Patent Description:
Administering an injection or drug is a process which presents a number of risks and challenges for users and healthcare professionals, both mental and physical. Injection devices typically fall into two categories - manual devices and 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 button / plunger that has to be continuously pressed during the injection. There are numerous disadvantages associated with this approach. For example, if the button / plunger is released prematurely, the injection will stop and may not deliver an intended dose. Furthermore, the force required to push the button / 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 a trigger button or other mechanism may be used to activate the injection. Autoinjectors may be single-use or reusable devices.

Furthermore, it is necessary to administer the full dose in order to achieve full effectiveness of the medicament within the patient.

Thus, there remains a need for a drug delivery device having an audible and/or tactile indicator.

Current indicators may be too quiet or too bulky to use in current autoinjectors and other drug delivery devices. The audible and/or tactile indicators described herein solve one or more of these problems. <CIT> discloses a drug delivery device and an audible/tactile indicator according to the state of the art.

An object of the present disclosure is to provide an improved audible and/or tactile indicator for use with a drug delivery device and an improved drug delivery device comprising such an audible and/or tactile indicator.

The object is achieved by an audible and/or tactile indicator according to claim <NUM> and by a drug delivery device according to claim <NUM>.

Exemplary embodiments are provided in the dependent claims.

According to the present disclosure, an audible and/or tactile indicator for use with a drug delivery device comprises a resilient force member that is configured to reside in two or more states having two or more different conformations, wherein in a relaxed state, the resilient force member is relaxed in a first conformation, wherein in a biased state, the resilient force member is biased to store energy in a second conformation different to the first conformation, and wherein the resilient force member releases stored energy to generate an audible signal when changing from the biased state into the relaxed state due to a transition from the second conformation to the first conformation, wherein the resilient force member is bent by a certain angle about a longitudinal axis forming a longitudinal round fold with two adjacent angled wing-shaped sections.

The longitudinal round fold reduces stress impact and risk of permanent deformation of the resilient force member during priming of the drug delivery device.

In an exemplary embodiment, a notch is formed into the longitudinal round fold, e.g. extending transversely to the longitudinal round fold. The notch is provided to support consistency of priming during assembly of the audible and/or tactile indicator. In the context of the present disclosure, priming means to move the resilient force member into the biased state.

In an exemplary embodiment, on at least one of the wing-shaped sections a supporting tab is provided outwardly protruding from a long side of the wing-shaped section. The supporting tab is provided to reduce sensitivity to manufacturing variations and to increase drop resistance of the resilient force member. Thus, the drug delivery device is improved in order to achieve a reliable indication of the end of medicament delivery and a full effectiveness of the medicament within the patient.

In an exemplary embodiment, the longitudinal round fold has a bend radius between <NUM> and <NUM>. This allows for pre-priming during manufacture of the resilient force member. According to a further exemplary embodiment, the supporting tab has a free end which is outwardly bent. This increases a reliability of the audible and/or tactile indicator as well as stability under drop.

In accordance with an aspect of the present disclosure, the notch is centrically arranged in the longitudinal round fold with respect to the longitudinal axis. This supports an assembly of the resilient force member in the drug delivery device, which requires bending the resilient force member in the centre about an axis running perpendicular to the longitudinal round fold.

Moreover, the supporting tab may be arranged on a region of the wing-shaped member extending between the notch and one of two end faces of the resilient force member with respect to the longitudinal axis. This increases reliability of function of the audible and/or tactile indication. The drop resistance will be increased as well.

According to the invention, the resilient force member is configured as a leaf spring having a longitudinal axis. The leaf spring comprises a resilient material, e. spring steel or spring plastic. Leaf springs are well known and easy to manufacture. The leaf spring may have a rectangular shape, a square shape or an oval shape.

