Drug delivery device

The present specification relates to a drug delivery device including a housing adapted to receive a primary container with a piston, a plunger slidably disposed in the housing and adapted to drive the piston for delivering a medicament, a drive spring pre-loaded between the housing and the plunger so as to urge the plunger in a distal direction, an audible and/or tactile indicator, and a trigger mechanism arranged between the indicator and the plunger. The trigger mechanism is configured to support the indicator in an initial state of the device and during delivery of the medicament and to couple with the plunger to activate the audible and/or tactile indicator at or near an end of delivery.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is the national stage entry of International Patent Application No. PCT/EP2018/079915, filed on Nov. 1, 2018, and claims priority to Application No. EP 17306518.6, filed on Nov. 3, 2017, the disclosures of which are incorporated herein by reference.

TECHNICAL FIELD

The present disclosure relates to a drug delivery device comprising an audible and/or tactile indicator mechanism.

BACKGROUND

Administering an injection is a process which presents a number of risks and challenges for users and healthcare professionals, both mental and physical. Drug delivery devices typically fall into two categories—manual drug delivery devices or autoinjectors. In a conventional manual device, manual force is required to drive a medicament through a needle. This is typically done by some form of plunger that has to be continuously pressed during the injection. There are numerous disadvantages associated with this approach. For example, if the plunger is released prematurely, the injection will stop and may not deliver an intended dose. Further, the force required to push the plunger may be too high (e.g., if the user is elderly or a child). And, aligning the injection device, administering the injection and keeping the injection device still during the injection may require dexterity which some patients (e.g., elderly patients, children, arthritic patients, etc.) may not have.

Autoinjector devices aim to make self-injection easier for patients. A conventional autoinjector may provide the force for administering the injection by a spring, and trigger button or other mechanism may be used to activate the injection. Autoinjectors may be single-use or reusable devices.

It is desirable to administer the full dose in order to achieve full effectiveness of the medicament within the patient.

SUMMARY

The present disclosure relates to an improved drug delivery device.

According to the present disclosure, a drug delivery device comprises at least a housing adapted to receive a cartridge or primary container with a piston and a plunger slidably disposed in the housing and adapted to drive the piston for delivering a drug or a medicament. The device further comprises a drive spring pre-loaded between the housing and the plunger so as to urge the plunger towards a distal direction. Furthermore, an audible and/or tactile indicator, e.g. a resilient force member, is provided, e.g. disposed at a proximal end of the device, in particular at a proximal end of the housing. A trigger mechanism for activating the indicator is provided and arranged between the indicator and the plunger, wherein the trigger mechanism is configured to support the indicator in an initial state of the device and/or during delivery of the medicament and to couple with the plunger to activate the audible and/or tactile indicator at or near an end of delivery, in particular when the plunger is in a distal position.

In particular, the trigger mechanism engages with the plunger to activate the audible and/or tactile indicator at or near the end of delivery of the medicament. In an exemplary embodiment, upon activating of the indicator said indicator disengages from the support of the trigger mechanism.

According to another aspect, as the trigger mechanism is being engaging with the plunger the trigger mechanism is being disengaged from the indicator to activate the indicator. In particular, the indicator can deform or relax when its support is disengaged. For instance, the indicator can disengage from the support by the trigger mechanism.

According to the disclosure, the indicator is engaged, e.g. in contact, with the trigger mechanism in the initial state and during injection. In particular, the trigger mechanism supports the indicator in an initial state, e.g. unbiased state, or in a biased state. Alternatively, the trigger mechanism may hold or press the indicator in or into an initial state, e.g. unbiased state, or in or into a biased state. Furthermore, the trigger mechanism only supports the indicator before its activation.

In particular, the housing may comprise an inner surface forming a cavity configured to retain the cartridge or a drug container or primary container. The primary container comprises an inner surface forming a cavity configured to slidably receive the piston. Due to coupling of the plunger and the piston, the piston moves in the distal direction when the plunger moves in the distal direction for delivering the medicament.

Such a drug delivery device ensures that the trigger mechanism fires or activates the indicator regardless of the length of the plunger. Hence, the length of the plunger could be changed without affecting activation or firing of the indicator. Furthermore, the number of parts, which would have to be replaced to accommodate a change in dose delivered by the drug delivery device, is minimised.

