Medicament delivery assembly with end of delivery signaling

Abstract

This text concerns a medicament delivery device (2) for accommodating a medicament containing a medicament and for expelling multiple pre-defined doses. It comprises a base assembly to which the medicament container is mountable. It comprises a plunger rod assembly which is axially movable relative to the base assembly for interacting with the medicament container for expelling the medicament. And a biasing member (9) forces the plunger rod assembly in a proximal direction. A loading mechanism enables a user to bias the biasing member (9). The device further comprises a signaling mechanism which comprises a signaling member (16) and which can initiate, for each of the doses, at the end of the expelling of the respective dose, a signaling movement of the signaling member (16) which causes a user-perceivable signal. The signaling member (16) is subject to a bias for carrying out the signaling movement. And the signaling mechanism can block the signaling movement and, at the end of the expelling of each dose, can unblock the signaling movement.

Description

[0001] MEDICAMENT DELIVERY ASSEMBLY WITH END OF DELIVERY SIGNALING

[0002] TECHNICAL FIELD

[0003] The invention is in the field of medicament delivery devices. In particular, it relates to automatic medicament delivery devices. The invention more particularly relates to medicament delivery devices for delivering multiple doses of a medicament from one medicament container. Specifically, it relates to automatic medicament delivery devices for delivering multiple doses of a medicament from one medicament container which produce a signal perceivable by a user indicating that an end of a dose delivery has been reached and / or that a dose delivery has started.

[0004] BACKGROUND

[0005] Medicament delivery devices for automatic delivery of a medicament by selfadministration are well-known. Especially, they may be equipped to accommodate a medicament container, for example a medicament container with a septum (or another seal) to be perforated immediately prior to use, or a syringe. Often, the medicament delivery device and the medicament container are pre-assembled to constitute a medicament delivery assembly for self-administration.

[0006] For large doses, single-use autoinjectors with a tensioned spring dominate the market, whereas for small doses pen injectors containing multiple doses have been the main route. Such pen injectors are mainly operated manually, in that the user presses a button to inject the medicament with manual force. This is not a viable option for larger doses. To increase sustainability and minimize the generated waste, an autoinjector suitable for large doses but also containing multiple doses would be desirable, even though this requires the patient to change needle before each dose.

[0007] Devices configured for expelling multiple doses and having a pre-tensioned spring, however, suffer from disadvantages: The spring needs to be very strong to store the energy for expelling a multitude of doses. This poses high demands on the materials used. For example, it has to be made sure that the material does not creep under storage. Also, the force profile differs from dose to dose, since the tension of the spring will decrease from dose to dose. Medicament delivery thus takes substantially more time for the last doses than for the first doses.

[0008] For these reasons, it has already been proposed to provide the medicament delivery device with a loading mechanism that tensions the used spring before each injection. However, such loading mechanisms come about with variable doses of the drug, and this affects safety, as the user may set a wrong dose.

[0009] Moreover, it is valuable for a user to perceive a signal indicating that the end of a dose delivery (“end-of-dose signal”; “end click”) has been reached. Mechanisms for producing such a signal are known for injectors providing merely a single dose. And it is valuable for a user to perceive a signal indicating that a dose delivery (“start signal”) has started.

[0010] SUMMARY

[0011] It is an object of the present invention to provide a medicament delivery device overcoming disadvantages of prior art medicament delivery devices. Especially, it is an object to provide a medicament delivery device suitable for delivering multiple doses of a medicament from one container which produces, for each dose, an end-of- dose signal and / or a start signal. The device should have a high usability and should be safe.

[0012] Another object of the invention is to provide a medicament delivery device which is particularly simple to operate.

[0013] Another object of the invention is to provide a medicament delivery device which is particularly safe to operate.

[0014] Another object of the invention is to provide a medicament delivery device can be operated by a user without having to apply high forces and torques, respectively.

[0015] Another object of the invention is to provide a medicament delivery device which is environment-friendly and has a low carbon footprint, respectively.

[0016] These objects are achieved by the device and assembly as defined in the claims. Further objects and various advantages emerge from the description and embodiments below.

[0017] The medicament delivery device is equipped for accommodating a medicament container containing a medicament and for expelling multiple pre-defined doses of the medicament from the medicament container. The medicament delivery device defines a device axis and comprises a base assembly and a plunger rod assembly.

[0018] The base assembly may comprise a housing, the housing for example comprising a device body and a container housing. The medicament container is mountable to the base assembly in a stationary manner.

[0019] The plunger rod assembly is axially movable relative to the base assembly and, by an axial movement in a proximal direction, interacts with the medicament container to expel the medicament therefrom. The medicament delivery device to this end further comprises a biasing member configured to force the plunger rod assembly in the proximal direction.

[0020] The medicament delivery device further comprises a loading mechanism configured for a user to cause a biasing of the biasing member. The step of biasing the biasing member and, more particularly the step of causing the first plunger rod device towards distally (cf. below for details) and thereby biasing the biasing member is also called "loading step" in the present text.

[0021] The medicament delivery device further comprises a signaling mechanism which comprises a signaling member. The signaling mechanism is configured to initiate, for each of the doses, at the end of the expelling of the respective dose, a signaling movement of the signaling member. The signaling movement causes a user- perceivable signal. The signaling movement comprises an axial movement in a distal direction, the distal direction being the direction pointing away from a dose delivery site during use of the medicament delivery device.

[0022] In other words, at the end of each dose delivery, the signaling member carries out a signaling movement, triggered by the signaling mechanism. And the signal is provoked by the signaling movement. In particular, the signaling mechanism can be configured to produce, for each of the doses, a user-perceivable signal at the end of expelling the respective dose.

[0023] In embodiments, the signal is an audible signal.

[0024] In embodiments, the signal is a tactile signal. In particular, it can be both, audible and tactile.

[0025] In embodiments, the signaling member is subject to a bias for carrying out the signaling movement, and the signaling mechanism is configured to block the signaling movement and, at the end of the expelling of each dose, to unblock the signaling movement.

[0026] This way, the signaling member can be in a biased (charged) state just before the end of the dose delivery is reached, while the signaling movement - which is forced by the bias - is impeded (blocked). And then, at the end of the dose delivery, the signaling member is released (unblocked), i.e., it can carry out the signaling movement. This way, the energy from the bias can quickly discharge inform of the signaling movement. Accordingly, much energy can be provided in short time, e.g., the signaling member can be strongly accelerated, and this way, the signaling member can reach a considerable speed. A well perceivable signal, such as a sound and / or a hit or vibration can be generated. More generally, the signaling movement could cause the signal in a different manner, e.g., operating a switch which causes the signal.

[0027] Generally, the signaling member can be biased by any energy storage device, in particular any device storing mechanical energy, such as a spring. That energy storage device can generally be different from the biasing member. However, it can be advantageous to use the biasing member not only for the plunger rod assembly, but also for producing the bias for the signaling member. Accordingly:

[0028] In embodiments, the bias on the signaling member is caused by the biasing member. In other words, the signaling member is biased by the biasing member, more specifically, for carrying out the signaling movement. This way, producing the signal makes use of the biasing member instead of an additional item such as an additional spring. Accordingly, the medicament delivery device can possibly comprise one part less. And the assembly of the medicament delivery device can be simplified, and its disposal after use can be simplified.

[0029] The biasing member can thus store energy for both, for expelling the medicament and for producing the signal. E.g., in case of a compression spring as the biasing member, the biasing member is compressed for expelling a respective dose and is subject to an additional compression for generating the signaling movement and thus the signal.

[0030] In embodiments, the biasing member comprises a compression spring.

[0031] As will be explained in more detail further below, the signaling member can be realized in a bearing which comprises a suitable cam curve.

[0032] In embodiments, the signaling mechanism comprises an initiating member configured to unblock the signaling movement at the end of the expelling of each dose by causing an initiating movement of the signaling member from a charged position of the signaling member to a start position of the signaling member. Therein, the signaling movement is a movement from the start position to a discharged position of the signaling member. In other words, to release the signaling movement, the signaling member carries out an initiating movement which more particularly is caused by the initiating member cooperating with the signaling member. The initiating movement takes place from a charged position in which, more particularly, the bias on the signaling member is higher than in the discharged position and in which the signaling movement is blocked, to a start position in which, more particularly, the signaling movement is not blocked anymore. Thus, the signaling movement, taking the signaling member from the start position to the discharged position, can take place, forced by the bias. In particular, the signaling movement can be forced by the bias difference between the start position and the discharged position; and the bias in the start position can be substantially the same as in the charged position. In embodiments, the movement from the start position to a discharged position is forced by the biasing member.

[0033] In embodiments, the initiating movement comprises a rotational movement.

[0034] In embodiments, the start position is proximal relative to the discharged position.

[0035] In embodiments, the signaling movement comprises a distal movement, more particularly, the signaling movement is a substantially distal movement.

[0036] In embodiments, the initiating member comprises an initiating surface abutting the signaling member for causing the initiating movement.

[0037] In embodiments, the plunger rod assembly is configured to carry out, for each of the doses, for expelling the respective dose, a proximal movement, wherein the initiating member is coupled to the plunger rod assembly such that the initiating member, at the end of the proximal movement, interacts with, e.g., abuts, the signaling member to cause the initiating movement.

[0038] This way, the proximal movement which anyway takes place for expelling respective doses of the medicament, is made use of for initiating the signaling movement. More particularly, the coupling between the initiating member and the plunger rod assembly can be embodied such that the time at which the initiating movement is caused, relative to the expelling of the dose, is suitably set, namely at the end of the dose delivery.

[0039] In embodiments, the initiating member is coupled to the plunger rod assembly such that the initiating member carries out the proximal movement together with the plunger rod assembly. E.g., the plunger rod assembly and the initiating member can be fixedly attached to one another, more particularly, the plunger rod assembly and the initiating member can form a unitary part.

[0040] In embodiments, the medicament delivery device comprises a distance varying feature and a cooperation feature, and the base assembly comprises a cooperation member. Furthermore, either the signaling member or the cooperation member comprises the distance varying feature; and the other one comprises the cooperation feature. The distance varying feature and the cooperation feature cooperate with one another, whereby a rotational relative movement of the distance varying feature and the cooperation feature in a first sense of rotation causes the signaling member to change, in particularly repeatedly change, from the discharged position via the charged position to the start position and back to the discharged position. This embodiment specifies a way of realizing a way of generating, in particular repeatedly generating, a signaling movement and an end-of-dose signal, respectively, with a possibility to increase the bias on the signaling member in order to make use of the bias for the signaling movement. Said rotational relative movement can, more particularly, cause an axial relative movement of the signaling member and the cooperation member.

[0041] The distance varying feature and the cooperation feature cooperate and can convert a rotational relative movement into changes in axial relative position of the two parts. In particular: In case the axial positions differ more strongly, the bias on the signaling member can be higher, and, relative thereto, in case the axial positions differ less strong, the bias on the signaling member can be lower.

[0042] The distance varying feature and the cooperation feature can be abutting one another, optionally with the exception that they may be not abutting during the signaling movement. The cooperation member can be considered, e.g., an abutting member.

[0043] The cooperation feature can be, e.g., a matching distance varying feature, or can be another abutting feature abutting the distance varying feature, such as abutting ledges.

[0044] During the rotational relative movement, the cooperation feature can slide along the distance varying feature. In embodiments, the signaling member comprises two cam curves of the described kind (with a base section, a sloped section, a top section, and a step feature), which are offset by 180° with respect to one another.

[0045] In embodiments, the cooperation member comprises two cooperation features, offset by 180° with respect to each other, one for each of the two cam curves.

[0046] In embodiments, the distance varying feature comprises a circumferential ridge.

[0047] In embodiments, the cooperation member is comprised in a bearing seat. This can be particularly simple and useful in case the signaling member comprises a bearing member, cf. below.

[0048] In embodiments, the signaling member comprises at least one first abutting surface, and the cooperation member comprises at least one second abutting surface, wherein a hitting of the at least one first abutting surface onto the at least one second abutting surface causes the signal. This can be a useful and simple way of generating the signal from the signaling movement - which causes the hitting. The signal can be both, audible and tactile.

[0049] The distance varying feature can, e.g., describe a suitable cam curve, such as described in the following.

