Drug delivery device

Abstract

A drug delivery device (100) is provided, comprising: a housing (110) with a proximal end and a distal end, a piston rod (150) movable in the distal direction relative to the housing, the piston rod (150) being rotatably coupled to the housing via a threaded interface, a drive member (180) movable relative to the housing in the proximal direction in a setting movement to set a dose and movable in the distal direction relative to the housing in a delivery movement to deliver the set dose, wherein the drug delivery device (100) is configured such that the drive member (180), during the delivery movement, is coupled to the piston rod (150) via a drive interface such that the piston rod (150) rotates relative to the housing driven by the delivery movement of the drive member (180) and such that the piston rod (150) moves in the distal direction on account of the threaded interface.

Description

[0001] PAT24241-WO-PCT

[0002] ZSP: 989-406 PCT

[0003] Drug delivery device

[0004] Description

[0005] The present disclosure relates to a drug delivery device.

[0006] Drug delivery devices are widely used to administer drugs by medically trained persons and also by medically untrained persons. Often, drug delivery devices are used for selfadministration by users. That is to say, the persons using the device may administer the drug to themselves. Of course, it is also possible that one person using the device administers the drug to a different person.

[0007] A drug delivery device is, for example, disclosed in WO 2008 / 058665 A1.

[0008] It is an object of the present disclosure to provide improvements for drug delivery devices, for example for the drug delivery device disclosed in the prior art mentioned above. The improvements may include, for example, devices which are suitable to deliver doses of liquid drug of a high liquid amount.

[0009] This object is achieved by the subject matter disclosed herein, for example by the subject matter as set forth in the appended independent claims. The dependent claims may relate to advantageous improvements and / or modifications.

[0010] In an embodiment, the present disclosure relates to a drug delivery device. The drug delivery device comprises:

[0011] - a housing with a proximal end and a distal end,

[0012] - a piston rod movable in the distal direction relative to the housing, the piston rod being rotatably coupled to the housing via a threaded interface,

[0013] - a drive member movable relative to the housing in the proximal direction in a setting movement to set a dose and movable in the distal direction relative to the housing in a delivery movement to deliver the set dose. The drug delivery device is configured such that the drive member, during the delivery movement, is coupled to the piston rod via a drive interface such that the piston rod rotates relative to the housing driven by the delivery movement of the drive member and such that the piston rod moves in the distal direction relative to the housing on account of or due to the threaded interface.

[0014] In an embodiment, the drive interface is a helical interface formed by a drive member thread structure of the drive member engaging a piston rod drive portion of the piston rod.

[0015] In an embodiment, the piston rod comprises a piston rod main body. The piston rod drive portion may be connected to the piston rod main body, e.g. proximally or at the proximal end of the main body. The main body may have a generally cylindrical shape.

[0016] In an embodiment, the threaded interface is formed by a piston rod thread structure and an associated nut structure. The piston rod thread structure may extend circumferentially around or along the piston rod. The nut structure may be axially fixed relative to the housing and / or may engage the piston rod thread structure. The nut structure may be rotationally fixed relative to the housing.

[0017] In an embodiment, the piston rod thread structure is restricted to the piston rod main body. Consequently, the piston rod drive portion may be free of the piston rod thread structure.

[0018] In an embodiment, the piston rod drive portion is or comprises a flexible portion. The flexible portion may be flexible to selectively disengage the drive member thread structure. The flexible portion may comprises one or more flexible sections, e.g. one or more flexible arms. The respective flexible section may have a thread structure interaction portion which is configured to interact with the drive member thread structure. The thread structure interaction portion may be arranged at the distal end or free end of the flexible section. The piston rod main body may be more rigid than the piston rod drive portion.

[0019] In an embodiment, the respective flexible section is elastically displaceable relative to the piston rod main body. During the dose setting movement, the respective flexible section may be radially, e.g. inwardly, displaced, thereby biasing the respective flexible section outwardly.

[0020] Before or at the end of the setting movement, the flexible section may relax and / or be displaced outwardly.

[0021] In an embodiment, during the setting movement, the respective flexible section is axially displaced relative to a section of the drive member thread structure until it engages a further section of the drive member thread structure. When it engages the further section, the flexible section may relax. In an embodiment, during the setting movement, the flexible sections are radially displaced, e.g. inwardly, relative to the drive member thread structure, e.g. due to the thread structure forcing the displacement due to a protrusion being arranged between different sections of the drive member thread structure. The flexible section may interact with one section of the drive member thread structure before the setting movement and with another section of the drive member thread structure after completion of the setting movement. The protrusion may be arranged between the sections of the drive member thread structure. The protrusion may have an angled proximally facing surface. A distally facing surface of the protrusion may be steeper than the proximally facing surface. The protrusion may define a thread or helix of the drive member thread structure.

[0022] In an embodiment, the piston rod drive portion has just one flexible section. Thus, only one flexible arm or section may be provided in the piston rod drive portion and / or at the proximal end of the piston rod.

[0023] In an embodiment, the piston rod drive portion comprises a plurality of flexible sections, e.g. two flexible sections. The flexible sections may be angularly offset from one another. The flexible sections may be arranged diametrically opposite to each other or offset angularly by 180°.

[0024] In an embodiment, the thread structure interaction portions of the plurality of flexible sections overlap axially. The flexible sections and / or their thread structure interaction portions may have equal lengths and / or be configured alike.

[0025] In an embodiment, the respective thread structure interaction portion is a helical portion or helically extending portion. The respective thread structure interaction portion may have a helical surface. The helix defining the surface may be identical to a helix defining a thread of the drive member thread structure.

[0026] In an embodiment, the thread structure interaction portions of the plurality of flexible sections are axially offset from one another, e.g. pairwise if there are more than two flexible sections. A proximal end of the thread structure interaction portion of a first flexible section may be arranged at an axial distance and / or an angular distance from a distal end of the thread structure interaction portion of a second flexible section. The axial and / or angular offset between the thread structure interaction portions of the flexible sections may be defined by a thread of the drive member thread structure, e.g. by a helix. The axial offset between the thread structure interaction portions may be less than a pitch or lead of a thread or helix of the drive member thread structure such as less than 3 / 4 of the a pitch or lead, e.g. half the pitch or lead, particularly for two diametrically opposite flexible sections. The axial offset between the thread structure interaction portions may be greater than 1 / 3 of the pitch or lead of a thread or helix of the drive member thread structure. The thread or helix may be the one engaged by the thread structure interface portions.

