachment member 106 may have one or more openings which are configured to deliver the drug into a lumen of the gastrointestinal tract at a predetermined location. Alternatively or additionally, the wall 114 of the capsule 102 and/or the wall 116 of the tissue attachment member 106 may degrade (e.g., dissolve, break apart into smaller pieces, etc.) in order to release the drug into a lumen of the gastrointestinal tract at a predetermined location. This degradation may occur as a result of exposure to enzyme(s) and/or other degrading element(s) in the gastrointestinal tract, including, for example, after exposure to such element(s) for a predetermined amount of time (for example, 8-12 hours after the swallowable drug delivery device 100 is swallowed by the patient) and/or exposure to enzyme(s), a concentration of enzyme(s), and/or a pH unique to a particular portion of the gastrointestinal tract such as the small intestine. In some embodiments, the swallowable drug delivery device 100 may be configured to deliver the drug via any combination of: the tissue penetrating delivery member(s) 108; opening(s) in the wall 114 of the capsule 102; opening(s) in the wall 116 of the tissue attachment member 106; degradation of the wall 114 of the capsule 102; and degradation of the wall 116 of the tissue attachment member 106.
In general terms, the tissue attachment member 106 may function as an anchor for stationarily or substantially stationarily positioning the capsule 102 in the gastrointestinal tract at a predetermined (e.g., preselected, targeted, chosen, preferred, etc.) location. The tissue attachment member 106 may have at least two states: an initial state (
The tissue attachment member 106 may be configured to change from the initial state to the activated state in response to an in vivo condition (e.g., in vivo stimuli) associated with the gastrointestinal tract at the predetermined location. The in vivo condition may be, for example, any one or combination of a predetermined temperature, pH, enzyme, and electrical conductivity in the gastrointestinal tract. In some embodiments the tissue attachment member 106 may passively sense the in vivo condition and in response change from the initial state to the activated state. In certain such embodiments, the tissue attachment member 106 may be made of a shape memory material such as, for example, a shape memory alloy and/or a shape memory polymer (e.g., a biodegradable shape memory polymer). Certain such shape memory materials may be deformed (e.g., compressed) at a first temperature and return to a pre-deformed shape when exposed to a second temperature that is higher than the first temperature. Other such shape memory materials, such as a pH-sensitive shape memory polymer, may change shape (e.g., expand or contract) in response to an increase or decrease of pH of a surrounding environment. In some embodiments, a pH-sensitive shape memory polymer used to construct the tissue attachment member 106 may cause the tissue attachment member 106 to change from the initial state to the activated state in response to a pH greater than or equal to approximately (e.g., ±10%) three (3), or a pH greater than or equal to approximately (e.g., ±10%) four (4), or a pH greater than or equal to approximately (e.g., ±10%) five (5). In some embodiments, the shape memory material may change shape in response to exposure to particular enzyme(s) or a concentration of enzyme(s) existing in the gastrointestinal tract including at the predetermination location in the gastrointestinal tract. In some embodiments, it may be any combination of temperature, pH, and enzyme(s) that cause the shape memory material used to construct the tissue attachment member 106 to change shape.
In some embodiments, electronic sensor(s), including, for example, optical and/or ultrasonic sensor(s), may be incorporated into the swallowable drug delivery device 100 for detecting the in vivo condition. In some embodiments, the electronic sensor(s) may output a signal to a local and/or remote controller, which, in turn, may analyze the signal and based on that analysis output a control signal causing the tissue attachment member 106 to change from the initial state to the activated state.
In some embodiments, a shape and/or orientation of the tissue attachment member 106 may change when the tissue attachment member 106 changes from the initial state to the activated state. For example, as seen in the transition from
In addition, or as an alternative, to a change in the shape and/or orientation of the tissue attachment member 106, the tissue attachment member 106 may move in a radial direction away from the longitudinal axis A of the capsule 102 when the tissue attachment member 106 changes from the initial state to the activated state in some embodiments. Alternatively, in some embodiments, the tissue attachment member 106 may not undergo a change in shape, orientation, radial position, etc. in changing from the initial state to the activated state and as such there is no change in an outer dimension of the swallowable drug delivery device 100. Instead, the tissue attachment member 106 may be an adhesive (e.g., a mucoadhesive or other bioadhesive) which goes from being covered to uncovered as a result of the transition from the initial state to the activated state. In some embodiments, an adhesive which goes from being covered to uncovered, or which is always uncovered, may be used in conjunction with (e.g., applied to) a tissue attachment member which changes shape, orientation, and/or radial position when transitioning from the initial state to the activated state.
In some embodiments, the tissue attachment member 106 and the tissue delivery member 108 may be separate structures; whereas, in other embodiments, the tissue attachment member 106 and the tissue delivery member 108 may be the same structure.
In the initial state, the tissue attachment member 106 may be disposed on the exterior surface of the wall 114 of the capsule 102, or alternatively, may be disposed partially or entirely within the interior space of the capsule 102. In some embodiments, a groove or recess may be formed in the exterior surface of the wall 114 of the capsule 102 and the tissue attachment member 106 may be received in this groove or recess. In certain such embodiments, in the initial state, an exterior surface of the tissue attachment member 106 may be flush with and/or match the contour of the exterior surface of the wall 114 of the capsule 102, in order to provide a smooth surface facilitating passage (e.g., sliding) of the swallowable drug delivery device 100 through the gastrointestinal tract until it reaches the predetermined location for attachment and drug delivery.
As described in more detail below with respect to various embodiments, the tissue attachment member 106 may be formed by one or more expandable members (e.g., one or more expandable anchors). The expandable member(s) may in certain embodiments be solid (i.e., not hollow) whereas in other embodiments the expandable member(s) may be hollow. In some embodiments, the expandable member(s) may be configured as one or more bladders each being made of a flexible material and capable of being filled with a gas (e.g., air) and/or fluid (e.g., a drug) which causes the bladder to expand.