[0050] In embodiments, the distance varying feature comprises, extending along a circumference, a bottom section adjacent a sloped section adjacent a top section adjacent a step feature. In other words, the distance varying feature comprises, in the following order of sequence and each one adjoining the next one: a bottom section, a sloped section, a top section, and a step feature. Furthermore, the bottom section defines a bottom level and is recessed relative to the top section. The sloped section interconnects the bottom section and the top section in a slope-like (or ramp-like) fashion. The step feature forms a step-like recess from the top section to the bottom level. Such a distance varying feature can effect, when rotating relative to the abutting cooperation feature, that the bias on the signaling member is gradually increased and then abruptly decreased for producing the signaling movement.

[0051] In embodiments, in the discharged position, the cooperation feature abuts the bottom section, and in the charged position, the cooperation feature abuts the top section at an end of the top section adjacent the step feature.

[0052] For realizing a particularly large axial movement during said rotational relative movement in a manner which nevertheless saves space in axial direction, the cooperation feature can be a distance varying feature which matches the distance varying feature of the signaling member. In particular, these two distance varying features can be embodied essentially identically, and thus the cooperation feature also comprises, extending over a circumference, a bottom section adjacent a sloped section adjacent a top section adjacent a step feature.

[0053] In that case, the situation can be as follows: In the discharged position, the bottom sections (of the signaling member and of the cooperation member, respectively) abut one another, and the top sections (of the signaling member and of the cooperation member, respectively) abut one another. In the charged position, the top sections (of the signaling member and of the cooperation member, respectively) abut one another at their respective ends adjacent the respective step features.

[0054] Furthermore, during increasing the bias, the sloped sections can abut one another.

[0055] The step-like recess can describe a step aligned essentially parallel to axis. Or even an undercut could be provided.

[0056] The sloped section can axially extend between the bottom level and a level (top level) defined by the top section.

[0057] The sloped section can describe a continuously rising slope. A gradual increase between bottom level and top level with a not too steep slope can reduce the torque that has to be applied by the user. In embodiments, the level present at an end of the step feature opposite an end of the step feature where the step feature adjoins the top section is equal to the bottom level.

[0058] In embodiments, the distance varying feature is a circumferential ridge which is higher in the top section than in the bottom section and sloped in the sloped section.

[0059] In embodiments, the sloped section defines a continuously rising slope. This is very effective for smoothly increasing the bias.

[0060] In embodiments, the medicament delivery device comprises a charging mechanism configured for a user to move the signaling member from the discharged position to the charged position to cause the signaling member to move proximally and thereby to increase the bias on the signaling member. This can be accomplished, e.g., by the rotational relative movement described above.

[0061] Moving the signaling member from the discharged position to the charged position can in particular be a movement in a proximal direction. It takes place against the force provided by the bias.

[0062] In particular, the medicament delivery device can be configured for the charging mechanism to be activated a plurality of times.

[0063] In embodiments, the plunger rod assembly has a first plunger rod device and a second plunger rod device. In this, the second plunger rod device is configured to interact with the medicament container to expel the medicament therefrom when the plunger rod assembly is moved in the proximal direction. For example, the second plunger rod device may act on a plunger of the medicament container, wherein the movement of the plunger towards proximally expels the medicament when a needle is mounted.

[0064] In embodiments, the loading mechanism is configured to allow the user to move the first plunger rod device in a distal direction relative to both, the base assembly and the second plunger rod device, and to thereby bias the biasing member. The approach may thus comprise having a first plunger rod device that is moved in a distal direction relative to both, the base assembly and the second plunger rod device, to bias the biasing member. This allows the user to load the medicament delivery device prior to expelling the first dose (if not already loaded ex-factory) and to reload it prior to expelling any further dose. For each dose, the first plunger rod device may be subject to an axial movement from essentially a same initial position (loaded position) to a same end position (unloaded position). The loaded position and the unloaded position are pre-defined and may be the same for every dose, so that dispensing errors can be excluded and so that the time for expelling the medicament may be the same for each dose. Also, due to the mentioned approach, the biasing member does not need to store the energy for all the doses. If not already loaded exfactory, it does not even need to store the energy for any dose until immediately before medicament delivery. Hence, the medicament delivery device does not have the problem of being under high load for a long time. The biasing member - for example, a compression spring - may rather be in a low load state during storage and be supported by rigid parts. This makes possible that for the medicament delivery device no materials fulfilling high demands concerning resistance to creeping have to be used. Rather, also simpler plastic such as Polypropylene (PP) can be used, and it is possible to make all parts - except the compression spring - of the medicament delivery device of a same material, which facilitates recycling. Especially, the base assembly and the plunger rod assembly (and optionally also an activation element, as described hereinafter) may be made of a same material, especially a same polymer material, for example PP.

[0065] When the user moves the first plunger rod device in the distal direction, the plunger rod assembly may be configured for the second plunger rod device to not participate in this movement and for example to stand essentially still.

[0066] Since the medicament delivery device is configured for expelling multiple doses of the medicament, the distance travelled by the plunger rod assembly for delivering a dose of the medicament will be less than, and only a fraction of, the distance the plunger of the medicament container travels from the initial, full state to a final, empty state. The second plunger rod device will move forward (towards proximally) together with the first plunger rod device, as part of the plunger rod assembly for expelling the medicament, whereas it is only the first plunger rod device that makes the backward (towards distally) movement during the loading step.

[0067] The loading mechanism may for example comprise the principle that the user twists a twisting element - for example, a loading sleeve - relative to the base assembly. The loading mechanism may further comprise a conversion of the rotational movement caused by the twisting of the twisting element into the translational movement of the first plunger rod device. To this end, the twisting element may be rotationally couplable (fixedly coupled or equipped to be coupled for the loading action) to the first plunger rod device, with respect to rotations around the axis. Then, at least one of the first plunger rod device and of the base assembly may comprise a helical feature, whereas the other one comprises a cooperating feature (not to be confused with the cooperation feature) cooperating with the helical feature to cause the movement towards distally upon the rotational movement of the first plunger rod device. For example, the base assembly may comprise a helically running slope as the helical feature, and the first plunger rod device may comprise a matching slope or an abutting element that is in contact with the slope. According to an alternative, the first plunger rod device may comprise a thread, for example an external thread, as the helical feature, cooperating with a thread engaging protrusion, for example inward protrusion, of the base assembly. Further alternatives include a thread (for example internal thread) of the base assembly as the helical feature, cooperating with a thread engaging protrusion, for example outward protrusion, of the first plunger rod device, etc.

[0068] In embodiments, the first plunger rod device comprises a first coupling feature, and the signaling member comprises a second coupling feature cooperating with the first coupling feature to derive from the rotation of the first plunger rod device around the axis a rotation of the signaling member around the axis to cause the rotational relative movement of the distance varying feature and the cooperation feature in the first sense of rotation.

[0069] In an example, the first coupling feature comprises a ledge, and the second coupling feature comprises a guiding slit in which the ledge is guided. Thus, operating the twisting element not only loads the biasing member (for dose delivery), but also increases the bias on the signaling member, so as to provide energy for producing the signal. I.e., a user action for operating the twisting element to load the biasing member also energizes the signaling mechanism.

[0070] Using one and the same user control (such as the twisting element) for loading the biasing member and for increasing the bias on the signaling member simplifies construction of the medicament delivery device (less parts) and simplifies operation of the medicament delivery device by a user.

[0071] The construction of the medicament delivery device is further simplified if, as described above, the biasing member produces the bias on the signaling member. E.g., in case the biasing member comprises a compression spring, it is compressed for storing energy for the dose deliver, more specifically for the proximal movement of the plunger rod assembly, and it is additionally compressed for storing energy for the signaling movement.

[0072] In embodiments, the first coupling feature comprises the initiating member. More particularly, the initiating member can cooperate with an initiation feature, such as an initiation surface of the signaling member to cause the initiating movement. The initiation feature can be comprised in or be adjacent to the second coupling feature.

[0073] In embodiments, the first coupling feature and the initiating member are comprised in the first plunger rod device. This way, the rotational movement of the first plunger rod device during loading can be made use of for energizing the signaling member, and the rotational movement of the first plunger rod device can be made use of for unblocking the signaling movement.

[0074] In embodiments, the additional compression takes place in an initial phase of the loading step, more particularly in an initial phase of the user’s twisting of the twisting element by which the user effects the compression of the spring. This can reduce the maximum torque to be applied by the user for operating the medicament delivery device. In embodiments, the top section comprises, adjacent the step feature, a range in which the distance varying feature is not sloped. More particularly, in said range, the distance varying feature lies in a plane perpendicular to the axis.

[0075] This way, the energizing of the signaling member for the signaling movement does not take place at the end of the loading step and thus takes place in an initial phase of the loading step. And the bias on the signaling member is maximum already for some angular range before the step feature is reached and the first plunger rod device has reached the loaded position.

[0076] In other words, the signaling mechanism can be configured to cause the increasing of the bias on the signaling member in an initial portion of the loading step, such as in an initial portion of a twisting by the user of the twisting element.

[0077] Accordingly, a maximum torque to be applied by a user is lower in this case than if still in a final phase of the twisting, both, the loading for the dose delivery and the energizing for the signaling take place.

[0078] A torque required to be exerted by the user for increasing the bias on the signaling does not add to a maximum torque occurring during loading (namely at the end of the loading step) but instead adds to a lower, rather initial torque, since the biasing member is not yet so strongly biased before the end of the loading, e.g., the compression spring is not yet so strongly compressed before the end of the loading.

[0079] In embodiments, the signaling member comprises a bearing member, and the cooperation member comprises a bearing seat cooperating with the bearing member, e.g., abutting the bearing member (and thus the signaling member). The bearing member and the bearing seat can cooperate to form a bearing for the biasing member. In particular, the bearing can form a glide bearing for the biasing member, especially in case the biasing member is a compression spring. The bearing can prevent wear between biasing member and base assembly. More particularly, as the first plunger rod device, during the loading, rotates and axially moves in distal direction to compress the biasing member (e.g., the compression spring), the bearing prevents wear that otherwise would occur from the rotational movement of the biasing member, because its distal end would, without the bearing, abut the base assembly such as a spring stop comprised in the base assembly.

[0080] In embodiments, the signaling member and the bearing member form a unitary part. This simplifies the construction of the medicament delivery device.

[0081] In embodiments, the cooperation member and the bearing seat form a unitary part. This simplifies the construction of the medicament delivery device.

[0082] Furthermore, the cooperation member can, in particular, comprise a spring stop.

[0083] In embodiments, the cooperation member and the spring stop form a unitary part, in particular together with the bearing seat. This simplifies the construction of the medicament delivery device.

[0084] In embodiments, the base assembly or the first plunger rod device comprises two helically running slopes as helical features, with a 180° axial symmetry between them. Accordingly, the first plunger rod device or the base assembly, respectively, comprises two cooperating features, offset by 180° with respect to each other, one for each of the helically running slopes. Thereby, the substantial axial force, to which the first plunger rod device is subject during the loading step, does not lead to any bending moment on the medicament delivery device.

[0085] In addition, the second plunger rod device may comprise a plunger rod thread, for example an external thread, cooperating with a thread engaging feature of the first plunger rod device, for example an inward protrusion or an internal thread. The helical feature(s) and the plunger rod thread both have the same direction of rotation. Further, the lead (axial advance per turn) of the plunger rod thread of the second plunger rod device may approximately correspond to the lead of the helical feature that causes the axial displacement of the first plunger rod device towards distally during the loading step. This makes possible that the second plunger rod device remains essentially stationary while the first plunger rod device is subject to the helical movement, i.e., rotation around the axis together with a translation along the axis, for the loading step. To this end, the second plunger rod device may be mounted to be not able to rotate relative to the base assembly, i.e., it may be rotationally coupled to the base assembly.

[0086] The medicament delivery device may further be configured for the first plunger rod device to be locked in the loaded position at the end of the loading step. Thereafter, once it is unlocked by suitable activation - for example by a user pressing an activation button - the biasing member forces the first plunger rod device forward towards proximally. During this expelling step, the first plunger rod device may be rotationally locked, i.e., prevented from rotating. Thereby, the engagement of the plunger thread with the thread engaging feature causes the second plunger rod device to be moved towards proximally with the first plunger rod device, i.e., the plunger rod assembly is moved as a whole. Thereby, the second plunger rod device acts on the medicament container to expel the desired dose of the medicament.

