Patent Description:
Drug delivery devices (i.e. devices capable of delivering medicaments from a medication container) typically fall into two categories - manual devices and auto-injectors.

In a manual device - the user must provide the mechanical energy to drive the fluid through the needle. This is typically done by some form of button / plunger that has to be continuously pressed by the user during the injection. There are numerous disadvantages to the user from this approach. If the user stops pressing the button / plunger then the injection will also stop. This means that the user can deliver an underdose if the device is not used properly (i.e. the plunger is not fully pressed to its end position). Injection forces may be too high for the user, in particular if the patient is elderly or has dexterity problems.

Auto-injectors are devices which completely or partially replace activities involved in parenteral drug delivery from standard syringes. These activities may include removal of a protective syringe cap, insertion of a needle into a patient's skin, injection of the medicament, removal of the needle, shielding of the needle and preventing reuse of the device. This overcomes many of the disadvantages of manual devices. Injection forces / button extension, hand-shaking and the likelihood of delivering an incomplete dose are reduced. Triggering may be performed by numerous means, for example a trigger button or the action of the needle reaching its injection depth. In some devices the energy to deliver the fluid is provided by a spring.

Plunger release mechanisms are applied to control motion of a plunger in a drug delivery device in a manner keeping the plunger in a defined position until a condition is met suddenly allowing the plunger to move within the drug delivery device thus delivering a dose of a drug from a syringe.

<CIT> discloses an injection device comprising a tubular elongated main body, a needle shield slidably arranged in said main body, a needle shield link slidably connected to said needle shield, an enclosure containing medicament arranged in said main body, a needle connected to said enclosure, a plunger operatively arranged to said enclosure for ejecting said medicament through said needle and arranged on its upper part with a number of outwardly extending stop members, spring means arranged to said plunger for operating said plunger, a dose activating means, and a needle shield spring surrounding the needle shield link. The injection device further comprises a first tubular member rotationally and slidably arranged inside said needle shield link, wherein said tubular member comprises a number or ridges and protrusions on both its outer and inner surfaces, said ridges and protrusions on the outer surface of the tubular member co-operate with guide members arranged on the inner surface of said needle shield link, and said ridges and protrusions on the inner surface of the tubular member co-operate with the outwardly extending stop members of the plunger. The injection device further comprises a second tubular member arranged inside said housing, arranged and designed with a number of ridges and protrusions on its inner and outer surfaces capable of setting and delivering a certain preset dose.

<CIT> discloses an injection assist device for automatically injecting a medicament into a subject once the device has been triggered. The device includes a medicament chamber and a plunger for injecting medicament from the medicament chamber through a needle, a retaining mechanism for securing the plunger against movement in a distal direction when the device is in an armed configuration, and an activator that slidingly and rotationally displaces the retaining mechanism when the device is triggered to allow distal movement of the plunger to inject the medicament from the medicament chamber through the needle. Methods of administering an injection using the device are also provided.

<CIT> discloses an autoinjector comprising a case adapted to hold a medicament container having a needle, a needle shroud telescopically coupled to the case and movable between a first extended position relative to the case in which the needle is covered and a retracted position relative to the case in which the needle is exposed, and a plunger rotationally and slidably disposed in the case. The plunger is rotatable relative to the case between a first rotational position in which the plunger is engaged to the case and a second rotational position in which the plunger disengages the case. The needle shroud is operably coupled to the plunger. When the needle shroud translates from the first extended position to the retracted position, the plunger rotates from the first rotational position to the second rotational position.

There remains a need for a drug delivery device with an improved plunger release mechanism.

An object of the present disclosure is to provide a drug delivery device with an improved plunger release mechanism as well as a method for assembling a drug delivery device.

The object is achieved by a drug delivery device according to claim <NUM>.

Exemplary embodiments are provided in the dependent claims.

As claimed, a drug delivery device comprises a housing adapted to receive a medicament container, a sleeve coupled to the housing to permit movement of the sleeve relative to the housing, a plunger and a plunger release mechanism adapted to release the plunger once the sleeve is depressed. The plunger release mechanism comprises:.

