WO2025146392A1

WO2025146392A1 - Medicament delivery device and medicament delivery assembly

Info

Publication number: WO2025146392A1
Application number: PCT/EP2024/088167
Authority: WO
Inventors: Daniel SÄLL
Original assignee: SHL Medical AG
Current assignee: SHL Medical AG
Priority date: 2024-01-03
Filing date: 2024-12-20
Publication date: 2025-07-10
Anticipated expiration: 2026-07-03

Abstract

The medicament delivery device (1) for accommodating a medicament container (3) containing a medicament and for expelling multiple fixed doses of the medicament from the medicament container (3), defines a device axis and comprises - a plunger rod device (6) which is axially movable; - a biasing device (7) configured to force the plunger rod device (6) in a proximal direction; - a control mechanism configured to control a dosing amount for each of the doses. The control mechanism comprises, for each of the doses, one or more control structures (9), wherein for each of the doses, the respective one or more control structures (9) are configured to control the dosing amount for the respective dose.

Description

TITLE

Medicament Delivery Device and Medicament Delivery Assembly

TECHNICAL FIELD

The invention is in the field of medicament delivery devices. In particular, it relates to automatic medicament delivery devices and to medicament delivery devices for delivering multiple fixed doses of a medicament.

BACKGROUND

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 to be perforated immediately prior to use, or a syringe. Often, the medicament delivery device and the medicament container are preassembled to constitute a medicament delivery assembly for selfadministration.

Such medicament delivery devices and medicament delivery assemblies should generally be safe to use and easy to handle, and they should ensure delivery of the designated dose of the medicament with high accuracy.

Many such medicament delivery devices which are to deliver a single predetermined dose are "empty all", coming with a pre-filled syringe or vial as medicament container containing said pre-determined dose of the medicament.

In many applications, such pre-determined (preset) medicament doses have to be delivered repeatedly. In view of environmental considerations, it is undesirable in that case to use pre-filled single-dose medicament delivery devices and dispose one of those for each dose to be delivered (disposable single-dose auto-injectors). One way of lowering the carbon footprint here is to reduce the amount of material involved, in particular plastics. This can be accomplished by allowing for the medicament delivery device to deliver multiple doses instead of only one, thus reducing the carbon footprint per injection.

Correspondingly large volume cartridges are available and allow for multiple injections with one medicament container instead of single dose injections with a pre-filled syringe per delivery. Accordingly, multi-dose medicament delivery devices (also referred to as partial doses medicament delivery devices) may be preferred.

For small doses, such as in case of insulin, pen injectors containing enough of the medicament for multiple doses are known. Such insulin pens are mainly operated manually so that the user (patient) presses a button and injects with the force of the thumb.

Corresponding multiple dose autoinjectors exist, but they are designed for variable doses of drugs, like in the case of insulin. In case fixed (predetermined) doses are to be administered, corresponding injector designs have the disadvantage that their usability and safety is compromised, because it is possible for a patient to set the wrong dose. Thus, overdosing and underdosing can easily happen.

Furthermore, it would be desirable to relieve the user from having to provide the force required for expelling the dose. In other words, it would be desirable to provide an autoinjector which does not require the user to exert high forces for delivering a dose.

And still furthermore, it would be desirable to have an autoinjector, in particular for multiple fixed doses, which can deliver high dosing amounts, such as around 1 ml. SUMMARY

Therefore, one object of the invention is to create a new medicament delivery device for delivering multiple doses, in particular multiple fixed (preset / predetermined) doses, of a medicament from a medicament container.

Another object of the invention is to create a medicament delivery device which is particularly environment-friendly and/or has a small carbon footprint.

Another object of the invention is to create a medicament delivery device which is particularly simple to use.

Another object of the invention is to create a medicament delivery device which works without a user having to exert high forces.

Another object of the invention is to create a medicament delivery device which is particularly safe to use.

Another object of the invention is to create a medicament delivery device which particularly effectively prevents overdosing.

Another object of the invention is to create a medicament delivery device which particularly effectively prevents underdosing.

Another object of the invention is to create a medicament delivery device which is configured to deliver doses with high accuracy.

Another object of the invention is to create a medicament delivery device which is configured to deliver doses of a relatively large dosing amount.

Furthermore, the medicament delivery device should be advantageous in terms of safety, reliability, ease of use.