In an exemplary embodiment, the trigger mechanism comprises at least one structure resiliently abutting the plunger. In particular, the at least one structure resiliently abuts the plunger before activating of the indicator. The at least one structure may protrude from an indicator holder towards the plunger. Alternatively, the at least one structure may protrude from the housing towards the plunger. The housing can also be configured to hold the indicator. In this embodiment, the holder may be formed as a part of an inner housing so a separate indicator holder is not required. In detail, the structure may protrude from the housing, for example from an inner part of the housing towards the plunger.

According to another aspect of the present disclosure, the structure may have an inclined surface. The inclined surface ensures guiding and coupling with the plunger. In particular, the structure may comprise a proximal inclined end and a distal stepped edge. The distal stepped edge secures coupling with the plunger.

In an exemplary embodiment, the structure comprises at least one fin.

Furthermore, the plunger may comprise at least one cut-out adapted to receive the at least one structure at or near the end of delivery, in particular when the plunger is in a distal position.

In an exemplary embodiment, the cut-out comprises a lateral inclined edge. The lateral inclined edge supports and ensures catching of the fin. Furthermore, the cut-out may comprise a distal stepped edge. This edge secures the coupling with the fin, in particular with the distal stepped edge of the fin.

In a further exemplary embodiment, the indicator comprises two adjacent fins and the plunger comprises two corresponding adjacent cut-outs adapted to receive the fins.

According to another aspect of the disclosure, a needle sleeve is telescopically coupled to the housing and has an inner surface with at least one radially inwardly protruding guide rail extending in parallel to a longitudinal axis.

Furthermore, the plunger may comprise at least one radially outwardly protruding guide pin. In an exemplary embodiment, the guide pin and the guide rail are configured to engage each other, e.g. coaxially to the longitudinal axis.

According to a further aspect of the disclosure, the guide pin may comprise a guide pin surface engaging a corresponding guide rail surface of the guide rail. In particular, the guide pin surface and the guide rail surface may be oppositely inclined to each other. For example, the guide pin surface and the guide rail surface may be engaged to each other in an angle between 30° and 60°, in particular between 40° and 50°.

In an exemplary embodiment, the guide pin is formed as a protruding boss. The guide pin may comprise an inclined distal end. The inclined distal end ensures correct positioning and alignment, in particular for controlling rotation of the plunger to ensure that the fin will fall into the cut-out.

Furthermore, the guide rail may be formed as a protruding elongated rib extending in parallel to the longitudinal axis. The elongated rib ensures a guiding of the pin during delivery of the medicament.

Moreover, the drug delivery device may be an auto-injector, a pen-injector or a syringe. The primary container may be prefilled with a drug.

The drug delivery device, as described herein, may be configured to inject a drug or medicament into a patient. For example, delivery could be sub-cutaneous, intra-muscular, or intravenous. Such a device could be operated by a patient or care-giver, such as a nurse or physician, and can include various types of safety syringe, pen-injector, or auto-injector.

The device can include a cartridge-based system that requires piercing a sealed ampule before use. Volumes of medicament delivered with these various devices can range from about 0.5 ml to about 2 ml. Yet another device can include a large volume device (“LVD”) or patch pump, configured to adhere to a patient's skin for a period of time (e.g., about 5, 15, 30, 60, or 120 minutes) to deliver a “large” volume of medicament (typically about 2 ml to about 5 ml).

In combination with a specific medicament, the presently described devices may also be customized in order to operate within required specifications. For example, the device may be customized to inject a medicament within a certain time period (e.g., about 3 to about 20 seconds for auto-injectors, and about 10 minutes to about 60 minutes for an LVD). Other specifications can include a low or minimal level of discomfort, or to certain conditions related to human factors, shelf-life, expiry, biocompatibility, environmental considerations, etc. Such variations can arise due to various factors, such as, for example, a drug ranging in viscosity from about 3 cP to about 50 cP. Consequently, a drug delivery device will often include a hollow needle ranging from about 25 to about 31 Gauge in size. Common sizes are 27 and 29 Gauge.

The delivery devices described herein can also include one or more automated functions. For example, one or more of needle insertion, medicament injection, and needle retraction can be automated. Energy for one or more automation steps can be provided by one or more energy sources. Energy sources can include, for example, mechanical, pneumatic, chemical, or electrical energy. For example, mechanical energy sources can include springs, levers, elastomers, or other mechanical mechanisms to store or release energy. One or more energy sources can be combined into a single device. Devices can further include gears, valves, or other mechanisms to convert energy into movement of one or more components of a device.

