Modular fluid path assemblies for drug delivery devices

Modular fluid path assemblies are provided that include conduit, coupling, and needle portions of a fluid path fluidly coupled to an outlet of a container. The modular fluid path assemblies further include a needle shield having a tip of the needle embedded therein. So configured, in embodiments, the modular fluid path assemblies can be sterilized, a medicament can be filled in the container, and a stopper inserted in the container so that the pre-sterilized and pre-filled modular fluid path assemblies can have a closed container integrity (CCI) seal.

FIELD OF THE DISCLOSURE

The present disclosure generally relates to drug delivery devices and, more particularly, to fluid path assemblies for drug delivery devices.

BACKGROUND

Some conventional drug delivery devices can utilize a container prefilled with medicament. In such devices, the container can be connected to a needle insertion mechanism. This configuration occupies a relatively large footprint during sterilization and filling. Further, the container, needle insertion mechanism, and fluid path assemblies can often include complex components that increase particulate risk and residuals from the sterilization process.

SUMMARY

In accordance with a first aspect, a modular fluid path assembly for a drug delivery device is described that includes a container having an interior for storing a medicament and an outlet. The assembly further includes a conduit portion of a fluid path fluidly coupled to the outlet of the container, a coupling portion of the fluid path fluidly coupled to the conduit portion and configured to couple the fluid path to a needle insertion mechanism, and a needle of the fluid path fluidly coupled to the coupling portion. The assembly further includes a needle shield having a tip of the needle embedded therein.

According to some forms, the modular fluid path assembly can further include the medicament disposed within the container and a stopper sealingly disposed within the interior of the container.

According to another form, the coupling portion can be a hub having the needle mounted thereto. The hub includes mounting structure that is configured to couple the hub to the needle insertion mechanism. In one approach, the mounting structure can include a tongue of a tongue-and-groove cooperating structure with the needle insertion mechanism.

According to another form, the assembly can further include a cannula of the fluid path that is configured to operably couple to the needle insertion mechanism to be driven thereby.

Any of the above modular fluid path assemblies can be combined with the needle insertion mechanism, wherein the needle insertion mechanism is a scotch yoke mechanism. In these versions, the hub can be a yoke member of the scotch yoke mechanism or can mount to a yoke member of the scotch yoke mechanism.

According to another form, the needle can provide the conduit and coupling portion, that needle having a proximal end of the needle coupled to the container to be fluidly coupled to the interior and a distal end. In this form, the modular fluid path assembly can further include a septum mounted to the needle and a cannula having a portion extending around the septum and an elongate body extending coaxially along and around the distal end of the needle, where a portion of the septum and cannula are received within an interior cavity of the needle shield.

This form of the modular fluid path assembly can include any of the following aspects. In one embodiment, the modular fluid path assembly can be provided in combination with a carrier having supports configured to engage the modular fluid path assembly to maintain the relative positions of the container, needle, septum, cannula, and needle shield after assembly. In another embodiment, the needle can have a bent configuration including a bend so that the distal end of the needle extends along an axis generally orthogonal to a longitudinal axis of the barrel. In a further embodiment, the modular fluid path assembly with the bent configuration can be provided in combination with a drug delivery device, where the drug delivery device includes a housing, a needle insertion mechanism, and a plunger drive mechanism configured to selectively drive the stopper through the container to thereby force the medicament through the needle and cannula. The bend of the needle can be the coupling portion of the fluid path and a sliding needle member of the needle insertion mechanism can be configured to engage the bend of the needle and drive the needle to insert the tip of the distal end of the needle to a predetermined subcutaneous depth. A sliding cannula member of the needle insertion mechanism can be configured to engage the cannula and insert the cannula to a predetermined subcutaneous depth following the needle, where the sliding needle member is further configured to retract the needle after insertion of the cannula. In one version, the cannula can include an outwardly projecting flange and the sliding cannula member can be configured to engage the outwardly projecting flange and hold the cannula in place during needle shield removal.

In accordance with a second aspect, a method of preparing a modular fluid path assembly for a drug delivery device is described that includes providing a container having an interior for storing a medicament and an outlet, coupling a conduit portion of a fluid path to an outlet of the container, where the fluid path further includes a coupling portion that is configured to couple the fluid path to a needle insertion mechanism and a needle fluidly coupled to the coupling portion. The method can further include embedding a tip of the needle in a needle shield, sterilizing the container, conduit, coupling portion, needle, and needle shield, dispensing a medicament into the container, and inserting a stopper into the interior of the container.

According to one form, the method can further include installing the modular fluid path assembly in a drug delivery device. Installing the modular fluid path assembly in the drug delivery device can include operably coupling the coupling portion of the fluid path to a needle insertion mechanism of the drug delivery device and aligning the container with a plunger drive mechanism of the drug delivery device. In a further form, the coupling portion can be a hub having the needle mounted thereto, and operably coupling the coupling portion of the fluid path to the needle insertion mechanism can include inserting mounting structure of the hub into a slot opening of the needle insertion mechanism. In yet a further form, the needle insertion mechanism can be a scotch yoke mechanism and inserting the mounting structure of the hub into the slot opening of the needle insertion mechanism can further include coupling the hub to a drive pin of the scotch yoke mechanism.

According to another form, the method can further include forming first and second bends in the needle so that a distal end of the needle extends along an axis generally orthogonal to a longitudinal axis of the container. In a further form, the second bend of the needle can be the coupling portion of the fluid path, and the method can include installing the modular fluid path assembly in a drug delivery device, where installing the modular fluid path assembly in the drug delivery device can include coupling the second bend of the needle to a needle insertion mechanism configured to drive the needle to insert a tip to a predetermined subcutaneous depth. In yet a further form, the modular fluid path assembly can include a cannula mounted to the needle and installing the modular fluid path assembly in the drug delivery device can include coupling the cannula to the needle insertion mechanism configured to insert the cannula to a predetermined subcutaneous depth following the needle.

In accordance with a third aspect, a syringe is described herein that includes a barrel that has an interior and a needle that has a proximal end coupled to the barrel to be fluidly coupled to the interior and a distal end. The syringe further includes a septum that is mounted to the needle, a cannula that has a portion that extends around the septum and an elongate body that extends coaxially along and around the distal end of the needle, and a needle shield that has an interior cavity. The syringe is configured so that the needle has a tip of the distal end embedded within the needle shield for a closed container integrity seal, and portions of the septum and cannula are received within the interior cavity of the needle shield.

The syringe can be provided in combination with a carrier that has supports that are configured to engage the syringe to maintain the relative positions of the barrel, needle, septum, cannula, and needle shield after assembly.

According to one form, the septum can be a one-way valve.