According to the invention, the plunger release mechanism further comprises a sleeve ramp arranged on the sleeve, the sleeve ramp adapted to engage a rib or boss on the plunger to rotate the plunger to release the first plunger boss from the profiled slot when the sleeve is moved in a proximal direction.

In an exemplary embodiment, the profiled slot further comprises a wall for limiting movement of the first plunger boss in the first rotational direction when engaged to the first angled surface and a second angled surface adjacent the wall and adapted to induce a torque in the first rotational direction to the plunger to release the first plunger boss from the profiled slot.

This allows for preventing the plunger from being released while the first plunger boss is engaged to the first angled surface and the wall. This state is particularly useful for storing and transporting a drug delivery device or a part thereof comprising the plunger and optionally a drive spring so that the drive spring cannot inadvertently advance the plunger, e.g. if the drug delivery device or the part thereof comprising the plunger is dropped. In order to transition the plunger into a state in which it may be released, the plunger may be moved away from the first angled surface along the wall and rotated so that the first plunger boss engages the second angled surface. The transition into this state may be performed during final assembly of a drug delivery device. If the plunger is not otherwise prevented from rotating further, the first plunger boss may slide down the second angled surface until disengaging it, allowing the plunger to advance, e.g. for displacing a medicament from a medicament container, in particular a syringe. In an exemplary embodiment, the plunger may be prevented from rotating further by a sleeve rib on a sleeve which may be moved on contact with an injection site to allow further rotation of the plunger.

In an exemplary embodiment, the drug delivery device may comprise the above described profiled slot with the firs and second angled surfaces and the wall without having a sleeve ramp adapted to engage a rib or boss on the plunger.

In an exemplary embodiment, the first angled surface and/or the second angled surface have/has an angle in a range from <NUM>° to <NUM>° relative to a perpendicular on a longitudinal axis of the plunger.

In an exemplary embodiment, the plunger release mechanism further comprises a second plunger boss arranged on the plunger and a sleeve rib arranged on the sleeve, the sleeve rib having a longitudinal face adapted to engage the second plunger boss preventing rotation of the plunger in the first rotational direction to keep the first plunger boss engaged to the angled surface, wherein the sleeve rib is adapted to disengage the second plunger boss when the sleeve rib is moved in a proximal direction thereby allowing the plunger to rotate in the first rotational direction and the first plunger boss to disengage the second angled surface.

In an exemplary embodiment, the plunger release mechanism further comprises an angled plunger rib on the plunger adapted to abut the sleeve rib so as to induce a torque to the plunger in the first rotational direction and push the plunger in the proximal direction when the first plunger boss is engaged to the first angled surface and to the wall.

In an exemplary embodiment, the sleeve rib comprises a distal face adapted to engage the second plunger boss so as to limit movement of the sleeve rib in a distal direction relative to the plunger.

In an exemplary embodiment, the release of the first plunger boss from the first angled surface and/or from the second angled surface and/or the release of the second plunger boss from the sleeve rib provides an audible feedback.

The sleeve may be adapted to be moved in a proximal direction relative to the housing upon contact with an injection site to disengage the sleeve rib from the second plunger boss.

In an exemplary embodiment, a drive spring is arranged within the housing and adapted to bias the plunger in the distal direction for displacing a piston of a medicament container.

In an exemplary embodiment, the plunger is hollow and the drive spring is arranged within the plunger.

In an exemplary embodiment, the housing comprises a distal region and a proximal region, wherein the proximal region comprises the profiled slot.

In an exemplary embodiment, the angled plunger rib is adapted to abut the sleeve rib upon coupling of the proximal region with the plunger and the drive spring to the distal region for moving the first plunger boss from the first angled surface to the second angled surface.

In an exemplary embodiment, the drug delivery device comprises a medicament container.

In an exemplary embodiment, the medicament container contains a medicament.

According to an aspect of the present disclosure, a method for assembling a drug delivery device, comprises:.

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>).

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. 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 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.

The drug delivery device <NUM> may be divided in two subassemblies, a control subassembly and a drive subassembly <NUM>. This allows for improving flexibility as to the time and location of manufacture of the subassemblies and final assembly with the syringe <NUM>.