The one or more automated functions of an auto-injector may be activated via an activation mechanism. Such an activation mechanism can include one or more of a button, a lever, a needle sleeve, or other activation component. Activation may be a one-step or multi-step process. That is, a user may need to activate one or more activation mechanism in order to cause the automated function. For example, a user may depress a needle sleeve against their body in order to cause injection of a medicament. In other devices, a user may be required to depress a button and retract a needle shield in order to cause injection.

In addition, such activation may activate one or more mechanisms. For example, an activation sequence may activate at least two of needle insertion, medicament injection, and needle retraction. Some devices may also require a specific sequence of steps to cause the one or more automated functions to occur. Other devices may operate with sequence independent steps.

Some delivery devices can include one or more functions of a safety syringe, pen-injector, or auto-injector. For example, a delivery device could include a mechanical energy source configured to automatically inject a medicament (as typically found in an auto-injector) and a dose setting mechanism (as typically found in a pen-injector).

DETAILED DESCRIPTION

According to some embodiments of the present disclosure, an exemplary drug delivery device10is shown inFIGS.1A and1B.

Device10, as described above, is configured to inject a drug or medicament into a patient's body.

Device10includes a housing11which typically contains a reservoir or cartridge containing the medicament to be injected (e.g., a syringe24or a container) and the components required to facilitate one or more steps of the delivery process.

Device10can also include a cap assembly12that can be detachably mounted to the housing11, in particular on a distal or front end D of the device10. Typically, a user must remove cap assembly or cap12from housing11before device10can be operated.

As shown, housing11is substantially cylindrical and has a substantially constant diameter along the longitudinal axis X. The housing11has a distal region20and a proximal region21. The term “distal” refers to a location that is relatively closer to a site of injection, and the term “proximal” refers to a location that is relatively further away from the injection site.

Device10can also include a needle sleeve13coupled to the housing11to permit movement of the sleeve13relative to the housing11. For example, the sleeve13can move in a longitudinal direction parallel to longitudinal axis X. Specifically, movement of the sleeve13in a proximal direction can permit a needle17to extend from distal region20of housing11.

Insertion of the needle17can occur via several mechanisms. For example, the needle17may be fixedly located relative to housing11and initially be located within an extended needle sleeve13.

Proximal movement of the sleeve13by placing a distal end of sleeve13against a patient's body and moving housing11in a distal direction or sleeve13in a proximal direction will uncover the distal end of needle17. Such relative movement allows the distal end of needle17to extend into the patient's body. Such insertion is termed “manual” insertion as the needle17is manually inserted via the patient's manual movement of the sleeve13relative to the housing11and the needle17or reverse.

Another form of insertion is “automated,” whereby the needle17moves relative to housing11. Such insertion can be triggered by movement of sleeve13or by another form of activation, such as, for example, a button22. As shown inFIGS.1A &1B, button22is located at a proximal or back end P of the housing11. However, in other embodiments, button22could be located on a side of housing11. In further embodiments, the button22has been deleted and is replaced for instance by a sleeve trigger mechanism, e.g. provided by pushing the needle sleeve13inside the housing when the drug delivery device is put onto an injection side.

Other manual or automated features can include drug injection, automatic needle insertion or needle retraction, or both. Injection is the process by which a bung or piston23is moved from a proximal location within a cartridge, container or syringe24to a more distal location within the syringe24in order to force a medicament from the syringe24through needle17.

In some embodiments, an energy source, e.g. a drive spring30is arranged in a plunger40and is under compression before device10is activated. A proximal end of the drive spring30can be fixed within proximal region21of housing11, and a distal end of the drive spring30can be configured to apply a compressive force to a proximal surface of piston23. Following activation, at least part of the energy stored in the drive spring30can be applied to the proximal surface of piston23. This compressive force can act on piston23to move it in a distal direction. Such distal movement acts to compress the liquid medicament within the syringe24, forcing it out of needle17.

Following injection, the needle17can be retracted within sleeve13or housing11. Retraction can occur when sleeve13moves distally as a user removes device10from a patient's body. This can occur as needle17remains fixedly located relative to housing11. Once a distal end of the sleeve13has moved past a distal end of the needle17, and the needle17is covered, the sleeve13can be locked. Such locking can include locking any proximal movement of the sleeve13relative to the housing11.

Another form of needle retraction can occur if the needle17is moved relative to the housing11. Such movement can occur if the syringe24within the housing11is moved in a proximal direction relative to the housing11. This proximal movement can be achieved by using a retraction spring (not shown), located in the distal region20. A compressed retraction spring, when activated, can supply sufficient force to the syringe24to move it in a proximal direction. Following sufficient retraction, any relative movement between the needle17and the housing11can be locked with a locking mechanism. In addition, button22or other components of device10can be locked as required.