Moreover, the resilient force member, e. the leaf spring, may be bent about the longitudinal bend such that the two-wing-shaped sections are at an angle of between <NUM> degrees and <NUM> degrees relative to each other. For example, the angle can be between <NUM> degrees and <NUM> degrees or between <NUM> degrees and <NUM> degrees or between <NUM> degrees and <NUM> degrees or between <NUM> degrees and <NUM> degrees or between <NUM> degrees and <NUM> degrees. In an exemplary embodiment, the angle is approximately or exactly <NUM> degrees or <NUM> degrees or <NUM> degrees or <NUM> degrees or <NUM> degrees. The angle provides best balance between noise and reliability.

According to another aspect of the present disclosure, the resilient force member, e. the leaf spring, is configured as a bistable spring element. A bistable spring element has two stable states or conformations in which it can rest without support from an external component. In order to move the bistable spring element from one stable state or conformation to the other, energy has to be used to move the bistable spring element into an intermediate state. This energy is then released as the bistable spring moves out of the intermediate state into one of the stable states.

It is understood that a bistable leaf spring can store energy in the form of tension on one or more outer edges of one or more wing-shaped sections. It is also understood that the bistable leaf spring can also store energy in the form of compression in a central region of one or more wing-shaped sections.

In an alternative embodiment, the resilient force member is configured as a monostable spring element. As opposed to a bistable spring element, a monostable spring element may have only one stable state. If resiliently deformed from out of this stable state and subsequently released, the monostable spring element will return to this stable state. In order to keep a monostable spring element in an instable state, an additional component supporting the monostable spring element in the instable state is required.

It is understood that a monostable leaf spring can store energy in the form of tension on one or more outer edges of one or more wing-shaped sections. It is also understood that the monostable leaf spring can also store energy in the form of compression in a central region of one or more wing-shaped sections.

In an exemplary embodiment, the resilient force member is supported in the biased state in order to prevent transition into the relaxed state. This mechanically stabilizes the biased state of the resilient force member.

According to another aspect of the present disclosure, a drug delivery device comprises an audible and/or tactile indicator.

Moreover, the audible and/or tactile indicator may be activated by a movement of a plunger. In particular, the audible and/or tactile indicator is activated by the movement of the plunger towards a proximal position at the end of a medicament delivery process. The plunger is used to displace a drug from a medicament container. For example, the resilient force member transitions from the biased state into the relaxed state when the plunger moves towards or reaches a proximal position at the end of a medicament delivery process.

According to a further exemplary embodiment, the resilient force member transitions from the biased state into the relaxed state when a proximal plunger section abuts a distal end face of the resilient force member.

In an exemplary embodiment, the drug delivery device may comprise a medicament container containing a medicament.

Furthermore, the resilient force member may be supported when the drug delivery device is in an initial state and the resilient force member may be unsupported when the drug delivery device is in a primed state. Alternatively, the resilient force member may be supported when the drug delivery device is in an initial state and in a primed state, wherein a distal end face of the resilient force member is supported by a supporting protrusion arranged on a proximal section of a housing. Alternatively, the resilient force member may be unsupported in the biased state.

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 <NUM> to about <NUM>. 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 <NUM>, <NUM>, <NUM>, <NUM>, or <NUM> minutes) to deliver a "large" volume of medicament (typically about <NUM> to about <NUM>).

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 <NUM> cP to about <NUM> cP (<NUM>-<NUM> Pa s).

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.

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. Other devices may operate with sequence independent steps.

However, it should be understood that the detailed description and specific examples, while indicating exemplary embodiments of the disclosure, are given by way of illustration only, since various changes and modifications within the scope of the disclosure will become apparent to those skilled in the art from this detailed description.

The present disclosure will become more fully understood from the detailed description given below and the accompanying drawings, which are given by way of illustration only, and do not limit the present disclosure, and wherein:.

According to some embodiments of the present disclosure, an exemplary drug delivery device <NUM> is shown in <FIG>.

Device <NUM>, as described above, is configured to inject a drug or medicament into a patient's body.

Device <NUM> includes a housing <NUM> which typically contains a reservoir containing the medicament to be injected (e.g., a syringe <NUM> or a container) and the components required to facilitate one or more steps of the delivery process.