Further objects and various advantages emerge from the description and embodiments below. These objects are at least partially achieved by devices and assemblies according to the patent claims.

The medicament delivery device for accommodating a medicament container containing a medicament and for expelling multiple fixed doses of the medicament from the medicament container defines a device axis which more particularly is a proximodistal axis, and it comprises a plunger rod device being axially movable; a biasing device configured to bias the plunger rod device in a proximal direction; a control mechanism configured to control a dosing amount for each of the doses.

Furthermore, the control mechanism comprises, for each of the doses, one or more control structures. For each of the doses, the respective one or more control structures are configured to control the dosing amount for the respective dose.

In particular, for each of the doses, the respective one or more control structures are configured to control an axial length of an expelling movement of the plunger rod device carried out for expelling the respective dose.

In other words, the dosing amounts are controlled via an axial distance along which the plunger rod device moves during the expelling movement; and these axial distances (or lengths) are defined by the respective control structures.

As stated before, the medicament delivery device delivers fixed doses - in contrast to, e.g., typical insulin injectors where dosing amounts can be selected (by the user) for each dose. And the control structures - which are fixed for a given medicament delivery device - define these pre-determined dosing amounts. Thus, using the medicament delivery device is particularly safe and simple. And underdosing as well as overdosing can be avoided very effectively.

These axial lengths can be identical for all doses, such as in case the dosing amount is identical for all doses, or can differ from one another in case the doses have different dosing amounts.

The plunger rod device can in particular be both, proximally movable and distally movable.

In embodiments, the plunger rod device is configured to carry out an expelling movement (which is a proximal movement) for each of the doses in order to proximally move the stopper to effect an expelling of the respective dose.

And the medicament delivery device is very environmental-friendly, as it is designed to deliver multiple doses and not only a single one.

In embodiments, the one or more control structures for different ones of the doses are different from one another. More particularly, in such embodiments, for each of the doses, at least one of the one or more control structures for the respective dose is different from at least one of the one or more control structures for any of the other doses. This way, e.g., doses to be expelled after one another can share at least one control structure. In other embodiments, each of the one or more control structures for any of the doses is different from any one of the one or more control structures for any of the other doses. In this case, the control structures for different doses are disjunct.

Thus, there is not, e.g., a single control structure which is used for each one of the doses. Accordingly, it is possible, e.g., to deliver doses having different dosing amounts. Even when the control structures for different doses are not identical they can be alike, e.g., identically embodied. This can be the case, e.g., when the dosing amount shall be the same for all doses. In embodiments, the control structures for different ones of the doses are arranged at different axial positions. E.g., from one dose to the next dose, the respective control structures can be further distal from one another.

In embodiments, the control structures are comprised in the plunger rod device. This is a simple and effective way of implementing the control structures.

In embodiments, the control structures comprises a first aggregation of control structures and a second aggregation of control structures.

In embodiments, the second aggregation of control structures is different from the first aggregation of control structures. In particular, each control structure of the first aggregation can be different from any of the control structures of the second aggregation.

In embodiments, for each of the doses, a respective control structure of the first aggregation comprises a starting feature defining a start reference for the expelling movement of the plunger rod device for expelling the respective dose.

In embodiments, and in particular in combination with the before-described embodiment, for each of the doses, a respective control structure of the second aggregation comprises a terminating feature defining a termination reference for the expelling movement of the plunger rod device for expelling the respective dose.

The first aggregation can in particular be identical to the first set (of control structures) described below.

The second aggregation can in particular be identical to the second set (of control structures) described below.

In embodiments, the first aggregation extends generally parallel to the device axis, e.g., the starting features can form a row extending generally parallel to the device axis. In embodiments, the control structures of the first aggregation comprise protrusions, e.g., each of the control structures of the first aggregation comprises a protrusion. In particular, each of the terminating features can comprise a protrusion.

In embodiments, the control structures of the first aggregation comprise indentations, e.g., each of the control structures of the first aggregation comprises an indentation. In particular, each of the terminating features can comprise an indentation.

In embodiments, the control structures of the second aggregation extend generally parallel to the device axis, e.g., these control structures form a (possibly curved) line extending generally parallel to the device axis. The terminating features can form a row extending generally parallel to the device axis.

In embodiments, the control structures of the second aggregation comprise indentations, in particular grooves. E.g., the control structures of the second aggregation can comprise a continuous groove.