[0087] At the end of the loading step, the engagement between the helical feature and the cooperating feature may end, so that the first plunger rod device can, upon activation, be forced towards proximally for the expelling step. For example, if the helical feature comprises a slope of the base assembly, it may be configured for the cooperating feature to reach the top (distal-most point) of the respective slope. When the loading step is about to be completed, a locking mechanism that locks the first plunger rod device until unlocking / activation, sets in. In embodiments, the transition between the engagement of the helical feature with the cooperating feature and the engagement of the locking mechanism comes about with a small movement of the first plunger rod device in the proximal direction, forced by the biasing member. This slight offset between the distal-most position during the loading movement on the one hand and the loaded position, in which the first plunger rod device is locked, on the other hand, firstly has the advantage that the locking mechanism will reliably engage. This engagement is secured even when there are some manufacturing tolerances in the parts of the medicament delivery device. Secondly, the small displacement in the proximal direction and the stopping thereof by the locking mechanism may produce audible feedback in the form of a click-like sound, indicating the user that the loading step has been successfully completed. Thirdly, if the helical feature is a slope of the base assembly, a cliff-like structure of the slope may, in the loaded position, impede a back rotation, so that the slope of the base assembly has effectively a double function. A separate limit may impede a further forward rotation once the loaded position has been reached.

[0088] In a group of embodiments, the lead of the helical feature is slightly larger than the lead of the plunger rod thread, the difference compensating for the mentioned optional small displacement in the proximal direction upon completion of the loading step. Thus, when activated, the second plunger rod device will be at the same position as it was before the loading step started, and the small displacement in the proximal direction upon completion of the loading step will not cause any medicament to be expelled.

[0089] In embodiments, the engagement of the plunger rod thread on the one hand and the thread engaging feature (for example internal thread) of the first plunger rod device on the other hand is subject to some clearance, by the thread grooves being wider than the axial extension of the thread ridges. The axial extension of the clearance may correspond to the difference between the axial advance of the helical feature during the loading step on the one hand and the axial advance of the plunger rod thread on the other hand - and for example also to the axial distance by which the first plunger rod device travels during the above-mentioned small displacement in the proximal direction upon completion of the loading step. Thereby, the clearance makes sure that the loading step can be completed without the second plunger rod device travelling back and forth.

[0090] Locking in the loaded position may in a group of embodiments take place as follows: One of the first plunger rod device and of the base assembly comprises a pair of locking arms with locking protrusions and the other one has a locking structure with which the locking protrusions can engage. Such locking structure may for example comprise a ridge, distally of which the respective locking protrusion can engage. Alternatively, it may comprise a hole in which the locking protrusion can engage. The locking arms are caused to flex in a resilient manner in the process of the movement of the first plunger rod device during the loading step and to flex back for the locking protrusions to engage the locking structure immediately before the loading step is completed, i.e., before the first plunger rod device reaches the loaded position.

[0091] In embodiments, the locking arms are locking arms of the first plunger rod device, and the locking structures each comprise an inner ramp of the base assembly. Therein, upon the combined rotational-translational movement of the first plunger rod device during the loading step, the locking protrusions slide along the inner ramp of the base assembly and thereby are caused to flex inwardly. Shortly before the loaded position is reached, the locking protrusions lose contact with the inner ramps and flex outwardly again due to their resilience. This locks the locking protrusions in front of the inner ramps and impedes a movement of the first plunger rod device towards more proximally.

[0092] The first plunger rod device may be a plunger nut, with an internal cavity that accommodates at least a portion of the second plunger rod device, and with the thread engaging feature being an interior thread of the plunger nut.

[0093] The second plunger rod device may comprise a plunger rod. In embodiments, with the plunger rod thread is an exterior thread on the plunger rod.

[0094] In a group of embodiments, the second plunger rod device further comprises a priming rod that is movable in the proximal direction relative to the plunger rod and that comprises an impact surface. The impact surface is in physical contact with the plunger of the medicament container for expelling the medicament. The priming rod may for example have a shaft extending in an axially running internal cavity of the plunger rod, and a proximal widening that comprises the impact surface.

[0095] Priming in these embodiments will take place before the medicament is expelled for the first time and for example also before the first time a loading step is performed: By moving the priming rod towards proximally, for example by the user pressing against an activation button, initial gaps in the medicament delivery assembly (that comprises the medicament delivery device and a medicament container mounted to it) are eliminated. If a needle is already affixed at this stage, this priming action can be performed until a small amount of the medicament is expelled through the needle so that priming includes removing any air remaining in the needle's lumen. A ratchet may be established by the plunger rod and the priming rod, whereby the priming rod can be displaced relative to the plunger rod towards proximally for the priming, but not back towards distally. Thus, once priming is established, the medicament delivery device may remain free from clearances.

[0096] In alternative embodiments, the second plunger rod device consists of the plunger rod, without any separate priming rod. It is even possible that the plunger rod also comprises the plunger, for example if the medicament container is syringe-like. In other words, it is not necessary that the plunger of the medicament container is separate from the plunger rod.

[0097] The medicament delivery device can further comprise an activation mechanism for activating the medicament delivery device by initiating the expelling step in which the biasing member forces the plunger rod assembly, comprising the first and second plunger rod devices, towards proximally. The activation mechanism may for example comprise an activation button, an activation slider or similar and may cause, when applied, unlocking of the plunger rod assembly in the loaded position.

[0098] In embodiments that comprise the above-mentioned locking arms of the first plunger rod device or of the base assembly, the activation mechanism may comprise an activation structure that in the course of the activation acts to flex the locking arms until their locking protrusions get out of engagement with the locking structure and thereby release the plunger rod assembly so that it can be displaced towards proximally.

[0099] In embodiments, the activation mechanism comprises an activation button that is arranged at the distal end of the medicament delivery device and that can be pressed towards proximally for the activation. The activation button may for example comprise activation wings serving as activation structures and that force the locking arms to flex when the activation button is pressed towards proximally when the first plunger rod device is in the loaded position. To this end, the locking arms at onset of the locking protrusions may comprise locking arm ramps along which the proximal end of the activation wings slide to gradually force the locking arms to flex until they get out of engagement with the locking structure.

[0100] Furthermore, we describe embodiments in which as start signal is generated. These embodiments can be combined with embodiments which comprise the generation of an end-of-dose signal. However, they can also be implemented independently of those.

[0101] In embodiments, more particularly: in embodiments which enable generation of signals indicative of the start of the expelling (of the dose), the medicament delivery device further comprises a spring stop member which comprises a spring stop coupling structure and which is forced towards distally by the biasing member. It is this way fixable to the base assembly by the spring stop coupling structure engaging with a base assembly coupling structure of the base assembly with a distal face of the spring stop coupling structure abutting a proximal face of a portion of the base assembly coupling structure. One of the first plunger rod device and of the spring stop member comprises a pair of locking arms with locking protrusions, and the other one of the first plunger rod device and of the spring stop member comprises a locking structure capable of engaging with the locking protrusions. Furthermore, the medicament delivery device is configured for the locking arms to flex in a resilient manner while the user causes the distal movement of the first plunger rod device for loading and to flex back for the locking protrusions to engage the locking structure immediately before a loaded position has been reached by the first plunger rod device. The medicament delivery further comprises an activation mechanism for the user to activate medicament delivery. The activation mechanism comprises an activation button with an activation structure which, when the activation button is pressed, moves towards proximally to cause the locking arms to flex until their locking protrusions get out of engagement with the locking structure. This causes a release of the plunger rod assembly so that the biasing member displaces the plunger rod assembly towards proximally. Still furthermore, the medicament delivery device comprises a signalization mechanism for causing a start signal for each of the doses, the start signals being perceivable by the user and being indicative of a start of the expelling of the respective dose, wherein the signalization mechanism is operated by operating the activation mechanism in that - when the activation button is pressed - the activation structure in a first position while moving towards proximally, causes, by sliding on locking protrusion ramps of the locking protrusions, the locking arms to flex and to this way cause a movement of the spring stop towards proximally (wherein it, more particularly counteracts a force exerted by the biasing member forcing the spring stop member towards distally); therein, the movement of the spring stop towards proximally is limited towards proximally by a limiting structure of the spring stop member abutting a limiting shoulder of the base assembly, and said movement opens up a gap between the distal face of the spring stop coupling structure and the proximal face of the portion of the base assembly coupling structure; and subsequently, the activation structure in a second position while moving towards proximally, causes the release of the plunger rod assembly, which causes the spring stop member to be forced by the biasing member to carry out a movement towards distally, which is limited towards distally by an abutment of the distal face of the spring stop coupling structure and the proximal face of the portion of the base assembly closing of the gap, and in particular, said movement towards distally also opens up a clearance between the limiting shoulder and the limiting structure.

[0102] Said abutment (of the distal face of the spring stop coupling structure and the proximal face of the portion of the base assembly) generates the start signal. And, in particular, the second position is located further towards proximally than the first position.

[0103] The herein described spring stop member, the herein described base assembly and the herein described activation mechanism (with the described locking arms) not only can be implemented in embodiments with start signal generation, but can also be implemented in embodiments without start signal generation, e.g., in embodiments with end-of-dose signal generation but without start signal generation. In embodiments having the priming rod, the activation button may have a double function by having, in addition to the activation wings (or similar structure for the activation), a priming structure, for example a priming protrusion, that acts to displace, when the activation button is pressed, the priming rod towards proximally for the above-described priming step.

[0104] In embodiments in which the activation button has this double function, the medicament delivery device may be equipped for the activation button to be re- set (displaced towards distally in a position in which it can again be pressed for activation) by the loading action. For example, the activation button may be rotationally coupled to the loading sleeve (or other twisting element) and may interact with a re-set structure of the base assembly to be displaced towards distally when rotated during the loading step. For example, the base assembly may comprise a reset slope interacting with a protruding boss of the activation button - or vice versa.

[0105] In a group of embodiments, the medicament delivery device is configured for the loading step to be caused by a 180° twist of the twisting element. A 180° twist can be caused by a user without loosening the grip on the twisting element and the base assembly relative to which the twisting element is twisted. Also, it allows to implement the mentioned 180° axial symmetry of the helical features without constraint. For example, the base assembly may comprise two identical slopes at identical axial positions, offset by 180° with respect to each other. Similarly, as described above, the signaling member can comprise two cam curves of the described kind which are offset by 180° with respect to one another. For most applications, the 180° twisting movement is sufficient to sufficiently load the medicament delivery device.

[0106] However, there are applications for which very a strong biasing member, for example a very strong compression spring, is required, for example if a relatively large dose of the medicament is to be expelled through a relatively thin needle. For some users, the torque that has to be applied to load such a strong biasing member by just a 180° twist may be too high to be convenient. Therefore, in an alternative group of embodiments, the medicament delivery device is configured for the loading step to be caused by a more-than-180° twist of the twisting element, especially a 360° twist.

[0107] Also in embodiments of this alternative group of embodiments, it the base assembly or the first plunger rod device may comprise two helical features, especially helically running slopes, and the first plunger rod device or the base assembly, respectively, comprises two cooperating features, offset by 180° with respect to each other so that there is no substantial bending moment when the twisting element is twisted against the biasing force of the biasing member. Especially, the two helical features may be at different radial positions, one further radially-inside than the other one, but may otherwise by subject to the mentioned 180° axial symmetry with respect to each other. The helical features extend by more than 180° around the axis.

[0108] Regarding the signaling mechanism, in an analogue manner, the cam curves may extend over more than 180° and may be at different radial positions, one further radially-inside than the other one.

[0109] Especially - but not only - in embodiments of this alternative group, the helical feature(s) may be provided with one or more step features that have the function of preventing a twisting back once the twisting movement has gone beyond a certain angle defined by the step feature(s), for example beyond 180°. Step features constitute deviations from a monotonously helical course of the helical feature(s) and may for example be formed by zags interrupting the respective slopes, or as zeroincline portions between slope portions.

[0110] The described approach makes possible that the biasing member is an element that causes a purely axial force, in contrast to for example a torsion spring. Especially, the biasing member may be a compression spring, for example a helical spring. Compression springs compared to torsion springs have substantial advantages in terms of manufacturing and assembly.