According to another form, the syringe can further include a medicament disposed within the interior of the barrel and a stopper received within the interior of the barrel. According to a further form, the needle can have a bent configuration so that the distal end of the needle extends along an axis generally orthogonal to a longitudinal axis of the barrel. The syringe of this form can be disposed within a drug delivery device. With this configuration, the drug delivery device can include a housing, a needle insertion mechanism that is configured to engage the bent configuration of the needle and drive the needle to insert the tip of the distal end of the needle to a predetermined subcutaneous depth, a cannula insertion mechanism that is configured to insert the cannula to a predetermined subcutaneous depth following the needle, where the needle insertion mechanism is further configured to retract the needle after insertion of the cannula, and a plunger drive mechanism that is configured to selectively drive the stopper through the barrel to thereby force the medicament through the needle and cannula.

According to one form, the cannula can include an outwardly projecting flange and the cannula insertion mechanism can be configured to engage the outwardly projecting flange and hold the cannula in place during removal of the needle shield.

According to another form, the needle insertion mechanism and the cannula insertion mechanism can have a common drive. According to a further form, the common drive can include a torsion spring having a thermal release mechanism.

In accordance with a fourth aspect, a method preparing a syringe is described that includes providing a barrel that has an interior and a needle that has a proximal end coupled to the barrel to be fluidly coupled to the interior and a distal end. The method further includes fitting a septum into a rearwardly opening chamber of a cannula, where the septum has a resilient throughbore extending longitudinally therethrough and the throughbore is aligned with a tubular body of the cannula, fitting the cannula, with the septum received within the chamber, into a needle shield, and sliding the needle through the throughbore of the septum and the tubular body of the cannula to a position so that a tip of the distal end is embedded within the needle shield for a closed container integrity seal.

In accordance with a fifth aspect, a method of preparing a syringe is described that includes providing a barrel that has an interior and a needle that has a proximal end coupled to the barrel to be fluidly coupled to the interior and a distal end. The method further includes inserting a needle through a throughbore of a septum so that the septum is spaced from a tip of the distal end of the needle, inserting the needle through a tubular body of a cannula and fitting the septum into a rearwardly facing chamber of the cannula, and inserting the needle, with the cannula and septum coupled thereto, into a needle shield until the tip of the distal end of the needle is embedded within the needle shield for a closed container integrity seal. According to one form, inserting the needle through the throughbore of the septum can include inserting an expansion tube through the throughbore of the septum, expanding the expansion tube so that a diameter of the throughbore is increased, and extracting the expansion tube.

In further accordance with the foregoing third and fourth aspects, the method can further include any one or more of the following.

According to one form, the method can include releasably coupling the syringe to a carrier, where the carrier has supports that are configured to engage the syringe to maintain the relative positions of the barrel, needle, septum, cannula, and needle shield after assembly. The method can also include sterilizing the syringe, filling the barrel with a predetermined amount of medicament, and/or inserting a stopper into the barrel.

According to another form, the method can include bending the needle so that the distal end extends along an axis generally orthogonal to a longitudinal axis of the barrel. Bending can include forming a first bend and a second bend in the needle. In this form, the method can include installing the syringe in a housing of a drug delivery device. Installing the syringe in the housing can includes coupling the needle to a needle insertion mechanism that is configured to engage the second bend of the needle to drive the needle to insert the tip of the distal end of the needle to a predetermined subcutaneous depth, coupling the cannula to a cannula insertion mechanism that is configured to insert the cannula to a predetermined subcutaneous depth following the needle, where the needle insertion mechanism is further configured to retract the needle after insertion of the cannula, and disposing the barrel adjacent to a plunger drive mechanism that is configured to selectively drive the stopper through the barrel to thereby force the medicament through the needle and cannula.

According to further forms, coupling the needle to the needle insertion mechanism can include coupling the needle to a scotch yoke mechanism, coupling the cannula to the cannula insertion mechanism can include coupling the cannula to the scotch yoke mechanism, and coupling the cannula to the cannula insertion mechanism can include coupling an outwardly projecting flange of the cannula to the cannula insertion mechanism to hold the cannula in place during removal of the needle shield.

DETAILED DESCRIPTION

Modular fluid path assemblies are provided that can be sterilized, filled, and coupled to an insertion mechanism of a suitable drug delivery device. As such, the modular fluid path assemblies described herein have a smaller footprint without the insertion mechanism for storage, filling, and sterilization. Further, the number of non-primary container parts in the fill and sterilization process are reduced aiding in minimizing particulate risk and complexity of sterilization and residuals.

In embodiments, a modular prefilled syringe and primary container and fluid path assembly is provided with an incorporated needle shield, such that the syringe and assembly can be sterilized prior to being disposed within a drug delivery device and maintain sterility until the needle shield is removed by a user prior to injection. This modular configuration also provides for cannula insertion, if desired, and needle insertion and extraction functions within a drug delivery device.

The modular fluid path assemblies described herein include conduit, coupling, and needle portions of a fluid path fluidly coupled to an outlet of a container. The modular fluid path assemblies further include a needle shield having a tip of the needle embedded therein. So configured, in embodiments, the modular fluid path assemblies can be sterilized, a medicament can be filled in the container, and a stopper inserted in the container so that the pre-sterilized and pre-filled modular fluid path assemblies can have a closed container integrity (CCI) seal.

Details of a modular fluid path assembly in the form of an example prefilled syringe10are shown inFIG. 1. The syringe10includes a container in the form of a barrel12having an interior14, a needle16mounted to the barrel12through a needle hub17to be fluidly coupled to the interior14, a septum18, a cannula20, and a needle shield22. In this embodiment, the needle16provides the conduit and coupling portion of the fluid path, as set forth in more detail below. The needle16may be made of a more rigid material than the cannula20. For example, the needle16may be made of metal, whereas the cannula20may be made of plastic. Moreover, the relative flexibility of the cannula20may render the cannula20suitable for being left inside the patient for several minutes, hours, or days without substantial discomfort to the patient. The barrel12can be filled with a suitable medicament24and closed off by a stopper26inserted into the barrel12to sealingly engage an interior surface28of the barrel12. The septum18is sized and configured to sealingly engage the needle16and the cannula20and the cannula sealingly engages the needle shield22, so that the assembly with the stopper26is hermetically sealed.

As shown inFIG. 1, the cannula20has a tubular configuration with an elongate forward portion30and an annular rear portion32defining a cavity34with a rear facing opening36. The cannula rear portion32can further include an outwardly projecting flange38that extends around the opening36. The septum18has a bore40extending longitudinally therethrough and the cavity34is sized to receive the septum18. So configured, with the needle16extending through the bore40of the septum18, the septum18can be used to mount the cannula20to the needle16. In one form, the cavity34and septum18are sized so that the septum18is fully received within the cavity34so that a rear surface42of the septum18is generally coplanar with a rear surface44of the cannula20.

