Drug delivery devices with configurable needle shield engagement components and associated methods - Patents.com

Abstract

A cap assembly for a drug delivery device is described, including a cap housing defining an internal cavity and a remover configured to be insertably mounted within the internal cavity of the cap housing and having a sidewall with a generally annular configuration. A plurality of retaining portions of the remover extend radially inward from the sidewall within the internal cavity such that the plurality of retaining portions are configured to grip a needle shield inserted through the remover into the internal cavity of the cap housing. A drug delivery device is also described, including a cap assembly kit including a cap housing having an internal cavity sized to interchangeably receive one of a first remover or a second remover, the first remover configured to receive a first type of needle shield and the second remover configured to receive a second type of needle shield.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Patent Application No. 62 / 891,042, filed Aug. 23, 2019, which is incorporated herein by reference in its entirety.

[0002] The present disclosure relates generally to drug delivery devices, and more particularly, to drug delivery devices having a configurable needle shield engagement component. [Background technology]

[0003] Drugs may be administered through the use of drug delivery devices such as autoinjectors or on-body injectors. Autoinjectors and on-body injectors can be used to help automate the injection and delivery or administration process, thereby simplifying the process for certain patient groups or subgroups for which the use of syringe / vial combinations or pre-filled syringe systems would be disadvantageous, whether due to physiological or psychological barriers, form factor, or ergonomic concerns.

[0004] Due to aversion to exposed needles and possible associated health and safety issues, various injectors and shields have been developed to hide the needle from the user. In one example, the syringe of the injector may include a needle shield that is engaged by a cap. With this configuration, when desired for use, the user can grasp and pull the cap, thereby removing the needle shield from the syringe and the injector is ready to deliver an injection. Current injectors may be configured to accept a variety of sizes and types of syringes. However, both needle shields with non-rigid and rigid outer walls may be provided. Thus, there is a need for a universal cap that is configured for use with injectors while accommodating needle shields with non-rigid and rigid outer walls. Summary of the Invention [Means for solving the problem]

[0005] According to a first aspect, a drug delivery device is disclosed that includes a housing, an injection assembly, a cassette, a syringe disposed within the cassette and including a reservoir containing a drug and a needle fluidly coupled to the reservoir, and a cap assembly kit. The cap assembly kit includes a cap housing having an internal cavity sized to interchangeably receive one of a first remover or a second remover. The first remover defines a central passageway and has a sidewall configured to receive a first type of needle shield, and the second remover defines a central passageway and has a sidewall configured to receive a second type of needle shield.

[0006] According to some forms, the drug delivery device may include one or more of the following aspects: the first type of needle shield may have a non-rigid outer wall and the second type of needle shield may have a rigid outer wall; the first remover and the second remover may each be configured to be insertably mounted within an internal cavity of the cap housing; or the cap may include a plurality of arms extending along its longitudinal axis, each of the arms being resiliently flexible and having an inwardly extending retaining surface for engaging the remover as the remover is inserted past the retaining surface and into the internal cavity of the cap housing.

[0007] According to some forms, the first remover can include a plurality of retainers extending inwardly into the central passage of the first remover. In some examples, the plurality of retainers can be angled to extend distally within the cap housing and can have a distally directed tip, or the plurality of retainers can be angled to extend distally within the cap housing and can have a flat distal end. In yet another example, the plurality of retainers can extend from a distal edge of the sidewall.

[0008] According to further aspects, the second remover can include a plurality of retention portions extending inwardly into the central passage of the second remover. In some examples, the drug delivery device can include one or more of the following aspects: the plurality of retention portions of the first remover and the plurality of retention portions of the second remover can be different from each other; the plurality of retention portions can include an engagement edge extending generally parallel to a longitudinal axis of the second remover; the engagement edge can have a blunt configuration; the plurality of retention portions can be disposed at a proximal axial location of the second remover; or the sidewall can include a contoured configuration, with the plurality of retention portions extending radially inwardly from a longitudinal edge of a portion of the contoured configuration.

[0009] According to a second aspect, a method of assembling a drug delivery device cassette is disclosed, comprising: providing a cap assembly including a cap housing having an internal cavity with a rear opening; selecting one of a first remover configured to accept a first type of needle shield and a second remover configured to accept a second type of needle shield; orienting the selected one of the first remover and the second remover to coincide with a longitudinal axis of the cap housing; and inserting the selected one of the first remover and the second remover into the internal cavity of the cap housing.

[0010] According to some embodiments, selecting one of the first remover and the second remover may include selecting one of the first remover and the second remover based on whether a needle shield of the drug delivery device cassette has a rigid outer wall or a non-rigid outer wall. Further, in some embodiments, the first remover and the second remover may each have a different number of retaining portions extending radially inward from the annular sidewall of the first remover and the second remover, and selecting one of the first remover and the second remover may include selecting one of the first remover and the second remover based on whether the number of retaining portions of the first remover and the second remover are configured to grip a needle shield having a rigid outer wall or a non-rigid outer wall.

[0011] According to a further aspect, the method may include providing a cassette, a syringe disposed within the cassette, the syringe including a reservoir containing a drug and a needle fluidly coupled to the reservoir, and a needle shield disposed over the needle, and coupling a cap assembly to the cassette such that the needle shield is disposed within an interior cavity of the cap housing through a selected one of the first remover and the second remover, and the plurality of retainers grip an outer wall of the needle shield. If desired, the method may also optionally include restricting linear and rotational movement of the needle shield with the remover and / or removing the cap assembly from the cassette, thereby separating the needle shield from the syringe and the needle.

[0012] According to a third aspect, a cap assembly for a drug delivery device is described that includes a cap housing defining an internal cavity and having a rear opening at a proximal end for receiving a needle shield along a longitudinal axis, and a remover insertably mounted within the internal cavity of the cap housing and having a sidewall with a generally annular configuration, wherein a plurality of retaining portions of the remover extend radially inward from the sidewall within the internal cavity such that the plurality of retaining portions are configured to grip a needle shield inserted through the remover into the internal cavity of the cap housing.

[0013] According to some embodiments, the plurality of retainers can be angled to extend distally within the cap housing. Each of the retainers can also include a distally directed point and / or extend from a distal edge of the sidewall. Additionally, a cap assembly can be provided in combination with a cassette, a syringe disposed within the cassette and including a reservoir including a drug and a needle fluidly coupled to the reservoir, and a needle shield having a non-rigid outer wall disposed over the needle, the cap assembly being coupled to the cassette, the needle shield being disposed within an interior cavity of the cap housing through a remover, and the plurality of retainers gripping the non-rigid outer wall such that removal of the cap assembly from the cassette separates the needle shield from the needle.

[0014] According to some embodiments, the sidewall can include a contoured configuration at an end thereof, with the plurality of retainers extending radially inward from a longitudinal edge of a portion of the contoured configuration. If desired, the plurality of retainers can extend inwardly away from the sidewall transverse to the longitudinal axis, with the interengaging edges of the plurality of retainers extending generally parallel to the longitudinal axis. Additionally, a cap assembly can be provided in combination with a cassette, a syringe disposed within the cassette and including a reservoir containing a drug and a needle fluidly coupled to the reservoir, and a needle shield having a rigid outer wall disposed over the needle, the cap assembly being coupled to the cassette, the needle shield being disposed within an internal cavity of the cap housing through a remover, and the plurality of retainers gripping the rigid outer wall such that removal of the cap assembly from the cassette separates the needle shield from the needle.

[0015] According to any of the above aspects, the cap housing can define opposing retention surfaces in the internal cavity spaced apart along a longitudinal axis of the cap housing, the retention surfaces spaced apart a distance for removably receiving the remover between them. In a further aspect, the cap can include a plurality of arms extending along the longitudinal axis, the arms having inwardly extending retention tabs for engaging the remover when the remover is inserted into the internal cavity of the cap housing. If desired, the plurality of arms can be configured to resiliently flex outwardly to permit insertion and removal of the remover into and from the internal cavity of the cap housing.

[0016] According to any of the above aspects, the cap housing and the remover may be constructed of different materials and / or the multiple retainers may be arranged in an array of sidewall retainers symmetrically disposed around the remover.

[0017] According to a second aspect, a cap assembly kit for a drug delivery device cassette assembly is described, the cap assembly kit including a cassette, a syringe disposed within the cassette and including a reservoir containing a drug and a needle fluidly coupled to the reservoir, and a needle shield disposed over the needle. The cap kit assembly includes a cap housing having an internal cavity sized to at least partially receive the needle shield therein, a first remover configured to be removably mounted within the internal cavity of the cap housing, the first remover having a sidewall defining a central passage and a plurality of retaining portions extending inwardly into the central passage, and a second remover configured to be removably mounted within the internal cavity of the cap housing, the second remover having a sidewall defining a central passage and a plurality of retaining portions extending inwardly into the central passage. Furthermore, the plurality of retaining portions of the first remover and the plurality of retaining portions of the second remover are different.

[0018] According to a fourth aspect, a method of assembling a drug delivery device cassette is described, comprising: providing a cap assembly including a cap housing having an internal cavity with a rear opening and a remover having a sidewall having a generally annular configuration; orienting the remover to coincide with a longitudinal axis of the cap housing; and inserting the remover into the internal cavity of the cap housing such that a plurality of retaining portions of the remover extend radially inward from the sidewall within the internal cavity.

