EP4661929A1

EP4661929A1 - A subassembly of a medicament delivery device

Info

Publication number: EP4661929A1
Application number: EP24702138.9A
Authority: EP
Inventors: Pei Yu Chao; Carrie ZHONG
Original assignee: SHL Medical AG
Current assignee: SHL Medical AG
Priority date: 2023-02-08
Filing date: 2024-01-25
Publication date: 2025-12-17
Also published as: WO2024165327A1

Abstract

The present disclosure generally relates to medicament delivery devices such as autoinjectors, and particularly concerns a subassembly for a medicament delivery device.

Description

A SUBASSEMBLY OF A MEDICAMENT DELIVERY DEVICE

TECHNICAL FIELD

BACKGROUND

A number of medical conditions require injections. These days, a number of different injection devices exist, including various types of pen injectors, autoinjectors and on-body devices. Although many of these devices have enabled major improvements in the management of a number of medical conditions, various limitations do still exist in the current technology. Not least amongst these are the difficulties faced by patients that require frequent injections and by patients that need to inject particularly viscous drugs. In considering these problems, the applicant has appreciated that various developments could be made to help improve the medicament delivery devices on the market today, for example concerning providing feedback to a user during injection events, which are set out in more detail below.

SUMMARY

An object of the present disclosure is to provide a subassembly for a medicament delivery device which solves, or at least mitigates problems of the prior art.

According to a first aspect of the present disclosure, there is provided a subassembly of a medicament delivery device, the sub-assembly comprising: a housing extending along a longitudinal axis between a distal end and a proximal end, a rotator arranged in the housing, the rotator is rotatable about the longitudinal axis with respect to the housing, the rotator comprising at least one radially inwards facing structure; a plunger rod arranged radially inside the rotator, the plunger rod comprising at least one radially outwards facing structure relative to the longitudinal axis; the rotator is rotatable with respect to the plunger rod between at least a first rotational position and a second rotational position, wherein in the second rotational position, the plunger rod is axially movable with respect to the rotator so that the at least one radially outwards facing structure interact with the radially inwards facing structure of the rotator to generate an audible click sound.

Embodiments of the present disclosure advantageously provides for audible feedback to the user that indicates delivery of a medicament. In other words, as drug delivery is performed under the action of the moving plunger rod, the interaction between the structures of the plunger rod and the corresponding structures of the rotator as they interact with each other.

The at least one radially inwards facing structure of the rotator and the at least one radially outwards facing structure of the plunger rod are configured such that when the plunger rod moves linearly with respect to the rotator, a mechanical interaction between the structures causes an audible sound, such as at least one click-sound.

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 components thereof, which under 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 under use of the medicament delivery device is/are located closest to the dose delivery site.

Further, the term “longitudinal”, “longitudinally”, “axially” or “axial” refer to a direction extending from the proximal end to the distal end, typically along the device or components thereof 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.

Further, the terms “circumference”, “circumferential”, “circumferentially” refer to a circumference or a circumferential direction 301 relative to an axis 102, typically a central axis extending in the direction of the longest extension of the device and/or component. Similarly, “radial” or “radially” refer to a direction 302 extending radially relative to the axis, and “rotation”, “rotational” and “rotationally” refer to rotation relative to the axis.

According to one embodiment, the sub-assembly may comprise: a needle shield configured to surround a needle at a proximal end of the medicament delivery device, the needle shield is movable inside the housing in an axial direction of the housing between a retracted position in which the needle is exposed at the proximal end of the needle shield, and an extended position in which the needle is covered by the needle shield, the rotator is arranged inside the needle shield, wherein the needle shield comprising radially inwards extending protrusions and the rotator comprises surfaces that are inclined with respect to the longitudinal axis, when the needle shield moves between the extended position and the retracted position, the radially inwards extending protrusions of the needle shield slide against the inclined surface of the rotator to cause the rotation of the rotator with respect to the plunger rod. Advantageously, the rotator rotates in response to that the needle shield is moved for an injection event. This rotation to the second portion leads to that the plunger rod is released and can move in the proximal direction.

According to one embodiment, the at least one radially inwards facing structure of the rotator may be at least one radially inwards extending protrusion and the at least one radially outwards facing structure of the plunger rod may be at least one radially outwards extending protrusion, the at least one protrusion of the plunger rod extend radially beyond the radially inwards extending protrusions of the rotator, wherein the at least one protrusion of the plunger rod interact with the radially inwards extending protrusions of the rotator to generate the audible click sound.