More particularly, for each of the doses, the respective one or more control structures are sections of the continuous groove.

In embodiments, each of the terminating features forms an indentation or a section of a groove, in particular of the continuous groove.

In embodiments, the control structures of the second aggregation comprise protrusions, in particular ridges. E.g., the control structures of the second aggregation can comprise a continuous ridge. Each control structure of the second aggregation can comprise (or constitute), e.g., a section of the ridge.

In embodiments, the medicament delivery device comprises a user-operable element comprising a cooperation feature, and a portion of the control structures forms a guiding feature for guiding the cooperation feature. The guiding feature comprises multiple sections, one for each of the doses, and each of the sections comprises a stopping location. The guiding feature and the cooperation feature are configured to cooperate to stop the expelling movement when the cooperation feature has been guided, by the guiding feature, during the expelling movement of the plunger rod device carried out for expelling the respective dose, to reach the respective stopping location.

In this way, each dose delivery can be terminated in a way controlled by the respective control features, more particularly at the stopping location of the respective section.

In embodiments, the guiding feature rotationally guides the cooperation feature.

The cooperation of the guiding feature and the cooperation feature can terminate respective expelling movements.

The guiding feature can be configured to cooperate with the user-operable element, in particular via the cooperation feature, so as to provide a guided movement, in particular a rotational guided movement, of the user-operable element. This can more particularly be the case during the expelling movement of the plunger rod device carried out for expelling respective dose. The guided movement can bring the cooperation feature to the respective stopping location for each of the doses.

Said portion of control structures and in particular the guiding feature can be identical to the second aggregation of control structures.

Said portion of control structures and in particular the guiding feature can be identical to the second set (of control structures) described below.

For each of the doses, the respective section can be formed by the respective one or more control structures associated with the respective dose.

The user-operable element can be identical to the second activation device described further below. The cooperation feature can be identical to the second retaining device described further below. It can comprise, e.g., a protrusion, such as a pin.

The guiding feature can in particular be a continuous guiding feature, more particularly a continuous groove.

In embodiments, the user-operable element and the cooperation feature form a unitary part. However, they could also be cooperating in different way.

In embodiments, adjacent the stopping location, the guiding feature describes a line describing a bend which is distally closed. This way, the force exerted by the biasing device cannot remove the cooperation feature out of the stopping location.

In embodiments, the guiding feature describes a line which is shaped so that a force counteracting the force exerted by the biasing device is required for moving the cooperation feature out of the stopping location. This way, the state in which the cooperation feature is in the stopping location is particularly stable.

In embodiments, the medicament delivery device comprises an activation mechanism comprising a first retaining device configured to assume a blocking state in which it blocks a proximal movement of the plunger rod device forced by the biasing device, and a releasing state which constitutes a pre-condition for a proximal movement of the plunger rod device forced by the biasing device; and a first activation device cooperating with the first retaining device and operable by a user to change from a base state to an activating state.

The activation mechanism is configured such that, for each of the doses, a pre-condition for expelling the respective dose is an operation of the first activation device which brings the first activation device from the base state to the activating state so that the first retaining device transitions from the blocking state to the releasing state.

This way, a user can start the expelling of a dose by operating the first activation device accordingly. E.g., the start of the expelling movement can be inhibited by first retaining device in the blocking state, and operating the first activation device can start the expelling.

More particularly, in the releasing state, a proximal movement of the plunger rod device forced by the biasing device is not inhibited (or is unblocked) by the first retaining device.

The releasing state can in particular constitute a pre-condition for each of the expelling movements of the plunger rod device.

In embodiments, the first retaining device is configured to cooperate, for each of the doses, with at least one of the respective one or more control structures so as to block, in the blocking state, the proximal movement of the plunger rod device forced by the biasing device.

Thus, the start of the expelling movement can be inhibited by the first retaining device cooperating with at least one of the control structures. In particular, this at least one control structure can be comprised in the first aggregation (or in the first set) of control structures.

In embodiments, the medicament delivery device comprises a terminating mechanism comprising a second retaining device configured to assume a termination state in which it blocks a proximal movement of the plunger rod device forced by the biasing device, and an unblocked state which constitutes a precondition for a proximal movement of the plunger rod device forced by the biasing device.