[0019] The above needs are met, at least in part, by the provision of the embodiments described in the following detailed description, particularly when studied in conjunction with the drawings. [Brief description of the drawings]

[0020] [Figure 1] 1 is a diagrammatic view of an exemplary autoinjector drug delivery device, according to various embodiments. [Diagram 2] FIG. 2 is a side view of an exemplary autoinjector apparatus including a cassette and autoinjector, showing the cassette prior to attachment to the autoinjector. [Diagram 3] FIG. 2 is an end view of the autoinjector end of the autoinjector device of FIG. 1. [Figure 4] FIG. 2 is an exploded perspective view of an exemplary cassette of the autoinjector device of FIG. [Figure 5A] 5 is a side cross-sectional view of a first exemplary medication container that may be provided within the cassette of FIG. 4. [Figure 5B] 5 is a side view of a second exemplary medication container that may be provided within the cassette of FIG. 4. [Figure 6A] FIG. 5 is a top-down front perspective view of the cassette of FIG. 4. [Figure 6B] FIG. 6B is a cross-sectional side view of the cassette of FIG. 6A. [Figure 7A] FIG. 5 is a perspective rear view of an exemplary cassette cap of the cassette of FIG. [Figure 7B] 7B is a side cross-sectional view of the proximal end of the cassette showing the cassette cap of FIG. 7A coupled to a needle shield of a drug container provided within the cassette. FIG. [Figure 7C] 7B is a front perspective view looking up from below a portion of the cassette with the cassette cap of FIG. 7A removed from the cassette. FIG. [Figure 7D] FIG. 7B is a cross-sectional side view of a proximal portion of a cassette mounted in an autoinjector, illustrating operation of the cantilever locking arm of the cassette cap of FIG. 7A. [Figure 8A] 7B is a top-down front perspective view of a proximal portion of the outer housing of the cassette of FIG. 4 with the cassette cap of FIG. 7A removed, showing one embodiment of a slot for receiving a key portion of the cassette cap. [Figure 8B] 7B is a top-down front perspective view of the cassette of FIG. 4 showing how an anti-rotation structure formed by a slot in the outer housing and a key in the cassette cap prevents the cassette cap of FIG. 7A from rotating or turning about its longitudinal axis Z when the cassette cap is within the cassette (before the needle shield is removed), thus preventing rotation of the needle shield. [Figure 9]FIG. 2 is an exploded perspective view of a first exemplary cap assembly including a cassette cap and a remover. [Figure 10] FIG. 10 is a cross-sectional view of the cap assembly of FIG. [Figure 11] FIG. 13 is an exploded perspective view of a second exemplary cap assembly including a cassette cap and a remover. [Figure 12] FIG. 13 is an exploded perspective view of a third exemplary cap assembly including a cassette cap and a remover. [Figure 13] FIG. 1 is a diagrammatic view of an on-body injector drug delivery device according to various embodiments. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0021] Disclosed herein is a cap assembly configured to engage and retain a needle shield such that removal of the cap assembly from the device also separates the needle shield from the injection needle. The cap assembly may include a cap housing and a remover inserted into the cap housing. A single cap housing with selectable removers allows reusable drug delivery devices, such as autoinjectors and on-body injectors, to accommodate syringes or other drug containers having both rigid and non-rigid needle shields. In other words, a remover may be selected to engage and retain a particular needle shield, regardless of whether the needle shield has a rigid or non-rigid outer wall. The remover may also be configured to retain the needle shield and limit its linear and rotational movement in combination with the cap housing.

[0022] In some configurations, such as shown in FIG. 1, a drug delivery device 10, such as an autoinjector, may have a vertically oriented configuration in which some or all of the drug delivery components, including the injection assembly, are arranged in a stacked relationship along a longitudinal axis L within a housing 11 of the device 10. As a more specific example, the device 10 may be configured to operate and inject into a user with the device 10 oriented substantially perpendicular to a skin surface of the user. The drug delivery components may include a reservoir 12 having a drug 14 contained therein, a stopper 16 disposed within the reservoir 12 and slidably movable within the reservoir 12 along the longitudinal axis L, a needle 20 oriented along the longitudinal axis L, and a fluid passage 22 fluidly coupling the reservoir 12 to the needle 20. The components may further include an injection assembly including a drive mechanism 18 coupled to a plunger 19 for driving the stopper 16 through the reservoir 12 and a needle insertion mechanism 24 configured to insert the needle 20 to a desired subcutaneous depth within the user. In one approach, the needle insertion mechanism 24 may be a retractable needle guard or a drive mechanism for longitudinally moving the needle a desired distance to expose the needle 20. For example, the drive mechanism 18 may be configured to drive the movement of both the stopper 16 and the needle 20 by moving some or all of the reservoir 12, the flow channel 22, and the needle 20. As generally configured, one or more of the components of the device 10, such as the drive mechanism 18 and the needle insertion mechanism 24, may be actuated in response to actuation of a user input device 26 accessible outside the housing 11. Suitable drive mechanisms include, but are not limited to, springs, gas sources, phase change materials, motors, or other electromechanical systems. Accordingly, the device 10 may include electronic components, such as a controller 28, for controlling the operation of one or more of the drug delivery components. Although FIG. 1 shows the components centrally located along the longitudinal axis L, it will be understood that one or more of the components may be located off-center from the longitudinal axis L within the housing 11 and still be considered to be in a stacked relationship.In one example, an autoinjector drug delivery device having drug delivery components in a stacked relationship corresponds to a reservoir 12 coaxially aligned with a needle 20. As described in more detail below, the device may include a cap assembly 400 including a cap housing 240 and removers 402, 403, 404. The device 10 may further include a needle shield 266, 266' disposed over the needle 20 in a storage state, where the needle shield 266, 266' engages and is retained by the removers 402, 403, 404. The needle shield 266, 266' is removable by removing the cap assembly 400 from the device 10. An exemplary autoinjector device is described in U.S. Patent Application Serial No. 62 / 447,174, filed January 17, 2017, which is incorporated herein by reference.

[0023] FIG. 2 illustrates one embodiment of an autoinjector system or device 100 that may be used to inject a dose of a medication (drug) into a patient. The injection is often self-administered by the patient (user). Alternatively, the drug may be administered by a healthcare provider. As illustrated, the autoinjector system or device 100 may include a removable cassette 200 and an autoinjector 300. Various embodiments of the cassette 200 may be fabricated to contain a drug to be injected into a user by the autoinjector 300. In various other embodiments, the cassette 200 may be fabricated for use in training a user to operate the autoinjector 300 (a training cassette). The autoinjector 300 may be fabricated to automatically deliver an injection when activated by the user or other person. Various embodiments of the autoinjector 300 may have a cassette door 308 that may be fabricated to pivot between an open position and a closed position to allow insertion of the cassette 200 into the autoinjector 300. In some embodiments, the cassette door 308 may include a “cassette” icon (not shown) indicating an insertion entry point for the cassette 200 .

[0024] 3, various embodiments of the autoinjector 300 may include a casing 302 having a handle portion 304 and a cassette receiving portion 306 aligned with the handle portion 304. The cassette receiving portion 306 includes a cassette door 308 that receives the cassette 200 in an open position (FIG. 2) and aligns the cassette 200 with the insertion and ejection drives, and that aligns with other structures and components of the autoinjector 300 in a closed position. The cassette receiving portion 306 and the cassette door 308 of the casing 302 may form a proximal end wall 318 of the autoinjector 300. The proximal end wall 318 may be configured as a wide, flat, stable base for easy placement of the autoinjector 300 on a support surface following removal of the shield remover 240 (FIG. 6A), described in more detail below, or when the autoinjector 300 is not housing a cassette 200. The portion of the proximal end wall 318 formed by the cassette door 308 may include an aperture 308A sized and shaped to allow the shield remover 240 to be removed from the cassette 200 and ejected through aperture 308A when the cassette 200 is installed in the autoinjector 300. The proximal end wall of the autoinjector 300 may further include a target light 320. The target light 320 may be made to be turned on when the shield remover 240 is removed from the cassette 200 and ejected through aperture 308A, thereby providing a visual indication that the shield remover 240 has been removed. When turned on, the target light assists the user in visualizing and selecting an injection site.

[0025] 4, various embodiments of the cassette 200 may include an outer housing 210, an inner sleeve 220, a drug container 260 for containing a drug, a cassette cap 240, a locking cap 230, and a cover 250. Such embodiments of the cassette 200 may facilitate and enable easy injection of the drug by an autoinjector and may be made for single disposable use. In various embodiments, the locking cap 230 and cover 250 of the cassette 200 may be made to prevent removal of the drug container 260 from the cassette 200, thereby preventing needle protrusion before and after use of the cassette 200 and also preventing the drug container 260 from being removed or replaced from the cassette 200. In addition, the locking cap 230 and cover 250 protect the drug container 260 during delivery and transportation. The cassette cap 240 of various embodiments may be made to remove a needle shield 266 covering an injection needle associated with the drug container 260. In various other embodiments, the cassette cap 240 may also be made to engage the outer housing 210 of the cassette 200 such that the cassette cap 240 cannot be rotated or turned, thereby preventing the injection needle from being damaged by the needle shield 266. Various embodiments of the inner sleeve 220 may be made to position the drug container 260 within the cassette housing 210 in either a needle-hidden position or a needle injection position during the injection cycle of the autoinjector. In various other embodiments, the outer housing 210 and inner sleeve 220 of the cassette 200 may include one or more locking features to protect the drug container 260 and prevent unintentional needle exposure or damage. Various other embodiments of the cassette 200 may include a cassette identification mechanism that interfaces with the autoinjector to communicate information regarding the installation of the cassette 200 within the autoinjector and / or the cassette 200.

[0026] As shown in FIGS. 5A and 5B, the drug container 260 may include a conventional glass or plastic syringe including a barrel 261 defining a fluid chamber 262. The fluid chamber 262 may be filled or pre-filled with a dose of drug 267 for treatment. The drug may have a viscosity that depends on the temperature of the product. The syringe 260 may further include an injection needle 265 removably or fixedly disposed at a proximal end of the barrel 261 and an outwardly extending flange 263 disposed at a distal end of the barrel 261. The injection needle 265 may be in communication with the fluid chamber 262 to allow administration of the dose of drug 267 released from the fluid chamber 262 of the syringe barrel 261. The syringe 260 may further include a movable plunger stopper 264 disposed in the fluid chamber 262 of the barrel 260 for expelling a dose of the drug 267 from the chamber 261 so that the dose of the drug 267 may be dispensed through the injection needle 265. In a first configuration shown in FIG. 5A, a protective needle shield 266 made of a non-rigid material may be provided to cover the injection needle 265. As shown, the needle shield 266 in this configuration is a one-piece component with a side wall 269 defining a cavity 271 for receiving therein at least a portion of the injection needle 265 and the needle hub 273 of the syringe 260. In a second configuration shown in FIG. 5B, a protective needle shield 266' including a rigid material or component may be provided to cover the injection needle 265. As shown, this form of protective needle shield 266' includes a non-rigid core 275 configured similarly to the needle shield 266 shown in FIG. 5A with a sidewall 269' defining a cavity 271' for receiving the infusion needle 265 and at least a portion of the needle hub 273 therein. Additionally, the protective needle shield 266' includes a rigid outer shell or casing 277 having a sidewall extending around the non-rigid core 275. As shown, the shell or casing 277 may have an asymmetrical configuration. The asymmetrical configuration may be the result of an opening passing through the shell or casing 277.