Protrusions are one advantageous and possible way to enable the audible feedback. Further possible implementations include that the rotator comprises one of a set of protrusions and cut-outs, and the plunger rod comprises the other one of protrusions and cut-outs. For example, the rotator may comprise radially inwards extending protrusions that interact with radially outwards facing cut-outs of the plunger rod. In another example, the rotator may comprise radially inwards facing cut-outs that interact with radially outwards extending protrusions of the plunger rod.

According to one embodiment, the rotator may comprise a plurality of the radially inwards extending protrusions arranged aligned in parallel with the longitudinal axis. The radially inwards extending protrusions maybe spaced apart from one another by the same distance, or by varying distances. For example, the distance between protrusions may be greater near the distal end and become narrower closer to the proximal end. The distance between the protrusions may be gradually smaller closer to the proximal end.

According to one embodiment, the plurality radially inwards extending protrusions may be distributed along longitudinal axis to provide a continuous click-sound during an injection event when the plunger rod moves axially in the proximal direction.

According to one embodiment, the radially inwards extending protrusions of the rotator may advantageously be parallel ribs or a sawtooth structure.

According to one embodiment, the at least one radially outwards extending protrusion of the plunger rod may include at least radially outwards extending protrusion arranged at a distal end of the plunger rod. This provides for audible feedback that last for a relatively long time. According to one embodiment, the at least one radially outwards extending protrusion of the plunger rod may be radially flexible to move radially when engaging with the radially inwards extending protrusions of the rotator. This is one advantageous and relatively straight-forward way to realise audible feedback.

According to one embodiment, the radially inwards extending protrusions of the rotator or the radially outwards extending protrusions of the plunger rod comprises an inclined surface configured to engage with the other one of the radially inwards extending protrusions of the rotator or the radially outwards extending protrusions of the plunger rod. The inclined surfaces facilitate for the protrusions of the plunger rod to move past the protrusions of the rotator so that audible feedback is provided.

According to one embodiment, the rotator may comprise two sets of radially inwards extending protrusions arranged on opposite sides of the rotator with respect to the longitudinal axis, the plunger rod comprising a corresponding one radially outwards extending protrusion for each of the sets of radially inwards extending protrusions of the rotator. Thereby, a symmetric arrangement of protrusions is provided that facilitates for a linear motion between the plunger rod and the rotator.

According to one embodiment, the sub-assembly may comprise a plunger rod spring configured to apply a spring force on a distally facing surface of the plunger rod to move the plunger rod proximally.

According to one embodiment, the rotator may comprise a first radially inwards extending protrusion and a second radially inwards extending protrusion separated in the longitudinal direction by a distance corresponding to the plunger rod travel distance in the proximal direction from start of injection to end of injection. This advantageously allows for start of injection audible feedback and end of injection audible feedback.

According to one embodiment, wherein the first radially inwards extending protrusion and the second radially inwards extending protrusion of the rotator are arranged on flexible arms that are radially flexible. The flexible arms are advantageously pushed radially outwards by the protrusions of the plunger rod and when they flex back, they hit the plunger rod and thereby cause the audible feedback.

According to one embodiment, the radially inwards extending protrusions of the rotator or the radially outwards extending protrusions of the plunger rod may comprise an inclined surface configured to engage with the other one of the radially inwards extending protrusions of the rotator and the radially outwards extending protrusions of the plunger rod.

According to one embodiment, no further protrusions are arranged between the first radially inwards extending protrusion and the second radially inwards extending protrusion. Thus, only start of injection audible feedback and end of injection audible feedback is provided.

There is further provided a medicament delivery device comprising the subassembly of any of the herein disclosed embodiments.

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 member, apparatus, component, means, etc.” are to be interpreted openly as referring to at least one instance of the member, apparatus, component, means, etc., unless explicitly stated otherwise.