The terminating mechanism is configured to terminate, for each of the doses, expelling the respective dose in reaction to the second retaining device cooperating with at least one of the respective one or more control structures so as to block, in the termination state, the proximal movement of the plunger rod device forced by the biasing device.

Thus, the end of the expelling movement can be determined by the second retaining device cooperating with at least one of the control structures. In particular, this at least one control structure can be comprised in the second aggregation (or in the second set) of control structures.

More particularly, in the unblocked state, a proximal movement of the plunger rod device forced by the biasing device is not inhibited (or is unblocked) by the second retaining device.

The unblocked state can in particular constitute a pre-condition for each of the expelling movements of the plunger rod device.

In embodiments, the termination mechanism comprises a second activation device cooperating with the second retaining device and operable by a user to change from a secured state to an activatable state.

And the activation mechanism in this case is configured such that, for each of the doses, a pre-condition for expelling the respective dose is an operation of the second activation device which brings the second activation device from the secured state to the activatable state to effect that the second retaining device changes from the termination state to the unblocked state.

This way, a user can enable a start the expelling of a dose by operating the second activation device. E.g., the start of the expelling movement can be inhibited by the second retaining device in the secured state, and operating the second activation device can enable to start the expelling.

Thus, the activatable state can also be considered an enabling state. In embodiments, the second activation device comprises the second retaining device. E.g., the second activation device and the second retaining device can form a unitary part.

In embodiments, the control structures comprise a first set of control structures and a second set of control structures, wherein the first retaining device is configured to cooperate, for each of the doses, with a respective one of the control structures comprised in the first set so as to block, in the blocking state, the proximal movement of the plunger rod device forced by the biasing device; and the second retaining device is configured to cooperate, for each of the doses, with a respective one of the control structures comprised in the second set so as to block, in the termination state, the proximal movement of the plunger rod device forced by the biasing device.

This way, the start of the expelling movements can be inhibited by cooperation of the first retaining device with respective control structures of the first set. And the end of the expelling movements can be determined by cooperation of the second retaining device with respective control structures of the second set.

It can be an important security feature to inhibit an unwanted expelling of two (or more) doses after one another. This can be accomplished in that a user, in order effect the expelling of a dose, first has to bring the second activation device from the secured state to the activatable state, before bringing the first activation device from the base state to an activating state.

In embodiments, the second set of control structures is different from the first set of control structures.

In embodiments, each control structure of the first set is different from any of the control structures of the second set. In embodiments, the one or more control structures configured to control the dosing amount for the respective dose comprise at least one control structure of the first set and at least one control structure of the second set, for example, as described above with reference to the starting feature defining a start reference for the expelling movement and the terminating feature defining a termination reference for the expelling movement.

In embodiments, each control structure of the first set comprises a protrusion or an indentation, in particular a protrusion. Each of these protrusions (or indentations), e.g., can cooperate with the first retaining device as described.

In embodiments, the second set comprises, in particular constitutes, a continuous feature, and each control structure of the second set comprises a part of the continuous feature. This way, the second set can form a guiding feature as herein described, such as for guiding the second retaining device.

Said parts of the continuous feature can be identical to the sections of the guiding feature described above.

The continuous feature can be, e.g., a continuous groove and a continuous protrusion, such as a continuous ridge.

In embodiments, the biasing device comprises, e.g., stores, in an initial state of the medicament delivery, an amount of energy sufficient for expelling all of the doses from the medicament container. The initial state can in particular be the state present just before an expelling of a first one of the doses.

This way, the user does not have to exert forces as high as required to expel medicament doses from the medicament container.

Furthermore, the biasing device can be sequentially released, for one dose after the other, in particular such that the energy stored in the biasing device is thereby reduced more and more. In embodiments, the medicament delivery device comprises a feedback mechanism configured to provide feedback perceivable by a user during the expelling movement. In particular the feedback mechanism can comprise features comprised in the plunger rod device, such as protrusions or indentations. The features can, e.g., cooperate with the first retaining device.

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 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.

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.

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

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.

BRIEF DESCRIPTION OF THE DRAWINGS

Embodiments of the present disclosure will now be described by way of example only and with reference to the following accompanying drawings.