[0027] 6A-6B collectively, various embodiments of the outer housing 210 of the cassette 200 may include a top wall 210t, a bottom wall 210b, side walls 210s connecting the top wall 210t and the bottom wall 210b, respectively, a front or proximal end wall 210pe, and an open back or distal end 210de. The proximal end wall 210pe of the outer housing 210 may include a hole 214 fabricated to removably receive the cassette cap 240. The outer housing 210 may be fabricated to retain the inner sleeve 220 within the outer housing 210 while allowing the inner sleeve 220 to slidably move freely within the outer housing 210 after removal of the cassette cap 240. Some embodiments of the outer housing 210 may include an elongated opening or window 212 in each side wall 210s thereof. The outer housing 210 of the cassette 200 may also include pins 215 (FIG. 6A) or any other suitable mechanical structure that prevents the cassette 200 from being inserted into the cassette door in the wrong direction and / or orientation. An "arrow" icon may be provided on the outer housing 210 (not shown) to indicate the proper direction and orientation for inserting the cassette into the cassette door.

[0028] 6A-6B, various embodiments of the inner sleeve 220 may each include a proximal end 222 and a distal end 224. The sleeve 220 may be sized and dimensioned to securely hold, directly or indirectly, the drug container 260 therein. The proximal end 222 of the inner sleeve 220 may define a bore 222a fabricated to allow the injection needle 265 of the drug container 260 to extend therein. The inner sleeve 220 may further include a drive post 268 that may be driven by an insertion drive of the autoinjector during a needle insertion cycle of an injection cycle of the autoinjector. The inner sleeve 220 may be driven through the outer housing 210 of the cassette 200 by an insertion drive of the autoinjector while the drug container 260 moves from a distal position within the outer housing 210 to a proximal position within the outer housing 210 and then back to the distal position. When the inner sleeve 220 is in the distal position (needle-hidden position), the injection needle of the drug container 260 is housed within the outer housing 210 of the cassette 200 and hidden from the user's view. When the inner sleeve 220 is in the proximal position (needle-injection position), the injection needle of the drug container 260 extends out through a hole 214 in the proximal end wall 210pe of the outer housing 210 of the cassette 200 and through an autoinjector (not shown). A locking cap 230 closes the open distal end 224 of the inner sleeve 220, thereby securing the drug container 260 within the inner sleeve 220 such that the drug container 260 moves with the inner sleeve 220 as the inner sleeve 220 is driven forward or backward through the outer housing 210 by the insertion drive of the autoinjector 300 during an insertion cycle of the autoinjector. A cover 250 closes the open distal end 210de of the outer housing 210 and encases the inner sleeve 220 and drug container 260 within the outer housing 210 of the cassette 200, thereby preventing tampering with the drug container 260 and completing the cosmetic appearance of the cassette 200. The inner sleeve 220 may be made from a transparent rigid material, such as clear polycarbonate, to allow viewing of the drug container 260 through a window 212 in the side wall 210s of the outer housing 210.

[0029] 7A and 7B collectively illustrate one embodiment of the cassette cap 240 of the cassette 200. The cassette cap 240 may function as a needle shield remover by engaging and gripping the needle shield 266 of the drug container 260 to allow a user to remove the needle shield 266 from the drug container 260 prior to operating the autoinjector 300. Additionally, the cassette cap 240 may lockingly engage the cassette outer housing 210 such that the cassette cap 240 cannot be easily removed from the cassette 200 unless the cassette 200 is properly installed within the autoinjector. This prevents the needle shield 266 from being unintentionally removed from the drug container 260, for example, when a user is handling the cassette 200. Additionally, the presence of the shield remover 240 provides an indication that the cassette 200 has not been previously used or tampered with.

[0030] As shown in FIG. 7A, various embodiments of the cassette cap 240 may include a hollow body 241 formed by a generally cylindrical portion 241c and a generally rectangular key portion (key) 241k disposed laterally of and in conjunction with the cylindrical portion 241c. The cassette cap 240 may further include a tapered portion 242 extending proximally from the cylindrical portion 241c of the body 241. An outwardly extending flange 244 terminates the tapered portion 242 and closes the cassette cap 240 at its proximal end 240pe. The flange 244 may function as a finger grip member that allows a user to grasp the cassette cap 240 and pull it out of the cassette 200 to remove the needle shield 266 from the drug container 260 after the cassette is properly installed in the autoinjector. To facilitate gripping and extraction of cassette cap 240, flange 244 may have a generally oval shape that is easily gripped by users with limited dexterity. An "arrow" icon 243 may be provided on tapered portion 242 of cassette cap 240 to indicate the proper direction and orientation for inserting the cassette into the cassette door of the autoinjector.

[0031] The cylindrical portion 241c and the key 241k are open at the distal end 240de of the cassette cap 240. The open distal end of the cylindrical portion 241c may be formed by a plurality of flexible outwardly extending tongues 245t that define an expandable collar structure 245 that mates with the open distal end of the key 241k. As shown in FIG. 7C, the expandable collar structure 245 prevents the cassette cap 240 from being reinserted into the cassette. The cylindrical portion 241c may include a flexible member 241cf that allows the cylindrical portion 241c to receive a metal insert 246 (FIG. 7B) that assists in engaging and gripping the needle shield.

[0032] 7A, the key 241k may include an end wall 241ke closing its proximal end. The end wall 241ke may extend slightly beyond the bottom wall 241kb of the key 241k, thereby forming a stop 241ks.

[0033] As shown in FIG. 8A, the proximal end wall 210pe of the cassette outer housing 210 may include a slot 214s extending from the aperture 214 toward the bottom wall 210b of the housing 210. The slot 214s may be sized and shaped to mate with a key 241k of the cassette cap 240 when the cassette cap 240 is within the cassette 200, with a front edge 2101e of the outer housing bottom wall 210b engaging a stop 241ks of the cassette cap key 241k, thereby forming a cassette cap anti-rotation structure. As shown in FIG. 8B, the anti-rotation structure formed by the slot 214s and the key 241k prevents the cassette cap 240 from rotating or turning about its longitudinal axis Z when the cassette cap 240 is within the cassette 200 (prior to removal of the needle shield), thus preventing rotation of the needle shield. This is important because rotation of the needle shield can result in cutting or coring of the needle shield by the sharp end of the infusion needle. Thus, the anti-rotation structure protects the needle shield from damage by the infusion needle when the cassette cap 240 is in the cassette 200. The stops 241ks of the cassette cap keys 241k can limit the cassette cap 240 from being pushed distally along the longitudinal axis Z toward the syringe, which also prevents the infusion needle from penetrating and thereby damaging the needle shield.

[0034] 7A-7C, bottom wall 241kb of key 241k may define a cassette cap locking structure formed by a distally extending cantilever spring member 247 and a downwardly extending protrusion or locking tab 248 provided at a free end of spring member 247. Locking tab 248 may include an undercut formed by a beveled surface 248s that defines an acute angle 0 with a bottom surface 247b of spring member 247.

[0035] As shown in Figures 7B and 7C, a metal tubular insert 246 may be provided on the inner surface 241i of the cylindrical body portion 241c to grip the outer surface of the needle shield 266 so that the needle shield 266 can be withdrawn with the cassette cap 240. In various other embodiments, the metal tubular insert 246 may be replaced with gripping teeth (not shown) formed on the inner surface 241i of the cylindrical body portion 241c. The cassette cap 240 may extend into a hole 214 formed in the proximal end wall 210pe of the outer housing 210 of the cassette 200, thereby positioning the flange or gripping member 244 of the cassette cap 240 outside the cassette 200. A locking structure of the cassette cap 240 formed by a cantilever spring member 247 and a locking tab 248 may be disposed within a peripheral proximal portion of the outer cassette housing 210 to tamper-resistantly lock the cassette cap 240 in place within the cassette 200. Locking may be facilitated by a cantilever spring member 247 that urges or biases a tab 248 into a locking hole 210a (FIG. 7C) that may be defined in a bottom wall 210b of the outer housing 210 of the cassette 200. The locking tab 248 engaged with the locking hole 210a of the cassette outer housing 210 substantially prevents withdrawal of the cassette cap 240 from the cassette 200 unless the cassette 200 is properly installed in an autoinjector. Because the cassette cap 240 is attached to the needle shield 266 and locked within the cassette 200, the needle shield 266 cannot be unintentionally removed from the syringe 260 prior to proper installation in the autoinjector. The presence of the cassette cap 240 also provides an indication that the cassette 200 has not been previously used or tampered with.

[0036] 7C, when the cassette cap 240 is removed, the tongues 245t of the expandable partial collar structure 245 expand or flare outwardly to prevent the cassette cap 240 and attached needle shield 266 (not shown) from being reinserted into the hole 214 in the proximal end wall 210pe of the cassette outer housing 210. Thus, the absence of the cassette cap 240 provides an indication to the user that the cassette 200 has previously been used or tampered with.

[0037] FIG. 7D shows cassette 200 after the autoinjector access door (both not shown) has been closed. As shown, cassette 200 is mounted on support surface 301s of autoinjector chassis 301. Chassis 301 may include a pin switch P that is coupled to the autoinjector's microprocessor to allow signals or data to be transmitted to the microprocessor. Closing of the autoinjector cassette door may cause pin switch P to press on locking tab 248 (if certain conditions for the cassette are met, as described below), thereby bending cantilever spring member 247 upward and releasing it from locking tab 248's locking tab receiving hole 210a (FIG. 7C) in bottom wall 210b of outer cassette housing 210, thereby unlocking cassette cap 240 from cassette 200. With the locking tab 248 unlocked, the user can now grasp the gripping member 244 of the cassette cap 240 and remove it from the cassette 200 and the autoinjector, thereby removing the needle shield 266 and uncovering the injection needle 265. A signal can also be sent to the autoinjector's microprocessor when the pin switch P engages the locking tab 248 so that the autoinjector knows that the cassette 200 is installed.

