Patent ID: 12251539

DETAILED DESCRIPTION

In the present application, the term “distal part/end” refers to the part/end of the device, or the parts/ends of the components or members thereof, which in accordance with the use of the device, is located the furthest away from a delivery/injection site of a patient. Correspondingly, the term “proximal part/end” refers to the part/end of the device, or the parts/ends of the members thereof, which in accordance with the use of the device is located closest to the delivery/injection site of the patient.

The dose setting mechanism30(seeFIG.3) of the present disclosure can be used in a number of variously designed complete injection devices. One such embodiment of a complete injection device10is illustrated in inFIG.1, which is shown in the zero dose state as indicated by indicia40showing a zero through the window3aof housing3.FIG.2shows the device ofFIG.1with cap1removed to expose the cartridge holder2and the proximal needle connector7. Pen needle4is attached to the needle connector7through a snap fit, thread, Luer-Lok, or other secure attachment with hub5such that a double ended needle cannula6can achieve a fluid communication with medicament contained in cartridge8. The cartridge8is sealed at the proximal end by septum8aand with a sliding piston9at the opposite distal end.

As explained above, the dose setting mechanism30of the present disclosure is unique compared to other known pen-type injection devices in that only a single component of the dose setting mechanism, namely dose selector35, is primarily responsible for determining a finite set of predetermined fixed doses within a maximum allowable dose range. Moreover, this finite set of predetermined fixed doses can contain fractional doses, meaning that each fixed dose does not have to be an equal multiple of the other fixed doses. For example, one fixed dose setting can equal an equal multiple of a lower fixed dose plus a fractional amount of that equal multiple.

The dose selector35is shown inFIG.6from both a proximal end view and a distal end view. The outer surface of the dose selector has a number of longitudinal grooves35athat are always engaged with longitudinal splines3blocated on the inner surface3dof housing3(seeFIG.11). This engagement prevents relative rotation between the dose selector and the housing, but allows the dose selector to move axially relative to the housing. The outer surface of the dose selector also has connecting cut-outs59that permanently engage and lock with snap fits31con the dose knob31(seeFIG.12) such that the dose knob is axially fixed to the dose selector35. These permanent snap fits31eallow the dose knob to rotate relative to the dose selector during both dose setting and dose cancellation. At the distal end of the inner surface35bof dose selector35there is a set of fixed splines54. The number and relative spacing between of splines54is equal to the number and relative spacing between of fixed splines31alocated on the inside proximal end surface of dose knob31. The reason for this equivalency, as explained more fully below, is to ensure the smooth transition between the dose setting procedure and the initiation of the dose delivery procedure when the dose knob disengages one set of splines and engages another set of splines. The space between each of the dose stops is a multiple of the space between each of the radially projecting longitudinal splines52on floating spline34.

In one embodiment of the dose setting mechanism of the present disclosure the number of equally spaced splines52is chosen to allow for eighty radial positions between knob and snap element. However, for ergonomic and other reasons, the zero dose hard stop55dand the chosen maximum dose hard stop55climit the usable relative rotation of the dose setting knob to 270°. As such, this limited rotation means that there are effectively only 60 (sixty) usable radial positions (80 splines×270°/360°). In one example, a customer may only want an injection device having a maximum dose of 0.60 ml. This would then mean that the sixty radial positions would lead to a raster (or increment) of 0.01 ml. The user could select a fixed dose of 0.20 ml or 0.21 ml for example, but not a dose of 0.205 ml. In most applications, a raster of 0.01 ml is sufficient for any practical use.

In another possible embodiment, if the maximum dose was chosen to be 0.30 ml using the 80 equally spaced splines52, then this would be a raster of 0.005 ml. This raster is typically finer than needed and an alternative approach for this chosen maximum dose would be to have 40 equally spaced splines instead of 80. The finer the raster the higher is the likelihood that a binding/blocking problem will occur when the splines on the dose knob engage with those on floating spline and the fixed splines44of snap element33. A preferred acceptable radial mismatch should be below 4.5° when 80 splines are used.

As illustrated inFIG.6, there is a non-contiguous radially projecting circumferential rib56also located on the inner surface of dose selector35that is selectively interrupted by a number of cut-outs56aat circumferential locations corresponding to dose stops55and to priming stop55a. The function of this rib56and the cut-outs56awill be explained in more detail below. The dose stops55correspond directly to the finite number of predetermined fixed doses that the dose setting mechanism is capable of setting, including in some cases a predetermined fixed priming dose. One or more dose stops can be included on the inner surface of dose selector35. Preferably, the dose stops55are formed as an integral part with the inner surface35bof dose selector35that can be manufactured as a single molded component. A single molded dose selector facilitates an important attribute of the dose setting mechanism of the present disclosure, which is the ability to change a single component of the injection device to obtain a different set of finite predetermined doses. This is achieved by changing the number and/or relative circumferential spacing of the dose stops on the inside of the dose selector.

The inner surface35balso has a zero dose hard stop55d. The circumferential spacing between each dose stop55and the zero dose hard stop55dis directly proportional to one of the finite set of predetermined fixed doses. As mentioned, in some cases, it is desirable to include a priming stop55acorresponding to a fixed priming dose that allows a user to initially position the foot42aof piston rod42in abutment with the distal end surface of piston9before a first injection is attempted. This priming step insures that the first injection accurately dispenses a dose of medicament that corresponds to one of the predetermined fixed dose settings. The dose stops55and the priming stop55aare configured with a shape that facilitates dose setting and dose cancelation, as will be explained in more detail below.FIG.6shows the dose stops having inclined surfaces55eand55f. This is in contrast to the zero dose hard stop55dthat is configured as a hard stop.

