WO2024251797A1

WO2024251797A1 - Drug delivery device

Info

Publication number: WO2024251797A1
Application number: PCT/EP2024/065441
Authority: WO
Inventors: Uwe Dasbach; Tim GLÄSSER; Moritz KEIM; Matthias Rau; Marc SCHADER; Lionel Vedrine; Stefan Wendland
Original assignee: Sanofi
Priority date: 2023-06-05
Filing date: 2024-06-05
Publication date: 2024-12-12

Abstract

A drug delivery device (20) is provided. The drug delivery device (20) comprises: a housing (22) for receiving a drug container (24); a plunger rod arrangement (35) for driving a stopper (32) of the drug container (24) in a dispensing direction (40); a drive member (39) for driving the plunger rod arrangement (35), the drive member (39) being coupled to the plunger rod arrangement (35) by a threaded interface, the threaded interface being configured such that a rotation of the drive member (39) causes a translatory movement of the plunger rod arrangement (35) in the dispensing direction (40); and an energy storage member (42) coupled to the drive member (39) for rotating the drive member (39).

Description

Title

Drug delivery device

Background

The present disclosure relates to a drug delivery device, in particular a very compact and wieldy drug delivery device.

In drug delivery devices, drug is often delivered to a user via a needle which pierces the skin of the user (or patient). The drug may be accommodated within a drug container of the drug delivery device, e.g. within a syringe arranged within the drug delivery device. Conventional drug delivery devices comprising syringes and an associated drive mechanism have a shape basically corresponding to the shape of the syringe. In particular, conventional drug delivery devices comprising syringes have an elongated cylindrical shape, wherein an axis of the drug delivery device may correspond to an axis of the needle. Such a drug delivery device may often be referred to as pen-type device. The cylindrical form may be hard to handle, in particular if the user has some motoric impairment.

Summary

It is an object of the present disclosure to facilitate improvements associated with drug delivery devices, particularly with respect to size, shape and operability.

This object is achieved by the disclosed subject-matter, for example by the subject-matter defined in the appended independent claim. Advantageous refinements and developments are subject to dependent claims and/or set forth in the description below.

One aspect of the present disclosure relates to a drug delivery device, comprising: a housing for receiving a drug container; a plunger rod arrangement for driving a stopper of the drug container in a dispensing direction; a drive member for driving the plunger rod arrangement, the drive member being coupled to the plunger rod arrangement by a threaded interface, the threaded interface being configured such that a rotation of the drive member causes a translatory movement of the plunger rod arrangement in the dispensing direction; and an energy storage member coupled to the drive member for rotating the drive member. The plunger rod arrangement and the threaded interface for coupling the plunger rod arrangement with the drive member enable to design the housing of the drug delivery device very compact and wieldy. This contributes to that the drug delivery device is easy to handle and to operate.

The energy storage member may be preloaded and/or biased in an initial state of the drug delivery device. The energy storage member may be released for initiating a dispensing operation. If the energy storage member is released, the energy storage member rotates the drive member. The drive member may be arranged such that it is rotatable around an axis, but not translatory movable relative to the housing, in particular not in the dispensing direction. The axis may be parallel to the dispensing direction. For example, the drive member may be rotatably coupled to the housing by a holder. The holder may be formed as a suspension. The plunger rod arrangement may be rotatably coupled to the stopper by a bearing.

The drug container may be arranged in the housing, in particular in a container socket of the housing. The drug container may be a syringe. Alternatively, the drug container may be a cartridge. The drug container may have a chamber, a dispensing end, a remote end facing away from the dispensing end, and the stopper within the chamber. The stopper may sealingly close the chamber of the drug container remotely, i.e. at or next to the remote end of the drug container. A drug may be arranged within the chamber, wherein the drug is sealingly enclosed by inner walls of the drug container and the stopper. The plunger rod arrangement may be coupled to the stopper at a first axial end of the plunger rod arrangement.

The drug delivery device may be a fully functional drug delivery device. The drug may be a medicament. The drug delivery device may be an autoinjector. In an autoinjector, the energy for the drug delivery operation may be prestored in the energy storage member. That is to say, the user does not have to provide the energy for the drug delivery operation, e.g. when preparing the drug delivery device for use. Rather, this energy may be preloaded into the system by the manufacturer. For example, a drive spring, e.g. a spiral spring or flat spiral spring, may be prestressed or pre-biased to provide the energy for the drug delivery operation.

The housing may have the shape of a mushroom including a stem and a cap on the stem. One advantage of this mushroom-shape is the compact and wieldy design. The stem may provide a bearing surface for being in contact with the skin of the user during the dispensing operation. The cap faces away from the injection site during the dispensing operation. The stem may provide sufficient space for accommodating the drug container, e.g. a syringe. The cap may provide a comfortable griping area opposite to the bearing surface, i.e. facing away from the skin of the user during usage. The mushroom-design therefore enables to provide a very large grip area compared to a cylindrical drug delivery device. The large grip area also makes the drug delivery device easier to hold for patients with limited dexterity, as is the case with rheumatic patients, for example.

In one embodiment, the plunger rod arrangement is a telescopic plunger rod arrangement comprising: a first segment being configured for being coupled to the stopper at a first axial end of the first segment; and a second segment being operatively coupled to the first segment and the drive member such that the rotation of the drive member is transferred to a translatory movement of the first segment in the dispensing direction by the second segment. The second segment may be in direct engagement with the drive member.

The first and/or second segment each may be rotatable around the same axis as the drive member. The telescopic plunger rod arrangement very efficiently contributes to the compact design and at the same time provides a large stroke for moving the stopper and thereby dispensing the drug. Optionally, the telescopic plunger rod arrangement may comprise one, two or more further corresponding (telescope-)segments.

In one embodiment, the second segment is operatively coupled to the first segment and the drive member such that the rotation of the drive member firstly is transferred to a translatory movement of the second segment in the dispensing direction, wherein the first segment is translatory moved together with the second segment by the second segment. At the end of the translatory movement of the second segment the second segment is rotated by the drive member and the rotation of the second segment causes a further translatory movement of the first segment in the dispensing direction. If the second segment rotates, it may be axially fixed such that there is no translatory movement of the second segment anymore. This enables to provide a very large stroke while keeping the telescopic plunger rod assembly very compact in an easy way.

In one embodiment, the threaded interface comprises a first threaded interface and a second threaded interface. In other words, the threaded interface may be a threaded interface arrangement comprising the first and second threaded interfaces. The first threaded interface may be configured to operatively couple the first segment to the second segment and the second threaded interface may be configured to operatively couple the second segment to the drive member. The term "threaded interface" may be used in this description to describe an interface comprising at least one thread and a structure which interacts with the thread, e.g. another thread or one or more pins or bars, with the threaded interface coupling at least two bodies with each other, wherein one of the bodies comprises the thread and the other body comprises the structure interacting with the thread and wherein the bodies are movable relative to each other.

In one embodiment, the first threaded interface comprises a first interface feature at the first segment and a second interface feature at the second segment, the first interface feature being engaged with the second interface feature. Alternatively or additionally, the second threaded interface comprises a third interface feature at the second segment and a fourth interface feature at the drive member, the third interface feature being engaged with the fourth interface feature. So, each threaded interface may comprise at least two interface features.

In one embodiment, the first interface feature is a first thread. Alternatively or additionally, the second interface feature is a second thread. Alternatively or additionally, the third interface feature is a third thread. Alternatively or additionally, the fourth interface feature is a fourth thread. In particular, at least one of the first and second interface features may be a thread and/or at least one of the third and fourth interface features may be a thread. For example, each of the interface features may be a thread. Alternatively, that interface feature interacting with the corresponding thread of the same threaded interface and not being a thread may comprise one or more bars or pins which engage with the corresponding thread and may provide the same or equivalent functionality as a thread. Each of the threads may comprise one, two or more turns. This contributes to a homogeneous transfer of the force around the circumference of the drive member or, respectively, the corresponding segment. If one of the treads comprises two or more turns, the starts and/or ends of the corresponding turns may be axially and/or angularly offset to each other. This contributes to a very good stability of the first and/or second segment.

In one embodiment, the second segment and the drive member are configured such that the rotation of the drive member is transferred to the translatory movement of the second segment until an end of the third thread of the second segment reaches an end of the fourth thread of the drive member and that a further rotation of the drive member is transferred to the rotation of the second segment. So, firstly the second segment is translatory moved in the dispensing direction without any rotation, wherein the second segment also moves the first segment, which is coupled to the second segment, in the dispensing direction. If the second segment cannot be translatory moved anymore, because the end of the fourth and/or third thread is reached, the second segments starts rotating together with the drive member. This rotation of the second segment is then transferred to the translatory movement of the first segment in the dispensing direction.

In one embodiment, the drive member has an axially extending drive member recess and the second segment has an axially extending second segment recess, wherein the second segment is arranged within the drive member recess and the first segment is arranged within the second segment recess. In this case, the first thread at the first segment is an external thread, the second thread at the second segment is an internal thread, the third thread at the second segment is an external thread, and the fourth thread at the drive member is an internal thread. Each of the drive member recess and/or the second segment recess may be a through-recess extending through the drive member and/or, respectively, the second segment.

In one embodiment, the first segment has an axially extending first segment recess and the second segment has an axially extending second segment recess, wherein the second segment is arranged within the first segment recess and the drive member is arranged within the second segment recess. In this case, the first thread at the first segment is an internal thread, the second thread at the second segment is an external thread, the third thread at the second segment is an internal thread, and the fourth thread at the drive member is an external thread. Each of the segment recesses may be a through-recess extending through the corresponding segment.