In some embodiments, the housing may comprise a window11athrough which the syringe24can be monitored.

In the present specification, the term “distal section/end” refers to the section/end of the device10, or the sections/ends of the components thereof, which during use of the device10is located closest to a medicament delivery site of a patient. Correspondingly, the term “proximal section/end” refers to the section/end of the device10, or the sections/ends of the components thereof, which during use of the device10is pointing away from the medicament delivery site of the patient.

In the shown exemplary embodiments, the drug delivery device10comprises the housing11with a front case11.1and a rear case11.2. The front case11.1is adapted to hold the medicament container or primary container24, such as a syringe. The medicament primary container is referred to hereinafter as the “syringe24”. The syringe24may be a pre-filled syringe, in particular a 1.0 ml pre-filled syringe, containing a medicament and having the needle17arranged at a distal end of the syringe24. In another exemplary embodiment, the medicament container may be a primary container which includes the medicament and engages a removable needle (e.g., by threads, snaps, friction, etc.).

The drug delivery device10may be configured as an autoinjector or as a manual drug delivery device.

Moreover, the drug delivery device10comprises an audible and/or tactile indicator50providing an audible and/or tactile indication to a user of the device10at the end of delivery of the medicament. In particular, the indicator50produces an audible and/or tactile feedback for a user or patient indicating completion of medicament delivery. In other words: The indicator50is provided to indicate to a user or a patient that the full dose of medicament was spent.

In an exemplary embodiment, the indicator50is disposed at the proximal end P of the device10. For example, the indicator50is arranged at a proximal end of the housing11and inside the housing11.

Further, a trigger mechanism60is arranged between the indicator50and the plunger40. The trigger mechanism60is configured to support the indicator50in an initial state of the device10, for example during storage and transportation as well as during delivery of the medicament and to couple with the plunger40to activate the indicator50at an end of delivery.

In particular, the trigger mechanism60engages with the plunger40to activate the audible and/or tactile indicator50at or near the end of delivery of the medicament.

In an exemplary embodiment, upon activating of the indicator50, said indicator50can disengage from the support of the trigger mechanism60. In particular, as the trigger mechanism60is being engaging with the plunger40near or at the end of delivery of the medicament, the trigger mechanism60is being disengaged from the indicator50to activate it. For example, the indicator50can deform or relax when its support is disengaged. For instance, the indicator50can disengage from the support by the trigger mechanism60.

For example, the indicator50is engaged, e.g. in contact, with the trigger mechanism in the initial state and during injection. In particular, the trigger mechanism60supports the indicator50in an initial state, e.g. unbiased state, or in a biased state. Alternatively, the trigger mechanism60may hold or press the indicator50in or into an initial state, e.g. unbiased state, or in or into a biased state. Furthermore, the trigger mechanism60only supports the indicator50before its activation and releases it upon activating.

In an exemplary embodiment, the indicator50is formed as a biasing member, a spring, a laminated spring, a flat spring, a plate spring or a leaf spring.

In an exemplary embodiment, the trigger mechanism60comprises at least one structure, e.g. a protrusion, a flap, projection, resiliently abutting the plunger40. In particular, the at least one structure resiliently abuts the plunger40before activating of the indicator50.

In particular, a part of the trigger mechanism60, e.g. one surface side, for instance an outer side of the trigger mechanism60, abuts and supports the indicator50and an opposite surface side, e.g. an inner side of the trigger mechanism60, abuts the plunger40before activating of the indicator50, e.g. before and during delivery of the medicament. Upon activating of the indicator50, the trigger mechanism60disengages from indicator50and a part of the trigger mechanism60couples or engages with the plunger40.

FIGS.2A to4Crespectively show embodiments of the indicator50which will be described further below.

FIG.2Ashows a longitudinal section of an exemplary embodiment of the rear case11.2. In an assembled state, the rear case11.2serves for example as a drive subassembly11.4of the drug delivery device10.

The drive sub assembly11.4is a sub assembly of the drug delivery device10and comprises the components required to deliver the medicament. The drive subassembly11.4comprises for example the rear case11.2, the plunger40, the drive spring30and the indicator50. The drug delivery device10further comprises a front sub assembly (not shown separately) to allow for flexibility as to the time and location of manufacture of the subassemblies and final assembly with the syringe24.