<FIG> is a perspective exploded view of the drive subassembly <NUM>. The drive subassembly <NUM> comprises components used to displace the medicament from the syringe <NUM>. If the viscosity or volume of the medicament M in the syringe <NUM> is varied, only parts of the drive subassembly <NUM> may need to be changed. The drive subassembly <NUM> comprises the plunger <NUM>, the drive spring <NUM> and the proximal region <NUM> of the housing <NUM>. In an exemplary embodiment, the drive subassembly <NUM> may be assembled in a process which requires virtually only axial motion except for the plunger <NUM>. In order to assemble the drive subassembly <NUM> the drive spring <NUM> is inserted into the plunger <NUM> and the plunger <NUM> is inserted in the proximal region <NUM> in the proximal direction P thereby compressing the drive spring <NUM>. Once the plunger <NUM> reaches a compressed position it is rotated by an angle, e.g. approximately <NUM> ° to lock it to the proximal region <NUM>. In an exemplary embodiment the proximal region <NUM> could have a cam surface which could induce this rotation prior to the plunger <NUM> reaching the compressed position.

Furthermore, a feedback element <NUM>, e.g. a spring element may be provided to indicate an event, e.g. an end of dose, by providing an audible and/or tactile feedback.

<FIG> is a schematic side view of the drive subassembly <NUM>. <FIG> are schematic detail views of the drive subassembly <NUM> showing part of a plunger release mechanism <NUM>.

The plunger release mechanism <NUM> controls the activation of syringe emptying. The plunger release mechanism <NUM> is adapted to release the plunger <NUM> once the sleeve <NUM> is depressed and reaches a retracted position RP within the housing <NUM>.

The plunger release mechanism <NUM> comprises a first plunger boss <NUM> arranged on the plunger <NUM> and a profiled slot <NUM> in the proximal region <NUM> of the housing <NUM>. The profiled slot <NUM> comprises a first angled surface <NUM> adapted to engage the first plunger boss <NUM> to induce a torque in a first rotational direction R1 to the plunger <NUM>, a wall <NUM> for limiting movement of the first plunger boss <NUM> in the first rotational direction R1 when engaged to the first angled surface <NUM>. Furthermore, the profiled slot <NUM> comprises a second angled surface <NUM> adapted to engage the first plunger boss <NUM> to induce a torque in the first rotational direction R1 to the plunger <NUM>.

The first angled surface <NUM> and/or the second angled surface <NUM> may have an angle in a range from <NUM>° to <NUM>° relative to a perpendicular on the longitudinal axis X of the drug delivery device <NUM> which may also be the longitudinal axis of the plunger <NUM>.

In a first state shown in <FIG>, the first plunger boss <NUM> is engaged to the first angled surface <NUM>. Due to the drive spring <NUM> acting on the plunger <NUM>, the first plunger boss <NUM> is pressed against the first angled surface <NUM> in a distal direction D such that a torque is induced to the plunger <NUM> in the first rotational direction R1 so that the first plunger boss <NUM> slides along the first angled surface <NUM> until it abuts the wall <NUM> so that rotation of the plunger <NUM> in the first rotational direction R1 is halted.

<FIG> shows the plunger release mechanism <NUM> in a second state. Starting from the first state, the plunger <NUM> has been moved a distance at least as long as the wall <NUM> in the proximal direction P such that the wall <NUM> no longer limits movement of the first plunger boss <NUM> in the first rotational direction R1. The plunger <NUM> has then been rotated further in the first rotational direction R1 so that the first plunger boss <NUM> engages the second angled surface <NUM>. Due to the drive spring <NUM> acting on the plunger <NUM>, the first plunger boss <NUM> is pressed against the second angled surface <NUM> in a distal direction D such that a torque is induced to the plunger <NUM> in the first rotational direction R1 so that the first plunger boss <NUM> slides along the second angled surface <NUM>. If the plunger <NUM> is not otherwise prevented from rotating further, the first plunger boss <NUM> may slide down the second angled surface <NUM> until disengaging it, allowing the plunger <NUM> to advance in the distal direction D to displace the medicament from the syringe <NUM>.

In an exemplary embodiment, movement of the plunger <NUM> from the first state in the proximal direction P and onto the second angled surface <NUM> may be achieved by the sleeve <NUM> interacting with the plunger <NUM>, e.g. by engaging the first plunger boss <NUM> or a further plunger boss or rib on the plunger (not shown).