The needle shield22includes a body46defining an internal cavity48with a rearwardly facing opening50. The internal cavity48has a cylindrical forward portion52sized to receive a tip54of the needle16, a conical intermediate portion56, and a cylindrical rear portion60sized to receive the rear portion32of the cannula20.

One example form of a septum18is shown inFIG. 2includes one-way functionalities for the syringe10the provide anti-siphon and anti-reflux features. The septum18includes a cylindrical body61having a conical front surface62. As discussed above, the bore40of the septum18extends longitudinally through the body61. The bore40includes an open rear portion63having a first diameter and a closed forward portion64. For example, the closed forward portion64can be formed with a slit through the body61. The body61can be made of a resilient material so that it elastically deforms when the member is inserted therethrough and resiliently rebounds so that the body61closes the forward portion64of the bore40when no structure extends therethrough. This configuration allows the septum to act as a one-way valve because fluid entering the bore40through the open rear portion63can force the closed forward portion64open with pressure, while fluid being pressed against the conical front surface62forces the body61to hold the forward portion64tightly closed.

The syringe10can be assembled in a number of suitable ways. In a first approach, the septum18is pressed into the cavity34of the cannula20. The cannula20, with the septum18received therein, is then inserted into the internal cavity48of the needle shield22until the flange38abuts a rear surface62of the needle shield22. Thereafter, the needle16is inserted through the bore40of the septum18, through the elongate forward portion30of the cannula20, and into the forward portion52of the internal cavity48until the needle tip54is embedded into the needle shield body46sufficient for a CCI seal.

In a second approach, an expansion tube (not shown) can be inserted through the bore40of the septum18, the needle18slid into the expansion tube, and expansion tube extracted from the bore40so that the septum18is mounted on the needle18without the needle18damaging the bore40. The cannula20can then be placed on the needle18until the needle tip54extends through the forward portion30and the septum18is received within the cavity34of the rear portion32. The needle16, septum18, and cannula20is then inserted into the internal cavity44of the needle shield22until the needle tip54is embedded into the needle shield body46sufficient for a CCI seal.

Regardless of the assembly method, after the septum18and cannula20are mounted on the needle16and the needle16embedded in the shield body46, the syringe10can be sterilized, the barrel12can be filled with a desired amount of medicament24, and the stopper26can be inserted into the container interior14. So assembled, a fluid pathway65(seen inFIG. 1) for the syringe10extending from the stopper26within the container interior14to the tip54of the needle16has a CCI seal.

Turning now toFIG. 3, to preserve the positioning of the components of the syringe10and aid in storage, the syringe10can mounted within a carrier66having supports and/or recesses68that engage the syringe10to hold the components, including the barrel12, the needle16, the septum18, the cannula20, and the needle shield22, relatively stationary with respect to one another so that the seal is maintained. The recesses68can include an end wall70that abuts the needle shield22, a slot72that receives the outwardly projecting flange38of the cannula20, and a surface74to abut a wall of the barrel12. As shown, the carrier66can include a base portion76and a cover78removably, using fasteners, snap fit, etc., and/or pivotably attached to the base portion76. The supports and/or recesses68can be provided in the base portion76, the cover78, or both as desired.

In a first approach, the carrier66can be configured to couple to and support a portion of the barrel12. For example, as shown inFIG. 3, the carrier66can couple around the needle hub17of the barrel12and extend forwardly to support and hold the needle shield22and cannula20in position. To retain the carrier66on the needle hub17, the hub17can include a radially projecting collar80and the surface74of the recesses68can abut the collar80to lock the barrel12to the carrier66. Further, the carrier66can be sized to abut a main reservoir portion82of the barrel12when secured to the collar80. In a second approach, the carrier66can be sized with a diameter and length to fully receive the syringe10. The carrier66can have any desired configuration, such as cylindrical as shown, box-shaped, and so forth.

After the syringe10is secured within the carrier66, an array of carriers66can be placed in a tray84for sterilization as shown inFIG. 4. Advantageously, the carriers66can be loaded vertically in the tray84to maximize the number of carriers66that can fit in a given tray. The tray84can then be sealed with an Ethylene Oxide (EtO) permeable lid86and transported for EtO sterilization with the carriers66protecting the components of the syringe10from movement throughout the process. After sterilization, the tray84can then be allowed to degas.

The sterilized syringes10are then suitable for filling with the medicament24. Advantageously, the carrier66that couples to the container collar80with the main reservoir portion82of the barrel12extending rearwardly therefrom can be utilized for efficient filling of the syringe10. More specifically, the carrier66can be positioned within the tray84so that an open end88of the barrel12is exposed upwardly. The medicament24can then be deposited into the container interior14without removing the syringe10from the carrier66and without removing both from the tray84.

By one approach, the tray84can be transported to an aseptic filling line that removes the lid86, fills the syringe barrel12with a predetermined quantity of the medicament24, and then inserts the stopper26into the barrel interior14to provide a CCI seal for the syringe10. Further, after filling, the syringe10may be subjected to rotary particle inspection and the carrier66can continue to provide support to the components of the syringe10during the inspection to maintain the relative position and alignment of the components. Finally, the filled syringe10may be stored in the carrier66until needed for assembly into a drug delivery device, described in more detail below.

In one embodiment, the syringe10can be prepared for assembly into a drug delivery device. As shown inFIGS. 5 and 6, to fit the syringe10in the device, the needle16can be shaped into a bent configuration including a first bend88adjacent to the needle hub17and a second bend90adjacent to the septum18. So configured, a portion91of the needle16extending between the hub17and the second bend90provides a conduit for the fluid path. Further, the second bend90provides a coupling portion for the fluid path, described in more detail below.

In the illustrated form, the first bend88is a slightly acute or generally 90 degree bend α, for example between approximately 90 degrees and approximately 70 degrees, so that an intermediate portion92of the needle16extends away from the longitudinal axis L of the barrel12. So configured, the bent configuration can position the assembly of the septum18, cannula20, and needle shield22in an offset position with respect to the barrel12. As shown, the second bend90can have an acute bend β, such that when the assembly is oriented generally vertically with respect to a horizontal plane extending parallel to the longitudinal axis L of the barrel12, the intermediate portion92of the needle16extends upwardly at an angle δ with respect to the horizontal plane to the second bend90. Angle δ can be between about 30 degrees and about 60 degrees, and more specifically about 45 degrees. Additionally, as shown inFIG. 6, the intermediate portion92and the forward portion30reside in a common vertical plane that intersects the longitudinal axis L and the portion the needle16adjacent to the barrel12.