According to the present embodiment, the rear case11.2comprises two support arms11.3adapted to support an axial position of the syringe24during storage, transportation and medicament delivery. The support arms11.3project distally from a proximal case end11.4of the rear case11.2. The rear case11.2further comprises additional flexible projections11.5that project distally from the distal end of the rear case11.2as well. In detail, the flexible projections11.5project distally from the distal end of the support arms11.3.

The projections11.5are adapted to damp impact forces and thus to stabilize the syringe24during storage, transportation and delivery.

In an exemplary embodiment, the indicator50is arranged on the housing11, in particular on the rear case11.2. In detail, the indicator50is arranged on an outer side of at least one of the support arms11.3. In this embodiment, in which the indicator50is arranged on the rear case11.2, the trigger mechanism60is also arranged on the rear case11.2. In detail, the trigger mechanism60is arranged on an inner side of the support arm11.3and thus on a side opposite the side of the support arms11.3where the indicator50is arranged. The trigger mechanism60is adapted to damp impact forces and thus to stabilize the indicator50in its biased state during storage, transportation, and medicament delivery.

In an alternative embodiment, the indicator50may arranged on a holder (not shown) which is arranged in the housing11. The trigger mechanism60may then also be arranged on the holder in a similar manner as on the rear case11.2.

In an assembled state, the indicator50is arranged within the device10at the proximal end P of housing11. A proximal end of the plunger40is at least partially received within the rear case11.2. The rear case11.2is closed at its outer proximal end11.4.

In detail, the indicator50is held in the rear case11.2such that the longitudinal axis X is in parallel with a longitudinal extension of the drug delivery device10. The indicator50may be coupled to the drug delivery device10by a snap connection, wherein one or more of the tabs50.1are engaged within a number of corresponding openings11.6in the rear case11.2. In another exemplary embodiment, the indicator50is held in the rear case11.2by a frictional connection, such as a screw or rivet connection or interference fit.

FIGS.2A and2Cshow the indicator50in a pre-assembly state and initial or relaxed state S1.FIG.2Bshows the indicator50in an assembly state in the rear case11.2and in a primed or biased state S2andFIG.2Dshows the indicator in the biased state S2, too.

The indicator50comprises a resilient force member50.2, e.g. having a substantially rectangular shape, comprising a longitudinal axis running in parallel to the longest side of the outer circumference of the resilient force member50.2. In other embodiments, the resilient force member50.2may have a triangular shape or any other geometrical shape suitable to couple the indicator50to the device10, e.g. an autoinjector.

The resilient force member50.2may be designed as a monostable leaf spring comprising a resilient material, e.g. spring steel or spring plastic. Thus, the resilient force member50.2is capable of residing in two states. That is, the resilient force member50.2may assume two different conformations, one of them stable with limited or no application of an external force and the other one unstable. For example, these two states can include a first or relaxed state S1(or pre-assembly state, or trigged state, or initial state), in which the resilient force member50.2has a first conformation. In a second or biased state S2(or primed state), the resilient force member50.2can have a second conformation. InFIG.2A, the resilient force member50.2is in the relaxed state S1which can correspond to the pre-assembly state as well as to a state at the end of medicament delivery.

In a possible embodiment, the resilient force member50.2comprises a longitudinal bend50.3. The longitudinal bend50.3can be arranged generally in the centre of the resilient force member50.2running in parallel to the longitudinal axis X. The longitudinal bend50.3can divide the indicator50into two wing-shaped sections angled to each other with an angle less than 180 degrees. In in the illustrated perspective ofFIGS.2A and2C, the wing-shaped sections are angled downwards.

Furthermore, the resilient force member50.2can comprise one or more tabs50.1projecting perpendicularly to the longitudinal axis X from the outer circumference. Specifically, the resilient force member50.2can include one, two, three, four or more tabs50.1.

As shown inFIGS.2A to2D, the resilient force member50.2includes two tabs50.1, wherein one of the tabs50.1is arranged opposite the other tab50.1. In another embodiment (not shown), the resilient force member50.2can include pairs of tabs50.1located generally opposite each other. The pairs of tabs50.1are arranged spaced to each other in the direction of the longitudinal axis X. In another exemplary embodiment, the number and arrangement of the tabs50.1may differ from the shown exemplary embodiment. In an exemplary embodiment, the tabs50.1may be angled with respect to the wing-shaped sections to facilitate assembly of the drug delivery device10.