[0038] One exemplary cap assembly 400 suitable for use with a cassette of a drug delivery device, such as an autoinjector or on-body injector device, is shown in detail in Figures 9-12. The cap assembly 400 includes a cassette cap 240 and one or more removers 402, 403, 404. The cap 240 can be configured as described in the above embodiments, and therefore only the differences will be described with reference to Figures 9-12. As shown, the flexible members 241cf can be opposed arms formed in the cylindrical portion 241c by cutouts extending into the cylindrical portion 241c. The flexible members 241cf of each flexible member 241cf can be formed of a plurality of opposed arms. Distal End 406 extends radially inward into a cavity 410 defined by cylindrical body portion 241c. Distal The cylindrical body portion 241c may further include a tab 408. Distal One or more spaced apart tabs 408 and extending into cavity 410 Proximal The tab 412 may be included. Distal Tab 408 and Proximal Tabs 412 define retention surfaces 414, 416 that face each other within cavity 410 and are spaced apart from each other a sufficient distance to receive one of removers 402, 403, 404 therebetween. Distal The tab 408 is coupled to or integral with the flexible member 241cf, such that a physician or other person assembling the cap assembly 400 can insert one of the removers 402, 403, 404 into the cavity 410 and move the remover 402, 403, 404 to the cavity 410. Distal The removers 402, 403, 404 can be pushed past the tabs 408, thereby bending the flexible members 241cf outward. Distal After removing the tabs 408, the flexible members 241cf resiliently return radially inward, DistalTabs 408 are located within the exit paths of removers 402, 403, 404, thereby preventing removers 402, 404 from moving longitudinally out of cap 240. Similarly, when a physician or other person assembling cap assembly 400 wishes to remove removers 402, 403, 404 from cap 240, such as to change to a different remover 402, 403, 404, the user can push flexible members 241cf outward to clear a longitudinal path for pulling removers 402, 403, 404 through rear opening 240o of cap 240. Proximal The tabs 412 can be substantially fixed within the longitudinal path of the removers 402, 403, 404 and limit the depth to which the removers 402, 403, 404 can be inserted into the cap 240. In some forms, the tabs 408, 412 can be spaced apart from one another to provide a small gap, e.g., 1-3 mm, to receive the removers 402, 403, 404 therebetween.

[0039] Exemplary removers 402, 403, 404 are shown in Figures 9-12. Each of the removers 402, 403, 404 shown in Figures 9-12 has a tubular configuration with an annular sidewall 418, although other configurations are suitable. The sidewall 418 may be continuous or discontinuous as desired. For example, the sidewall 418 may have a slot opening extending longitudinally along the sidewall 418, such as when a piece of material is formed into a ring or other shape. The annular sidewall 418 in the illustrated form defines a cylindrical longitudinal passageway 420 therethrough. As shown, each remover 402, 403, 404 includes one or more retainers 422 extending inwardly from the sidewall 418 into the passageway 420. In some forms, the retainers 422 may be integrally formed with the sidewall 418 and / or may be symmetrically disposed about the sidewall 418. For example, the removers 402 , 403 , 404 can include any number of retaining portions 422 , such as one, two, three, four, eight, or more retaining portions 422 .

[0040] In a first configuration, shown in FIGS. 9 and 10, the remover 402 can be configured to grip and retain the non-rigid outer wall of the needle shield 266 within the cap 240. In this configuration, the retaining portion 422 can be a tab that is integral with the sidewall 418 and angled into the passageway 420. For example, the tab 422 can extend angularly into the passageway 420 up to about one-quarter of the diameter of the sidewall 418. In one example, the tab 422 can be connected to the sidewall 418 at an edge that extends approximately perpendicular to its longitudinal axis along the periphery of the sidewall 418. As such, the tab 422 extends distally into the passageway 420. As shown, the tab 422 can have a curved configuration similar to the curvature of the sidewall 418. If desired, the tab 422 can include a tip 424 to better grip the needle shield 266. The tip 424 allows the remover 402 to recess or pierce the non-rigid outer wall of the needle shield 266, thereby retaining the needle shield 266 within the cap 240. In some forms, the tab 422 may have a thin cross-section, or the edges of the tab 422 may be sharpened to enhance the gripping effect of the remover 402. As shown, the tab 422 is located at a mid-point along the axial length of the remover 402, with its tip 424 located at the distal half of the remover 402. This positioning allows the tip 424 of the tab 422 to be recessed and insert the end of the needle shield 266 through the majority of the remover 402 before beginning to grip the needle shield 266. The needle shield 266 can then be forced to a desired end position within the cap 240, with the tab 422 dragging along the non-rigid outer wall of the needle shield 266 before establishing the final position. Additionally, the tabs 422 can have a distal length that is greater than one-third the axial length of the remover 402. In the illustrated form, the remover 402 includes three tabs 422 arranged symmetrically about the sidewall 418 in a single plane perpendicular to the longitudinal axis of the remover 402.

[0041] In a second configuration shown in FIG. 11 , the remover 403 can be configured to grip and retain the non-rigid outer wall of the needle shield 266 within the cap 240. In this configuration, the retaining portion 422 can be a tab that is integral with the side wall 418 and extends from a distal edge 426 of the side wall 418. As shown, the tab 422 can angle radially inwardly to extend distally into the path of an object inserted through the passageway 420 of the side wall 418. As shown, the tab 422 can have a curved configuration similar to the curvature of the side wall 418. If desired, the tab 422 can include a tip 424 to better grip the needle shield 266. As with the above configuration, the tip 424 allows the remover 402 to be recessed or penetrate the non-rigid outer wall of the needle shield 266, thereby retaining the needle shield 266 within the cap 240. In alternative configurations, the tab 422 may have a flat distal edge. In some configurations, the tab 422 may have a thin cross-section, or the edges of the tab 422 may be sharpened to enhance the gripping effect of the remover 402. The distal positioning of the tab 422 allows the tip 424 of the tab 422 to be recessed, allowing the end of the needle shield 266 to be inserted through the remover 402 before beginning to grip the needle shield 266. The needle shield 266 may then be forced to a desired end position within the cap 240, and the tab 422 may be dragged along the non-rigid outer wall of the needle shield 266 before establishing a final position. Additionally, the tab 422 may have a distal length that is greater than one-third the axial length of the remover 403. In the illustrated form, the remover 402 includes three tabs 422 arranged symmetrically about the sidewall 418 in a single plane perpendicular to the longitudinal axis L of the remover 402 .

[0042] In a third configuration shown in FIG. 12, the remover 404 can be configured to grip and retain the rigid outer wall of the needle shield 266' within the cap 240. In this configuration, the retaining portion 422 can be a tab integral with the side wall 418 and extending generally perpendicular to the longitudinal axis into the passageway 420. For example, the tab 422 can have a generally rectangular configuration with an inner edge 438 extending generally parallel to the longitudinal axis of the remover 403. In one example, the tabs 422 can be symmetrically arranged in a single plane perpendicular to the longitudinal axis L of the remover 404 about the side wall 418. The inner edge 438 of the tab 422 can define an inner diameter that is slightly smaller than the outer diameter of the rigid outer wall of the needle shield 266', e.g., about 0.1 to 1.0 mm. With this configuration, when the needle shield 266' is inserted through the remover 404, the edge 438 exerts a compressive force on the needle shield 266' that is distributed over the extending axial length of the inner edge 438. As shown, the remover 404 includes eight tabs 422, which further distribute the compressive force around the needle shield 266'. This arrangement advantageously retains the rigid outer wall of the needle shield 266' without relying on the point of application. In the illustrated form, the tabs 422 are provided on the remover 404 by a contoured configuration 428 having a repeating pattern of spaces 430 extending between upstanding portions 432 of the sidewall 418. As shown, the contoured configuration 428 is formed on the proximal end 434 of the sidewall 418 such that the tabs 422 engage the needle shield 266' as the needle shield 266' is inserted through the remover 404. In one approach, the tabs 422 may be formed by manipulating the material of the spaces 430 of the uneven configuration 428 to bend into a radially inward extending configuration. With this configuration, the tabs 422 extend from one of the longitudinal edges 436 of the upright portion 432. The uneven pattern 428 is shown with a pattern of eight spaces 430 and protrusions 432, although more or fewer may be used as desired. Additionally, the tabs 422 may have an axial length that is greater than one-quarter the axial length of the remover 402.

[0043] This configuration allows a user to select a desired remover 402, 403, 404 configured for a particular needle shield 266, 266' for the autoinjector system 100 and insert the remover 402, 403, 404 in an orientation such that the retainer 422 is configured to retain the needle shield 266, 266' within the cap 240 when the cap 240 is removed from the cassette 200. The cap 240 may then be coupled to the cassette 200 as described above such that the needle shield 266, 266' is inserted through the remover 402, 403, 404. As the needle shield 266, 266' is inserted through the remover 402, 403, 404, the retainer 422 engages and grips the outer wall of the needle shield 266, 266', whether rigid or non-rigid. Thus, when operation of the autoinjector system 100 is desired, the user can remove the cap 240, thereby separating the needle shield 266, 266' from the syringe 260 and exposing the injection needle 265.

[0044] In all of the above configurations, the removers 402, 403, 404 and the cap 240 may be made of different materials. For example, the removers 402, 403, 404 may be metal and the cap 240 may be plastic. Additionally, in some configurations, multiple removers 402, 403, 404 may be provided in a kit so that a physician or other person assembling the cap assembly 400 can adapt the autoinjector system 100 to needle shields 266, 266' having rigid and non-rigid outer walls as desired.