Bending the needle16can be performed by any suitable mechanism and method. In one approach, the cover78of the carrier66is removed. As shown inFIG. 3, the base portion76can include hinge and pivot mechanisms94aligned with portions of the needle16intended to be bent. Accordingly, when installation of the syringe10into a suitable device is desired, a user can remove the cover78and manipulate the base portion76to create the first and second bends88,90in the needle16while the base portion76holds the components of the syringe10in position relative to one another. The base portion76can include stops or guides96so that the manipulation of the base portion76creates the first and second bends88,90in desired angles and directions. In another approach, the syringe10may be removed from the carrier66and the first and second bends88,90performed with suitable fixtures or devices. In order to maintain the sterility and CCI of the syringe10during the bending process, care can be taken to avoid putting excessive loads on the needle hub17and displacing the needle16, septum18, or cannula20within the needle shield22.

As shown inFIGS. 7-9, the syringe10can be installed within an on-body injector drug delivery device100having a needle and cannula insertion mechanism (NIM)102and a plunger drive mechanism106. The plunger drive mechanism106includes a plunger rod132and a drive134operably coupled to the plunger rod132. The drive134may be in the form of a spring, pneumatic, hydraulic, or motor driven assembly. The components of the device100may be operated by a controller107, for example, in response to user actuation of an actuator105. The controller107can include a processor and a memory storing logic that is executable by the processor. More specifically, the memory may include one or more tangible non-transitory readable memories having logic (e.g., executable instructions) stored thereon, which instructions when executed by the processor may cause the at least one processor to carry out the actions that the controller is adapted to perform. Additionally, the controller107may include other circuitry for carrying out certain actions in accordance with the principles of the present disclosure.

In the form illustrated inFIGS. 8 and 9, the NIM102can be a scotch yoke mechanism that includes a needle sliding block108and a cannula sliding member124projecting forwardly from a housing110of the NIM102. The needle sliding block108and cannula sliding member124are operably coupled to a crank and drive (not shown) of the NIM102, as commonly configured, so that rotation of the crank drives linear movement of the block108and member124. The drive can be a spring, pneumatics, hydraulics, a motor, and/or a mechanical linkage.

The needle sliding block108includes a slot112shaped to receive the second bend90of the needle16therein during assembly of the pre-sterilized and pre-filled syringe10. The slot112can have a first opening114in a side116of the block108and a second opening118in a bottom120of the block108so that the needle16can extend into the block108from the side116and project out of the block108downwardly so that the needle tip54projects downwardly below the block108toward a bottom wall122of the device100.

The cannula sliding member124couples to the cannula20to drive the cannula20downwardly into a patient. The sliding member124includes an inwardly opening groove126configured to receive the flange38of the cannula20. The flange38can be generally rigid so that movement of the sliding member124drives movement of the cannula20. Further, the sliding member124is adapted to hold the cannula20in place when a user removes the needle shield22.

The bottom wall122includes a through opening128disposed adjacent to the NIM102and aligned with the needle shield22of the syringe10when the syringe10is installed in the device100. As shown, the needle shield22preferably projects through the opening128to a position where the needle shield22can be easily grasped by a user and removed prior to use.

In use, the NIM102is configured to insert the needle16and cannula20through the opening128and into subcutaneous tissue of a patient when activated. In one approach, the needle block108and the cannula member124can have separate couplings to the NIM102. In other approaches, the NIM102may drive both the block108and member124or can drive the block108with the block108driving movement of the member124.

As shown inFIG. 9, the cannula20is held in an inserted state during operation of the device100. By one approach, the cannula member124may hold the cannula20in place against the housing bottom wall122to form a water tight seal against fluid ingress into the device100. For example, the cannula20, cannula member124, and/or the bottom wall122can include elastic, adhesive, or force concentrating features to form the seal. In an alternative approach, the cannula member124may advance the cannula20into a locking mechanism in or on the bottom wall122. Further, cannula member124may be deflected away from the flange38during activation so that the flange38can fully engage the bottom wall122and any sealing features and/or locking mechanisms thereon.

The NIM102inserts the needle16to the designed depth in subcutaneous tissue and then retracts the needle16with the cannula20held in the inserted state so that the tip54of the needle16is disposed within a sharps protected location130of the cannula20and septum18. The sharps protected location130can preferably be within the open rear portion63of the septum bore40to maintain the one-way valve functionality of the septum18while keeping the needle tip54a sufficient distance within the septum18for a fluid tight seal. By one approach, the tip54of the needle16can be steeply beveled, such as approximately 23 degrees, and the needle16can be a 27-31 gauge needle, which can combine to minimize the overall height of the assembly while still being comfortable for the patient. Moreover, a needle16having a gauge in the range of 27-31 is sufficiently flexible to be rotated and bent, such as due to movement by the block108and edges of the first opening114acting on the needle16, to maintain a satisfactory hollow interior for drug delivery and resist crimping or fracturing. Further, due to the flexibility of the needle16, the needle16does not rotate inside of the hub17of the barrel12, such that the seal between the needle16and barrel12is not compromised by movement driven by the NIM102.

After the NIM102, inserts the needle16and cannula20and retracts the needle16, the device100can then operate the plunger drive mechanism106. Upon activation, the drive134of the plunger drive mechanism moves the plunger rod132longitudinally through the barrel12until the plunger rod132engages and pushes the stopper26through the barrel12to dispense the medicament24.

An alternative embodiment for a cannula assembly150is shown inFIG. 10. Instead of an outwardly projecting flange38as with the above embodiment, this assembly150includes a member152having a cylindrical configuration with a central bore154to receive the needle16therethrough and an outwardly facing annular channel or eyelets156. The member152is disposed rearwardly of a septum158and cannula160. A needle shield162receives the assembly150and can be configured similar to the needle shield22described above. The member152can be mounted to the needle16in a similar fashion as described above with respect to the septum18, and can form a portion of the septum158or be secured to the septum158and/or cannula160.

In this embodiment, the cannula member124can include rods or a flange configured to engage the channel156with the operation being similar to that described above. In this embodiment, however, the rods would not need to be deflected to seal the cannula160to the bottom wall122and may instead by used as a locking mechanism for a water tight seal.

Another modular fluid path assembly200is described with reference toFIGS. 11-26that includes a primary container202having a tubular body204, a stopper205disposed within the body204of the primary container202, a medicament206disposed within the primary container202forward of the stopper205, an end cap208mounted on an outlet210of the primary container202, a needle and cannula insertion hub212configured to couple to a NIM, and a conduit214extending between the end cap208and needle and cannula insertion hub212. The conduit214can be generally rigid, flexible, and combinations thereof. After assembly, sterilization, and filling, the modular fluid path assembly200, between the stopper205and an end of a needle233within the hub212, described below, has a CCI seal.

This embodiment allows the primary container202and components of the fluid path to be separated from a cannula and needle insertion mechanism (NIM)216discussed in more detail below. As such, the modular fluid path assembly200has a smaller footprint without the NIM216, enables more assemblies to fit within sterilization and fill lines, similar to that discussed above with respect toFIGS. 1-4.