In one embodiment, the energy storage member is a flat spiral spring, which is coupled to the drive member, and which is loaded and locked in the initial state of the drug delivery device. The flat spiral spring may be arranged obliquely, in particular perpendicular to the axis around which the drive member is rotatable. Alternatively or additionally, an axis of the spiral spring may correspond to the above axis. The flat spiral spring may be attached to and/or may be arranged within the cap of the mushroom-shaped housing. For example, the cap comprises a cavity accompanying the flat spiral spring. In case of the spiral spring or flat spiral spring the energy storage member may be pre-loaded by biasing the spiral spring or, respectively, the flat spiral spring. The energy storage member may allow for a given activation dynamic.

In one embodiment, the drug delivery device comprises a needle for injecting the drug into an injection site, wherein the needle is configured for being communicatively coupled to the drug container. The needle may extend in a direction parallel to the above axis. So, the needle may extend parallel to the dispensing direction. The needle may be configured for piercing the skin of the user. The needle may be permanently coupled to the drug container such that the needle permanently communicates with the chamber of the drug container. Alternatively, the drug delivery device may comprise a further needle. In this context, the needle piercing the skin of the user may be referred to as first needle and the further needle may be referred to as second needle. The second needle may be used for piercing a septum of the drug container. The first needle may communicate with the second needly, e.g. by a conduit, for guiding the drug from the drug container through the second needle towards the first needle. The second needle may extend parallel to the dispensing direction. In one embodiment, the drug delivery device comprises a needle sleeve for protecting the needle in the initial state and optionally in a final state after the use of the drug delivery device. The needle sleeve may be operatively coupled to the energy storage member and may be configured such that a release of the energy storage member is prevented as long as the needle sleeve protects the needle and that the energy storage member is released, when the needle sleeve exposes the needle. The needle sleeve may be at least partly movable into the housing, if the drug delivery device is arranged on an injection site and is pressed against the injection site. The needle sleeve may expose the needle, if it is at least partly moved into the housing. The needle sleeve may be provided to cover the needle, in particular the first needle for piercing the skin, in the initial state before the drug delivery device is arranged on the injection site and in the final state after removing the drug delivery device from the injection site. So, the needle sleeve may be provided to cover the needle before the needle pierces the skin and/or after the needle has been removed from the skin, e.g. after completion of the drug delivery operation. Before the drug delivery operation is commenced, the needle sleeve may protrude from the housing, e.g. to cover the tip of the needle (such as by axially extending beyond the tip of needle, e.g. at least with a bearing surface of the needle sleeve). For the drug delivery operation, the needle sleeve may be displaced relative to the housing. After completion of the drug delivery operation, the needle sleeve may be moved relative to the housing, e.g. to cover the tip of needle and/or into a third position relative to the housing.

In one embodiment, the drug delivery device comprises a needle sleeve spring which is coupled to the needle sleeve and the housing such that the needle sleeve spring is loaded, if the drug delivery device is arranged on the injection site during a dispensing operation, and that the needle sleeve is pushed out of the housing by the needle sleeve spring, if the drug delivery device is removed from the injection site. The needle sleeve spring may be operatively couplable to or coupled to the needle sleeve in order to move the needle sleeve, e.g. into the axial direction relative to the housing. The force of the needle sleeve spring may have to be overcome in order to move the needle sleeve into the housing. In a final position, e.g. after the drug delivery operation has been completed and the drug delivery device has been removed from the skin, the needle sleeve may be locked against a further movement with respect to the housing, such as by a locking mechanism. This may contribute to a safe handling of the drug delivery device after its usage by protecting the used needle.

In one embodiment, the drug delivery device comprises a retainer for locking the energy storage member in the initial state, the retainer being operatively coupled to the needle sleeve such that the retainer releases the energy storage member upon moving the needle sleeve into the housing. The retainer may be coupled to the housing and may be movable, e.g. rotatable, relative to the housing.

In one embodiment, the drug delivery device comprises a bearing for coupling the plunger rod arrangement to the stopper. The plunger rod arrangement, in particular the first segment, may be rotatable relative the stopper. The rotation of the first segment may be decoupled from the stopper by the bearing. The bearing may comprise a ball joint coupled to the plunger rod arrangement, in particular to the first segment.

In one embodiment, the housing is mushroom-shaped, the mushroom-shaped housing comprising the stem accommodating at least a part of the drug container and the cap accommodating the energy storage member. The mushroom-shaped housing is very easy to handle and to grab, and may be designed very compact.

We note that features described above and below in conjunction with different embodiments or aspects can be combined with one another, even if such a combination is not explicitly disclosed herein above or below. Further features, advantages and expediencies of the disclosure and, particularly, of the proposed concepts will become apparent from the following description of the exemplary embodiments in conjunction with the drawings.

Brief description of the drawings

Figure 1 illustrates a cross-sectional side view of an interior of an exemplary embodiment of a drug delivery device in a first state.

Figure 2 illustrates cross-sectional side view of the interior of the drug delivery device of figure 1 in a second state.

Figure 3 illustrates a bottom view of an exemplary embodiment of an energy storage member of the drug delivery device of figure 1.

Figure 4 illustrates cross-sectional side view of the interior of the drug delivery device of figure 1 in a third state.

Figure 5 illustrates cross-sectional side view of the interior of the drug delivery device of figure 1 in a fourth state. Figure 6 illustrates cross-sectional side view of the interior of the drug delivery device of figure 1 in a fifth state.

Figure 7 illustrates a cross-sectional side view of an interior of an exemplary embodiment of a drug delivery device.

Figure 8 illustrates a cross-sectional side view of an interior of an exemplary embodiment of a drug delivery device.

Figure 9 illustrates a perspective view of an exemplary embodiment of a drug delivery device and a hand of a user gripping the drug delivery device.

Figure 10 illustrates an exemplary embodiment of a needle sleeve and a stem in a first state.

Figure 11 illustrates the needle sleeve and the stem of figure 10 in a second state.

Figure 12 illustrates the needle sleeve and the stem of figure 10 in a third state.

Figure 13 illustrates the needle sleeve and the stem of figure 10 in a fourth state.

Figure 14 illustrates the needle sleeve and the stem of figure 10 in a fifth state.

Figure 15 illustrates the needle sleeve and the stem of figure 10 in a sixth state.

Figure 16 illustrates an expanded structural formula, molecular formula, and molecular weight of fitusiran.

Description of the exemplary embodiments

Identical elements, elements of the same kind and identically or similarly acting elements may be provided with the same reference numerals in the drawings.

Figure 1 illustrates a cross-sectional side view of an interior of an exemplary embodiment of a drug delivery device 20 in a first state. In particular, figure 1 shows the drug delivery device 20 in an initial or as delivered state. The drug delivery device 20 comprises a housing 22. The housing 22 is provided to retain and/or retains a drug container 24. A shape and/or size of the housing 22 may correspond to the shape and, respectively, size of a large mushroom comprising a stem 21 and a cap 23. The mushroom-shaped housing may be basically rotation symmetric with respect to an axis 45.

The drug container 24 may be arranged within the stem 21 , e.g. within a container socket 25 of the stem 21. The drug container 24 comprises a dispensing end 28 and a remote end 30 opposite the dispensing end 28. The drug container 24 comprises a chamber 26. A drug, i.e. a medicament, e.g. liquid medicament, may be arranged within the chamber 26. The chamber 26 is fluid-tight closed by a stopper 32. The stopper 32 is movably retained in the drug container 24 and may seal the drug container 24 remotely. The stopper 32 may be displaced towards an outlet of the drug container 24 at the dispensing end 28 to dispense the drug retained within the chamber 26 through the outlet. In particular, the stopper 32 may be movable in a dispensing direction 40 towards the dispensing end 28. If the stopper 32 is moved in the dispensing direction 40, the drug is dispensed through the outlet at the dispensing end 28. The dispensing direction 40 may be parallel to the axis 45.

The outlet of the drug container 24 at the dispensing end 28 may be formed or defined by the needle 27. The needle 27 may be an integral part of the drug container 24, e.g. (permanently or releasably) connected to a drug container body or separate from the drug container 24. In the first case, the drug container 24 may be a syringe. In the second case, the drug container 24 may be a cartridge. In case a cartridge is used as drug container 24, initially, the drug container 24 and the needle 27 may be fluidly disconnected, and a fluid communication between an interior of the drug container 24 and the needle 27 may be only established during operation of the drug delivery device 20. Further, instead of the one single needle 27 two separate needles may be arranged, one needle, e.g. needle 27, for piercing the skin and another needle (not shown) for piercing a septum of the drug container 24, wherein this other needle communicates with the needle 27 for piercing the skin.

A drive mechanism provided to drive a drug delivery operation is expediently provided in the housing 22. The drive mechanism comprises a plunger rod arrangement 35 for driving the stopper 32 of the drug container 24 in the dispensing direction, a drive member 39 for driving the plunger rod arrangement 35 and an energy storage member 42 coupled to the drive member 39 for rotating the drive member 39.

The plunger rod arrangement 35 may be coupled to the stopper 32 by a bearing 34. The plunger rod arrangement 35 may be configured as a telescopic plunger rod arrangement 35. The telescopic plunger rod arrangement 35 may comprise several segments, e.g. a first segment 37, a second segment 38, and optionally more corresponding segments (not shown). The first segment 37 may be coupled to the stopper 32 by the bearing 34. In particular, a first axial end of the first segment 37 may be coupled to the bearing 34, in particular to a ball joint 36 of the bearing.

