Patent ID: 12201817

The exemplifications set out herein illustrate exemplary aspects of the disclosure, and such exemplifications are not to be construed as limiting the scope of the disclosure in any manner.

DETAILED DESCRIPTION

The following description is provided to enable those skilled in the art to make and use the described embodiments contemplated for carrying out the invention. Various modifications, equivalents, variations, and alternatives, however, will remain readily apparent to those skilled in the art. Any and all such modifications, variations, equivalents, and alternatives are intended to fall within the spirit and scope of the present invention.

For purposes of the description hereinafter, the terms “upper”, “lower”, “right”, “left”, “vertical”, “horizontal”, “top”, “bottom”, “lateral”, “longitudinal”, and derivatives thereof shall relate to the invention as it is oriented in the drawing figures. However, it is to be understood that the invention may assume various alternative variations, except where expressly specified to the contrary. It is also to be understood that the specific devices illustrated in the attached drawings, and described in the following specification, are simply exemplary embodiments of the invention. Hence, specific dimensions and other physical characteristics related to the embodiments disclosed herein are not to be considered as limiting.

Referring toFIGS.1-16, a drug delivery system10according to one aspect of the present invention includes a drive assembly12, a container14, a valve assembly16, and a needle actuator assembly18. The drive assembly12, the container14, the valve assembly16, and the needle actuator assembly18are at least partially positioned within a housing20. The housing20includes a top portion22and a bottom portion24, although other suitable arrangements for the housing20may be utilized. In one aspect, the drug delivery system10is an injector device configured to be worn or secured to a user and to deliver a predetermined dose of a medicament provided within the container14via injection into the user. The system10may be utilized to deliver a “bolus injection” where a medicament is delivered within a set time period. The medicament may be delivered over a time period of up to 45 minutes, although other suitable injection amounts and durations may be utilized. A bolus administration or delivery can be carried out with rate controlling or have no specific rate controlling. The system10may deliver the medicament at a fixed pressure to the user with the rate being variable. The general operation of the system10is described below in reference toFIGS.1-16with the specifics of the drive assembly12, needle actuator assembly18, and other features of the system10, discussed below in connection withFIGS.17-93.

Referring again toFIGS.1-16, the system10is configured to operate through the engagement of an actuation button26by a user, which results in a needle28of the needle assembly18piercing the skin of a user, the actuation of the drive assembly12to place the needle28in fluid communication with the container14and to expel fluid or medicament from the container14, and the withdrawal of the needle28after injection of the medicament is complete. The general operation of a drug delivery system is shown and described in International Publication Nos. 2013/155153 and 2014/179774, which are hereby incorporated by reference in their entirety. The housing20of the system10includes an indicator window30for viewing an indicator arrangement32configured to provide an indication to a user on the status of the system10and a container window31for viewing the container14. The indicator window30may be a magnifying lens for providing a clear view of the indicator arrangement32. The indicator arrangement32moves along with the needle actuator assembly18during use of the system10to indicate a pre-use status, use status, and post-use status of the system10. The indicator arrangement32provides visual indicia regarding the status, although other suitable indicia, such an auditory or tactile, may be provided as an alternative or additional indicia.

Referring toFIGS.4-6, during a pre-use position of the system10, the container14is spaced from the drive assembly12and the valve assembly16and the needle28is in a retracted position. During the initial actuation of the system10, as shown inFIGS.7-9, the drive assembly12engages the container14to move the container14toward the valve assembly16, which is configured to pierce a closure36of the container14and place the medicament within the container14in fluid communication with the needle28via a tube (not shown) or other suitable arrangement. The drive assembly12is configured to engage a stopper34of the container14, which will initially move the entire container14into engagement with the valve assembly16due to the incompressibility of the fluid or medicament within the container14. The initial actuation of the system10is caused by engagement of the actuation button26by a user, which releases the needle actuator assembly18and the drive assembly12as discussed below in more detail. During the initial actuation, the needle28is still in the retracted position and about to move to the extended position to inject the user of the system10.

In the use position of the system10, as shown inFIGS.10-12, the needle28is in the extended position at least partially outside of the housing20with the drive assembly12moving the stopper34within the container14to deliver the medicament from the container14, through the needle28, and to the user. In the use position, the valve assembly16has already pierced a closure36of the container14to place the container14in fluid communication with the needle28, which also allows the drive assembly12to move the stopper34relative to the container14since fluid is able to be dispensed from the container14. At the post-use position of the system10, shown inFIGS.13-15A, the needle28is in the retracted position and engaged with a pad38to seal the needle28and prevent any residual flow of fluid or medicament from the container14. The container14and valve assembly16may be the container14and valve assembly16shown and described in International Publication No. WO 2015/081337, which is hereby incorporated by reference in its entirety.

Referring toFIGS.15A-15C, the pad38is biased into the pad as the needle actuator body96moves from the use position to the post-use position. In particular, the pad38is received by a pad arm122having a cam surface124that cooperates with a cam track126on the bottom portion24of the housing20. The pad arm122is connected to the needle actuator body96via a torsion bar128. The cam surface124is configured to engage the cam track126to deflect the pad arm122downwards thereby allowing the pad38to pass beneath the needle28before being biased upwards into the needle28. The torsion bar128allows the pad arm122to twist about a pivot of the needle actuator body96. The pad38may be press-fit into an opening of the pad arm122, although other suitable arrangements for securing the pad38may be utilized.

Referring toFIGS.1-33, the drive assembly12according to one aspect of the present invention is shown. As discussed above, the drive assembly12is configured to move the container14to pierce the closure36of the container14and also to move the stopper34within the container14to dispense fluid or medicament from the container14.

For manufacturing purposes, using one size for a medicament container14is often desirable, even if multiple fill volumes or dosages are contemplated for use with the container14. In such cases, when medicament containers are filled, the differing fill volumes result in different positions of the stopper34. To accommodate such different stopper34positions, as well as accommodate manufacturing differences of the stoppers34, aspects of the present invention include a bespoke or custom spacer or spacer assembly40disposed in a proximal end of the container14, proximal to the stopper34. The custom spacer or spacer assembly40is selected from a plurality of different size spacers or spacer assemblies40to occupy space from a proximal end of the stopper34to a proximal end of the container14. In other words, the custom spacer or spacer assembly40provides an option that allows dispensing of a range of manufacturer-set pre-defined fill volumes by selection of different spacers or spacer assemblies40, and reduces or eliminates the need for assembly configuration operations. The size of the custom spacer or spacer assembly40can be employed to account for under-filled volumes of the container14, and provide a consistent bearing surface at the proximal end of the container14.

The drive assembly12shown inFIGS.17-33is configured to engage and cooperate with a spacer assembly40received by the stopper34of the container14. The spacer assembly40includes a spacer42and a spacer holder44. The spacer holder44is received by the stopper34and the spacer42is received by the spacer holder44. The spacer holder44includes a first threaded portion46that engages a corresponding threaded portion of the stopper34, although other suitable arrangements may be utilized. The spacer42also includes a threaded portion48that engages a corresponding second threaded portion50of the spacer holder44for securing the spacer42to the spacer holder44, although other suitable arrangements may be utilized. The drive assembly12is configured to dispense a range of pre-determined fill volumes of the container14while maintaining the functional features of the system10described above, including, but not limited to, retraction of the needle28after the end of the dose and providing an indication of the status of the system10while also minimizing abrupt engagement of the stopper34by the drive assembly12. A discussed above, the drive assembly12is configured to dispense a plurality of discrete fill volume ranges by utilizing a plurality of sizes of the spacers42. In one aspect, twelve fill volume ranges and twelve spacer42sizes are provided.

Referring toFIGS.17-26, the drive assembly12includes a first plunger member52, a second plunger member54received by the first plunger member52, a first biasing member56, a second biasing member58, a plunger actuation member60, and an index member62. The first plunger member52is moveable from a pre-use position (shown inFIG.18), to a use position (shown inFIG.19), to a post-use position (shown inFIG.20) with the first plunger member52configured to engage the spacer assembly40and move the stopper34within the container14to dispense medicament from the container14. The first plunger member52is configured to move axially. The second plunger member54and the first plunger member52form a telescoping arrangement with the second plunger54configured to move axially after the first plunger member52moves a predetermined axial distance. The movement of the first and second plunger members52,54is provided by the first and second biasing members56,58, which are compression springs, although other suitable arrangements for the biasing members56,58may be utilized.

The first biasing member56is received by the second plunger member54and is constrained between the plunger actuation member60(and index member62) and a first spring seat64of the second plunger member54. The second biasing member58is positioned radially inward from the first biasing member56and received by the second plunger member54. The second biasing member58is constrained between a second spring seat66of the second plunger member54and the first plunger member52. The second biasing member58is configured to bias the first plunger52member towards the container14from the pre-use position, to the use position, and to the post-use position. The first biasing member56is configured to bias the second plunger member54towards the container14, which, in turn, biases the first plunger member52towards the container14from the pre-use position, to the use position, and to the post-use position. More specifically, the second biasing member58is configured to drive the first plunger member52against the spacer assembly40or stopper34to move the container14into engagement the valve assembly16thereby piercing the closure36of the container14and placing the container14in fluid communication with the needle28. The first biasing member56is configured to move the stopper34within the container14to dispense the medicament within the container14. The second biasing member58has a different spring constant than the first biasing member56. In particular, the second biasing58member is stiffer than the first biasing member56to provide a high force for piercing the closure36of the container14while the first biasing member56provides a lower force for dispensing as appropriate for the viscosity of the fluid or medicament within the container14.