The coating 112 may cover a limited portion of the exterior surface of the wall 114 of the capsule 102 as shown in
The actuator 110 may be disposed partially or entirely within the interior space of the capsule 102. The actuator 110 may be configured to move the drug out of the reservoir 104 and into the gastrointestinal tract, including, for example, into the wall 118 of the gastrointestinal tract. Additionally or alternatively, the actuator 110 may be configured to move the tissue attachment member 106 from the initial state to the activated state. In some embodiments, the actuator 110 may include but is not limited to: an electromechanical drive mechanism such as, for example: a piezoelectric pump; a MEMS pump; a sonophoresis drive mechanism; a positive displacement pump; a spring such as, for example, a spring made of a shape memory polymer and/or a shape memory alloy; an inflatable bladder; and/or an osmotic pump. In some embodiments, the actuator 110 may push on a piston (e.g., a plunger) which, in turn, moves through the reservoir 104 to expel the drug from the reservoir 104.
In some embodiments, the actuator 110 may be omitted and the drug may be pushed out of the reservoir 104 into the gastrointestinal tract and as a result of natural movements (e.g., peristaltic movements) of the gastrointestinal tract. In some embodiments where the actuator 110 is omitted, an external (e.g., ex vivo) device may provide the energy needed for moving the drug out of the reservoir 104. In such embodiments, the external device may include a magnet, an electromagnet, an inductor, and/or a radiofrequency (RF) energy source for generating the needed to move the drug out of the reservoir 104.
In use, a patient may place the swallowable drug delivery device 100 in his or her mouth and swallow the swallowable drug delivery device 100. The swallowable drug delivery device 100 may then be pushed by, for example, natural movements (e.g., peristaltic movements) of the wall of the gastrointestinal tract, through the gastrointestinal tract toward a predetermined location (e.g., a region, an area, or a specific position) where attachment and drug delivery is to occur. In some embodiments, the predetermined location may correspond to a location where the thickness of the wall 118 of the gastrointestinal tract is at or near its thinnest. In some embodiments, the predetermined location is in the small intestine, although the predetermined location is not limited to the small intestine and may be anywhere along the gastrointestinal tract where optimal conditions for drug delivery exist. Gradually on the journey towards and/or at the predetermined location the coating 112 may dissolve or otherwise degrade to uncover the tissue attachment member 106 and the tissue penetrating delivery member 108. Simultaneous with the coating 112 degrading or subsequent to the coating 112 degrading, the tissue attachment member 106 may change from the initial state (
Turning to
Some embodiments of the swallowable drug delivery device may utilize a tissue attachment member that includes one or more expandable members (e.g., expandable anchors). The one or more expandable members may in the initial state have a non-expanded form or shape and in the activated state have an expanded form or shape. In some embodiments, after drug delivery is complete, the one or more expandable members may degrade (e.g., dissolves, breaks apart into smaller pieces, etc.) from exposure to enzyme(s) and/or other degrading element(s) in the gastrointestinal tract, including, for example, after exposure to such element(s) for a predetermined amount of time (for example, 8-12 hours after the swallowable drug delivery device is swallowed by the patient) and/or exposure to enzyme(s), a concentration of enzyme(s), and/or a pH unique to a particular portion of the gastrointestinal tract such as the small intestine. As an alternative to or in addition to degrading after drug delivery, the one or more expandable members may retract or return to their non-expanded form or shape. After the one or more expandable members have degraded and/or returned to their non-expanded form or shape, the capsule may detach from the inner wall 118 of the gastrointestinal tract and as a consequence continue its natural passage through the gastrointestinal tract and/or degrade (e.g., dissolve, breaks apart into smaller piece, etc.) and thereafter be absorbed by the gastrointestinal tract or expelled via the anus.
In the initial state shown in
In the activated state shown in
In some embodiments, the expandable members 230 may be covered with a coating (e.g., the coating 112) in the initial state. The coating may restrain the expandable members 230 from expanding. As the swallowable drug delivery device 200 moves through the gastrointestinal tract, the coating may degrade, thereby allowing the expandable members 230 to change into the activated state. In certain such embodiments, the expandable members 230 each may be made of an elastic material that is held in a compressed state by the coating and, when the coating degrades, the elastic material returns to its uncompressed state, thereby resulting in expansion of the expandable member 230.
The swallowable drug delivery device 300 has a single expandable member 330 which functions as the tissue attachment member 306. It has circular or substantially circular shape in both the initial state (
In order to achieve the insertion functionality described above, the tissue penetrating delivery members 308 may, in some embodiments, be disposed on the same side of the capsule 302 as the first end of the expandable member 330, as seen in
The swallowable drug delivery device 400 includes an expandable member 430 having an outer surface 434, which may be a radially outwardly facing surface, configured to meshingly engage with the wall 118 of the gastrointestinal tract in order to immobilize or substantially impede the swallowable drug delivery device 400 from further movement relative to the wall 118 of the gastrointestinal tract.
The swallowable drug delivery device 500 includes an expandable member 530 configured as an inflatable bladder 540. The inflatable bladder 540 may have an interior space that is empty or only partially filled with a gas (e.g., air) and/or fluid (e.g., a drug) in the initial state (
Tissue penetrating delivery members 508 may be coupled to the second end of the inflatable bladder 540. In some embodiments, the tissue penetrating delivery members 508 may be configured as one or more microneedles, one or more needles, one or more nozzles, or any combination thereof. As shown in
In some embodiments, a pressurized source of gas and/or fluid may be included in the capsule 502 for inflating the inflatable bladder 540 with gas and/or fluid at the appropriate time. In some embodiments, the pressurized source of gas and/or fluid may include a liquefied propellant that when released rapidly expands. In embodiments where the inflatable bladder 450 is inflated with a substance other than the drug, one of more fluid conduits (e.g., flexible tubing) may be disposed at least partially within the inflatable bladder 540 and may connect the tissue penetrating delivery members 508 in fluid communication with a drug reservoir in the capsule 502.