[0111] The medicament delivery assembly comprises the medicament delivery device as herein described and further comprises the medicament container assembled with the medicament delivery device. In addition, it may comprise a needle assembly that is equipped to pierce a septum of the medicament container and that has a needle for injecting the medicament, especially subcutaneously.

[0112] In the present disclosure, when the term “distal direction” is used, this refers to the direction pointing away from the dose delivery site during use of the medicament delivery device. When the term “distal part / end” is used, this refers to the part / end of the delivery device, or the parts / ends of the members thereof, which during use of the medicament delivery device is / are located furthest away from the dose delivery site. Correspondingly, when the term “proximal direction” is used, this refers to the direction pointing towards the dose delivery site during use of the medicament delivery device. When the term “proximal part / end” is used, this refers to the part / end of the delivery device, or the parts / ends of the members thereof, which during use of the medicament delivery device is / are located closest to the dose delivery site.

[0113] Further, the terms “longitudinal”, “longitudinally”, “axially” and “axial” refer to a direction extending from the proximal end to the distal end and along the device or components thereof, typically in the direction of the longest extension of the device and / or component.

[0114] Similarly, the terms “transverse”, “transversal” and “transversally” refer to a direction generally perpendicular to the longitudinal direction.

[0115] Generally, all terms used in the claims are to be interpreted according to their ordinary meaning in the technical field, unless explicitly defined otherwise herein. All references to a / an / the element, apparatus, member, component, means, etc. are to be interpreted openly as referring to at least one instance of the element, apparatus, member component, means, etc., unless explicitly stated otherwise.

[0116] BRIEF DESCRIPTION OF THE DRAWINGS

[0117] Embodiments of the present disclosure will now be described by way of example only and with reference to the following accompanying drawings. The drawings show: Figure 1 a medicament delivery device with a medicament container, in a perspective view;

[0118] Figure 2 a medicament delivery assembly comprising the medicament delivery device of Fig. 1 assembled with a needle assembly;

[0119] Figure 3 the medicament delivery assembly of Fig. 2, with a needle case removed;

[0120] Figure 4 a container housing of the medicament delivery device;

[0121] Figure 5 the medicament container;

[0122] Figure 6 a device body of the medicament delivery device;

[0123] Figure 7 the device body as shown in Fig. 6, shown transparent to illustrate structures in its interior;

[0124] Figure 8 a priming rod of the medicament delivery device;

[0125] Figure 9 a plunger rod of the medicament delivery device;

[0126] Figure 10 a plunger nut of the medicament delivery device;

[0127] Figure 11 the plunger nut of Fig. 10, shown transparent to illustrate structures in its interior;

[0128] Figure 12 a drive spring of the medicament delivery device;

[0129] Figure 13A a spring stop of the medicament delivery device;

[0130] Figure 13A the spring stop as shown in Fig. 13 A, from a different perspective;

[0131] Fig. 14A a bearing member of the medicament delivery device;

[0132] Fig. 14B the bearing member as shown in Fig. 14A, from a different perspective;

[0133] Figure 15 a loading sleeve of the medicament delivery device;

[0134] Figure 16 an activation button of the medicament delivery device;

[0135] Figure 17 a view of the plunger rod assembly after the priming step; Figure 18 the medicament delivery device of Figs. 1-3 with the medicament container during different stages of its use;

[0136] Figure 19 a detail of a section through the medicament delivery device of Figs. 1-3;

[0137] Figure 20 a detail of the device body, which is shown transparent;

[0138] Figure 21 a detail of a distal portion of the medicament delivery device without the loading sleeve;

[0139] Figure 22 schematically, the working principle of the locking arms and the inner ramp:

[0140] Figure 23 a detail of a section through the medicament delivery device of Figs. 1-3 when the plunger nut is in the loaded position and the medicament delivery device is in the locked state;

[0141] Figure 24 another detail of the section through the medicament delivery device of Figs. 1-3 when the plunger nut is in the loaded position;

[0142] Figure 25 the bearing member and the bearing seat of the medicament delivery device during different stages of its use;

[0143] Figure 26 the bearing member and the plunger nut of the medicament delivery device during different stages of its use;

[0144] Figure 27 the bearing member of the medicament delivery device, highlighting the sections of the distance varying feature;

[0145] Figure 28 the bearing seat of the medicament delivery device, highlighting the sections of the cooperation feature;

[0146] Figure 29 a plunger nut of an alternative embodiment of the medicament delivery device;

[0147] Figure 30 a view of a slope part of this alternative embodiment;

[0148] Figure 31 an other view of the slope part; Figure 32 a detail of elements of the alternative embodiment, in the unloaded state;

[0149] Figure 33 a detail of elements of the alternative embodiment, half-way through the loading step; and

[0150] Figure 34 a detail of elements of the alternative embodiment, upon completion of the loading step

[0151] Figures 35A-35D a perspective view onto a detail of an axial cross-section through a medicament delivery device in different stages regarding the generation of the start signal;

[0152] Figures 36A-36D enlarged details of Figures 35A-35D;

[0153] Figures 37A-37D a perspective view onto a detail of the distal portion of the medicament delivery device of Figs. 35A-35D, in corresponding stages regarding the generation of the start signal;

[0154] Figure 38 a perspective view of an enlarged detail of the medicament delivery device in the stage shown in Fig. 37B;

[0155] Figure 39 the spring stop of the medicament delivery device of Figs. 35A-35D, in a perspective view;

[0156] Figures 40A, 40B the device body of the medicament delivery device of Figs. 35A-35D, in two different perspective views.

[0157] DETAILED DESCRIPTION

[0158] Fig. 1 shows a medicament delivery device 2 and a medicament container 3 of a medicament delivery assembly., the medicament container 3 being seated in the container housing 4. The medicament delivery device 2 comprises a device body 5 with body window 51 and a container housing 4 with housing windows 41. The container housing 4 is fastened to the device body 5 by a click connection and is, in the assembled state, essentially immovable relative to the device body 5. Distally of the device body 5, the medicament delivery device has a loading sleeve 12 and, inside the loading sleeve, an activation button. Fig. 2 depicts the medicament delivery assembly 1, which comprises in addition to the medicament delivery device 2 and the medicament container 3 also a needle assembly 15 couplable to a proximal end (a fore end) of the medicament delivery device, namely to a needle assembly thread 42 of the container housing 4. Fig. 3 shows the medicament delivery assembly 1 in a ready-to use state with a needle case 150 removed. In addition to the needle case 150 (that may comprise an inner and an outer needle cap), the needle assembly comprises a needle hub 15a and the needle 15b. By screwing the needle assembly onto the container housing, the needle is caused to pierce a septum of the medicament container, whereafter the medicament can be dispensed via the needle by displacing a plunger 31 of the medicament container towards proximally. Needle assemblies suitable for this purpose are known in the field and are not described in any more detail here.

[0159] Figs. 4-16 illustrate, in addition to the medicament container 3 (Fig. 5), the elements of the medicament delivery device. The container housing 4 (Fig. 4) accommodates the medicament container 3 by having a seat open towards distally into which the medicament container 3 is insertable. The proximal end of the container housing 4 has an outer thread 42 for mounting the needle assembly. Through the housing windows 41, the user may see the medicament container 3 and can determine how many doses are left in it, with the assistance of dose indicators 43.

[0160] The container housing is, in the assembled state of the medicament delivery device, affixed to the device body 5 by container housing coupling structures 44 engaging into first coupling holes 52 of the latter.

[0161] The medicament container 3 (Fig. 5) may be of the kind known in the field, with the plunger 31 initially seated near its distal end, and with a septum 32 that can be pierced by a needle and that closes off the medicament container towards proximally.

[0162] The device body 5 (Fig. 6, Fig. 7) comprises a reload status window 51, which is also visible in Figs. 2 and 3. The purpose of this reload status window 51 is explained hereinafter. The device body 5 has the general shape of a hollow circular cylinder, with a plunger rod guiding portion 54 protruding towards the interior near the proximal end of the device body 5. Distally thereof, the device body 5 has helical slopes 55 formed by distally facing shoulders of protrusions along the interior surface of the hollow circular cylinder. The two helical slopes are offset with respect to each other by a rotation of 180° around the device axis A (see Fig. 1).

[0163] The medicament delivery device has a plunger rod assembly that for dispensing the medicament by being moved towards proximally and thereby acting on the plunger. The plunger rod assembly comprises a priming rod 6 (Fig. 8), a plunger rod 7 (Fig. 9) and a plunger nut 8 (Fig 10 and Fig. 11). The priming rod 6 has a priming rod shaft 61 seated inside the plunger rod 7 and a proximal impact surface 62 proximally of the plunger rod 7. The impact surface 62 is configured to be brought into physical contact with the plunger 31 of the medicament container to move the plunger 31 towards proximally for expelling the medicament. The priming rod 6 is, to some extent, movable relative to the plunger rod 7 in the proximal direction. A ratchet made up of priming rod ratchet structures 63 and plunger rod ratchet ridges 71 engaging into the grooves of the ratchet structures 63 allows a movement of the priming rod 6 towards proximally relative to the plunger rod 7 but prevents movements towards distally so that any movement of the plunger rod 7 towards proximally is transferred to the priming rod 6 and its impact surface 62.

[0164] The plunger rod 7 has a plunger rod thread 72 being an exterior thread running along a substantial portion of its axial extension. It is seated, at least partially (depending on the state of the medicament delivery device) in an interior of a plunger nut 8. The plunger nut has an internal thread 82 that engages with the plunger rod thread 72 of the plunger rod. The plunger nut 8 further comprises an outwardly protruding, flange-like circumferential ridge 81.

[0165] A distal portion of the plunger nut 8 runs inside a sleeve-like spring stop 11 (Fig. 13A and Fig. 13B). The spring stop 11 has spring stop coupling structures 111 engaging with second coupling holes 56 (as base assembly coupling structures) of the device body 5 and fixedly connecting the spring stop 11 to the device body 5 in the assembled state - at least while not being pushed towards proximally by a user during activation (cf. below regarding the generation of the start signal). The device body 5, the container housing 4, and the spring stop 11 are therefore fixed to each other and together constitute the base assembly. Spring stop 11 at the same time forms, at its proximal end, a bearing seat 18 which cooperates with a bearing member 16 (Figs. 14A, 14B) so as to function as a bearing for a drive spring 9 (Fig. 12).

[0166] The drive spring 9 - serving as the biasing member - is arranged between the circumferential ridge 81 of the plunger nut 8 and a bearing surface 16f of bearing member 16 which faces proximally. The medicament delivery device further comprises a loading sleeve 12 (Fig. 15) that is distally of the device body 5 and surrounds a distal portion of the spring stop 11, while a proximal portion thereof and the bearing seat 18 are surrounded by the device body 5, as is the bearing member 16.

[0167] Inside of the loading sleeve 12 and extending into an interior of the spring stop 11, the medicament delivery device further has an activation button 13.

[0168] Fig. 17 shows the plunger rod assembly 101 with the plunger nut 8, the plunger rod 7 and the priming rod 6. The priming rod 6 proximally slightly protrudes out of the mouth of the axially running internal cavity in the plunger rod 7, as is may be the case after the priming step.

[0169] For medicament delivery, the following steps are carried out:

[0170] • A. Needle assembly affixing: Initially, the needle assembly 15 is mounted to the pre-assembled medicament delivery device with the medicament container 3 already seated in the container housing 4. This will cause the septum of the medicament container to be penetrated by the needle, whereupon the medicament is capable of being expelled through the needle. In Fig. 18, panels I and II illustrate the needle assembly affixing step.

[0171] • B. Priming (panel III in Fig. 18): The user presses the activation button 13 towards proximally. The activation button 13 has a priming protrusion 131 that acts to transfer this movement towards proximally on to the priming rod 6 so that the latter moves towards proximally until its impact surface 62 is in physical contact with the plunger. A small amount of medicament may thereby be caused to be expelled if the user exerts sufficient pressure. This indicates to the user that the assembly is ready for medicament delivery. The ratchet prevents the priming rod 6 from being moved back towards distally in all further steps. Either before priming (preferable in most cases) or at the latest before medicament delivery, the needle case 150 is removed. Panel III in Fig. 18 shows the assembly with the needle case removed.