Referring again toFIGS.17-26, the plunger actuation member60has an annular portion68and a spindle portion70. The plunger actuation member60is rotationally moveable relative to the first plunger member52between a first rotational position and a second rotational position spaced from the first rotational position. The first rotational position may be 15 degrees from the second rotational position, although other suitable positions may be utilized. The annular portion68includes a drive surface72including a plurality of gears74, although other suitable arrangements may be utilized for the drive surface72. The spindle portion70includes an actuator locking surface76configured for engagement and release from a plunger locking surface78of the first plunger member52. The plunger locking surface78includes a plurality of projections80configured to be received by a plurality of slots or cutouts81defined by the actuator locking surface76.

As shown inFIGS.18and23, in the first rotational position of the plunger actuation member60, the plurality of projections80and the plurality of slots or cutouts81are out of alignment such that the plunger actuation member80is engaged with the first plunger member52to prevent movement of the first and second plunger members52,54with the first and second biasing members56,58biasing the first and second plunger members52,54away from the plunger actuation member60. As shown inFIGS.19and24, in the second rotational position of the plunger actuation member60, the plurality of projections80and the plurality of slots or cutouts81are aligned with each other such that the plunger actuation member60is disengaged with the first plunger member52to allow movement of the first and second plunger members52,54thereby starting the dispensing process from the container14.

Referring toFIGS.7and33, the drive surface72of the plunger actuation member60is configured to be engaged by a portion of the needle actuator assembly18. After engagement of the actuator button26and release of the needle actuator assembly18, which is discussed in more detail below, the needle actuator assembly18moves within the housing20from the pre-use position, to the use position, and to the post-use position. During the initial movement of the needle actuator assembly18, a portion of the needle actuator assembly18engages the drive surface72of the plunger actuation member60to move the plunger actuation member60from the first rotational position to the second rotational position. As shown inFIG.33, an angled blade portion82of the needle actuator assembly18engages the drive surface72of the plunger actuation member60to cause rotation of the plunger actuation member60.

Referring toFIGS.11,13, and26, the second plunger member52includes a plurality of coded projections84with a preselected one of the plurality of coded projections84configured to engage a restriction member86of the system10. As discussed in more detail below, the restriction member86cooperates with the needle actuation assembly18and restricts movement of the needle actuator assembly18from the use position to the post-use position until a predetermined end-of-dose position of the stopper34is reached. In one aspect, the restriction member86is configured to restrict axial movement of the needle actuation assembly18from the use position through engagement between the restriction member86and a portion of the needle actuation assembly18. Such engagement between the restriction member86and the needle actuation assembly18is released by rotation of the restriction member86when the stopper34reaches the end-of-dose position. During the use position of the needle actuator assembly18, the restriction member86is biased in a rotational direction with the rotation of the restriction member86being prevented through engagement between the restriction member86and one of the plurality of coded projections84of the second plunger member54. The plurality of coded projections84may be axial ribs of varying length, although other suitable arrangements may be utilized. Each coded projection84defines a point at which the restriction member86is able to rotate thereby releasing the needle actuator assembly18. The smooth portion of the second plunger member52may also provide a further “code” for determining when the system10transitions to the end-of-dose position.

As discussed above, the indicator arrangement32moves with different portions of the indicator arrangement32visible through the indicator window30as the system10moves from the pre-use, use, and post-use or end-of-dose positions. More specifically, the indicator arrangement32engages a portion of the restriction member86and moves along with the restriction member86through the various stages of the system10to provide an indication to the user regarding the state of the system10.

During assembly of the system10, the dosage of the container14is matched with a specific spacer42having a set length and a corresponding one of the plurality of coded projections84is aligned with the restriction member86. Accordingly, as discussed above, the container14may be provided with a plurality of dosage volumes with each volume corresponding to a specific spacer42and coded projection84. Thus, even for different dosage volumes, the system10is configured to inject the needle28into the user to deliver a dose of medicament from the container14, retract the needle28after the end of the dose, and provide an indication of the status of the system10while minimizing abrupt engagement of the stopper34by the drive assembly12. In particular, the size of the stopper34may be selected to minimize the distance between the first plunger member52and the spacer assembly40and does not require the use of damping.

Referring toFIGS.27-33, a drive assembly12A according to a further aspect of the present invention is shown. The drive assembly12A shown inFIGS.27-33is similar to and operates in the same manner as the drive assembly12shown inFIGS.17-26and described above. In the drive assembly ofFIGS.27-33, however, the first plunger member52is received by the second plunger member54and extends from the second plunger member54during axial movement from the pre-use position to the use position. Further, the first plunger member52includes an extension portion88configured to engage the second plunger member54after the first plunger member52moves predetermined axial distance such that the first and second plunger members52,54move together. The first and second biasing members56,58engage and act on the first and second plunger members52,54in the same manner as the drive assembly12ofFIGS.17-26.

Referring toFIGS.27-32, the index member62is positioned about the first and second plunger members52,54and includes a plurality of ratchet teeth90configured to engage a flexible tab92positioned on the bottom portion24of the housing20. When the drive assembly12,12A is installed into the bottom portion24of the housing20, the engagement of the ratchet teeth90of the index member62with the flexible tab92of the housing20provide a one-way rotation of the index member62. The index member62is configured to rotate to align one of the coded projections84of the second plunger member52with the restriction member86based on the dosage volume and spacer42size as discussed above. The index member62may provide the drive assembly12,12A with 24 rotational positions of which 12 may have unique dose values associated with them.

Referring toFIGS.1-16and34-40B, the needle actuator assembly18according to one aspect of the present invention is shown. The needle actuator assembly18includes a needle actuator body96having guide surfaces98, a needle shuttle102having cam surfaces104, and the needle28received by the needle shuttle102and configured to be in fluid communication with the container14as discussed above. The needle actuator body96is generally rectangular with the guide surfaces98protruding radially inward. The needle shuttle102is received within the needle actuator body96. As described above, the needle actuator body96is moveable within the housing20from a pre-use position (shown inFIGS.4-6), an initial actuation position (FIGS.7-9), a use position (FIGS.10-12), and a post-use position (FIGS.13-15A). The needle actuator body96is biased from the pre-use position to the post-use position via an extension spring106, although other suitable biasing arrangements may be utilized. The needle actuator body96is released and free to move from the pre-use position to the use position upon engagement of the actuator button26, which is discussed in more detail below. The needle actuator body96moves from the use position to the post-use position after rotation of the restriction member86as discussed above in connection withFIGS.17-33.

Referring toFIGS.34-40B, the needle shuttle102is moveable along a vertical axis between a retracted position where the needle28is positioned within the housing20and an extended position where at least a portion of the needle28extends out of the housing20. The needle shuttle102is configured to move between the retracted position and the extended position through engagement between the guide surfaces98of the needle actuator96and the cam surfaces104of the needle shuttle102. The cam surfaces104are provided by first and second cam members108,110, with the first cam member108spaced from the second cam member110. The housing20includes a guide post112having recess configured to receive a T-shaped projection114on the needle shuttle102, although other shapes and configurations may be utilized for the guide post112and T-shaped projection114. The needle shuttle102moves along the guide post112between the retracted and extended positions. The guide post112is linear and extends about perpendicular from the housing20, although other suitable arrangements may be utilized. The guide surfaces98of the needle actuator body86are non-linear and each include a first side116and a second side118positioned opposite from the first side116.

As discussed below, the guide surfaces98of the needle actuator body96cooperate with the cam members108,110of the needle shuttle102to move the needle shuttle102vertically between the retracted and extended positions as the needle actuator body96moves axially from the pre-use position to the post-use position. The needle shuttle102also includes a shuttle biasing member120configured to engage the housing20or the actuator button26. In particular, the shuttle biasing member120engages the housing20or actuator button26and provides a biasing force when the needle actuator body96is transitioning from the use position to the post-use position. When the needle actuator body96is fully transitioned to the post-use position, the cam members108,110of the needle shuttle102are disengaged from the guide surfaces98of the needle actuator body96and the shuttle biasing member120biases the needle shuttle102downward such that the needle28engages the pad38, as discussed above. As discussed above in connection withFIGS.1-16, however, the pad38may also be biased into the needle28rather than biasing the needle shuttle102downwards via the shuttle biasing member120. The needle actuator body96may interact with the actuator button26to prevent the actuator button26from popping back up until the post-use position is reached, which is discussed below in more detail.