[0027] In an embodiment, the thread structure interaction portions of the plurality of flexible sections are designed to engage the same helix of a thread of the drive member thread structure.

[0028] In an embodiment, the thread structure interaction portions of the plurality of flexible sections are arranged on a common helix.

[0029] In an embodiment, an angular extension of the respective flexible section is less than or equal to one of: 120°, 110°, 100°, 90°, 80°, 70°, 60°.

[0030] In an embodiment, the drive member thread structure is a single-start thread structure with one thread, e.g. a single-start thread, or one helix.

[0031] In an embodiment, the drive member thread structure is a multi-start thread structure with more than one thread, e.g. more than one helical threads or helixes expediently having the same hands, the same pitches and / or the same leads. For example, the thread structure may be formed by a two-start thread with two, e.g. axially offset, helical threads or helixes with the same hands, the same pitches and / or the same leads.

[0032] In an embodiment, the thread structure interaction portions of the plurality of flexible portions are arranged to engage different threads or helixes of the drive member thread structure.

[0033] In an embodiment, the piston rod thread structure is a multi-start thread structure with more than one thread, e.g. more than one helical threads or helixes having the same hands, the same pitches and / or the same leads. For example, the thread structure may be formed by a two-start thread with two, e.g. axially offset, threads or helixes with the same hands, the same pitches and / or the same leads.

[0034] In an embodiment, the number of threads or thread starts of the drive member thread structure is different from or equal to the number of threads or thread starts of the piston rod thread structure. In an embodiment, the number of threads or thread starts of the drive member thread structure is less than the number of threads or thread starts of the piston rod thread structure.

[0035] In an embodiment, the drive member thread structure has a pitch or lead greater than the pitch or lead of the piston rod thread structure. The thread structures may have the same number of thread starts.

[0036] In an embodiment, the drive member thread structure has a pitch or lead equal to the pitch or lead of the piston rod thread structure. The thread structures may have a different number of thread starts. Expediently the number of thread starts of the piston rod thread structure is greater than the number of thread starts of the drive member thread structure.

[0037] In an embodiment, the drive member thread structure and / or the piston rod thread structure is a helically extending structure.

[0038] In an embodiment, the respective thread structure interaction portion is connected to the piston rod main body by a connecting portion of the flexible section, expediently the one comprising the thread structure interaction portion. The connecting portion may extend axially. The connecting portion may be axially oriented. As opposed to the thread structure interaction portion, the connecting portion may not interact with the drive member thread structure. The thread structure interaction portion may have a radial extension which is greater than the one of the connecting portion. The thread structure interaction portion may protrude radially, e.g. inwardly and / or outwardly, from the connecting portion.

[0039] In an embodiment, the connecting portion has an axial extension which is less than or greater than the axial extension or length of the thread structure interaction portion of the flexible section.

[0040] In an embodiment, the connecting portions of different flexible sections are configured differently or alike.

[0041] In an embodiment, the connecting portions of different flexible sections have the same axial extension or length.

[0042] In an embodiment, the connecting portions of different flexible sections have different axial extensions or lengths. The respective axial extension or length may be measured from the proximal end of the piston rod main body to the distal end of the thread structure interaction portion.

[0043] In an embodiment, the connecting portions of different flexible sections have the same angular extension or angular width.

[0044] In an embodiment, the thread structure interaction portions of different flexible sections have the same axial extension or length and / or the same angular extension or angular width.

[0045] In an embodiment, the thread structure interaction portions of different flexible sections are designed to cooperate with or engage different helixes of the same hand (or sense of rotation) and pitch or lead or with the same helix.

[0046] In an embodiment, the piston rod, e.g. the piston rod main body, comprises one or more last dose stop features, e.g. two last dose stop features. The respective last dose stop feature may protrude radially, e.g. outwardly, from the piston rod, e.g. from the piston rod main body. The respective last dose stop feature may be arranged to interact with, e.g. abut, an associated stop feature of the drive member, e.g. to prevent setting of a dose when the piston rod has reached a distal end position relative to the housing, e.g. after the last delivery movement of the drive member has been performed. The respective stop feature of the drive member may protrude radially inwardly, e.g. from an inner wall of the drive member.

[0047] In an embodiment, the drive member comprises one or more stop features. The drive member may comprise just one or only one stop feature or more than one stop feature, e.g. two stop features.

[0048] In an embodiment, two stop features of the drive member are axially aligned but angularly offset.

[0049] In an embodiment, two stop features of the drive member are axially offset and / or angularly offset. The offset (e.g. angular and axial offset) may be chosen such that the two stop features are arranged on a helical path corresponding to or defined by a helix or a helical thread, e.g. a helix or helical thread of the drive member thread structure. The angular offset may be less than 180°.

[0050] Offsets as mentioned herein may be defined by the center-to-center distance (axial offset) or the center-to-center angle (angular offset) between the elements which are offset from one another. The distance or angle may be measured relative to a longitudinal axis of the device or a rotation axis of the piston rod.

[0051] In an embodiment, two last dose stop features of the piston rod are axially aligned but angularly offset.

[0052] In an embodiment, two last dose stop features of the piston rod are axially offset and angularly offset. The offset (e.g. angular and axial offset) may be chosen such that the two stop features are arranged on a helical path corresponding to or defined by a helix or a helical thread, e.g. a helix or helical thread of the drive member thread structure. The angular offset may be less than 180°.

[0053] In an embodiment, a first last dose stop feature of the piston rod is provided, e.g. partly or in its entirety, in the flexible portion of the piston rod drive portion, e.g. on a flexible section of the piston rod drive portion. A second last dose stop feature of the piston rod may be arranged on the piston rod main body.

[0054] In an embodiment, the piston rod main body is more rigid than the respective flexible section.

[0055] In an embodiment, the proximal end of one or more than one stop feature of the drive member moves axially past the proximal end of the piston rod main body during dose setting, e.g. when setting the last dose.

[0056] In an embodiment, the distal end of a stop feature of the drive member, e.g. of only one stop feature, moves axially past the proximal end of the piston rod main body during dose setting, e.g. when setting the last dose.

[0057] In an embodiment, the piston rod, e.g. the main body, comprises a plurality of rotation prevention structures. The rotation prevention structures are arranged to interact with one feature or more features of the drive member to prevent rotation of the piston rod during the setting movement, e.g. to prevent rotation in a direction opposite to the rotation during the dose delivery movement.

[0058] In an embodiment, the drive member is rotationally locked with respect to the housing.