The inflatable bladder(s) described above in connection with the swallowable drug delivery devices 500 and 600 are disposed outside of the capsule in the initial state. In other embodiments, such as the embodiment described below in conjunction with
A pressurized source of gas and/or fluid 750 (e.g., a pressurized canister or cylinder) may be positioned within the interior space of the capsule 702 and may be configured for inflating the inflatable bladders 740a and 740b with gas and/or fluid. In some embodiments, the pressurized source of gas and/or fluid 750 may include a liquefied propellant that when released rapidly expands. In some embodiments, the gas and/or fluid released from the pressurized source of gas and/or fluid 750 may, in addition to inflating the inflatable bladders 740a and 740b, assist with moving the drug out of the reservoir 704 for delivery into the patient. In the present embodiment, an actuator 710 which is separate from the gas and/or fluid 750 is included for moving the drug out of the reservoir 704 for delivery into the patient. In some embodiment, the actuator 710 may be configured as a piezoelectric pump and, in some embodiments, may be controllable via a wireless signal (e.g., a Bluetooth) signal from an ex vivo device.
As shown in
While the foregoing embodiments of the swallowable drug device include a tissue attachment member that expands or otherwise changes shape in transitioning from the initial state to the activated state, other embodiments may have a tissue attachment member whose shape is the same or substantially the same in both the initial state and the activated state. Such embodiments are discussed below in conjunction with
An actuator 810 is disposed within the capsule 802 adjacent to and in contact with the wall of the reservoir 804. As described below, the actuator 810 may be configured to expand and compress the reservoir 804 against an inner surface of the wall 814 of the capsule 802. In some embodiments, the actuator 810 may be an inflatable bladder which is inflated by a pressurized source of gas and/or fluid (e.g., a pressurized canister or cylinder). In some embodiments, the pressurized source of gas and/or fluid may include a liquefied propellant that when released expands rapidly. In other embodiments, the actuator 810 may be configured as a plurality of temperature-sensitive beads which expand in response to a change (e.g., increase or decrease) in temperature. In certain such embodiments, the beads may be made of a shape memory material (e.g., a shape memory polymer or a shape memory alloy).
In some embodiments, the swallowable drug delivery device 800 may include a sensing and communication module 850. The sensing and communication module 850 may be coupled (e.g., electrically coupled) with tissue attachment members 806 and may detect electrical continuity between the tissue attachment members 806 to confirm proper submucosa placement of the tissue attachment members 806.
The swallowable drug delivery device 1000 includes an actuator 1010 disposed at least partially within the capsule 1002 and which is configured to expand to move the drug out of the reservoir 1004 into the wall 118 of the gastrointestinal tract. The reservoir 1004 may be defined at least by the wall 1014 of the capsule 1002 and a piston 1052 moveably disposed in the capsule 1002. Expansion of the actuator 1010 may cause the actuator 1010 to push on or otherwise act on the piston 1052 to move the piston 1052 relative to the wall 1014 to decrease a volume of the reservoir 1004, thereby expelling the drug from the reservoir 1004 into the wall 118 of the gastrointestinal tract.
The actuator 1010 may be configured to expand, or contract depending on the configuration of the piston 1052, in response to an in vivo condition of the gastrointestinal tract at a predetermined location. To achieve this change in shape, the actuator 1010 may be constructed of a shape memory material such as, for example, a shape memory alloy and/or a shape memory polymer (e.g., a biodegradable shape memory polymer). Certain such shape memory materials may be deformed (e.g., compressed) at a first temperature and return to a pre-deformed shape when exposed to a second temperature that is higher than the first temperature. Other such shape memory materials, such as a pH-sensitive shape memory polymer, may change shape (e.g., expand or contract) in response to an increase or decrease in pH of a surrounding environment. In some embodiments, the shape memory material may change shape in response to exposure to particular enzyme(s) or concentration of enzyme(s) existing in the gastrointestinal tract including at a particular location in the gastrointestinal tract. In some embodiments, it may be any combination of temperature, pH, and enzyme(s) that cause the shape memory material used to construct the actuator 1010 to change shape. In some embodiments, opening(s) may be formed in the wall of the 1014 of the capsule 1002 to allow bodily fluids to flow into the interior space or compartment of the capsule 1002 where the actuator 1010 is disposed, such that the shape memory material used to construct the actuator 1010 is directly exposed to the temperature, pH, enzyme(s), or other in vivo condition intended to cause the shape memory material to change shape.
The actuator 1010 illustrated in
The swallowable drug delivery device 1000 may have tissue attachment members 1006 which, in addition to securing the swallowable drug delivery device 1000 to the wall 118 of the gastrointestinal tract in the activated state, are configured to deliver the drug into the wall 118 of the gastrointestinal tract. The tissue attachment members 1006 are coupled to the wall 1014 (e.g., a circumferential wall) of the capsule 1002 and have pointed ends which extend outwardly from the wall 1014 of the capsule 1002. In some embodiments, the tissue attachment member 1106 may be fixedly coupled to the wall 1014 and thus may be immoveable relative to the wall 1014. A coating such as, for example, the coating 112 described above, may cover the pointed ends of the tissue attachment members 1006 in the initial state and subsequently degrade as a result of exposure to elements of the gastrointestinal tract to uncover the pointed ends of the tissue attachment members 1006 to enable the activated state at the predetermined location within the gastrointestinal tract.
The swallowable drug delivery device 1100 includes a tissue attachment member 1106 comprised of an adhesive 1154. The adhesive 1154 may be applied to an exterior surface of the wall 1114 of the capsule 1102. In the initial state shown in
In some embodiments, the adhesive 1154 may be a mucoadhesive including, for example, biocompatible adhesive polymer chains that intermingle with mucosa proteins to form a bond. The adhesive 1154 may be selected based on a particular gastrointestinal organ (e.g., the small intestine) where drug delivery is intended to occur.
The adhesive 1154 may be applied to a circumferential portion of the wall 1114 located on a first side of the capsule 1102, as shown in
The coating 1112 may be made of a material that degrades (e.g., dissolves, breaks apart into smaller pieces, etc.) when exposed to enzyme(s) and/or other degrading element(s) in the gastrointestinal tract, including, for example, after exposure to such element(s) for a predetermined amount of time (for example, 8-12 hours after the swallowable drug delivery device 1100 is swallowed by the patient) and/or exposure to enzyme(s), a concentration of enzyme(s), and/or a pH unique to a particular portion of the gastrointestinal tract such as the small intestine. In some embodiments, the coating 1112 may be a pH-sensitive coating that does not dissolve until exposure to the higher pH environment of the small intestine. In some embodiments, the coating 1112 may be an enteric coating including, for example, a polymer based enteric coating.