Details of the needle and cannula insertion hub212are shown inFIGS. 11-16. The hub212includes a yoke body218having an outwardly extending port220connected to the conduit214, a cannula carrier222, and a needle shield224. The yoke body218is configured to snap fit to the NIM216. For this functionality, the yoke body218includes lateral wall portions226(see, e.g.,FIGS. 13 and 14) that fit within an aperture228(see, e.g.,FIGS. 12 and 14) in the NIM216and a rearwardly opening channel230(see, e.g.,FIG. 13) defined by a top wall232and bottom wall234. The NIM216further includes a slot opening229extending along a height of the aperture228to allow components of the insertion hub212to extend forwardly of the NIM216, such as the port220, cannula carrier222, and so forth. The generally T-shaped configuration of the yoke body218cooperate with the aperture228and slot opening229with a tongue-and-groove functionality to couple the components together. As shown inFIGS. 19-23, the hub212further includes a needle233mounted to the yoke body218and fluidly coupled to the port220and a cannula235mounted to the cannula carrier222.

The NIM216is a scotch yoke rotary to linear conversion device that includes a rolling scotch member236driving movement of the sliding yoke body218using a spring237. Pneumatics, hydraulics, motors, and mechanical linkages can alternatively be utilized. The scotch member236includes a disc-shaped crank238having a drive pin240projecting outwardly from a spaced radial position on the crank238. As shown inFIG. 13, the bottom wall234defining the channel230of the yoke body218includes a downwardly facing angled surface242that engages the drive pin240as the yoke body218is slid into the aperture228. The angled surface242radially displaces the drive pin240in opposition to the spring237until the drive pin240aligns with the channel230and the spring237drives the drive pin240into the channel230. The NIM216is held in this charged state until injection is desired.

If desired, the needle and cannula insertion hub212can be inserted into an assembly aid243that both protects the components of the insertion hub212and also facilitates assembly of the insertion hub212into the aperture228of the NIM216. As shown inFIG. 15, the assembly aid243includes an interior slot244sized to receive the insertion hub212. A resilient retention catch246projects over an open top248of the slot244, such that the catch246is deflected when the insertion hub212is inserted through the open top248. The catch246then resiliently returns to position over the open top248to prevent the insertion hub212from sliding out of the slot244.

The assembly aid243can then mount to the NIM216, such as by cooperating tabs and openings250, so that the slot244of the assembly aid243aligns with the aperture228of the NIM216. Then a user, or an automated process, need only slide the insertion hub212downward into the aperture228of the NIM216until the drive pin240is deflected and pivoted into the channel230to hold the insertion hub212in a storage position.

As shown inFIG. 16, the cannula carrier222includes arms252that project upwardly at an angle from a main portion254of the carrier222. With the insertion hub212mounted to the NIM216, the arms252are resiliently deflected inwardly by walls256running along edge portions258of the slot opening229. In the illustrated form, the arms252includes retention catches260that project inwardly to engage upper surfaces262of the yoke body218when the arms252are in the deflected position to thereby operably couple the carrier222to the yoke body218. Further, the walls256define locking tabs264at ends thereof so that as the NIM216drives the yoke body218and the carrier222downwardly, the arms252resiliently flex outwardly into the locking tabs264. As such, when the yoke body218is driven back upward by the NIM216, the locking tabs264prevent the carrier222moving upward.

With this configuration, the modular fluid path assembly200can be easily installed within a housing265of an on-body injector drug delivery device (OBI)266having the NIM216disposed therein as illustrated inFIG. 17. As with the above device100, the OBI266of this form can include a similarly configured plunger drive mechanism268, described in detail above, that is configured so that a drive269moves a plunger rod270to engage the stopper205of the assembly200when the assembly200is installed in the OBI266. The OBI266may further include a controller274configured to control operation of the components of the OBI266. The controller274can include a processor and a memory storing logic that is executable by the processor. More specifically, the memory may include one or more tangible non-transitory readable memories having logic (e.g., executable instructions) stored thereon, which instructions when executed by the processor may cause the at least one processor to carry out the actions that the controller is adapted to perform. Additionally, the controller274may include other circuitry for carrying out certain actions in accordance with the principles of the present disclosure.

Additional details of the insertion process are shown inFIGS. 18-23. When insertion is desired, such as in response to user actuation of an actuator272of the OBI266, the controller274of the OBI266can send a signal to the NIM216to operate a trigger276and release the spring237. In the illustrated form, the crank238includes a cut-out portion280having a stop surface282configured to engage the trigger276to hold the spring237in a charged state. To release the spring237, the trigger276is shifted out of engagement with the crank238.

When the spring237is released, the spring237drives rotation of the scotch member237. As such, the drive pin240rotates 180 degrees while sliding in the channel230of the yoke body218to drive the yoke body218to a fully inserted position. As shown, inFIGS. 19-21, this inserts both the needle233and cannula235into a patient. Additionally, in this position, the arms252of the carrier222lock into deflect into the locking tabs264to hold the cannula235in an inserted position. As shown inFIGS. 22 and 23, the spring237continues to drive rotation of the drive pin237such that the drive pin237completes a full 360 degree rotation. As the drive pin237starts rotating back upward, the drive pin237slides the yoke body218and the needle233upward.

To stop the injection operation, the NIM218can include a ball bearing284disposed in a track286a first portion288defined by the housing265and a second portion290defined by the scotch member236, where the first and second portions288,290are rotatable with respect to one another. The housing portion288of the track286includes first and second ends292,294and the scotch member portion290of the track286includes first and second ends296,298.

As shown inFIGS. 24-26, the ball bearing284starts at the first end292of the housing portion288of the track286. Thereafter, the spring237drives rotation of the scotch member236so that the housing and scotch member portions288,290of the track286align. Thereafter, the first end296of the scotch member portion290of the track286moves the ball bearing284along the housing portion288of the track286until the ball bearing284is trapped between the first end296of the scotch member portion290of the track286and the second end294of the housing portion288of the track286, effectively stopping rotation of the scotch member236and therefore the insertion operation. The track286can be sized to allow any desired amount of rotation, such as a full 360 degree rotation as described above.

Another modular fluid path assembly300is described with reference toFIGS. 27-33that includes a primary container302having a tubular body304, a stopper305disposed within the body304of the primary container302, a medicament306disposed within the primary container302forward of the stopper303, an end cap308mounted on an outlet310of the primary container302, a needle insertion hub312configured to couple to a NIM, and a conduit314extending between the end cap308and needle insertion hub312. The conduit314can be generally rigid, flexible, and combinations thereof. As discussed in more detail below, the fluid path assembly300can further include a needle shield313and a needle315mounted to the needle insertion hub312to be fluidly coupled to the conduit314. After assembly, sterilization, and filling, the modular fluid path assembly300, between the stopper303and an end of a needle315embedded within the needle shield313has a CCI seal.