[0059] In an embodiment, the rotation prevention structures are arranged in a linear arrangement along the piston rod main body. In an embodiment, a thread or helix of the piston rod thread structure extends through one or more of the rotation prevention structures.

[0060] In an embodiment, the respective rotation prevention structure protrudes radially from the piston rod, e.g. the piston rod main body. The respective rotation prevention structure may be formed by one or more spline features. Axial gaps between spline features of the same rotation prevention structure (e.g. in the region where the thread or helix extends through the structure) may be expediently smaller than the axial extension of the stop feature(s) interacting with the rotation prevention structure to reliably prevent rotation.

[0061] In an embodiment, the axial extension of the respective rotation prevention structure is less than the axial distance by which the drive member is moved proximally during dose setting.

[0062] In an embodiment, the axial extension of the respective rotation prevention structure is greater than the axial distance or the axial gap between two adjacent rotation prevention structures, e.g. between any two adjacent rotation prevention structures of the piston rod.

[0063] In an embodiment, the rotation prevention structures are arranged in a linear arrangement, e.g. a line, along the piston rod main body, e.g. to form a group of rotation prevention structures. Different groups may be angularly offset from each other, e.g. by 120° or 180°. The piston rod may comprise two or three groups of rotation prevention structures.

[0064] In an embodiment, the axial distance between adjacent rotation prevention structures is greater than the axial extension of the one or more features of the drive member which are arranged to interact with the rotation prevention structures to prevent rotation of the piston rod in the setting movement. This ensures reliable rotation of the piston rod during dose delivery.

[0065] In an embodiment, the drug delivery device is a fixed dose device. The fixed doses to be delivered by the device may be of the same size or may comprise the same amount of liquid drug.

[0066] In an embodiment, the drug delivery device is an injection device, e.g. a pen-type injector and / or a needle-based injector.

[0067] In an embodiment, the drug delivery device is configured to receive or comprises a container with a drug or medicament. In an embodiment, the drug delivery device is a disposable device. Disposable devices can be used only in conjunction with one container with drug and are disposed after the last delivery operation to deliver drug from that container. Disposable devices cannot be reused with a different container.

[0068] In an embodiment, the drug delivery device is configured such that the distal displacement of the piston rod relative to the housing during the delivery movement is greater than or equal to any one of the following: 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm.

[0069] In an embodiment, the drug delivery device is configured such that the distal displacement of the piston rod relative to the housing during the delivery movement is less than or equal to any one of the following: 12 mm, 11 mm, 10 mm, 9 mm, 8.5 mm.

[0070] The distance may be between 3 mm and 12 mm.

[0071] In an embodiment, the drug delivery device is configured such that, during the delivery movement, the piston rod rotates relative to the housing by an angle of greater than or equal to: 90°, 100°, 110°, 120°, 130°, 140°, 150°, 160°, 170°, 180°.

[0072] In an embodiment, the drug delivery device is configured such that, during the delivery movement, the piston rod rotates relative to the housing by an angle of less than or equal to: 270°, 260°, 250°, 240°, 230°, 220°, 210°, 200°, 190°, 180°, 170°, 160°, 150°, 140°, 130°, 120°.

[0073] The rotation angle of the piston rod may be between 90° and 270°.

[0074] In an embodiment, the drug delivery device is configured to dispense more than one dose per revolution (i.e. per rotation by 360° relative to the housing) of the piston rod.

[0075] In an embodiment, the drug delivery device is configured to dispense one of the following numbers of doses per revolution of the piston rod: 2, 3. Thus, the piston rod may rotate by 120° or 180° per dose.

[0076] In an embodiment, the drug delivery device is configured such that, during the delivery movement, the drive member is moved distally relative to the housing by an axial distance of less than or equal to any one of the following: 35 mm, 34 mm, 33 mm, 32 mm, 31 mm, 30 mm, 29 mm, 28 mm, 27 mm, 26 mm, 25 mm, 24 mm, 23 mm, 22 mm, 21 mm, 20 mm, 19 mm, 18 mm, 17 mm, 16 mm, 15 mm, 14 mm, 13 mm, 12 mm, 11 mm, 10 mm, 9 mm.

[0077] In an embodiment, the drug delivery device is configured such that, during the delivery movement, the drive member is moved distally relative to the housing by an axial distance of greater than or equal to any one of the following: 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm, 20 mm.

[0078] The distal drive member movement may be between 8 mm and 35 mm. The setting movement may involve the same or substantially the same distances as the delivery movement.

[0079] In an embodiment, the amount of liquid drug delivered from the container in one delivery movement is greater than or equal to one of the following: 0.25 mL, 0.3 mL, 0.35 mL, 0.4 mL, 0.45 mL, 0.5 mL, 0.55 mL, 0.6 mL.

[0080] In an embodiment, the amount of liquid drug delivered from the container in one delivery movement is less than or equal to one of the following: 0.9 mL, 0.85 mL, 0.8 mL, 0.75 mL, 0.7 mL, 0.65 mL, 0.6 mL.

[0081] In an embodiment, the drive member axial displacement during dose delivery is greater than the axial displacement of the piston rod relative to the housing to provide a mechanical advantage. The mechanical advantage may be 2 or more, e.g. 3.

[0082] In an embodiment, the drug delivery device is designed to deliver a number of doses which is less than or equal to one of the following: 10, 7, 6, 5, 4.

[0083] In an embodiment, the drug delivery device is designed to deliver a number of doses which is greater than or equal to one of the following: 2, 3, 4.

[0084] 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. Also, features described in combination with one another should be considered as being disclosed separately from each other throughout the entire disclosure.

[0085] Further features, advantages and expediencies of the disclosure will become apparent from the following description of the exemplary embodiments in conjunction with the drawings. Brief description of the drawings

[0086] Figure 1 shows an embodiment of a drug delivery device based on a side view of the device.

[0087] Figure 2 shows an explosive view of an embodiment of the drug delivery device of figure 1.

[0088] Figure 3 shows a sectional view of the drug delivery device.

[0089] Figure 4A illustrates dose setting movement and Figure 4B illustrates dose delivery movement based on sectional views.

[0090] Figures 5A and 5B illustrate a rotation prevention mechanism operating during dose setting to prevent unwanted piston rod rotation and permitting rotation of the piston rod during dose delivery.

[0091] Figures 6A and 6B illustrate a last dose stop mechanism.

[0092] Figures 7A to C illustrate some modifications to a reference device for delivering larger doses.

[0093] Figure 8 shows an embodiment of a piston rod.

