Activation mechanism for drug delivery device

Abstract

To provide a drug delivery device which assists a user in performing injection, ensures reliable delivery of a medicament, and secures patient safety.SOLUTION: A drug delivery device includes a housing, an injection assembly at least partially disposed in the housing, a shield, and a drive assembly at least partially disposed in the housing and coupled with the injection assembly and the shield. The injection assembly includes a needle or cannula having an endpoint. Upon the shield moving a predetermined distance axially towards a distal end of the housing, a retraction profile commences so that the drive assembly administers a medicament via the injection assembly. Peak resistance force is exerted within approximately the first 12 mm of the axial movement of the shield.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS Priority is claimed to U.S. Provisional Patent Application No. 62 / 719,367, filed August 17, 2018, the entire contents of which are incorporated herein by reference.

[0002] FIELD OF THE DISCLOSURE The present disclosure relates generally to drug delivery devices, and more particularly to mechanisms and methods for inserting or placing needles and / or cannulas in drug delivery devices. [Background technology]

[0003] Drug delivery devices, such as injectors, are used to deliver liquid medication to a patient. When actuated, the drug delivery device expels a drug stored in an internal reservoir through a needle, cannula, or other delivery member into the patient. Some drug delivery devices, such as on-body injectors, may be temporarily attached to a patient to deliver the drug over an extended period of time via an injection needle or other means. The drug delivery device may be adhesively attached to tissue in the patient's abdomen, thigh, arm, or other part of the patient's body.

[0004] Some devices may have drawbacks. In particular, users may be afraid of the exposed injection needle or may feel essentially unable to perform the injection. Due to the aversion to exposed needles, as well as the health and safety issues that may be involved, various types of injectors and other devices have been developed to hide the needle from the user and automate the injection process to assist users in performing injections, ensure reliable delivery of the medication, and ensure patient safety.

[0005] Typically, three tasks may be performed when injecting a drug into a patient with a subcutaneous syringe: 1) inserting a needle into the patient; 2) injecting the drug from the syringe into the patient; and 3) removing the needle after the injection is complete. In each task, the magnitude and direction of force on the syringe, as well as the location of the force application, may differ from the other tasks. For example, inserting a needle may require minimal force to be applied to the syringe for a very short period of time. On the other hand, injecting a drug may require a larger force to be applied to the plunger of the syringe. This force may need to be applied for a relatively longer period of time. Furthermore, removing the needle may require a force to be applied in the opposite direction to the needle insertion. Thus, combining a desirable actuation experience with a robust actuation mechanism presents unique challenges. These and other similar concerns may become relevant when the injection process is automated.

[0006] Generally, shield-activated devices use a manual needle insertion technique whereby the user simultaneously inserts the needle and initiates administration via the actuation of retracting the shield relative to the rest of the device. In these devices, the needle may be inserted automatically upon manual activation of the device. Typically, button-activated devices use an automated needle insertion mechanism whereby the needle is mechanically inserted and automatically delays release by the administration mechanism until the correct device state is achieved. In any or all of these devices, the needle may be retracted using manual and / or automatic withdrawal mechanisms. Each of these approaches may have relative advantages and disadvantages that affect user operation and satisfaction, and therefore any combination of these approaches may also have associated advantages and disadvantages. Summary of the Invention [Means for solving the problem]

[0007] According to a first aspect, the drug delivery device includes a housing defining a shell, an injection assembly at least partially disposed within the housing, a shield, and a drive assembly at least partially disposed within the housing and coupled to the injection assembly and the shield. The shield has an extended position in which at least a proximal end of the shield extends a distance beyond the proximal end of the housing. The injection assembly includes a needle or cannula having an end point. A retraction profile is initiated when the shield moves axially a predetermined distance toward the distal end of the housing, thereby causing the drive assembly to administer the medicament through the injection assembly. A peak resistance force is exerted within about the first 12 mm of axial movement of the shield. In some examples, the peak resistance force is exerted within about the first 8 mm of axial movement of the shield. Further, in some of these examples, the peak resistance force is exerted within about the first 3 mm of axial movement of the shield.

[0008] In some examples, the drive assembly includes a container disposed within the shell, a nut disposed within the shell and adjacent a second end of the container, a trigger ring disposed within the shell, a plunger rod guide disposed within the shell, and a plunger rod disposed at least partially within an opening in the plunger rod guide. The container has a first end, a second end, and an internal volume that contains a medicament to be administered to a user. The nut has a first engagement region and a second engagement region. The trigger ring has a first engagement region that slidably engages the first engagement region of the nut and also has a second engagement region. The trigger ring also engages a portion of the shield for axial movement with the shield. The plunger rod guide has a first engagement region and an opening. The first engagement region of the plunger rod guide slidably engages the second engagement region of the trigger ring. The plunger rod guide is further operably coupled to a drive mechanism, which in some forms may be a spiral spring or a torque spring. As the shield, and thus the trigger ring, moves axially toward the distal end of the housing, a first engagement region of the trigger ring disengages from a first engagement region of the nut and / or a second engagement region of the trigger ring disengages from a first engagement region of the plunger rod guide, thereby causing the drive mechanism to urge the plunger toward the proximal end of the housing.

[0009] In some approaches, the trigger ring may be coupled to the nut such that relative rotation between the trigger ring and the nut is limited while a first engagement region of the trigger ring engages a first engagement region of the nut. The trigger ring may also or separately be coupled to the plunger rod guide such that relative rotation between the trigger ring and the plunger rod guide is limited while a second engagement region of the trigger ring engages a first engagement region of the plunger rod guide. In other examples, the trigger ring may slidably engage directly with the shell rather than the nut.

[0010] In an example, the peak force is exerted within about the first 30% of the duration of the injection process, beginning when the shield first moves axially and ending when the drive assembly has fully administered the medicament. The shield may have a maximum axial movement of about 10 mm toward the distal end of the housing. In this example, the peak force may occur within about the first 1 mm of shield movement. In other examples, the peak force may occur at any point within the full range of motion leading up to the device being actuated.

[0011] In some forms, the nut further includes at least one biasing finger that projects inwardly toward the longitudinal axis of the housing and thereby contacts an outer surface of the trigger ring. The at least one biasing finger can exert a combined frictional force and axial reaction force on the nut sufficient to create a peak resistance force before disengagement from the nut. In some examples, the peak resistance force can be created by at least one of a frictional force between the plunger rod guide and the trigger ring caused by the drive mechanism, a frictional force between the trigger ring and the nut caused by the drive mechanism, an axial spring force exerted by a compression spring coupled to the shield, or a biasing force exerted by the nut. In still other forms, the drug delivery device can include a dose lockout mechanism that stops movement of the plunger rod upon movement of the device in a direction toward the proximal end of the housing.

[0012] According to a second aspect, a drive assembly of a drug delivery device includes a container having a first end and a second end, a nut disposed adjacent the second end of the container, a trigger ring, a plunger rod guide, and a plunger rod. An interior volume of the container is adapted to contain a medicament to be administered to a user. The nut has a first engagement region and a second engagement region. The trigger ring has a first engagement region that slidably engages the first engagement region of the nut and further includes a second engagement region. The trigger ring is movable between a first position and a second position. The plunger rod guide has a first engagement region and an opening. The first engagement region of the plunger rod guide slidably engages the second engagement region of the trigger ring. The plunger rod guide is operably coupled to a drive mechanism. The plunger rod is at least partially disposed within the opening of the plunger rod guide. Movement of the trigger ring in a first direction from the first position to the second position causes at least one of the first engagement regions of the trigger ring to disengage from the first engagement region of the nut or the second engagement region of the trigger ring to disengage from the first engagement region of the plunger rod guide, causing the drive mechanism to urge the plunger in a direction opposite to the first direction.

[0013] According to a third aspect, the drug delivery device includes a housing defining a shell, an injection assembly (or a prefilled syringe) at least partially disposed within the housing, a shield, and a drive assembly at least partially disposed within the housing and coupled to the injection assembly and the shield. The injection assembly includes a needle or cannula. Axial movement of the shield toward a distal end of the housing initiates a retraction profile in which the drive assembly administers a medicament through the injection assembly. A peak resistance force is exerted before the needle or cannula contacts the skin of the user.