The drive member 39 may be coupled to the housing 22 by a holder. The holder may be configured as suspension. The suspension may be configured to hold the drive member 39 such that the drive member 39 is axially fixed in the dispensing direction 40 and that the drive member 39 may be rotated around the axis 45. The drive member 39 is coupled to the plunger rod arrangement 35 by a threaded interface. The threaded interface is configured such that a rotation of the drive member 39 causes a translatory movement of the plunger rod arrangement 35, in particular of the first and second segment 37, 38 in the dispensing direction 40. In particular, the second segment 38 may be operatively coupled to the first segment 37 and the drive member 39 such that a rotation of the drive member 39 may be transferred to a translatory movement of the first segment 37 in the dispensing direction by the second segment 38. In particular, the second segment 38 may be operatively coupled to the first segment 37 and the drive member 39 such that the rotation of the drive member 39 firstly is transferred to a translatory movement of the second segment 38 in the dispensing direction 40, wherein the first segment 37 may be translatory moved together with the second segment 38 by the second segment 38, that the second segment 38 is rotated by the drive member 39 at the end of the translatory movement of the second segment 38, and that the rotation of the second segment 38 causes a further translatory movement of the first segment 37 in the dispensing direction 40.

The threaded interface may comprise a first threaded interface and a second threaded interface. The first threaded interface may be configured to operatively couple the first segment 37 to the second segment 38. The second threaded interface may be configured to operatively couple the second segment 38 to the drive member 39. The second threaded interface may be configured to couple the second segment 38 directly to the drive member 39. The second segment 38 can be in direct engagement with the drive member 39. The first threaded interface may comprise a first interface feature at the first segment 37 and a second interface feature at the second segment 38, the first interface feature being engaged with the second interface feature. Alternatively or additionally, the second threaded interface comprises a third interface feature at the second segment 38 and a fourth interface feature at the drive member 39, the third interface feature being engaged with the fourth interface feature. The first interface feature may be a first thread. Alternatively or additionally, the second interface feature may be a second thread. The third interface feature may be a third thread. Alternatively or additionally, the fourth interface feature may be a fourth thread. In other words, at least one of the first and second interface features may be a thread and/or at least one of the third and fourth interface features may be a thread. For example, each of the interface features may be a thread. Alternatively, that interface feature interacting with the corresponding thread of the same threaded interface and not being a thread may comprise one or more bars or pins which engage with the corresponding thread and may provide the same or equivalent functionality as a thread. Each of the threads may comprise one, two or more turns. If one of the threads comprises two or more turns, the starts and/or ends of the corresponding turns may be axially offset to each other. The threads may have different pitches, e.g. in order to steer or control the injection speed, in particular to provide different injection speeds. In particular, a first pitch may be provided in the first thread and a second pitch may be provided in the second thread, wherein the first pitch may be larger than the second pitch.

The second segment 38 and the drive member 39 may be configured such that the rotation of the drive member 39 is transferred to the translatory movement of the second segment 38 until an end of the third thread and/or an end of the fourth thread may be reached, and that a further rotation of the drive member 39 may be transferred to the rotation of the second segment 38. For example, the second segment 38 and the drive member 39 may be configured such that the rotation of the drive member 39 may be transferred to the translatory movement of the second segment 38 until an end of the third thread of the second segment 38 reaches an end of the fourth thread of the drive member 39 and that a further rotation of the drive member 39 may be transferred to the rotation of the second segment 38.

The drive member 39 has an axially extending drive member recess and the second segment 38 has an axially extending second segment recess. The second segment 38 is arranged within the drive member recess and the first segment 37 is arranged within the second segment recess. In this case, the first thread at the first segment is an external thread, the second thread at the second segment is an internal thread, the third thread at the second segment is an external thread, and the fourth thread at the drive member is an internal thread. The drive member recess and/or the second segment recess each are through-recesses extending through the drive member and/or, respectively, the second segment. Alternatively, the drive member recess and/or the second segment recess may be closed at their ends facing away from the stopper 32.

Alternatively, the first segment 37 may have an axially extending first segment recess and the second segment 38 may have an axially extending second segment recess, wherein the second segment 38 may be arranged within the first segment recess and the drive member 39 may be arranged within the second segment recess (not shown in the figures). In this case, the first thread at the first segment is an internal thread, the second thread at the second segment is an external thread, the third thread at the second segment is an internal thread, and the fourth thread at the drive member is an external thread. Each of the segment recesses may be a through-recess extending through the corresponding segment. Alternatively, the segment recesses may be closed at their ends facing the stopper 32.

The energy storage member 42 may be a flat spiral spring, which is coupled to the drive member 39. Other potential drive energy sources different from a spring may comprise an electrical power cell or battery for driving the plunger rod arrangement 35 by a motor or a reservoir suitable to provide gas pressure, where the gas pressure can be used to drive the drug delivery operation. The flat spiral spring may be is loaded and locked in the initial state of the drug delivery device 24. The energy storage member 42 is coupled to the drive member 39. In the initial and loaded state, energy is stored in the loaded energy storage member 42, i.e. the flat spiral spring is biased. If the energy storage member 42 is released, the energy stored in the energy storage member 42 is released and transferred to the drive member 39 such that the drive member 39 is rotated. If the drive member 39 rotates, the rotation is transferred via the threaded interface, in particular the first threaded interface, to the plunger rod arrangement 35.

The drive member 39 may be coupled to the energy storage member 42 such that a locking of the rotatable member 39 corresponds to a locking of the energy storage member 42. So, if the drive member 39 is held in its initial state, the energy storage member 42 may be held in its initial state also. To hold the drive member 39 in its initial state, the drug delivery device 24 may comprise a retainer 44. The retainer 44 for locking the energy storage member 42 in the initial state may be operatively coupled to a needle sleeve 46 such that the retainer 44 releases the energy storage member 42 upon moving the needle sleeve 46 into the housing. The retainer 44 may be coupled to the housing 22 and may be movable, e.g. rotatable, relative to the housing 22.

The needle sleeve 46 may be arranged for protecting the needle 27 of the drug delivery device 20. The needle sleeve 46 may protrude from the housing 22 in the initial state. The needle sleeve 46 may be movable relative to the housing 22 from an initial position or first position in the initial state to a second position or trigger position. The needle sleeve 46 may provide a bearing surface for being in contact with the injection site during the dispensing operation, the bearing surface facing away from the cap 23. The needle sleeve 46 may comprise a release member 56 for operating the retainer 44. The release member 56 may be formed as a protrusion, which protrudes from the rest of the needle sleeve 46 in radial direction. The release member 56 may be formed at a side of the needle sleeve 46 facing away from the bearing surface.

The needle sleeve 46 may be provided to extend beyond a tip of the needle 27, which may protrude from the bottom of the housing 22 before the drug delivery operation is commenced. The needle sleeve 46 may be movably arranged within the stem 21. In particular, the needle sleeve 46 may be moved parallel to the axis 45 and as such may be further introduced into the stem 21. During this movement, e.g. before the needle sleeve 46 reaches the second position, the needle 27 may pierce the skin of the user. The needle sleeve 46 may be pushed into the stem 21 when the drug delivery device 20 is arranged on the injection site, e.g. the skin of the user. In particular, if the drug delivery device 20 is positioned on the skin with a bottom surface of the stem 21 touching the skin, the needle sleeve 46 is pushed into the stem 21. If the needle sleeve 46 is pushed into the stem 21 , the needle 27 is exposed and may pierce the skin. The bottom surface of the stem 21 may provide at least a part of a bearing surface for being in contact with the injection site during the dispensing operation.

The needle sleeve 46 may serve as a trigger member of the drug delivery device 20. The needle sleeve 46 as trigger member, when displaced from the initial or first position depicted in figures 1 and 2 to a second or trigger position (see figures 4 and 5), may automatically initialize the drug delivery operation, preferably when it is in the second position. The needle sleeve 46, when moved from the first position to the second position and expediently when in the second position, may initiate the drug delivery operation via releasing the retainer 44. Operating the retainer 44 to initiate the drug delivery operation may only be possible when the needle sleeve 46 is in the second position. In particular, if the needle sleeve 46 is pushed into the stem 21 , the release member 56 may act on the retainer 44 such that the retainer 44 releases the locked and biased energy storage member 42. Then, the energy storage member 42 rotates the drive member 39 such that the first segment 37 and thereby the stopper 32 are moved in the dispensing direction 40. So, the stopper 32 may be moved only, if the drug delivery device 20 is positioned on the skin and the needle sleeve 46 exposes the needle 27.

The needle 27 may be protected by a needle shield 50 prior to its use. The needle shield 50 may cover the needle 27 until it is removed by hand. The needle shield 50 may comprise one or more engaging feature 52, which may interact with an engaging recess 54 of the needle sleeve 46. For example, the engaging features 52 may comprise one or more protrusions and/or pins, which may be arranged within the engaging recess 54 for holding the needle shield 50 at the needle sleeve 46. The needle shield 50 may be removed from the needle sleeve 46 by rotating the needle shield 50 relative to the needle sleeve 46 and by removing the engaging feature 52 from the engaging recess 54 at the end of the rotation. The needle shield 50 may comprise a ring 59 facing away from the needle sleeve 46, the ring 59 providing a comfortable gripping structure for gripping and removing the needle shield 50. Alternatively, the needle shield 50 and the ring 59 may be configured such that the needle shield 50 may be simply removed by pulling the ring 59, in particular without any rotation. Alternatively or additionally, for removing the needle shield 50, an end cap may be coupled to the needle shield, e.g. via a gripping component or grabber. This may result in an end cap-grabber-needle shield configuration. The needle shield 50 may be removed from the needle via the end cap e.g. by pulling the end cap with the gripping component interlocking with the needle shield 50. Removing the end cap (and the needle shield) may involve no rotation of the end cap (and the needle shield), i.e. just axial movement. .