[0094] Figure 9 shows an embodiment of a piston rod.

[0095] Figure 10 shows an embodiment of a drive member.

[0096] Figure 11 illustrates an embodiment of a last dose stop mechanism.

[0097] Figure 12 illustrates an embodiment of a drive member.

[0098] Figure 13 illustrates an embodiment of a last dose stop mechanism with the drive member of figure 12.

[0099] Figure 14 illustrates an embodiment of a drive member.

[0100] Figure 15 illustrates an embodiment of a last dose stop mechanism. Figure 16 illustrates a prime indicator.

[0101] Description of exemplary embodiments

[0102] Like elements, elements of the same kind and identically acting elements may be provided with the same reference numerals or signs throughout the figures.

[0103] “Distal” is used herein to specify directions, ends or surfaces which are arranged or are to be arranged to face or point towards a dispensing end of the drug delivery device and / or point away from, are to be arranged to face away from or face away from the proximal end of the drug delivery device or components thereof. On the other hand, “proximal” is used to specify directions, ends or surfaces which are arranged or are to be arranged to face away from or face away from the dispensing end and / or from the distal end of the drug delivery device or components thereof. The distal end may be the end closest to the dispensing end and / or furthest away from the proximal end. The proximal end may be the end furthest away from the dispensing end. A proximal surface may face away from the distal end and / or towards the proximal end. A distal surface may face towards the distal end and / or away from the proximal end. The dispensing end may be the needle end where a needle is arranged or a needle or needle unit is or is to be mounted to the device, for example.

[0104] Figure 1 shows an exemplary embodiment of a drug delivery device 100. The drug delivery device 100 comprises a body or housing 110. At the proximal end of the device 100 and / or the housing 110, a dose member 120 is provided. The dose member 120 provides the user interface of the drug delivery device 100 which may be operated by a user for setting and / or delivering a dispensing a dose of drug from the device 100. The dose member 120 may be a dose button. The dose member 120 is expediently movable in the proximal direction relative to the housing 110 (in the depicted configuration to the right) to set a dose of drug to be delivered from the device 100 and in the distal direction relative to the housing 110 (in the depicted configuration to the left) to deliver the set dose. The drug delivery device 100 further comprises an optional cap 130 at its distal end. The cap 130 is removably coupled to the drug delivery device, e.g. by a snap fit. The cap 130 may be removed from the device before the delivery operation for delivering drug is performed.

[0105] Figure 2 shows an explosive view of an embodiment of the drug delivery device 100 of figure 1. In addition to the cap 130, the housing 110, and the dose member 120 further components of the drug delivery device 100 are shown. Specifically, the device 100 comprises a container holder 140, e.g. a cartridge holder. The container holder 140 may be, e.g. non-releasably, connected to the housing 110, such as by a snap-fit. The container holder 140 may be designed to receive or comprises in its interior a drug container, e.g. a cartridge with a septum which can be produced by the needle at its distal end. The proximal end of the container may be closed by a bung which is movable in a distal direction relative to a body of the container in order to deliver liquid drug from the container during the dose delivery operation. A needle unit may be, e.g. releasably, coupled to the distal end of the container holder 140, e.g. by a threaded interface. The drug delivery device 100 may be an injection device, e.g. a needle-based injector. The drug delivery device 100 may be a pen-type drug delivery device. The drug delivery device may be a disposable device. In consequence, the device may be disposed after a predetermined maximum amount of drug content has been delivered from the container, e.g. distributed over various doses. In particular, in a disposable device (as opposed to reusable devices), the container may not be replaced with an unused container. The drug delivery device may be a fixed dose device. That is to say, the device may be designed to deliver doses the size or liquid amount of which are preset by the manufacturer and the size of the dose cannot be changed by the user. All doses delivered by the fixed dose device may have equal sizes.

[0106] The device 100 further comprises a piston rod 150, e.g. a lead screw. The piston rod 150 may be designed to rotate relative to the housing 110 during the dose delivery operation, e.g. by force transferred to the piston rod 150 from the user via the dose member 120 druing distal movement of the dose member relative to the housing 110. The drug delivery device 100 further comprises a nut member 160. The nut member 160 may be axially and rotationally secured to the housing 110. A nut structure (not shown in figure 2, see 161 in figure 3) may be formed on the nut member 160, e.g. in its interor. The nut member, particularly its nut structure, is designed to engage with a piston rod thread structure 152 on a main body 151 of the piston rod 150. In some embodiments, the nut structure may be integrated into the housing 110 and, in consequence, a separate nut member 160 can be dispensed with.

[0107] On account of the threaded interface formed between the nut structure and the thread structure the piston rod 150 is displaced distally relative to the housing 110 during dose delivery as its rotation relative to the housing (and the nut structure) is converted into axial displacement by the threaded interface.

[0108] The device may further comprise a bearing 170. The bearing 170 may be axially secured to the piston rod 150. However, the piston rod 150 may be rotatable relative to the bearing 170. The bearing 170 may be designed to abut the bung of the container to displace the bung in order to deliver a dose of drug from the container. Thus a rotational load on the bung of the container may be avoided or such a load may be at least significantly reduced by the bearing 170. The device further comprises a drive member 180. The drive member 180 may be rotationally and axially locked to the dose member 120. These two members may act as a single component. Hence, referrals to one of these members above and below may be regarded as a referral to the other one of these members. Specifically, their functionalities could be integrated into a single member, where using two members may have advantages from a manufacturing perspective. The drive member 180 and / or the dose member 120 may formed as a sleeve. The drive member 180 may have a thread structure (not explicitly shown in figure 2, see 182 in other figures), which is designed to interact with a drive portion 153 of the piston rod 150. The interaction between the drive member 180 and the piston rod drive portion 153 during dose delivery may cause rotation of the piston rod 150 relative to the housing and its nut structure.

[0109] The drug delivery device 100 may further comprise an indicator 190. The indicator 190 may be received in the dose member 120 and be rotatable relative to the dose member. The indicator is configured to indicate whether a first delivery operation has been performed with the drug delivery device. In other words, the indicator may indicate whether the drug delivery device has been primed. In some situations, the first amount of drug delivered from the drug delivery device might not correspond to a target fixed dose to be delivered by the device, e.g. due to tolerances of the components which involve variations in the initial position of the bearing relative to the container, e.g. to the bung. Hence, an initial dose deliver operation or priming operation may be performed to ensure that doses delivered after this operation has been completed match the target fixed dose as tolerances have been removed. As set out below, priming is optional.