In the embodiment illustrated in
In the illustrated embodiment, the adhesive 1154 is applied to an exterior surface of the wall 1114 of the capsule 1102 in the initial state. In alternative embodiments, the adhesive 1154 may be disposed within the interior space of the capsule 1102 in the initial state. In such embodiments, the adhesive 1154 may be expelled through opening(s) in the wall 1114 of the capsule 1102 when the swallowable drug delivery device 1100 reaches the predetermined location. The coating 1112 may cover these opening(s) in the initial state and leave them uncovered in the activated state. The adhesive 1154 may be expelled from the interior of the capsule 1102 by a pump or other actuator included in the capsule 1102, thermal or chemical expansion, and/or natural peristaltic movement of the gastrointestinal tract. In some embodiments, the adhesive 1154 may be an expanding foam that partially or entirely fills a diameter of the intestinal tract and which dissolves after a short period of exposure to gastric fluids.
The foregoing embodiments of the swallowable drug delivery device utilize self-deploying tissue attachment member(s) responsive to an in vivo condition in order to anchor the swallowable drug delivery device at the predetermined location in the gastrointestinal tract. In other embodiments, the swallowable drug delivery device may be used in conjunction with an ex vivo (e.g., outside of the patient's body) device in order to anchor the swallowable drug delivery device at the predetermined location in the gastrointestinal tract. An embodiment of a system including a swallowable drug delivery device and ex vivo device is described below in connection with
In some embodiments, the ex vivo device 1370 may be configured to magnetically interact (e.g., magnetically attract and/or magnetically repel) the swallowable drug delivery device 1300 in order to position (e.g., hold, immobilize, etc.) the swallowable drug delivery device 1300 against the inner wall 118 of the gastrointestinal tract at the predetermined (e.g., preselected, targeted, chosen, preferred, etc.) location for drug delivery. The swallowable drug delivery device 1300 may include a magnetic element that experiences a magnetic pull or push in the presence of a magnetic element included in the ex vivo device 1370. The magnetic element included in the swallowable drug delivery device 1300 may be any one or combination of: a permanent magnet, an electromagnet, a metallic element, a magnetic ceramic element, and any other magnetic-field generating element. The magnetic element included in the ex vivo device 1370 may be any one or combination of: a permanent magnet, an electromagnet, a metallic element, a magnetic ceramic element, and any other magnetic-field generating element.
The swallowable drug delivery device 1300 may include tissue penetrating delivery member(s) similar to those described above in connection with
In some embodiments, the ex vivo device 1370 may be configured to wirelessly transmit power to (e.g., via inductive charging) the swallowable drug delivery device 1300 including, for example, when the swallowable drug delivery device 1300 is within the gastrointestinal tract. The swallowable drug delivery device 1300, in turn, may use this power to expel the drug from the swallowable drug delivery device and/or move the tissue penetrating delivery member(s) from the initial position to the delivery position. This may eliminate the need for including a pre-charged internal battery source within the swallowable drug delivery device 1300 and in some instances reduce the size of the swallowable drug delivery device 1300.
In some embodiments, the ex vivo device 1370 may be configured to transmit control signal(s) to the swallowable drug delivery device 1300 causing, for example, activation of an actuator included the swallowable drug delivery device 1300 for expelling the drug from the swallowable drug delivery device 1300, movement of the tissue penetrating delivery member(s) from the initial position to the delivery position, and/or the activation or execution of other functionalities of swallowable drug delivery device 1300.
As illustrated in
In some embodiments, the ex vivo device 1370 may include a proximity sensor configured to determine whether the swallowable drug delivery device 1300 is within a predetermined distance of the ex vivo device 1370.
In the embodiment illustrated in
The foregoing embodiments of the swallowable drug delivery device generally operate to perform drug delivery by transferring a drug contained in a reservoir, which is coupled to a capsule, into the gastrointestinal tract. In other embodiments, the reservoir may physically separate from the capsule at the time of drug delivery.
Each of the projectiles 1482 may contain a drug and a propellant 1484, which may be stored in separate internal chambers walled off from each other. Each projectile 1482 may have first end and a second end. In some embodiments, the first end may be pointed to facilitate penetration into the wall 118 of the gastrointestinal tract. One or more openings may be formed in the first end of the projectile 1482 so that the drug can move out of the projectile 1482 when the projectile 1482 has penetrated into the wall 118 of the gastrointestinal tract. Additionally or alternatively, a wall of the projectile 1482 at the first end and/or the second end may be made of a material that degrades (e.g., dissolves, breaks apart into smaller pieces, etc.) when exposed to enzyme(s) and/or other degrading element(s) in the gastrointestinal tract, including, for example, after exposure to such element(s) for a predetermined amount of time. So configured, the drug contained in the projectile 1482 may be released into the wall 118 of the gastrointestinal tract at least partly as a result of degradation of the wall of the projectile 1482.
The second end of each projectile 1482 may have an opening 1488 (
In some embodiments, the propellant 1484 may be made, partially or entirely, of zinc and/or the gas 1486 generated in the activated state may be made, partially or entirely, of hydrogen. In some embodiments, the propellant 1484 may be made of PANI/Zn. In some embodiments, the chemical reaction that occurs when the propellant 1484 is exposed to an acidic environment in the gastrointestinal tract may be described by the following chemical formula: 2H*(aq)+Zn(s)→H2(g)+Zn2+(aq).
As will be recognized, the devices and methods according to the present disclosure may have one or more advantages relative to conventional technology, any one or more of which may be present in a particular embodiment in accordance with the features of the present disclosure included in that embodiment. Other advantages not specifically listed herein may also be recognized as well.