[0014] According to a fourth aspect, the drug delivery device includes a housing, an injection assembly, a shield, and a drive assembly. The housing has a proximal end, a distal end, and a longitudinal axis extending between the proximal and distal ends. The injection assembly includes a needle or cannula at least partially disposed within the housing at its proximal end and having an end point. The shield assembly is coupled to the housing and has an extended position in which at least the proximal end of the shield extends a distance beyond the proximal end of the housing. The drive assembly is also at least partially disposed within the housing and operably coupled to the injection assembly and the shield. A retraction profile is initiated when the shield moves a predetermined distance axially toward the distal end of the housing, thereby causing the drive assembly to administer the medicament through the injection assembly. A peak resistive force is exerted when the axial distance from the proximal end of the shield to the end point of the needle or cannula is about 12 mm or less, as measured in the distal direction.

[0015] The above needs are met, at least in part, by the provision of the drug delivery device actuation and safety mechanisms described in the following detailed description, particularly when studied in conjunction with the drawings. [Brief description of the drawings]

[0016] [Figure 1] 1A-1D show schematic diagrams of exemplary configurations of drug delivery devices having activation and safety mechanisms according to various embodiments. [Diagram 2] 2 is a perspective view of an exemplary drive assembly of the drug delivery device of FIG. 1 according to various embodiments. [Diagram 3] 3 is a cross-sectional view of a drive assembly of the drug delivery device of FIGS. 1 and 2 according to various embodiments. FIG. [Figure 4] 4 is a cross-sectional view of the drug delivery device of FIGS. 1-3 in a loaded configuration according to various embodiments. FIG. [Diagram 5] FIG. 5 is a front view of the drug delivery device of FIGS. 1-4 in a loaded configuration according to various embodiments. [Figure 6]Cross-sectional views of the drug delivery devices of FIGS. 1-5 in an actuated configuration according to various embodiments. [Figure 7] Front views of the drug delivery devices of FIGS. 1-6 in an actuated configuration according to various embodiments. [Figure 8a] Front cross-sectional views of the drug delivery devices of FIGS. 1-7 showing a part of the drive assembly according to various embodiments. [Figure 8b] Front views of the exemplary drive assembly of FIG. 8a according to various embodiments. [Figure 9a] Perspective views of the drug delivery devices of FIGS. 1-8b showing the operation of the drive mechanism according to various embodiments. [Figure 9b] Perspective views of the drug delivery devices of FIGS. 1-8b showing the operation of the drive mechanism according to various embodiments. [Figure 9c] Perspective views of the drug delivery devices of FIGS. 1-8b showing the operation of the drive mechanism according to various embodiments. [Figure 10] Exemplary force profiles of the drug delivery devices of FIGS. 1-9c according to various embodiments. [Figure 11] Perspective views of an exemplary drug delivery device having an alternative drive assembly according to various embodiments. [Figure 12] Perspective views of the exemplary drive assembly of FIG. 11 of the drug delivery device according to various embodiments. [Figure 13a] Cross-sectional views of the exemplary drive assembly of the drug delivery devices of FIGS. 11 and 12 according to various embodiments. [Figure 13b] Enlarged views of the exemplary drive assembly of FIG. 13a according to various embodiments.

DETAILED DESCRIPTION OF THE INVENTION

[0017] Those skilled in the art will appreciate that elements in the figures are depicted for simplicity and clarity and are not necessarily drawn to scale. For example, the dimensions and / or relative positions of some of the elements in the figures may be exaggerated relative to other elements to improve understanding of the various embodiments of the present invention. Also, common but well-understood elements that are useful or necessary in commercially feasible embodiments are often not shown in order to not overly distract from the illustrations of these various embodiments. Furthermore, it will be appreciated that certain acts and / or steps may be described or shown in a particular occupying order, although those skilled in the art will appreciate that such specificity with respect to order is not actually required. The terms and expressions used herein have the ordinary technical meanings, as set forth above, that would be given to such terms and expressions by those skilled in the art, unless a different specific meaning is explained herein.

[0018] Generally, according to these various embodiments, the injector includes a housing, a reservoir or syringe assembly that contains the medicament to be injected into the user, and a rotatable drive or actuation assembly that uses a spring (e.g., a spiral spring or a torque spring) to inject the medicament into the user. The injector can be actuated by axial movement (i.e., by pressing the injector against the injection site) and provides sufficient feedback force against the injection site to allow the user to anticipate that actuation will occur upon application of sufficient force. Only a single step by the user is required to actuate the injector, and even when used in combination with a high energy injection mechanism, relatively small forces are required both to actuate the device and to hold it during administration. Furthermore, the actuation element is configured to reduce the possibility of unexpected injection due to inertial impacts, such as if the device is dropped, which can be difficult to perform in a robust manner when using more viscous, more energetic systems.

[0019] As will be explained in more detail, the described force profile also relies on a peak or maximum force resisting distal and / or axial movement of the shield during the retraction period. This serves a number of functions. First, the requirement of a peak resistance at the beginning of retraction serves to increase the likelihood that the user will actuate the device and fully insert the syringe once they overcome the peak resistance resulting from the difference in force between the peak resistance and the force required to retract the shield the remaining travel distance. After the peak resistance occurs, the force drops off quickly as the user is reluctant to remove the autoinjector 100. In other words, since the peak force occurs just prior to needle insertion, the user has a limited time window to change his / her mind. Additionally, the requirement of a peak resistance at the beginning of retraction provides a clear indication to the user that the device has been actuated.

[0020] 1-3, an exemplary autoinjector 100 includes a housing 102 defining a shell, a shield 110, an injection assembly 120 (e.g., a prefilled syringe), and a drive assembly or actuation mechanism 150. At least a portion of the shield 110, injection assembly 120, and drive assembly 150 are disposed within the housing 102. The housing 102 has a proximal end 102a, a distal end 102b, and a longitudinal axis "L" extending between the proximal end 102a and the distal end 102b. The shield 110 has a proximal end 110a and a distal end 110b. The injection assembly 120 includes a container or syringe barrel 122, and a needle or cannula 124 having an end point 124a. In some examples, the injection assembly 120 includes the syringe barrel 122, the needle or cannula 124, and a plunger 184. At least some of these components may be disposed at least partially within the housing 102. The drive assembly 150 is operably coupled to the shield 110 and the injection assembly 120. Any number of additional components (e.g., a shield spring 111, a syringe holder, a shield lock, a filter member, etc.) may be used to aid in the operation of the autoinjector 100.

[0021] The syringe barrel 122 stores a medication to be injected into a user. In the illustrated example, the syringe barrel 122 includes a base 122a and a sidewall 122b that define a cavity for storing the medication. Additionally, the syringe barrel 122 may include at least one opening 122c disposed through the base 122a to allow the medication to be delivered to a needle or cannula 124. An end 122d of the syringe barrel 122 may be open to accommodate a plunger assembly 180, which will be described in more detail below. The syringe barrel 122 may be of any desired shape and / or size to accommodate various amounts of medication. In some examples, the syringe barrel 122 may be made of a cyclic olefin polymer ("COP"). Other example materials are possible.

[0022] The needle or cannula 124 is coupled to the second end 122e of the syringe barrel 122 via any type of coupling mechanism and / or coupling structure (e.g., a needle hub 126). The needle hub 126 defines a cavity that allows the medicament to enter the needle 124 through any number of openings. The needle hub 126 is disposed below an opening 122c formed in the base 122a of the syringe barrel 122. So configured, the needle hub 126 receives the medicament as it exits the syringe barrel 122, which then enters the needle or cannula 124 and is administered to the user. It should be understood that the injector 100 may include any number of additional components, such as a return spring, additional needle shields and / or guards, etc., to assist in administering the medicament to the user. For the sake of brevity, these additional components will not be described in particular detail.