This embodiment allows the primary container302and components of the fluid path to be separated from a needle insertion mechanism (NIM)316discussed in more detail below. As such, the modular fluid path assembly300has a smaller footprint without the NIM316, enabling more assemblies to fit within sterilization and fill lines, as discussed above.

The NIM316is a scotch yoke rotary to linear conversion device that includes a rolling scotch member318driving movement of a sliding yoke member320using a spring322. Pneumatics, hydraulics, motors, and mechanical linkages can alternatively be utilized. The scotch member318includes a disc-shaped crank324having a drive pin (not shown) projecting outwardly from a spaced radial position on the crank324. The yoke member320includes a horizontal channel326in which the pin slides to drive the yoke member320upward and downwardly through a full revolution. The NIM316is held with the spring322in a charged state until needle insertion is desired.

With the needle315being utilizes to inject the medicament306subcutaneously in a patient, the NIM316can have a two stage operation with a first stage inserting the needle315to a desired subcutaneous depth and a delayed second stage to retract the needle315after a predetermined amount of medicament306has been dispensed. In a first approach, as shown inFIGS. 29 and 30, the NIM316can include a first trigger328that shifts to release the scotch member318until it abuts a stop330generally halfway through a revolution with the needle315fully inserted. Then, as shown inFIGS. 31 and 32, the NIM316can include a second trigger332that includes muscle wire334coupled to the stop330and a base336, where the muscle wire334pivots the stop330out of engagement with the scotch member318so that scotch member318can complete a full revolution to retract the needle315. The delay between completing the full insertion of the needle and operating the second trigger332can correspond to the time needed to dispense a predetermined amount of medicament306. Of course, other configurations can be utilized, such as a channel with a dwell and other stop and release mechanisms.

Details of the needle insertion hub312and the connection to the NIM316are shown inFIGS. 28 and 29. The hub312includes a body338with a forwardly extending port340fluidly coupled to the conduit314and a rearwardly extending coupling portion342. The coupling portion342includes a T-shaped rib344and a top tab346. The yoke member320of the NIM316includes a corresponding aperture348with a slot opening350configured to sliding receive the T-shaped rib344. Further, as shown, with the rib344inserted into the aperture348, the top tab346projects over a top surface352of the yoke member320. As such, a fastener354, such as a screw as shown, can secure the needle insertion hub312to the yoke member320. The tab346and yoke member320may include openings356to threadingly receive the fastener354. Other securing mechanisms can be utilized, such as snap-fit, adhesive, and so forth.

With this configuration, the modular fluid path assembly300can be easily installed within a housing358of an on-body injector drug delivery device (OBI)360having the NIM316disposed therein as shown inFIG. 33. As with the above device100, the OBI360of this form can include a similarly configured plunger drive mechanism362, described in detail above, that includes a drive363that is configured to move a plunger rod364of the mechanism362to engage the stopper305of the assembly300when the assembly300is installed in the OBI360. The OBI360may further include a controller366configured to operate the components of the OBI360. The controller366can include a processor and a memory storing logic that is executable by the processor. More specifically, the memory may include one or more tangible non-transitory readable memories having logic (e.g., executable instructions) stored thereon, which instructions when executed by the processor may cause the at least one processor to carry out the actions that the controller is adapted to perform. Additionally, the controller366may include other circuitry for carrying out certain actions in accordance with the principles of the present disclosure. When operation of the OBI360is desired, such as in response to user actuation of an actuator368of the OBI266, the controller366of the OBI360can send a activation signal to the NIM316to sequentially operate the first and second trigger328,332.

The above description describes various assemblies, devices, and methods for use with a drug delivery device. It should be clear that the assemblies, drug delivery devices, or methods can further comprise use of a medicament listed below with the caveat that the following list should neither be considered to be all inclusive nor limiting. The medicament will be contained in a reservoir. In some instances, the reservoir is a primary container that is either filled or pre-filled for treatment with the medicament. The primary container can be a cartridge or a pre-filled syringe.

For example, the drug delivery device or more specifically the reservoir of the device may be filled 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 products, such as an erythropoiesis stimulating agent (ESA), which may be in a liquid or a lyophilized form. An ESA is any molecule that stimulates erythropoiesis, such as Epogen® (epoetin alfa), Aranesp® (darbepoetin alfa), Dynepo® (epoetin delta), Mircera® (methyoxy polyethylene glycol-epoetin beta), Hematide®, MRK-2578, INS-22, Retacrit® (epoetin zeta), Neorecormon® (epoetin beta), Silapo® (epoetin zeta), Binocrit® (epoetin alfa), epoetin alfa Hexal, Abseamed® (epoetin alfa), Ratioepo® (epoetin theta), Eporatio® (epoetin theta), Biopoin® (epoetin theta), epoetin alfa, epoetin beta, epoetin zeta, epoetin theta, and epoetin delta, as well as the molecules or variants or analogs thereof as disclosed in the following patents or patent applications, each of which is herein incorporated by reference in its entirety: U.S. Pat. Nos. 4,703,008; 5,441,868; 5,547,933; 5,618,698; 5,621,080; 5,756,349; 5,767,078; 5,773,569; 5,955,422; 5,986,047; 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.

Examples of other pharmaceutical products for use with the device may include, but are not limited to, antibodies such as Vectibix® (panitumumab), Xgeva™ (denosumab) and Prolia™ (denosamab); other biological agents such as Enbrel® (etanercept, TNF-receptor/Fc fusion protein, TNF blocker), Neulasta® (pegfilgrastim, pegylated filgastrim, 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 a therapeutic antibody, a polypeptide, a protein or other chemical, such as an iron, for example, ferumoxytol, iron dextrans, ferric glyconate, and iron sucrose. The pharmaceutical product may be in liquid form, or reconstituted from lyophilized form.