Device <NUM> can also include a cap assembly <NUM> that can be detachably mounted to the housing <NUM>, in particular on a distal or front end D of the device <NUM>. Typically, a user must remove cap assembly or cap <NUM> from housing <NUM> before device <NUM> can be operated.

As shown, housing <NUM> is substantially cylindrical and has a substantially constant diameter along the longitudinal axis X. The housing <NUM> has a distal region <NUM> and a proximal region <NUM>. 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.

Device <NUM> can also include a needle sleeve <NUM> coupled to the housing <NUM> to permit movement of the sleeve <NUM> relative to the housing <NUM>. For example, the sleeve <NUM> can move in a longitudinal direction parallel to longitudinal axis X. Specifically, movement of the sleeve <NUM> in a proximal direction can permit a needle <NUM> to extend from distal region <NUM> of housing <NUM>. Insertion of the needle <NUM> can occur via several mechanisms. For example, the needle <NUM> may be fixedly located relative to housing <NUM> and initially be located within an extended needle sleeve <NUM>. Proximal movement of the sleeve <NUM> by placing a distal end of sleeve <NUM> against a patient's body and moving housing <NUM> in a distal direction will uncover the distal end of needle <NUM>. Such relative movement allows the distal end of needle <NUM> to extend into the patient's body. Such insertion is termed "manual" insertion as the needle <NUM> is manually inserted via the patient's manual movement of the housing <NUM> relative to the sleeve <NUM>.

Another form of insertion is "automated," whereby the needle <NUM> moves relative to housing <NUM>. Such insertion can be triggered by movement of sleeve <NUM> or by another form of activation, such as, for example, a button <NUM>. As shown in <FIG>, button <NUM> is located at a proximal or back end P of the housing <NUM>. However, in other embodiments, button <NUM> could be located on a side of housing <NUM>. In further embodiments, the button <NUM> has been deleted and is replaced for instance by a sleeve trigger mechanism, e.g. provided by pushing the needle sleeve <NUM> inside the housing when the drug delivery device is put onto an injection side.

Other manual or automated features can include drug injection or needle retraction, or both. Injection is the process by which a bung or piston <NUM> is moved from a proximal location within a container or syringe <NUM> to a more distal location within the syringe <NUM> in order to force a medicament from the syringe <NUM> through needle <NUM>.

In some embodiments, an energy source, e.g. a drive spring <NUM> is arranged in a plunger <NUM> and is under compression before device <NUM> is activated. A proximal end of the drive spring <NUM> can be fixed within proximal region <NUM> of housing <NUM>, and a distal end of the drive spring <NUM> can be configured to apply a compressive force to a proximal surface of piston <NUM>. Following activation, at least part of the energy stored in the drive spring <NUM> can be applied to the proximal surface of piston <NUM>. This compressive force can act on piston <NUM> to move it in a distal direction. Such distal movement acts to compress the liquid medicament within the syringe <NUM>, forcing it out of needle <NUM>.

Following injection, the needle <NUM> can be retracted within sleeve <NUM> or housing <NUM>. Retraction can occur when sleeve <NUM> moves distally as a user removes device <NUM> from a patient's body. This can occur as needle <NUM> remains fixedly located relative to housing <NUM>. Once a distal end of the sleeve <NUM> has moved past a distal end of the needle <NUM>, and the needle <NUM> is covered, the sleeve <NUM> can be locked. Such locking can include locking any proximal movement of the sleeve <NUM> relative to the housing <NUM>.

Another form of needle retraction can occur if the needle <NUM> is moved relative to the housing <NUM>. Such movement can occur if the syringe <NUM> within the housing <NUM> is moved in a proximal direction relative to the housing <NUM>. This proximal movement can be achieved by using a retraction spring (not shown), located in the distal region <NUM>. A compressed retraction spring, when activated, can supply sufficient force to the syringe <NUM> to move it in a proximal direction. Following sufficient retraction, any relative movement between the needle <NUM> and the housing <NUM> can be locked with a locking mechanism. In addition, button <NUM> or other components of device <NUM> can be locked as required.