BRIEF DESCRIPTION OF THE DRAWINGS

The specific embodiments of the inventive concept will now be described, by way of example, with reference to the accompanying drawings, in which:

Fig. 1 is a perspective view of an autoinjector according to embodiments of the present disclosure;

Fig. 2 is an exploded view of a subassembly according to embodiments of the present disclosure; Fig. 3 is a perspective view of a plunger rod according to embodiments of the present disclosure;

Fig. 4 is a perspective view of a rotator according to embodiments of the present disclosure;

Fig. 5 is a perspective view of a rotator according to embodiments of the present disclosure;

Fig. 6 is a perspective view of a needle shield according to embodiments of the present disclosure;

Fig. 7A is a perspective view of the subassembly with the rotator in a first rotational position according to embodiments of the present disclosure;

Fig. 7B is a perspective view of the subassembly with the rotator in a first rotational position according to embodiments of the present disclosure;

Fig. 8A shows a perspective view of the subassembly where the needle shield has moved linearly for start of injection according to embodiments of the present disclosure;

Fig. 8B is a perspective view of the subassembly with the rotator in a second rotational position according to embodiments of the present disclosure;

Fig. 9 is a cross-section of the medicament delivery device after injection according to embodiments of the present disclosure;

Fig. io is a cross-section of an embodiment of the subassembly according to embodiments of the present disclosure;

Fig. n is an exploded view of a subassembly according to embodiments of the present disclosure;

Fig. 12 is a perspective view of a plunger rod according to embodiments of the present disclosure; Fig. 13 is a perspective view of a rotator according to embodiments of the present disclosure;

Fig. 14 is a perspective view of a rotator according to embodiments of the present disclosure;

Fig. 15 illustrates the first rotational position of the rotator according to embodiments of the present disclosure;

Fig. 16A illustrates the plunger rod in its initial position once the rotator has moved to the second rotational position according to embodiments of the present disclosure; and

Fig. 16B illustrates the plunger rod in its final position after an injection event according to embodiments of the present disclosure.

DETAILED DESCRIPTION

The inventive concept will now be described more fully hereinafter with reference to the accompanying drawings, in which exemplifying embodiments are shown. The inventive concept may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided by way of example so that this disclosure will be thorough and complete, and will fully convey the scope of the inventive concept to those skilled in the art. Like numbers refer to like members throughout the description.

Fig 1 shows an example of a medicament delivery device 1 such as an autoinjector according to embodiments of the present disclosure. The medicament delivery device 1 is configured to expel medicament from a medicament container via a medicament delivery member such as a needle, to a user at a dose delivery site. The medicament delivery device 1 extends from a proximal end la to a distal end lb relative to the axis 102.

The medicament delivery device 1 comprises a housing 3 with a window 4. The housing 3 has a proximal end 3a and a distal end 3b. A needle shield 6 configured to cover a needle extends out from the proximal end 3a of the housing 3.

The medicament delivery device 1 comprises a subassembly 2 which will now be described in more detail with reference to subsequent drawings.

An exploded view of the subassembly 2 according to one embodiment is shown in fig. 2.

The subassembly 2 comprises a rotator 7 arranged in the housing 3. The rotator 7 is rotatable about the longitudinal axis 102 with respect to the housing 3. The rotator 7 comprising at least one radially inwards facing structure as will be described in more detail with respect to subsequent drawings.

The subassembly 2 further comprises a plunger rod 9 arranged radially inside the rotator 7. The plunger rod 7 comprising at least one radially outwards facing structure 11 relative to the longitudinal axis 102.

Fig. 3 is a perspective view of the plunger rod 9. The plunger rod 9 comprises a radially outwards extending protrusion 13 on its distal end 15b. Here the radially outwards extending protrusion 13 is arranged on the distal end 16b of a flexible arm 16. The proximal end 16a of the flexible arm is a fixed end in relation to the plunger rod 9 whereas the protrusion 13 is on the free end of the flexible arm 16. The flexible arm 16 allows for the protrusion to move radially with respect to the longitudinal axis 102.

The protrusion 13 comprises a proximally facing inclined surface 18 that is configured to slide on radially inwards extending protrusions of the rotator or interact with radially inwards facing cut-outs of the rotator to generate an audible sound when the plunger rod 9 moves axially with respect to the rotator 7.

The plunger rod 9 comprises a proximally facing surface 20 that is part of a radially outwards extending support 22 on which also the fixed end 16a of the flexible arm 16 is attached. The proximally facing surface 20 abuts against a distally facing surface 39, 40 of the rotator 7 in the first rotational position to prevent proximal motion of the plunger rod 9 in relation to the housing 3.