Also shown inFIG.6on the inside surface of the dose selector is an optional end of injection bump55b. During the dose delivery procedure, as the protrusion45rotates with the snap element relative to the dose selector the protrusion will eventually arrive at the end of injection bump55bwhen the snap element returns to the zero dose setting. The protrusion will ride up and over the bump55bgenerating a notification signal to the user that the injection device10has returned to the initial zero dose starting condition. This notification does not necessarily indicate that that the expulsion of the set dose medicament is reached, but it does signal to the user to begin the recommended 10 second hold time of needle insertion to ensure complete delivery of the dose.

The setting of one or more of the predetermined fixed doses is achieved through the interaction of snap element33with dose selector35.FIG.4shows snap element33with and without the floating spline34rotatably connected to the outer surface33aof snap element33. The snap element can be rotationally and axially connected to dose sleeve38through splines48and snap element48a. Protrusion45is arranged on a flexible arm45aand only engages the dose stops55and priming stop55aduring dose setting and dose cancellation. In other words, for reasons explained below, protrusion45does not engage the dose stops during dose delivery as the snap element rotates in a counter-rotation direction relative to the dose selector during dose delivery. A second or blocking protrusion46is located on the outer surface33dat the proximal end of snap element33. The location of this blocking protrusion is selected so that it can abut the distal facing surface of the radially projecting rib56in the event dose delivery is interrupted. As explained below, this abutment will prevent the dose knob from moving axially in the distal direction if during dose delivery the user stops exerting a proximally directed axial force on the dose knob when the dose setting mechanism is in between two predetermined fixed dose settings.

FIGS.14A-14Eillustrate the relative positions of the blocking protrusion46, the protrusion45, the projecting rib56and the zero dose hard stop55dand the maximum dose hard stop55c.FIG.14Ashows the dose setting mechanism in an initial zero set dose position where there is no axial force applied to the dose knob. i.e., a so-called released state. Here blocking protrusion is abutting zero dose hard stop55dpreventing dialing a dose less than zero, i.e., turning the snap element33in a clockwise direction. The protrusion45is on the back side of priming stop55a.

FIG.14Bshows the dose setting mechanism set with one of the finite predetermined set doses (0.1 ml) set before the dose knob is pressed to initiate the dose delivery procedure. Protrusion45is positioned on the front side of dose stop55and blocking protrusion46is positioned on the proximal side of projecting rib56, but is in axial alignment with cut-out56a.

FIG.14Cshows the initiation of the dose delivery of the set 0.10 ml dose ofFIG.14Bprior to the beginning of the rotation of the snap element33. Here the dose selector35has now moved proximally relative to the snap element33causing the blocking protrusion46to be positioned on the distal side of projecting rib56. This relative position change is only possible because to the cut-out56abeing aligned with the blocking protrusion46. Dose stops55have now come out of radial alignment with protrusion45, thus allowing snap element33counter-rotate counter clock-wise relative to the dose selector as the dose delivery procedure continues.

FIG.14Dshows the relative position of the blocking protrusion46and the projecting rib56in a condition where the user releases (removes) the proximally directed axial force on the dose knob during the dose delivery procedure. The projecting rib56comes into abutment with the blocking protrusion46thus preventing distal axial movement of the dose selector. This also prevents the splines on the dose knob from reengaging with fixed splines on the snap element.FIG.14Eillustrates the interaction of the maximum dose hard stop55cwith the blocking protrusion46in cases where the user dials past the maximum predetermined fixed dose setting. As illustrated the protrusion45has moved up and over the maximum predetermined fixed dose stop55and the blocking protrusion is in abutment with the maximum dose hard stop55cpreventing any further rotation of the snap element33.

Snap element33also has a set of fixed splines44, preferably that are formed integral to the snap element during the manufacture of the snap element, for example during a molding process. These fixed splines44do not rotate or move axially relative to the snap element. The number and spacing of these splines44are equal to that of splines54on the inner surface of the dose selector and the splines31aon the inside of the dose knob. The function of splines44will be explained below. Snap element33also can have a clicker47, shown inFIG.4as a flexible arm with a radially directed nib. The clicker is configured to engage the splines31aon the dose knob only during dose delivery such that rotation of the snap element produces an audible and/or tactile feedback as the clicker nib travels over the splines31aof dose knob31. During dose setting the engagement of protrusion45with dose stops55and priming stop55aalso produce tactile and/or audible notification, but only as each predetermined dose setting is reached. The number of notifications during dose setting is less than the number of notifications generated by the clicker47during dose delivery. This is because the clicker engages each of the equally spaced splines on the inside surface of the dose knob.