Referring toFIGS.37A-40B, in a pre-use position (FIG.37A), the needle shuttle102is in the retracted position with the cam members108,110spaced from the guide surface98of the needle actuator body96. As the needle actuator body96moves to the use position (FIGS.37B and38A), the second cam member110of the needle shuttle102engages the second side118of the guide surfaces98to move the needle shuttle102from the retracted position to the extended position. During the transition from the use position to the post-use position of the needle actuator body96(FIG.37C), the first cam member108of the needle shuttle102is engaged with the first side116of the guide surfaces98to move the needle shuttle102from the second position to the first position. After the needle actuator body96is fully transitioned to the post-use position (FIGS.37D and38B), the shuttle biasing member120biases the needle shuttle102downward as the cam members108,110disengage from the guide surfaces98of the needle actuator body96with the needle28engaging the pad38. The transition of the needle actuator body96and the corresponding position of the needle shuttle102is also shown inFIGS.39-40B. The interaction between the actuator button26and the needle actuator body96is discussed in detail in connection withFIGS.65A-67. Referring toFIGS.41-64, a drug delivery system200according to a further embodiment is shown. The system200includes a housing202having an upper housing204and a lower housing206. The housing has a proximal end205and a distal end207. The upper housing204has a status view port208so that a user can view the operating status of the system200. The system200also includes a valve assembly212, a tube214fluidly connecting the valve assembly214with a patient needle215that is disposed in a proximal end of a needle arm216. A spring218biases a needle actuator220distally.

As shown inFIGS.42-46, the system200additionally includes a container or medicament container222with a stopper224movably disposed therein, although the stopper224is omitted from various figures to aid clarity. Preferably, the distal end of the medicament container222has a septum assembly228that is spaced apart from the valve assembly212prior to actuation of the device222, as best shown inFIG.47.

As shown inFIGS.45-47, the spacer226is selected from a plurality of different size spacers226to occupy space from a proximal end of the stopper224to a proximal end of the container222. The spacer226is substantially flush with the proximal end of the container222. Additionally, the spacer226has a “top hat” shape, which includes a central column230and a distal flange232, as best shown inFIG.45.

Returning toFIGS.44-47, the system200also includes a drive assembly234for displacing the container222distally to establish the fluid connection between the container222and the patient needle215, as well as dispensing the medicament from the container222. In more detail, the drive assembly234includes an inner spring236disposed within a central plunger238, an outer plunger240, an outer spring242disposed between the central plunger238and the outer plunger240, a telescoping member244, and a release gate246.

Preferably, the inner spring236has a greater spring constant than the outer spring242, and is therefore, stronger or stiffer than the outer spring242. The inner spring236is disposed inside the central plunger238, and pushes between a spring flange248in the lower housing (best shown inFIG.46) and the central plunger238, which bears directly on the proximal end of the spacer226subsequent to device activation. The outer spring242is disposed inside outer plunger240, and pushes between a proximal external flange250of the central plunger238and a distal internal flange252of the outer plunger240. Thus, the inner and outer springs236and242are nested, and can provide a more compact drive assembly (and thus, a more compact system200) than employing a single spring.

According to one aspect, the inner spring236acts only to displace the container222to establish the fluid connection with the patient needle215, and the outer spring242acts only to subsequently dispense the medicament from the container222. According to another aspect, the inner spring236acts to displace the container222to establish the fluid connection with the patient needle215, and also acts to begin dispensing the medicament from the container222, and the outer spring242acts to complete dispensing the medicament. In a further aspect, the inner spring236causes the initial piercing of the container222with the outer spring242completing the piercing and dispensing of the medicament from the container222.

As shown inFIGS.44-47, and as subsequently described in greater detail, the outer plunger240includes a pair of proximal flanges or feet254that each have a slanted surface that interacts with a corresponding slanted surface (or surfaces) on the release gate to retain and subsequently release the power module subsequent to actuation of the device200.

As best shown inFIGS.46and47, as initially assembled, the container222is disposed in clearance from the drive assembly234and the valve assembly212. A lateral flange256on the needle actuator220axially retains the medicament container222, and the needle actuator220prevents the release gate246from displacing laterally. According to one embodiment, a spring (not shown) biases the needle actuator220distally, but the actuation button210(and/or its associated assembly) prevents distal displacement of the needle actuator220prior to actuation of the device200. A status bar258is disposed on the needle actuator220, and has a top surface that is visible through the status view port208. According to one embodiment, the top surface of the status bar has a plurality of colors or patterns, and when the device is in a pre-actuated state, a first color or pattern, such as yellow, is visible through the status view port208.

FIGS.48-52are top views of the system200illustrating the operation of events at and subsequent to actuation of the system200. InFIG.47, a user slides the actuation button210proximally and then displaces the button210vertically into the housing202, thereby freeing the needle actuator220to displace distally under the influence of the spring (omitted for clarity). As shown inFIG.49, as the needle actuator displaces distally, tracks260on the needle actuator220interact with lateral bosses262on the needle arm216to insert the patient needle215. Preferably at this stage, the proximal end of the needle actuator220has not yet cleared the release gate246, and thus, the drive assembly234has not yet been released. But the lateral flange256has displaced distally and therefore, the container222is unrestrained.

Subsequently, as shown inFIGS.50and51, with continued distal displacement, the proximal end of the needle actuator220clears the release gate246(thereby releasing the drive assembly234). The needle actuator220comes to temporarily rest against a feature on a rotatable release flipper264, driving the release flipper264against an outrigger266(best shown inFIGS.44and59) of the telescoping member244. The needle actuator220remains in this position until the medicament has been dispensed. In this position, preferably, a second color or pattern of the status bar258, such as green, is visible through the status view port208.

At this stage, the force of the springs236and242and the interaction of the angled surfaces of the proximal flanges or feet254with the corresponding angled surface (or surfaces) on the release gate246causes the release gate246to displace laterally, thereby freeing the outer plunger240from restraining interaction with the release gate246. Up to this point, the outer plunger240has been restraining the central plunger238.

Referring toFIGS.52and53(the inner spring236is omitted fromFIG.52for clarity), the stiff inner spring236distally drives central plunger238to contact the spacer226. Because the medicament container222is filled with a substantially incompressible fluid, the continued distal displacement of the central plunger238distally displaces the spacer226, the stopper224, and the container222relative to the housing202. This distal displacement causes the septum assembly228to be pierced by the valve assembly212, establishing fluid communication between the container222and the patient needle215. The central plunger238travels distally until its proximal external flange250(best shown inFIG.59) contacts a flange on the lower housing206, thereby limiting the “piercing travel.” Preferably, another flange on the lower housing206and/or the lateral flange256of the needle actuator220limits distal travel of the container222.

Subsequently, because the inner spring236can no longer distally displace the central plunger238, the lighter outer spring242distally displaces the outer plunger240relative to the central plunger238to contact the distal flange232of the spacer226, as shown inFIGS.54and55. As subsequently described in greater detail, preferably, the contact between the outer plunger240and the spacer226is damped to minimize the impact force. Further expansion of the outer spring242distally displaces the outer plunger240to dispense the medicament.

As shown inFIGS.56and57, as the outer spring242continues to expand and distally displace the outer plunger240, upon a predetermined distal displacement of the outer plunger240relative to the telescoping member244, an external feature or flange268of the outer plunger240interacts with an internal distal feature or flange270of the telescoping member244to “pick up” the telescoping member244. This ensures that further distal displacement of the outer plunger240causes corresponding distal displacement of the telescoping member244. This paired distal displacement continues until the end of the medicament dispensing.

As previously noted, the outrigger266is disposed on the telescoping member244. The axial length of the outrigger and the distal travel of the telescoping member144controls the timing of the disengagement of the outrigger266with the release flipper264. As shown inFIGS.58and59, at the end of medicament dispensing, the proximal end of the outrigger266bypasses the release flipper264. This allows the release flipper264to rotate out of engagement with the needle actuator220(FIG.60), and allows the needle actuator220to continue its distal displacement and withdraw the patient needle215(FIG.61). At this stage, another color or pattern of the status bar258, such as red, is visible through the status view port208, signifying that the device200has completed operation.

As previously noted, the contact between the outer plunger240and the spacer226, as illustrated inFIGS.62and63, is preferably damped to minimize the impact force. The highest level of energy dissipation is desirable for under-filled syringes containing viscous fluid, as the outer spring242will be stiffer to provide desired dispense rates. The lowest level of energy dissipation is desirable for maximum-filled syringes containing low-viscosity fluid, as the outer spring can be less stiff to provide desired dispense rates. Various methods can be employed to adjust damping levels, such as air damping, or closed-cell foam damping.

As another method of damping the impact force,FIG.64illustrates an embodiment of a spacer226in which one or more axial interface ribs272are circumferentially arrayed about the central column230of the spacer226. In this embodiment, the outer plunger240must drive past the interference ribs272, which provide frictional resistance to the distal displacement of the outer plunger240relative to the spacer226. The frictional force created by the interference between interference ribs272and the outer plunger240is independent of plunger speed. Preferably, the frictional force does not exceed the minimum dispense spring load, to avoid stalling weaker springs. The interference can be tuned to give the desired level of frictional resistance. For different fluid viscosities, there can be different sizing (axial and/or radial) of the interference ribs272. This could mean a bespoke or custom spacer for each viscosity and fill-level combination, or, depending on the number of springs required for a viscosity range, there can be a number of tined positions, whereby the spacer can be set to a particular position for a particular modular spring (the position have had the interference/damping tuned for that particular spring load/viscosity scenario).