[0172] • C. Loading: The drive spring 12 is compressed between the circumferential ridge 81 of the plunger nut 8 and the bearing surface 16f of bearing member 16, and bearing member 16 abuts bearing seat 18 (formed as a unitary part with the spring stop 11) by causing the plunger nut 8 to move towards distally. This loading step is caused by a loading action by the user, namely a twisting of the loading sleeve 12 relative to the device body 5 by 180°. In this, the container housing 4 (with the medicament container 3), the bearing seat 18 and the spring stop 11 are fixedly connected to the device body 5. The plunger rod 7 with the priming rod 6 is prevented from rotating by the shape of the outer geometry of the plunger rod 7 cooperating with the plunger rod guiding portion 54. The rotation of the loading sleeve 12 is, however, transferred to the plunger nut 8 and to the activation button 13 by an inwardly protruding structure, namely by inwardly protruding ledges 121 (Fig. 15). The rotation of the plunger nut causes the plunger nut 8 to move backward, i.e., towards distal, against the spring force of the drive spring 9. This movement of the plunger nut 8 for loading the device can be observed through the reload status windows 51. For example, the outer surface of the circumferential ridge 81 may have a distinct colour, and its backward movement may be well visible through the reload status windows 51. In Fig. 18, the progress of the loading step is illustrated in panels IV through VII.

[0173] • D. Expelling. When the medicament delivery device is in the loaded state, the medicament delivery step may be initiated by pressing the activation button 13 again. This is illustrated in panel VIII of Fig. 18. Upon activation, the plunger rod assembly comprising the plunger nut 8, the plunger rod 7, and the priming rod 6 is allowed to travel towards distally, driven by the drive spring 9 that expands from the compressed state to a relaxed state and thereby acts on the circumferential ridge of the plunger nut 8. This causes a dose of the medicament to be expelled through the needle, the dose being defined by the axial distance the assembly travels from the loaded state back to the unloaded state. The user may view the resulting position of the plunger 31 through the housing windows 41. Thereby, she / he can see how many doses are left, aided by the dose indicator 43.

[0174] • E. Needle assembly removal. After delivery of a full dose (panel IX), the user removes the needle assembly (if no dose is left, as an alternative, the medicament delivery assembly may be disposed of directly). Panel X of Fig. 18 illustrates the medicament delivery device with the medicament container in this state, in which state the medicament delivery device with the medicament container can be stored away awaiting further use.

[0175] • Steps A., C., D., and E. - thus all steps except the priming step - are repeated for each one of the further doses.

[0176] Fig. 19 illustrates a detail of the medicament delivery device in the unloaded state in a section. The drive spring 9 presses the plunger nut 8 towards proximally, with the proximal end face of the plunger nut abutting against a stop shoulder 57 of the device body 5.

[0177] In Fig. 19, one also sees that the thread grooves 73 of the plunger rod thread 72 are broader than the width of the thread ridge of the plunger nut's internal thread 82 so that there is some clearance between the external thread and the internal thread.

[0178] In the loading step (step C.), the user twists the loading sleeve by 180° in case of the embodiment of Figs. 1-22. The rotation of the plunger nut 8 caused by the twisting of the loading sleeve 12 causes the movement of the plunger nut 8 towards distally by plunger nut ledges 84 sliding against the helical slopes 55 of the device body 5. Initially, in the unloaded state, the plunger nut ledges 84 rest at the bottom 58 of the respective helical slopes 55 (Fig. 20). Shortly before the 180° rotation is completed, the plunger nut ledges 84 reach the top 59 of the respective slopes and, upon completion of the 180° rotation, get beyond the top 59 of the slopes and 'fall off the cliff, i.e., are subject to a small movement towards proximally so that the edges of the slopes prevent an unintended unwinding rotation. A rotation beyond 180° is prevented by limit ledges 87 (Fig. 10, Fig. 11) of plunger nut 8 abutting against spring stop tabs 114 of the immovable spring stop 11 (Fig. 13B).

[0179] In an initial phase of the rotation caused by the user twisting the loading sleeve 12, a spring stop slope 112 of the spring stop also acts as a reset slope as described above and causes the activation button to be pushed out towards distally by cooperating with a protruding boss 132 that slides up the spring stop slope 112 when the activation button 13 is rotated (Fig. 21).

[0180] The plunger nut 8 has two locking arms 85 (Fig. 10) that are capable of being flexed inwardly in a resilient manner and that each comprise a locking protrusion 86 (Fig. 22). Towards the end of the 180° rotation, the locking protrusions 86, which are subject to a helical movement when the plunger nut 8 is rotated and thereby displaced towards distally, each glide over an inner ramp 113 (Fig. 13B) of the spring stop 11, the inner ramp being shaped to gradually flex the locking arms 85 inwardly. Fig. 22 schematically depicts the principle of the inner ramp 113 flexing the locking arm 85 inwardly. The arrow in Fig. 22 indicates the movement of plunger nut 8 towards distally. Shortly before plunger nut 8 reaches the position in which the plunger nut ledges 84 get beyond the top 59 of the slopes 55 (Fig. 20), the locking protrusions 86, due to the movement of the plunger nut 8 towards distally, lose contact with the inner ramps 113, and the locking arms 85 are allowed to spring back to their relaxed position, so that their proximal stop faces 89 lie distally of the respective inner ramp 113. When the plunger nut ledges 84 get beyond the top 59 of the slopes, the drive spring 9 causes the plunger nut 8 to move proximally until the proximal stop faces 89 hit against the inner ramps 113 (functioning, accordingly, as locking structures), thereby generating a click sound indicating to the user that the loading action has been completed. Fig. 23, showing a cross section of the distal- most portion of the medicament delivery device 2, depicts the situation at the end of the loading step.

[0181] During the rotation and backward movement (towards distally) of the plunger nut 8, the plunger rod 7 essentially stands still. It cannot rotate due to the non-round cross section of the plunger rod guiding portion 54. Also, the plunger nut's internal thread 82 and the plunger rod thread 72 have a thread lead (the thread lead is the axial advance per turn, being an integer multiple of the thread pitch) allowing the plunger nut 8 to travel without displacing the plunger rod 7 axially. More particularly, the lead of the helical slopes 55 is slightly larger than the thread lead, so that the plunger nut 8 travels a small extra distance, this extra distance corresponding to the clearance between the plunger rod thread 72 and the internal thread 82. This extra distance allows the plunger rod to make the before-mentioned movement towards proximally until the proximal stop faces 89 hit against the inner ramps 113. Because of the clearance between the plunger rod thread 72 and the internal thread 82, this is possible without plunger rod 7 moving back or forth during the loading step. A movement of plunger rod 7 backward during the reloading could leave clearances before the activation, whereas a movement forward could cause the expelling of some of the medicament upon reloading, both being undesired.

[0182] For activation, to initiate step D., the user pushes the activation button 13 after reloading. At the end of the rotation, the activation button 13 is in the orientation relative to the spring stop 11 as shown in Fig. 21, in which the protruding boss 132 allows a movement of the activation button 13 towards proximally when the user pushes it. This movement will cause activation wings 133 (which function as activation structures; cf. Figs. 16 and 22) of the activation button 13, the distal ends of which slide along locking protrusion ramps 90 of the locking protrusions when the activation button is pushed proximally, to flex the locking arms 85 again inwardly. As a consequence, the drive spring 9 can push the plunger nut 8 proximally. The internal thread 82 of the plunger nut 8 transfers this movement to the plunger rod 7 (Fig. 24) and thereby to the priming rod.

[0183] The dosing ends when the plunger nut 8 hits the stop face 57 (Fig. 19) of the device body 5. It is thus the interplay between the plunger nut 8, the device body 5 and the spring stop 11 (that is fixedly connected to the device body 5) that determines the distance by which the plunger assembly -comprising the plunger nut 8, the plunger rod 7 and the priming rod 6 - travels towards proximally for dosing and thus determines the dosing amount. Both, the dosing amount and the time it takes to expel it are the same for every dose. The described medicament delivery device 2 not only provides a click sound indicating to the user that the loading action has been completed as described above, but it also provides a signal at the end of each dose delivery. This is accomplished by the bearing formed by bearing member 16 (as a signaling member) cooperating with bearing seat 18 as a cooperation member (not to be confused with the cooperating member). The signal - which can be perceived by the user as a click (audibly) and in a tactile manner - is caused by a movement (signaling movement) of the bearing member 16. The energy required for producing the movement of the bearing member

[0184] 16 is provided by the drive spring 9, and the user can repeatedly produce a corresponding bias on the bearing member 16 just by the same user action he / she carries out when loading the spring to provide the energy for the expelling of the doses, i.e., by the twisting of the loading sleeve 12.

[0185] To this end, bearing member 16 has, at its distal end, a circumferential ridge 17 forming a cam curve and acting as a distance varying feature. And bearing seat 18 has, as a cooperation feature 19, an identically shaped cam curve. Alternatively, the bearing member 16 or the bearing seat 18 could have, e.g., one or two (or more) ledges sliding against the cam curve of the ridge 17 as cooperation feature(s) 19. Rotation of the ridge (distance varying feature) relative to the cooperation feature 19 causes a change in axial distance of bearing member 16 and bearing seat 18.

[0186] With reference to Fig. 14B, the ridge 17 has, along a circumference of the bearing member 16, a bottom section SI adjacent a sloped section S2 adjacent a top section S3 adjacent a step feature S4, and, adjacent thereto (only partially visible in Fig. 14B) another bottom section SI’ adjacent another sloped section adjacent another top section adjacent another step feature, providing a 180° symmetry for increased stability. This can be considered two identical cam curves extending over 180° each.

[0187] Fig. 27 shows the bearing member 16 in a perspective view, highlighting the ridge

[0188] 17 and its sections, enlarged, for increased clarity.

[0189] Fig. 28 shows a part of the base assembly, highlighting the cooperation feature 19 of bearing seat 18 (as a cooperation member). Since in the illustrated embodiment, the ridge 17 and the cooperation feature 19 are identically shaped, the same reference signs are used for corresponding sections.

[0190] For the bearing member 16, a bottom level defined by the bottom section SI is further proximal than a top level defined by the top section. For the bearing seat, it is the other way round: A bottom level defined by the bottom section is further distal than a top level defined by the top section.

[0191] Drive spring 9 forces bearing member 16 distally against bearing seat 18 so that they abut one another. Bearing seat 18 is rotationally fix (affixed to the base assembly).

[0192] Initially, the bearing member 16 and the bearing seat 18 are positioned close to one another as shown in Fig. 25, panel I (minimum axial distance of bearing member 16 and bearing seat 18). During loading (step C.), the rotation of plunger nut 8 causes a rotation of bearing member 16 because the limit ledge 87 of plunger nut 8, acting as a first coupling feature, cooperates accordingly with a guiding slit 16b in a sleeve 16s of bearing member 16, acting as a second coupling member. The thick curved arrow indicates the sense of rotation of the bearing member 16 during loading. Fig. 25 panel II shows the situation after 45° rotation of bearing member 16, panel III after 90°, panel IV after 135°. In a range between about 45° (panel II) an 135° (panel IV), the sloped sections S2 are abutting and sliding on one another, so as to increase the axial distance of bearing member 16 and bearing seat gradually, with proceeding the plunger nut rotation. Effectively, a proximal movement of bearing member 16 is achieved - against the bias of drive spring 9.

[0193] Panel V shows the situation after about 175° (i.e., briefly before 180°) rotation of the bearing member 16, which is at the end of the loading step. Fig. 26 illustrates the reason why the loading step ends already before the bearing member 16 has rotated full 180° - even though the plunger nut 8 rotates full 180° until the end of the loading step.