An exemplary embodiment of the plunger release mechanism <NUM> is shown in more detail in <FIG>, <FIG>.

<FIG> shows the plunger release mechanism during assembly of the drive subassembly <NUM>.

The plunger release mechanism <NUM> is adapted to release the plunger <NUM> once the sleeve <NUM> is depressed and reaches a retracted position within the housing <NUM>.

The plunger release mechanism <NUM> comprises the plunger <NUM>, the proximal region <NUM>, and the sleeve13 interacting with each other. The sleeve <NUM> and the proximal region <NUM> are configured to move only in parallel with the longitudinal axis X relative to each other whereas the plunger <NUM> can move both in parallel with the longitudinal axis X and rotate about the longitudinal axis X. The parts of the plunger release mechanism <NUM> may be essentially rigid and require no deformation in order to function correctly.

The parts arranged for engaging the plunger <NUM>, proximal region <NUM> and sleeve <NUM> comprise:.

The profiled slot <NUM> comprises a first angled surface <NUM> adapted to engage the first plunger boss <NUM> to induce a torque in a first rotational direction R1 to the plunger <NUM>, a wall <NUM> for limiting movement of the first plunger boss <NUM> in the first rotational direction R1 when engaged to the first angled surface <NUM>. Furthermore, the profiled slot <NUM> comprises a second angled surface <NUM> adapted to engage the first plunger boss <NUM> to induce a torque in the first rotational direction R1 to the plunger <NUM>.

During assembly of the drive subassembly <NUM> the plunger <NUM> with the drive spring <NUM> is inserted into the proximal region <NUM>. Once the plunger <NUM> reaches a proximal position the first plunger boss <NUM> is axially aligned with the profiled slot <NUM>. By rotating the plunger <NUM> in a second rotational direction R2 by an angle, e.g. approximately <NUM> °, the first plunger boss <NUM> is moved into the profiled slot <NUM>. In this position the first angled surface <NUM> moves the first plunger boss <NUM> against the wall <NUM> by inducing a torque to the plunger <NUM> in the first rotational direction R1 due to the drive spring <NUM> biasing the plunger <NUM> in the distal direction D.

In order to assemble the drug delivery device <NUM>, a syringe <NUM> may be inserted into the control subassembly which may comprise the distal region <NUM> of the housing <NUM>.

Afterwards, the drive subassembly <NUM> is inserted into the control subassembly in the distal direction D. The proximal region <NUM> and the distal region <NUM> may comprise snap connections to lock them together when assembled. During the final assembly of the drug delivery device <NUM> the sleeve <NUM> may be partially depressed to allow initiation of the plunger release mechanism <NUM>, e.g. by an assembly jig (not illustrated) or in a different way.

<FIG> shows the plunger release mechanism <NUM> during the final assembly. The sleeve rib <NUM> proximally abuts the angled plunger rib <NUM> thereby inducing a torque to the plunger <NUM> in the first rotational direction R1 and pushing the plunger <NUM> in the proximal direction P so that the first plunger boss <NUM> moves along the wall <NUM> until it disengages from the wall <NUM>. Due to the induced torque, the first plunger boss <NUM> moves in the first rotational direction R1 and engages the second angled surface <NUM>. The depression of the sleeve <NUM> may cease and, due to the first plunger boss <NUM> engaging the second angled surface <NUM> and the drive spring <NUM> acting on the plunger <NUM> in the distal direction D, the plunger <NUM> rotates further in the first rotational direction R1. As the sleeve <NUM> is not being depressed further it may move in the distal direction D relative to the housing <NUM>, e.g. under the action of a sleeve spring (not illustrated). This movement is limited by the second plunger boss <NUM> abutting the distal face <NUM> on the sleeve rib <NUM>. Further rotation of the plunger <NUM> in the first rotational direction R1 is prevented by the second plunger boss <NUM> abutting the longitudinal face <NUM> of the sleeve rib <NUM>. The load of the drive spring <NUM> is resolved within the proximal region <NUM> by the first plunger boss <NUM> engaging the profiled slot <NUM>. This state of the plunger release mechanism <NUM> is illustrated in <FIG>.