The snap element33also has an outer surface33athat accepts and axially contains floating spline34. The floating spline is axially contained to limit the axial movement of the floating spline relative to the snap element. As indicated inFIG.4, the axial containment of the floating spline to prevent movement distally and proximally is achieved by radial ribs33b,33cthat define outer surface33a. Floating spline34is shown inFIG.5where a preferred configuration is two halves34a,34bthat can be connected to each other after assembly onto surface33a. The connection of the two halves can be through a snap fit shown as the combination of arms49,51engaging detents50a,50b, respectively. Regardless of the connection type, it is important that the engagement with the snap element33is such that the floating spline and snap element can rotate relative to each other. The number and spacing of the splines52on the floating spline34are equal to that of splines44, equal to splines54on the inner surface of the dose selector, and the splines31aon the inner surface of the dose knob. This is necessary because the floating spline34function as a connector, as explained in more detail below, during dose delivery where the dose knob is prevented from rotating relative to the dose selector35. When the dose setting mechanism is assembled, the splines54on the inner surface of dose selector35are fully engaged or meshed with splines52. This meshing of splines52and54rotationally fixes the floating spline34to the dose selector35. Since the dose selector35is splined to the housing3to prevent rotation, this results in the floating spline34also being rotationally fixed to housing3.

As shown inFIG.5, the terminal proximal end52aand terminal distal end52bof each spline52is chamfered to assist in the smooth meshing with splines31aon dose knob3during the initiation of dose delivery. When the dose setting mechanism is assembled, the dose knob31is splined to the snap element33through meshing of only splines44and splines31aon the dose knob. Because splines44are fixed rotationally to snap element33, rotation of dose knob31necessarily causes rotation of snap element33such that surface33arotates relative to the rotationally fixed inner surface53of floating spline34. This rotation of the dose knob and snap element occurs during dose setting and is relative to housing3. During the initiation of the dose delivery procedure the dose knob is pressed in the proximal direction causing it to move axially relative to the snap element. This initial movement disengages splines31afrom splines44and causes splines31ato then engage floating spline34. This new engagement of splines31aand52then prevents the doe knob from rotating relative to the housing3during dose delivery.

Details of dose knob31are illustrated inFIG.12. During assembly of dose setting mechanism the dose knob is axially fixed and attached to dose selector35through snap elements31cthat are engaged with corresponding cut-outs59. This connection allows the dose knob to rotate relative to the dose selector. The dose knob also has gripping surfaces31don the outer surface and includes a radially projecting rib31bthat functions as an anti-roll feature, as well as, a leverage feature to assist the user in setting or cancelling a dose.

FIG.10illustrates the nut36and the clutch32which are permanently splined to each other during assembly of the dose setting mechanism through a splined connection. The splined connection is established by connection elements37of nut36and connection elements71of clutch32. This splined connection ensures that clutch32and nut36are always rotationally fixed to each other during both dose setting and dose delivery. This splined connection also allows the clutch and the nut to move axially relative to each other. The sliding connection is necessary in order to compensate for pitch differences between the threads60on the piston rod42(seeFIG.8), the outer thread39on the dose sleeve38(seeFIG.3) and the thread67on the driver41(seeFIG.9). The sliding connection is necessary to compensate for the difference in the pitch of the thread between nut and the outer surface of the piston rod and the pitch of the thread between dose sleeve and body. The thread between driver and piston guide has basically the same pitch as the thread between piston rod and nut.

The proximal end of nut36has internal threads70that match threads60of piston rod42. The distal end of clutch32is configured as a dose button72and is permanently attached to distal end of the dose knob31through engagement of connectors73, which may also include snap locks, an adhesive and/or a sonic weld. This connection ensures that the clutch is both rotationally and axially fixed to the dose knob during both dose setting and dose delivery.

As shown inFIG.8, in addition to threads60on the outer surface of the piston rod42, there is also included two longitudinal flats61that give piston rod42a non-circular cross section. At the terminal proximal end is connector62, shown as a snap fit, that connects with a disc or foot42a(seeFIG.3). At the distal end of piston rod42is a last dose feature of the dose setting mechanism, illustrated as an enlarged section63. This enlarge section63is designed to stop the rotation of nut36about threads60when the amount of medicament remaining in the cartridge8is less than the next highest predetermined dose setting. In other words, if the user tries to set one of the predetermined fixed dose settings that exceeds the amount of medicament remaining in the cartridge, then the enlarged section63will act as a hard stop preventing the nut from further rotation along threads60as the user attempts to reach the desired predetermined fixed dose setting.

The piston rod42is held in a non-rotational state relative to housing3during both dose setting and dose delivery because it is arranged within the non-circular pass through hole64in the center of piston rod guide43(seeFIG.7). The piston rod guide is both rotationally and axially fixed to housing3. This fixation can be achieved when the piston rod guide is a separate component from the housing3as illustrated in the figures or the piston rod guide could be made integral with the housing. Piston rod guide43also has a connector65configured to engage the proximal end of a rotational biasing member, shown inFIG.3as torsion spring90, the function of which will be explained below. This connection of the rotational biasing member to the piston rod guide anchors one end in a rotational fixed position relative to the housing.

The distal end of the rotational biasing member, for example torsion spring90, is connected to connector66on the driver41(seeFIG.9). Driver41is connected and rotationally fixed with the inner surface of dose sleeve38through splines69on the distal outer surface of the driver. On the proximal end of driver41on the outer surface is threads67that are engaged with matching threads on the inner distal surface of the piston rod guide43. The thread between driver and piston guide has a significantly different pitch than the thread between dose sleeve and housing. The nut and the driver rotate together both during dose setting and dose cancellation and, as such, they perform essentially the same axial movement. However, this movement is independent from each other, i.e., the nut is turned by the clutch and performs an axial movement due to the thread to the piston rod, while the driver is rotated by the dose sleeve and performs an axial movement due to the thread to the piston guide. The driver is rotating during injection also, and so it actively moves in the proximal direction during injection. But, the nut does not rotate during injection and as such does not perform an active axial movement. The nut is only moving in proximal direction during injection because it is being pushed axially by the driver. The rotating driver pushing the non-rotating nut causes the injection because the piston rod is pushed forward due to the threaded engagement with the nut.