For assembling the indicator50into the drug delivery device10, the resilient force member50.2is bent in the centre about an axis A running perpendicular to the longitudinal axis X. The bending angle may be less than 90 degrees. This bending is achieved by applying a predetermined force onto or near the centre point of the resilient force member50.2when engaging the tabs50.1within the openings11.6in the rear case11.2. As a result, the resilient force member50.2changes from the relaxed state S1into the biased state S2. Two ends50.4.1,50.4.2of the resilient force member50.2at opposite ends along the longitudinal axis X are angled upwards from the centre point50.5in the illustrated perspective ofFIG.2C, which shows the biased state S2. Hence, the biased state S2corresponds with the primed state, wherein the resilient force member50.2stores a certain amount of energy.

After removing the applied force, the resilient force member50.2is held in the biased state S2as it is shown inFIG.2Cand described below.

The resilient force member50.2is in the biased state S2and held in the rear case11.2by the snap connection as described above. The distally pointing end50.4.1of the resilient force member50.2and the biased state S2of the indicator50is supported and activated by the trigger mechanism60arranged on the support arm11.3as described further below.

The proximally pointing end50.4.2of the resilient force member50.2is free and not in contact with any other component and located above the trigger mechanism60or another section of the rear case11.2.

After changing from the relaxed state S1into the biased state S2as described before, only a small force may be required to hold the resilient force member50.2in the biased state S2. This is achieved by the longitudinal bend50.3that provides a bent cross section of the resilient force member50.2which buckles into a new configuration by changing from the relaxed state S1into the biased state S2. In this configuration, a stiffness of the material structure is significantly reduced and thus only a small holding force is required to maintain the resilient force member50.2in the biased state S2.

In detail, the trigger mechanism60comprises at least one structure60.1resiliently abutting the plunger40. The structure60.1may protrude from an indicator holder towards the plunger40. The structure60.1may be formed as a fin. The protruding structure60.1is referred to hereinafter as “fin60.1”. Due to the support of the fin60.1on the plunger40during storage, transportation and delivery, the indicator50is supported in its biased state S2, too.

In detail, the at least one fin60.1protrudes from the housing11, in particular from the rear case11.2, e.g. from its inner support arm11.3towards the plunger40. The support arm11.3is formed as an indicator holder. The indicator50and the fin60.1are arranged on opposite surface side of the support arm11.3. The indicator50is held on a surface side of arm11.3facing to the outer housing11. The fin60.1is formed on the opposite side of the arm11.3facing inwards and towards to the plunger40.

Alternatively, the fin60.1may protrude from a separate indicator holder (not shown) towards the plunger40. The separate indicator holder may be arranged between the indicator50and the plunger40within the housing11.

In an exemplary embodiment, the fin60.1has an inclined surface60.2. In particular, an upper or top surface of the fin60.1is rounded or inclined. The inclined surface60.2ensures guiding along the plunger40during delivery of the medicament.

Further, the fin60.1may comprise a proximal inclined end60.3and a distal stepped edge60.4. The proximal inclined end60.3allows an easy coupling of the fin60.1with the plunger40. The distal stepped edge60.4is configured to secure the coupling of the fin60.1with the plunger40.

According to another aspect of the disclosure, the plunger40comprises at least one cut-out40.1adapted to receive the at least one fin60.1at the end of delivery, for example when the plunger40is in the distal position. Due to the fin60.1falling into the cut-out40.1at the end of delivery, the indicator50relaxes and generates an acoustic noise. Additionally, the indicator50may be configured to generate a tactile feedback on the outer housing11, too. The indicator50thus provides an end-of-delivery feedback to a user.

Furthermore, the cut-out40.1may comprise a lateral inclined edge40.1.1. Such a lateral inclined edge40.1.1facilitates the fin60.1falling into the cut-out40.1. The cut-out40.1may further comprise a distal stepped edge40.1.2. The distal stepped edge40.1.2corresponds with the distal stepped edge60.4of the fin60.1to facilitate the coupling of the fin60.1and the cut-out40.1.

In the exemplary embodiment, the trigger mechanism60comprises two adjacent fins60.1and the plunger40comprises two correspondingly adjacent cut-outs40.1adapted to receive the fins60.1. The two fins60.1are arranged spaced to each other in the direction of the transversal direction. The pair of fins60.1protrudes from the inner surface of the rear case11.2facing the plunger40when received inside the housing11. The radially inwardly protruding and adjacent fins60.1abut the plunger40, thereby supporting the resilient force member50.2in its biased state S2. In another exemplary embodiment, the number and arrangement of the fins60.1may differ from the shown exemplary embodiment.

In another exemplary embodiment, the number and arrangement of the indicators50and trigger mechanism60may differ from the shown exemplary embodiment. The device10may comprise two trigger mechanism60and two indicators50described above. Each of a pair of trigger mechanism60and indicators50may be arranged on one of the support arms11.3of the rear case11.2.