A sequence of operation of the drug delivery device <NUM> may be as follows:
The user removes the cap assembly <NUM> pulling it in the distal direction D away from the housing <NUM>. Removal of the cap assembly <NUM> may at the same time remove a protective needle sheath from the needle <NUM>.

The sleeve <NUM> is in an extended position protruding from the housing <NUM> in the distal direction D. The extended position may be defined by the second plunger boss <NUM> proximally abutting the distal face <NUM> of the sleeve rib <NUM>.

The user may then press the drug delivery device <NUM> with the sleeve <NUM> ahead against an injection site, e.g. a patient's skin thereby moving the sleeve <NUM> from the extended position towards a retracted position against the bias of the shroud spring.

<FIG> is a schematic view of the plunger release mechanism <NUM> after depression of the sleeve <NUM> into the retracted position. As the sleeve <NUM> is being moved from the extended position towards the retracted position the second plunger boss <NUM> moves (starting from the position shown in <FIG>) relative to the sleeve <NUM> in the distal direction D guided along the longitudinal face <NUM> of the sleeve rib <NUM>.

In an exemplary embodiment the longitudinal face <NUM> of the sleeve rib <NUM> may comprise an interruption or bump feature (not illustrated) for creating an increase in the force required to depress the sleeve <NUM> further. This may be used to indicate to the user that needle insertion would commence with further depression of the sleeve <NUM>. Up until this point, the user is free to remove the drug delivery device <NUM> from the injection site and reposition as the sleeve <NUM> will re-extend to its initial position under the force of the shroud spring.

If the user continues pressing the drug delivery device <NUM> against the injection site the sleeve <NUM> is moved into the retracted position exposing the needle <NUM> and inserting it into the injection site.

Once the sleeve <NUM> is depressed into the retracted position, and the needle <NUM> inserted, the second plunger boss <NUM> has moved distally beyond the sleeve rib <NUM> such that the plunger <NUM> is no longer prevented from rotating in the first rotational direction R1 due to the torque induced by the drive spring <NUM> and the first plunger boss <NUM> engaging the second angled surface <NUM> on the profiled slot <NUM>. The plunger <NUM> rotates in the first rotational direction R1 due to this torque and the first plunger boss <NUM> comes clear of the profiled slot <NUM>. The plunger <NUM> is thus released and advances the piston <NUM> in the distal direction D displacing the medicament from the syringe <NUM> through the needle <NUM>. The release of the first or second plunger boss <NUM>, <NUM> may provide audible feedback that delivery of the medicament has started.

<FIG> is a schematic detail view of the plunger release mechanism <NUM> after final assembly and prior to depression of the sleeve <NUM>. Movement of the sleeve <NUM> in the distal direction D relative to the housing <NUM> is limited by the second plunger boss <NUM> abutting the distal face <NUM> on the sleeve rib <NUM>. Further rotation of the plunger <NUM> in the first rotational direction R1 is prevented by the second plunger boss <NUM> abutting the longitudinal face <NUM> of the sleeve rib <NUM>.

<FIG> is a schematic detail view of the plunger release mechanism <NUM> during depression of the sleeve <NUM>. As the sleeve <NUM> is being moved from the extended position towards the retracted position in the proximal direction P the second plunger boss <NUM> moves (starting from the position shown in <FIG>) relative to the sleeve <NUM> in the distal direction D guided along the longitudinal face <NUM> of the sleeve rib <NUM>.

Once the sleeve <NUM> is depressed into the retracted position, and the needle <NUM> inserted, the second plunger boss <NUM> has moved distally beyond the sleeve rib <NUM> such that the plunger <NUM> is no longer prevented from rotating in the first rotational direction R1 due to the torque induced by the drive spring <NUM> and the first plunger boss <NUM> engaging the second angled surface <NUM> on the profiled slot <NUM>. The plunger <NUM> rotates in the first rotational direction R1 due to this torque and the first plunger boss <NUM> comes clear of the profiled slot <NUM>. The plunger <NUM> is thus released and advances the piston <NUM> in the distal direction D displacing the medicament from the syringe <NUM> through the needle <NUM>.