If, for example, the thread of the nut had a higher pitch than the thread of the driver, the nut could not freely move in the distal direction during dose setting because it would be hindered by the slower moving driver. As such, this would cause drug to be expelled during dose setting. Alternatively, if the thread of the nut had a significantly lower pitch than the thread of the driver, the driver would move away from the nut during dose setting and the driver would not push the nut at the beginning of the injection already, but would do so only after the gap is closed. Accordingly, it is preferred that the pitch of the thread on the driver is equal or a slightly higher than the pitch of the thread on the nut. And, the thread between the dose sleeve and the housing has a higher pitch than that of the nut and piston rod. This is desirable because it yields a mechanical advantage that makes the dose delivery process easier for the user. For example, when pushing the knob a distance of 15 mm, the piston rod only moves by 4.1 mm. This results in a gearing ratio of about 3.6:1. A lower gearing ratio would result increase the force the user needs to complete the injection.

As will be explained in more detail below, because the torsion spring is attached to the driver41and the driver is rotationally fixed to the dose sleeve38, then rotation of the dose sleeve in a first direction during dose setting will wind the torsion spring such that it exerts a counter rotational force on the dose sleeve in an opposite second direction. This counter rotational force biases the dose sleeve to rotate in a dose canceling direction and provides the necessary force for the first fail-safe feature mentioned earlier.

The function of the complete injection device10and the dose setting mechanism30according to this disclosure will now be described. Injection device10is provided to a user with or without the cartridge8of medicament positioned within the cartridge holder2. If the injection device10is configured as a reusable device, then cartridge holder2is connected to housing3of the dose setting mechanism30in a releasable and reusable manner. This allows the user to replace the cartridge with a new full cartridge when all the medicament is expelled or injected from the cartridge. If the device is configured as a disposable injection device, then the cartridge of medicament is not replaceable because the connection between the cartridge holder2and the housing3is permanent. Only through breaking or deformation of this connection can the cartridge be removed from the injection device. Such a disposable device is designed to be thrown out once the medicament has been expelled from the cartridge.

The user first removes the cap1from the device and installs an appropriate pen needle4to the cartridge holder2using connector7. If the device is not pre-primed during the device assembly, or does not have an automatic or forced priming feature as discussed above, then the user will need to manually prime the device as follows. The dose knob31is rotated such that the protrusion45engages a first dose stop, such as the priming stop55a, which corresponds to a predetermined small fixed dose of medicament. Rotation of the dose knob rotates protrusion45on snap element33relative to dose selector35because the fixed splines44are meshed with splines31aon the dose knob. During dose setting an axial biasing member, shown inFIG.3as a compression spring91, which is located between the snap element and dose knob, exerts an axial force on the dose knob in the distal direction to ensure that splines44and31aare and remain engaged during dose setting.

The injection device10of this disclosure can also have a so-called forced or automatic priming feature, one embodiment of which is illustrated inFIG.13, where the clutch32is initially not rotatably fixed to the dose knob31. A sliding lock80is located between the distal end of the clutch and the inside surface of the dose knob. Prior to using the dose setting mechanism, i.e., before a user could dial one of the predetermined fixed dose setting, the sliding lock80would necessarily need to pushed in the proximal direction such that is moves distally relative to the dose knob. This axial movement causes the snap fingers81to engage the proximally facing surface32dof the clutch forming an irreversible locking relationship between the dose knob and the distal end of the clutch. This locking relationship also causes teeth32cof clutch32and the corresponding teeth82of sliding lock80to mesh and interlock such that the dose knob and clutch are rotationally fixed to each other. Before the sliding lock80is engaged with the clutch, the clutch can be rotated, which also causes rotation of the nut, to cause the piston rod42to move axially relative to the housing. The clutch is rotated until a visual observation and/or tactile notification indicates that the foot42alocated on the piston rod42is in firm abutment with distal facing surface of the sliding piston9. This abutment between the foot and the sliding piston will ensure that an accurate dialed dose will be delivered out of the needle cannula. This rotation of the clutch is preferably performed during the assembly of the injection device and likewise after ensuring abutment of the foot with the sliding piston9, the manufacturing process would cause the sliding lock80to be pushed to the final, locked position. One possible means to achieve rotation of the clutch would be to use a gripper with a vacuum cup to turn the clutch. Alternatively, a slot or other connector could be designed into the distal surface of the clutch that cooperates with a matching tool in order to engage and rotate the clutch. This optional connector is shown as a slit32finFIG.13.

The rotation of protrusion45and subsequent contact with one side of the priming stop55a, or for that matter any of the predetermined dose stops on the dose selector, will cause the flexible arm45ato flex radially inward allowing the protrusion45to ride up, over and down the reverse side of the dose stops55a,55. This movement and contact of the protrusion45generates the audible and/or tactile notification that a dose stop has been reached during the dose setting procedure. The type or level of notification can be modified by changing the design of protrusion45, flexible arm45a, and/or configuration of the dose stops55or priming stop55a. In some cases, it may be desirable to have different notifications for each of the predetermined dose settings. Likewise, it may also be desirable to have the notifications during dose setting be different than the notifications generated by clicker47during dose delivery.