[0023] In some examples, the drive assembly 150 includes the container or syringe barrel 122, a nut 152 disposed adjacent the end 122d of the syringe barrel 122, a trigger ring 160, a plunger rod guide 170, a plunger rod assembly 180, and a drive mechanism 190. The nut 152 may be fixedly coupled to the housing 102 using any number of techniques. In some configurations, the nut 152 may be integrally formed with the housing 102. The nut 152 may have a base portion 152a and at least one tab 153 extending generally axially therefrom, an opening 154, and may optionally include at least one flexible and / or resilient finger 155 biased inwardly toward the opening 154, as illustrated in FIGS. 2 and 8. The nut 152 may be constrained and / or fixed to the housing 102 via a friction or other joint within the device 100. In some examples, the resilient finger 155 may be part of the shell 102. In yet another example, the trigger ring 160 may carry a deflection finger (not shown) that deflects outwardly toward the shell 102. Other examples are possible.

[0024] At least one tab 153 defines a first engagement region 153a. More specifically, first engagement region 153a is defined by an end or side of at least one tab 153. Additionally, opening 154 may define a second threaded engagement region 154a (FIGS. 1 and 8), and at least one finger 155 defines a third engagement region 155a at its distal end 155b.

[0025] The trigger ring 160 is also disposed within the shell of the housing 102 and includes a top or first surface 160a, a bottom or second surface 160b, and a body 160c extending therebetween and defining an inner surface 160d and an outer surface 160e. As seen in Figures 2 and 3, the body 160c of the trigger ring 160 is generally cylindrical ring-shaped, has a generally circular inner surface 160d, and any number of ledges, protrusions, and grooves disposed around and / or within the circumference of the ring. By way of example, the trigger ring 160 may include a first ledge 161 disposed adjacent the bottom 160b and defining a first engagement area 161a. The trigger ring 160 may further include any number of grooves 162 formed by an inner surface 160d that defines a second engagement region 162a, and any number of grooves 163 formed by an outer surface 160e that defines a third engagement region 163a (FIGS. 5 and 8). In the example illustrated in FIG. 8a, a stopper 164 in the form of a peripheral bump or protrusion is disposed adjacent one or more of the grooves 163.

[0026] The trigger ring 160 may be coupled to the shield 110 by any number of techniques. For example, a bottom surface 160b of the trigger ring 160 may abut the distal end 110b of the shield 110. In other examples, the trigger ring 160 may include a fastening component for fastening the shield 110 to the trigger ring. Additionally, the first engagement region 161a of the trigger ring 160 slidably engages the first engagement region 153a of the nut 152.

[0027] The plunger rod guide 170 includes a rod portion 172 and a base portion 174 coupled thereto. The plunger rod guide 170 includes an opening 175 extending at least partially through the rod portion 172, and the base portion 174. The base portion 174 includes a lower surface 174a having any number of protrusions or tabs 176 (FIGS. 2 and 3) extending therefrom. The one or more protrusions 176 define a first engagement region 176a that slidably engages a second engagement region 162a of the trigger ring 160. For example, the one or more protrusions 176 of the base portion 174 may be disposed within one or more grooves 162 of the trigger ring, thereby permitting relative axial movement while limiting relative rotational movement.

[0028] The plunger rod assembly 180 includes a plunger rod 182, a washer 183, and a plunger 184 movable along the longitudinal axis L of the device 100. The plunger rod 182 has a threaded portion 182a that is threadably coupled to and disposed within the opening 175 of the plunger rod guide 170 and the threaded opening 154 of the nut 152. The washer 183 minimizes friction losses between the rotating plunger rod 182 and the non-rotating plunger. In some approaches, the washer 183 can also be used to adjust the volume of the drug by making it thicker or thinner. Thus, the washer 183 can be used to accommodate different fill volumes of drugs with the same device, thereby allowing better control of the gap between the bottom of the washer 183 and the top of the plunger 184. The rod portion 172 of the plunger rod guide 170 is coupled to the plunger assembly 180 in any number of ways, including, for example, by a splined connection or a grooved configuration that allows the plunger assembly 180 to move axially relative to the plunger rod guide 170. The plunger rod guide 170 thus guides the rotational movement of the plunger assembly 180. The threaded portion 182a of the plunger rod 182, and similarly the threaded opening 154 of the nut 152, may have a thread pitch suitable for any desired drug delivery rate or force / torque combination when driven by the drive mechanism 190. Relative rotation between the plunger rod 182 and the nut 152 advances the plunger rod 182 axially toward the proximal end 102a of the housing 102. The plunger 184 has an upper surface 184a disposed near the first end 122d of the syringe barrel 122.

[0029] In the illustrated example, the drive mechanism 190 is in the form of a spiral or torque spring 190 having an inner portion 190a that is connected to the rod portion 172 of the plunger rod guide 170 by any known means, and exerts a torque on the plunger rod guide 170 to rotate it about the axis L. In some examples, the torque spring 190 may have many turns to provide the appropriate rotational movement required to expel the drug from the syringe barrel 122. However, further parameters in the spring design, such as material properties and any applied heat treatments, may affect the torque output of the spring. Preforming the torque spring 190 may also affect its performance. As an example, in an autoinjector, a prestressed spring may be preferred because the prestressing process generally increases the torque output of the spring by first coiling the spring in the opposite direction to the intended operating conditions, thereby creating a permanent strain in the steel bands. This strain maximizes the stress in the material, thereby increasing the torque. Such an increase in torque is advantageous in minimizing the size and weight of the device.

[0030] In some examples, the torque spring 190 may have about 1 to about 30 turns in a wound or loaded configuration, preferably about 12 turns. In some examples, the total number of turns of the spring may be greater with a margin of about 20% on both ends of the operating range, which may result in a range of about 1*1.4=1.4 to 30*1.4=42 turns. The number of turns of the dosing mechanism is derived from the pitch and the required travel length. As mentioned above, a smaller pitch is preferred because it requires lower torque input and actuation force. Actuation force is correspondingly reduced. If high axial forces are not required, the pitch can be increased to require fewer spring turns, thus allowing for a smaller device. In some examples, the torque spring 190 may have some initial or preload turns to have a useful torque. After the preload turns, the torque spring 190 is further wound with working turns, i.e., the number of turns used by the device during injection. As a non-limiting example, the torque spring 190 may have about 2.5 preload turns and about 6 working turns. Thus, the total number of turns during assembly is about 8.5. However, due to potentially large tolerances in the angular position of the spring ends, the torque spring 190 may have some initial play before reaching a solid state, and thus may have a total of about 10 turns. Devices with different drug amounts and viscosities may require different average torques to be generated from the torque spring 190 if the same dosage is desired. The average torque output can be controlled by adjusting the width of the band used for the torque spring 190 (e.g., the axial length of the torque spring 190 when placed in the device) and maintaining the same number of working turns. In this way, it may be possible to use different springs in the same configuration as the device and have similar injection times while being able to change the amount and / or viscosity of the drug.

[0031] In some examples, the energy required to expel a drug through a needle (EFLOW) is determined by any combination of drug amount, viscosity, needle channel dimensions, and target administration time. The energy delivered by the torque spring 190 (ESPRING) may be determined by any combination of the number of functional turns (N) and the average spring torque (T) during the functional turns. The energy delivered by the spring can be calculated using the following formula: ESPRING=2*π*N*T. If friction losses in the system are excluded, the following relationship exists: EFLOW=ESPRING=2*π*N*T. Thus, the following relationship is obtained: EFLOW / (2*π)=N*T. In other words, for the torque spring 190 to have enough energy to expel a given amount of a given drug through a given needle in a given time, the higher the torque, the fewer the functional turns may be, since the product (N*T) remains constant.