Referring toFIGS.65A-69, an actuator button arrangement280for actuating the system10according to one aspect of the present invention is shown. The actuator button arrangement280includes the actuator button26, a button spring284, and a needle actuator body286. The needle actuator body286may be similar to the needle actuator bodies96,220discussed above and configured to move within the housing20to transition the needle shuttle102or needle28between retracted and extended positions. As shown inFIG.69, the actuator button26includes a user interface portion288for interacting with a user. Preferably, the user interface portion288is about 22 mm long and about 10 mm wide, although other suitable dimensions may be utilized. The actuator button26includes two pairs of lockout arms290,292that interact with button contacting surfaces294,296on the needle actuator body286prior to device actuation to prevent the needle actuator body286from rocking upward. As shown inFIG.65H, an overlap between the needle actuator body286and the housing20prevents premature actuation. Referring toFIG.66, the button spring284includes a first bearing surface298and a second bearing surface300spaced from the first bearing surface298, and a cantilevered central spring arm302surrounded by a pair of outer arms304that are joined by the first bearing surface298.

The actuation button arrangement280is configured to provide one or more of the following features, which are discussed in more detail below: one-way axial displacement or sliding of the actuator button26; transverse movement (raised and depressed positions) of the actuator button26where the actuator button26remains depressed during the use position of the needle actuator body286; and lockout of the actuator button26in the post-use position of the needle actuator body286such that the button26is in the raised position and cannot be depressed by a user.

To actuate the system10using the actuator button26, the user first slides the user interface portion288in a first axial direction, shown as being to the right inFIGS.65G and65H. The user may be required to slide the user interface portion288about 10 mm or about 8 mm, although other suitable distances may be utilized. Moving the actuator button26axially moves the lockout arms290,292to clear the button contact surfaces294,296on the needle actuator body286to allow movement of the actuator button26from the raised position to the depressed position.

As the user distally slides the user interface portion288, the central spring arm302of the button spring284rides over a spring arm306bearing surface on the housing20while the first and second bearing surfaces298,300engage first and second bearing ramps308,310on the housing20. The forces on the button spring284are balanced through the engagement with the spring arm bearing surface306and the first and second bearing ramps308,310to provide a smooth axial displacement or sliding of the actuator button26.

As the actuator button26and the button spring284reach the end of their axial sliding travel, the central spring arm302and the first bearing surface298pass the end of a respective stops312,314to prevent the actuator button26from sliding backward to its original position, as shown inFIG.65H. Further, when the actuator button26and the button spring284reach the end of their axial sliding travel, the user engages the user interface portion288to move the actuator button26downward to its depressed position. The actuator button26may be depressed about 2 mm and the minimum force required to depress the actuator button26is about 3 N, and most preferably, about 2.8 N, although other suitable distances and minimum forces may be utilized.

As the user depresses the user interface portion288, shown inFIGS.65A and65B, the actuator button26rotates the needle actuator body286to release the needle actuator body286thereby allowing the needle actuator body286to move from the pre-use position to the use position. As shown inFIG.65B, as the needle actuator body286travels to the use position, the lockout arms290,292run along the underside of the button contact surfaces294,296to prevent the actuator button26springing upward. After the medicament has been delivered and as the needle actuator body286is transitioning from the use position to the post-use position, shown inFIG.65C, the lockout arms290,292are disengaged from the button contact surfaces294,296allowing the actuator button26to spring back up under the influence of the button spring284. Once the needle actuator body286fully transitions to the post-use position, shown inFIG.65D, the actuator button26has finished moving from the depressed position to the raised position due to the biasing force of the button spring284. When the needle actuator body286is in the post-use position, a spring arm316on the needle actuator body286engages the actuator button26to prevent the actuator button26from moving to the depressed position while axial movement is still restricted by the engagement of the spring arm302with the stops312,314. Thus, the actuator button26is locked after delivery of the medicament is complete to provide a clear indication between a used system and an unused system.

Furthermore, if the user holds down the actuator button26during dispensing of the medicament, proper dosing and needle retraction will still complete, but the actuator button26will not spring back up to the raised position until the button26is released.

In one aspect, the button spring284is made of plastic. The button spring284may also be a pressed metal spring could be used instead, although any other suitable material may be utilized.

Referring toFIGS.68A-68G, rather than providing a separate actuator button26and button spring284, the spring may be provided integrally with the button26. More specifically, an actuator button320according to a further aspect of the present invention includes an integral spring arm322. The actuator button320also includes lockout arms324, retention arms326, and a rear pivot328. As shown inFIGS.68D and68E, the spring arm322engages prongs330in the top portion22of the housing20. During transition of the system10from the pre-use position to the use position, the spring arm322slides past a detent of the prongs330providing an axial spring force. The end of the spring arm322engages a portion of the top portion22of the housing20to provide the vertical spring force as the spring arm322deflects. The actuator button320is configured to a fluid motion between the sliding and depression movements of the button320even though two separate motions are occurring, which is similar to the operation of the button26discussed above. During transition between the pre-use position and the use position, the button320pivots about the rear pivot328with the retention arm326engaging a portion of the needle actuator body286thereby maintaining a depressed position of the button320until the end-of-dose position is reached in a similar manner as actuator button26. The lockout arms324deflect inwards and engages a portion of the needle actuator body286as the needle actuator body286moves to the end-of-dose position thereby preventing further movement of the actuator button320in a similar manner as the actuator button26discussed above.

Aspects of the present invention provide improvements over previous button designs. For example, the actuation button arrangement280provides multiple surfaces to hold the needle actuator body286in place against a needle actuator spring106prior to actuation, thereby reducing the likelihood of premature actuation during a drop impact. The actuation button arrangement280physically prevents the needle actuator body286from moving prior to actuation by holding it in a tilted (locked) state in such a way that the surfaces have no room to separate and pre-activate.

In addition, button slide forces of the actuation button arrangement280are controlled more precisely by utilizing a flexing arm rather than using a simple bump detent. This permits longer sliding strokes of the button26with better force control, resulting in a more ergonomically effective design. Further, the actuation button arrangement280causes the button26to pop back out at the end of injection, giving the user an additional visual, audible, and tactile indication that the medicament delivery is completed.

According to one aspect, the fluid delivery volume of the system10is determined by the end position of a plunger relative to a point inside the housing regardless of actual fill volume, container inner diameter, and stopper starting position and length. The dosing accuracy variability can be significant because the tolerances of the factors above can be quite large. Aspects of the present invention allow for the elimination of some or all of these tolerances from the dosing equation, resulting in a more precise and less variable injection volume of medicament.

Referring toFIGS.69and70, a restriction member452according to one aspect of the present invention is disposed with the drive assembly. The restriction member452governs the timing of the final displacement of the needle actuator bodies96,220subsequent to the completion of the medicament dose. Instead of rotating about a fixed post, the restriction member452floats freely. Once a plunger displaces sufficiently distally for a gap to align with the restriction member452(as shown inFIGS.70and71), the restriction member452displaces laterally into the gap because of the force of the spring on the needle actuator96,220and the angled face454on the rear of the arm of the restriction member174that engages the needle actuator body (best shown inFIG.71). Once the restriction member no longer retains the needle actuator body96,220, the needle actuator body96,220is free to complete the axial movement to the post-use position. Further, as shown inFIG.71, the restriction member452is biased onto the rear of the barrel portion of the container14, which minimizes the tolerance chain of the various components and improves dose accuracy.

Referring toFIGS.72-77, a drive assembly500for a drug delivery system according to one aspect of the present invention is shown. The drive assembly500includes an actuation button506, a container508, a needle actuator assembly510, an actuation release or flipper512, a lead screw514, and a plunger516. The lead screw includes a drum portion518with external radially-protruding vanes520, and, as best shown inFIGS.74and75and subsequently described in greater detail, a screw thread portion522. Prior to activation, as best shown inFIGS.73and76one end513of the actuation release512engages one of the vanes520to prevent rotation of the lead screw514.

According to one aspect, as shown inFIGS.74-76, the screw thread portion522of the lead screw514engages internal threads of a nut524connected with the plunger516. According to another aspect, the nut and its internal threads are integrally formed with the plunger as a unitary structure. Additionally, a constant force spring526is received within the drum portion518and biases the lead screw514in a rotational direction. According to one aspect, the spring526is secured to the base cover504. According to another aspect, as shown inFIGS.74-76, a drive assembly housing528is disposed within the system and the spring526is secured to the power pack housing528.