[0110] Figure 3 shows a schematic sectional view of the drug delivery device 100. In figure 3, a container 200 is arranged in the container holder 140. In the depicted example, the container 200 is a cartridge. The proximal end of the container 200 is closed by the movable bung 201. The distal end of the container 200 is close by a septum 202. The septum 202 can be pierced by a needle of a needle unit (not shown) which can be, preferably releasably, attached, e.g. via a thread, to the distal end of the container holder 140.

[0111] In this representation, the engagement between the piston rod thread structure 152 and the nut structure 161 of the nut member 160 is shown. A, e.g. radially inwardly directed, protrusion of the nut structure engages the thread structure 152 provided on the piston rod main body 151, e.g. on the outer surface of the piston rod 150. The nut structure 161 may comprise a plurality of protrusions engaging the thread structure (not shown). The protrusions may be angularly offset from one another. Two protrusions may be axially aligned with each other and / or two protrusions may be axially offset from one another. On account of the engagement of the piston rod thread structure 152 and the nut structure 161 , rotation of the piston rod 150 relative to the nut structure 161 is converted into distal displacement of the piston rod (to the right in figure 3).

[0112] Moreover, the interaction between the piston rod drive portion 153 and the drive member 180 is illustrated. The drive member 180 comprises a drive member thread structure 182, which is designed to interact with the piston rod drive portion 153 of the piston rod 150. The piston rod drive portion 153 is or comprises a flexible portion with one or more flexible sections or flexible arms 154. Each flexible arm may be designed to engage the drive member thread structure 182.

[0113] During dose setting, the user pulls the drive member 180 in the proximal direction relative to the housing. A contact angle (e.g. of a sloped proximal surface of a protrusion of the thread structure) between the drive member thread structure 182 and the respective arm 154 forces the arms to bend inwards. The thread structure on the drive member 180 is then able to slip past the flexible arms, so that the drive member 180 can translate axially relative to the housing 110 and the piston rod 150. Expediently, the piston rod 150 remains stationary during dose setting.

[0114] During dose delivery, when the user pushes the drive member 180 in a distal direction relative to the housing, the flexible arms 154 are prevented from bending inwards (e.g. due to a steeper contact angle between the arms 154 and (helical) thread structure 182). The force transferred in this way to the piston rod via the drive member causes the piston rod to rotate and, due to the threaded engagement with the nut member 160, drives the piston rod 150 forward I the distal direction. The flexible arms 154 slide along the drive member thread structure 182 while the drive member 180 translates axially and the piston rod 150 rotates. The piston rod 150 rotates relative to the housing 110 on its own thread interface (formed between nut member 160 and the (helical) piston rod thread structure 152) and, therefore, is axially displaced in the distal direction, e.g. to dispense drug from the container 200. The thread structures 152 of the piston rod 150 and the drive member 180 may comprise oppositely handed threads.

[0115] Figure 4A shows the drive member thread structure 182 and the piston rod drive portion 153 during dose setting when the drive member 180 is moved proximally (as illustrated by the arrow) relative to the piston rod 150. The depicted situation is right before the flexible arms 154 are radially inwardly displaced. Figure 4B shows the situation during dose delivery (and after the flexible arms have been inwardly elastically displaced and relaxed again to re-engage the thread structure 182). Here, the drive member 180 is moved distally relative to the housing towards its initial position (as illustrated by the arrow). The piston rod 150 is distally displaced relative to the drive member 180.

[0116] The device may be designed to deliver a number of fixed doses, e.g. 14 doses (and, optionally, an additional priming dose).

[0117] The general functionality of the drug delivery device 100 described above is similar to the one disclosed in WO 2008 / 058665 A1 , the disclosure of which is therefore incorporated by reference into the present disclosure in its entirety.

[0118] The device 100 expediently comprises a mechanism to prevent rotation of the piston rod 150 during dose setting in a direction which would displace the piston rod 150 proximally with respect to the housing (in other words, backwinding of the piston rod 150 is expediently prevented). The contact angle between the drive member thread structure 182 and the flexible arms 154 may impart a torque on the piston rod 150 which could cause it to 'backwind', i.e. rotate in the opposite direction to delivery or dispense, during dose setting. Such an unwanted rotation would negatively impact dose accuracy, which is undesirable, of course. Such a rotation can be prevented by splines or rotation prevention structures 155 on the piston rod 150 (the structures 155 may protrude, e.g. radially and / or outwardly, from the piston rod main body 151). The structures 155 are arranged to contact one or more stop features 181 of the drive member 180 if a backwinding torque is applied to the piston rod 150 during dose setting. This abutment prevents rotation of the piston rod as the drive member is rotationally locked relative to the housing. The respective stop feature 181 may be a protrusion, such as a radially inwardly directed protrusion. A plurality of stop features 181, e.g. two stop features, may be circumferentially disposed on the drive member 180, e.g. diametrically opposite to one another. The stop features may be angularly offset, e.g. by 180° or less than 180°. The stop features 181 may be axially offset or axially aligned. In some embodiments, a single stop feature 181 may be sufficient.

[0119] A thread or helix of the piston rod thread structure 152 can extend through one or more of the structures 155. A potential gap in the structure 155 (e.g. in the region where the thread structure 152 extends through or across the structure 155) is expediently smaller than the axial extension of the stop feature 181. Any gap between adjacent structures 155 is expediently greater than the axial extension of the stop feature 181. Thus, rotation of the piston rod 150 relative to the drive member 180 during dose delivery is not prevented by the stop feature 181 abutting the structure 155 as the stop feature 181 can pass through the gap between adjacent structures 155 when the piston rod 150 rotates relative to the drive member 180 and, accordingly, also relative to the stop feature 181.

[0120] The rotation prevention mechanism is illustrated in figures 5A and 5B. Figure 5A illustrates the involved features and figure 5B illustrates the relative movement between piston rod 150 and stop feature 181 (or drive member 180) during dose setting (see arrow "S", i.e. only axial movement of the drive member relative to the piston rod is allowed) and dose delivery (see arrow "D", indication helical movement of the piston rod relative to the drive member such that the stop feature 181 passes through the gap between adjacent rotation prevention structures 155).

[0121] The drug delivery device 100 further comprises a last dose stop mechanism. The last dose stop mechanism is operable to prevent proximal movement of the drive member 180 and / or the dose member 120 relative to the housing 110 to a position which would be required to set a dose once a predetermined number of doses has been delivered from the device (i.e. after delivery of the last dose). In other words, once the piston rod 150 has travelled distally with respect to the housing in successive delivery movements from a proximal initial position to a distal end position when the last dose has been delivered, a setting movement for a further dose is prevented.