The plunger rod 9 comprises a further protrusion on the opposite side of the plunger rod 9 with respect to the longitudinal axis 102.

Fig. 4 and fig. 5 are two perspective views of the rotator 7. Turning firstly to fig 4, the rotator 7 comprises a first inclined surface 30 facing in a distal direction and a second inclined surface 32 facing in a proximal direction. There is further a slot 34 that runs in a longitudinal direction parallel with the longitudinal axis 102. The slot 34 is arranged to guide a radially inwards extending protrusion of a needle shield towards the first inclined surface 30. When the needle shield first moves proximally (e.g., during priming) the protrusion of the needle shield slides on the first inclined surface 30 which causes the rotator 7 to rotate (opposite the rotation direction 301) about the longitudinal axis 102. When the needle shield subsequently moves distally (for exposing the needle) the interaction of the protrusions of the needle shield with the second inclined surface 32 occurs which causes further rotation of the rotator 7 to the second rotational position.

Turning now fig. 5 illustrating another perspective view of the rotator 7. On the inside of the rotator 7, a plurality of radially inwards extending protrusions 36 are arranged aligned in parallel with the longitudinal axis 102. The radially inwards extending protrusions 36 are arranged to interact with the protrusion 13 of the plunger rod to generate an audible click sound, for each of the protrusions 36. The distribution the protrusions along longitudinal axis 102 provides for a continuous click-sound during an injection event when the plunger rod 9 moves axially in the proximal direction.

The radially inwards extending protrusions 36 may be evenly distributed with the same distance between neighbouring protrusions 36. In other possible implementations, the distance between adjacent protrusions 36 may be smaller closer to the proximal end so that the click sound is varied as the plunger rod 9 travel proximally inside the rotator 7.

The radially inwards extending protrusions 36 of the rotator 7 may be parallel ribs or a sawtooth structure. Furthermore, the radially inwards extending protrusions of the rotator 7 comprises an inclined surface 38 that faces distally and that is configured to engage with the radially outwards extending protrusion 13 of the plunger rod 9.

The rotator 7 comprising two sets of radially inwards extending protrusions arranged on opposite sides of the rotator with respect to the longitudinal axis 102. To generate an improved audible sound, the plunger rod 9 comprises a corresponding one radially outwards extending protrusion 13 for each of the sets of radially inwards extending protrusions of the rotator 7. The protrusions 36 form the first set of protrusions, and the second set is arranged facing the first set on the opposite side of the rotator 7.

Moreover, the rotator 7 comprises distally facing surfaces 39 and 40 which abut against the proximally facing surface 20 of the plunger rod 9 before the rotator 7 has rotated to its second rotational position.

Fig. 6 is a perspective view of a cover structure or more specifically a needle shield 6. The needle shield 6 is configured to surround a needle at a proximal end lb of the medicament delivery device 1 shown in fig. 1. The needle shield 6 is movable inside the housing 3 in an axial direction of the housing 3 between a retracted position in which the needle is exposed at the proximal end 3b of the housing 3, and an extended position in which the needle is covered by the needle shield. The needle shield 6 is typically spring -loaded towards the extended position by a spring.

The rotator 7 is arranged inside the needle shield 6. The needle shield 6 comprises radially inwards extending protrusions 42 which interact with the inclined surface 30 and 32 of the rotator to cause a rotation of the rotator 7 about the longitudinal axis 102. Thus, when the needle shield 6 moves between the extended position and the retracted position, the radially inwards extending protrusions 40 of the needle shield slide against the inclined surface 32 of the rotator 7 to cause the rotation of the rotator with respect to the plunger rod 9.

Fig. 7A and fig. 7B show two different perspectives of the subassembly with the rotator 7 in a first rotational position. An initial axial motion of the needle shield 6 in the proximal direction, pushed by the spring 44, cause an initial rotation of the rotator 7 by an interaction between the protrusion 42 of the needle shield 6 and the inclined surface 30 of the rotator 7. In this position of the rotator 7, the proximal surface 20 of the support 22 of the plunger rod abut against the distally facing surface 40 of the rotator 7.