The above description describes various devices, assemblies, components, subsystems and methods for use related to a drug delivery device. The devices, assemblies, components, subsystems, methods or drug delivery devices can further comprise or be used with a drug including but not limited to those drugs identified below as well as their generic and biosimilar counterparts. The term drug, as used herein, can be used interchangeably with other similar terms and can be used to refer to any type of medicament or therapeutic material including traditional and non-traditional pharmaceuticals, nutraceuticals, supplements, biologics, biologically active agents and compositions, large molecules, biosimilars, bioequivalents, therapeutic antibodies, polypeptides, proteins, small molecules and generics. Non-therapeutic injectable materials are also encompassed. The drug may be in liquid form, a lyophilized form, or in a reconstituted from lyophilized form. The following example list of drugs should not be considered as all-inclusive or limiting.
The drug will be contained in a reservoir. In some instances, the reservoir is a primary container that is either filled or pre-filled for treatment with the drug. The primary container can be a vial, a cartridge or a pre-filled syringe.
In some embodiments, the reservoir of the drug delivery device may be filled with or the device can be used with colony stimulating factors, such as granulocyte colony-stimulating factor (G-CSF). Such G-CSF agents include but are not limited to Neulasta® (pegfilgrastim, pegylated filgastrim, pegylated G-CSF, pegylated hu-Met-G-CSF) and Neupogen® (filgrastim, G-CSF, hu-MetG-CSF), UDENYCA® (pegfilgrastim-cbqv), Ziextenzo® (LA-EP2006; pegfilgrastim-bmez), or FULPHILA (pegfilgrastim-bmez).
In other embodiments, the drug delivery device may contain or be used with an erythropoiesis stimulating agent (ESA), which may be in liquid or lyophilized form. An ESA is any molecule that stimulates erythropoiesis. In some embodiments, an ESA is an erythropoiesis stimulating protein. As used herein, “erythropoiesis stimulating protein” means any protein that directly or indirectly causes activation of the erythropoietin receptor, for example, by binding to and causing dimerization of the receptor. Erythropoiesis stimulating proteins include erythropoietin and variants, analogs, or derivatives thereof that bind to and activate erythropoietin receptor; antibodies that bind to erythropoietin receptor and activate the receptor; or peptides that bind to and activate erythropoietin receptor. Erythropoiesis stimulating proteins include, but are not limited to, Epogen® (epoetin alfa), Aranesp® (darbepoetin alfa), Dynepo® (epoetin delta), Mircera® (methyoxy polyethylene glycol-epoetin beta), Hematide®, MRK-2578, INS-22, Retacrit® (epoetin zeta), Neorecormon® (epoetin beta), Silapo® (epoetin zeta), Binocrit® (epoetin alfa), epoetin alfa Hexal, Abseamed® (epoetin alfa), Ratioepo® (epoetin theta), Eporatio® (epoetin theta), Biopoin® (epoetin theta), epoetin alfa, epoetin beta, epoetin iota, epoetin omega, epoetin delta, epoetin zeta, epoetin theta, and epoetin delta, pegylated erythropoietin, carbamylated erythropoietin, as well as the molecules or variants or analogs thereof.
Among particular illustrative proteins are the specific proteins set forth below, including fusions, fragments, analogs, variants or derivatives thereof: OPGL specific antibodies, peptibodies, related proteins, and the like (also referred to as RANKL specific antibodies, peptibodies and the like), including fully humanized and human OPGL specific antibodies, particularly fully humanized monoclonal antibodies; Myostatin binding proteins, peptibodies, related proteins, and the like, including myostatin specific peptibodies; IL-4 receptor specific antibodies, peptibodies, related proteins, and the like, particularly those that inhibit activities mediated by binding of IL-4 and/or IL-13 to the receptor; Interleukin 1-receptor 1 (“IL1-R1”) specific antibodies, peptibodies, related proteins, and the like; Ang2 specific antibodies, peptibodies, related proteins, and the like; NGF specific antibodies, peptibodies, related proteins, and the like; CD22 specific antibodies, peptibodies, related proteins, and the like, particularly human CD22 specific antibodies, such as but not limited to humanized and fully human antibodies, including but not limited to humanized and fully human monoclonal antibodies, particularly including but not limited to human CD22 specific IgG antibodies, such as, a dimer of a human-mouse monoclonal hLL2 gamma-chain disulfide linked to a human-mouse monoclonal hLL2 kappa-chain, for example, the human CD22 specific fully humanized antibody in Epratuzumab, CAS registry number 501423-23-0; IGF-1 receptor specific antibodies, peptibodies, and related proteins, and the like including but not limited to anti-IGF-1R antibodies; B-7 related protein 1 specific antibodies, peptibodies, related proteins and the like (“B7RP-1” and also referring to B7H2, ICOSL, B7h, and CD275), including but not limited to B7RP-specific fully human monoclonal IgG2 antibodies, including but not limited to fully human IgG2 monoclonal antibody that binds an epitope in the first immunoglobulin-like domain of B7RP-1, including but not limited to those that inhibit the interaction of B7RP-1 with its natural receptor, ICOS, on activated T cells; IL-15 specific antibodies, peptibodies, related proteins, and the like, such as, in particular, humanized monoclonal antibodies, including but not limited to HuMax IL-15 antibodies and related proteins, such as, for instance, 145c7; IFN gamma specific antibodies, peptibodies, related proteins and the like, including but not limited to human IFN gamma specific antibodies, and including but not limited to fully human anti-IFN gamma antibodies; TALL-1 specific antibodies, peptibodies, related proteins, and the like, and other