In some embodiments, the housing may comprise a window 11a through which the syringe <NUM> can be monitored.

<FIG> is a perspective partial section of an exemplary embodiment of a drug delivery device <NUM> comprising an audible and/or tactile indicator <NUM>. The drug delivery device <NUM> further comprises the components as described before.

The housing <NUM> has two parts, a rear case <NUM> and a front case <NUM> which are coupled to each other in the assembled state.

The plunger <NUM> may comprise a proximal plunger section <NUM> and a distal plunger section <NUM> (see <FIG>, <FIG> and <FIG>) that are configured with different diameters, wherein the diameter of the proximal plunger section <NUM> is larger than the diameter of the distal plunger section <NUM>.

The drug delivery device <NUM> further comprises the audible and/or tactile indicator <NUM> that is arranged in the proximal region <NUM> of the device <NUM> and that is adapted for producing an audible feedback for a user or patient indicating completion of drug delivery. In other words: The audible and/or tactile indicator <NUM> is provided to indicate to a user or a patient that the full dose of drug was spent.

<FIG> is an exploded view of the respective components, e.g. the rear case <NUM>, the plunger <NUM> with its proximal plunger section <NUM> and its distal plunger section <NUM>, the drive spring <NUM> and the indicator <NUM>. The rear case <NUM> has inner and outer surfaces forming cavities to contain the indicator <NUM> and the plunger <NUM> and, thus, forms a drive sub-assembly <NUM> of the device <NUM>. The plunger <NUM> has an inner cavity adapted to contain the drive spring <NUM>.

Due to the close arrangement of the indicator <NUM> to the outer housing <NUM>, in particular the front case <NUM>, a transition of the indicator <NUM> from a biased state S2 into a relaxed state S1 (shown in <FIG> and <FIG>) generates a tactile feedback in a region of the housing <NUM> which is typically held by a user, in particular at the proximal region <NUM> of the device <NUM>, in particular of the front case <NUM>.

<FIG> shows the device <NUM> in an assembled state. <FIG> shows the component of the drive sub assembly <NUM> in an pre-assembled state.

<FIG> are schematic views of audible and/or tactile indicators <NUM> in different exemplary embodiments.

Both, <FIG> show an audible and/or tactile indicator <NUM> that comprises a resilient force member <NUM> having a substantially rectangular shape and comprising a longitudinal axis L running in parallel to the longest side of the outer circumference of the resilient force member <NUM>. In other embodiments, the resilient force member <NUM> may have a triangular shape or any other geometrical shape suitable to couple the audible and/or tactile indicator <NUM> to the drug delivery device <NUM>.

The resilient force member <NUM> may be designed as a monostable leaf spring comprising a resilient material, e. spring steel or spring plastic. Thus, the resilient force member <NUM> is capable of residing in two states. That is, the resilient force member <NUM> may 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 triggered state), in which the resilient force member <NUM> has a first conformation. In a second or biased state S2 (or primed state, see <FIG>), the resilient force member <NUM> can have a second conformation. In the present <FIG>, the resilient force member <NUM> is in the relaxed state S1 which can correspond to the pre-assembly state as well as to a state at the end of drug delivery.

The resilient force member <NUM> is bent by a certain angle about the longitudinal axis L forming a longitudinal round fold <NUM> with two adjacent angled wing-shaped sections angled to each other with an angle less than <NUM> degrees. The longitudinal round fold <NUM> may have a bend radius between <NUM> and <NUM>, in particular <NUM> +/- <NUM>. In other embodiments, the bend radius may be outside these ranges. This bend radius reduces a stress impact during priming and the risk of permanent deformation.

The angle between the two adjacent angled wing-shaped sections can be between <NUM> degrees and <NUM> degrees or between <NUM> degrees and <NUM> degrees or between <NUM> degrees and <NUM> degrees or between <NUM> degrees and <NUM> degrees or between <NUM> degrees and <NUM> degrees. In an exemplary embodiment, the angle is approximately or exactly <NUM> degrees or <NUM> degrees or <NUM> degrees or <NUM> degrees or <NUM> degrees. In in the present figure, the wing-shaped sections are angled downwards. The longitudinal round fold <NUM> is located in the centre of the resilient force member <NUM> running in parallel to the longitudinal axis L.