Fig. 8A shows a perspective view of the subassembly where the needle shield 6 has moved linearly for start of injection. The protrusion 42 has interacted with the inclined surface 32 to cause a rotation of the rotator 7 to the second rotational position. In fig. 8B, the rotator 7 is shown in the second rotational position with respect to the plunger rod 9. The support 22 has now moved away from the distally facing surface 40 of the rotator 7 and the plunger rod 9 is free to move axially under the spring force of a plunger rod spring 46. Thus, in the second rotational position, the plunger rod 9 is axially movable with respect to the rotator 7 so that the at least one radially outwards facing structure, here depicted as protrusions 13 interact with the radially inwards facing structure, here depicted as protrusions 36, of the rotator 7 to generate an audible click sound.

The plunger rod spring 46 is configured to apply a spring force on a distally facing surface of the plunger rod 9 to move the plunger rod 9 proximally. The plunger to spring 46 is guided by a guide rod 48.

Fig. 9 is a cross-section of the medicament delivery device 1 after injection. Here, the plunger rod 9 has travelled axially under the spring force exerted by the plunger rod spring 46 when the engagement between the plunger rod proximally facing surface 20 and the surface 40 of the rotator was lost in the second rotational position of the rotator 7. When the protrusion 13 of the plunger rod 9 pass and interact with the radially inwards extending protrusions 36 of the rotator 7, an audible click sound is generated.

Fig. 10 is a cross-section of an alternative embodiment of the subassembly 2. Here, the plunger rod 9 comprises a radially outwards extending protrusion in the form of hooks 50 comprising a proximally facing inclined surface 52 that interact with ribs 54 of the rotator 7 that extend radially inwards. The at least one protrusion 52 of the plunger rod 9 extend radially beyond the radially inwards extending protrusions 54 of the rotator 7.

When the plunger rod 9 is released and moves proximally under the influence of the plunger rod spring 46, the hooks 52, travel past and interact with the ribs 54 of the rotator 7. The flexible hooks 52 are deflected inwards by the ribs 54 and as they flex back, they hit the rotator inner surface and cause a click sound.

Fig. 11 is an exploded view of another example embodiment of a subassembly 200. The subassembly 200 comprises a rotator 207 arranged in the housing 203. The rotator 207 is rotatable about the longitudinal axis 102 with respect to the housing 203. The rotator 207 comprising at least one radially inwards facing structure as will be described in more detail with respect to subsequent drawings.

The subassembly 200 further comprises a plunger rod 209 arranged radially inside the rotator 207. The plunger rod 207 comprising at least one radially outwards facing structure 211 relative to the longitudinal axis 102.

Fig. 12 is a perspective view of the plunger rod 209. The plunger rod 209 comprises a radially outwards extending protrusion 213. The radially outwards extending protrusion 13 is arranged relatively centred along the longitudinal extension of the plunger rod 209.

The protrusion 213 is configured to slide on radially inwards extending protrusions of the rotator 207 or interact with radially inwards facing cutouts of the rotator to generate an audible sound. Fig. 13 is perspective view of the rotator 207. The rotator 207 comprises inclined surface 230 facing in a distal direction and an inclined surface 232 facing in a proximal direction. A radially inwards extending protrusion of needle shield or a shield link interact with the inclined surfaces 230 and 232 so that the rotator 7 is caused to rotate (opposite the rotation rotational direction 301) about the longitudinal axis 102 when the needle shield first moves proximally (e.g., during priming) whereby interaction with the first inclined surface 30 occurs and subsequently the needle shield moves distally (for exposing the needle) whereby interaction with the second inclined surface 32 occurs.

Fig. 14 is a second perspective view of the rotator 207. The rotator 207 comprises radially inwards extending protrusions 236a-b. More specially, the rotator 207 comprises a first radially inwards extending protrusion 236a and a second radially inwards extending protrusion 236b. The first and second protrusions 236a-b are aligned parallel with the longitudinal axis 102 and separated in the longitudinal direction by a distance corresponding to the plunger rod 209 travel distance in the proximal direction from start of injection to end of injection.

The first radially inwards extending protrusion 236a and the second radially inwards extending protrusion 236b of the rotator 207 are each arranged on respective flexible arms 240 that are radially flexible. The protrusions 236a-b are arranged on the proximal free end 242a of the flexible arms, opposite a distal fixed end 242b of the flexible arms 240.

A further set of first and second radially inwards extending protrusions are arranged on the opposite side with respect to the longitudinal axis 102. Here, the flexible arms 240 are indicated.