Returning to the priming procedure, once the priming stop55ais reached, the user may need to cancel the priming procedure and can do so by using the dose canceling procedure. This cancellation procedure also applies to any of the predetermined dose settings. Dose cancellation is accomplished by turning the dose knob in the opposite direction so that the protrusion45is caused to counter rotate in the opposite direction relative to the dose stop55or priming stop55a. This will again generate a notification that can be the same or different as the dose setting notification and/or dose delivery notification. Because the snap element33is rotationally fixed to the dose sleeve38, and the dose sleeve is threaded engaged to the inner surface of housing3, rotation of the dose knob during dose setting and dose cancellation causes relative rotation between the dose sleeve and the housing. The threaded connection between the housing and the dose sleeve causes the dose sleeve, snap element, clutch, and dose knob to translate axially as the dose knob is rotated. During dose cancellation, these components rotate and translate axially in the opposite or proximal direction.

Rotation of the dose knob also causes rotation of nut36about threads60on the outer surface of piston rod42, which does not rotate and remains axially fixed relative to the housing3because of relative pitch differences in the threaded parts as explained above. The rotation of the nut relative to the stationary piston rod, which is supported by its contact with the sliding piston, causes the nut to translate or climb up the piston rod in the distal direction. A reverse rotation during dose cancellation causes the nut to translate in the reverse direction relative to piston rod. The distance traveled by the nut to achieve the desired dose setting is directly proportional to an amount of medicament that would be expelled if the dose delivery procedure were initiated and completed. Because the pitch of the threaded connection between the dose sleeve and the housing is greater than pitch of the threads on the nut, the dose sleeve, snap element, clutch and dose knob will travel a greater axial distance than the nut as it climbs up or down the piston rod. The difference in axial movement would normally bind the dose setting mechanism, but does not do so because the difference in pitch is compensated for by the sliding splined connection between the nut and the clutch, thus allowing the clutch to travel axially a greater distance longitudinally than the nut. During injection, the clutch pushes on the snap element and as such on the dose sleeve. This axial force causes the dose sleeve to turn due to the thread to the body. The dose sleeve will only start to turn when it is pushed, if the pitch of the thread is high enough. If the pitch is too low the pushing will not cause rotation because the low pitch thread becomes what is called a “self-locking thread.”

Rotation of the dose knob also causes rotation of the driver because of the splined rotationally fixed connection to the dose sleeve. Since the torsion spring90is fixed at one end to the driver and at the other end to the piston rod guide, which in turn is fixed axially and rotationally to the housing, the torsion spring is wound up increasing in tension during dose setting. As mentioned, the torque of the tension spring exerts a counter rotational force on the dose sleeve. Preferably during assembly of the dose setting mechanism, the torsion spring is pre-tensioned so that even at the zero dose condition the torsion spring exerts a counter rotational force on the dose sleeve. The counter rotation force provides a first fail-safe feature of the dose setting mechanism. This first fail-safe mechanism prevents a user from setting a dose that is not one of the finite set of predetermined dose settings. In other words, if a user is rotating the dose knob and the protrusion45is between two dose stops, or between the zero dose hard stop and a first dose stop55or a priming stop55a, and the user releases the dose knob, the counter rotational force of the torsion spring will return the protrusion to the last engaged dose stop or to the zero dose hard stop. Additionally, during a dose cancellation procedure the counter rotational force will assist the user in rotating the dose knob back down to the next lower fixed dose setting or possibly all the way back to the zero dose setting.

During dose setting, the dose knob translates out and away from the distal end of housing3. As the dose sleeve rotates and translates, the progress of the dose setting (or dose cancellation) is observed in window3aof housing3as the printed indicia40on the dose sleeve moves past the open window. When a desired predetermined dose setting is reached the indicia for that dose will appear in the window. Because the dose stop55or the priming stop55ais engaged with the protrusion45, the torsion spring will not have sufficient force to counter rotate the set dose to the next lower fixed dose setting. At this point the injection device10is ready for a priming procedure or, if already primed, the delivery of the medicament to an injection site. In either the case, the user will push on the dose knob in the proximal direction until the zero dose hard stop55dis reached and a zero dose indicia is observed in the window. During a priming step the user will observe whether medicament is expelled out of the cannula6of pen needle4. If no medicament is expelled this means the piston foot42ais not in abutment with the distal surface of sliding piston9. The priming step is then repeated until medicament is observed exiting the cannula.

The dose setting mechanism of the present disclosure can also have a maximum dose hard stop feature that prevents a user from setting a dose greater than the highest predetermined dose setting. This is achieved through the use of a maximum dose hard stop55cthat comes into engagement with second protrusion46if a user dials, i.e. rotates the dose knob, past the dose stop corresponding to the highest predetermined dose setting. (seeFIGS.4and6). The engagement of the second protrusion with the maximum dose hard stop55cwill prevent further rotation of the snap element. The maximum dose hard stop55cis configured with a shape such that the second protrusion46cannot be rotated past the hard stop without deforming or breaking one or more components of the dose setting mechanism. In the event a user dials past the last dose stop and engages the maximum dose hard stop55cwith the second protrusion46, a release of the dose knob will allow the torsion spring to counter rotate the dose sleeve, snap element and dose knob back to the last dose stop.