Figure 1A a medicament delivery assembly, in a perspective view;

Figure 1B a partially exploded view of the medicament delivery assembly of Fig. 1A;

Figure 1C an exploded view of the medicament delivery assembly of Fig. 1A;

Figure 2A a distal housing part of the medicament delivery assembly of Fig. 1A, in a perspective view approximately in proximal direction;

Figure 2B the distal housing part of Fig. 2A, in another perspective view, assembled with the second activation device;

Figure 3 a first activation device of the medicament delivery assembly of Fig. 1A, in a perspective view;

Figure 4 a first retaining device of the medicament delivery assembly of Fig. 1A, in a perspective view;

Figure 5A a second activation device of the medicament delivery assembly of Fig. 1A, in a perspective view;

Figure 5B the second activation device of Fig. 5A, in another perspective view, also showing the second retaining device;

Figure 6 a plunger rod device of the medicament delivery assembly of Fig. 1A, in a perspective view, showing two sets of control structures; Figure 7A the plunger rod of Fig. 6, assembled with the second activation device of Figs. 5A, 5B, in a perspective view;

Figure 7B the plunger rod and second activation device of Fig. 7A, in a perspective view, in a different state;

Figure 8A a cross-section of a detail of the medicament delivery assembly of Fig. 1A, the first retaining device in a blocking state;

Figure 8B a cross-section of a detail of the medicament delivery assembly of Fig. 1A, the first retaining device in a releasing state;

Figures 9A to 9H the medicament delivery assembly of Fig. 1A in different states, in a perspective view, the distal housing part not shown.

The described embodiments are meant as examples or for clarifying the invention and shall not limit the invention.

DETAILED DESCRIPTION

Fig. 1A shows, in a perspective view, a medicament delivery assembly 1. Fig. 1B shows medicament delivery assembly 1 in a partially exploded. Fig. 1C shows the medicament delivery assembly 1 in a fully exploded view.

Medicament delivery assembly 1 and medicament delivery device, respectively, define a proximodistal axis A.

With reference to Figs. 1A to 1C and further figures, medicament delivery assembly 1 comprises: a needle assembly 5, a proximal housing part 4a (cf. Figs. 2A, 2B), a medicament container 3 containing a medicament, a second activation device 12 (cf. Figs. 5A, 5B) comprising a second retaining device 16 (cf. Fig 5B), a plunger rod device 6 (cf. Figs. 6, 7A, 7B), a biasing device 7, a first retaining device 15 (cf. Fig. 4), a distal housing part 4b (cf. Figs. 2A, 2B), an activation force device 13, and a first activation device 10 (cf. Fig. 3).

Needle assembly 5 is attachable to and detachable from the medicament delivery device and comprises a needle device, such as cannula, to pierce a seal of container 3, such as a septum. Container 3 comprises a stopper 3b, such as a plunger. For each of the doses of the medicament to be expelled, a new needle assembly is attached and, after the medicament delivery, detached.

Plunger rod device 6 comprises control structures 9 which control the dose amount for each dose. Together with first activation device 10 and second activation device 12, plunger rod device 6 enables a secure control by a user of the delivery of each single dose. In particular, the user can start the delivery, and the medicament delivery device 1 terminates it.

Control structures 9 comprise a first set 91 (also referred to as first aggregation) and a second set 92 (also referred to as second aggregation or as portion of the control structures 9). The small thick circle in Fig. 6 approximately encircles a control structure 9 of first set 91. The thick dashed ellipse approximately encircles a control structure 9 of second set 92.

The control structures 9 of first set 91 are embodied as protrusions forming a row. As an option for increased stability, first set 91 comprises two such rows (on opposite sides of plunger rod device 6).

The control structures 9 of second set 92 are embodied as indentations or grooves which form a continuous feature, i.e., a continuous groove, which functions as a guiding feature, guiding second retaining device 16 which is embodied as a protrusion or pin of second activation device 12, referred to as pin 16 in the following. Second retaining device 16 is also referred to as cooperation feature. Each of the control structures 9 of the second set 92 can be considered a section (or a part) of the continuous feature.

Plunger rod device 6 is forced proximally by biasing device 7 embodied as a spring which proximally abuts proximal end 6a of plunger rod device 6 and distally abuts distal end 15b of first retaining device 15 which in the illustrated case embodies a plunger rod holding device. Plunger rod device 6 is axially movable. But it is not rotatable, as three ridges 4bi inside distal housing part 4b cooperate accordingly with plunger rod device 6 and in particular with a groove running generally parallel to device axis A on the outside of plunger rod device 6 (not visible in Figs 6, 7A, 7B).