The protrusions 238 comprise a distally facing inclined surface 238 configured to engage with the radially outwards extending protrusions 213 of the plunger rod 209. In the first rotational position of the rotator 207, the proximally facing surface 249 of the protrusion 213 of the plunger rod 209 abuts against a distally facing surface 245 of the rotator. The distally facing surface 245 is only barely more distally located than the first protrusion 236a of the rotator 207.

No further protrusions are arranged between the first radially inwards extending protrusion 236a and the second radially inwards extending protrusion 236b that are adapted to provide audible feedback.

Fig. 15 illustrates the first rotational position of the rotator 207 where the proximally facing surface 249 of the protrusion 213 abuts against a distally facing surface 245 of the rotator 207. As with the above embodiments, a plunger rod spring 246 and a guide rod 248 are also shown.

As the rotator 207 is rotated to the second rotational position, the protrusion 213 is rotated to lose contact with the distally facing surface 245 of the rotator 207 and can thereby be moved proximally under the influence of the plunger rod spring 246.

Fig. 16A illustrates the plunger rod 209 in its initial position once the rotator 207 has moved to the second rotational position. The protrusions 213 are aligned with the protrusions 236a and 236b of the rotator 207. When the plunger rod spring 246 moves the plunger rod 209 proximally for an injection event, the interaction between the protrusion 213 of the plunger rod 209 and the first protrusion 236a of the rotator 207 provides audible feedback in the form of a click sound to indicate start of injection.

Subsequently, now turning to fig. 16B, the interaction between the protrusion 213 of the plunger rod 209 and the second protrusion 236b of the rotator 207 provides audible feedback to indicate end of injection.

A medicament delivery device (such as an autoinjector) may generally include various other components. For example, a sensor unit which may recognize injection events, such as the autoinjector inserted into an attachment portion of e.g., a pad, injection started, and injection ends, a memory unit which is configured to store the recorded data during the injection, a connectivity unit configured to transmit the stored data to a smart device or the network directly, a processing unit configured to control the entire system and processes the data before transmitting it, and/or user interface units that are configured to provide feedback to the patient, such as status LEDs, haptic, and/or audio feedback.

When the medicament delivery device is placed into the attachment portion, the sensors inside of the support pad are configured to recognize the event and give feedback to the patient via haptic/visual or audio elements.

When the injection finishes, the sensors are configured to recognize the event and give feedback to the patient again. Further, the collected data is stored in the memory unit and maybe transmitted to the smart device/network via the connectivity unit after the injection event finishes.

The sensor can be one of or the combination of the following: a mechanical switch, a Hall-effect sensor, an accelerometer.

The mechanical switch, hall-effect sensor, or accelerometer can be used for detection of the insertion of the auto-injector into an injection port.

The accelerometer can be used for detecting injection events.

Possible wireless communication methods include Bluetooth and Cellular Networks.

Bluetooth connectivity requires a smart device to transmit the stored data to the network and it requires a pairing action between the support pad and the smart device before being able to use the supporting pad. But it’s a cheaper alternative and it requires less space on PCB.

The cellular network does not require any pairing process, it can be used as a plug-n-play device, no prior setup is needed, but it’s more expensive and it requires more space on PCB. Depending on the requirements of the product any of those two technologies can be used.

Such processing units may comprise a logic circuit or control unit including a microprocessor, microcontroller, programmable digital signal processor or another programmable device. The processing circuitry may also, or instead, each include an application specific integrated circuit, a programmable gate array or programmable array logic, a programmable logic device, or a digital signal processor. Where the processing circuitry includes a programmable device such as the microprocessor, microcontroller or programmable digital signal processor mentioned above, the processor may further include computer executable code that controls operation of the programmable device.

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, Behgef 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-1/PD-L1) 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.

The inventive concept has mainly been described above with reference to a few examples. However, as is readily appreciated by a person skilled in the art, other embodiments than the ones disclosed above are equally possible within the scope of the inventive concept, as defined by the appended claims.