Among particular illustrative proteins are the specific proteins set forth below, including fusions, fragments, analogs, variants or derivatives thereof:

OPGL specific antibodies, peptibodies, and related proteins, and the like (also referred to as RANKL specific antibodies, peptibodies and the like), including fully humanized and human OPGL specific antibodies, particularly fully humanized monoclonal antibodies, including but not limited to the antibodies described in PCT Publication No. WO 03/002713, which is incorporated herein in its entirety as to OPGL specific antibodies and antibody related proteins, particularly those having the sequences set forth therein, particularly, but not limited to, those denoted therein: 9H7; 1862; 2D8; 2E11; 16E1; and 22B3, including the OPGL specific antibodies having either the light chain of SEQ ID NO:2 as set forth therein inFIG. 2and/or the heavy chain of SEQ ID NO:4, as set forth therein inFIG. 4, each of which is individually and specifically incorporated by reference herein in its entirety fully as disclosed in the foregoing publication;

Myostatin binding proteins, peptibodies, and related proteins, and the like, including myostatin specific peptibodies, particularly those described in U.S. Publication No. 2004/0181033 and PCT Publication No. WO 2004/058988, which are incorporated by reference herein in their entirety particularly in parts pertinent to myostatin specific peptibodies, including but not limited to peptibodies of the mTN8-19 family, including those of SEQ ID NOS:305-351, including TN8-19-1 through TN8-19-40, TN8-19 con1 and TN8-19 con2; peptibodies of 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 those of SEQ ID NOS:615-631, each of which is individually and specifically incorporated by reference herein in their entirety fully as disclosed in the foregoing publication;

IL-4 receptor specific antibodies, peptibodies, and related proteins, and the like, particularly those that inhibit activities mediated by binding of IL-4 and/or IL-13 to the receptor, including those described in PCT Publication No. WO 2005/047331 or PCT Application No. PCT/US2004/37242 and in U.S. Publication No. 2005/112694, which are incorporated herein by reference in their entirety particularly in parts pertinent to IL-4 receptor specific antibodies, particularly such antibodies as are described therein, particularly, and without limitation, those designated therein: 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 herein in its entirety fully as disclosed in the foregoing publication;

Interleukin 1-receptor 1 (“IL1-R1”) specific antibodies, peptibodies, and related proteins, and the like, including but not limited to those described in U.S. Publication No. 2004/097712, which is incorporated herein by reference in its entirety in parts pertinent to IL1-R1 specific binding proteins, monoclonal antibodies in particular, especially, without limitation, those designated therein: 15CA, 26F5, 27F2, 24E12, and 10H7, each of which is individually and specifically incorporated by reference herein in its entirety fully as disclosed in the aforementioned publication;

Ang2 specific antibodies, peptibodies, and related proteins, and the like, including but not limited to those described in PCT Publication No. WO 03/057134 and U.S. Publication No. 2003/0229023, each of which is incorporated herein by reference in its entirety particularly in parts pertinent to Ang2 specific antibodies and peptibodies and the like, especially those of sequences described therein and including but not limited to: 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 1K; Con4-L1 (N); Con4-L1C; TN-12-9 (N); C17 (N); TN8-8(N); TN8-14 (N); Con 1 (N), also including anti-Ang 2 antibodies and formulations such as those described in PCT Publication No. WO 2003/030833 which is incorporated herein by reference in its entirety as to the same, particularly Ab526; Ab528; Ab531; Ab533; Ab535; Ab536; Ab537; Ab540; Ab543; Ab544; Ab545; Ab546; A551; Ab553; Ab555; Ab558; Ab559; Ab565; AbF1AbFD; AbFE; AbFJ; AbFK; AbG1D4; AbGC1E8; AbH1C12; AbIA1; AbIF; AbIK, AbIP; and AbIP, in their various permutations as described therein, each of which is individually and specifically incorporated by reference herein in its entirety fully as disclosed in the foregoing publication;

NGF specific antibodies, peptibodies, and related proteins, and the like including, in particular, but not limited to those described in U.S. Publication No. 2005/0074821 and U.S. Pat. No. 6,919,426, which are incorporated herein by reference in their entirety particularly as to NGF-specific antibodies and related proteins in this regard, including in particular, but not limited to, the NGF-specific antibodies therein designated 4D4, 4G6, 6H9, 7H2, 14D10 and 14D11, each of which is individually and specifically incorporated by reference herein in its entirety fully as disclosed in the foregoing publication;

CD22 specific antibodies, peptibodies, and related proteins, and the like, such as those described in U.S. Pat. No. 5,789,554, which is incorporated herein by reference in its entirety as to CD22 specific antibodies and related proteins, particularly human CD22 specific antibodies, such as but not limited to humanized and fully human antibodies, including but not limited to humanized and fully human monoclonal antibodies, particularly including but not limited to human CD22 specific IgG antibodies, such as, for instance, a dimer of a human-mouse monoclonal hLL2 gamma-chain disulfide linked to a human-mouse monoclonal hLL2 kappa-chain, including, but limited to, for example, the human CD22 specific fully humanized antibody in Epratuzumab, CAS registry number 501423-23-0;

Also among non-limiting examples of anti-IGF-1R antibodies for use in the methods and compositions of the present invention are each and all of those described in:

(vii) U.S. Publication Nos. 2005/0136063 (published Jun. 23, 2005) and 2004/0018191 (published Jan. 29, 2004), including but not limited to antibody 19D12 and an antibody comprising a heavy chain encoded by a polynucleotide in plasmid 15H12/19D12HCA (γ4), deposited at the ATCC under number PTA-5214, and a light chain encoded by a polynucleotide in plasmid 15H12/19D12 LCF (κ), deposited at the ATCC under number PTA-5220, as described therein; and

(viii) U.S. Publication No. 2004/0202655 (published Oct. 14, 2004), including but not limited to 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, as described therein; each and all of which are herein incorporated by reference in their entireties, particularly as to the aforementioned antibodies, peptibodies, and related proteins and the like that target IGF-1 receptors;

B-7 related protein 1 specific antibodies, peptibodies, related proteins and the like (“B7RP-1,” also is referred to in the literature as B7H2, ICOSL, B7h, and CD275), particularly B7RP-specific fully human monoclonal IgG2 antibodies, particularly fully human IgG2 monoclonal antibody that binds an epitope in the first immunoglobulin-like domain of B7RP-1, especially those that inhibit the interaction of B7RP-1 with its natural receptor, ICOS, on activated T cells in particular, especially, in all of the foregoing regards, those disclosed in U.S. Publication No. 2008/0166352 and PCT Publication No. WO 07/011941, which are incorporated herein by reference in their entireties as to such antibodies and related proteins, including but not limited to antibodies designated therein as follow: 16H (having light chain variable and heavy chain variable sequences SEQ ID NO:1 and SEQ ID NO:7 respectively therein); 5D (having light chain variable and heavy chain variable sequences SEQ ID NO:2 and SEQ ID NO:9 respectively therein); 2H (having light chain variable and heavy chain variable sequences SEQ ID NO:3 and SEQ ID NO:10 respectively therein); 43H (having light chain variable and heavy chain variable sequences SEQ ID NO:6 and SEQ ID NO:14 respectively therein); 41H (having light chain variable and heavy chain variable sequences SEQ ID NO:5 and SEQ ID NO:13 respectively therein); and 15H (having light chain variable and heavy chain variable sequences SEQ ID NO:4 and SEQ ID NO:12 respectively therein), each of which is individually and specifically incorporated by reference herein in its entirety fully as disclosed in the foregoing publication;