TALL specific binding proteins; Parathyroid hormone (“PTH”) specific antibodies, peptibodies, related proteins, and the like; Thrombopoietin receptor (“TPO-R”) specific antibodies, peptibodies, related proteins, and the like; Hepatocyte growth factor (“HGF”) specific antibodies, peptibodies, related proteins, and the like, including those that target the HGF/SF:cMet axis (HGF/SF:c-Met), such as fully human monoclonal antibodies that neutralize hepatocyte growth factor/scatter (HGF/SF); TRAIL-R2 specific antibodies, peptibodies, related proteins and the like; Activin A specific antibodies, peptibodies, proteins, and the like; TGF-beta specific antibodies, peptibodies, related proteins, and the like; Amyloid-beta protein specific antibodies, peptibodies, related proteins, and the like; c-Kit specific antibodies, peptibodies, related proteins, and the like, including but not limited to proteins that bind c-Kit and/or other stem cell factor receptors; OX40L specific antibodies, peptibodies, related proteins, and the like, including but not limited to proteins that bind OX40L and/or other ligands of the OX40 receptor; Activase® (alteplase, tPA); Aranesp® (darbepoetin alfa) Erythropoietin [30-asparagine, 32-threonine, 87-valine, 88-asparagine, 90-threonine], Darbepoetin alfa, novel erythropoiesis stimulating protein (NESP); Epogen® (epoetin alfa, or erythropoietin); GLP-1, Avonex® (interferon beta-1a); Bexxar® (tositumomab, anti-CD22 monoclonal antibody); Betaseron® (interferon-beta); Campath® (alemtuzumab, anti-CD52 monoclonal antibody); Dynepo® (epoetin delta); Velcade® (bortezomib); MLN0002 (anti-α4β7 mAb); MLN1202 (anti-CCR2 chemokine receptor mAb); Enbrel® (etanercept, TNF-receptor/Fc fusion protein, TNF blocker); Eprex® (epoetin alfa); Erbitux® (cetuximab, anti-EGFR/HER1/c-ErbB-1); Genotropin® (somatropin, Human Growth Hormone); Herceptin® (trastuzumab, anti-HER2/neu (erbB2) receptor mAb); Kanjinti™ (trastuzumab-anns) anti-HER2 monoclonal antibody, biosimilar to Herceptin®, or another product containing trastuzumab for the treatment of breast or gastric cancers; Humatrope® (somatropin, Human Growth Hormone); Humira® (adalimumab); Vectibix® (panitumumab), Xgeva® (denosumab), Prolia® (denosumab), Immunoglobulin G2 Human Monoclonal Antibody to RANK Ligand, Enbrel® (etanercept, TNF-receptor/Fc fusion protein, TNF blocker), Nplate® (romiplostim), rilotumumab, ganitumab, conatumumab, brodalumab, insulin in solution; Infergen® (interferon alfacon-1); Natrecor® (nesiritide; recombinant human B-type natriuretic peptide (hBNP); Kineret® (anakinra); Leukine® (sargamostim, rhuGM-CSF); LymphoCide® (epratuzumab, anti-CD22 mAb); Benlysta™ (lymphostat B, belimumab, anti-BlyS mAb); Metalyse® (tenecteplase, t-PA analog); Mircera® (methoxy polyethylene glycol-epoetin beta); Mylotarg® (gemtuzumab ozogamicin); Raptiva® (efalizumab); Cimzia® (certolizumab pegol, CDP 870); Solids™ (eculizumab); pexelizumab (anti-05 complement); Numax® (MEDI-524); Lucentis® (ranibizumab); Panorex® (17-1A, edrecolomab); Trabio® (lerdelimumab); TheraCim hR3 (nimotuzumab); Omnitarg (pertuzumab, 2C4); Osidem® (IDM-1); OvaRex® (B43.13); Nuvion® (visilizumab); cantuzumab mertansine (huC242-DM1); NeoRecormon® (epoetin beta); Neumega® (oprelvekin, human interleukin-11); Orthoclone OKT3® (muromonab-CD3, anti-CD3 monoclonal antibody); Procrit® (epoetin alfa); Remicade® (infliximab, anti-TNFα monoclonal antibody); Reopro® (abciximab, anti-GP IIb/IIia receptor monoclonal antibody); Actemra® (anti-IL6 Receptor mAb); Avastin® (bevacizumab), HuMax-CD4 (zanolimumab); Mvasi™ (bevacizumab-awwb); Rituxan® (rituximab, anti-CD20 mAb); Tarceva® (erlotinib); Roferon-A®-(interferon alfa-2a); Simulect® (basiliximab); Prexige® (lumiracoxib); Synagis® (palivizumab); 145c7-CHO (anti-IL15 antibody, see U.S. Pat. No. 7,153,507); Tysabri® (natalizumab, anti-α4integrin mAb); Valortim® (MDX-1303, anti-B. anthracis protective antigen mAb); ABthrax™ Xolair® (omalizumab); ETI211 (anti-MRSA mAb); IL-1 trap (the Fc portion of human IgG1 and the extracellular domains of both IL-1 receptor components (the Type I receptor and receptor accessory protein)); VEGF trap (Ig domains of VEGFR1 fused to IgG1 Fc); Zenapax® (daclizumab); Zenapax® (daclizumab, anti-IL-2Ra mAb); Zevalin® (ibritumomab tiuxetan); Zetia® (ezetimibe); Orencia® (atacicept, TACI-Ig); anti-CD80 monoclonal antibody (galiximab); anti-CD23 mAb (lumiliximab); BR2-Fc (huBR3/huFc fusion protein, soluble BAFF antagonist); CNTO 148 (golimumab, anti-TNFα mAb); HGS-ETR1 (mapatumumab; human anti-TRAIL Receptor-1 mAb); HuMax-CD20 (ocrelizumab, anti-CD20 human mAb); HuMax-EGFR (zalutumumab); M200 (volociximab, anti-α5β1 integrin mAb); MDX-010 (ipilimumab, anti-CTLA-4 mAb and VEGFR-1 (IMC-18F1); anti-BR3 mAb; anti-C. difficile Toxin A and Toxin B C mAbs MDX-066 (CDA-1) and MDX-1388); anti-CD22 dsFv-PE38 conjugates (CAT-3888 and CAT-8015); anti-CD25 mAb (HuMax-TAC); anti-CD3 mAb (NI-0401); adecatumumab; anti-CD30 mAb (MDX-060); MDX-1333 (anti-IFNAR); anti-CD38 mAb (HuMax CD38); anti-CD40L mAb; anti-Cripto mAb; anti-CTGF Idiopathic Pulmonary Fibrosis Phase I Fibrogen (FG-3019); anti-CTLA4 mAb; anti-eotaxinl mAb (CAT-213); anti-FGF8 mAb; anti-ganglioside GD2 mAb; anti-ganglioside GM2 mAb; anti-GDF-8 human mAb (MY0-029); anti-GM-CSF Receptor mAb (CAM-3001); anti-HepC mAb (HuMax HepC); anti-IFNα mAb (MEDI-545, MDX-198); anti-IGF1R mAb; anti-IGF-1R mAb (HuMax-Inflam); anti-IL12 mAb (ABT-874); anti-IL12/1L23 mAb (CNTO 1275); anti-IL13 mAb (CAT-354); anti-IL2Ra mAb (HuMax-TAC); anti-IL5 Receptor mAb; anti-integrin receptors mAb (MDX-018, CNTO 95); anti-IP10 Ulcerative Colitis mAb (MDX-1100); BMS-66513; anti-Mannose Receptor/hCGβ mAb (MDX-1307); anti-mesothelin dsFv-PE38 conjugate (CAT-5001); anti-PD1mAb (MDX-1106 (ONO-4538)); anti-PDGFRa antibody (IMC-3G3); anti-TGFβ mAb (GC-1008); anti-TRAIL Receptor-2 human mAb (HGS-ETR2); anti-TWEAK mAb; anti-VEGFR/Flt-1 mAb; and anti-ZP3 mAb (HuMax-ZP3).