[0194] In Fig. 26, the plunger nut 8 and the bearing member 16 are shown. Drive spring 9 proximally abutting ridge 81 and distally abutting bearing surface 16f is not shown. Panel I of Fig. 26 shows the initial situation, corresponding to panel I of Fig. 25. An initiation member of plunger nut 8, formed by a (circumferentially extending) protrusion 83 of limit ledge 87, abuts guiding slit 16b (more particularly: surface 83a) and forces bearing member 16 to rotate. After around 90° of rotation of plunger nut 8, an intermediate portion 87b of limit ledge 87 abuts bearing member 16 - which is recessed (circumferentially) with respect to protrusion 83. Accordingly, the rotation of the bearing member 16 is reduced with respect to the rotation of the plunger nut 8, by a couple of degrees, e.g., bearing member 16 being rotated by about 85° while plunger nut 8 has already rotated 90°. Panel II of Fig. 26 shows this situation. Panel III shows the situation at the end of the loading step, i.e., plunger nut 8 having rotated 180°, bearing member 16 having rotated abut 175° only, corresponding to panel V of Fig. 25. Bearing member 16 now abuts limit ledge 87 in a base portion 87a where limit ledge 87 is wider and, cooperating with guiding slit 16b, inhibits any rotation of bearing member 16 relative to plunger nut 8, in contrast to the situation in panel II of Fig. 26, where bearing member 16 can (and does) rotate by several degrees, relative to plunger nut 8.

[0195] As can be seen in panel V of Fig. 25, at the end of the loading step, the axial distance of bearing member 16 and bearing seat 18 is maximum. In this situation, the respective top sections S3, close to the step feature S4, are abutting.

[0196] Due to the fact that the top section S3 is (circumferentially) flat for a range of degrees (about 40° in the illustrated case) before the position at the end of the loading step is reached, the torque for providing the compression of drive spring 9 by the proximal movement of bearing member 16 does not add up at the end of the loading step, but earlier than that; in the illustrated example in the range from about 45° to about 135°. Accordingly, a reduction of a maximum torque to be applied by the user for the loading is achieved.

[0197] Panel V of Fig. 25 and panel III of Fig. 26 show the initial situation for the expelling of a dose (cf. step D.). The medicament delivery device 2 is in the loaded state, and the bearing member 16 (as the signaling member) is in a charged position (maximum distance between bearing member 16 and bearing seat 18). A signaling movement of bearing member 16, which essentially is a distal movement of bearing member 16 towards and onto the bearing seat 18, is blocked during expelling the dose before the end thereof is reached. In an early phase during dose delivery, bearing member 16 cannot rotate, as the (wide) base portion 87a inhibits such rotations by cooperation with guiding slit 16b, cf. panel III of Fig. 26. In a later phase, a slight rotation of bearing member 16 is possible, due to the reduced circumferential width of limit ledge 87 at the intermediate portion of limit ledge 87. However, this slight rotation does not enable a rotation which would terminate the abutting of the step features S4 ensuring the maximum axial distance of bearing member 16 and bearing seat 18 (cf. panel V of Fig. 25).

[0198] But at the end of the dose, with the proximal movement of plunger nut 8 (relative to bearing member 16) having made progress, the protrusion 83 and, more particularly, its surface 83a (as an initiating surface) abuts bearing member 16 and, more particularly, its surface 16c (initiating feature) to force a rotation of bearing member 16. This rotational movement (initiating movement) takes the bearing member 16 from a charged position to a start position which is symbolized in panel VI of Fig. 25, namely to a start position for the signaling movement. Now, the two step features S4 (of bearing member 16 and of bearing seat 18, respectively) do not interact anymore to block a distal movement (the signaling movement) of the bearing member 16; the mutual support of the cam structures of bearing member 16 and bearing seat 18 is lost. Instead, in a short time, and forced by the drive spring 9, the bearing member 16 moves distally and hits bearing seat 18. More particularly, first abutting surface 16a, e.g., the distally facing surfaces of the bottom sections SI and of the top surfaces S3 of bearing member 16, hit second abutting surface 18a, e.g., the proximally facing surfaces of the top sections and of the bottom sections of the bearing seat 18. The abutting of the first and second abutting surfaces 16a, 18a generates a click sound and can also be perceived in a tactile manner. The bearing member 16 ends up in a discharged position; the energy that was stored in drive spring 9 due to the maximized axial distance of bearing member 16 and bearing seat 18 achieved by the rotation of the bearing member 16 has been used for accelerating bearing member 16 against bearing seat 18. The signaling movement takes the signaling mechanism back to the initial situation for the loading, which is illustrated in panel I of Fig. 25 and in panel I of Fig. 26.

[0199] The described signaling mechanism contributes, in an elegant way, to a safer handling of the medicament delivery device.

[0200] Elements of a further, second embodiment are described referring to Figs. 29 to 34. The second embodiment is distinct from the first embodiment of Figs. 1 to 24 in that it is configured for a rotation by 360° instead of 180° for the loading step. The advantage of a greater rotation is that more energy can be stored in the biasing member (drive spring) for a given torque, or less torque is required for a given energy. This may especially be an issue if the user wants to use a comparably thin needle to minimize pain during injections. A thin needle comes about with the need for a higher plunger force and hence a higher energy stored in the biasing member for a given dosage.

[0201] In Figs. 29 to 34, Fig. 29 shows a view of the plunger nut and Fig. 30 a view of a slope part 201. Fig. 31 depicts an enlarged view of the stop part 201 from a different perspective. Figs. 32-34 show, in part, the plunger nut and the slope part 201 in different stages of the loading step, namely in an initial state (Fig. 32), after a 180° rotation (Fig. 33), and in a final state, after a 360° rotation (Fig. 34). The arrow indicates the increase of the axial length of the assembly constituted by the slope part 201 and a slope extension 141 of the plunger nut 8.

[0202] In contrast to the first embodiment, the helical slopes extend by 360° around axis A. To this end, the following measures are taken in the second embodiment compared to the first embodiment:

[0203] • In order for there not being any bending force on plunger rod 7 and plunger nut 8 when the latter is subject to the rotation during the loading step, the device has two slopes, offset by 180° with respect to one another. In the first embodiment, this is readily possible by arranging the two slopes 55 at the same axial position, offset by 180° with respect to one another. This solution, however, does not work for slopes that extend by more than 180° around the axis. In the second embodiment, the two slopes 211, 212 are at different radial positions (i.e., the second slope 212 is further inside than the first slope 211), but they otherwise have a 180° axial symmetry with respect to one another. A rotation by 180° thus transfers one slope to the other slope, but with different radial positions.

[0204] • The slopes 211, 212 have step features 213 that prevent unwinding. The user usually cannot twist a full turn (360°) but has to change grip between partial rotations. The step features define stops for any unwinding movement. In the depicted embodiment, the step features are arranged at 90°, 180°, and 270°. However, it would be sufficient if one step feature per slope, arranged at 180°, was present. Alternatives include step features at 120° and 240°, or more step features arranged with regular or also irregular spacings.

[0205] The step features may be in the form of zags (as illustrated, see Figs. 29-34) or may be in the form of platforms, i.e., zero-inclined portions.

[0206] The following features of the second embodiment are distinct from the first embodiment but do not necessarily depend on the twisting-by-360°-concept and do also not depend on each other. In other words, they are optional modifications of the first embodiment, too, and also the second embodiment could be modified to be implemented without them:

[0207] • The first and second slopes 211, 212 are present on a separate part, namely a slope part 201 instead of being features of the device body 5 itself. The slope part 201 is mounted to be essentially immovable relative to the device body 5.

[0208] • The plunger nut 8 instead of having a plunger nut ledge 84 of a relatively limited extension in circumferential direction (the ledge cooperating with the slopes) has slopes 142, 143, too, namely an outer slope 142 cooperating with the first slope 211 of the slope part 201 and an inner slope 143 cooperating with the second slope 212 of the slope part 201. The outer slope 142 and the inner slope 143 both have steps 144 matching with the step features 213 of the slope part 201. The outer slope 142 and the inner slope 143 belong to a slope extension 141 of the plunger nut 8 a distally facing shoulder 145 of which also serves as face against which the drive spring 9 presses, whereby the slope extension 141 also has the function that in the first embodiment is fulfilled by the circumferential ridge 81.

[0209] The signaling mechanism described above for the first embodiment (180° twist;

[0210] Figs. 1-28) can be modified analogously to the modification described for the second embodiment (360° twist; Figs 29-34) to be applicable in the second embodiment. Instead of having, at the bearing member and at the bearing seat, two cam curves (or ridge sections) of 180° each with a bottom section, a sloped section, a top section, and a step feature, two cam curves (or ridge sections) of more than 180° each, e.g., of 360° each, with a bottom section, a sloped section, a top section can be provided at different radial positions.

[0211] In the following, we describe an implementation which generates yet another signal to the user, namely a signal indicative of the start of the expelling, which we shall refer to as start signal. In order to distinguish the mechanism for causing the start signal from the mechanisms described above, we shall refer to it as signalization mechanism.

[0212] The signalization mechanism can be implemented in combination with any of the above-described embodiments, irrespective of, e.g., whether they implement a 180° or a 360° rotation for loading, but can be also implemented independently. Accordingly, the signalization mechanism can, in particular, also be implemented without the signaling mechanism.

[0213] Providing a start signal can be particularly advantageous for a multi-dose medicament delivery device. For single-dose medicament delivery devices, the movement of the plunger can be a useful visual indicator informing the user that the expelling of the medicament is ongoing. However, the axial speed of the plunger during expelling in case of a multi-dose device is only a fraction of the axial speed for a single-dose device (provided the total plunger travel and the plunger’s travel speed is the same). Accordingly, the usefulness of the plunger movement as a (visual) indicator is rather limited for multi-dose devices - and a start signal can be a good choice, in particular when implemented together with an end-of-dose signal.

[0214] The implementation of the signalization mechanism is described basically with reference to the embodiments above, in particular to the 360° loading embodiment, wherein the spring stop 11 is generally fixed to the device body 5 in the assembled state, but a small travel towards proximally of spring stop 11 relative to device body 5 is possible. That small travel can be caused counteracting a force exerted by drive spring 9, e.g., by the user. Some shapes of some parts of the medicament delivery device with the signalization mechanism illustrated in the figures are different from what is illustrated in the figures above, while still having basically the same functionalities.

[0215] Fig. 39 shows the spring stop 11 of this implementation in a perspective view.

[0216] Figs. 40A, 40B show the device body 5 of this implementation, in different perspective views.

[0217] The start signal provides an audible and tactile feedback to the user indicating that the expelling starts, more particularly that the plunger rod assembly 101 (and, accordingly, also the plunger 31) starts to move towards proximally.

[0218] The user initiates the generation of the start signal by pressing the activation button 13. And the start signal is generated by the spring stop 11 rapidly hitting the device body 5, driven by the drive spring 9. The details are described with reference to Figs. 35A-35d; 36A-36D, 37A-37D; 38.

[0219] Figs. 35A-35D show a perspective view onto a detail of an axial cross-section through a medicament delivery device, each in a different stage regarding the generation of the start signal.

[0220] Figs. 36A-36D show enlarged details of respective ones of Figures 35A-35D.

[0221] Figs. 37A-37D show a perspective view onto a detail of the distal portion of the medicament delivery device of Figs. 35A-35D, each in a corresponding stage regarding the generation of the start signal. Fig. 38 shows a perspective view of an enlarged detail of the medicament delivery device in the same stage as shown in Fig. 37B.

[0222] Figs. 35A, 36A, 37A show the situation in an initial stage, namely before activation starts, more particularly in the loaded state, before the user presses the activation button 13.

[0223] Figs. 35B, 36B, 37B, 38 show the situation in a first stage, namely with partially pressed activation button 13, resulting in a gap, as will be described below.

[0224] Figs. 35C, 36C, 37C show the situation in a second stage, namely where the drive spring 9 is released.

[0225] Figs. 35D, 36D, 37D show the situation in a third stage, namely where the released drive spring 9 has moved the spring stop 11 towards distally, resulting in a rapid closing of the gap, generating the start signal, as will be described below.

[0226] In the initial state, plunger nut 8 is in its distal, loaded position, as forced by drive spring 9.

[0227] Then, the user presses activation button 13 (towards proximally), leading to the first stage, where activation wings 133 slide on locking protrusion ramps 90, so that friction and the force required to bend locking arms 85 of plunger nut 8 inwardly effect that the movement of activation wings 133 towards proximally cause a movement towards proximally of plunger nut 8, which again causes a movement towards proximally of spring stop 11, because proximal stop faces 89 of locking arms 85 abut inner ramps 113 of spring stop 11.