A gripping ring 58 may be arranged at and/or at least partly within the cap 23. For example, the cap 23 may provide a groove in which the gripping ring 58 is arranged such that at least an outer part of the gripping ring 58 may protrude from the groove. The gripping ring 58 may comprise a material which provides a strong frictional force when it is gripped by a hand of the user. The gripping ring 58 may comprise or may be made from rubber.

The drug delivery device 20 is an autoinjector. The energy for driving the drug delivery operation in an autoinjector may be provided by components integral to the drug delivery device 20 and does not have to be loaded into the drug delivery device 20 by the user during the operation as is the case in many spring driven pen-type variable dose injectors, where, usually, the energy is loaded into a spring by the user during a dose setting procedure. The drug delivery device 20 expediently is a single shot device, i.e. it is provided to dispense only one dose. The drug delivery device 20 may be a disposable drug delivery device 20, that is to say a drug delivery device 20 which is disposed of after its use. The drug container 24 and/or the needle 27 may be secured within the drug delivery device 20, e.g. within the housing 22. So, the user may have to perform the movement for piercing the skin with the needle 27 by placing the drug delivery device 20 on the skin.

Figure 2 illustrates cross-sectional side view of the interior of the drug delivery device 20 of figure 1 in a second state. In the second state, the drug delivery device 20 is still in its initial position. However, in the second state, the needle shield 50 is removed from the needle 27 and the needle sleeve 46.

Figure 3 illustrates a bottom view of an exemplary embodiment of the energy storage member 42 of the drug delivery device 20 of figure 1. In particular, figure 3 illustrates a bottom view of a cross-section of the drug delivery device 20 along line III. shown in figure 2. From figure 3 it may be seen that the energy storage member 42 may comprise a hook 60, which is hooked into a corresponding hook recess of the drive member 39. A force of rotation provided by the energy storage member 42 may be transferred to a rotational movement of the drive member 39 by the hook 60. Figure 4 illustrates cross-sectional side view of the interior of the drug delivery device 20 of figure 1 in a third state. In the third state, the needle sleeve 46 is in its second position and triggers the retainer 44. For example, the needle sleeve 46 has been moved into its second position by placing the drug delivery device 20 on the injection site and by pressing the drug delivery device 20 against the injection site while overcoming the force of and biasing the needle sleeve spring 48. The triggered retainer 44 releases the energy storage member 42. So, in the third state, the energy of the energy storage member 42 is at least partly released such that the energy storage member 42 rotates the drive member 39. In particular, in the third state, the drive member 39 already has been rotated so far that the second segment 38 has been translatory moved in the dispensing direction 40 by the rotating drive member 39 until an end of a range of the second threaded interface, e.g. the third and/or fourth interface feature, is reached and the second segment 38 may not be translatory moved further. Because of the coupling between the first and second segment 37, 38, the first segment 37 has been translatory moved in the dispensing direction 40 also, together with the second segment 38. Further, in the third state, the stopper 32 has been moved in the dispensing direction 40 by the first segment 37 such that the dispensing operation is carried out. In the moment in which the second segment 38 may not be translatory moved further, the second segment 38 starts rotating.

Figure 5 illustrates cross-sectional side view of the interior of the drug delivery device 20 of figure 1 in a fourth state. In the fourth state, the second segment 38 has been rotated by the rotating drive member 39. If the second segment 38 rotates, the first segment 37 is translatory moved in the dispensing direction 40 because of the first threaded interface. In particular, in the fourth state, the first segment 37 has translatory moved so far that the stopper 32 already completed its full stroke and may not be moved further in the dispensing direction 40. So, in the fourth state, an end of the dispensing operation is reached and a given dose of the drug has been dispensed.

Figure 6 illustrates cross-sectional side view of the interior of the drug delivery device 20 of figure 1 in a fifth state. In the fifth state, the needle sleeve 46 has been pushed out of the stem 21 by the needle sleeve spring 48 such that the needle sleeve 46 protects the needle 27. The stem 21 for guiding the needle sleeve 46 and the needle sleeve 46 may be configured such that the needle sleeve 46 may not be pushed into the stem 21 anymore after the dispensing operation is finished and the drug delivery device 20 is removed from the injection site. The corresponding structure is explained in the following with respect to figures 10 to 13.

Figure 7 illustrates a cross-sectional side view of an interior of an exemplary embodiment of a drug delivery device 20. The drug delivery device shown in figure 7 widely corresponds to the above drug delivery device 20. Therefore, only those features are discussed in the following, in which the drug delivery device 20 shown in figure 7 differs from the above drug delivery device 20. The drug delivery device 20 comprises a stabilizing cone 62. The stabilizing cone 62 protrudes outwardly from the needle sleeve 46. The stabilizing cone 62 provides a bearing surface, which is bigger than the bearing surface of the needle sleeve 46. Both bearing surfaces together provide an even larger bearing surface. The larger the bearing surface is, the more stable the drug delivery device 20 may be arranged on the injection site.

Figure 8 illustrates a cross-sectional side view of an interior of an exemplary embodiment of a drug delivery device 20. The drug delivery device 20 shown in figure 8 widely corresponds to one of the above drug delivery devices 20. Therefore, only those features are discussed in the following, in which the drug delivery device 20 shown in figure 8 differs from the above drug delivery devices 20. The stem 21 of the drug delivery device 20 of figure 8 is cone-shaped and comprises a large bearing surface facing the injection site, if the drug delivery device 20 is arranged on the injection site. The cone-shaped stem 21 provides a bearing surface, which is bigger than the bearing surface of the needle sleeve 46. Both bearing surfaces together provide an even larger bearing surface. The larger the bearing surface is, the more stable the drug delivery device 20 may be arranged on the injection site.

Figure 9 illustrates a perspective view of an exemplary embodiment of a drug delivery device 20 and a hand 66 of a user gripping the drug delivery device 20. The drug delivery device 20 shown in figure 9 may correspond to one of the above drug delivery devices 20. Therefore, only those features are discussed in the following, which have not been discussed above. The drug delivery device 20 may comprise finger grooves 64 at the cap 23. The finger grooves 64 may be provided for placing at least some of the fingers of the hand 66 on the cap 23. The finger grooves 64 contribute to an easy and comfortable handling of the drug delivery device 20.

Figure 10 illustrates an exemplary embodiment of the needle sleeve 46 and the stem 21 in a first state. In particular, figure 10 illustrates a side view of the needle sleeve 46 and a cutaway side view of the stem 21 in the first state. In the first state of the needle sleeve 46, the drug delivery device 20 is not yet arranged on the skin of the user and the needle sleeve 46 protects the needle 27.

The needle sleeve 46 comprises a guide pin 90, a torsion protection 92, and flexible bars 94. The guide pin 90 protrudes from an outer wall of the needle sleeve 46 outwardly. The flexible bars 94 are separated by through-recesses extending through the wall of the needle sleeve 46. So, the flexible bars 94 and the body of the needle sleeve 46 may be made of one piece. The torsion protection 92 may comprise a bar extending vertically in figure 12. The stem 21 comprises a first channel 96 and a second channel 104. The first channel 96 extends firstly with a slide inclination against the vertical direction and then basically verticality towards a bent 98 of the first channel 96 and then back towards a dead end 100 of the first channel 96. The dead end 100 is separated from the rest of the first channel 96 by a barb 102. In the first state of the needle sleeve 46, the guide pin 90 is arranged in a part of the first channel 96 below the dead end 100 and at the beginning of the inclination of the first channel 96.

The torsion protection 92 of the needle sleeve 46 is arranged within the second channel 104 and is guided by the second channel 104 during the movement of the needle sleeve 46 relative to the stem 21. The second channel 104 is straight and parallel to the axis 45 and as such parallel to the moving direction of the needle sleeve 46. The torsion protection 92 within the second channel 104 serves as a protection of the needle sleeve 46 against a rotation of the needle sleeve 46.

Figure 11 illustrates the needle sleeve 46 and the stem 21 of figure 10 in a second state. In the second state of the needle sleeve 46, the needle sleeve 46 may be partly arranged within the stem 21, e.g. because of the drug delivery device 20 being partly arranged on the skin of the user. In the second state of the needle sleeve 46, the guide pin 90 is moved within the first channel 96 towards the bent 98. When the guide pin 90 passes the inclination of the first channel 96, an upper portion of the needle sleeve 46 is moved perpendicular to the moving direction of the needle sleeve 46 and the flexible bars 94 are flexed, because the rest of the needle sleeve 46 is secured against any rotation by the torsion protection 92 within the second channel 104. Then, the flexible bars 94 are biased.

Figure 12 illustrates the needle sleeve 46 and the stem 21 of figure 10 in a third state. In the third state of the needle sleeve 46, the needle sleeve 46 is pressed into the stem 21 completely, e.g. because of the user arranging the drug delivery device 20 on his/her skin. So, in the third state of the needle sleeve 46, the needle 27 is exposed by the needle sleeve 46. In this situation, the guide pin 90 has arrived in the bent 98 of the first channel 96 and may be moved perpendicular to the moving direction of the needle sleeve 46 within the bent 98. In the third state of the needle sleeve 46, the biased flexible bars 94 force the guide pin 90 through the bent 98.