In some embodiments, the drug delivery device may contain or be used with a sclerostin antibody, such as but not limited to romosozumab, blosozumab, BPS 804 (Novartis), Evenity™ (romosozumab-aqqg), another product containing romosozumab for treatment of postmenopausal osteoporosis and/or fracture healing and in other embodiments, a monoclonal antibody (IgG) that binds human Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9). Such PCSK9 specific antibodies include, but are not limited to, Repatha® (evolocumab) and Praluent® (alirocumab). In other embodiments, the drug delivery device may contain or be used with rilotumumab, bixalomer, trebananib, ganitumab, conatumumab, motesanib diphosphate, brodalumab, vidupiprant or panitumumab. In some embodiments, the reservoir of the drug delivery device may be filled with or the device can be used with IMLYGIC® (talimogene laherparepvec) or another oncolytic HSV for the treatment of melanoma or other cancers including but are not limited to OncoVEXGALV/CD; OrienX010; G207, 1716; NV1020; NV12023; NV1034; and NV1042. In some embodiments, the drug delivery device may contain or be used with endogenous tissue inhibitors of metalloproteinases (TIMPs) such as but not limited to TIMP-3. In some embodiments, the drug delivery device may contain or be used with Aimovig® (erenumab-aooe), anti-human CGRP-R (calcitonin gene-related peptide type 1 receptor) or another product containing erenumab for the treatment of migraine headaches. Antagonistic antibodies for human calcitonin gene-related peptide (CGRP) receptor such as but not limited to erenumab and bispecific antibody molecules that target the CGRP receptor and other headache targets may also be delivered with a drug delivery device of the present disclosure. Additionally, bispecific T cell engager (BITE®) molecules such as but not limited to BLINCYTO® (blinatumomab) can be used in or with the drug delivery device of the present disclosure. In some embodiments, the drug delivery device may contain or be used with an APJ large molecule agonist such as but not limited to apelin or analogues thereof. In some embodiments, a therapeutically effective amount of an anti-thymic stromal lymphopoietin (TSLP) or TSLP receptor antibody is used in or with the drug delivery device of the present disclosure. In some embodiments, the drug delivery device may contain or be used with Avsola™ (infliximab-axxq), anti-TNF α monoclonal antibody, biosimilar to Remicade® (infliximab) (Janssen Biotech, Inc.) or another product containing infliximab for the treatment of autoimmune diseases. In some embodiments, the drug delivery device may contain or be used with Kyprolis® (carfilzomib), (2S)-N-((S)-1-((S)-4-methyl-1-(R)-2-methyloxiran-2-yl)-1-oxopentan-2-ylcarbamoyl)-2-phenylethyl)-2-((S)-2-(2-morpholinoacetamido)-4-phenylbutanamido)-4-methylpentanamide, or another product containing carfilzomib for the treatment of multiple myeloma. In some embodiments, the drug delivery device may contain or be used with Otezla® (apremilast), N-[2-[(1S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]acetamide, or another product containing apremilast for the treatment of various inflammatory diseases. In some embodiments, the drug delivery device may contain or be used with Parsabiv™ (etelcalcetide HCl, KAI-4169) or another product containing etelcalcetide HCl for the treatment of secondary hyperparathyroidism (sHPT) such as in patients with chronic kidney disease (KD) on hemodialysis. In some embodiments, the drug delivery device may contain or be used with ABP 798 (rituximab), a biosimilar candidate to Rituxan®/MabThera™ or another product containing an anti-CD20 monoclonal antibody. In some embodiments, the drug delivery device may contain or be used with a VEGF antagonist such as a non-antibody VEGF antagonist and/or a VEGF-Trap such as aflibercept (Ig domain 2 from VEGFR1 and Ig domain 3 from VEGFR2, fused to Fc domain of IgG1). In some embodiments, the drug delivery device may contain or be used with ABP 959 (eculizumab), a biosimilar candidate to Soliris®, or another product containing a monoclonal antibody that specifically binds to the complement protein C5. In some embodiments, the drug delivery device may contain or be used with Rozibafusp alfa (formerly AMG 570) is a novel bispecific antibody-peptide conjugate that simultaneously blocks ICOSL and BAFF activity. In some embodiments, the drug delivery device may contain or be used with Omecamtiv mecarbil, a small molecule selective cardiac myosin activator, or myotrope, which directly targets the contractile mechanisms of the heart, or another product containing a small molecule selective cardiac myosin activator. In some embodiments, the drug delivery device may contain or be used with Sotorasib (formerly known as AMG 510), a KRASG12c small molecule inhibitor, or another product containing a KRASG12c small molecule inhibitor. In some embodiments, the drug delivery device may contain or be used with Tezepelumab, a human monoclonal antibody that inhibits the action of thymic stromal lymphopoietin (TSLP), or another product containing a human monoclonal antibody that inhibits the action of TSLP. In some embodiments, the drug delivery device may contain or be used with AMG 714, a human monoclonal antibody that binds to Interleukin-15 (IL-15) or another product containing a human monoclonal antibody that binds to Interleukin-15 (IL-15). In some embodiments, the drug delivery device may contain or be used with AMG 890, a small interfering RNA (siRNA) that lowers lipoprotein(a), also known as Lp(a), or another product containing a small interfering RNA (siRNA) that lowers lipoprotein(a). In some embodiments, the drug delivery device may contain or be used with ABP 654 (human IgG1 kappa antibody), a biosimilar candidate to Stelara®, or another product that contains human IgG1 kappa