IL-15 specific antibodies, peptibodies, and related proteins, and the like, such as, in particular, humanized monoclonal antibodies, particularly antibodies such as those disclosed in U.S. Publication Nos. 2003/0138421; 2003/023586; and 2004/0071702; and U.S. Pat. No. 7,153,507, each of which is incorporated herein by reference in its entirety as to IL-15 specific antibodies and related proteins, including peptibodies, including particularly, for instance, but not limited to, HuMax IL-15 antibodies and related proteins, such as, for instance, 14667;

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

TALL-1 specific antibodies, peptibodies, and the related proteins, and the like, and other TALL specific binding proteins, such as those described in U.S. Publication Nos. 2003/0195156 and 2006/0135431, each of which is incorporated herein by reference in its entirety as to TALL-1 binding proteins, particularly the molecules of Tables 4 and 5B, each of which is individually and specifically incorporated by reference herein in its entirety fully as disclosed in the foregoing publications;

Parathyroid hormone (“PTH”) specific antibodies, peptibodies, and related proteins, and the like, such as those described in U.S. Pat. No. 6,756,480, which is incorporated herein by reference in its entirety, particularly in parts pertinent to proteins that bind PTH;

Thrombopoietin receptor (“TPO-R”) specific antibodies, peptibodies, and related proteins, and the like, such as those described in U.S. Pat. No. 6,835,809, which is herein incorporated by reference in its entirety, particularly in parts pertinent to proteins that bind TPO-R;

Hepatocyte growth factor (“HGF”) specific antibodies, peptibodies, and related proteins, and the like, including those that target the HGF/SF:cMet axis (HGF/SF:c-Met), such as the fully human monoclonal antibodies that neutralize hepatocyte growth factor/scatter (HGF/SF) described in U.S. Publication No. 2005/0118643 and PCT Publication No. WO 2005/017107, huL2G7 described in U.S. Pat. No. 7,220,410 and OA-5d5 described in U.S. Pat. Nos. 5,686,292 and 6,468,529 and in PCT Publication No. WO 96/38557, each of which is incorporated herein by reference in its entirety, particularly in parts pertinent to proteins that bind HGF;

TRAIL-R2 specific antibodies, peptibodies, related proteins and the like, such as those described in U.S. Pat. No. 7,521,048, which is herein incorporated by reference in its entirety, particularly in parts pertinent to proteins that bind TRAIL-R2;

Activin A specific antibodies, peptibodies, related proteins, and the like, including but not limited to those described in U.S. Publication No. 2009/0234106, which is herein incorporated by reference in its entirety, particularly in parts pertinent to proteins that bind Activin A;

TGF-beta specific antibodies, peptibodies, related proteins, and the like, including but not limited to those described in U.S. Pat. No. 6,803,453 and U.S. Publication No. 2007/0110747, each of which is herein incorporated by reference in its entirety, particularly in parts pertinent to proteins that bind TGF-beta;

Amyloid-beta protein specific antibodies, peptibodies, related proteins, and the like, including but not limited to those described in PCT Publication No. WO 2006/081171, which is herein incorporated by reference in its entirety, particularly in parts pertinent to proteins that bind amyloid-beta proteins. One antibody contemplated 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 foregoing publication;

c-Kit specific antibodies, peptibodies, related proteins, and the like, including but not limited to those described in U.S. Publication No. 2007/0253951, which is incorporated herein by reference in its entirety, particularly in parts pertinent to proteins that bind c-Kit and/or other stem cell factor receptors;

OX40L specific antibodies, peptibodies, related proteins, and the like, including but not limited to those described in U.S. Publication No. 2006/0002929, which is incorporated herein by reference in its entirety, particularly in parts pertinent to proteins that bind OX40L and/or other ligands of the OX40 receptor; and

Also included can be a sclerostin antibody, such as but not limited to romosozumab, blosozumab, or BPS 804 (Novartis). Further included can be therapeutics such as rilotumumab, bixalomer, trebananib, ganitumab, conatumumab, motesanib diphosphate, brodalumab, vidupiprant, panitumumab, denosumab, NPLATE, PROLIA, VECTIBIX or XGEVA. Additionally, included in the device can be a monoclonal antibody (IgG) that binds human Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9). Such PCSK9 specific antibodies include, but are not limited to, Repatha® (evolocumab) and Praluent® (alirocumab), as well as molecules, variants, analogs or derivatives thereof as disclosed in the following patents or patent applications, each of which is herein incorporated by reference in its entirety for all purposes: U.S. Pat. No. 8,030,547, U.S. Publication No. 2013/0064825, WO2008/057457, WO2008/057458, WO2008/057459, WO2008/063382, WO2008/133647, WO2009/100297, WO2009/100318, WO2011/037791, WO2011/053759, WO2011/053783, WO2008/125623, WO2011/072263, WO2009/055783, WO2012/0544438, WO2010/029513, WO2011/111007, WO2010/077854, WO2012/088313, WO2012/101251, WO2012/101252, WO2012/101253, WO2012/109530, and WO2001/031007.

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 or and is present in the extracellular matrix; it inhibits all the major cartilage-degrading metalloproteases, and may play a role in 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 a DNA that encodes TIMP-3, are disclosed in U.S. Pat. No. 6,562,596, issued May 13, 2003, the disclosure of which is incorporated by reference herein. Description of TIMP mutations can be found in U.S. Publication No. 2014/0274874 and PCT Publication No. WO 2014/152012.

Also included are antagonistic antibodies for human calcitonin gene-related peptide (CGRP) receptor and bispecific antibody molecule that target the CGRP receptor and other headache targets. Further information concerning these molecules can be found in PCT Application No. WO 2010/075238.

Additionally, bispecific T cell engager (BiTE®) antibodies, e.g. BLINCYTO® (blinatumomab), can be used in the device. Alternatively, included can be an APJ large molecule agonist e.g., apelin or analogues thereof in the device. Information relating to such molecules can be found in PCT Publication No. WO 2014/099984.

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

Although the modular fluid path assemblies, drug delivery devices, methods, and components thereof, have been described in terms of exemplary embodiments, they are not limited thereto. The detailed description is to be construed as exemplary only and does not describe every possible embodiment of the invention because describing every possible embodiment would be impractical, if not impossible. Numerous alternative embodiments could be implemented, using either current technology or technology developed after the filing date of this patent that would still fall within the scope of the claims defining the invention. For example, while the modular fluid path assemblies are described herein with reference to on-body injector drug delivery devices, the assemblies can also be utilized in other drug delivery devices, such as autoinjector drug delivery devices.

It should be understood that the legal scope of the invention is defined by the words of the claims set forth at the end of this patent. The appended claims should be construed broadly to include other variants and embodiments of same, which may be made by those skilled in the art without departing from the scope and range of equivalents of the modular fluid path assemblies, drug delivery devices, methods, and their components.