Furthermore, the resilient force member <NUM> comprises one or more supporting tabs <NUM> projecting outwardly from a long side of at least one of the wing-shaped sections. In particular, the resilient force member <NUM> includes a pair of supporting tabs <NUM>, wherein each wing-shaped section comprises one supporting tab <NUM>. The supporting tabs <NUM> may be respectively arranged between a notch <NUM> and a proximal end face <NUM>. <NUM> of the resilient force member <NUM> with respect to the longitudinal axis L in order to increase a reliability of function of the audible and/or tactile indication as well as stability under drop. Furthermore, the supporting tabs <NUM> may be arranged opposite to each other with respect to a cross axis A running perpendicular to the longitudinal axis L.

In order to facilitate assembly of the audible and/or tactile indicator <NUM> into the drug delivery device <NUM>, the supporting tabs <NUM> respectively have a free end <NUM>. <NUM> which is outwardly bent. <FIG> illustrates a first embodiment, wherein the supporting tabs <NUM> have a rectangular shape. Respectively, the free end <NUM>. <NUM> of the supporting tabs <NUM> is entirely bent upwards in an angle about an axis running perpendicular to the longitudinal axis L and to the cross axis A.

<FIG> illustrates a second embodiment, wherein the supporting tabs <NUM> have a rectangular shape as well. Respectively, one edge of the free end <NUM>. <NUM> of the supporting tabs <NUM> is bent downwardly and thus perpendicular to the longitudinal axis L and to the cross axis A.

The resilient force member <NUM> further comprises the notch <NUM> that is formed into the longitudinal round fold <NUM> and that extends transversely with respect to the longitudinal round fold <NUM>. The notch <NUM> may be centrically arranged in the longitudinal round fold <NUM> with respect to the longitudinal axis L. The notch <NUM> supports priming of the resilient force member <NUM> as illustrated for example in <FIG>. The notch <NUM> may be configured as an opening or alternatively as a blind hole.

The <FIG> are different views of the drug delivery device <NUM> according to the second embodiment of <FIG>. In particular, <FIG> is a top view of the drug delivery device <NUM>. <FIG> is a side view of the drug delivery device <NUM> and <FIG> is a perspective view of the drug delivery device <NUM> having wing-shaped sections angled upwards. <FIG> is a cross section of the drug delivery device <NUM>.

For assembling the audible and/or tactile indicator <NUM> into the drug delivery device <NUM>, the resilient force member <NUM> is bent in the centre about the cross axis A with an angle less than <NUM> degrees. This bending is achieved by applying a predetermined force onto or near a centre point of the resilient force member <NUM> when engaging the tabs <NUM> within corresponding openings in a proximal region <NUM> of the housing <NUM>. Due to the bending, the audible and/or tactile indicator <NUM> transitions the second biased state S2. This transition from the relaxed state S1 into the biased state S2 will be understood as priming of the audible and/or tactile indicator <NUM>.

<FIG> is a perspective view of the audible and/or tactile indicator <NUM> according to the second embodiment in the biased state S2.

In the biased state S2, two end faces <NUM>. <NUM>, <NUM>. <NUM> of the resilient force member <NUM> are angled upwards from the centre point. The biased state S2 corresponds with the primed state, wherein the resilient force member <NUM> stores a certain amount of energy. Due to the notch <NUM>, priming of the audible and/or tactile indicator <NUM> is easier and more consistent. After removing the applied force, the resilient force member <NUM> is held in the biased state S2.

The audible and/or tactile indicator <NUM> is coupled to the housing <NUM> as illustrated in <FIG>. In detail, the resilient force member <NUM> is held in the proximal section <NUM> of the housing <NUM> such that the longitudinal axis L is in parallel with the longitudinal axis X of the drug delivery device <NUM>. The cross axis A may be in parallel with a cross axis Y of the drug delivery device <NUM>.