[0032] The threaded connection between the plunger rod 182 and the nut 152 provides a conversion between the input torque and the output axial force of the torque spring 190. Providing the torque spring 190 with a high turn count reduces the overall torque and reduces the variation between the start and end torque compared to a linear spring with comparable transmission specifications or other torsion springs with fewer turns and a smaller pitch. In addition, the threads of the plunger rod 182 and the nut 152 can have a smaller pitch with an increased number of turns while still achieving a similar linear motion of the plunger assembly 180. With a smaller thread pitch, less input torque is required to provide the same output as a high pitch thread and high torque spring. Thus, the high turn count (e.g., about 1 to about 30 turns), low torque system described herein can reduce the actuation force since the actuation force is directly related to the input torque that must be used to drive the plunger assembly 180. Additionally, the internal structural forces required to resist the torque from the torque spring 190 during storage (e.g., prior to use) are reduced, allowing for the use of smaller injector designs and less expensive raw materials. Additionally, the threaded connection between the plunger rod 182 and the nut 152 allows the threaded plunger rod 182 to be adjusted to accommodate different amounts of drug stored in the syringe barrel 122. If desired, the threaded plunger rod 182 may be first installed in a lower position within the injector 100 where a smaller amount of drug product is located within the syringe barrel 122. Thus, the number of unique components is reduced and variation management is simplified. The threaded plunger rod 182 may also be adjustably installed to various depths as needed during the manufacturing and / or assembly process.

[0033] As illustrated in FIGS. 1-5 and 8, when the device 100 is in a loaded configuration (i.e., when the torque spring 190 is in a wound configuration), the torque spring 190 is rotationally limited by its coupling with the rod portion 172 of the plunger rod guide 170. The plunger rod guide 170 is rotationally limited by engagement between one or more protrusions 176 (and thus the first engagement region 176a) of the base portion 174 of the plunger rod guide 170 and one or more grooves 162 (and thus the second engagement region 162a) of the trigger ring 160. Additionally, the trigger ring 160 is rotationally limited by engagement between a ledge 161 (and thus the first engagement region 161a) of the trigger ring 160 and at least one tab 153 (and thus the first engagement region 154) of a nut 152 that is fixed to the housing 102 in a non-rotatable manner. In addition, at least one finger 155 of the nut 152 is at least partially retained within at least one groove 163 in the outer surface 160e of the trigger ring 160 such that the third engagement region 155a of the nut 152 engages the third engagement region 163a of the trigger ring 160.

[0034] 6 and 7, to administer a medication, a user presses the device 100 against their skin (10 in FIG. 6), thereby urging the shield 110 toward the distal end 102b of the housing 102 and initiating a retraction profile. Continuing to press the shield 110 causes both the shield 110 and the trigger ring 160 to move toward the distal end 102b of the housing 102. In the extended configuration, at least the proximal end 110a of the shield 110 extends a distance beyond the proximal end 102a of the housing 102. Because the first engagement region 161a of the trigger ring 160 slidably engages the first engagement region 153a of the nut 152 and the second engagement region 162a of the trigger ring 160 slidably engages the first engagement region 176a of the plunger rod guide 170, the trigger ring 160 moves axially or slides relative to the nut 152 and the plunger rod guide 170. The trigger ring 160 must move axially to a point where it no longer rotationally constrains the nut 152 and / or the plunger rod guide 170. Continued axial movement disengages the first engagement region 161a of the trigger ring 160 from the first engagement region 153a of the nut 152 and / or the second engagement region 162a of the trigger ring 160 from the first engagement region 176a of the plunger rod guide 170. As used herein, the term "retraction profile" refers to the point at which device 100 is actuated such that an injection process is initiated and / or progresses without further external input. For example, FIG. 6 illustrates device 100 in an actuated state in which the retraction profile has been initiated. As a more specific example, in the operation described above, the retraction profile is initiated when shield 110 moves axially to a point where trigger ring 160 no longer rotationally constrains nut 152 and / or plunger rod guide 170. In other configurations or examples, the retraction profile may be initiated based on or due to different conditions.

[0035] In some examples, trigger ring 160 may disengage from plunger rod guide 170 at approximately the same time as it disengages from nut 152. However, in other examples, trigger ring 160 may disengage from plunger rod guide 170 before it disengages from nut 152, or vice versa. In some examples, trigger ring 160 need not disengage from nut 152 and operation of device 100 may continue as intended. In examples where trigger ring 160 disengages only from nut 152, trigger ring 160 rotates with plunger rod guide 170. In examples where trigger ring 160 disengages only from plunger rod guide 170, trigger ring 160 may remain rotatably locked to nut 152.

[0036] Additionally, as the trigger ring 160 moves toward the distal end 102b of the housing 102, the at least one finger 155 begins to deflect outwardly and disengage from the at least one groove 163 of the trigger ring 160. The at least one finger 155 continues to deflect outwardly as it moves over a stop 164 disposed on the trigger ring 160.

[0037] 9a-9c, disengagement of trigger ring 160 from nut 152 and plunger rod guide 170 allows clock spring 190 to rotate, which in turn rotates plunger rod guide 170. This rotation in turn rotates plunger rod 182, and because of the threaded connection between plunger rod 182 and nut 152, advances plunger rod 182 and plunger 184 from first end 122d of syringe barrel 122 to second end 122e of syringe barrel 122, thereby inserting needle or cannula 124 and administering the medication.

[0038] During this actuation process (i.e., the beginning of the retraction profile), the user must overcome a number of forces that contribute to the resistance experienced when compressing the shield 110 due to mechanical interactions (i.e., resistance forces) between the components. For example, a major contributor to the overall force required by the user at any point during the injection process includes the frictional force between the trigger ring 160 and the plunger rod guide 170 resulting from the static load from the torque spring 190. This force may be approximately constant during retraction until the dosing mechanism is released at a point where the components disengage and the force drops to a fairly low resistance force for the remainder of the injection process. Additionally, the frictional force between the trigger ring 160 and the nut 152 resulting from the static load from the clock spring 190 also contributes to the overall force required. This force is also constant during retraction until the dosing mechanism is released at a point where the components disengage and the force drops to a fairly low resistance force for the remainder of the injection process. The force required to pressurize the shield spring 111 also contributes to the overall force required. This force increases incrementally throughout the injection process as the spring continues to be pressurized. Still further, the force required to deflect the resilient fingers 155 as they disengage from the grooves 163 and / or stops 164 of the trigger ring 160 contributes to the total force required. This force can be in the form of friction and / or axial reaction force. In some examples, the reaction force may be used as a major contributor to the force profile to provide low variability to the forces experienced. In other words, low friction materials may be used to reduce or minimize the friction force. Other examples are possible. In examples where the deflecting fingers are part of the trigger ring 160, the fingers may induce axial reaction and / or friction forces against the nut 152 and / or shell 102. Other approaches are possible.

[0039] As illustrated in FIG. 10, an exemplary shield force profile 50 is provided, plotting force (N) versus retraction displacement (mm). It is understood that force profile 50 is only one example of desired force and displacement values, and thus these values ​​may vary depending on the design of the interactions discussed above. Nonetheless, as shown in FIG. 10, the initial resistance is relatively low for approximately the first mm of shield 110 travel, whereupon the resistance rapidly increases to a peak resistance (indicated by "I" in FIG. 10) indicated at the onset or beginning of the retraction period (e.g., within approximately the first 1-3 mm of shield 110 travel), and then drops off within a short distance (e.g., within approximately another 1-2 mm of shield 110 travel), resembling a "quick trigger" effect. In some instances, the peak resistance is indicated within approximately the first 30% of shield 110 travel. In other instances, the peak resistance is indicated at any point within the full range of motion leading up to actuation of device 100. In yet other examples, the peak force is indicated at any point before the needle or cannula contacts the skin of the user. In still other examples, the axial distance "d1" is defined as the distance from the proximal end 110a of the shield 110 to the end point 124a, as illustrated in FIG. 4. In these examples, the peak force is exerted when the distance "d1" is about 12 mm or less as measured in the distal direction, preferably the peak force is exerted within about the first 8 mm of the axial movement of the shield, and more preferably the peak force is exerted within about the first 3 mm of the axial movement of the shield. It is understood that the distance d1 illustrated in FIG. 4 is greater than about 3 mm. It is further understood that in other configurations, such as the configuration of FIG. 6 where the end point 124a of the needle 124 has already passed through the needle shield 110, the distance d1 may be a negative number (and thus less than 3 mm). After reaching the peak force value, the force profile 50 is followed by a period of gradually increasing force (indicated by "II" in FIG. 10). At point "III", the force drops upon release of the dosing mechanism followed by a final lower force retraction period where the force gradually increases. At the end of the force profile 50, the force increases sharply as the shield 110 is restricted from further movement towards the housing 102.