[0228] This movement towards proximally of spring stop 11 on the one hand causes an abutment of a limiting structure 115 of spring stop 11 (which, e.g., is an outwardly protruding ridge, as illustrated), and a limiting shoulder 53 of device body 5 (which, e.g., is a distally facing internal shoulder, as illustrated). The arrow in Fig. 36B points at the abutment. And on the other hand, a gap opens up between spring stop coupling structure 111 and device body 5, more particularly between a distal face 11 la of spring stop coupling structure 111 (cf. Fig. 38) and a proximal face 56b of a portion 56a of device body 5, more particularly of second coupling holes 56. The dashed arrows in Figs. 37B, 37C, 38 point at the gap.

[0229] Pushing activation button 13 further (towards proximally) causes, in the second stage, locking arms 85 to be bend inwardly even further, namely so far that the abutment of locking arms 85 and inner ramps 113 terminates. This way, plunger nut 8 can be driven towards proximally by drive spring 9.

[0230] Accordingly, powered by drive spring 9, plunger nut 8 moves towards proximally, and, also driven by drive spring 9, spring stop 11 rapidly moves towards distally, which leads to the third stage.

[0231] The rapid movement of spring stop 11 towards distally effects that distal face 11 la of spring stop coupling structure 111 hits onto proximal face 56b, resulting in the start signal, cf. the open arrow in Fig. 37D.

[0232] This opens up a clearance between limiting structure 115 of spring stop 11 and limiting shoulder 53, symbolized by the pair of dashed lines in Fig. 36D.

[0233] The start signal can be perceived by the user as both, as an audible and as a tactile signal.

[0234] The drug delivery devices described herein can be used for the treatment and / or prophylaxis of one or more of many different types of disorders.

[0235] Exemplary disorders include, but are not limited to: rheumatoid arthritis, inflammatory bowel diseases (e.g. Crohn’s disease and ulcerative colitis), hypercholesterolaemia and / or dyslipidemia, cardiovascular disease, diabetes (e.g. type 1 or 2 diabetes), psoriasis, psoriatic arthritis, spondyloarthritis, hidradenitis suppurativa, Sjogren's syndrome, migraine, cluster headache, multiple sclerosis, neuromyelitis optica spectrum disorder, anaemia, thalassemia, paroxysmal nocturnal hemoglobinuria, hemolytic anaemia, hereditary angioedema, systemic lupus erythematosus, lupus nephritis, myasthenia gravis, Behcet's disease, hemophagocytic lymphohistiocytosis, atopic dermatitis, retinal diseases (e.g., age-related macular degeneration, diabetic macular edema), uveitis, infectious diseases, bone diseases (e.g., osteoporosis, osteopenia), asthma, chronic obstructive pulmonary disease, thyroid eye disease, nasal polyps, transplant, acute hypoglycaemia, obesity, anaphylaxis, allergies, sickle cell disease, Alzheimer’s disease, Parkinson’s disease, dementia with Lewy bodies, systemic infusion reactions, immunoglobulin E (IgE)- mediated hypersensitivity reactions, cytokine release syndrome, immune deficiencies (e.g., primary immunodeficiency, chronic inflammatory demyelinating polyneuropathy), enzyme deficiencies (e.g., Pompe disease, Fabry disease, Gaucher disease), growth factor deficiencies, hormone deficiencies, coagulation disorders (e.g., hemophilia, von Willebrand disease, Factor V Eeiden), and cancer.

[0236] Exemplary types of drugs that could be included in the delivery devices described herein include, but are not limited to, small molecules, hormones, cytokines, blood products, enzymes, vaccines, anticoagulants, immunosuppressants, antibodies, antibody-drug conjugates, neutralizing antibodies, reversal agents, radioligand therapies, radioisotopes and / or nuclear medicines, diagnostic agents, bispecific antibodies, proteins, fusion proteins, peptibodies, polypeptides, pegylated proteins, protein fragments, nucleotides, protein analogues, protein variants, protein precursors, protein derivatives, chimeric antigen receptor T cell therapies, cell or gene therapies, oncolytic viruses, or immunotherapies.

[0237] Exemplary drugs that could be included in the delivery devices described herein include, but are not limited to, immuno-oncology or bio-oncology medications such as immune checkpoints, cytokines, chemokines, clusters of differentiation, interleukins, integrins, growth factors, coagulation factors, enzymes, enzyme inhibitors, retinoids, steroids, signaling proteins, pro-apoptotic proteins, anti- apoptotic proteins, T-cell receptors, B-cell receptors, or costimulatory proteins.

[0238] Exemplary drugs that could be included in the delivery devices described herein include, but are not limited to, those exhibiting a proposed mechanism of action, such as human epidermal growth factor receptor 2 (HER-2) receptor modulators, interleukin (IL) modulators, interferon (IFN) modulators, complement modulators, glucagon-like peptide- 1 (GLP-1) modulators, glucose-dependent insulinotropic polypeptide (GIP) modulators, cluster of differentiation 38 (CD38) modulators, cluster of differentiation 22 (CD22) modulators, Cl esterase modulators, bradykinin modulators, C-C chemokine receptor type 4 (CCR4) modulators, vascular endothelial growth factor (VEGF) modulators, B-cell activating factor (BAFF), P- selectin modulators, neonatal Fc receptor (FcRn) modulators, calcitonin gene-related peptide (CGRP) modulators, epidermal growth factor receptor (EGFR) modulators, cluster of differentiation 79B (CD79B) modulators, tumor-associated calcium signal transducer 2 (Trop-2) modulators, cluster of differentiation 52 (CD52) modulators, B-cell maturation antigen (BCMA) modulators, enzyme modulators, platelet-derived growth factor receptor A (PDGFRA) modulators, cluster of differentiation 319 (CD319 or SLAMF7) modulators, programmed cell death protein 1 and programmed death-ligand 1 (PD-1 / PD-L1) inhibitor s / modulators, B-lymphocyte antigen cluster of differentiation 19 (CD19) inhibitors, B-lymphocyte antigen cluster of differentiation 20 (CD20) modulators, cluster of differentiation 3 (CD3) modulators, cytotoxic T- lymphocyte-associated protein 4 (CTLA-4) inhibitors, T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) modulators, T cell immunoreceptor with Ig and ITIM domains (TIGIT) modulators, V-domain Ig suppressor of T cell activation (VISTA) modulators, indoleamine 2,3-dioxygenase (IDO or INDO) modulators, poliovirus receptor-related immunoglobulin domain-containing protein (PVRIG) modulators, lymphocyte- activation gene 3 (LAG3; also known as cluster of differentiation 223 or CD223) antagonists, cluster of differentiation 276 (CD276 or B7-H3) antigen modulators, cluster of differentiation 47 (CD47) antagonists, cluster of differentiation 30 (CD30) modulators, cluster of differentiation 73 (CD73) modulators, cluster of differentiation 66 (CD66) modulators, cluster of differentiation wl37 (CDwl37) agonists, cluster of differentiation 158 (CD 158) modulators, cluster of differentiation 27 (CD27) modulators, cluster of differentiation 58 (CD58) modulators, cluster of differentiation 80 (CD80) modulators, cluster of differentiation 33 (CD33) modulators, cluster of differentiation 159 (CD 159 or NKG2) modulators, glucocorticoid-induced TNFR- related (GITR) protein modulators, Killer Ig-like receptor (KIR) modulators, growth arrest-specific protein 6 (GAS6) / AXL pathway modulators, A proliferation-inducing ligand (APRIL) receptor modulators, human leukocyte antigen (HLA) modulators, epidermal growth factor receptor (EGFR) modulators, B-lymphocyte cell adhesion molecule modulators, cluster of differentiation wl23 (CDwl23) modulators, Erbb2 tyrosine kinase receptor modulators, endoglin modulators, mucin modulators, mesothelin modulators, hepatitis A virus cellular receptor 2 (HAVCR2) antagonists, cancer-testis antigen (CTA) modulators, tumor necrosis factor receptor superfamily, member 4 (TNFRSF4 or 0X40) modulators, adenosine receptor modulators, inducible T cell co-stimulator (ICOS) modulators, cluster of differentiation 40 (CD40) modulators, tumor-infiltrating lymphocytes (TIL) therapies, or T-cell receptor (TCR) therapies.

[0239] Exemplary drugs that could be included in the delivery devices described herein include, but are not limited to: etanercept, abatacept, adalimumab, evolocumab, exenatide, secukinumab, erenumab, galcanezumab, fremanezumab-vfrm, alirocumab, methotrexate (amethop terin), tocilizumab, interferon beta- la, interferon beta- lb, peginterferon beta- la, sumatriptan, darbepoetin alfa, belimumab, sarilumab, semaglutide, dupilumab, reslizumab, omalizumab, glucagon, epinephrine, naloxone, insulin, amylin, vedolizumab, eculizumab, ravulizumab, crizanlizumab-tmca, certolizumab pegol, satralizumab, denosumab, romosozumab, benralizumab, emicizumab, tildrakizumab, ocrelizumab, ofatumumab, natalizumab, mepolizumab, risankizumab-rzaa, ixekizumab, and immune globulins.

[0240] Exemplary drugs that could be included in the delivery devices described herein may also include, but are not limited to, oncology treatments such as ipilimumab, nivolumab, pembrolizumab, atezolizumab, durvalumab, avelumab, cemiplimab, rituximab, trastuzumab, ado-trastuzumab emtansine, fam-trastuzumab deruxtecan- nxki, pertuzumab, transtuzumab-pertuzumab, alemtuzumab, belantamab mafodotin- blmf, bevacizumab, blinatumomab, brentuximab vedotin, cetuximab, daratumumab, elotuzumab, gemtuzumab ozogamicin, 90-Yttrium-ibritumomab tiuxetan, isatuximab, mogamulizumab, moxetumomab pasudotox, obinutuzumab, ofatumumab, olaratumab, panitumumab, polatuzumab vedotin, ramucirumab, sacituzumab govitecan, tafasitamab, or margetuximab.

[0241] Exemplary drugs that could be included in the delivery devices described herein include “generic” or biosimilar equivalents of any of the foregoing, and the foregoing molecular names should not be construed as limiting to the “innovator” or “branded” version of each, as in the non-limiting example of innovator medicament adalimumab and biosimilars such as adalimumab-afzb, adalimumab-atto, adalimumab-adbm, and adalimumab-adaz.

[0242] Exemplary drugs that could be included in the delivery devices described herein also include, but are not limited to, those used for adjuvant or neoadjuvant chemotherapy, such as an alkylating agent, plant alkaloid, antitumor antibiotic, antimetabolite, or topoisomerase inhibitor, enzyme, retinoid, or corticosteroid. Exemplary chemotherapy drugs include, by way of example but not limitation, 5-fluorouracil, cisplatin, carboplatin, oxaliplatin, doxorubicin, daunorubicin, idarubicin, epirubicin, paclitaxel, docetaxel, cyclophosphamide, ifosfamide, azacitidine, decitabine, bendamustine, bleomycin, bortezomib, busulfan, cabazitaxel, carmustine, cladribine, cytarabine, dacarbazine, etoposide, fludarabine, gemcitabine, irinotecan, leucovorin, melphalan, methotrexate, pemetrexed, mitomycin, mitoxantrone, temsirolimus, topotecan, valrubicin, vincristine, vinblastine, or vinorelbine.

[0243] Exemplary drugs that could be included in the delivery devices described herein also include, but are not limited to, analgesics (e.g., acetaminophen), antipyretics, corticosteroids (e.g. hydrocortisone, dexamethasone, or methylprednisolone), antihistamines (e.g., diphenhydramine or famotidine), antiemetics (e.g., ondansetron), antibiotics, antiseptics, anticoagulants, fibrinolytics (e.g., recombinant tissue plasminogen activator [r-TPA]), antithrombolytics, or diluents such as sterile water for injection (SWFI), 0.9% Normal Saline, 0.45% normal saline, 5% dextrose in water, 5% dextrose in 0.45% normal saline, Lactated Ringer’s solution, Heparin Lock Flush solution, 100 U / mL Heparin Lock Flush Solution, or 5000 U / mL Heparin Lock Flush Solution.

[0244] Pharmaceutical formulations including, but not limited to, any drug described herein are also contemplated for use in the delivery devices described herein, for example pharmaceutical formulations comprising a drug as listed herein (or a pharmaceutically acceptable salt of the drug) and a pharmaceutically acceptable carrier. Such formulations may include one or more other active ingredients (e.g., as a combination of one or more active drugs), or may be the only active ingredient present, and may also include separately administered or co-formulated dispersion enhancers (e.g. an animal-derived, human-derived, or recombinant hyaluronidase enzyme), concentration modifiers or enhancers, stabilizers, buffers, or other excipients.