Figure 13 illustrates the needle sleeve 46 and the stem 21 of figure 10 in a fourth state. In the fourth state of the needle sleeve 46, the flexible bars 94 are released and the guide pin 90 has moved perpendicular to the moving direction of the needle sleeve 46 within the bent 98. Figure 14 illustrates the needle sleeve 46 and the stem 21 of figure 10 in a fifth state. In the fifth state of the needle sleeve 46, the drug delivery device 20 may be partly removed from the skin of the user. The guide pin 90 is forced over the barb 102 of the first channel 100 such that the flexible bars 94 are biased again. When the drug delivery device 20 is removed from the skin of the user, the needle sleeve 46 may be pushed out of the housing 22, for example by the needle sleeve spring 48 such that the guide pin 90 is forced over the barb.

Figure 15 illustrates the needle sleeve 46 and the stem 21 of figure 10 in a sixth state. In the sixth state of the needle sleeve 46, the drug delivery device 20 may be completely removed from the skin of the user. The needle sleeve 46 may completely cover the needle 27. The guide pin 90 snaps into the dead end 100 of the first channel 96 such that the needle sleeve 46 is fixedly engaged to the stem 21.

The terms “drug” or “medicament” are used synonymously herein and describe a pharmaceutical formulation containing one or more active pharmaceutical ingredients or pharmaceutically acceptable salts or solvates thereof, and optionally a pharmaceutically acceptable carrier. An active pharmaceutical ingredient (“API”), in the broadest terms, is a chemical structure that has a biological effect on humans or animals. In pharmacology, a drug or medicament is used in the treatment, cure, prevention, or diagnosis of disease or used to otherwise enhance physical or mental well-being. A drug or medicament may be used for a limited duration, or on a regular basis for chronic disorders.

As described below, a drug or medicament can include at least one API, or combinations thereof, in various types of pharmaceutical formulations, for the treatment of one or more diseases. Examples of API may include small molecules having a molecular weight of 500 Da or less; 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 drugs are also contemplated.

The drug or medicament may be contained in a primary package or “drug reservoir” adapted for use with a drug delivery device. The drug reservoir 101a may be, e.g., a cartridge, syringe, reservoir, or other solid or flexible vessel (bag) configured to provide a suitable chamber for storage (e.g., short- or long-term storage) of one or more drugs. 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 reservoir may be or may include a dual-chamber cartridge configured to store two or more components of the pharmaceutical formulation to-be-administered (e.g., an API and a diluent, or two different drugs) separately, one in each chamber. In such instances, the two chambers of the dualchamber cartridge may be configured to allow mixing between the two or more components 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 drugs or medicaments contained in the drug delivery devices as described herein can be used for the treatment and/or prophylaxis of many different types of medical disorders.

Examples of 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 examples of disorders are acute coronary syndrome (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and/or rheumatoid arthritis. Examples of APIs and drugs are those as described in handbooks such as Rote Liste 2014, for example, without limitation, main groups 12 (antidiabetic drugs) or 86 (oncology drugs), and Merck Index, 15th edition.

Examples of APIs for the treatment and/or prophylaxis of type 1 or type 2 diabetes mellitus or complications associated with type 1 or type 2 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 terms “analogue” and “derivative” refers to a polypeptide which has a molecular structure which formally can be derived from the structure of a naturally occurring peptide, for example that of human insulin, by deleting and/or exchanging at least one amino acid residue occurring in the naturally occurring peptide and/or by adding at least one amino acid residue. The added and/or exchanged amino acid residue can either be codable amino acid residues or other naturally occurring residues or purely synthetic amino acid residues. Insulin analogues are also referred to as "insulin receptor ligands". In particular, the term derivative” refers to a polypeptide which has a molecular structure which formally can be derived from the structure of a naturally occurring peptide, for example that of human insulin, in which one or more organic substituent (e.g. a fatty acid) is bound to one or more of the amino acids. Optionally, one or more amino acids occurring in the naturally occurring peptide may have been deleted and/or replaced by other amino acids, including non-codeable amino acids, or amino acids, including non-codeable, have been added to the naturally occurring peptide.

Examples of insulin analogues are Gly(A21), Arg(B31), Arg(B32) human insulin (insulin glargine); Lys(B3), Glu(B29) human insulin (insulin glulisine); Lys(B28), Pro(B29) human insulin (insulin lispro); Asp(B28) human insulin (insulin aspart); human insulin, wherein proline in position B28 is replaced by Asp, Lys, Leu, Vai or Ala and wherein in position B29 Lys may be replaced by Pro; Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human insulin.

Examples of insulin derivatives are, for example, B29-N-myristoyl-des(B30) human insulin, Lys(B29) (N- tetradecanoyl)-des(B30) human insulin (insulin detemir, Levemir®); 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-omega- carboxypentadecanoyl-gamma-L-glutamyl-des(B30) human insulin (insulin degludec, Tresiba®); B29-N-(N-lithocholyl-gamma-glutamyl)-des(B30) human insulin; B29-N-(w- carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(w-carboxyheptadecanoyl) human insulin.

Examples of GLP-1 , GLP-1 analogues and GLP-1 receptor agonists are, for example, Lixisenatide (Lyxumia®), Exenatide (Exendin-4, Byetta®, Bydureon®, a 39 amino acid peptide which is produced by the salivary glands of the Gila monster), Liraglutide (Victoza®), Semaglutide, Taspoglutide, Albiglutide (Syncria®), Dulaglutide (Trulicity®), rExendin-4, CJC- 1134-PC, PB-1023, TTP-054, Langlenatide / HM-11260C (Efpeglenatide), HM-15211, CM-3, GLP-1 Eligen, ORMD-0901, NN-9423, NN-9709, NN-9924, NN-9926, NN-9927, Nodexen, Viador-GLP-1 , CVX-096, ZYOG-1, ZYD-1 , GSK-2374697, DA-3091, MAR-701 , MAR709, ZP- 2929, ZP-3022, ZP-DI-70, TT-401 (Pegapamodtide), BHM-034. MOD-6030, CAM-2036, DA- 15864, ARI-2651 , ARI-2255, Tirzepatide (LY3298176), Bamadutide (SAR425899), Exenatide- XTEN and Glucagon-Xten.

An example of an oligonucleotide is, for example: mipomersen sodium (Kynamro®), a cholesterol-reducing antisense therapeutic for the treatment of familial hypercholesterolemia or RG012 for the treatment of Alport syndrom. Examples of DPP4 inhibitors are Linagliptin, Vildagliptin, Sitagliptin, Denagliptin, Saxagliptin, Berberine.

Examples of hormones include hypophysis hormones or hypothalamus hormones or regulatory active peptides and their antagonists, such as Gonadotropine (Follitropin, Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin, Buserelin, Nafarelin, and Goserelin.

Examples of polysaccharides include a glucosaminoglycane, a hyaluronic acid, a heparin, a low molecular weight heparin or an ultra-low molecular weight heparin or a derivative thereof, or a sulphated polysaccharide, e.g. a poly-sulphated form of the above-mentioned polysaccharides, and/or a pharmaceutically acceptable salt thereof. An example of a pharmaceutically acceptable salt of a poly-sulphated low molecular weight heparin is enoxaparin sodium. An example of a hyaluronic acid derivative is Hylan G-F 20 (Synvisc®), a sodium hyaluronate.

The term “antibody”, as used herein, refers to an immunoglobulin molecule or an antigenbinding portion thereof. Examples of antigen-binding portions of immunoglobulin molecules include F(ab) and F(ab')2 fragments, 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 term antibody also includes an antigen-binding molecule based on tetravalent bispecific tandem immunoglobulins (TBTI) and/or a dual variable region antibody-like binding protein having cross-over binding region orientation (CODV).

The terms “fragment” or “antibody fragment” refer to a polypeptide derived from an antibody polypeptide molecule (e.g., an antibody heavy and/or light chain polypeptide) that does not comprise a full-length antibody polypeptide, but that still comprises at least a portion of a full- length antibody polypeptide that is capable of binding to an antigen. Antibody fragments can comprise a cleaved portion of a full length antibody polypeptide, although the term is not limited to such cleaved fragments. Antibody fragments that are useful in the present invention include, for example, Fab fragments, F(ab')2 fragments, scFv (single-chain Fv) fragments, linear antibodies, monospecific or multispecific antibody fragments such as bispecific, trispecific, tetraspecific and multispecific antibodies (e.g., diabodies, triabodies, tetrabodies), monovalent or multivalent antibody fragments such as bivalent, trivalent, tetravalent and multivalent antibodies, minibodies, chelating recombinant antibodies, tribodies or bibodies, intrabodies, nanobodies, small modular immunopharmaceuticals (SMIP), binding-domain immunoglobulin fusion proteins, camelized antibodies, and VHH containing antibodies. Additional examples of antigen-binding antibody fragments are known in the art.

The terms “Complementarity-determining region” or “CDR” refer to short polypeptide sequences within the variable region of both heavy and light chain polypeptides that are primarily responsible for mediating specific antigen recognition. The term “framework region” refers to amino acid sequences within the variable region of both heavy and light chain polypeptides that are not CDR sequences, and are primarily responsible for maintaining correct positioning of the CDR sequences to permit antigen binding. Although the framework regions themselves typically do not directly participate in antigen binding, as is known in the art, certain residues within the framework regions of certain antibodies can directly participate in antigen binding or can affect the ability of one or more amino acids in CDRs to interact with antigen.

Examples of antibodies are anti PCSK-9 mAb (e.g., Alirocumab), anti IL-6 mAb (e.g., Sarilumab), and anti IL-4 mAb (e.g., Dupilumab).