The dose setting mechanism also can have an anti-counterfeit or anti-disassembly feature that corresponds generally to the maximum dose hard stop. This anti-counterfeit feature is formed between a hard stop or hook36blocated on the outside surface of nut36and a distal facing end wall32bof a cut-out32aof clutch32(seeFIG.10). As mentioned, the difference in pitch between threads60of the piston rod42and the outer threads39of the dose sleeve38requires that the clutch translates further distally than the nut36as it climbs up the piston rod42during dose setting. The cut-out32aand/or hard stop36bcan be positioned so that the axial translation of the clutch relative to the piston rod is stopped at a predetermined position that generally corresponds to the engagement of the second protrusion with maximum dose hard stop. The interaction of the hard stop36bwith the distally facing wall32bwill prevent further distal movement of the clutch relative to the nut and thus can prevent disassembly of the dose setting mechanism. Typically, an attempt to disassemble the injection device is for the purposes of replacing the expelled cartridge of medicament with a counterfeit cartridge to allow the injection device to be sold and reused as a faux new device. The anti-counterfeit feature inhibits disassembly if a person where to pull on the dose knob, which pulls on the clutch, and which in turn pulls on the snap element33and dose sleeve38. Although the threaded connection of the dose sleeve with the inside of the housing works as a primary disassembly feature, when the device is dialed to the maximum dose setting, this primary disassembly feature may not be sufficient to prevent disassembly. The secondary disassembly feature where the hard stop36bengages facing wall32bas described above can compensate for this insufficiency.

Once the dose setting mechanism is primed, the user then selects and sets a desired fixed dose by repeating the same steps used for priming except that the dose knob will be rotated past the priming stop55auntil the appropriate dose stop is engaged by the protrusion45and the desired dose value appears in the window3a. In some cases, it is preferred to have no indicia show in the window when dialing between predetermined dose settings, while in other cases it is desirable to show an indicia in the window that is indicative of a non-settable dose position between the fixed dose settings.

Once one of the predetermined dose settings has been dialed on the dose setting mechanism, the user can then exert an axial force in the proximal direction to initiate the dose delivery procedure. The axial force exerted by the user overcomes the distally directed force exerted by the second biasing member91causing the dose knob31, clutch32and dose selector35to move axially in the proximal direction relative to the snap element33and housing3. This initial movement disengages the splines31afrom splines44and causes engagement of splines31awith floating spline34, thus rotationally fixing the clutch and dose knob to the housing through the splined connection between the floating spline34and splines54. Splines54and floating spline34remain engaged during dose setting and during dose delivery even though the dose selector35moves axially with the dose knob31and relative to the floating spline34.

The initial axial movement of the dose selector relative to the snap element causes the dose stops to come out of radial alignment with protrusion45such that a rotation of the snap element relative to the dose selector would not allow the protrusion45to engage any of the dose stops, except of course the end of injection bump55b, which provides an audible and/or tactile notification, i.e., a so-called end of injection notification, to the user that the mechanical dose delivery procedure of the device is completed. As mentioned, this notification also informs the user to maintain the cannula in the injection site for the recommend time, typically 10 seconds. Likewise, the initial axial movement of the dose selector relative to the snap element also moves the radially projecting rib56proximally relative to the second protrusion46such that the protrusion46faces the distal side of the projecting rib56when rotation of the snap element relative to the dose selector occurs during the remaining dose delivery procedure. The projecting rib is able to move axially past second protrusion46because of the cut-outs56athat are in the projecting rib56in positions coinciding with each dose stop55a,55. At the end of injection, further rotation of snap element will cause the second protrusion to abut zero dose hard stop55d, which will prevent any further rotation of the snap element.

In addition to the end of injection feature described above, another end of injection notification feature can be incorporated as part of driver41. This alternative or additional end of injection feature also provides tactile and/or audible notification to the user when the mechanical dose delivery procedure is complete. One configuration of this end of injection feature is shown inFIG.9as the combination of flexible arms68a,68b. The flexible arm68bis loaded during dose setting by a geometry of the inside of the dose sleeve38. This holds arm68binside of the dose sleeve38because the flexible arm68bis bent to the right and inwards (seeFIG.9) and held in place by the flexible arm68a. When reaching zero after dose delivery, the flexible arm68ais bent by a geometry of the dose sleeve to release flexible arm68b. This is possible because the driver41is turned by the dose sleeve38, so that both components have a purely linear movement relative to each other due to the difference in the pitch of the two respective threads39and67.

As the user maintains the axial force on both the dose knob31and the dose button72during the continuation of the dose delivery procedure, the clutch32will abut the distal end of the snap element causing it to move axially in the proximal direction. The clutch pushes on the snap element. The snap element is fixed to the dose sleeve, so the clutch pushes on the dose sleeve. As the dose sleeve has a thread with a sufficiently high pitch relative to the body, the axial force on the dose sleeve will cause the dose sleeve and as such the snap element to turn relative to the body, and by turning relative to the body it moves in the proximal direction. The dose selector slides into the housing, but does not rotate relative to the housing3due to the splined engagement between spline3band the groove35a. The rotation of the dose sleeve38also causes rotation of the driver41into the threaded connection with piston rod guide43, which drives the piston rod proximally and results in a concurrent de-tensioning of torsion spring90. The driver does not directly drive the piston rod. As the driver rotates, the driver moves in the proximal direction and pushes the nut forwards. As the nut doesn't turn, the driver pushes the nut and the piston rod forward.