[0245] Exemplary drugs that could be included in the delivery devices described herein include, but are not limited to, a multi-medication treatment regimen such as AC, Dose-Dense AC, TCH, GT, EC, TAC, TC, TCHP, CMF, FOLFOX, mF0LF0X6, mF0LF0X7, FOLFCIS, CapeOx, FLOT, DCF, FOLFIRI, FOLFIRINOX, FOLFOXIRI, IROX, CHOP, R-CHOP, RCHOP-21, Mini-CHOP, Maxi-CHOP, VR- CAP, Dose-Dense CHOP, EPOCH, Dose- Adjusted EPOCH, R-EPOCH, CODOX- M, IVAC, HyperCVAD, R-HyperCVAD, SC-EPOCH-RR, DHAP, ESHAP, GDP, ICE, MINE, CEPP, CDOP, GemOx, CEOP, CEPP, CHOEP, CHP, GCVP, DHAX, CALGB 8811, HIDAC, MOpAD, 7 + 3, 5 +2, 7 + 4, MEC, CVP, RBAC500, DHA- Cis, DHA-Ca, DHA-Ox, RCVP, RCEPP, RCEOP, CMV, DDMVAC, GemFLP, ITP, VIDE, VDC, VAI, VDC-IE, MAP, PCV, FCR, FR, PCR, HDMP, OFAR, EMA / CO, EMA / EP, EP / EMA, TP / TE, BEP, TIP, VIP, TPEx, ABVD, BEACOPP, AVD, Mini- BEAM, IGEV, C-MOPP, GCD, GEMOX, CAV, DT-PACE, VTD-PACE, DCEP, ATG, VAC, VelP, OFF, GTX, CAV, AD, MAID, AIM, VAC-IE, ADOC, or PE.

[0246] Various modifications to the embodiments described are possible and will occur to those skilled in the art without departing from the invention which is defined by the following claims.

Claims

CLAIMS1. A medicament delivery device (2) for accommodating a medicament container (3) containing a medicament and for expelling multiple pre-defined doses of the medicament from the medicament container (3), the medicament delivery device (2) defining a device axis (A) and comprising: a base assembly to which the medicament container (3) is mountable in a stationary manner; a plunger rod assembly (101) being axially movable relative to the base assembly for interacting with the medicament container (3) for expelling the medicament therefrom; and a biasing member (9) configured to force the plunger rod assembly (101) in a proximal direction; characterized in that the medicament delivery device further comprises a loading mechanism configured for a user to cause a biasing of the biasing member (9); and in that the medicament delivery device (2) further comprises a signaling mechanism which comprises a signaling member (16) and is configured to initiate, for each of the doses, at the end of the expelling of the respective dose, a signaling movement of the signaling member (16), the signaling movement comprising an axial movement in a distal direction, the distal direction being the direction pointing away from a dose delivery site during use of the medicament delivery device, the signaling movement causing a user-perceivable signal.

2. The medicament delivery device (2) according to claim 1, wherein the signaling member (16) is subject to a bias for carrying out the signaling movement, and wherein the signaling mechanism is configured to block thesignaling movement and, at the end of the expelling of each dose, to unblock the signaling movement.

3. The medicament delivery device (2) according to claim 2, the signaling mechanism comprising an initiating member (83) configured to unblock the signaling movement at the end of the expelling of each dose by causing an initiating movement of the signaling member (16) from a charged position of the signaling member (16) to a start position of the signaling member (16), the signaling movement being a movement from the start position to a discharged position of the signaling member, in particular wherein the bias on the signaling member in the charged position and in the start position is higher than the bias on the signaling member in the discharged position.

4. The medicament delivery device (2) according to claim 3, wherein the plunger rod assembly (101) is configured to carry out, for each of the doses, for expelling the respective dose, a proximal movement, wherein the initiating member (83) is coupled to the plunger rod assembly (101) such that the initiating member (83), at the end of the proximal movement, interacts with the signaling member (16) to cause the initiating movement, in particular such that the initiating member (83) carries out the proximal movement together with the plunger rod assembly (101).

5. The medicament delivery device (2) according to claim 3 or claim 4, comprising a distance varying feature (17) and a cooperation feature (19), the base assembly comprising a cooperation member (18), the signaling member (16) comprising at least one first abutting surface (16a), and the cooperation member (18) comprising at least one second abutting surface (18a), a hitting of the at least one first abutting surface (16a) onto the at least one second abutting surface (18a) causing the signal, wherein one of the signaling member (16) and of the cooperation member (18) comprises the distance varying feature (17) and the other one comprises the cooperation feature (19), the distance varying feature (17) and the cooperation feature (19) cooperating with one another, whereby a rotational relative movement of the distance varying feature (17) and the cooperation feature (19) in a first sense of rotation causes the signalingmember (16) to change from the discharged position via the charged position to the start position and back to the discharged position.

6. The medicament delivery device (2) according to claim 5, the distance varying feature comprising, extending along a circumference, a bottom section (SI) adjacent a sloped section (S2) adjacent a top section (S3) adjacent a step feature (S4), the bottom section (SI) defining a bottom level and being recessed relative to the top section (S3), the sloped section (S2) interconnecting the bottom section (SI) and the top section (S3) in a slope-like fashion, the step feature (S4) forming a step-like recess from the top section (S3) to the bottom level, wherein, in the discharged position, the cooperation feature (19) abuts the bottom section (SI), and in the charged position, the cooperation feature (19) abuts the top section (S3) at an end of the top section (S3) adjacent the step feature (S4).

7. The medicament delivery device (2) according to one of claims 2 to 6, wherein the bias on the signaling member (16) is caused by the biasing member (9).

8. The medicament delivery device (2) according to one of claims 3 to 7, comprising a charging mechanism configured for a user to move the signaling member (16) from the discharged position to the charged position to cause the signaling member (16) to move proximally and thereby to increase the bias on the signaling member (16), wherein the medicament delivery device (2) is configured for the charging mechanism to be activated a plurality of times.

9. The medicament delivery device (2) according to claim 8, wherein the plunger rod assembly (101) comprises a first plunger rod device (8) and a second plunger rod device (7), wherein the second plunger rod device (7) is configured to act, by moving in proximal direction, on a plunger (31) of the medicament container (3) for expelling the medicament therefrom; the loading mechanism is configured for a user to cause a distal movement of the first plunger rod device (8), relative to the base assembly and to thesecond plunger rod device (7), from an unloaded position to a loaded position, and to thereby bias of the biasing member (9); wherein the medicament delivery device (2) comprises a twisting element (12) that is configured to be twisted by the user relative to the base assembly to cause the movement of the first plunger rod device (8) in the distal direction; wherein the first plunger rod device (8) is rotationally couplable to the twisting element (12), and wherein one of the first plunger rod device (8) and of the base assembly comprises a helical feature (55) and the other one comprises a cooperating feature (84) cooperating with the helical feature (55), whereby a rotation of the first plunger rod device (8) around the axis (A) causes a translational movement of the first plunger rod device (8) relative to the base assembly; and wherein the first plunger rod device (8) comprises a first coupling feature (87), and the signaling member comprises a second coupling feature (16b) cooperating with the first coupling feature (87) to derive from the rotation of the first plunger rod device (8) around the axis (A) a rotation of the signaling member (16) around the axis (A) to cause the rotational relative movement of the distance varying feature (17) and the cooperation feature (19) in the first sense of rotation.

10. The medicament delivery device (2) according to claim 9, wherein the top section (S3) comprises, adjacent the step feature (S4), a range in which the distance varying feature (17) is not sloped.

11. The medicament delivery device (2) according to claim 9 or claim 10, wherein the base assembly defines a stop (57) for a movement of the plunger rod assembly (101) in the proximal direction when the first plunger rod device (8) has reached the unloaded position, wherein the loading mechanism is equipped for the user to cause another distal movement of the first plunger rod device (8) relative to the base assembly and the second plunger rod device (7) in a reloading action after the plunger rod assembly has reached the stop (57),whereby the medicament delivery device is configured for the loading mechanism to be activated a plurality of times, wherein the unloaded position of the first plunger rod device (8) and the loaded position of the first plunger rod device (8) is the same for each dose.

12. The medicament delivery device according to any one of claims 9 to 11, wherein one of the first plunger rod device (8) and of the base assembly comprises a pair of locking arms (85) with locking protrusions (86), and the other one of the first plunger rod device (8) and of the base assembly comprises a locking structure capable of engaging with the locking protrusions (86), wherein the medicament delivery device (2) is configured for the locking arms (85) to flex in a resilient manner while the user causes the distal movement of the first plunger rod device (8) for loading and to flex back for the locking protrusions (86) to engage the locking structure immediately before a loaded position has been reached by the first plunger rod device (8), the medicament delivery (2) further comprising an activation mechanism for the user to activate medicament delivery, the activation mechanism comprising an activation button (13) with an activation structure that, when the activation button is pressed, causes the locking arms (85) to flex until their locking protrusions (86) get out of engagement with the locking structure to release the plunger rod assembly (101) so that the biasing member displaces the plunger rod assembly (101) towards proximally.

13. The medicament delivery device according to any one of claims 9 to 11, further comprising a spring stop member (11) which comprises a spring stop coupling structure (111) and is forced towards distally by the biasing member (9) to be fixable to the base assembly by the spring stop coupling structure(111) engaging with a base assembly coupling structure (56) of the base assembly with a distal face (11 la) of the spring stop coupling structure (111) abutting a proximal face (56b) of a portion (56a) of the base assembly coupling structure (56); wherein one of the first plunger rod device (8) and of the spring stop member (11) comprises a pair of locking arms (85) with locking protrusions (86), and the other one of the first plunger rod device (8) and of thespring stop member (11) comprises a locking structure (113) capable of engaging with the locking protrusions (86); wherein the medicament delivery device (2) is configured for the locking arms (85) to flex in a resilient manner while the user causes the distal movement of the first plunger rod device (8) for loading and to flex back for the locking protrusions (86) to engage the locking structure (113) immediately before a loaded position has been reached by the first plunger rod device (8); the medicament delivery (2) further comprising an activation mechanism for the user to activate medicament delivery, the activation mechanism comprising an activation button (13) with an activation structure (133) which, when the activation button (13) is pressed, moves towards proximally to cause the locking arms (85) to flex until their locking protrusions (86) get out of engagement with the locking structure (113) to cause a release of the plunger rod assembly (101) so that the biasing member (9) displaces the plunger rod assembly (101) towards proximally; wherein the medicament delivery device furthermore comprises a signalization mechanism for causing a start signal for each of the doses, the start signals being perceivable by the user and being indicative of a start of the expelling of the respective dose, wherein the signalization mechanism is operated by operating the activation mechanism in that, when the activation button (13) is pressed, the activation structure (133) in a first position while moving towards proximally, causes, by sliding on locking protrusion ramps (90) of the locking protrusions (86), the locking arms (85) to flex and to cause a movement of the spring stop (11) towards proximally which is limited towards proximally by a limiting structure (115) of the spring stop member (11) abutting a limiting shoulder (53) of the base assembly and opens up a gap between the distal face (11 la) of the spring stop coupling structure (111) and the proximal face (56b) of the portion (56a) of the base assembly coupling structure (56); and subsequently, in a second position while moving towards proximally, causes the release of the plunger rod assembly (101), which causes the spring stop member (11) to be forced by the biasing member (9) to carry out a movementtowards distally, which is limited towards distally by an abutment of the distal face (11 la) of the spring stop coupling structure (111) and the proximal face (56b) of the portion (56a) of the base assembly closing of the gap; said abutment generating the start signal.

14. The medicament delivery device (2) according to one of claims 1 to 13, wherein the signaling member (16) comprises a bearing member, and the cooperation member (18) comprises a bearing seat cooperating with the bearing member to form a bearing for the biasing member (9).

15. A medicament delivery assembly (1), comprising the medicament delivery device (2) according to one of claims 1 to 14, further comprising the medicament container (3) assembled with the medicament delivery device (2).

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