<FIG> is a schematic detail view of another embodiment of the plunger release mechanism <NUM> during depression of the sleeve <NUM>. In addition to the embodiment described above, a sleeve ramp <NUM> is provided on the sleeve <NUM>. As the sleeve <NUM> approaches the retracted position, the sleeve ramp <NUM> engages a rib or boss on the plunger <NUM>, e.g. the angled plunger rib <NUM> to actively rotate the plunger <NUM> in the first rotational direction R1. If the plunger <NUM> should not rotate spontaneously due to the features of the previous embodiments, the additional sleeve ramp <NUM> will induce rotation of the plunger <NUM>.

During normal use, the plunger <NUM> will release as in the previous embodiments. The sleeve ramp <NUM> is positioned to only interact with the angled plunger rib <NUM> if the plunger <NUM> has not spontaneously rotated near the end of the depression of the sleeve <NUM>. The skilled person will readily understand that the embodiment of <FIG> would likewise work if only one of the rib or boss on the plunger <NUM>, e.g. the angled plunger rib <NUM>, or the sleeve ramp <NUM> was ramped or angled.

Another benefit of the embodiment of <FIG> is that it provides additional guidance of the plunger <NUM> movement as it activates.

In another exemplary embodiment, the sleeve ramp <NUM> engaging the rib or boss on the plunger <NUM>, e.g. the angled plunger rib <NUM>, may be the only way to rotate the plunger <NUM> out of engagement with the profiled slot <NUM>. For example, the profiled slot <NUM> may not have an angled surface causing the plunger <NUM> to rotate in the first rotational direction R1 out of engagement with the profiled slot <NUM>. In an exemplary embodiment, the profiled slot <NUM> may only have a transversal surface towards the distal direction D and transversally oriented relative to the longitudinal axis X. The transversal surface may have a detent or bump. In another exemplary embodiment the profiled slot <NUM> may only have an angled surface causing the plunger to rotate in the second rotational direction R2 maintaining the first plunger boss <NUM> engaged within the profiled slot <NUM>.

In an exemplary embodiment, the drug delivery device <NUM> may be an auto-injector.

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:
A drug delivery device (<NUM>), comprising a housing (<NUM>) adapted to receive a medicament container (<NUM>), a sleeve (<NUM>) coupled to the housing (<NUM>) to permit movement of the sleeve (<NUM>) relative to the housing (<NUM>), a plunger (<NUM>) and a plunger release mechanism (<NUM>) adapted to release the plunger (<NUM>) once the sleeve (<NUM>) is depressed, the plunger release mechanism (<NUM>) comprising:
- a first plunger boss (<NUM>) arranged on the plunger (<NUM>),
- a profiled slot (<NUM>) arranged on the housing and adapted to be engaged by the first plunger boss (<NUM>) so as to inhibit movement of the plunger (<NUM>) in a distal direction (D), wherein the profiled slot (<NUM>) is adapted to induce a torque to the plunger (<NUM>) when an axial force is applied to the plunger (<NUM>), wherein the profiled slot (<NUM>) comprises at least one angled surface (<NUM>, <NUM>) adapted to engage the first plunger boss (<NUM>) to induce a torque in a first rotational direction (R1) to the plunger (<NUM>) to release the first plunger boss (<NUM>) from the profiled slot (<NUM>), wherein the plunger (<NUM>) is rotatable about a longitudinal axis (X) to release the first plunger boss (<NUM>) from the profiled slot (<NUM>), wherein the first plunger boss (<NUM>) may slide down the angled surface (<NUM>) until disengaging it so as to allow movement of the plunger (<NUM>) in the distal direction (D),
characterized in the plunger release mechanism (<NUM>) further comprising a sleeve ramp (<NUM>) arranged on the sleeve (<NUM>), the sleeve ramp (<NUM>) adapted to engage a rib (<NUM>) or boss (<NUM>, <NUM>) on the plunger (<NUM>) to rotate the plunger (<NUM>) to release the first plunger boss (<NUM>) from the profiled slot (<NUM>) when the sleeve (<NUM>) is moved in a proximal direction (P), wherein the sleeve ramp (<NUM>) is positioned to only interact with the rib (<NUM>) or boss (<NUM>, <NUM>) on the plunger (<NUM>) if the plunger (<NUM>) has not spontaneously rotated near the end of the depression of the sleeve (<NUM>).