Second activation device 12 is rotatable but not axially movable due to cooperation of ridges 12a with an inside circumferential groove in distal housing part 4b (not shown).

In an initial state, cf. Fig. 9A, pin 16 is located in a position Pi of second set 92 (cf. Fig. 6).

To effect an initial (large) priming step, so as to proximally move plunger rod device 6 until it abuts stopper 3b and, optionally, to expel a small portion of the medicament, the user operates second activation device 12 by rotating it, briefly counteracting the force exerted by biasing device 7. Then, biasing device 7 moves plunger rod device 6 further proximally, until a position P2 of pin 16 in second set 92 is reached. This state is shown in Fig. 9B. Second retaining device 16 is in an unblocked state.

This state is also shown in Fig. 8A.

Further proximal movement of plunger rod device 6 is blocked by cooperation of first retaining device 15 cooperating with a control structure 9 of first set 91 referred to as starting feature 9s (encircled in Fig. 6). This detail is encircled in Fig. 8A. More particularly, first retaining device 15 comprises an arm 151 and, at a proximal end of arm 151, an abutting member 152 such as a protrusion abutting the encircled control structure 9.

A radially outward bending of arm 151 is prevented by second activation device 10 outwardly abutting arm 151. First retaining device 15 is in a blocking state.

Medicament delivery assembly 1 in this state is prepared for delivery of the first dose. Now, the user operates first activation device io which is embodied as a button, distally forced by activation force device 13 which is embodied as a spring; i.e. the user presses the button distally against the force of the spring.

This way, arm 151 which is biased to bend radially outwardly bend radially outwardly, as is shown in Fig. 8B in the encircled detail. For making this possible, first activation device 10 comprises a slit 10s through which abutting member 152 and the proximal end of second retaining device 15, respectively, can move. This state is also shown in Fig. 9C. First retaining device 15 is in a releasing state.

Accordingly, plunger rod device 6 now can move proximally, as it is not blocked anymore by first retaining device 15. And pin 16 is, during that proximal movement of plunger rod device 6, guided by second set 92, i.e., by the guiding structure.

The proximal movement of plunger rod device 6 is stopped when pin 16 reaches position P3. There, the respective control feature 9 of the second set 92 forms a terminating feature 9t, at a stopping location. This state is shown in Fig. 9D; second retaining device 16 is in a termination state. The end of expelling the first dose is reached.

At this point, first retaining device 15 is not abutting one of the control features 9 of the first set 91, but is distant from the next one. This is symbolically shown in Fig. 6 for the third dose, thick lines symbolizing first retaining member 15, with abutting member 152 being distant from the middle control feature 9 which is the control feature which is associated with the third of the five doses. This axial distance will define an amount of medicament to be expelled in a subsequent priming step to take place before delivery of the second dose, cf. below.

Another pressing of the button (first activation device 10) will not result in expelling more of the medicament at this point (pin 16 in position P3, i.e., in a stopping location). In the vicinity of position P3, a line described by second set 92, i.e., by the guiding structure, has a bend which is distally closed, and even more, both line sections adjacent to position P3 bend at least partially proximally (not fully circumferentially, and especially not even in part distally). Accordingly, in order to move pin 16 out of position P3, the force exerted by biasing device 7 has to be overcome.

The fact that at position P3, the guiding feature not only runs purely circumferentially, but has a distal component, effects that this position is relatively stable (a notable force needs to be overcome for moving out of position P3).

As will have become clear, the axial position of plunger device 6 at the beginning of the first dose is defined by a control structure 9 of the first set (cf. encircled starting feature 9s in Fig. 6) - in cooperation with first retaining device 15; and the axial position of plunger device 6 at the end of the first dose is defined by a control structure 9 of the second set (cf. item P3 in Fig. 6) - in cooperation with second retaining device 16.

Thus, the dosing amount which is determined by the proximal travel of stopper 3b and thus by the proximal travel of plunger rod device 6, is determined by the control structures 9, starting feature 9s defining a start reference and terminating feature 9t defining a termination reference.

For delivering the second dose, the process is very similar to what is described above. Firstly, second activation device 12 is operated (rotated) again, counteracting biasing device 7, to move out of the termination state (at position P3). This results in a proximal travel of plunger rod device 6, until first retaining device 15 abuts the next control structure of the first set, thus providing a priming, taking place before the delivery of the second dose.