[0045] Any of the above components may be assembled in a particular manner. For example, a cap assembly 400 may be provided that includes a cap housing 240 having an interior cavity 410 with a rear opening 240o, and removers 402, 403, 404 having a sidewall 418 with a generally annular configuration. A physician or other person assembling the cap assembly 400 may then orient the removers 402, 403, 404 to coincide with a longitudinal axis of the cap housing 240 and insert the removers 402, 403, 404 into the interior cavity 410 of the cap housing 240 such that the retainers 422 of the removers 402, 403, 404 extend radially inward from the sidewall 418 within the interior cavity 410. Inserting the removers 402, 403, 404 may include inserting the removers 402, 403, 404 between the arms 241cf of the cap housing 240, which may be configured to bend outward and resiliently return inward to retain the removers 402, 403, 404 within the interior cavity 410. If desired, the method of assembling may include selecting one of the removers 402, 403, 404 based at least in part on an outer wall of the needle shield 266, 266′ intended for use with the cap assembly 400, with each of the removers 402, 403, 404 having a different number of retaining portions 422 as described above. In some forms, the method may include limiting the linear and rotational movement of the needle shield 266, 266' with removers 402, 403, 404, and / or providing a cassette 200, a syringe 260 disposed within the cassette 200 and including a reservoir 262 containing a drug 267 and a needle 265 fluidly coupled to the reservoir 262, and a needle shield 266, 266' disposed over the needle 265, and coupling the cap assembly 400 to the cassette 200 such that the needle shield 266, 266' is disposed within an internal cavity 410 of the cap housing 240 through the removers 402, 403, 404 and the multiple retaining portions 422 grip an outer wall of the needle shield 266, 266'.Additionally, the method may include removing the cap assembly 400 from the cassette 200, thereby separating the needle shield 266, 266' from the syringe 260 and exposing the needle 265.

[0046] Although the above disclosure has been described with reference to the structure and operation of an autoinjector drug delivery device, the present disclosure is also suitable for and can be incorporated into on-body drug delivery devices. As shown in Fig. 13, the on-body injector 400 can have a horizontally oriented configuration, with the drug delivery components disposed generally along a horizontal plane P within the housing 401 of the device 400. In these devices 400, the housing 401 is low-profile with a width greater than a height, so that when a user places the housing 401 on the skin, the components spread out over an area of ​​the skin rather than being stacked as in the above embodiments. The drug delivery components may include a reservoir 402 having a drug 404 contained therein, which may be removably disposed within the housing 401, a stopper 406 disposed within the reservoir 402 and slidably movable therein along a horizontal plane P, a drive mechanism 408 coupled to a plunger 410 for driving the stopper 406 within the reservoir 402, a needle 412 oriented along an axis X extending generally perpendicular to the horizontal plane P, a flow channel 414 fluidly coupling the reservoir 402 to the needle 412, and a needle insertion mechanism 416 configured to insert the needle 412 to a desired subcutaneous depth within a user. As generally configured, one or more of the components of the device 400, such as the drive mechanism 408 and the needle insertion mechanism 416, may be actuated in response to actuation of a user input device 418 accessible on the exterior of the housing 401. In accordance with this, the device 400 may include electronic components, such as a controller 419, for controlling the operation of one or more of the drug delivery components. As mentioned above, this version of the device 400 may also include a cap assembly 400 including the cap housing 240 and the removers 402, 403, 404. The device 400 may further include a needle shield 266, 266' disposed over the needle 412 in a storage state, where the needle shield 266, 266' engages and is retained by the removers 402, 403, 404. The needle shield 266, 266' is removable by removing the cap assembly 400 from the device 400.Of course, it will be understood that some components may be located partially or entirely above or below the horizontal plane P that extends through approximately the center of the housing 401 and still be considered to have a horizontally oriented configuration. Suitable drive mechanisms include, but are not limited to, springs, gas sources, phase change materials, motors, or other electromechanical systems. Examples of on-body injector devices are described in U.S. Patent Application No. 62 / 536,911, filed July 25, 2017, which is incorporated herein by reference.

[0047] The above description describes various components of the drug delivery device and the use and / or assembly method associated with the drug delivery device. It should be clear that the drug delivery device or method can further include the use of the following drugs, but note that the following list should not be considered exhaustive or limiting. The drug is placed in a reservoir. In some cases, the reservoir is a primary container that is filled or pre-filled with a drug for treatment. The primary container can be a cartridge or a pre-filled syringe.

[0048] For example, the drug delivery device, or more specifically, the reservoir of the device, may be loaded with colony stimulating factors, such as granulocyte colony stimulating factor (G-CSF). Such G-CSF agents include, but are not limited to, Neupogen® (filgrastim) and Neulasta® (pegfilgrastim). In various other embodiments, the drug delivery device may be used with various pharmaceutical agents, such as erythropoietin stimulating agents (ESAs), which may be in liquid or lyophilized form.ESAs include 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®, and others. any molecule that stimulates erythropoiesis, such as Epoetin Alpha, Epoetin Beta, Epoetin Zeta, Epoetin Theta, and Epoetin Delta, as well as ... Zeta, Epoetin Zeta, Epoetin The following patents or patent applications, each of which is incorporated herein by reference in its entirety: U.S. Pat. No. 4,703,008; U.S. Pat. No. 5,441,868; U.S. Pat. No. 5,547,933; U.S. Pat. No. 5,618,698; U.S. Pat. No. 5,621,080; U.S. Pat. No. 5,756,349; U.S. Pat. No. 5,767,078; U.S. Pat. No. 5,773,569; U.S. Pat. No. 5,955,422; U.S. Pat. No. 5,986,047 Nos. 6,583,272, 7,084,245 and 7,271,689, and PCT Publication Nos. WO 91 / 05867, WO 95 / 05465, WO 96 / 40772, WO 00 / 24893, WO 01 / 81405 and WO 2007 / 136752, or variants or analogs thereof.

[0049] The ESA may be an erythropoiesis stimulating protein. As used herein, "erythropoiesis 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. Erythropoiesis 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. Erythropoiesis stimulating proteins include, but are not limited to, epoetin alpha, epoetin beta, epoetin delta, epoetin omega, epoetin iota, epoetin zeta, and analogs thereof, PEGylated erythropoietin, carbamylated erythropoietin, mimetic peptides (including EMP1 / hematide), and mimetic antibodies. Exemplary erythropoiesis stimulating proteins include erythropoietin, darbepoietin, erythropoietin agonist variants, and peptides or antibodies that bind to and activate the erythropoietin receptor (as well as the compounds reported in U.S. Patent Application Publication Nos. 2003 / 0215444 and 2006 / 0040858, the entire disclosures of each of which are incorporated herein by reference), as well as the following patents or patent applications, the entire disclosures of which are incorporated herein by reference: U.S. Patent No. 4,703,008; U.S. Patent No. 5,441,868; U.S. Patent No. 5,547,93 ... US Patent No. 5,618,698, US Patent No. 5,621,080, US Patent No. 5,756,349, US Patent No. 5,767,078, US Patent No. 5,773,569, US Patent No. 5,955,422, US Patent No. 5,830,851, US Patent No. 5,856,298, US Patent No. 5,986,047, US Patent No. 6,030,086, US Patent No. 6,310,078, US Patent No. 6,391,633, US Patent No. 6,583,272, US Patent No. 6,586,398, US Patent No. 6,900,292,U.S. Patent No. 6,750,369, U.S. Patent No. 7,030,226, U.S. Patent No. 7,084,245 and U.S. Patent No. 7,217,689, U.S. Patent Application Publication No. 2002 / 0155998, U.S. Patent Application Publication No. 2003 / 0077753, U.S. Patent Application Publication No. 2003 / 0082749, U.S. Patent Application Publication No. 2003 / 0143202, U.S. Patent Application Publication No. 2004 / 0009902, U.S. Patent Application Publication No. 2004 / 0071694, U.S. Patent Application Publication No. US Patent Application Publication No. 2004 / 0091961, US Patent Application Publication No. 2004 / 0143857, US Patent Application Publication No. 2004 / 0157293, US Patent Application Publication No. 2004 / 0175379, US Patent Application Publication No. 2004 / 0175824, US Patent Application Publication No. 2004 / 0229318, US Patent Application Publication No. 2004 / 0248815, US Patent Application Publication No. 2004 / 0266690, US Patent Application Publication No. 2005 / 0019914, US Patent Application Publication No. 2005 / 0026834, U.S. Patent Application Publication No. 2005 / 0096461, U.S. Patent Application Publication No. 2005 / 0107297, U.S. Patent Application Publication No. 2005 / 0107591, U.S. Patent Application Publication No. 2005 / 0124045, U.S. Patent Application Publication No. 2005 / 0124564, U.S. Patent Application Publication No. 2005 / 0137329, U.S. Patent Application Publication No. 2005 / 0142642, U.S. Patent Application Publication No. 2005 / 0143292, U.S. Patent Application Publication No. 2005 / 01538 79, U.S. Patent Application Publication No. 2005 / 0158822, U.S. Patent Application Publication No. 2005 / 0158832, U.S. Patent Application Publication No. 2005 / 0170457, U.S. Patent Application Publication No. 2005 / 0181359, U.S. Patent Application Publication No. 2005 / 0181482, U.S. Patent Application Publication No. 2005 / 0192211, U.S. Patent Application Publication No. 2005 / 0202538, U.S. Patent Application Publication No. 2005 / 0227289, U.S. Patent Application Publication No. 2005 / 0244409,U.S. Patent Application Publication No. 2006 / 0088906 and U.S. Patent Application Publication No. 2006 / 0111279, and PCT Publication Nos. WO 91 / 05867, WO 95 / 05465, WO 99 / 66054, WO 00 / 24893, WO 01 / 81405, WO 00 / 61637, WO 01 / 36489, WO 02 / 014356, and WO 02 / 19963. , WO 02 / 20034, WO 02 / 49673, WO 02 / 085940, WO 03 / 029291, WO 2003 / 055526, WO 2003 / 084477, WO 2003 / 094858, WO 2004 / 002417, WO 2004 / 002424, WO 2004 / 009627, WO 2004 / 024 No. 761, International Publication No. 2004 / 033651, International Publication No. 2004 / 035603, International Publication No. 2004 / 043382, International Publication No. 2004 / 101600, International Publication No. 2004 / 101606, International Publication No. 2004 / 101611, International Publication No. 2004 / 106373, International Publication No. 2004 / 018667, International Publication No. 2005 / 001025, International Publication No. 2005 / 001136 brochure, International Publication No. 2005 / 021579 pamphlet, International Publication No. 2005 / 025606 pamphlet, International Publication No. 2005 / 032460 pamphlet, International Publication No. 2005 / 051327 pamphlet, International Publication No. 2005 / 063808 pamphlet, International Publication No. 2005 / 063809 pamphlet, International Publication No. 2005 / 070451 pamphlet, International Publication No. 2005 / 081687 pamphlet, International Publication No. 2005 / 084711 pamphlet, International Publication No. 2005 / 103076 pamphlet,The erythropoietin molecules disclosed in WO 2005 / 100403, WO 2005 / 092369, WO 2006 / 50959, WO 2006 / 02646 and WO 2006 / 29094, or variants or analogs thereof, are included.