[0122] An embodiment of the last dose stop mechanism is illustrated in figures 6A and 6B. The last dose stop mechanism comprises one or more last dose stop features 156 on the piston rod 150, e.g. the main body 151. The features 156 are arranged in a proximal end region of the piston rod or the main body. If there is more than one last dose stop feature, e.g. two, they may be angularly offset, e.g. by 180° or less than 180° and / or axially offset. The last dose stop features may be axially offset or axially aligned. Figures 6A and 6B show one last dose stop feature 156, where a second one may be provided on the non-visible the backside of the main body 151 of the piston rod 150 or dispensed with. The respective last dose stop feature 156 may be arranged to cooperate with a stop feature of the drive member 180. Each last dose stop feature 156 may have an associated stop feature on the drive member 180. In some embodiments, the number of last dose stop features 156 on the piston rod 150 is equal to the number of stop features on the drive member. One of, more of, or all of the stop features 181 described previously in relation to the rotation prevention mechanism may be used as stop features for last dose stop mechanism as well. In some embodiments, one or more further stop features may be provided on the drive member, which interact with the last dose stop feature on the piston rod. These one or more stop features may be involved in the last of stop mechanism but not for the rotation prevention mechanism. For ease of reference, the stop features in figures 6A and 6B are denoted with 181. However, one or more distinct stop features could be used for the last dose stop mechanism only but not for the rotation prevention mechanism.

[0123] After the predetermined number of (fixed) doses has been dispensed from the device (the path of the stop feature 181 during dose delivery of the last dose is again represented by arrow "D" in figure 6A), movement of the dose member 120 in the proximal direction causes the drive member last dose stop feature(s) 181 to engage with the piston rod last dose stop feature(s) 156 (see arrow "L" in figure 6A). The stop feature 156 has an angled surface, e.g. V-like. Hence, the drive member 180 may then moved in the proximal direction until the (respective) piston rod last dose stop feature 156 engages the (respective) stop feature 181. During the proximal movement the piston rod may rotate until some overtravel is taken up and / or a flat thread section (see 157) of the piston rod thread structure 152 engages with the nut structure 161 (see figure 6B). The engagement of stop feature 181 and last dose stop feature 156 (as depicted in figure 6B) prevents further movement of any of the components in the proximal direction and, in consequence, setting of a dose when the piston rod has reached its distal end position is prevented. Particularly, the flexible arms can no longer pass into a more distal section of the drive member thread structure.

[0124] The axial displacement of the drive member during dose delivery is expediently larger than the axial displacement of the piston rod during dose delivery. Thereby, a mechanical advantage may be achieved. The mechanical advantage may be defined by the ratio of the drive member axial displacement in the distal direction during dose delivery to the piston rod axial displacement in the distal direction relative to the housing during dose delivery. The mechanical advantage may be adjusted by choosing the pitch or lead of the thread(s) or helixes of the drive member thread structure 182 and of the thread(s) or helixes of the piston rod thread structure accordingly.

[0125] The piston rod thread structure 152 may comprise one or more threads or helixes. The respective thread or helix may extend helically along the piston rod, e.g. an outer surface thereof. In case there is a plurality of threads or helixes, the threads or helixes may be part of a multi-start piston rod thread structure 152. The number of thread starts of the piston rod thread structure may be one or greater than one, e.g. two.

[0126] The drive member thread structure 182 may comprise one or more threads or helixes. The respective thread or helix may extend helically along the drive member 180, e.g. an inner surface thereof. In case there is a plurality of threads or helixes, the threads or helixes may be part of a multi-start drive member thread structure 182. The number of threads starts of the drive member thread structure may be one or greater than one, e.g. two.

[0127] Thus, the drive member thread structure and / or the piston rod thread structure may comprise or be formed of a multi-start thread. In a multi-start thread, helixes or threads of equal hand and lead or pitch may be provided which are axially offset from one another. The helixes or threads may be engaged by different, e.g. axially aligned or axially offset and / or angularly aligned or angularly offset, elements, e.g. of the piston rod drive portion 153 (such as the flexible arms 154) for the drive member thread structure 182 or of the nut member 160 (e.g. nut structures 161) for the piston rod thread structure 152.

[0128] The pitch and / or the lead of the thread(s) or helix(es) of the drive member thread structure 182 may be greater than the pitch and / or the lead of the thread(s) or helix(es) of the piston rod thread structure 152.

[0129] The number of thread starts of the drive member thread structure 182 may be less than or equal to the number of thread starts in the piston rod thread structure 152. For example, both thread structures may have one or two thread starts or the drive member thread structure may have a thread with just one thread start and the piston of thread structure may have a multi-start thread with two thread starts.

[0130] The drug delivery device which has been described above has been designed to deliver a number of fixed doses, e.g. 10 or more doses, such as 14 doses (and a potential additional priming dose to prime the mechanism), e.g. from a 3 mL cartridge. The volume of liquid delivered in a single dose may be comparatively small, e.g. 0.2 mL.

[0131] In the following, some concepts are described which facilitate an increase of the size of the dose delivered by a drug delivery device, e.g. the device as discussed above but not restricted to this device. Increasing the dose size is not trivial, e.g. as the device should be able to be operated manually, expediently single-handedly, and / or for self administration.

[0132] In order to modify a device design for a larger dose size, the travel of the piston rod per dose needs to increase. This may be achieved by: increasing the pitch or lead of the piston rod thread structure; increasing the rotation of the piston rod per dose; or a combination both. Any modifications should be compatible with the pitch of the drive member thread structure and the location of features involved in the last dose stop mechanism. Two options (denoted as option A and option B in the following) for a drug delivery device with the aim to increase the size of the delivered dose (i.e. an increased amount of liquid) are compared with a reference device below, where the reference device is similar to the device described further above. The piston rods 150 of the reference device as well as options A and B and, schematically, the associated drive members 180 are depicted in figures 7A to C, where figure 7A shows the reference device, figure 7B shows option B, and figure 7C shows option A.

[0133] Both options, A and B, are designed to result in a distal displacement of the piston rod by approximately 8.12 mm when delivering the (fixed) dose. For a cylindrical cartridge as container 200 with an interior diameter of 9.7 mm, this displacement results in a dose of 0.6 mL being delivered from the container (e.g. a 3.0 mL container) during one delivery operation. Some design characteristics for options A and B are set out in the tables below.