Unlike a helical spring, such as a compression spring, which has a force profile proportional to its displacement, the constant force spring526and the like maintain a relatively flat or even force profile over a long working length. The even force profile advantageously provides an injection force that is proportional to the spring force. This will provide a flat or even injection force, and thus, a substantially constant injection rate for the medicament. Although the spring526is illustrated inFIG.76as having only two turns of material, one skilled in the art will appreciate that fewer or greater numbers of turns can be employed. Preferably, an assembler winds the spring526when the drive assembly500is assembled, and the spring526is stored in the wound position until the time of actuation.

Upon actuation of the system, the needle actuator assembly510is released to axially displace (to the right inFIGS.72-75) from the pre-use position to the post-use position under the influence of a biasing member530(best shown inFIG.73). During this displacement, the needle actuator assembly510bears against a second end532of the actuation release512and rotates the release512counter-clockwise, as shown inFIG.77. This counter-clockwise rotation of the actuation release512frees the first end513thereof from engagement with the vane520. Subsequent to the disengagement of the first end513from the vane520, the spring526unwinds and drives rotation of the lead screw514, which, in combination with the nut524, advances the plunger514to dispense the medicament.

As the lead screw514is rotating, the rotation of the drum portion518and the vanes520is visible through a window534in the housing. This window534indicates progress of the screw in a way that is much more apparent than viewing the linear movement of the stopper536in the container508. In fact, this rotational movement is many times more sensitive than the linear movement. One skilled in the art will appreciate that the exact amount of advantage or increase depends on the pitch of screw thread portion522of the lead screw514, the diameter of the drum portion518, and number of vanes520on the drum portion518.

Referring toFIGS.78-83, a drive assembly600for a drug delivery system according to a further aspect of the present invention is shown. The drive assembly600acts to store a spring's mechanical energy and to activate it when triggered. The drive assembly600includes a medicament barrel601, a stopper602slidably disposed in the barrel601, a first valve plunger603, a second valve plunger604, a first revolve nut605, and a second revolve nut606. The drive assembly600also includes a rotary indicator607, a locking element608, a constant force spring609disposed within the rotary indicator607, and an actuation release or flipper610. The drive assembly600is at least partially disposed within a housing611that can be assembled into a drug delivery system.

The constant force spring609is contained between the housing611and the rotary indicator607within a drum portion616of the rotary indicator607. The drive assembly's inactive state is such that energy is applied by uncoiling the spring609and harnessing this energy geometrically with the housing611, rotary indicator607, and actuation release610. When the drive assembly600is deactivated, the spring recoils and translates the mechanical energy into rotational motion of the rotary indicator.

The telescoping multi-part plunger is oriented along a force axis between the medicament barrel601and the rotary indicator607. The rotary indicator607features a threaded shaft618. According to one aspect, the threads are dual lead, and are either square or rectangular in nature. The multi-part telescoping plunger includes a two-part threaded nut (first revolve nut605and second revolve nut606) and a two-part plunger (first valve plunger603and second valve plunger604). The second revolve nut606is a threaded shaft that mates with the rotary indicator607and first revolve nut605and features matching threads on its inner and outer surfaces (internal and external threads, respectively) to mate with them. The second revolve nut606also has a circular collar620(best shown inFIG.82) on its proximal end that bottoms down on the second valve plunger604. The second revolve nut606is free to spin along the force axis. The first revolve nut605is also a threaded shaft that features threads on its inner diameter corresponding to the external threads of the second revolve nut606to mate with the second revolve nut606.

According to one aspect, on one end, the first revolve nut605has a hexagonal collar that press fits on the first valve plunger603to fixedly connect the first valve plunger603with the first revolve nut605. In the drive assembly600, the first revolve nut is not free to rotate and will only translate when the power module subassembly is actuated.

The second valve plunger604is a hollow cylindrical component with a small collar622on its distal end, a large collar624on its proximal end, and an extended L-shaped arm626(best shown inFIG.83) protruding from the large proximal collar624. According to one embodiment, the small collar622is discontinuous and features four leaf cantilevered arms or leaf springs623that allow the collar to bend and mate with the first valve plunger603. The inner surface of the second valve plunger604has an undercut through its length terminating at its proximal end a radially inward protruding shelf628of the large collar624. The shelf628engages the second revolve nut606within the telescoping assembly.

The first valve plunger603attaches to the stopper602and is also a hollow cylindrical component that mates with the second valve plunger604. More specifically, the first valve plunger603features a cylindrical protrusion630on its distal end to mate with the stopper602. According to one aspect, as best shown inFIG.79, four thru slots632are disposed on the proximal quadrants of the first valve plunger603to mate with the leaf springs or arms623and small collar portion622of the second valve plunger604. Both the first and second valve plungers603and604are free to slide.

Telescoping is achieved when the constant force spring609recoils and the rotary indicator607starts spinning. The threaded attachment between the rotary indicator607and the second revolve nut606causes second revolve nut606to rotate. But because the second revolve nut606is threaded to the first revolve nut605, which cannot rotate and experiences resistance to distal translation due to the pressure caused by medicament in the barrel601, the second revolve nut606will displace proximally and bottom out on the second valve plunger's radially inward protruding shelf628. The second valve plunger604is prevented from displacing proximally by the housing611. Subsequently, and with continued rotation of the rotary indicator607, because the second revolve nut606is threaded with the first revolve nut605(which cannot rotate) the first revolve nut605translates distally to push the first valve plunger603(and the stopper602) to dispense medicament from the barrel601.

The first valve plunger603displaces distally relative to the second valve plunger604until the small collar sections622(respectively disposed on the distal ends of the leaf springs or arms623of the second valve plunger604) engage the corresponding proximal ends of the slots632of the first valve plunger603. This locks the relative positon of the first and second valve plungers603and604, with continued rotation of the rotary indicator607, both valve plungers translate distally while also pushing the second revolve nut along (because of its proximal engagement with the shelf624).

The initial and final positions of the telescoping plunger, and thus the medicament dose, are controlled by the rectangular thread form of the threaded shaft618of the rotary indicator607, a threaded shaft on the drum portion616of the rotary indicator607, and a stepped pin that acts as the locking element608. According to one aspect, threaded shaft on the drum portion616of the rotary indicator607is single lead, and because the rest of the components in the telescoping chain have dual lead threads, the axial travel of the other threaded components is twice the axial travel of the lock608relative to the rotary indicator.

According to one embodiment, the lock608is cylindrical and features a domed tip on one end and a cylindrical collar on the other. The threads on the exterior of the rotary indicator's drum portion616along with a slot and undercut636at the bottom of the housing611captures the lock608in place, allowing it to slide parallel to the force axis. Thus, as the spring609is released and the rotary indicator607turns, the lock608translates as well and creates a positive stop when the distal end of the thread on the exterior of the rotary indicator's drum portion616is reached.

One benefit of aspects of the drive assembly600include the use of a constant force spring609, the mechanical energy of which is converted into substantially constant linear force to the medicament in the barrel601. In turn, this creates a uniform medicament delivery rate. Another benefit is that employing the telescoping plunger driven by a thread form, the drive assembly can create in-line space savings of up to 0.75 inches compared to other plunger designs. Additionally, the drive assembly provides a controlled medicament dose through an initial and final mechanical constraint within the same component.

As previously noted, other drug delivery systems utilize a compressed coil spring, which exerts a maximum force at actuation that eventually decreases as the spring expands. A decreasing force at the plunger translates into variable medicament delivery time and medicament exit pressure. By using a constant force spring, the force exerted on the plunger is constant from the beginning to the end of the dosage. In addition, the distance a coil spring has to travel in addition to the length of a static plunger that needs translate inside the drug container can create a long assembly. In contrast, in embodiments of the present invention, the constant force spring is contained radially and does not require any additional space before or after activation. Furthermore, the aspects of the telescoping plunger allow that the plunger length of the can be significantly reduced in comparison to the length of a static plunger.

Previous drug delivery systems have variable dose accuracy performance because the mechanical components enabling the drug delivery create a geometric dependence by bottoming down on the container, which cannot be fabricated with tight tolerances. Some embodiments of the present invention create a control to the start and end times of the translating plunger via a thread form in the rotary indicator and the use of the constant force spring.

The drive assembly creates a space saving geometry in addition to well-controlled time, volume and pressure for the drug delivery device, which translates to a more attractively compact and precise drug delivery device.

Some aspects of the drive assembly implement three rotating threaded shafts to create a linear space savings of about 0.75 inch. In other aspects, the same concept can be employed using two rotating threaded shafts and result in a space savings of about 0.5 inch. Some aspects of the present invention convert the rotational energy of a constant force spring to a translational force motion of a plunger.

Referring toFIGS.84A-84G, a plunger assembly400for use in connection with a drive assembly according to one aspect of the present invention is shown.

Elements in a chain of tolerances in the plunger assembly400include a thickness (A) of a flange402of an inner plunger404, an internal length (B) of an outer plunger406between an internal proximal end408and an internal shoulder410, and an initial offset distance (C1) between the inner plunger flange402and the internal proximal end408of the outer plunger. This initial offset distance (C1) is preferably greater than a gap distance (C2) between outer plunger406and the proximal end of the medicament barrel412. The chain of tolerances in the stopper spacer assembly400also includes the internal barrel diameter (D). Once assembled, the stopper spacer414and the outer plunger406are unique for a given medicament volume.