[0050] Examples of other pharmaceuticals for use with the device may include, but are not limited to, antibodies such as Vectibix® (panitumumab), Xgeva™ (denosumab) and Prolia™ (denosumab); other biologics such as Enbrel® (etanercept, TNF receptor / Fc fusion protein, TNF blocker), Neulasta® (pegfilgrastim, PEGylated filgastriam, PEGylated G-CSF, PEGylated hu-Met-G-CSF), Neupogen® (filgrastim, G-CSF, hu-MetG-CSF) and Nplate® (romiplostim); small molecule drugs such as Sensipar® (cinacalcet). The device may also be used with therapeutic antibodies, polypeptides, proteins, or other chemicals such as iron, e.g., ferumoxytol, iron dextran, ferric gluconate, and ferric oxide. The pharmaceutical agent may be in liquid form or may be reconstituted from a lyophilized form.

[0051] Among certain exemplary proteins are the specific proteins described below, including fusions, fragments, analogs, variants, or derivatives thereof.

[0052] As disclosed in PCT Publication WO 03 / 002713, each of which is individually and specifically incorporated herein by reference in its entirety in its entirety, including OPGL-specific antibodies having either a light chain of SEQ ID NO:2 as set forth in Figure 2 of said publication and / or a heavy chain of SEQ ID NO:4 as set forth in Figure 4 of said publication, with regard to OPGL-specific antibodies and antibody-related proteins, in particular those having the sequences set forth in said publications, specifically but not limited to those set forth above (9H7, 18B2, 2D8, 2E11, 16E1, and 22B3), including but not limited to the antibodies described in said publications, which are incorporated herein in their entirety, OPGL-specific antibodies (also referred to as RANKL-specific antibodies, peptibodies, etc.), peptibodies, and related proteins, including fully humanized and human OPGL-specific antibodies, in particular fully humanized monoclonal antibodies;

[0053] The following publications are individually and specifically incorporated by reference in their entirety as disclosed in the following publications: TN8-19-1 to TN8-19-40, TN8-19 con1, and TN8-19 myostatin binding proteins, peptibodies, and related proteins, including myostatin-specific peptibodies, particularly those described in U.S. Patent Application Publication No. 2004 / 0181033 and PCT Publication No. WO 2004 / 058988, which are incorporated by reference in their entireties, particularly with reference in part to myostatin-specific peptibodies, including, but not limited to, the mTN8-19 family of peptibodies, including those of SEQ ID NOs: 305-351, including con2, the mL2 family of SEQ ID NOs: 357-383, the mL15 family of SEQ ID NOs: 384-409, the mL17 family of SEQ ID NOs: 410-438, the mL20 family of SEQ ID NOs: 439-446, the mL21 family of SEQ ID NOs: 447-452, the mL24 family of SEQ ID NOs: 453-454, and the peptibodies of SEQ ID NOs: 615-631;

[0054] IL-4 receptor specific antibodies, including, but not limited to, L1H1, L1H2, L1H3, L1H4, L1H5, L1H6, L1H7, L1H8, L1H9, L1H10, L1H11, L2H1, L2H2, L2H3, L2H4, L2H5, L2H6, L2H7, L2H8, L2H9, L2H10, L2H11, L2H12, L2H13, L2H14, L3H1, L4H1, L5H1, L6H1, each of which is individually and specifically incorporated by reference in its entirety herein, as disclosed in the following publications: Antibodies such as those described in the following publications, particularly those that inhibit the activity mediated by the binding of IL-4 and / or IL-13 to the receptor, including those described in PCT Publication No. WO 2005 / 047331 or International Application No. PCT / US2004 / 37242 and US Patent Publication No. 2005 / 112694, the entireties of which are incorporated herein by reference, with particular reference in part to those set forth in the following publications, including IL-4 receptor-specific antibodies, peptibodies, and related proteins:

[0055] Interleukin 1-receptor 1 ("IL1-R1") specific antibodies, peptibodies, and related proteins, including, but not limited to, those set forth in U.S. Patent Application Publication No. 2004 / 097712, i.e., 15CA, 26F5, 27F2, 24E12, and 10H7, each of which is individually and specifically incorporated herein by reference in its entirety as disclosed in U.S. Patent Application Publication No. 2004 / 097712 ...

[0056] The sequences of the following publications, each of which is individually and specifically incorporated herein by reference in its entirety as disclosed in the following publications, in particular those sequences described in the following publications: L1(N), L1(N)WT, L1(N)1K WT, 2xL1(N), 2xL1(N)WT, Con4(N), Con4(N)1K WT, 2xCon4(N)1K, L1C, L1C 1K, 2xL1C, Con4C, Con4C 1K, 2xCon4C Ang2 specific antibodies and peptibodies, including, but not limited to, those described in PCT Publication No. WO 03 / 057134 and U.S. Patent Application Publication No. 2003 / 0229023, each of which is incorporated by reference in its entirety in part with particular reference to Ang2 specific antibodies and peptibodies, including, but not limited to, those described in the following publications ... Ang2 specific antibodies, peptibodies, and related proteins, including anti-Ang2 antibodies and formulations such as those described in PCT Publication WO 2003 / 030833, which is incorporated by reference in its entirety with respect to Ab533, Ab535, Ab536, Ab537, Ab540, Ab543, Ab544, Ab545, Ab546, A551, Ab553, Ab555, Ab558, Ab559, Ab565, AbF1AbFD, AbFE, AbFJ, AbFK, AbG1D4, AbGC1E8, AbH1C12, AblA1, AblF, AblK, AblP, and AblP;

[0057] NGF-specific antibodies, peptibodies, and related proteins, including, but not limited to, those described in U.S. Patent Application Publication No. 2005 / 0074821 and U.S. Patent No. 6,919,426, each of which is individually and specifically incorporated herein by reference in its entirety, specifically including, but not limited to, the NGF-specific antibodies 4D4, 4G6, 6H9, 7H2, 14D10, and 14D11 set forth in said publications, each of which is individually and specifically incorporated herein by reference in its entirety, and specifically including, but not limited to, those described in said publications, specifically including, but not limited to, the NGF-specific antibodies and related proteins set forth therein,

[0058] Humanized and fully human antibodies, including but not limited to, humanized and fully human monoclonal antibodies, including but not limited to, particularly human CD22 specific IgG antibodies, such as, for example, a dimer of human-mouse monoclonal hLL2 gamma chain disulfide linked to a human-mouse monoclonal hLL2 kappa chain, including, but not limited to, the human CD22 specific fully humanized antibody of epratuzumab (CAS Registry Number 501423-23-0), specifically human CD22 specific antibodies, CD22 specific antibodies, peptibodies, and related proteins, such as those described in U.S. Pat. No. 5,789,554, the entirety of which is incorporated herein by reference with respect to CD22 specific antibodies and related proteins;

[0059] The IGF-1 specific antibodies L1H1, L2H2, L3H3, L4H4, L5H5, L6H6, L7H7, L8H8, L9H9, L10H10, L11H11, L12H12, L13H13, L14H14, L15H15, L16H16, L17H17, L18H18, L19H19, L20H20, L21H21, L22H22, L23H23, L24H24, L25H25, L26H26, L27H27, L28H28, L29H29, L30H30, L31H30, L32H30, L33H30, L34H30, L35H30, L36H30, L37H30, L38H30, L39 ... 31, L32H32, L33H33, L34H34, L35H35, L36H36, L37H37, L38H38, L39H39, L40H40, L41H41, L42H42, L43H43, L44H44, L45H45, L46H46, L47H47, L48H48, L49H49, L50H50, L51H51, L52H52, and IGF-1 R-binding fragments and derivatives thereof, including but not limited to those described in the above publications, which are incorporated by reference in their entireties herein with respect to IGF-1 receptor specific antibodies and related proteins;

[0060] Also among the non-limiting examples of anti-IGF-1R antibodies for use in the methods and compositions of the invention are each of those described below.

[0061] U.S. Patent Application Publication No. 2006 / 0040358 (published February 23, 2006), U.S. Patent Application Publication No. 2005 / 0008642 (published January 13, 2005), U.S. Patent Application Publication No. 2004 / 0228859 (published November 18, 2004) (including, but not limited to, Antibody 1A (DSMZ Accession No. DSM ACC 2586), Antibody 8 (DSMZ Accession No. DSM ACC 2589), Antibody 23 (DSMZ Accession No. DSM ACC 2588), and Antibody 18 described in the above publications);

[0062] including, but not limited to, antibodies 2F8, A12 and IMC-A12, described in PCT Publication Nos. WO 06 / 138729 (published December 28, 2006) and WO 05 / 016970 (published February 24, 2005), and Lu et al. (2004), J. Biol. Chem. 279:2856-2865;

[0063] PCT International Publication No. 07 / 012614 (published February 1, 2007), International Publication No. 07 / 000328 (published January 4, 2007), International Publication No. 06 / 013472 (published February 9, 2006), International Publication No. 05 / 058967 (published June 30, 2005) and International Publication No. 03 / 059951 (published July 24, 2003),

[0064] including, but not limited to, antibody 7C10, chimeric antibody C7C10, antibody h7C10, antibody 7H2M, chimeric antibody *7C10, antibody GM 607, humanized antibody 7C10 version 1, humanized antibody 7C10 version 2, humanized antibody 7C10 version 3, and antibody 7H2HM described in U.S. Patent Application Publication No. 2005 / 0084906 (published April 21, 2005);

[0065] U.S. Patent Application Publication No. 2005 / 0249728 (published November 10, 2005), U.S. Patent Application Publication No. 2005 / 0186203 (published August 25, 2005), U.S. Patent Application Publication No. 2004 / 0265307 (published December 30, 2004) and U.S. Patent Application Publication No. 2003 / 0235582 (published December 25, 2003), and Maloney et al. (2003), Cancer Res. 63:5073-5083 (including, but not limited to, antibodies EM164, resurfaced EM164, humanized EM164, huEM164 v1.0, huEM164 v1.1, huEM164 v1.2, and huEM164 v1.3 described therein);

[0066] No. 7,037,498, issued May 2, 2006, U.S. Patent Application Publication No. 2005 / 0244408, published November 30, 2005, and U.S. Patent Application Publication No. 2004 / 0086503, published May 6, 2004, as well as Cohen, et al. (2005), Clinical Cancer Res. 11:2063-2073, including, but not limited to, each of the antibodies produced by hybridomas having ATCC deposit numbers PTA-2792, PTA-2788, PTA-2790, PTA-2791, PTA-2789, PTA-2793, and antibodies 2.12.1, 2.13.2, 2.14.3, 3.1.1, 4.9.2, and 4.17.3.