antibody and/or binds to the p40 subunit of human cytokines interleukin (IL)-12 and IL-23. In some embodiments, the drug delivery device may contain or be used with Amjevita™ or Amgevita™ (formerly ABP 501) (mab anti-TNF human IgG1), a biosimilar candidate to Humira®, or another product that contains human mab anti-TNF human IgG1. In some embodiments, the drug delivery device may contain or be used with AMG 160, or another product that contains a half-life extended (HLE) anti-prostate-specific membrane antigen (PSMA)×anti-CD3 BiTE® (bispecific T cell engager) construct. In some embodiments, the drug delivery device may contain or be used with AMG 119, or another product containing a delta-like ligand 3 (DLL3) CART (chimeric antigen receptor T cell) cellular therapy. In some embodiments, the drug delivery device may contain or be used with AMG 119, or another product containing a delta-like ligand 3 (DLL3) CART (chimeric antigen receptor T cell) cellular therapy. In some embodiments, the drug delivery device may contain or be used with AMG 133, or another product containing a gastric inhibitory polypeptide receptor (GIPR) antagonist and GLP-1R agonist. In some embodiments, the drug delivery device may contain or be used with AMG 171 or another product containing a Growth Differential Factor 15 (GDF15) analog. In some embodiments, the drug delivery device may contain or be used with AMG 176 or another product containing a small molecule inhibitor of myeloid cell leukemia 1 (MCL-1). In some embodiments, the drug delivery device may contain or be used with AMG 199 or another product containing a half-life extended (HLE) bispecific T cell engager construct (BITE®). In some embodiments, the drug delivery device may contain or be used with AMG 256 or another product containing an anti-PD-1×IL21 mutein and/or an IL-21 receptor agonist designed to selectively turn on the Interleukin 21 (IL-21) pathway in programmed cell death-1 (PD-1) positive cells. In some embodiments, the drug delivery device may contain or be used with AMG 330 or another product containing an anti-CD33×anti-CD3 BiTE® (bispecific T cell engager) construct. In some embodiments, the drug delivery device may contain or be used with AMG 404 or another product containing a human anti-programmed cell death-1(PD-1) monoclonal antibody being investigated as a treatment for patients with solid tumors. In some embodiments, the drug delivery device may contain or be used with AMG 427 or another product containing a half-life extended (HLE) anti-fms-like tyrosine kinase 3 (FLT3)×anti-CD3 BiTE® (bispecific T cell engager) construct. In some embodiments, the drug delivery device may contain or be used with AMG 430 or another product containing an anti-Jagged-1 monoclonal antibody. In some embodiments, the drug delivery device may contain or be used with AMG 506 or another product containing a multi-specific FAP×4-1BB-targeting DARPin® biologic under investigation as a treatment for solid tumors. In some embodiments, the drug delivery device may contain or be used with AMG 509 or another product containing a bivalent T-cell engager and is designed using XmAb® 2+1 technology. In some embodiments, the drug delivery device may contain or be used with AMG 562 or another product containing a half-life extended (HLE) CD19×CD3 BiTE® (bispecific T cell engager) construct. In some embodiments, the drug delivery device may contain or be used with Efavaleukin alfa (formerly AMG 592) or another product containing an IL-2 mutein Fc fusion protein. In some embodiments, the drug delivery device may contain or be used with AMG 596 or another product containing a CD3×epidermal growth factor receptor vIII (EGFRvIII) BiTE® (bispecific T cell engager) molecule. In some embodiments, the drug delivery device may contain or be used with AMG 673 or another product containing a half-life extended (HLE) anti-CD33×anti-CD3 BiTE® (bispecific T cell engager) construct. In some embodiments, the drug delivery device may contain or be used with AMG 701 or another product containing a half-life extended (HLE) anti-B-cell maturation antigen (BCMA)×anti-CD3 BiTE® (bispecific T cell engager) construct. In some embodiments, the drug delivery device may contain or be used with AMG 757 or another product containing a half-life extended (HLE) anti-delta-like ligand 3 (DLL3)×anti-CD3 BiTE® (bispecific T cell engager) construct. In some embodiments, the drug delivery device may contain or be used with AMG 910 or another product containing a half-life extended (HLE) epithelial cell tight junction protein claudin 18.2×CD3 BiTE® (bispecific T cell engager) construct.
Although the drug delivery devices, assemblies, components, subsystems and methods have been described in terms of exemplary embodiments, they are not limited thereto. The detailed description is to be construed as exemplary only and does not describe every possible embodiment of the present disclosure. Numerous alternative embodiments could be implemented, using either current technology or technology developed after the filing date of this patent that would still fall within the scope of the claims defining the invention(s) disclosed herein.
Those skilled in the art will recognize that a wide variety of modifications, alterations, and combinations can be made with respect to the above described embodiments without departing from the spirit and scope of the invention(s) disclosed herein, and that such modifications, alterations, and combinations are to be viewed as being within the ambit of the inventive concept(s).
Priority is claimed to U.S. Provisional Patent Application No. 63/076,291, filed Sep. 9, 2020, the entire contents of which are hereby incorporated by reference.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/US21/48805 | 9/2/2021 | WO |
| Number | Date | Country | |
|---|---|---|---|
| 63076291 | Sep 2020 | US |