FIGS.84B-84Gillustrate operation of the plunger assembly400. As shown inFIG.84B, when the system is actuated, the both inner and outer plungers404and406are released. An outer spring416pushes the outer plunger406into the barrel412, compressing damping material418, and an inner spring420. The stopper422does not yet moved relative to the barrel412due to the fluid column of medicament.

Next, as shown inFIG.84C, the outer spring416distally displaces the outer plunger406and the barrel412to open a valve (not shown) at the distal end of the barrel412that establishes fluid communication with the needle (not shown). Due to the incompressibility of the liquid medicament, the stopper422cannot displace relative to the barrel412until the valve is opened and the fluid path to the patient needle is established.

Subsequently, as shown inFIGS.84D and84E, the inner spring420displaces the inner plunger404, the stopper spacer414, and the stopper422, to dispense the fluid.

FIG.84Fillustrates the end of medicament delivery when the proximal flange402of the inner plunger404contacts the internal shoulder410of the outer plunger406, thereby ceasing displacement of the inner plunger404(and the stopper spacer414and stopper422) relative to the medicament barrel212and stopping the flow of medicament.

According to one aspect, as shown inFIG.84G, the cessation of displacement of the inner plunger404relative to the medicament barrel412triggers an end-of-dose indicator for the system.

While a specific spacer assembly40and spacer226have been described above, the custom spacer assembly may have a variety of configurations. The custom spacer assembly may be situated against a proximal end of the stopper in the container or connected to the stopper in another manner. The spacer design is such that its effective length can be changed in order to allow the dispensing of a precise quantity of medicament. The length adjustment is intended to compensate for manufacturing tolerances within the container, the fill volume, and especially the stopper length, which can add up to ⅓ of the variability in a delivered dose using a non-adjustable spacer. The spacer length can be adjusted through several techniques, depending on the specific aspect. The spacer length can be self-adjusting based on its location to the back of the container, adjustable by assembly equipment at the time of final assembly of the primary container into the subassembly, and it can be made an integral part of the stopper and adjusted as a subassembly prior to filling. The adjustable spacer allows a more precise volume of fluid to be injected compared to a non-adjustable stopper.

Referring toFIGS.85and86, a collapsible spacer assembly430includes a forward spacer portion432secured to a stopper434, an inner plunger436, a rear spacer portion438, and a rotating shuttle440. The inner plunger436can translate relative to the forward spacer portion432, but not rotate relative thereto. Similarly, the rear spacer portion438can also move axially relative to the forward spacer portion432, but not rotate relative to the forward spacer portion432. As subsequently described in greater detail, the rotating shuttle440first rotates, and subsequently translates.

According to one aspect, forward spacer portion432is fixedly secured to the stopper434. One skilled in the art will understand that many methods can be employed to secure the forward spacer portion432to the stopper434, for example, adhesive, mechanical fasteners, or any other suitable arrangement. Preferably, the forward spacer portion432includes threads that engage mating threads in the stopper434.

When the stopper spacer assembly430is screwed into the stopper434, an axial load is applied through access openings442in the rear spacer portion438. This force can be used to push the stopper434forward, applying pressure to the fluid medicament. This pressure causes the front (distal) face of the stopper434to deflect and press proximally, pushing back on the rear spacer portion438and rotating the rotating shuttle into its “as assembled” condition. In other words, when a medicament barrel is filled with medicament and the system's plunger is applying axial force to the medicament via the spacer assembly430, the distal face of the stopper434is deformed by the pressure of the medicament. During medicament delivery, pressure is applied by a drive assembly (via the plunger) to the rear spacer portion438, which in turn applies a rotational torque to the rotating shuttle440via helical faces444of the rear spacer portion438. But the stopper deformation from the medicament provides a rearward or proximal force on the inner plunger436, which prevents rotation of the rotating shuttle440.

According to one aspect, an axial reaction load on the inner plunger436can be increased by increasing the length of the inner plunger436.

Once the medicament delivery is complete, as shown inFIG.87, the pressure on the stopper434decreases, thereby permitting the distal end of the inner plunger436to displace distally. This distal displacement permits the rotating shuttle440to rotate. The continued axial force applied by the drive assembly rotates and distally displaces the rotating shuttle440due to interaction of the helical faces444in the rear spacer portion438with corresponding cam-faced arms446of the rotating shuttle440. According to one aspect, this final movement of the rotating shuttle440causes the drive assembly to trigger needle retraction.

Referring toFIGS.88-90, a spacer assembly460according to a further aspect of the present invention is shown. The spacer assembly460shown inFIGS.88-90allows for the removal of the effect of manufacturing tolerance build up through adjustment of the spacer assembly thereby allowing each system to inject the same amount of medicament.

As shown inFIG.89, the spacer assembly460includes a stopper462and a stopper spacer464. The stopper spacer464includes a fixed spacer piece or fixed spacer466that is fixedly connected with the stopper462, and an adjustable spacer piece or adjustable spacer468that is rotationally displaceable in one direction relative to the fixed spacer466.

One skilled in the art will understand that many methods can be employed to secure the fixed spacer466to the stopper462, for example, adhesive, mechanical fasteners, or any other suitable arrangement. Preferably, the fixed spacer466includes one or more external threads that engage one or more mating threads in the stopper462. According to one aspect, the adjustable spacer468has a distal stem with an external thread470. The distal stem thread470engages an internal thread472in the fixed spacer466(best shown inFIG.90) to rotationally control axial displacement of the adjustable spacer468relative to the fixed spacer466.

As shown inFIGS.88and89, the fixed spacer466includes radially spaced detents474and the adjustable spacer468includes a spring detent arm476, the free end of which engages a selected one of the detents474to prevent rotation and axial displacement of the adjustable spacer468toward the fixed spacer466. The free end of the spring detent arm476is shaped to pass over the detents474in one direction, thereby permitting rotation and proximal axial displacement of the adjustable spacer468away from the fixed spacer466.

Despite variations in the dimensions of stoppers and containers, the adjustable spacer468can be adjusted relative to the fixed spacer466to provide a consistent axial length of the stopper assembly460.

As shown inFIG.90, once the container is filled, an axial load, such as a load that would be encountered when installed in the system10,200, can be applied to the adjustable spacer468(and thus, the fixed spacer466and the stopper462). Once the axial load is applied, the adjustable spacer468can be proximally backed out to ensure a consistent gap478between the proximal end of a medicament barrel480and the proximal face of the adjustable spacer468, thereby accounting for variations in the medicament barrel glass and the compressibility of any entrapped air. In other words, the spacer assembly460allows the adjustable spacer468to have a predetermined set position relative to the container14independent of the variables of the container14and stopper length. Accordingly, the start position of the spacer assembly460is a predetermined distance from the container14and the end position of the spacer assembly460is also a predetermined distance from the container14such that the travel of the stopper462is defined by the effective length of the plungers52,54of the drive assembly12.

Referring toFIGS.91and92, a base column482and a cap484of an automatically adjusting spacer486according to one aspect of the present invention is shown. The base column482includes a base portion488and an axially extending column490. According to one embodiment, the base column482includes a plurality of columnar protrusions491that each have a plurality of ratchet teeth492disposed on a proximal portion thereof. A locking barb493is disposed at the proximal end of each of the plurality of ratchet teeth492. The cap484is hollow, and a distal end of the cap484includes one or more axial springs494. According to one aspect, the axial springs494are bent, cantilevered arms formed during molding of the cap484. According to another aspect, a separate biasing member, such as a compression spring can be employed in the automatically adjusting spacer486. When assembled with the base column482, the springs494engage the base portion488and maintain an initial spacing between the base column482and the cap484. According to one aspect, the springs494are omitted. The cap484also includes a plurality of flexible cantilevered arms or tabs496, which each have a free proximal portion with a plurality internal of ratchet teeth497. The proximal end of each flexible tab496includes a foot498.

FIGS.93A and93Billustrate the cap of the automatically adjusting spacer deployed within a proximal recess of a stopper499at a proximal portion of a medicament barrel. The base column482is assembled into the hollow cap484with the base portion482engaging the stopper499and the feet498disposed outside the proximal end of the barrel.

In operation, as shown inFIGS.93A and93B, the cap484displaces distally relative to the base column482(as well as the stopper499and the barrel) until the proximal end of the cap484is flush with the end of the medicament barrel. This action causes the feet498to engage the internal surface of the barrel and displace radially inward, thereby forcing the ratchet teeth492into locking engagement with the ratchet teeth497. The locking barb493, the engagement of the ratchet teeth492and497, and the engagement of the feet498with the internal surface of the barrel prevents the displacement of the cap484relative to the base column482. Thus, the automatically adjusting spacer486can accommodate differences in stoppers, barrel diameters, and medicament fill volumes, to automatically provide a bearing surface flush the proximal end of the medicament barrel.