[0067] including, but not limited to, antibody 19D12, as described in U.S. Patent Application Publication No. 2005 / 0136063 (published June 23, 2005) and U.S. Patent Application Publication No. 2004 / 0018191 (published January 29, 2004), and antibodies comprising a heavy chain encoded by the polynucleotide of plasmid 15H12 / 19D12 HCA(γ4) deposited with the ATCC under deposit number PTA-5214 and a light chain encoded by the polynucleotide of plasmid 15H12 / 19D12 LCF(κ) deposited with the ATCC under deposit number PTA-5220,

[0068] With respect to the aforementioned antibodies, peptibodies, and related proteins specifically targeting the IGF-1 receptor, including, but not limited to, the antibodies PINT-6A1, PINT-7A2, PINT-7A4, PINT-7A5, PINT-7A6, PINT-8A1, PINT-9A2, PINT-11A1, PINT-11A2, PINT-11A3, PINT-11A4, PINT-11A5, PINT-11A7, PINT-11A12, PINT-12A1, PINT-12A2, PINT-12A3, PINT-12A4, and PINT-12A5, which are described in U.S. Patent Application Publication No. 2004 / 0202655 (published October 14, 2004), each of which is incorporated herein by reference in its entirety;

[0069] B-7 related protein 1 specific antibodies, peptibodies, related proteins and the like ("B7RP-1," also referred to in the literature as B7H2, ICOSL, B7h, and CD275), particularly B7RP specific fully human monoclonal IgG2 antibodies, particularly fully human IgG2 monoclonal antibodies that bind to an epitope in the first immunoglobulin-like domain of B7RP-1, particularly those that inhibit the interaction of B7RP-1 with ICOS, the natural receptor for B7RP-1, particularly on activated T cells, and ... as disclosed in the following publications, each of which is individually and specifically incorporated by reference in its entirety herein: 16H (within which are SEQ ID NOs: 1 and 7 for the light and heavy chain variable region sequences, respectively), 5D (within which are SEQ ID NOs: 2 and 3 for the light and heavy chain variable region sequences, respectively), and / or and SEQ ID NO:9), 2H (having therein light chain variable region sequences SEQ ID NO:3 and SEQ ID NO:10, respectively), 43H (having therein light chain variable region sequences SEQ ID NO:6 and SEQ ID NO:14, respectively), 41H (having therein light chain variable region sequences SEQ ID NO:5 and SEQ ID NO:13, respectively), and 15H (having therein light chain variable region sequences SEQ ID NO:4 and SEQ ID NO:12, respectively) and those disclosed in U.S. Patent Publication No. 2008 / 0166352 and PCT Publication No. WO 07 / 011941, which are incorporated by reference in their entireties with respect to such antibodies and related proteins, including, but not limited to, the antibodies set forth in the following publications:

[0070] IL-15 specific antibodies, peptibodies, and related proteins, particularly antibodies, particularly humanized monoclonal antibodies, such as those disclosed in U.S. Patent Application Publication Nos. 2003 / 0138421, 2003 / 023586, and 2004 / 0071702, and U.S. Patent Application Publication No. 7,153,507, each of which is incorporated herein by reference in its entirety for IL-15 specific antibodies and related proteins, including, inter alia, peptibodies, including, but not limited to, HuMax IL-15 antibody and related proteins, such as 146B7;

[0071] IFNγ-specific antibodies, peptibodies, and related proteins, and the like, particularly human IFNγ-specific antibodies, in particular fully human anti-IFNγ antibodies, such as, for example, IFNγ-specific antibodies, in particular, fully human anti-IFNγ antibodies, such as those described in U.S. Patent Application Publication No. 2005 / 0004353, which is incorporated herein by reference in its entirety for the antibodies designated 1118, 1118*, 1119, 1121, and 1121* in the following patent publications: The entire sequences of the heavy and light chains of each of these antibodies, and the sequences of their heavy and light chain variable regions and complementarity determining regions, are individually and specifically incorporated herein by reference in their entirety as disclosed in the aforementioned publications and in Thakur et al. (1999), Mol. Immunol. 36:1107-1115, respectively. In addition, the descriptions of the properties of these antibodies provided in the above publications are also incorporated herein by reference in their entirety. Specific antibodies include those having a heavy chain of SEQ ID NO:17 and a light chain of SEQ ID NO:18, those having a heavy chain variable region of SEQ ID NO:6 and a light chain variable region of SEQ ID NO:8, those having a heavy chain of SEQ ID NO:19 and a light chain of SEQ ID NO:20, those having a heavy chain variable region of SEQ ID NO:10 and a light chain variable region of SEQ ID NO:12, those having a heavy chain of SEQ ID NO:32 and a light chain of SEQ ID NO:20, those having a heavy chain variable region of SEQ ID NO:30 and a light chain variable region of SEQ ID NO:12, those having a heavy chain sequence of SEQ ID NO:21 and a light chain sequence of SEQ ID NO:22, those having a heavy chain variable region of SEQ ID NO:14 and a light chain variable region of SEQ ID NO:16, those having a heavy chain of SEQ ID NO:21 and a light chain of SEQ ID NO:33, and those having a heavy chain variable region of SEQ ID NO:14 and a light chain variable region of SEQ ID NO:31, as disclosed in the aforementioned publications. A specific antibody contemplated is antibody 1119, disclosed in the aforementioned U.S. Patent Application Publication, having a complete heavy chain of SEQ ID NO: 17, disclosed in the aforementioned U.S. Patent Application Publication, and a complete light chain of SEQ ID NO: 18, disclosed in the aforementioned U.S. Patent Application Publication.

[0072] TALL-1 specific antibodies, peptibodies, and related proteins, such as those described in U.S. Patent Application Publication Nos. 2003 / 0195156 and 2006 / 0135431, as well as other TALL specific binding proteins (the above publications are each incorporated by reference in their entirety with respect to TALL-1 binding proteins, particularly the molecules in Table 4 and Table 5B, each of which is individually and specifically incorporated by reference in its entirety as fully disclosed in the above publications);

[0073] Parathyroid hormone ("PTH")-specific antibodies, peptibodies, and related proteins, such as those described in U.S. Pat. No. 6,756,480, which is incorporated by reference in its entirety, with particular reference in part to proteins that bind PTH;

[0074] Thrombopoietin receptor ("TPO-R")-specific antibodies, peptibodies, and related proteins, such as those described in U.S. Pat. No. 6,835,809, which is incorporated by reference in its entirety, with particular reference in part to proteins that bind TPO-R;

[0075] Hepatocyte growth factor ("HGF") specific antibodies, peptibodies, and related proteins, 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 (HGF / SF), as described in U.S. Patent Application Publication No. 2005 / 0118643 and PCT Publication No. WO 2005 / 017107, huL2G7, as described in U.S. Patent No. 7,220,410, and OA-5d5, as described in U.S. Patent Nos. 5,686,292 and 6,468,529, and PCT Publication No. WO 96 / 38557, each of which is incorporated by reference in its entirety with particular reference in part to proteins that bind HGF;

[0076] TRAIL-R2 specific antibodies, peptibodies, related proteins, etc., such as those described in U.S. Pat. No. 7,521,048, which is incorporated herein by reference in its entirety with particular reference in part to proteins that bind TRAIL-R2;

[0077] Activin A-specific antibodies, peptibodies, related proteins, etc., including, but not limited to, those described in U.S. Patent Application Publication No. 2009 / 0234106, which is incorporated by reference in its entirety, with particular reference in part to proteins that bind activin A;

[0078] TGF-β specific antibodies, peptibodies, related proteins, etc., including, but not limited to, those described in U.S. Pat. No. 6,803,453 and U.S. Patent Application Publication No. 2007 / 0110747, each of which is incorporated by reference in its entirety, with particular reference in part to proteins that bind TGF-β;

[0079] Amyloid β protein specific antibodies, peptibodies, related proteins, etc., including but not limited to those described in PCT Publication WO 2006 / 081171, which is hereby incorporated by reference in its entirety, particularly in relation to proteins that bind to amyloid β protein. One possible antibody is an antibody having a heavy chain variable region comprising SEQ ID NO:8 and a light chain variable region having SEQ ID NO:6, as disclosed in the above publication.

[0080] c-Kit specific antibodies, peptibodies, related proteins, etc., including, but not limited to, those described in U.S. Patent Application Publication No. 2007 / 0253951, which is incorporated by reference in its entirety, with particular reference in part to proteins that bind c-Kit and / or other stem cell factor receptors;

[0081] OX40L-specific antibodies, peptibodies, related proteins, and the like, including, but not limited to, those described in U.S. Patent Application Publication No. 2006 / 0002929, which is incorporated by reference in its entirety, with particular reference in part to proteins that bind OX40L and / or other ligands of the OX40 receptor;

[0082] Activase® (alteplase, tPA), Aranesp® (darbepoetin alfa), 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-alpha4beta7 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), Hum atrope® (somatropin, human growth hormone), Humira® (adalimumab), 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), TheraCim hR3 (nimotuzumab), Omnitarg (pertuzumab, 2C4), Osidem® (IDM-1), OvaRex® (B43.13), Nuvion® (vigilizumab), cantuzumab mertansine (huC242-DM1), NeoRecormon® (epoetin beta), Neumega® (oprelvekin, human interleukin-11), Neulasta® (PEGylated filgastrim, PEGylated G-CSF, PEGylated hu-Met-G-CSF), Neupogen® (filgrastim, G-CSF, hu-MetG-CSF), Orthoclone OKT3® (muromonab-CD3, anti-CD3 monoclonal antibody), Procrit® (epoetin alfa), Remicade® (infliximab, anti-TNFα monoclonal antibody), Reopro® (abciximab, anti-GP lIb / Ilia 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-α4 integrin mAb), Valortim® (MDX-1303, anti-anthrax protective antigen mAb), ABthrax™, Vectibix® (panitumumab), Xolair® (omalizumab), ETI211 (anti-MRSAmAb), 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 (the Ig domain of VEGFR1 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-CD23 mAb (lumiliximab), BR2-Fc (huBR3 / huFc fusion protein, soluble BAFF antagonist), CNTO 148 (golimumab, anti-TNFα mAb), HGS-ETR1 (mapatuzumab, 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 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-IL12mAb (ABT-874), anti-IL12 / IL23 mAb (CNTO 1275), anti-IL13 mAb (CAT-354), anti-IL2Ra mAb (HuMax-TAC), anti-IL5 receptor mAb, anti-integrin receptor mAb (MDX-018, CNTO 95), anti-IP10 ulcerative colitis mAb (MDX-1100), anti-LLY antibody, 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-TGFβ Other exemplary proteins include mAb (GC-1008), anti-TRAIL receptor-2 human mAb (HGS-ETR2), anti-TWEAK mAb, anti-VEGFR / Flt-1 mAb, anti-ZP3 mAb (HuMax-ZP3), NVS antibody no. 1, and NVS antibody no. 2.