Further examples of APIs for the prophylaxis of hemophilia A or B, with or without inhibitors, include an siRNA targeting antithrombin. An example of an siRNA targeting antithrombin is fitusiran. The term “prophylaxis” and “prophylactic treatment” are used interchangeably herein

Pharmaceutically acceptable salts of any API described herein are also contemplated for use in a drug or medicament in a drug delivery device. Pharmaceutically acceptable salts are for example acid addition salts and basic salts.

Those of skill in the art will understand that modifications (additions and/or removals) of various components of the APIs, pharmaceutical formulations, apparatuses, methods, systems and embodiments described herein may be made without departing from the full scope and spirit of the present invention, which encompass such modifications and any and all equivalents thereof.

An example drug delivery device may involve a needle-based injection system as described in Table 1 of section 5.2 of ISO 11608-1 :2014(E). As described in ISO 11608-12014(E), needlebased injection systems may be broadly distinguished into multi-dose container systems and single-dose (with partial or full evacuation) container systems. The container may be a replaceable container or an integrated non-replaceable container. As further described in ISO 11608-1 :2014(E), a multi-dose container system may involve a needle-based injection device with a replaceable container. In such a system, each container holds multiple doses, the size of which may be fixed or variable (pre-set by the user). Another multi-dose container system may involve a needle-based injection device with an integrated non-replaceable container. In such a system, each container holds multiple doses, the size of which may be fixed or variable (pre-set by the user).

As further described in ISO 11608-1 :2014(E), a single-dose container system may involve a needle-based injection device with a replaceable container. In one example for such a system, each container holds a single dose, whereby the entire deliverable volume is expelled (full evacuation). In a further example, each container holds a single dose, whereby a portion of the deliverable volume is expelled (partial evacuation). As also described in ISO 11608-1 :2014(E), a single-dose container system may involve a needle-based injection device with an integrated non-replaceable container. In one example for such a system, each container holds a single dose, whereby the entire deliverable volume is expelled (full evacuation). In a further example, each container holds a single dose, whereby a portion of the deliverable volume is expelled (partial evacuation).

Fitusiran as the API for the medicament in the device

Fitusiran is a synthetic, chemically modified double-stranded small interfering RNA (siRNA) oligonucleotide covalently linked to a tri-antennary N-acetyl-galactosamine (GalNAc) ligand targeting AT3 mRNA in the liver, thereby suppressing the synthesis of antithrombin. See, e.g., Pasi et al., N Engl J Med. (2017) 377(9):819-28. The nucleosides in each strand of fitusiran are connected through either 3’-5’ phosphodiester or phosphorothioate linkages, thus forming the sugar-phosphate backbone of the oligonucleotide.

The sense strand and the antisense strand contain 21 and 23 nucleotides, respectively. The 3’ end of the sense strand is conjugated to the GalNAc containing moiety (referred to herein as L96) through a phosphodiester linkage. The sense strand contains two consecutive phosphorothioate linkages at its 5’ end. The antisense strand contains four phosphorothioate linkages, two at the 3’ end and two at the 5’ end. The 21 nucleotides of the sense strand hybridize with the complementary 21 nucleotides of the antisense strand, thus forming 21 nucleotide base pairs and a two-base overhang at the 3’-end of the antisense strand. See also U.S. Pat. 9,127,274, U.S. Pat. 11,091 ,759, US2020/0163987A1, and WO 2019/014187, the entire contents each of which are expressly incorporated herein by reference.

The two nucleotide strands of fitusiran are shown below: sense strand: 5’Gf-ps-Gm-ps-Uf-Um-Af-Am-Cf-Am-Cf-Cf-Af-Um-Uf-Um-Af-Cm-Uf-Um-Cf-Am-

Af-L96 3’ (SEQ ID N0:1), and antisense strand: 5’ Um-ps-Uf-ps-Gm-Af-Am-Gf-Um-Af-Am-Af-Um-Gm-Gm-Uf-Gm-Uf-Um-Af-

Am-Cf-Cm-ps-Am-ps-Gm 3’ (SEQ ID N0:2), wherein

Af = 2’ -deoxy- 2’-fluoroadenosine

Cf = 2’ -deoxy- 2’-fluorocytidine

Gf = 2’ -deoxy- 2’-fluoroguanosine

Uf = 2’ -deoxy- 2’-fluorouridine

Am = 2’-O-methyladenosine

Cm = 2’-O-methylcytidine

Gm = 2’-O-methylguanosine

Um = 2’-O-methyluridine

(hyphen) = 3’-5’ phosphodiester linkage sodium salt

“-ps-” = 3’-5’ phosphorothioate linkage sodium salt and wherein L96 has the following formula:

As used herein, the terms 2’ -deoxy- 2’-fluoroadenosine and 2’-fluoroadenosine may be used interchangeably.

As used herein, the terms 2’ -deoxy- 2’-fluorocytidine and 2’-fluorocytidine may be used interchangeably.

As used herein, the terms 2’ -deoxy- 2’-fluoroguanosine and 2’-fluoroguanosine may be used interchangeably.

As used herein, the terms 2’ -deoxy- 2’-fluorouridine and 2’-fluorouridine may be used interchangeably.

The expanded structural formula, molecular formula, and molecular weight of fitusiran are shown in Figure 16.

The structure of fitusiran can also be described using the following diagram, wherein the X is O:

Fitusiran is shown in Figure 16 in sodium salt form.

In some embodiments, the device delivers fitusiran in an aqueous solution, wherein fitusiran is at a concentration of about 40 to about 200 mg/mL (e.g., about 50 to about 150 mg/mL, about 80 to about 110 mg/mL, or about 90 to about 110 mg/mL). As used herein, values intermediate to recited ranges and values are also intended to be part of this disclosure. In addition, ranges of values using a combination of any of recited values as upper and/or lower limits are intended to be included. In further embodiments, the pharmaceutical formulation comprises fitusiran in an aqueous solution at a concentration of about 40, about 50, about 75, about 100, about 125, about 150, or about 200 mg/mL. In certain embodiments, fitusiran is provided in an aqueous solution at a concentration of about 100 mg/mL.

The term “deliver,” “delivers,” or “delivering” is intended to mean “administer,” “administers,” or “administering.”

Unless specifically stated or otherwise evident from the context, as used herein, the term “approximately” or "about" refers to a value that is within an acceptable error range for a particular value determined by a person of ordinary skill, a portion of which will depend on how the measurement or determination is made. For example, “approximately” or "about" may mean a range of up to 10% (ie, ±10%). Therefore, “approximately” or "about" can be understood as greater than or less than 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, 0.1 %, 0.05%, 0.01%, or 0.001%. When a specific value is provided in this disclosure, unless otherwise stated, the meaning of “approximately” or "about" should be assumed to be within an acceptable error range for that specific value.

While the fitusiran dosage weight described herein refers to the weight of fitusiran free acid (active moiety), administration of fitusiran to patients herein refers to administration of fitusiran sodium (drug substance) provided in a pharmaceutically suitable aqueous solution (e.g., a phosphate-buffered saline at a physiological pH). For example, about 100 mg/mL fitusiran means about 100 mg of fitusiran free acid (equivalent to about 106 mg fitusiran sodium, the drug substance) per ml_. Unless otherwise indicated, a fitusiran weight recited in the present disclosure is the weight of fitusiran free acid (the active moiety).

In some embodiments, a pharmaceutical formulation in the device comprises fitusiran in a phosphate-buffered saline. The phosphate concentration in the solution may be about 1 to about 10 mM (e.g., about 2, about 3, about 4, about 5, about 6, about 7, about 8, or about 9 mM), with a pH of about 6.0-8.0. The pharmaceutical formulations herein may include a stabilizing agent such as EDTA. The pharmaceutical formulations may be preservative-free. In some embodiments, the fitusiran pharmaceutical formulation in the device is preservative-free and comprises, consists of, or consists essentially of about 100 mg of fitusiran per mL of an approximately 5 mM phosphate buffered saline (PBS) solution. In some embodiments, the fitusiran pharmaceutical formulation in the device is preservative-free and comprises, consists of, or consists essentially of fitusiran in an approximately 5 mM phosphate buffered saline (PBS) solution. The PBS solution is composed of sodium chloride, dibasic sodium phosphate (heptahydrate), and monobasic sodium phosphate (monohydrate). Sodium hydroxide solution and diluted phosphoric acid may be used to adjust the pH of the pharmaceutical formulation to about 7.0 or about 7.1.

In some embodiments, the fitusiran pharmaceutical formulation in the device for subcutaneous delivery contains fitusiran in a 5 mM phosphate buffered saline having 0.64 mM Na^PC , 4.36 mM Na2HPC>4, and 84 mM NaCI at pH 7.0. In certain embodiments, the pharmaceutical formulation of fitusiran solution for subcutaneous delivery is shown in Table 1 below:

Table 1. Exemplary Fitusiran Pharmaceutical Formulation

*q.s.: quantum satis

In some embodiments, the pharmaceutical formulation of fitusiran solution for subcutaneous delivery with the device can be described as shown in Table 2 below.

Table 2. Exemplary Fitusiran Pharmaceutical Formulation

In some embodiments, the device may be used to deliver a single dose of fitusiran wherein the single dose comprises about 20 to about 80 mg of fitusiran (e.g., about 20 mg, about 25 mg, about 30 mg, about 40 mg, about 50 mg, or about 80 mg). In some embodiments, the device may be used to deliver single dose of fitusiran, wherein the single dose comprises about 1 to about 30 mg of fitusiran (e.g., about 1.25 mg, about 2.5 mg, about 5 mg, about 10 mg, about 20 mg, or about 30 mg).