[0040] The exemplary force profile 50 of FIG. 10 also shows how, by using the described drive assembly 150, shield displacement regions can be clearly defined. In these regions, certain interactions occur, which can be controlled by part tolerance specifications and proper dimensional design. As an example, FIG. 10 shows that the dose release point is defined to occur after a minimum needle insertion region, thereby ensuring that the needle tip is inserted beyond a minimum depth before any drug is released. In the illustrated example, the forces both before and after the peak force are as low as possible to ensure that the user does not change his or her mind.

[0041] As previously mentioned, the value of the peak resistance force may result from a combination of interactions of any number of components. Specifically, as the trigger ring 160 moves toward the distal end 102b of the housing 102, the force increases to a peak level due to the principle of beam deflection, where at least one finger 155 of the nut 152 is forced to deflect outward by at least one groove 163 and / or bump 164 of the trigger ring 160. By using the principle of beam deflection to generate the peak resistance force, the predicted peak resistance force can be calculated using relatively simple calculations depending on the surface friction of the two parts, the tilt angle, and the amount of overlap between the two geometries that cause the beam deflection, the geometry and / or dimensions (e.g., length, width, etc.) of the at least one finger 155, and the material stiffness of the at least one finger 155.

[0042] 8b illustrates an example finger 155 with a number of variables. In some examples, the peak resistance force can be calculated according to the following mathematical model: Parameters for the peak force contribution of deflecting fingers

[0043] [Table 1]

[0044] Other examples of contributing factors to the absolute value of the peak force include the force of the shield spring, the sliding force from the trigger ring against the plunger rod guide, and the sliding force from the trigger ring against the frame components (e.g., the nut or the housing). Other examples are possible. Furthermore, using this flexure arm principle to create the peak force is also advantageous during assembly, as the at least one finger 155 helps to ensure that the trigger ring moves with the nut 152 during assembly by securing the trigger ring 160 as the nut 152 is pushed back and forward during winding and locking of the torque spring 190, and is also advantageous for improving the robustness of the design. The at least one finger 155 also ensures that the device 100 cannot be inadvertently actuated if the device 100 is dropped or searched and / or inspected by a user. Furthermore, the at least one finger 155 may be adjusted as needed to change the peak force. For example, the size, thickness, stiffness, material used, or other parameters of the finger 155 may be adjusted to change the peak force. This type of adjustment can be made much easier than conventional spring adjustments.

[0045] As illustrated in Figures 11-13b, an alternative drug delivery device 200 is provided. The drug delivery device 200 includes similar features and elements as the drug delivery device 100, and therefore has reference numbers with the same two-digit suffix as those of the drug delivery device 100 of Figures 1-10. Therefore, for brevity, the similar components will not be described in detail. The drug delivery device 200 may include additional components not shown, and any components present in the device 200 may be incorporated into the device 100. In some instances, if the user prematurely removes the device from the injection site (i.e., before all the drug is delivered), a spray of drug will be visible coming out of the needle as administration continues even though the user is not benefiting from it.

[0046] The device 200 may include a dose lockout mechanism 292 in the form of a spring-loaded tab 293 recessed within the housing 202. The spring-loaded tab 293 is aligned with the plunger rod guide 270, and more specifically, with at least one protrusion 276 of the base portion 274 of the plunger rod guide 270. The spring-loaded tab 293 abuts the trigger ring 260. Because the trigger ring 260 moves past the spring-loaded tab 293 to interact with the shield 210, the spring-loaded tab 293 remains hidden within the housing 202 with little or no interference with other components other than minimal friction exerted during the insertion phase.

[0047] In these examples, when actuated, the trigger ring 260 does not follow the shield 210, and thus as the shield 210 moves toward the proximal end 202a of the housing 202 (e.g., during removal of the device 200 from an injection site), the distal end 210b of the shield 210 passes the spring-loaded tab 293, allowing the spring-loaded tab to protrude into the path of the at least one protrusion 276 of the plunger rod guide 270 (which rotates until delivery of the medication is complete). Once the at least one protrusion 276 has rotated into the path of the spring-loaded tab 293, the motion of the plunger rod guide 270 is arrested by interfering geometry.

[0048] In some examples, multiple spring-loaded tabs 293 may be used to reduce the overall travel of the plunger rod guide 270 from removal of the device 200 to dose lockout. Other combinations of plunger rod thread pitch and / or ribs on the plunger rod guide 270 may be used to provide variation in the reaction time of the system. In some examples, alternative approaches to the dose lockout mechanism may include increasing the force of the shield spring (not shown) and / or mating the trigger ring 260 and shield 210 such that removal from the user results in re-engagement of the trigger ring 260.

[0049] In some cases, a dose lockout mechanism 292 may be advantageous to stop delivery at or near the same time as removal from the site. Such a mechanism 292 may be advantageous when the treatment is an emergency one with high risks associated with under-delivery. In addition, such a mechanism 292 may simplify the design of companion "smart" device elements, such as capturing the dose delivered to the patient by storing data in the form of the remaining volume level of the container. Without such a dose lockout mechanism 292, the information would be highly time-dependent, for example with multiple sensors monitoring the depth of insertion and delivery status, resulting in a more complex system with faster processing requirements. Static information such as the remaining volume after injection (and conversely, the dose delivered to the patient) may be read by a reusable companion system, such as a sharps container equipped with imaging, mass balance, or other sensors designed for such purposes. Alternatively or additionally, for example, a smartphone app can be used to collect post-injection images and analyze them for the completeness of the dose given, which may not be possible if the autoinjector always expels the total volume regardless of the insertion status. In the event of an injection error in which the patient accidentally removes the device before the entire dose is completed, the prescribing medical professional will want to know how much of the dose has been lost before deciding on the next course of action. A dose lockout mechanism 292 may stop delivery at a particular state, such as "removed from subcutaneous depth" or "removed from patient", and the associated mechanical engagement of such a mechanism may be aligned with some associated surrogate for the needle or needle depth. If subsequently queried by the medical professional (HCP), the patient can observe the autoinjector (here locked out for needle safety) and relay to the HCP the amount of volume remaining based on graduations, indicator markings, or similar user-recognizable features.

[0050] Another potential benefit of the dose lockout mechanism 292 is that it provides a second load bearing surface once actuation is complete. While it is important for the plunger rod 282 to support the transfer of force from the torque spring 290 during injection, plastic components can be prone to creep if exposed to high forces over time. If the injector is not discarded promptly and the plunger rod creeps due to residual spring load, it will be evident through the window and give the user the impression of a poor quality product, even if it functions as intended. By incorporating a dose lockout mechanism, the amount that the torque spring 290 can rotate after being removed from the injection site is limited. Thus, it has redundant support for residual forces, reducing the risk of breakage after injection.

[0051] The above description describes various devices, assemblies, components, subsystems, and methods of use related to drug delivery devices. The devices, assemblies, components, subsystems, methods, or drug delivery devices may further include or be used with drugs, including but not limited to the drugs identified below, and their generic and biosimilar equivalents. As used herein, the term drug may be used interchangeably with other similar terms and may be used to refer to any type of pharmaceutical or therapeutic material, including traditional and non-traditional medicines, nutraceuticals, supplements, biologics, biologically active agents and compositions, large molecules, biosimilars, bioequivalents, therapeutic antibodies, polypeptides, proteins, small molecules, and generic drugs. Non-therapeutic injectable materials are also included. Drugs may be in liquid form, lyophilized form, or reconstituted from a lyophilized form. The following list of exemplary drugs should not be considered exhaustive or limiting.