For delivering a medicament, as can be seen in more detail in an exploded view inFIG.2B, the plunger40is driven by a drive spring30that is arranged between the plunger40and the rear case11.2. The drive spring30may be arranged within the plunger40and be pre-loaded such as to urge the plunger40towards the distal end D of the device10.

As can be seen in detail inFIGS.3A and3B, two circumferentially adjacent cut-outs40.1corresponding to the adjacent fins60.1of the trigger mechanism60are arranged near the proximal end P of the plunger40. The plunger40is aligned in an angular position relative to the rear case11.2such that each of the fins60.1is axially aligned with its corresponding cut-out40.1. During the injection, the plunger40is translated in a distal direction towards a distal position until reaching a position at the end of the injection, where the fins60.1will snap into the cut-outs40.1. Thereby, the resilient force member50.2will relax from its biased state S2into its relaxed state S1. An audible and/or tactile click emitted upon this relaxation indicates the end of the injection process to the user.

As shown inFIG.3B, the fins60.1are formed in the shape of shark fins with a proximally arranged inclined end60.3and with a distally arranged stepped edge60.4. Thereby, the resilient force member50.2relaxes immediately with a sharp click noise, when the plunger40reaches its distal end position.

FIG.4Ashows a further aspect of the disclosure concerning the sleeve13comprising a guide rail13.2.FIG.4Bshows a guide pin40.2corresponding to the guide rail13.2and protruding from a proximal end of the plunger40.FIG.4Cis a schematic view of a guiding mechanism for guiding the plunger40along the needle sleeve13due to the interrelation of guide pin40.2and guide rail13.2.

In detail, the needle sleeve13is telescopically coupled to the housing11and has an inner surface13.1with at least one radially inwardly protruding guide rail13.2extending in parallel to the longitudinal axis X. The guide rail13.2is formed for example as a protruding rib elongated parallel to the longitudinal axis X.

Furthermore, the plunger40may comprise at least one radially outwardly protruding guide pin40.2. In an exemplary embodiment, the guide pin40.2and the guide rail13.2are configured to engage each other, e.g. coaxially to the longitudinal axis X. In particular, the guide pin40.2engages the at least one guide rail13.2as best seen inFIG.4C.

In more detail, the guide pin40.2may comprise a guide pin surface40.2.1engaging a corresponding guide rail surface13.2.1of the guide rail13.2.

Furthermore, the guide pin surface40.2.1and the guide rail surface13.2.1may be oppositely inclined to each other. For example, the guide pin surface40.2.1and the guide rail surface13.2.1are engaged to each other in an angle between 30° and 60°, in particular between 40° and 50°.

In an exemplary embodiment, the guide pin40.2is formed as a protruding boss as shown inFIG.4D. The guide pin40.2may comprise an inclined distal end40.2.2. The inclined distal end40.2.2ensures correct positioning and alignment, in particular controlling rotation of the plunger40to ensure that the fin60.1will fall into the cut-out40.1.

Moreover, the drug delivery device10may be an auto-injector, a pen-injector or a syringe. The primary container or syringe24may be prefilled with a drug.

The terms “drug” or “medicament” are used herein to describe one or more pharmaceutically active compounds. As described below, a drug or medicament can include at least one small or large molecule, or combinations thereof, in various types of formulations, for the treatment of one or more diseases. Exemplary pharmaceutically active compounds may include small molecules; polypeptides, peptides and proteins (e.g., hormones, growth factors, antibodies, antibody fragments, and enzymes); carbohydrates and polysaccharides; and nucleic acids, double or single stranded DNA (including naked and cDNA), RNA, antisense nucleic acids such as antisense DNA and RNA, small interfering RNA (siRNA), ribozymes, genes, and oligonucleotides. Nucleic acids may be incorporated into molecular delivery systems such as vectors, plasmids, or liposomes. Mixtures of one or more of these drugs are also contemplated.

The term “drug delivery device” shall encompass any type of device or system configured to dispense a drug into a human or animal body. Without limitation, a drug delivery device may be an injection device (e.g., syringe, pen injector, auto injector, large-volume device, pump, perfusion system, or other device configured for intraocular, subcutaneous, intramuscular, or intravascular delivery), skin patch (e.g., osmotic, chemical, micro-needle), inhaler (e.g., nasal or pulmonary), implantable (e.g., coated stent, capsule), or feeding systems for the gastro-intestinal tract. The presently described drugs may be particularly useful with injection devices that include a needle, e.g., a small gauge needle.