Afterwards, first activation device 10 has to be operated (pressing the button) in order to start delivery of the second dose. Fig. 9E shows the state in which medicament delivery assembly 1 is primed (by operation of second activation device 12) and ready for operating first activation device 10 in order to deliver the second dose.

Fig. 9F shows the state in which medicament delivery assembly 1 has emitted the second dose, initiated by operating first activation device 10.

Fig. 9G shows the state in which medicament delivery assembly 1 is primed (by operation of second activation device 12) and ready for operating first activation device 10 in order to deliver the fifth (=last) dose.

Fig. 9H shows the state in which medicament delivery assembly 1 has emitted the fifth (=last) dose, initiated by operating first activation device 10.

As has been stated before, the priming is an option. No priming would take place, e.g., if the dosing amount would be determined solely by control features of the first set 91, such as when the end of dose is defined by another feature of the first set 91, in particular if one and the same control feature 9 defines the end of the dose and, in addition, also the start of the next dose, in particular for all doses except for the first and for the last one.

Another option is embodied in the described embodiment: Feedback features 9f are provided with provide feedback during delivery of a dose perceivable by the user. The feedback can be, e.g., haptically and/or acoustic. Abutting member 152 cooperates with feedback features 9f, creating vibration and sound. This way, a user can be informed that the dose delivering is still ongoing while the feedback is perceived. This helps to avoid that a user removes the medicament delivery device before the end of the dose is reached.

Fig. 6 shows, as feedback structure 9f, a row of small features on plunger rod device 6, e.g., small protrusions, such as ripples. These cooperate with first retaining member 15 in that first retaining member 15 slides over these during the expelling movement carried out by plunger device 6. Fig. 7A shows plunger rod 6, assembled with second activation device 12 at the end of the third dose.

Fig. 7B shows plunger rod 6, assembled with second activation device 12 after priming before the fourth dose, before start of delivery of the fourth dose.

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

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, Behget’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 Leiden), and cancer.

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.

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.

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-i (GLP-i) modulators, glucose-dependent insulinotropic polypeptide (GIP) modulators, cluster of differentiation 38 (CD38) modulators, cluster of differentiation 22 (CD22) modulators, Ci 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-i/PD-Li) inhibitors/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 W137 (CDW137) agonists, cluster of differentiation 158 (CD158) 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 (CD159 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 W123 (CDwi23) 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, tumorinfiltrating lymphocytes (TIL) therapies, or T-cell receptor (TCR) therapies. 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 (amethopterin), tocilizumab, interferon beta-ia, interferon beta-ib, peginterferon beta-ia, 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.

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.

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.

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.

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.

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. 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, mFOLFOXy, 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.

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

1. A medicament delivery device (2) for accommodating a medicament container (3) containing a medicament and for expelling multiple fixed doses of the medicament from the medicament container (3), the medicament delivery device (2) defining a device axis (A) and comprising a plunger rod device (6) axially movable, in particular proximally movable; a biasing device (7) configured to bias the plunger rod device (6) in a proximal direction; a control mechanism configured to control a dosing amount for each of the doses; wherein the control mechanism comprises, for each of the doses, one or more control structures (9), wherein for each of the doses, the respective one or more control structures (9) are configured to control the dosing amount for the respective dose; in particular wherein for each of the doses, the respective one or more control structures (9) are configured to control an axial length of an expelling movement of the plunger rod device (6) carried out for expelling the respective dose.

2. The medicament delivery device (2) according to claim 1, wherein the one or more control structures (9) for different ones of the doses are different from one another.

3. The medicament delivery device (2) according to claim 1 or claim 2, the control structures (9) being comprised in the plunger rod device (6).

4. The medicament delivery device (2) according to one of claims 1 to 3, the control structures (9) comprising a first aggregation (91) of control structures and a second aggregation (92) of control structures, wherein one or both of: for each of the doses, a respective control structure (9) of the first aggregation (91) comprises a starting feature (9s) defining a start reference for the expelling movement of the plunger rod device (6) for expelling the respective dose; for each of the doses, a respective control structure (9) of the second aggregation (92) comprises a terminating feature (9t) defining a termination reference for the expelling movement of the plunger rod device (6) for expelling the respective dose; in particular wherein the second aggregation (92) of control structures is different from the first aggregation (91) of control structures.