The nut36does not rotate during dose delivery because of the rotationally fixed relationship with clutch32that is rotationally fixed to the housing through rotationally fixed relationship of the dose knob, floating spline and the housing. The nut therefore can only move axially carrying the piston rod42with it because the piston rod is prevented form rotating by the non-circular opening64engaged with the flats61on the piston rod. The piston rod is moved axially the same distance that the nut originally translated relative to the piston rod during dose setting. This axial movement without rotation is caused by the rotational and axial movement of the proximal end of the driver in abutment with flange36aof the nut. Axial movement of the piston rod causes the sliding piston9to also move axially relative to the inside walls of the stationary cartridge8forcing an amount of medicament out of the needle cannula6that is equivalent to the predetermined fixed dose that was set during the dose setting procedure.

If the user stops the dose delivery procedure by removing the axial force on the dose knob the second fail-safe mechanism is activated. Removal of the axial force causes the compression spring91to bias the dose knob in the distal direction. If the user halts the dose delivery between two predetermined fixed dose settings, then the dose knob and the axially fixed dose selector will both be prevented from moving proximally because the second protrusion46will come into abutment with the distally facing side of projecting rib56, which will stop the axially movement of dose selector and dose knob. Without this abutment of protrusion46with projecting rib56, the dose selector would move distally such that the splines31awould re-engage with splines44on the snap element, thus placing the dose knob, clutch and nut back into rotational engagement with the snap element. The torque exerted on the snap element through the driver would then counter rotate the nut, thus reducing the set dose by an unknown amount. This counter rotation would continue until the next lowest predetermined fixed dose setting is reached, where the corresponding dose stop would stop the counter rotation.

If on the other hand the dose delivery is halted at one of the lower predetermined fixed dose settings, the cut-out56ain the projecting rib56would allow dose selector to move distally such that the second protrusion46is positioned on the proximal side of rib56. This would also re-engage the splines31aof dose knob31with the fixed splines44placing the dose knob, clutch and nut into rotational engagement with the snap element as described above. However, because the cut-outs56aare only located at circumferential positions corresponding to the dose stops, there will be no counter-rotation of the snap element, and hence the nut, because the dose stop and the first protrusion45are engaged. Because there is no counter rotation of the nut, there can be no unknown reduction in the set dose. Therefore, a resumption of the halted dose delivery procedure will continue without any unknown decrease in the set dose, thus allowing the originally set predetermined dose to be delivered.

Alternative designs of both the snap element and the floating spline are illustrated inFIGS.15-16, showing floating spline134as a single component piece, as opposed to the two-part clam shell design illustrated inFIG.5. To aid assembly of the floating spline134onto the outer housing133aof snap element133, a longitudinal slit134ais provided that allows the diameter of the floating spline to be enlarged and clipped onto the snap element between radial ribs133b,133c, which define outer surface133a. In other words, the floating spline is shaped like a split c-ring that can be expanded to open the slit such that it can be pressed or snapped over the outer surface of the snap element. This placement of the floating spline134prevents axial movement distally and proximally relative to the snap element133. To prevent rotational movement of the floating spline134relative to the device housing, the proximal end has one or more radially outward projecting ribs134bthat engage corresponding slots135dof dose selector135. Dose selector135is rotationally fixed to the device housing through ribs135a. As with the design discussed above, snap element133can rotate relative to the floating spline134.

Snap element133, again like the design described above, has a set of fixed splines144, preferably that are formed as an integral part or extension the snap element during the manufacture of the snap element. However, these fixed splines144are positioned in discrete sections around the outside circumference of the distal end of snap element133. This is in contrast to having the fixed set of splines be continuous around the circumference of the snap element as illustrated inFIG.4. The fixed splines144do not rotate or move axially relative to the snap element. The spacing of these splines144are equal to that of the splines31aon the inside of the dose knob and function in an equivalent manner as splines44described below. Snap element133incorporates a clicker145bextending proximally from radial protrusion145, as shown inFIG.15. The clicker145bis configured to engage a grooves or teeth154on the proximal surface of projecting rib156of the alternative dose selector135(seeFIG.17). In this alternative design of the snap element133, splines134bremain engaged during dose setting and during dose delivery even though the dose selector135moves axially with the dose knob31and relative to the alternative design floating spline134.

The alternative dose selector135includes an alternatively design protruding rib156that functions as an alternative second fail safe feature. In this alternative design, the rib156is no longer interfering with the second protrusion146, but with the protrusion145, i.e. the protrusion on the flexible arm145a. In this alternative design, the axial position of this projecting rib156has changed relative to rib56as shown inFIG.6. Once the user has started an injection the dose selector is held at radial projecting rib156in a manner such that the knob31cannot jump out in the distal direction when a user removes axial force in the proximal direction.

The alternative projecting rib design156can be useful when torsion spring90is designed to be strong enough to maintain the injection even when the user stops pressing on the knob, thus causing the snap element to rotate relative to the knob. In the above described first design, the compression spring91pushes the projecting rib56against the protrusion45, and the protrusion glides on the rib. But, when the protrusion45reaches the cut-out56ain the projecting rib56, the compression spring91pushes the dose selector in the distal direction and the automatic injection stops. Even though the torsion spring is strong enough to maintain the injection, if the user keeps the thumb on the knob, applying a low force, the user could experience an uneven injection force when the protrusion45reaches a cut-out56a, as the compression spring could start to work. So, the first design of the fail safe mechanism can lead to unwanted effects when the torsion spring is strong enough to maintain the injection. Additionally, the torsion spring could intentionally be just slightly too weak for an automatic injection and this would require the user to keep pressing the knob to maintain the injection. This would result in the user experiencing a very low dispense force because the spring assists in the injection. This could be called a “spring assisted injection”.