The drug or medicament may be contained in a primary package or “drug container” adapted for use with a drug delivery device. The drug container may be, e.g., a cartridge, syringe, reservoir, or other vessel configured to provide a suitable chamber for storage (e.g., short- or long-term storage) of one or more pharmaceutically active compounds. For example, in some instances, the chamber may be designed to store a drug for at least one day (e.g., 1 to at least 30 days). In some instances, the chamber may be designed to store a drug for about 1 month to about 2 years. Storage may occur at room temperature (e.g., about 20° C.), or refrigerated temperatures (e.g., from about −4° C. to about 4° C.). In some instances, the drug container may be or may include a dual-chamber cartridge configured to store two or more components of a drug formulation (e.g., a drug and a diluent, or two different types of drugs) separately, one in each chamber. In such instances, the two chambers of the dual-chamber cartridge may be configured to allow mixing between the two or more components of the drug or medicament prior to and/or during dispensing into the human or animal body. For example, the two chambers may be configured such that they are in fluid communication with each other (e.g., by way of a conduit between the two chambers) and allow mixing of the two components when desired by a user prior to dispensing. Alternatively or in addition, the two chambers may be configured to allow mixing as the components are being dispensed into the human or animal body.

The drug delivery devices and drugs described herein can be used for the treatment and/or prophylaxis of many different types of disorders. Exemplary disorders include, e.g., diabetes mellitus or complications associated with diabetes mellitus such as diabetic retinopathy, thromboembolism disorders such as deep vein or pulmonary thromboembolism. Further exemplary disorders are acute coronary syndrome (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and/or rheumatoid arthritis.

Exemplary drugs for the treatment and/or prophylaxis of diabetes mellitus or complications associated with diabetes mellitus include an insulin, e.g., human insulin, or a human insulin analogue or derivative, a glucagon-like peptide (GLP-1), GLP-1 analogues or GLP-1 receptor agonists, or an analogue or derivative thereof, a dipeptidyl peptidase-4 (DPP4) inhibitor, or a pharmaceutically acceptable salt or solvate thereof, or any mixture thereof. As used herein, the term “derivative” refers to any substance which is sufficiently structurally similar to the original substance so as to have substantially similar functionality or activity (e.g., therapeutic effectiveness).

An exemplary oligonucleotide is, for example: mipomersen/Kynamro, a cholesterol-reducing antisense therapeutic for the treatment of familial hypercholesterolemia.

The term “antibody”, as used herein, refers to an immunoglobulin molecule or an antigen-binding portion thereof. Examples of antigen-binding portions of immunoglobulin molecules include F(ab) and F(ab′)2fragments, which retain the ability to bind antigen. The antibody can be polyclonal, monoclonal, recombinant, chimeric, de-immunized or humanized, fully human, non-human, (e.g., murine), or single chain antibody. In some embodiments, the antibody has effector function and can fix complement. In some embodiments, the antibody has reduced or no ability to bind an Fc receptor. For example, the antibody can be an isotype or subtype, an antibody fragment or mutant, which does not support binding to an Fc receptor, e.g., it has a mutagenized or deleted Fc receptor binding region.

The compounds described herein may be used in pharmaceutical formulations comprising (a) the compound(s) or pharmaceutically acceptable salts thereof, and (b) a pharmaceutically acceptable carrier. The compounds may also be used in pharmaceutical formulations that include one or more other active pharmaceutical ingredients or in pharmaceutical formulations in which the present compound or a pharmaceutically acceptable salt thereof is the only active ingredient. Accordingly, the pharmaceutical formulations of the present disclosure encompass any formulation made by admixing a compound described herein and a pharmaceutically acceptable carrier.

Pharmaceutically acceptable salts of any drug described herein are also contemplated for use in drug delivery devices. Pharmaceutically acceptable salts are for example acid addition salts and basic salts. Acid addition salts are e.g. HCI or HBr salts. Basic salts are e.g. salts having a cation selected from an alkali or alkaline earth metal, e.g. Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), wherein R1 to R4 independently of each other mean: hydrogen, an optionally substituted C1-C6-alkyl group, an optionally substituted C2-C6-alkenyl group, an optionally substituted C6-C10-aryl group, or an optionally substituted C6-C10-heteroaryl group. Further examples of pharmaceutically acceptable salts are known to those of skill in the arts.

Pharmaceutically acceptable solvates are for example hydrates or alkanolates such as methanolates or ethanolates.

LIST OF REFERENCES