Claims

1. A sub-assembly (2,200) of a medicament delivery device (1), the subassembly comprising: a housing (3, 203) extending along a longitudinal axis between a distal end (3b) and a proximal end (3a), a rotator (7, 207) arranged in the housing, the rotator is rotatable about the longitudinal axis (102) with respect to the housing, the rotator comprising at least one radially inwards facing structure (36, 236); a plunger rod (9, 209) arranged radially inside the rotator, the plunger rod comprising at least one radially outwards facing structure (11, 211) relative to the longitudinal axis; the rotator is rotatable with respect to the plunger rod between at least a first rotational position and a second rotational position, wherein in the second rotational position, the plunger rod is axially movable with respect to the rotator so that the at least one radially outwards facing structure interact with the radially inwards facing structure of the rotator to generate an audible click sound.

2. The subassembly of claim 1, comprising: a needle shield (6) configured to surround a needle at a proximal end of the medicament delivery device, the needle shield is movable inside the housing in an axial direction of the housing between a retracted position in which the needle is exposed at the proximal end of the housing, and an extended position in which the needle is covered by the needle shield, the rotator is arranged inside the needle shield, wherein the needle shield comprising radially inwards extending protrusions (42) and the rotator comprises surfaces (30,32,230,232) that are inclined with respect to the longitudinal axis, when the needle shield moves between the extended position and the retracted position, the radially inwards extending protrusions of the needle shield slide against the inclined surface of the rotator to cause the rotation of the rotator with respect to the plunger rod.

3. The sub-assembly according to any one of claims 1 and 2, wherein the at least one radially inwards facing structure of the rotator is/are at least one radially inwards extending protrusion and the at least one radially outwards facing structure of the plunger rod is/are at least one radially outwards extending protrusion, the at least one protrusion of the plunger rod extend radially beyond the radially inwards extending protrusions of the rotator, wherein the at least one protrusion of the plunger rod interact with the radially inwards extending protrusions of the rotator to generate the audible click sound.

4. The sub-assembly according to claim 3, wherein the rotator comprises a plurality of the radially inwards extending protrusions (36) arranged aligned in parallel with the longitudinal axis.

5. The sub-assembly according to claim 4, where the plurality of radially inwards extending protrusions are distributed along longitudinal axis to provide a continuous click-sound during an injection event when the plunger rod moves axially in the proximal direction.

6. The sub-assembly according to any one of claims 4 and 5, wherein the radially inwards extending protrusions of the rotator are parallel ribs or a sawtooth structure.

7. The sub-assembly according to any one of claims 4 to 6, wherein the at least one radially outwards extending protrusion of the plunger rod includes at least one radially outwards extending protrusion arranged at a distal end

8. The sub-assembly according to any one of claims 4 to 7, wherein the at least one radially outwards extending protrusion of the plunger rod is radially flexible to move radially when engaging with the radially inwards extending protrusions of the rotator.

9. The sub-assembly according to any one of claims 4 to 7, wherein the radially inwards extending protrusions of the rotator or the radially outwards extending protrusions of the plunger rod comprises an inclined surface (38, 18, 52, 238) configured to engage with the other one of the radially inwards extending protrusions of the rotator or the radially outwards extending protrusions of the plunger rod.

10. The sub-assembly according to any one of claims 4 to 9, the rotator comprising two sets of radially inwards extending protrusions arranged on opposite sides of the rotator with respect to the longitudinal axis, the plunger rod comprising a corresponding one radially outwards extending protrusion for each of the sets of radially inwards extending protrusions of the rotator.

11. The sub-assembly according to claim 3, wherein the rotator comprising a first radially inwards extending protrusion (236a) and a second radially inwards extending protrusion (236b) separated in the longitudinal direction by a distance corresponding to the plunger rod travel distance in the proximal direction from start of injection to end of injection.

12. The sub-assembly according to claim 11, wherein the first radially inwards extending protrusion and the second radially inwards extending protrusion of the rotator are arranged on flexible arms (240) that are radially flexible.

13. The sub-assembly according to any one of claims 11 and 12, wherein the radially inwards extending protrusions of the rotator or the radially outwards extending protrusions of the plunger rod comprises an inclined surface configured to engage with the other one of the radially inwards extending protrusions of the rotator and the radially outwards extending protrusions of the plunger rod.

14- The sub-assembly according to any one of claims n to 13, wherein no further protrusions are arranged between the first radially inwards extending protrusion and the second radially inwards extending protrusion.

15. A medicament delivery device comprising the sub-assembly according to any one of the preceding claims.