Referring toFIGS.94-100, a spacer assembly660according to a further aspect of the present invention is shown. The spacer assembly660is similar to the spacer assembly460discussed above and shown inFIGS.88-90and operates in a similar manner to achieve similar advantages. The spacer assembly660includes a fixed spacer666and an adjustable spacer668. The fixed spacer666is configured to be received by the stopper462with lugs670engaging the stopper462to secure the fixed spacer666within the stopper462, although other suitable securing arrangements, such as threads, may be utilized. The fixed spacer666includes interior threads672that receive exterior threads678of the adjustable spacer668. The fixed spacer666includes a plurality of detents674positioned on a helical portion of the fixed spacer666. The adjustable spacer668includes a spring detent arm676that engages one of the detents674to prevent rotation and axial displacement of the adjustable spacer668relative toward the fixed spacer666. The spring detent arm676is shaped and configured to pass over the detents674in one direction to allow rotation and axial displacement of the adjustable spacer668away from the fixed spacer666. The adjustable spacer668may be initially secured to the fixed spacer666via the threads672,678by applying a force to the top of the spring detent arm676, which biases the spring detent arm676away from the detents674to allow the spacers666,668to be secured to each other. Accordingly, in the same manner as discussed above in connection with spacer assembly460, the adjustable spacer is free to rotate in one axial direction to adjust the length of the spacer assembly660.

Referring again toFIGS.94-100, the spacer assembly660further includes a shim680configured to be received and secured to the adjustable spacer668. Rather than providing a plurality of sizes of adjustable spacers468,668, a plurality of shim680sizes can be provided to accommodate a plurality of different fill volumes within the container14. The shim680may be secured to the adjustable spacer668via a connector682extending from the shim680that is received by the adjustable spacer668using a snap-fit, although other suitable securing arrangements may be utilized. A center portion684of the fixed spacer666is configured to be engaged while the adjustable spacer668is rotated relative to the fixed spacer666to prevent rotation of the fixed spacer666along with the adjustable spacer668. The center portion684of the fixed spacer666is accessible through an opening in the shim680.

Referring toFIGS.101-103, a spacer assembly700according to a further aspect of the present invention is shown. The spacer assembly700has a spacer702and shims704. The spacer702has a central column706and a proximal flange708. The central column706is received within and attached to the stopper710of the container712such that the proximal flange708abuts the proximal end of the stopper710. The spacer702may be attached to the stopper710using any suitable method including, but not limited to, adhesive, a threaded connection, and a snap-fit connection. Rather than providing spacers702having proximal flanges708of different thicknesses, a plurality of shims704having different sizes are provided to accommodate a plurality of different fill volumes within the container712. The shims704may have a shape corresponding to the shape of the proximal flange708and may be secured to the proximal flange708via a snap-fit connection or an adhesive, although other suitable securing arrangements may be utilized. The sizes of the available shims704may be arranged in a binary fashion, i.e., each successively thicker shim704is twice as thick as the previous shim704, as shown inFIG.103. The shims704may be attached to the spacer702before it is attached to the stopper710and/or after it is attached to the stopper710.

Referring toFIGS.104and105, a spacer assembly800according to a further aspect of the present invention is shown. The spacer assembly800has a movable spacer802and a fixed spacer holder804. The spacer802has a central column806and a proximal flange808. The spacer holder804is received by the stopper810and has a central cavity812that receives the central column806of the spacer802. The spacer holder804may be fixedly attached to the stopper810using any suitable method including, but not limited to, adhesive, a threaded connection, and a snap-fit connection. An adhesive814attaches the outer surface of the sidewall816of the central column806to the inner surface of the sidewall818of the central cavity812of the spacer holder804. The adhesive814may be any suitable adhesive including, but not limited to, contact adhesive, UV curable adhesive, and a laser curable adhesive. As shown inFIG.104, the inner surface of sidewall818of the central cavity812of the spacer holder804may include a threaded portion820that engages a corresponding threaded portion822in the outer surface of the sidewall816of the central column806of the spacer802. The adhesive may be provided on the threaded portion of the spacer802and/or the spacer holder804. After the spacer802is threaded into the central cavity812of the spacer holder804and the desired length of the spacer assembly800is set, the adhesive814is cured attaching the spacer802to the spacer holder804, thereby fixing the length of the spacer assembly800. Alternatively, as shown inFIG.105, a laser or ultrasonic weld824may be used to attach the spacer802to the spacer holder804, thereby fixing the length of the spacer assembly800. The spacer802may be transparent while the spacer holder is opaque.

Referring toFIG.106, a spacer assembly900according to a further aspect of the present invention is shown. The spacer assembly900has a spacer902and a spacer holder904. The spacer902has a central column906and a proximal flange908. The spacer holder904is received by the stopper910and has a central cavity912that receives the central column906of the spacer902. The spacer holder904may be attached to the stopper910using any suitable method including, but not limited to, adhesive, a threaded connection, and a snap-fit connection. An ultrasonic or laser weld914attaches the outer distal surface916of the central column906to the inner bottom surface918of the central cavity912of the spacer holder904locking the positon of the spacer902with respect to the spacer holder904, thereby fixing the length of the spacer assembly900. The height of the spacer902may be adjusted relative to the spacer holder904to provide an infinite number of height increments.

Referring toFIGS.107and108, a spacer assembly1000according to a further aspect of the present invention is shown. The spacer assembly1000has a spacer1002and a spacer holder1004. The spacer1002has a central column1006and a proximal flange1008. The spacer holder1004is received by the stopper1010and comprises a sidewall1012extending in a proximal direction from a bottom portion1014. The sidewall1012and the bottom portion1014define a central cavity1016that receives the central column1006of the spacer1002. The spacer holder1004may be attached to the stopper1010using any suitable method including, but not limited to, adhesive, a threaded connection, and a snap-fit connection. The inner surface of sidewall1012of the spacer holder1004includes a threaded portion1018that engages a corresponding threaded portion1020in the outer surface of the central column1006of the spacer1002. As shown inFIG.107, the proximal end surface of the sidewall1012of the spacer holder1004includes a plurality of ratchet teeth configured to engage a flexible tab1024that extends axially in a distal direction from the proximal flange1008of the spacer1002. The proximal end surface of the sidewall1012of the spacer holder1004on which the ratchet teeth are positioned is angled in a distal direction around the circumference of the sidewall1012to assure that, as the central column1006of the spacer1002is threaded into the central cavity1016of the spacer holder1004, the flexible tab1024stays engaged with the ratchet teeth. The engagement between the ratchet teeth on the spacer holder1004and the flexible tab1024only allows the spacer1002to be rotated in one direction with respect to the spacer holder1004. As a result, the central column1006of the spacer1002may be threaded into the central cavity1016of the spacer holder1004, but is kept from being unthreaded from the central cavity1016of the spacer holder1004by the locking engagement of between the ratchet teeth and the flexible tab1024.

Alternatively, as shown inFIG.108, a flange1026may extend from the proximal end surface of the sidewall1012of the spacer holder1004. The flange1026includes a plurality of ratchet teeth configured to engage a flexible tab1028that extends in a radial direction from the proximal flange1008of the spacer1002. The flange1026on which the ratchet teeth are positioned is configured around the circumference of the sidewall1012of the spacer holder1004to assure that, as the central column1006of the spacer1002is threaded into the central cavity1016of the spacer holder1004, the flexible tab1028stays engaged with the ratchet teeth.

The bottom portion1014of the spacer holder1004may be provided at a variety of thicknesses as shown inFIG.107in order to provide another dimension of adjustability for containers having different fill volumes.

Referring toFIGS.109and110, a spacer assembly1100according to a further aspect of the present invention is shown. The spacer assembly1100has a spacer1102and a spacer holder1104. The spacer1102has a central column1106and a proximal flange1108. The spacer holder1104is received by the stopper1110and comprises a sidewall1112extending in a proximal direction from a bottom portion1114. The sidewall1112and the bottom portion1114define a central cavity1116that receives the central column1106of the spacer1102. The spacer holder1104may be attached to the stopper1010using any suitable method including, but not limited to, adhesive, a threaded connection, and a snap-fit connection. The spacer1102includes a protrusion1118extending axially in a distal direction from the proximal bottom surface1120of the central column1106. The protrusion1118extends around less than half of the circumference of the proximal bottom surface1120of the central column1106. The spacer holder1104includes a protrusion1122extending axially into the central cavity1116from the bottom portion1114of the spacer holder1104. The protrusion1122extends around less than half of the circumference of the bottom portion1114of the spacer holder1004. When the spacer1102is in a first position, as shown inFIG.109, the protrusion1118on the spacer1102contacts the bottom portion1114of the spacer holder1104and the protrusion1122on the spacer holder1104contacts the proximal bottom surface1120of the spacer1102such that the spacer assembly has a first length. When the spacer1102is in a second position, as shown inFIG.110, the protrusion1118on the spacer1102contacts the protrusion1122on the spacer holder1104such that the spacer assembly has a second length that is greater than the first length. While a specific embodiment using a spacer and a spacer holder having configurations that allow for the length of the spacer assembly to be changed based on the relative position of the spacer to the spacer holder has been described, other similar configurations may also be utilized.