In one embodiment, the device may be used to deliver a single dose of about 80 mg of fitusiran. In one embodiment, the device may be used to deliver a single dose of about 50 mg of fitusiran. In one embodiment, the device may be used to deliver a single dose of about 20 mg of fitusiran. In one embodiment, the device may be used to deliver a single dose of about 30 mg of fitusiran. In one embodiment, the device may be used to deliver a single dose of about 10 mg of fitusiran. In one embodiment, the device may be used to deliver a single dose of about 5 mg of fitusiran. In one embodiment, the device may be used to deliver a single dose of about 2.5 mg of fitusiran. In one embodiment, the device may be used to deliver a single dose of about 1.25 mg of fitusiran.

In some embodiments, the single dose of fitusiran may be delivered in about 0.5 mL to about 1 mb delivery volumes (e.g., about 0.5 mb, about 0.6 mb, about 0.7 mb, about 0.8 mb, about 0.9 mb, or about 1 mb). Other delivery volumes described herein may also be used. In one embodiment, the device may be used to deliver a single dose of about 80 mg of fitusiran in about 0.8 mb (about 100 mg fitusiran/mL). In one embodiment, the device may be used to deliver a single dose of about 50 mg of fitusiran in about 0.5 mL (about 100 mg fitusiran/mL). In one embodiment, the device may be used to deliver a single dose of about 20 mg of fitusiran in about 0.5 mL (about 40 mg fitusiran/mL). In one embodiment, the device may be used to deliver a single dose of about 30 mg of fitusiran in about 0.5 mL (about 60 mg fitusiran/mL). In one embodiment, the device may be used to deliver a single dose of about 10 mg of fitusiran in about 0.5 mL (about 20 mg fitusiran/mL). In one embodiment, the device may be used to deliver a single dose of about 5 mg of fitusiran in about 0.5 mL (about 10 mg fitusiran/mL). In one embodiment, the device may be used to deliver a single dose of about 2.5 mg of fitusiran in about 0.5 mL (about 5 mg fitusiran/mL). In one embodiment, the device may be used to deliver a single dose of about 1.25 mg of fitusiran in about 0.5 mL (about 2.5 mg fitusiran/mL).

In one embodiment, the device delivers fitusiran at a prophylactically effective amount to prophylactically treat hemophilia (e.g., hemophilia A or B, in a patient with or without inhibitors) in a patient in need thereof (e.g., a hemophilia A or B patient, with or without inhibitors). “Prophylactically effective amount” refers to the amount of fitusiran that helps the patient with hemophilia A or B, with or without inhibitors to achieve a desired clinical endpoint such as reducing the Annualized Bleeding Rate (ABR), Annualized Joint Bleeding Rate (AjBR), Annualized Spontaneous Bleeding Rate (AsBR), or the frequency of bleeding episodes. As used herein in the context of fitusiran, the term “treat” “treating,” or “treatment” includes prophylactic treatment of the disease and refers to achievement of a desired clinical endpoint.

A hemophilia A or B patient with inhibitors refers to a patient who has developed alloantibodies to the factor he/she has previously received (e.g., factor VIII for hemophilia A patients or factor IX for hemophilia B patients). A hemophilia A or B patient with inhibitors may become refractory to replacement coagulation factor therapies. A patient without inhibitors refers to a patient who does not have such alloantibodies. The present treatment methods may be beneficial for hemophilia A patients with inhibitors, as well as for hemophilia B patients with inhibitors.

As used herein, a patient with “hemophilia A or B, with or without inhibitors,” or refers to 1 ) a hemophilia A patient with inhibitors, or 2) a hemophilia B patient with inhibitors, 3) a hemophilia A patient without inhibitors, or 4) a hemophilia B patient without inhibitors. As used herein, a patient refers to a human patient. A patient can also refer to a human subject.

In some embodiments, the device may be used to prophylactically treat a patient with hemophilia A or B, with or without inhibitors, with a subcutaneous dose of about 50 mg of fitusiran once every two months (or every eight weeks). In other embodiments, the device may be used to prophylactically treat a patient with hemophilia A or B, with or without inhibitors, with a subcutaneous dose of about 50 mg of fitusiran every month (or every four weeks). In yet other embodiments, the device may be used to prophylactically treat a patient with hemophilia A or B, with or without inhibitors, with a subcutaneous dose of about 80 mg of fitusiran every two months (or every eight weeks). In yet other embodiments, the device may be used to prophylactically treat a patient with hemophilia A or B, with or without inhibitors, with a subcutaneous dose of about 80 mg of fitusiran every month (or every four weeks). In yet other embodiments, the device may be used to prophylactically treat a patient with hemophilia A or B, with or without inhibitors, with a subcutaneous dose of about 20 mg of fitusiran every two months (or every eight weeks). In yet other embodiments, the device may be used to prophylactically treat a patient with hemophilia A or B, with or without inhibitors, with a subcutaneous dose of about 20 mg of fitusiran every month (or every four weeks). In yet other embodiments, the device may be used to prophylactically treat a patient with hemophilia A or B, with or without inhibitors, with a subcutaneous dose of about 10 mg of fitusiran every month (or every four weeks). In yet other embodiments, the device may be used to prophylactically treat a patient with hemophilia A or B, with or without inhibitors, with a subcutaneous dose of fitusiran at about 30 mg every month (or every four weeks). In yet other embodiments, the device may be used to prophylactically treat a patient with hemophilia A or B, with or without inhibitors, with a subcutaneous dose of fitusiran at about 5 mg every month (or every four weeks). In yet other embodiments, the device may be used to prophylactically treat a patient with hemophilia A or B, with or without inhibitors, with a subcutaneous dose of fitusiran at about 2.5 mg every month (or every four weeks). In yet other embodiments, the device may be used to prophylactically treat a patient with hemophilia A or B, with or without inhibitors, with a subcutaneous dose of fitusiran at about 1.25 mg every month (or every four weeks).

Accordingly, provided herein is a method of prophylactic treatment of a patient with hemophilia A or hemophilia B, with or without inhibitors, comprising subcutaneously delivering with the device a prophylactically effective amount of fitusiran to the patient in need thereof. The prophylactically effective amount of fitusiran may be any dose provided herein, such as about 1 to about 80 mg, about 1 to about 30 mg, or about 20 to about 80 mg. The prophylactically effective amount of fitusiran may be, for example, about 1.25 mg, about 2.5 mg, about 5 mg, about 25 mg, about 30 mg, about 50 mg, or about 80 mg. The prophylactically effective amount of fitusiran may be delivered every month (or every four weeks) or once every two months (or every eight weeks). Fitusiran may be delivered in about 0.5 mL to about 1 mb delivery volumes (e.g., about 0.5 mL, about 0.6 mL, about 0.7 mL, about 0.8 mL, about 0.9 mL, or about 1 mL). As an example, a method of prophylactic treatment of a patient with hemophilia A or hemophilia B, with or without inhibitors, may comprise subcutaneously delivering with the device about 50 mg of fitusiran to the patient in need thereof every month (or every four weeks) or once every two months (or every eight weeks). The about 50 mg of fitusiran may be delivered in about 0.5 mL PBS (at a concentration of about 100 mg fitusiran/mL).

Further provided herein is a method of reducing the frequency of bleeding episodes in a patient with hemophilia A or B, with or without inhibitors, comprising subcutaneously delivering with the device a prophylactically effective amount of fitusiran to the patient in need thereof. The prophylactically effective amount of fitusiran may be any dose provided herein, such as about 1 to about 80 mg, about 1 to about 30 mg, or about 20 to about 80 mg. The prophylactically effective amount of fitusiran may be, for example, about 1.25 mg, about 2.5 mg, about 5 mg, about 25 mg, about 30 mg, about 50 mg, or about 80 mg. The prophylactically effective amount of fitusiran may be delivered every month (or every four weeks) or once every two months (or every eight weeks). Fitusiran may be delivered in about 0.5 mL to about 1 mL delivery volumes (e.g., about 0.5 mL, about 0.6 mL, about 0.7 mL, about 0.8 mL, about 0.9 mL, or about 1 mL).

As an example, a method of reducing the frequency of bleeding episodes in a patient with hemophilia A or B, with or without inhibitors, may comprise subcutaneously delivering with the device about 50 mg of fitusiran to the patient in need thereof every month (or every four weeks) or once every two months (or every eight weeks). The about 50 mg of fitusiran may be delivered in about 0.5 mL PBS (at a concentration of about 100 mg fitusiran/mL).

Also, provided herein is a method of reducing the ABR in a patient with hemophilia A or B, with or without inhibitors, comprising subcutaneously delivering with the device a prophylactically effective amount of fitusiran to the patient in need thereof. The prophylactically effective amount of fitusiran may be any dose provided herein, such as about 1 to about 80 mg, about 1 to about 30 mg, or about 20 to about 80 mg. The prophylactically effective amount of fitusiran may be, for example, about 1.25 mg, about 2.5 mg, about 5 mg, about 25 mg, about 30 mg, about 50 mg, or about 80 mg. The prophylactically effective amount of fitusiran may be delivered every month (or every four weeks) or once every two months (or every eight weeks). Fitusiran may be delivered in about 0.5 mL to about 1 mL delivery volumes (e.g., about 0.5 mL, about 0.6 mL, about 0.7 mL, about 0.8 mL, about 0.9 mL, or about 1 mL).

As an example, a method of reducing the ABR in a patient with hemophilia A or B, with or without inhibitors, may comprise subcutaneously delivering with the device about 50 mg of fitusiran to the patient in need thereof every month (or every four weeks) or once every two months (or every eight weeks). The about 50 mg of fitusiran may be delivered in about 0.5 mL PBS (at a concentration of about 100 mg fitusiran/mL).