[0083] Sclerostin antibodies, such as, but not limited to, romosozumab, brosozumab, or BPS804 (Novartis), may also be included. Further therapeutic agents may be included, such as rilotumumab, bixalomer, trebananib, ganitumab, conatumumab, motesanib diphosphate, brodalumab, vidupiprant, panitumumab, denosumab, NPLATE, PROLIA, VECTIBIX, or XGEVA. Additionally, monoclonal antibodies (IgG) that bind to human proprotein convertase subtilisin / kexin type 9 (PCSK9) may be included in the device.Such PCSK9-specific antibodies include those described in the following patents or patent applications, each of which is incorporated herein by reference in its entirety for all purposes: U.S. Pat. No. 8,030,547, U.S. Patent Application Publication No. 2013 / 0064825, WO 2008 / 057457, WO 2008 / 057458, WO 2008 / 057459, WO 2008 International Publication No. 2008 / 133647, International Publication No. 2009 / 100297, International Publication No. 2009 / 100318, International Publication No. 2011 / 037791, International Publication No. 2011 / 053759, International Publication No. 2011 / 053783, International Publication No. 2008 / 125623, International Publication No. 2 International Publication No. 011 / 072263, International Publication No. 2009 / 055783, International Publication No. 2012 / 0544438, International Publication No. 2010 / 029513, International Publication No. 2011 / 111007, International Publication No. 2010 / 077854, International Publication No. 2012 / 088313, International Publication No. 2012 / 101251, International These include, but are not limited to, Repatha® (evolocumab) and Praluent® (alirocumab) and molecules, variants, analogs, or derivatives thereof as disclosed in Publication No. WO 2012 / 101252, WO 2012 / 101253, WO 2012 / 109530, and WO 2001 / 031007.

[0084] Also included may be talimogene laherparepvec or another oncolytic HSV for the treatment of melanoma or other cancers. Examples of oncolytic HSV include, but are not limited to, talimogene laherparepvec (U.S. Pat. Nos. 7,223,593 and 7,537,924), OncoVEXGALV / CD (U.S. Pat. No. 7,981,669), OrienX010 (Lei et al. (2013), World J. Gastroenterol., 19:5138-5143), G207, 1716, NV1020, NV12023, NV1034, and NV1042 (Vargehes et al. (2002), Cancer Gene Ther., 9(12):967-978).

[0085] Also included are TIMPs. TIMPs are endogenous tissue inhibitors of metalloproteinases (TIMPs) and are important in many natural processes. TIMP-3 is expressed by various cells and / or present in the extracellular matrix, inhibits all major cartilage-degrading metalloproteases, and may play a role in many degradative diseases of connective tissue, including rheumatoid arthritis and osteoarthritis, as well as in cancer and cardiovascular conditions. The amino acid sequence of TIMP-3 and the nucleic acid sequence of DNA encoding TIMP-3 are disclosed in U.S. Patent No. 6,562,596, issued May 13, 2003, the disclosure of which is incorporated herein by reference. Descriptions of TIMP mutations can be found in U.S. Patent Application Publication No. 2014 / 0274874 and PCT Publication No. WO 2014 / 152012.

[0086] Also included are antagonistic antibodies of the human calcitonin gene-related peptide (CGRP) receptor and bispecific antibody molecules targeting the CGRP receptor and other headache targets. More information regarding these molecules can be found in PCT Publication WO 2010 / 075238.

[0087] Additionally, bispecific T cell engaging (BiTE®) antibodies, such as BLINCYTO® (blinatumomab), can be used in the device. Alternatively, an APJ macromolecule agonist, such as apelin or an analog thereof, can be included in the device. Information regarding such molecules can be found in PCT Publication WO 2014 / 099984.

[0088] In certain embodiments, the medicament comprises a therapeutically effective amount of anti-thymic stromal lymphopoietin (TSLP) or a TSLP receptor antibody. Examples of anti-TSLP antibodies that may be used in such embodiments include, but are not limited to, those described in U.S. Patent Nos. 7,982,016 and 8,232,372, and U.S. Patent Publication No. 2009 / 0186022. Examples of anti-TSLP receptor antibodies include, but are not limited to, those described in U.S. Patent No. 8,101,182. In a particularly preferred embodiment, the medicament comprises a therapeutically effective amount of the anti-TSLP antibody designated A5 in U.S. Patent No. 7,982,016.

[0089] Although the drug delivery device, method and elements thereof have been described in terms of exemplary embodiments, the drug delivery device, method and elements thereof are not limited thereto. The detailed description is to be construed as an example only and does not describe all possible embodiments of the invention, since describing all possible embodiments would be impractical, if not impossible. 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. For example, components described herein with reference to a particular type of drug delivery device, such as an on-body injector drug delivery device, or other types of drug delivery devices, can also be utilized in other types of drug delivery devices, such as an autoinjector drug delivery device.

[0090] Those skilled in the art will understand that various modifications, alterations and combinations may be made to the above-described embodiments without departing from the scope of the present invention, and such modifications, alterations and combinations are to be construed as being within the scope of the concept of the present invention.

Claims

1. 1. A drug delivery device comprising: a housing; an injection assembly; a cassette; a syringe disposed within the cassette and including a reservoir containing a drug and a needle fluidly coupled to the reservoir; and a cap assembly kit, The cap assembly kit comprises: a first remover defining a central passage and having a sidewall configured to receive a first type of needle shield; a second remover defining a central passage and having a sidewall configured to receive a second type of needle shield; a cap housing having an interior cavity sized to interchangeably receive one of the first remover and the second remover; 13. A drug delivery device comprising:

2. 2. The drug delivery device of claim 1, wherein the first type of needle shield has a non-rigid outer wall and the second type of needle shield has a rigid outer wall.

3. The drug delivery device of claim 1 or 2, wherein the first remover and the second remover are each configured to be insertably mounted within the internal cavity of the cap housing.

4. The drug delivery device of claim 1 , wherein the first remover includes a plurality of retaining portions extending inwardly into the central passage of the first remover.

5. The drug delivery device of claim 4 , wherein the plurality of retention portions are angled to extend distally within the cap housing and have distally directed tips.

6. The drug delivery device of claim 4 , wherein the plurality of retention portions are angled to extend distally within the cap housing and have flat distal ends.

7. The drug delivery device of any one of claims 4 to 6, wherein the plurality of retention portions extend from a distal edge of the side wall.

8. The drug delivery device of claim 4 , wherein the second remover includes a plurality of retaining portions extending inwardly into the central passage of the second remover.

9. The drug delivery device of claim 8 , wherein the plurality of retention portions of the first remover and the plurality of retention portions of the second remover have different characteristics.

10. The drug delivery device of claim 8 or 9, wherein the plurality of retention portions include engagement edges extending generally parallel to a longitudinal axis of the second remover.

11. The drug delivery device of claim 10 , wherein the engagement edge has a blunt configuration.

12. The drug delivery device of any one of claims 8 to 11, wherein the plurality of retaining portions are disposed at proximal axial positions of the second remover.

13. The drug delivery device of any one of claims 8 to 12, wherein the side wall includes a concave-convex configuration, and the plurality of retention portions extend radially inward from a longitudinal edge of a portion of the concave-convex configuration.

14. A cap assembly according to any one of claims 1 to 13, wherein the cap includes a plurality of arms extending along a longitudinal axis of the cap, each of the arms being resiliently flexible and having an inwardly extending retaining surface for engaging the remover when the remover is inserted past the retaining surface into the internal cavity of the cap housing.

15. 1. A method of assembling a drug delivery device cassette, comprising: Providing a cap assembly including a cap housing having an internal cavity with a rear opening; selecting one of a first remover configured to receive a first type of needle shield and a second remover configured to receive a second type of needle shield; orienting the selected one of the first remover and the second remover to coincide with a longitudinal axis of the cap housing; inserting the selected one of the first remover and the second remover into the interior cavity of the cap housing; A method comprising:

16. 16. The method of claim 15, wherein selecting the one of the first remover and the second remover includes selecting the one of the first remover and the second remover based on whether a needle shield of the drug delivery device cassette has a rigid outer wall or a non-rigid outer wall.

17. 17. The method of claim 16, wherein the first remover and the second remover each have a different plurality of retaining portions extending radially inward from an annular sidewall of the first remover and the second remover, respectively, and selecting the one of the first remover and the second remover includes selecting the one of the first remover and the second remover based on whether the plurality of retaining portions of the first remover and the second remover are configured to grip a needle shield having a rigid outer wall or a non-rigid outer wall.

18. providing a cassette, a syringe disposed within the cassette, the syringe including a reservoir containing a drug and a needle fluidly coupled to the reservoir, and a needle shield disposed over the needle; coupling the cap assembly to the cassette such that the needle shield is disposed within the interior cavity of the cap housing through the selected one of the first remover and the second remover and the plurality of retaining portions grip an outer wall of the needle shield; 20. The method of claim 17, further comprising:

19. The method of claim 18, further comprising limiting linear and rotational movement of the needle shield with the remover.

20. 20. The method of claim 18 or 19, further comprising removing the cap assembly from the cassette, thereby separating the needle shield from the syringe and the needle.

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