Referring toFIG.111, a spacer assembly1200according to a further aspect of the present invention is shown. The spacer assembly1200has a spacer1202and a spacer holder1204. The spacer1202has a central column1206and a proximal flange1208. The spacer holder1204is received by the stopper1210and comprises a sidewall1212extending in a proximal direction from a bottom portion1214. The sidewall1212and the bottom portion1214define a central cavity1216that receives the central column1206of the spacer1202. The spacer holder1204may be attached to the stopper1210using any suitable method including, but not limited to, adhesive, a threaded connection, and a snap-fit connection. The inner surface of sidewall1212of the spacer holder1204includes a non-overhauling threaded portion1218that engages a corresponding non-overhauling threaded portion1220in the outer surface of the central column1206of the spacer1202. A non-overhauling thread as used herein results in a threaded connection where application of torque to the first component of the threaded system will cause the first component to rotate with respect to the second component, but no amount of axial force applied to the first component will cause it to rotate with respect to the second component. In the present embodiment, the threaded portion1220of the central column1206of the spacer1202and the threaded portion1218of the sidewall1212of the spacer holder1204are configured such that after torque is applied to the spacer1202to threadingly attach it to the spacer holder1204, application of a subsequent axial force will not cause the spacer1202to turn with respect to the spacer holder1204. At least a portion of the threaded portion1220in the outer surface of the central column1206of the spacer1202may have threads that extend radially outward to increase the locking engagement between the threaded portion1218of the spacer holder1204and the threaded portion1220of the spacer1202. In addition or alternatively, as shown inFIG.112, the threaded portion1220of the spacer may have threads1224with an upper outer face1226that is angled downward in the proximal direction and a bottom outer face1228that extends in a radial direction forming a pointed tooth-shaped structure. When an axial force in the distal direction, as shown by the arrow1230, is placed on the spacer1202in order to move the stopper1210in the distal direction, the pointed threads1224dig into the sidewall1212of the spacer holder1204to lock the spacer1202to the spacer holder1204.

Referring toFIGS.113-115, a spacer assembly1300according to a further aspect of the present invention is shown. The spacer assembly1300has a spacer1302and a spacer holder1304. The spacer1302has an annular ring1306extending from a proximal flange1308. The spacer holder1304is received by the stopper1310and comprises a sidewall1312and a central post1314both extending in a proximal direction from a bottom portion1316. The sidewall1312, the central post1314, and the bottom portion1316define an annular cavity1318that receives the annular ring1306of the spacer1302. The spacer holder1304may be attached to the stopper1310using any suitable method including, but not limited to, adhesive, a threaded connection, and a snap-fit connection. The inner surface of the sidewall1312of the spacer holder1304includes an overhauling threaded portion1320that engages a corresponding overhauling threaded portion1322in the outer surface of the annular ring1306of the spacer1302, and the outer surface of the central post1314includes a non-overhauling threaded portion1324that engages a corresponding non-overhauling threaded portion1326in the inner surface of the annular ring1306of the spacer1302. A non-overhauling threaded portion as used herein results in a threaded connection where application of torque to a first component of the threaded system will cause the first component to rotate with respect to the second component, but no amount of axial force applied to the first component will cause it to rotate with respect to the second component. An overhauling threaded portion as used herein results in a threaded connection where application of either torque or an axial force to a first component of the threaded system will cause the component to rotate with respect to the second component. The threads of the overhauling threaded portions and the threads of the non-overhauling threaded portions may have the same pitch.

In the present embodiment, as shown inFIG.113, when a proximal axial force, indicated by arrow1328, is applied the central post1314, the load path for a distal axial force, indicated by arrow1330, is directed through the overhauling threaded connection between the overhauling threaded portion1320in the inner surface of the sidewall1312of the spacer holder1304and the overhauling threaded portion1322in the outer surface of the annular ring1306of the spacer1302. Because this threaded connection has overhauling threads, the axial force1330causes the spacer1302to rotate and thread into the annular cavity1318of the spacer holder1304. When the force1328is released, the load path for an axial force1330is directed through the non-overhauling threaded connection between the non-overhauling threaded portion1324in the outer surface of the central post1314of the spacer holder1304and the non-overhauling threaded portion1326in the inner surface of the annular ring1306of the spacer1302(FIG.114). Because this threaded connection has non-overhauling threads, the axial force1330does not cause the spacer1302to rotate such that movement of the spacer1302with respect to the spacer holder1304is restricted.

FIGS.115A-115Cshow how the spacer assembly1300is assembled. In a first step, shown inFIG.115A, a distal axial force, indicated by arrow1332, is applied to the proximal end of the sidewall1312of the spacer holder1304and a proximal axial force, indicated by arrow1334, is applied to the central post1314. A fixture1336is then used to apply a proximal axial force, indicated by arrow1338, to the proximal flange1308of the spacer1302(FIG.115B). The fixture1336has bearing surfaces1340that contact the proximal flange1308of the spacer1302allowing the spacer1302to rotate. When a distally extending flange1342on the fixture1336contacts the proximal end1344of the container1344, the rotation of the spacer1302stops as the proximal axial load1338is transferred to the container1344(FIG.115C).

Referring toFIGS.116and117, a spacer assembly1400according to a further aspect of the present invention is shown. The spacer assembly1400has a spacer1402, a spacer holder1404, and a locking pin1406. The spacer1402has a sidewall1408extending in a proximal direction from a bottom portion1410and a proximal flange1412. The sidewall1408and the bottom portion1410define a recess1414that receives the locking pin1406. The spacer holder1404is received by the stopper1416and comprises a sidewall1418extending in a proximal direction from a bottom portion1420. The sidewall1418and the bottom portion1420define a central cavity1422that receives the spacer1402. The spacer holder1404may be attached to the stopper1416using any suitable method including, but not limited to, adhesive, a threaded connection, and a snap-fit connection. The inner surface of sidewall1418of the spacer holder1404includes a threaded portion1424that engages a corresponding threaded portion1426in the outer surface of the sidewall1408of the spacer1402. After the spacer1402is threaded into the central cavity1422of the spacer holder1404such that the spacer assembly1400has the desired length, the locking pin1406is inserted into the recess1414of the spacer1402. The locking pin1406has substantially the same shape as the recess1414of the spacer1402. The locking pin1406keeps the threaded portion1426of the sidewall1408of the spacer1402in good contact with the threaded portion1424of the sidewall1418of the spacer holder1404, thereby creating a locking engagement between the sidewall1408of the spacer1402and the sidewall1418of the spacer holder1404.

Referring toFIG.118, a spacer assembly1500according to a further aspect of the present invention is shown. The spacer assembly1500has a spacer1502, a spacer holder1504, and an expandable container1506. The spacer1502has a sidewall1508extending in a distal direction from a proximal flange1510. The spacer holder1504is received by the stopper1512and comprises a sidewall1514extending in a proximal direction from a bottom portion1516. The sidewall1514and the bottom portion1516define a central cavity1518that receives the sidewall1508of the spacer1502. The spacer holder1504may be attached to the stopper1512using any suitable method including, but not limited to, adhesive, a threaded connection, and a snap-fit connection. An opening having a valve1520extends through the proximal flange1510of the spacer1502and into the expandable container1506. The expandable container1506may be filled with air or any other suitable fluid via the valve1520in order to change the distance that the proximal flange1510is separated from the proximal end of the sidewall1514of the spacer holder1504, thereby changing the length of the spacer assembly1600.

An adjustable plunger assembly1700may be provided as an alternative to an adjustable spacer assembly. In this embodiment, shown inFIG.119, the container remains stationary and the valve assembly is configured to pierce the septum without any movement of the container. A single plunger assembly1700comprising a plunger1702having a central passageway1704, a plunger extension1706, and a biasing member1708is provided. The inner surface of the central passageway1704includes a threaded portion1710that engages a corresponding threaded portion1712in the outer surface of the plunger extension1706. During assembly of the drug delivery system, the distance that the plunger extension1706extends beyond the distal end1714of the plunger1702can be changed by adjusting the length of the plunger extension1706that is inserted into the central passageway1704of the plunger1702. The plunger assembly1700is adjusted by rotating the plunger extension1706until the distal end1716of the plunger extension1706contacts a standard spacer1718attached to the stopper1720. In this manner, the plunger extension1706replaces the adjustable spacer assemblies described above while still allowing containers having different fill volumes to be used.

Elements of one disclosed aspect can be combined with elements of one or more other disclosed aspects to form different combinations, all of which are considered to be within the scope of the present invention.

While this disclosure has been described as having exemplary designs, the present disclosure can be further modified within the spirit and scope of this disclosure. This application is therefore intended to cover any variations, uses, or adaptations of the disclosure using its general principles. Further, this application is intended to cover such departures from the present disclosure as come within known or customary practice in the art to which this disclosure pertains and which fall within the limits of the appended claims.