Also, provided herein is a method of reducing the AjBR in a patient with hemophilia A or B, with or without inhibitors, comprising subcutaneously delivering with the device a prophylactically effective amount of fitusiran to the patient in need thereof. The prophylactically effective amount of fitusiran may be any dose provided herein, such as about 1 to about 80 mg, about 1 to about 30 mg, or about 20 to about 80 mg. The prophylactically effective amount of fitusiran may be, for example, about 1.25 mg, about 2.5 mg, about 5 mg, about 25 mg, about 30 mg, about 50 mg, or about 80 mg. The prophylactically effective amount of fitusiran may be delivered every month (or every four weeks) or once every two months (or every eight weeks). The fitusiran may be delivered in about 0.5 mL to about 1 mL delivery volumes (e.g., about 0.5 mL, about 0.6 mL, about 0.7 mL, about 0.8 mL, about 0.9 mL, or about 1 mL).

As an example, a method of reducing the AjBR in a patient with hemophilia A or B, with or without inhibitors, may comprise subcutaneously delivering with the device about 50 mg of fitusiran to the patient in need thereof every month (or every four weeks) or once every two months (or every eight weeks). The about 50 mg of fitusiran may be delivered in about 0.5 mL PBS (at a concentration of about 100 mg fitusiran/mL).

Also, provided herein is a method of reducing the AsBR in a patient with hemophilia A or B, with or without inhibitors, comprising subcutaneously delivering with the device a prophylactically effective amount of fitusiran to the patient in need thereof. The prophylactically effective amount of fitusiran may be any dose provided herein, such as about 1 to about 80 mg, about 1 to about 30 mg, or about 20 to about 80 mg. The prophylactically effective amount of fitusiran may be, for example, about 1.25 mg, about 2.5 mg, about 5 mg, about 25 mg, about 30 mg, about 50 mg, or about 80 mg. The prophylactically effective amount of fitusiran may be delivered every month (or every four weeks) or once every two months (or every eight weeks). Fitusiran may be delivered in about 0.5 mL to about 1 mL delivery volumes (e.g., about 0.5 mL, about 0.6 mL, about 0.7 mL, about 0.8 mL, about 0.9 mL, or about 1 mL).

As an example, a method of reducing the AsBR in a patient with hemophilia A or B, with or without inhibitors, may comprise subcutaneously delivering with the device about 50 mg of fitusiran to the patient in need thereof every month (or every four weeks) or once every two months (or every eight weeks). The about 50 mg of fitusiran may be delivered in about 0.5 mL PBS (at a concentration of about 100 mg fitusiran/mL). Any invention described herein is not limited by the description in conjunction with the exemplary embodiments. Rather, the invention and the associated disclosure comprise any new feature as well as any combination of features, particularly including any combination of features in the patent claims, even if said feature or said combination per se is not explicitly stated in the patent claims or exemplary embodiments.

Reference numerals

20 drug delivery device

21 stem

22 housing

23 cap

24 drug container

25 container socket

26 chamber

27 needle

28 dispensing end

30 remote end

32 stopper

34 bearing

35 plunger rod arrangement

36 ball joint

37 first segment

38 second segment

39 drive member

40 dispensing direction

42 energy storage member

44 retainer

45 axis

46 needle sleeve

48 needle sleeve spring

50 needle shield

52 engaging features

54 engaging recess

56 release member

58 gripping ring

59 ring

60 hook

62 stabilizing cone

64 finger grooves 66 hand

90 guide pin

92 torsion protection

94 flexible bars 96 first channel

98 bend

100 dead end

102 barb

104 second channel

Claims

1. A drug delivery device (20), comprising: a housing (22) for receiving a drug container (24); a plunger rod arrangement (35) for driving a stopper (32) of the drug container (24) in a dispensing direction (40); a drive member (39) for driving the plunger rod arrangement (35), the drive member (39) being coupled to the plunger rod arrangement (35) by a threaded interface, the threaded interface being configured such that a rotation of the drive member (39) causes a translatory movement of the plunger rod arrangement (35) in the dispensing direction (40); and an energy storage member (42) coupled to the drive member (39) for rotating the drive member (39).

2. The drug delivery device (20) of claim 1 , wherein the plunger rod arrangement (35) is a telescopic plunger rod arrangement (35) comprising: a first segment (37) being configured for being coupled to the stopper (34) at a first axial end of the first segment (37); and a second segment (38) being operatively coupled to the first segment (37) and the drive member (39) such that the rotation of the drive member (39) is transferred to a translatory movement of the first segment (37) in the dispensing direction (40) by the second segment (38).

3. The drug delivery device (20) of claim 2, wherein the second segment (38) is operatively coupled to the first segment (37) and the drive member (39) such that the rotation of the drive member (39) firstly is transferred to a translatory movement of the second segment (38) in the dispensing direction (40); the first segment (37) is translatory moved together with the second segment (38) by the second segment (38); the second segment (38) is rotated by the drive member (39) at the end of the translatory movement of the second segment (38), and the rotation of the second segment (38) causes a further translatory movement of the first segment (37) in the dispensing direction (40).

4. The drug delivery device (20) of one of claims 2 or 3, wherein the threaded interface comprises a first threaded interface and a second threaded interface; the first threaded interface is configured to operatively couple the first segment (37) to the second segment (38); and the second threaded interface is configured to operatively couple the second segment (38) to the drive member (39).

5. The drug delivery device (20) of claim 4, wherein the first threaded interface comprises a first interface feature at the first segment (37) and a second interface feature at the second segment (38), the first interface feature being engaged with the second interface feature; and/or the second threaded interface comprises a third interface feature at the second segment (38) and a fourth interface feature at the drive member (39), the third interface feature being engaged with the fourth interface feature.

6. The drug delivery device (20) of claim 5, wherein the first interface feature is a first thread and/or the second interface feature is a second thread; and/or the third interface feature is a third thread and/or the fourth interface feature is a fourth thread.

7. The drug delivery device (20) of claim 6, wherein the second segment (38) and the drive member (39) are configured such that the rotation of the drive member (39) is transferred to the translatory movement of the second segment (38) until an end of the third thread of the second segment (38) reaches an end of the fourth thread of the drive member (39) and that a further rotation of the drive member (39) is transferred to the rotation of the second segment (38).

8. The drug delivery device (20) of one of claims 2 to 7, wherein the drive member (39) has an axially extending drive member recess; the second segment (38) has an axially extending second segment recess; the second segment (38) is arranged within the drive member recess; and the first segment (37) is arranged within the second segment recess.

9. The drug delivery device (20) of one of claims 2 to 7, wherein the first segment (37) has an axially extending first segment recess; the second segment (38) has an axially extending second segment recess; the second segment (38) is arranged within the first segment recess; and the drive member (39) is arranged within the second segment recess.

10. The drug delivery device (20) of any one of the preceding claims, wherein the energy storage member (42) is a flat spiral spring, which is coupled to the drive member (39), and which is loaded and locked in the initial state of the drug delivery device (20).

11. The drug delivery device (20) of any one of the preceding claims, comprising a needle (27) for injecting the drug into an injection site, wherein the needle (27) is configured for being communicatively coupled to the drug container (24).

12. The drug delivery device (20) of claim 11 , comprising a needle sleeve (46) for protecting the needle (27) in the initial state, the needle sleeve (46) being operatively coupled to the energy storage member (42) and being configured such that a release of the energy storage member (42) is prevented as long as the needle sleeve (46) protects the needle (27) and that the energy storage member (42) is released, when the needle sleeve (46) exposes the needle (27).

13. The drug delivery device (20) of claim 11, comprising a retainer (44) for locking the energy storage member (42) in the initial state, the retainer (44) being operatively coupled to the needle sleeve (46) such that the retainer (44) releases the energy storage member (42) upon moving the needle sleeve (46) into the housing (22).

14. The drug delivery device (20) of any one of the preceding claims, comprising a needle sleeve spring (48) which is coupled to the needle sleeve (46) and the housing (22) such that the needle sleeve spring (48) is loaded, if the drug delivery device (20) is arranged on the injection site during a dispensing operation, and that the needle sleeve (46) is pushed out of the housing (22) by the needle sleeve spring (48), if the drug delivery device (20) is removed from the injection site.

15. The drug delivery device (20) of any one of the preceding claims, comprising bearing (34) for coupling the plunger rod arrangement (35) to the stopper (32).

16. The drug delivery device (20) of any one of the preceding claims, wherein the housing (22) is mushroom-shaped, the mushroom-shaped housing (22) comprising a stem (21) accommodating at least a part of the drug container (24) and a cap (23) accommodating the energy storage member (42).

17. The drug delivery device (20) of any one of the preceding claims, wherein the plunger rod arrangement (35) is a telescopic plunger rod arrangement (35) comprising: a first segment (37) being configured for being coupled to the stopper (34) at a first axial end of the first segment (37); and a second segment (38) being operatively coupled to the first segment (37) and the drive member (39) such that the rotation of the drive member (39) is transferred to a translatory movement of the first segment (37) in the dispensing direction (40) by the second segment (38), and wherein the second segment (38) is in direct engagement with the drive member (39).

18. The drug delivery device (20) of any one of the preceding claims, wherein the energy storage member (42) is a flat spiral spring, which is coupled to the drive member (39), and which is loaded and locked in the initial state of the drug delivery device (20), and wherein the housing (22) is mushroom-shaped, the mushroom-shaped housing (22) comprising a stem (21) accommodating at least a part of the drug container (24) and a cap (23) accommodating the energy storage member (42).