The advantage of a spring assisted injection over an automatic injection is, that the user can influence the injection speed (as in a manual device). The advantage of a spring assisted injection over a purely manual injection is, that the user does not need to apply a high force for the injection (as in an automatically injecting device). An intended spring assisted injection may become an automatic injection (albeit possibly very slow), when the force needed to expel the drug from the cartridge is lower than expected, or when the user presses slower than expected. As mentioned, the above described first design of the second fail safe mechanism can lead to an uneven injection force when the device has a spring assisted injection.

The alternative second fail safe design to prevent the automatic injection, illustrated inFIGS.15and17, includes sufficient friction between the protrusion145and the projecting rib156. When the injection speed is dictated by the user (and not by the torsion spring), the protrusion145has a distance of about 0.5 mm to the radial projecting rib156. When the user releases the knob during injection, the compression spring91presses the rib156to the protrusion145. If the torsion spring is strong enough to maintain the injection, the protrusion glides over the rib. In the alternative of the second fail safe design, the goal is to introduce sufficient friction between the protrusion145and the rib156. This could, for example, be caused by having grooves or teeth154located on the distal side of the rib156, as shown inFIG.17, which could then interact with a proximally projecting tooth145bon the protrusion145. The friction will stop the rotation of the snap element133once the user releases the knob (or pushes the knob at a speed slower than the speed induced by the torsion spring). If the torsion spring is strong enough to maintain the injection, the user can apply just the force to compress the compression spring. In this case the protrusion has the above-mentioned distance from the rib and the injection speed is determined by the torsion spring.

The user can also apply a higher force to accelerate the injection. In this case, if the user releases the knob, the injection stops. When the user releases the knob31, the tooth145bon the still rotating snap element133reaches the grooves or teeth154on the rib156before the rotation is halted. There may be an unintended side effect if the user intends to keep the speed induced by the torsion spring by following the knob with the thumb, but presses with a force slightly lower than that of the compression spring. In this case, the tooth may scrape over the tips. However, this unintended effect can be avoided by using an appropriate geometry leading to the friction between the protrusion and the rib.

As mentioned, the knob jumps out when the knob is released at one of the predetermined dose settings, where the rib has a cut-out. The likelihood to release the knob at exactly one of those positions is low. However, if the user intends to press the knob only with the force necessary to compress the compression spring, the knob could jump out at a cut out56a.

Yet another alternative of the second fail safe design is possible and is illustrated inFIGS.18-19where a second alternative dose selector235is shown that has no cut-outs in the protruding rib256at the predetermined dose settings.FIG.19Ashows an enlarged section of the cross-sectional view ofFIG.19. This is in contrast to the to the above two designs previously described. Instead, the protruding rib256has a reduced or indented rib section256awith a lead-in chamfer256a. The protrusion145could also have a lead-in chamfer145c. When the knob31is pressed proximally to initiate an injection, the snap arm145aand protrusion145on the snap element133has to flex to overcome the reduced rib256a. When this occurs, the user feels a tactical and/or audible feedback in the form of a “click.” Once the protrusion has passed the reduced rib256a, the compression spring91cannot press the knob31into the distal position any more, as the non-chamfered side256dof the reduced rib256ais pressed against the non-chamfered side145dof the protrusion145(seeFIG.20).

If the torsion spring90is strong enough, then the torsion spring can maintain the injection, as the compression spring91cannot press the knob in the distal position at one of the lower predetermined fixed dose settings. This second alternative design of the second fail safe feature will also ensure that a spring assisted injection is smooth. As in the above described design, the user can accelerate the injection using this design, but the user cannot halt the injection. As illustrated inFIGS.18and19, if the rib has a cut-out256bat the zero position, the compression spring91will press the knob to the distal position at the end of the injection. However, if the rib does not have a cut-out at the zero position, the knob will stay in the proximal position relative to the snap element. In this position the knob is linearly guided by the dose selector235through the floating spline134and cannot be turned. A rib without a cut out at the zero position thus provides a reuse prevention feature.

The reduction256aof the rib256at the predetermined fixed dose settings and the chamfers256bcan be chosen to adjust the strength of the tactical and/or audible click at the beginning of the injection. For a device with a reuse prevention feature, as described above, the initial click may be designed to be intentionally strong so as to avoid an unintended start of the injection (and as such an unwanted disabling of the device). In some circumstances it may be beneficial to combine the above two alternative second fail safe designs into a single design. One possible way would be to use the first alternative described above where the rib256would be manufactured without a cut out at the zero position to create a reuse prevention mechanism. Likewise, the second alternative second fail safe design could include a friction surface similar to surface154between the protrusion145and the rib256. In a preferred design, the friction surface could have the function of an adjustable break, where if the user presses with a force lower than that of the compression spring, the rib256is pressed against the protrusion145. The lower the force on the knob31, the higher the force between the rib256and the protrusion145, and the higher the friction. Such an adjustable break could for example use rubber-like materials on the friction surface, the protrusion or both. In this preferred embodiment the user is able to both reduce the speed and accelerate the speed, which is given by the torsion spring. Of course, if the design of the protruding rib included cut-outs, then this adjustable break feature would not be applicable.

It is to be understood that the embodiments described above and shown in the drawings are to be regarded only as non-limiting examples of the possible designs of the safety assembly and such designs may be modified in many ways within the scope of the patent claims.