The audible and/or tactile indicator <NUM> is coupled to the drug delivery device <NUM> by a snap connection, wherein the supporting tabs <NUM> are engaged within a number of corresponding openings (not shown) in the proximal region <NUM> of the housing <NUM>. Alternatively, the resilient force member <NUM> may be held in the proximal section <NUM> of the housing <NUM> by a frictional connection, such as a screw or rivet connection or interference fit.

<FIG> and <FIG> are longitudinal sections of a drive subassembly <NUM> of the drug delivery device <NUM> and the audible and/or tactile indicator <NUM> in an assembled state. <FIG> illustrates the audible and/or tactile indicator <NUM> in the biased state S2. <FIG> illustrates the audible and/or tactile indicator <NUM> in the relaxed state S2.

The drive sub assembly <NUM> is a sub assembly of the drug delivery device <NUM> and comprises the components required to deliver the drug. The drive subassembly <NUM> comprises the proximal region <NUM> of the housing <NUM>, the plunger <NUM> and the audible and/or tactile indicator <NUM>. The drug delivery device <NUM> further 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 syringe <NUM>.

The illustrated proximal region <NUM> of the housing <NUM> comprises two support arms <NUM> adapted to support an axial position of the syringe <NUM> during storage, transportation and medicament delivery. The support arms <NUM> project distally from a distal end of the proximal region <NUM> of the housing <NUM>. The proximal region <NUM> of the housing <NUM> further comprises an additional flexible arm <NUM> that projects distally from the distal end of the proximal region <NUM> of the housing <NUM> as well. The flexible arm <NUM> is adapted to damp impact forces and thus to stabilize the resilient force member <NUM> in its biased state S2 during storage, transportation, and medicament delivery.

The resilient force member <NUM> is in the biased state S2 and held in the proximal region <NUM> of the housing <NUM> by the snap connection as described above. The distal end face <NUM>. <NUM> of the resilient force member <NUM> is supported by a projection <NUM>. <NUM> of the flexible arm <NUM> arranged on a distal end of the flexible arm <NUM>. The proximal end face <NUM>. <NUM> of the resilient force member <NUM> is free and not in contact with any other component and located above the flexible arm <NUM> or another section of the proximal region <NUM> of the housing <NUM>. In an exemplary embodiment, the proximal region <NUM> of the housing <NUM> may comprise a plurality of flexible arms <NUM> that are arranged around a circumference of the proximal end of the proximal region <NUM> of the housing <NUM>. Furthermore, the flexible arm <NUM> is deflected outwards supported by the outer circumference of the plunger <NUM>.

After transition of the audible and/or tactile indicator <NUM> from the relaxed state S1 into the biased state S2 as described before, only a small force is required to hold the resilient force member <NUM> in the biased state S2. This is achieved by the longitudinal round fold <NUM> that provides a bent cross section of the resilient force member <NUM> which buckles into a new configuration by changing from the relaxed state S1 into 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 member <NUM> in the biased state S2.

At the end of a drug delivery process, the resilient force member <NUM> is in the relaxed state S1 as illustrated in <FIG>.

For delivering the drug through the needle <NUM> into an injection site, e.g. a patient's skin, the plunger <NUM> is moved distally from a proximal position to a distal position due to an activation of the drive spring <NUM> (not illustrated). The activation of the drive spring <NUM> may be initiated by pressing a button or by depressing the needle sleeve <NUM> as it is pushed against the injection site.