[0052] The drug is contained within a reservoir. In some cases, the reservoir is a primary container that is either filled or pre-filled with the drug for the treatment. The primary container can be a vial, cartridge, or pre-filled syringe.

[0053] In some embodiments, the reservoir of the drug delivery device may be loaded with or the device may be used with colony stimulating factors such as granulocyte colony stimulating factor (G-CSF). Such G-CSF formulations include, but are not limited to, Neulasta® (pegfilgrastim, PEGylated filgrastim, PEGylated G-CSF, PEGylated hu-Met-G-CSF) and Neupogen® (filgrastim, G-CSF, hu-MetG-CSF).

[0054] In other embodiments, the drug delivery device may contain or be used with an erythropoietin stimulating agent (ESA), which may be in liquid or lyophilized form. An ESA is any molecule that stimulates erythropoietin. In some embodiments, an ESA is an erythropoietin stimulating protein. As used herein, "erythropoietin stimulating protein" refers to any protein that directly or indirectly causes activation of the erythropoietin receptor, for example, by binding to the receptor and causing receptor dimerization. Erythropoietin stimulating proteins include erythropoietin and its variants, analogs, or derivatives that bind to and activate the erythropoietin receptor, antibodies that bind to and activate the erythropoietin receptor, or peptides that bind to and activate the erythropoietin receptor. Erythropoietin stimulating proteins include Epogen® (epoetin alfa), Aranesp® (darbepoetin alfa), Dynepo® (epoetin delta), Mircera® (methoxypolyethylene glycol-epoetin beta), Hematide®, MRK-2578, INS-22, Retacrit® (epoetin zeta), Neorecormon® (epoetin beta), Silapo® (epoetin zeta), Binocrit® (epoetin alfa), Epoetin alpha, epoetin beta, epoetin iota, epoetin omega, epoetin delta, epoetin zeta, epoetin theta, and epoetin delta, PEGylated erythropoietin, carbamylated erythropoietin, and molecules or variants or analogs thereof.

[0055] Among certain exemplary proteins are the following specific proteins, including fusions, fragments, analogs, variants, or derivatives thereof: OPGL-specific antibodies (also referred to as RANKL-specific antibodies, peptibodies, etc.), peptibodies, related proteins, etc., including fully humanized and human OPGL-specific antibodies, particularly fully humanized monoclonal antibodies; myostatin-binding proteins, peptibodies, related proteins, etc., including myostatin-specific peptibodies; and receptors for IL-4 and / or IL-13, among others. and the like; interleukin 1-receptor 1 ("IL1-R1") specific antibodies, peptibodies, related proteins, etc.; Ang2 specific antibodies, peptibodies, related proteins, etc.; NGF specific antibodies, peptibodies, related proteins, etc.; CD22 specific antibodies, peptibodies, related proteins, etc., particularly dimers of human-mouse monoclonal hLL2 gamma chain disulfide-linked to human-mouse monoclonal hLL2 kappa chain, e.g. Human CD22-specific antibodies, including 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 the human CD22-specific fully humanized antibody of epratuzumab (CAS Registry Number 501423-23-0); IGF-1 receptor-specific antibodies, peptibodies, and related proteins, including but not limited to, anti-IGF-1R antibodies; B7RP-specific fully human monoclonal IgG2 antibodies B-7 related protein 1 specific antibodies, peptibodies, related proteins, etc. (also referred to as "B7RP-1", B7H2, ICOSL, B7h, and CD275), including but not limited to fully human IgG2 monoclonal antibodies that bind to 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 ICOS, the natural receptor for B7RP-1 on activated T cells; HuMaxIL-15 specific antibodies, peptibodies, related proteins, etc., including but not limited to IL-15 antibodies and related proteins, particularly humanized monoclonal antibodies; IFNγ specific antibodies, peptibodies, related proteins, etc., including but not limited to human IFNγ specific antibodies, and including but not limited to fully human anti-IFNγ antibodies; TALL-1 specific antibodies, peptibodies, related proteins, etc., as well as other TALL specific binding proteins; parathyroid hormone ("PTH") specific antibodies, peptibodies, related proteins, etc.; Thrombopoietin receptor ("TPO-R") specific antibodies, peptibodies, related proteins, etc.; Hepatocyte growth factor ("HGF") specific antibodies, peptibodies, related proteins, etc., including those that target the HGF / SF:c-Met axis (HGF / SF:c-Met), such as fully human monoclonal antibodies that neutralize hepatocyte growth factor / scatter factor (HGF / SF); TRAIL-R2 specific antibodies, peptibodies, related proteins, etc.; Activin A specific antibodies, peptibodies, proteins, etc.; TGF-β specific antibodies, peptibodies, related proteins, etc. amyloid beta protein specific antibodies, peptibodies, related proteins, etc.; c-Kit specific antibodies, peptibodies, related proteins, etc., including but not limited to proteins that bind to c-Kit and / or other stem cell factor receptors; OX40L specific antibodies, peptibodies, related proteins, etc., including but not limited to proteins that bind to OX40L and / or other ligands of the OX40 receptor; Activase® (alteplase, tPA), Aranesp® (darbepoetin amyloidosis), LUFA), Epogen® (epoetin alfa, or erythropoietin), GLP-1, Avonex® (interferon beta-1a), Bexxar® (tositumomab, an anti-CD22 monoclonal antibody), Betaseron® (interferon-beta), Campath® (alemtuzumab, an anti-CD52 monoclonal antibody), Dynepo® (epoetin delta), Velcade® (bortezomib), MLN0002 (anti-alpha4beta7mAb), 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), Humatrope® (somatropin, human growth hormone), Humira® (adalimumab), Vectibix® (panitumumab), Xgeva (denosumab), Prolia® (denosumab), 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® (methoxypolyethylene glycol-epoetin beta), Mylotarg® (gemtuzumab ozogamicin), Raptiva® (efalizumab), Cimzia® (certolizumab pegol, CDP870), Soliris™ (eculizumab), pexelizumab (anti-complement C5), Numax® (MEDI-524), Lucentis® (ranibizumab), Panorex® (17-1A, edrecolomab), Trabio® (lerdelimumab), TheraCimhR3 (nimotuzumab), Omnitarg (pertuzumab, 2C4), Osidem® (IDM-1), OvaRex® (B43.13), Nuvion® (vigilizumab), 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), Rituxan® (rituximab, anti-CD20 mAb), Tarceva® (erlotinib), Roferon-A® (interferon alpha-2a), Simulect® (basiliximab), Prexige® (lumiracoxib), Synagis® (palivizumab), 146B7-CHO (anti-IL15 antibody, see U.S. Pat. No. 7,153,507), Tysabri® (natalizumab, anti-alpha4 integrin mAb), Valortim® (MDX-1303, anti-anthrax 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 (type I receptor and receptor accessory protein)), VEGF trap (VEGFR1 Ig domain fused to IgG1 Fc), Zenapax® (daclizumab), Zenapax® (daclizumab, anti-IL-2Rα mAb), Zevalin® (ibritumomab tiuxetan), Zetia® (ezetimibe), Orencia® (atacicept, TACI-Ig), anti-CD80 monoclonal antibody (galiximab), anti-CD23mAb (lumiliximab), BR2-Fc (huBR3 / huFc fusion protein, soluble BAFF antagonist), CNTO148 (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-Clostridium difficile toxin A and toxin BC mAbs MDX-066 (CDA-1) and MDX-1388), anti-CD22 dsFv-PE38 conjugate (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 stage 1 fibrogen (FG-3019), anti-CTLA4 mAb, anti-eotaxin 1 mAb (CAT-213), anti-FGF8 mAb, anti-ganglioside GD2 mAb, anti-ganglioside GM2 mAb, anti-GDF-8 human mAb (MYO-029), anti-GM-CSF receptor mAb (CAM-3001), anti-HepC mAb (HuMax HepC), anti-IFNα mAb (MEDI-545, MDX-1103), anti-IGF1R mAb, anti-IGF-1R mAb (HuMax-Inflam), anti-IL12 mAb (ABT-874), anti-IL12 / IL23 mAb (CNTO1275), anti-IL13 mAb (CAT-354), anti-IL2Ra mAb (HuMax-TAC), anti-IL5 receptor mAb, anti-integrin receptor mAb (MDX-018, CNTO95), anti-IP10 ulcerative colitis mAb (MDX-1100), BMS-66513, anti-mannose receptor / hCGβ mAb (MDX-1307), anti-mesothelin dsFv-PE38 conjugate (CAT-5001), anti-PD1 mAb (MDX-1106(ONO-4538)), anti-PDGFRα antibody (IMC-3G3), anti-TGFβmAb(GC-1008), TRAIL-2 mAb (HGS-ETR2), TWEAK mAb, VEGFR / Flt-1 mAb, ZP3 mAb (HuMax-ZP3)