[0134] We note that different configurations and characteristics are possible, e.g. for devices delivering a higher dose than the reference device, and the above specifications should not be regarded as limiting the present disclosure to these specifications. Also, the concepts disclosed herein may be suitable for different devices as well.

[0135] Option B may maintain many of the same geometrical relationships as in the reference device (including the mechanical advantage of 3:1), so features such as the last dose stop mechanism can function in the same way. However, when compared to option A which has a smaller mechanical advantage, option B has a longer body or housing, and a larger dose member or button travel, e.g. for dose setting and / or delivery. As compared to the reference device, option B has a dose member displacement distance (for dose setting and / or delivery) which is increased by 8 mm. Option A even increases the dose member displacement distance by 16 mm over the reference device. However, typical devices, e.g. some insulin injectors, involve axial displacements of an actuation member or dose member relative to the housing which is even greater than option B, such as up to approximately 48 mm. The length of the housing may increase by 16 to 34 mm for option B and 8 to 21 mm for option A as compared to the reference device. The dispense forces, i.e. the force which the user has to exert on the dose member 120 for delivering a dose may be below any one of the following, e.g. for any one of options A and B and the reference: 10 N, 9 N, 8 N, 7 N, 6 N. The dispense force for the reference device may be below 5 N and / or greater than 4 N, e.g. 4.72 N. The dispense force for option A may be greater than 5 N, e.g. 5.15 N. The dispense force for option B may be below 5 N and / or greater than 4 N, e.g. 4.52 N. Thus, option B may have a slightly lower dispense force than option A.

[0136] As noted above, there may be a back-off functionality implemented in the device. The back-off functionality, after the delivery movement has been completed, may move the drive member and the piston rod in the proximal direction relative to the housing and the container, e.g. to remove the pressure of the piston rod on a bung within the cartridge, e.g. by establishing a gap between bearing 170 and bung 201. This functionality may be achieved by a resilient structure axially fixed relative to the housing, e.g. integrated into the nut member 160. The resilient structure may be biased at the end of the delivery movement of the drive member, e.g. by the drive member abutting the resilient structure and having elastically deformed the structure during the delivery movement. When the user releases the dose member 120, after dose delivery, the biased resilient structure may move the drive member 180 (the dose member as well, of course) and the piston rod 150 proximally. Such a resilient structure is not explicitly shown in the drawings but may nevertheless be incorporated, e.g. integrated into the nut member 160, into a separate component axially fixed to the housing 110, or into the housing 100. In the reference device and option B there are two starts on the drive member thread structure 182. This allows two flexible arms 154 on the piston rod 150 that are of the same length and diametrically opposite each other, the arms 154 interacting with threads or helixes of the drive member thread structure 182 having a different start (see figure 7B). The two threads or helixes with different starts are denoted as 182a and 182b in figure 7B.

[0137] The respective flexible arm 154 (in the reference device as well as in option A and option B) has a thread structure interaction portion or thread interaction portion 154a. The thread interaction portion 154a may be arranged at the free end of the respective flexible arm 154. The free end may be the proximal end. Between the thread interaction portion and the piston rod main body 151 a connecting portion 154b is arranged. The respective thread interaction portion is connected to the piston rod main body 151 via the connecting portion 154b. The connecting portion may provide flexibility to the flexible arms. The flexible arms may pivot about the boundary between the piston rod main body 151 and the connecting portion 154b during dose setting. The thread interaction portion 154a expediently has an interaction surface which extends helically, e.g. to match the helix of the thread(s) of the drive member thread structure 182 with which the portion 154a cooperates. The interaction surface may be arranged to abut or abuts the drive member thread structure 182 during dose delivery. The thread interaction portion 154a may protrude radially, e.g. radially outwardly and / or inwardly, with respect to the connecting portion 154b.

[0138] In option B, as depicted in figure 7B, the arms 154 have the same length. However, arms of different lengths cold be used as well (potentially requiring an increase in length of the device). The axial extension of the thread interaction portion 154a, e.g. the axial distance between the distal end of the thread interaction portion and the proximal end of the thread interaction portion, is greater than the axial extension of the connecting portion 154b of the arms 154, e.g. the axial distance between the distal end of the arm 154 and the distal end of the thread interaction portion 154a. The thread interaction portion 154a may extend over more than half of the axial extension or length of the respective arm 154.

[0139] In option A, as depicted in figure 7C, there is only one start on the thread of the drive member thread structure 182 (i.e. a single-start (helical) thread or one helix is used). Hence, one solution for the piston rod drive portion 153 is to is to use a single flexible arm 154 (see figure 8). While this is a feasible solution, loading between the drive member 180 and piston rod 150 might be asymmetrical during dose setting and dispense potentially increasing the chance that the parts tilt, causing extra friction or possibly causing unwanted disengagements from other features. Another solution is to use two arms 154 with different lengths and / or axially offset thread interaction portions (as shown in figure 7C). The arms 154 may be arranged diametrically opposite from each other. The length difference or offset may be half of the pitch or lead of the single-start drive member thread or helix. The connecting portions 154b may have different lengths. The axial extension of the thread interaction portion 154a may be greater than one quarter (1 / 4) or greater than one third (1 / 3) of the axial extension of the shorter flexible arm 154. Although the solution with two flexible arms 154 increases the device length over the solution with one flexible arm 154 (see figure 8), it allows a more symmetrical force distribution during setting and dispense. The thread interface portions 154a in option A are designed to interact with the same thread or helix during dose delivery.

[0140] The angular extension of the (respective) flexible arm 154 (in the reference device, in option A, and / or in option B) may be less than or equal to one of the following: 120°, 90°, 80° 70°, 60°, the rotation angle which the piston rod rotates during delivery of one dose.

[0141] In the figure 8 embodiment, the axial extension of the thread interaction portion 154a of the single flexible arm is expediently greater than one quarter or than one third of the axial extension of the arm 154.

[0142] The axial extension of the rotation prevention structures 155 in option A can be smaller than in option B. Expediently, the length is greater than the gap 158 between adjacent rotation prevention structures 155 in both options.

[0143] Figure 9 depicts a proximal region of a piston rod 150, e.g. one suitable for option B. The last dose stop feature 156 angularly overlaps with a rotation prevention structure 155, e.g. the most proximal one. The last dose stop feature 156 may be integrated into the rotation prevention structure 155. A side surface angularly delimiting the last dose stop feature may be arranged to interact with the stop feature of the drive member, e.g. feature 181 , to prevent rotation of the piston rod 150 during dose setting.