In the present <FIG>, the plunger <NUM> has reached the distal position, wherein the flexible arm <NUM> is no longer engaged with the plunger <NUM>. When the proximal plunger section <NUM>, comprising the increased diameter with respect to the distal plunger section <NUM>, passes the distal end of the flexible arm <NUM>, the flexible arm <NUM> is allowed to relax and can thus move radially inwards driven by the distal end face <NUM>. As the distal end face <NUM>. <NUM> moves, the resilient force member <NUM> can transition from a generally biased state S2 into a generally relaxed state S1 releasing stored energy to generate an audible signal, such as a click noise, due to a transition from the second conformation to the first conformation. Due to the large amount of stored energy, the audible signal can be generated with a high intensity, e. up to <NUM> decibels. Signals of lesser intensity can also be generated. The proximal end face <NUM>. <NUM> can also swing radially inwards, thereby hitting the flexible arm <NUM> or the housing <NUM> or another component of the drug delivery device <NUM>. This impact may also contribute to the generation of the audible signal.

The user or patient recognizing the audible signal knows that the drug delivery process is finished and that the full dose was spent.

Exemplary insulin derivatives are, for example, B29-N-myristoyl-des(B30) human insulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin; B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl- ThrB29LysB30 human insulin; B29-N-(N-palmitoyl-gamma-glutamyl)-des(B30) human insulin; B29-N-(N-lithocholyl-gamma-glutamyl)-des(B30) human insulin; B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(ω-carboxyheptadecanoyl) human insulin. Exemplary GLP-<NUM>, GLP-<NUM> analogues and GLP-<NUM> receptor agonists are, for example: Lixisenatide / AVE0010 / ZP10 / Lyxumia, Exenatide / Exendin-<NUM> / Byetta / Bydureon / ITCA <NUM> / AC-<NUM> (a <NUM> amino acid peptide which is produced by the salivary glands of the Gila monster), Liraglutide / Victoza, Semaglutide, Taspoglutide, Syncria / Albiglutide, Dulaglutide, rExendin-<NUM>, CJC-<NUM>-PC, PB-<NUM>, TTP-<NUM>, Langlenatide / HM-11260C, CM-<NUM>, GLP-<NUM> Eligen, ORMD-<NUM>, NN-<NUM>, NN-<NUM>, NN-<NUM>, Nodexen, Viador-GLP-<NUM>, CVX-<NUM>, ZYOG-<NUM>, ZYD-<NUM>, GSK-<NUM>, DA-<NUM>, MAR-<NUM>, MAR709, ZP-<NUM>, ZP-<NUM>, TT-<NUM>, BHM-<NUM>. MOD-<NUM>, CAM-<NUM>, DA-<NUM>, ARI-<NUM>, ARI-<NUM>, Exenatide-XTEN and Glucagon-Xten.

Antibody fragments that are useful in the present disclosure include, for example, Fab fragments, F(ab')<NUM> fragments, scFv (single-chain Fv) fragments, linear antibodies, monospecific or multispecific antibody fragments such as bispecific, trispecific, and multispecific antibodies (e.g., diabodies, triabodies, tetrabodies), minibodies, chelating recombinant antibodies, tribodies or bibodies, intrabodies, nanobodies, small modular immunopharmaceuticals (SMIP), binding-domain immunoglobulin fusion proteins, camelized antibodies, and VHH containing antibodies.

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.

Claim 1:
An audible and/or tactile indicator (<NUM>) for use with a drug delivery device (<NUM>) comprising a resilient force member (<NUM>) being a leaf spring and comprising a resilient material, the resilient force member (<NUM>) being configured to reside in two or more states (S1, S2) having two or more different conformations,
- wherein in a relaxed state (S1), the resilient force member (<NUM>) is relaxed in a first conformation,
- wherein in a biased state (S2), the resilient force member (<NUM>) is biased to store energy in a second conformation different to the first conformation,
- wherein the resilient force member (<NUM>) releases stored energy to generate an audible signal when changing from the biased state (S2) into the relaxed state (S1) due to a transition from the second conformation to the first conformation,
- wherein the resilient force member (<NUM>) is bent by a certain angle about a longitudinal axis (L) forming a longitudinal round fold (<NUM>) with two adjacent angled wing-shaped sections,
characterised in that
a notch (<NUM>) is formed in the longitudinal round fold (<NUM>), wherein the notch (<NUM>) extends transversely to the longitudinal round fold (<NUM>).