[0056] In some embodiments, the drug delivery device may contain or be used in conjunction with a sclerostin antibody, such as, but not limited to, romosozumab, brosozumab, or BPS804 (Novartis), or in other embodiments, a monoclonal antibody (IgG) that binds to 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 in conjunction with rilotumumab, bixalomer, trebananib, ganitumab, conatumumab, motesanib diphosphate, brodalumab, vidupiprant, or panitumumab. In some embodiments, the reservoir of the drug delivery device may be loaded with, or the device may be used in conjunction with, IMLYGIC® (talimogene laherparepvec) or another oncolytic HSV for the treatment of melanoma or other cancers, including but 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 in conjunction with an endogenous tissue inhibitor of metalloproteinase (TIMP), such as but not limited to TIMP-3. Antagonist antibodies of the human calcitonin gene-related peptide (CGRP) receptor, such as but not limited to erenumab, and bispecific antibody molecules targeting the CGRP receptor and other headache targets, may also be delivered using the drug delivery device of the present disclosure. Additionally, bispecific T cell engaging (BiTE®) antibodies, such as, but not limited to, BLINCYTO® (blinatumomab), may be used in or with the drug delivery devices of the present disclosure. In some embodiments, the drug delivery devices may contain or be used with APJ large molecule agonists, such as, but not limited to, apelin or analogs thereof.In some embodiments, a therapeutically effective amount of anti-thymic stromal lymphopoietin (TSLP) or a TSLP receptor antibody is used in or with the drug delivery device of the present disclosure.

[0057] The drug delivery devices, assemblies, components, subsystems, and methods have been described in terms of exemplary embodiments, but are not limited thereto. The detailed description should be construed as merely exemplary and does not describe all possible embodiments of the present disclosure. Many alternative embodiments can be implemented using either current technology or technology developed after the filing date of this patent, and such embodiments still fall within the scope of the claims that define the invention disclosed herein.

[0058] The claims at the end of this patent application are not to be construed under 35 U.S.C. 112(f) unless conventional means-plus-function language, such as "means for" or "step for" language, is expressly recited in the claim. The systems and methods described herein are directed to improving computer functionality, as well as improving the functionality of conventional computers.

Claims

1. a housing having a proximal end, a distal end and a longitudinal axis extending between said proximal end and said distal end; an injection assembly including a needle or cannula disposed at least partially within the housing at the proximal end thereof and having an end point; a shield slidably coupled to the housing, the shield having an extended position in which at least a proximal end of the shield extends a distance beyond the proximal end of the housing; a drive assembly disposed at least partially within the housing and operatively coupled to the injection assembly and the shield, A drug delivery device wherein a retraction profile is initiated when the shield moves a predetermined axial distance toward the distal end of the housing, whereby the drive assembly administers medication through the injection assembly and a peak resistance force is exerted within approximately the first 12 mm of axial movement of the shield.

2. 2. The drug delivery device of claim 1, wherein the peak force is exerted within about the first 8 mm of axial movement of the shield.

3. 3. The drug delivery device of claim 2, wherein the peak force is exerted within about the first 3 mm of axial movement of the shield.

4. The drive assembly includes: a container disposed within the shell, the container having a first end and a second end, an interior volume of the container adapted to contain the medicament to be administered to a user; a nut disposed within the shell adjacent the second end of the container, the nut having a first engagement region and a second engagement region; a trigger ring disposed within the shell, the trigger ring having a first engagement region and a second engagement region that slidably engage the first engagement region of the nut and engages a portion of the shield for axial movement therewith; and a plunger rod guide disposed within the shell, the plunger rod guide having a first engagement region and an opening, the first engagement region of the plunger rod guide slidably engaging the second engagement region of the trigger ring, the plunger rod guide operably coupled to a drive mechanism; a plunger rod at least partially disposed within the opening of the plunger rod guide, The drug delivery device of claim 2 or 3, wherein when the shield moves axially toward the distal end of the housing, at least one of the first engagement regions of the trigger ring disengages from the first engagement region of the nut or the second engagement region of the trigger ring disengages from the first engagement region of the plunger rod guide, thereby causing the drive mechanism to urge the plunger toward the proximal end of the housing.

5. 5. The drug delivery device of claim 4, wherein the trigger ring is coupled to the nut such that relative rotation between the trigger ring and the nut is restricted while the first engagement region of the trigger ring engages the first engagement region of the nut.

6. 6. The drug delivery device of claim 4 or 5, wherein the trigger ring is coupled to the plunger rod guide such that relative rotation between the trigger ring and the plunger rod guide is restricted while the second engagement region of the trigger ring engages the first engagement region of the plunger rod guide.

7. 7. The drug delivery device of claim 4, wherein the injection process begins when the shield first moves axially and ends when the drive assembly has fully administered the medication, and wherein the peak resistance force is exerted within about the first 15% of the duration of the injection process.

8. The drug delivery device of any one of claims 4 to 7, wherein the shield has a maximum axial movement towards the distal end of the housing of about 10 mm.

9. The drug delivery device of claim 8 , wherein the peak force occurs within about the first 1 mm of travel of the shield.

10. A drug delivery device according to any one of claims 4 to 9, wherein the nut further comprises at least one deflectable finger projecting inwardly towards the longitudinal axis of the housing thereby in contact with an outer surface of the trigger ring.

11. 11. The drug delivery device of claim 10, wherein the at least one biasing finger applies a frictional force to the nut sufficient to cause the peak resistance force to develop before disengaging from the nut.

12. The peak resistance is a friction force exerted between the plunger rod guide and the trigger ring caused by the drive mechanism; a friction force exerted between the trigger ring and the nut caused by the drive mechanism; an axial spring force exerted by a compression spring coupled to the shield; or The drug delivery device according to any one of claims 4 to 10, wherein the force exerted by the nut is caused by at least one of:

13. A drug delivery device according to any one of claims 4 to 12, further comprising a dose lockout mechanism that stops movement of the plunger rod upon movement of the device in a direction towards the proximal end of the housing.

14. The drug delivery device according to any one of claims 4 to 13, wherein the drive mechanism comprises at least one torque spring.

15. a container having a first end and a second end, an interior volume of the container adapted to contain a medicament to be administered to a user; a nut disposed adjacent the second end of the container, the nut having a first engagement region and a second engagement region; a trigger ring having a first engagement region and a second engagement region that slidably engage the first engagement region of the nut, the trigger ring being movable between a first position and a second position; a plunger rod guide having a first engagement region and an opening, the first engagement region of the plunger rod guide slidably engaging the second engagement region of the trigger ring, the plunger rod guide operably coupled to a drive mechanism; a plunger rod at least partially disposed within the opening of the plunger rod guide, A drive assembly for a drug delivery device, wherein when the trigger ring moves in a first direction from the first position to the second position, at least one of the first engagement regions of the trigger ring disengages from the first engagement region of the nut or the second engagement region of the trigger ring disengages from the first engagement region of the plunger rod guide, thereby causing the drive mechanism to press the plunger in a direction opposite to the first direction.

16. 16. The drive assembly of claim 15, wherein the trigger ring is coupled to the nut such that relative rotation between the trigger ring and the nut is limited while the first engagement region of the trigger ring engages the first engagement region of the nut.