5. The medicament delivery device (2) according to one of claims 1 to 4, comprising a user-operable element (12) comprising a cooperation feature (12a), a portion (92) of the control structures forming a guiding feature (92), in particular a continuous guiding feature (92), for guiding the cooperation feature (12a), the guiding feature (92) comprising multiple sections, one for each of the doses; each of the sections comprising a stopping location (9t), wherein the guiding feature (92) and the cooperation feature (12a) are configured to cooperate to stop the expelling movement when the cooperation feature (12a) has been guided, by the guiding feature (92) during the expelling movement of the plunger rod device (6) carried out for expelling the respective dose, to reach the respective stopping location (9t).

6. The medicament delivery device (2) according to one of claims 1 to 5, comprising an activation mechanism comprising a first retaining device (15) configured to assume a blocking state in which it blocks a proximal movement of the plunger rod device (6) forced by the biasing device (7), and a releasing state which constitutes a pre-condition for a proximal movement of the plunger rod device (6) forced by the biasing device (7); and a first activation device (io) cooperating with the first retaining device (15) and operable by a user to change from a base state to an activating state; wherein the activation mechanism is configured such that, for each of the doses, a pre-condition for expelling the respective dose is an operation of the first activation device (10) which brings the first activation device (10) from the base state to the activating state so that the first retaining device (15) transitions from the blocking state to the releasing state.

7. The medicament delivery device (2) according to claim 6, the first retaining device (15) being configured to cooperate, for each of the doses, with at least one of the respective one or more control structures (9) so as to block, in the blocking state, the proximal movement of the plunger rod device (6) forced by the biasing device (7).

8. The medicament delivery device (2) according to one of claims 1 to 7, comprising a terminating mechanism comprising a second retaining device (12a) configured to assume a termination state in which it blocks a proximal movement of the plunger rod device (6) forced by the biasing device (7), and an unblocked state which constitutes a pre-condition for a proximal movement of the plunger rod device forced by the biasing device (7); and wherein the terminating mechanism is configured to terminate, for each of the doses, expelling the respective dose in reaction to the second retaining device (12a) cooperating with at least one of the respective one or more control structures so as to block, in the termination state, the proximal movement of the plunger rod device (6) forced by the biasing device (7).

9. The medicament delivery device (2) according to claim 8, the termination mechanism comprising a second activation device (12) cooperating with the second retaining device (12a) and operable by a user to change from a secured state to an activatable state; wherein the activation mechanism is configured such that, for each of the doses, a pre-condition for expelling the respective dose is an operation of the second activation device (12) which brings the second activation device (12) from the secured state to the activatable state to effect that the second retaining device (12a) changes from the termination state to the unblocked state.

10. The medicament delivery device (2) according to claim 7 AND to one of claims 8 to 9, the control structures comprising a first set (91) of control structures (9) and a second set (92) of control structures (9) which is different from the first set (91) of control structures (9), wherein the first retaining device (15) is configured to cooperate, for each of the doses, with a respective one of the control structures (9) comprised in the first set (91) so as to block, in the blocking state, the proximal movement of the plunger rod device (6) forced by the biasing device (7); and the second retaining device (12a) is configured to cooperate, for each of the doses, with a respective one of the control structures (9) comprised in the second set (92) so as to block, in the termination state, the proximal movement of the plunger rod device (6) forced by the biasing device (7); in particular wherein the second set (92) of control structures (9) is different from the first set (91) of control structures (9).

11. The medicament delivery device (2) according to claim 10, each control structure (9) of the first set (91) comprises a protrusion or an indentation.

12. The medicament delivery device (2) according to claim 10 or claim 11, the second set (92) comprising a continuous feature, each control structure (9) of the second set (92) comprising a part of the continuous feature.

13. The medicament delivery device (2) according to one of claims 1 to 12, the biasing device (7) comprising, in an initial state of the medicament delivery device (2), an amount of energy sufficient for expelling all of the doses from the medicament container (3).

14. The medicament delivery device (2) according to one of claims 1 to 13, comprising a feedback mechanism configured to provide feedback perceivable by a user during the expelling movement, in particular wherein the feedback mechanism comprises features comprised in the plunger rod device (6), more particularly wherein said feedback is audible and/or haptic.

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).