17. 17. The drive assembly of claim 15 or 16, wherein the trigger ring is coupled to the plunger rod guide such that relative rotation between the trigger ring and the plunger rod guide is limited while the second engagement region of the trigger ring engages the first engagement region of the plunger rod guide.

18. 18. The drive assembly of claim 15, wherein an injection process begins when the shield first moves axially and ends when the drive assembly has fully administered the medicament, and wherein the peak resistance force is exerted within about the first 30% of the duration of the injection process.

19. A drive assembly according to any one of claims 15 to 18, wherein the shield has a maximum axial movement towards the distal end of the housing of about 10 mm.

20. 20. The drive assembly of claim 19, wherein the peak force occurs within about the first 1 mm of travel of the shield.

21. A drive assembly according to any one of claims 15 to 20, wherein the nut further comprises at least one deflectable finger projecting inwardly towards the longitudinal axis of the housing thereby in contact with an outer surface of the trigger ring.

22. 22. The drive assembly of claim 21, wherein the at least one biasing finger applies a frictional force to the nut sufficient to cause the peak resistance force to occur before disengaging from the nut.

23. The peak resistance is a friction force exerted between the plunger rod guide and the trigger ring caused by the drive mechanism; a friction force exerted between the trigger ring and the nut caused by the drive mechanism; an axial spring force exerted by a compression spring coupled to the shield; or A drive assembly according to any one of claims 15 to 22, wherein the force exerted by the nut is caused by at least one of:

24. A drive assembly according to any one of claims 15 to 22, wherein the drive mechanism includes at least one torque spring.

25. A drive assembly according to any one of claims 15 to 24, further comprising a dose lockout mechanism that stops movement of the plunger rod upon movement of the device in a direction towards the proximal end of the housing.

26. a housing defining a shell having a proximal end, a distal end and a longitudinal axis extending between said proximal end and said distal end; an injection assembly disposed at least partially within the housing at the proximal end thereof and including a needle or cannula; a shield slidably coupled to the housing, the shield extending a distance beyond the proximal end of the housing; a drive assembly disposed at least partially within the housing and operably coupled to the injection assembly and the shield, A drug delivery device wherein as the shield moves axially toward the distal end of the housing, a retraction profile is initiated in which the drive assembly administers medication through the injection assembly, and a peak resistance force is exerted before the needle or cannula contacts the user's skin.

27. The drive assembly includes: a container disposed within the shell, the container having a first end and a second end, an interior volume of the container adapted to contain the medicament to be administered to a user; a nut disposed within the shell adjacent the second end of the container, the nut having a first engagement region and a second engagement region; a trigger ring disposed within the shell, the trigger ring having a first engagement region and a second engagement region that slidably engage the first engagement region of the nut and engages a portion of the shield for axial movement therewith; and a plunger rod guide disposed within the shell, the plunger rod guide having a first engagement region and an opening, the first engagement region of the plunger rod guide slidably engaging the second engagement region of the trigger ring, the plunger rod guide operably coupled to a drive mechanism; a plunger rod at least partially disposed within the opening of the plunger rod guide, 27. The drug delivery device of claim 26, wherein when the shield moves axially toward the distal end of the housing, at least one of the first engagement regions of the trigger ring disengages from the first engagement region of the nut or the second engagement region of the trigger ring disengages from the first engagement region of the plunger rod guide, thereby causing the drive mechanism to urge the plunger toward the proximal end of the housing.

28. 28. The drug delivery device of claim 27, wherein the trigger ring is coupled to the nut such that relative rotation between the trigger ring and the nut is restricted while the first engagement region of the trigger ring engages the first engagement region of the nut.

29. 29. The drug delivery device of claim 27 or 28, wherein the trigger ring is coupled to the plunger rod guide such that relative rotation between the trigger ring and the plunger rod guide is restricted while the second engagement region of the trigger ring engages the first engagement region of the plunger rod guide.

30. 30. The drug delivery device of any one of claims 28 to 29, wherein the injection process begins when the shield first moves axially and ends when the drive assembly has fully administered the medication, and wherein the peak resistance force is exerted within about the first 15% of the duration of the injection process.

31. The drug delivery device of any one of claims 27 to 30, wherein the shield has a maximum axial movement towards the distal end of the housing of about 10 mm.

32. 32. The drug delivery device of claim 31, wherein the peak force occurs within about the first 3 mm of travel of the shield.

33. A drug delivery device according to any one of claims 27 to 32, wherein the nut further comprises at least one deflectable finger projecting inwardly towards the longitudinal axis of the housing thereby in contact with an outer surface of the trigger ring.

34. 34. The drug delivery device of claim 33, wherein the at least one biased finger applies a frictional force to the nut sufficient to cause the peak resistance force to occur before disengaging from the nut.

35. The peak resistance is a friction force exerted between the plunger rod guide and the trigger ring caused by the drive mechanism; a friction force exerted between the trigger ring and the nut caused by the drive mechanism; an axial spring force exerted by a compression spring coupled to the shield; or A drug delivery device according to any one of claims 27 to 33, wherein the force exerted by the nut is caused by at least one of:

36. A drug delivery device according to any one of claims 27 to 35, further comprising a dose lockout mechanism that stops movement of the plunger rod upon movement of the device in a direction towards the proximal end of the housing.

37. The drug delivery device according to any one of claims 27 to 36, wherein the drive mechanism comprises at least one torque spring.

38. a housing having a proximal end, a distal end and a longitudinal axis extending between said proximal end and said distal end; an injection assembly including a needle or cannula disposed at least partially within the housing at the proximal end thereof and having an end point; a shield slidably coupled to the housing, the shield having an extended position in which at least a proximal end of the shield extends a distance beyond the proximal end of the housing; a drive assembly disposed at least partially within the housing and operatively coupled to the injection assembly and the shield, A drug delivery device wherein a retraction profile is initiated when the shield moves a predetermined axial distance toward the distal end of the housing, thereby causing the drive assembly to administer medication through the injection assembly, and wherein a peak resistive force is exerted when the axial distance from the proximal end of the shield to the end point of the needle or cannula is about 12 mm or less, as measured in the distal direction.

39. The drive assembly includes: a container disposed within the shell, the container having a first end and a second end, an interior volume of the container adapted to contain the medicament to be administered to a user; a nut disposed within the shell adjacent the second end of the container, the nut having a first engagement region and a second engagement region; a trigger ring disposed within the shell, the trigger ring having a first engagement region and a second engagement region that slidably engage the first engagement region of the nut and engages a portion of the shield for axial movement therewith; and a plunger rod guide disposed within the shell, the plunger rod guide having a first engagement region and an opening, the first engagement region of the plunger rod guide slidably engaging the second engagement region of the trigger ring, the plunger rod guide operably coupled to a drive mechanism; a plunger rod at least partially disposed within the opening of the plunger rod guide, 39. The drug delivery device of claim 38, wherein when the shield moves axially toward the distal end of the housing, at least one of the first engagement regions of the trigger ring disengages from the first engagement region of the nut or the second engagement region of the trigger ring disengages from the first engagement region of the plunger rod guide, thereby causing the drive mechanism to urge the plunger toward the proximal end of the housing.

40. 40. The drug delivery device of claim 39, wherein the trigger ring is coupled to the nut such that relative rotation between the trigger ring and the nut is restricted while the first engagement region of the trigger ring engages the first engagement region of the nut.

41. 40. The drug delivery device of claim 38 or 39, wherein the trigger ring is coupled to the plunger rod guide such that relative rotation between the trigger ring and the plunger rod guide is restricted while the second engagement region of the trigger ring engages the first engagement region of the plunger rod guide.

42. 42. The drug delivery device of any one of claims 39 to 41, wherein the injection process begins when the shield first moves axially and ends when the drive assembly has fully administered the medicament, and wherein the peak resistance force is exerted within about the first 15% of the duration of the injection process.

43. 43. The drug delivery device of any one of claims 39 to 42, wherein the shield has a maximum axial movement towards the distal end of the housing of about 10 mm.

44. 44. The drug delivery device of claim 43, wherein the peak force occurs within about the first 1 mm of travel of the shield.

Images