[0144] Regarding the last dose stop mechanisms:

[0145] In option B, and in the reference device, the two starts on the drive member thread structure 182 allow two stop features 181 at the same axial position and diametrically opposite each other (see figure 10). The stop features may interact with last dose stop features 156 on the piston rod 150 to prevent setting of a dose after the last dose has been delivered from the device 100. As there are 3 doses per revolution of the piston rod, the stop features 181 on the drive member and the last dose stops 156 on the piston rod only line up rotationally or angularly every three doses, and the stop features 181 pass to the side of the last dose stop feature of the piston rod for doses 3 and 4. For dose 2, the piston rod has not advanced far enough for the stops to contact during dose setting. Figure 11 illustrates the sequence for setting of dose 2 (see representation (a)), setting of dose 3 (see representation (b)), setting of dose 4, which is the last dose in option B (see representation (c)), and after delivery of the last dose (see representation (d)). Notably, at least a part of the stop feature 181 moves past the proximal end of the piston rod main body.

[0146] In option A, there is only one start on the drive member thread. If there are two angularly offset stop features 181 and / or last dose stop features 156, they are advantageously offset axially, e.g. so they can run on the same helix. However, as the rotation during dose delivery is 180° in option A, it may be advantageous to arrange stop features 181 and / or last dose stop features 156 not diametrically opposite to each other (or offset by 180°). Thus, stop features 181 and / or last dose stop features 156 may be unevenly distributed in the angular or circumferential direction on the drive member or the piston rod, respectively. The angular offset may be less than 180°, e.g. 160° or less, 150° or less, 140° or less or 130° or less, or 120° or less. Such an embodiment of the drive member 180 is depicted in figure 12. If the stop features (181 and / or 156) were arranged diametrically opposite from one another the higher (more proximal) stop feature 181 of the drive member would interfere with the lower (more distal) last dose stop feature 156 of the piston rod 150 during setting of the last dose and, hence, prevent dose setting before the last dose has been dispensed. Hence, it is advantageous to use, e.g. two, axially offset stop features 181 and / or, e.g. two, axially offset last dose stop features 156 which are diametrically opposite to one another. Hence, the stop features 181 and / or the last dose stop features 156 are expediently angularly offset by less than 180° as noted already. Figure 13 illustrates the sequence for setting of dose 2 (see representation (a)), setting of dose 3 (see representation (b)), setting of dose 4, which is the last dose in option A (see representation (c)), and after delivery of the last dose (see representation (d)). The drive member 180 is the one of figure 12 with axially and angularly offset stop feature, the angular offset being less than 180°. Notably, at least a part of at least one of the stop features 181 (e.g. of the more proximal one and / or of the more distal one) moves past the proximal end of the piston rod main body 151, e.g. so as to axially overlap with the piston rod drive portion and / or the arms 154. One or more stop features 181 may be displaced entirely beyond the proximal end of the piston rod main body 151. A proximal end and / or a distal end of one of the stop features 181 (e.g. of the more proximal one) may be closer to a proximal end of the piston rod than to the main body. At least one last dose stop feature 156of the piston rod 150 (or only one) may axially overlap with the drive portion 153 or a flexible arm 154 thereof. The last dose stop feature 156 may be provided at least partly (or entirely) on the flexible arm 154 (see representations (c) and (d) in figure 13). This may reduce the required length increase. As can be seen, for dose 3 (representation (b)), the piston rod 150 has not advanced far enough for the drive member stop feature 181 (e.g. the more distal one) to contact the last dose stop feature 156 during dose setting. For the setting of dose 4, the drive member stop feature 181 (e.g. the more proximal one) passes the last dose stop feature 156 as it is angularly offset to the last dose stop feature during setting of the second-to-last dose.

[0147] In some embodiments, the drive member 180 may have just one stop feature 181. Such a drive member 180 is depicted in figure 14. This stop feature 181 may be arranged diametrically opposite from the last dose stop feature 156 when the last deliverable dose has been set. Then, after delivery movement for the last dose (which involves a rotation by 180° of the piston rod) the stop feature 181 and the last dose stop feature 156 are angularly aligned as well. The single stop feature might not provide a last dose stop of a strength as high as a last dose stop using a plurality of stop features 181. However, one stop feature 181 may nevertheless be sufficient.

[0148] In the drawings discussed above, the distal side of the last dose stop 156 is angled or has angled surfaces (e.g. arranged V-like). If a user tries to pull the drive member 180 after the last dose, further axial travel of the drive member 180 is prevented when it contacts the last dose stop 156. In addition, rotation of the piston rod 150 is prevented due to the angled faces. However, these angled faces may be difficult to manufacture and other shapes of the last dose stop feature may also be feasible. For example, the last dose stop feature 156 may have a distal surface which is flat and / or not oblique to the axis A (see figure 3). Axis A may be the (main) longitudinal axis of the piston rod and / or the device. The piston rod 150 may rotate about this axis. The distal surface of the last dose stop feature 156 may extend perpendicular to the axis A. Such an embodiment is shown in figure 15. The shape of the surface of the stop feature 181 facing the last dose stop feature 156 after the last dose has been dispensed may be adjusted to the shape of the surface of the last dose stop feature 156 facing stop feature 181. Consequently, the surface of stop feature 181 may extend perpendicularly to the axis as well and be flat.

[0149] In general, contact between the bearing 170 and the bung 201 of the container 200 should be avoided during storage and transport (e.g. for primary pack stability reasons etc.). Manufacturing tolerances imply that, to avoid contact, a small gap is needed. This gap reduces the size of the first dose, so dispensing a prime dose often called “priming the device” is typically recommended before the first therapeutic or regular dose. The reference device described above may include the indicator 190 to show that priming of the device has been completed. The indicator 190 is axially retained in but rotatable relative to the dose member 120. As discussed already, there are two flexible arms 154 on the proximal end of the piston rod 150. The indicator 190 has two ribs 191 which can be driven by the flexible arms. During priming, the leading angular edge of each flexible arm on the piston rod drives the corresponding driven rib on the prime indicator to rotate the indicator 190. Before priming, there is clearance between the flexible arms and the driven ribs, so that, when the piston rod rotates, e.g. 120°, during prime (i.e. the rotation also performed during delivery of a regular dos), the prime indicator rotates less, e.g. approximately 70°. Figure 16 shows the drive member 180, the indicator 190 and the ribs 191 in representation (a) before priming and in representation (b) when the device has been primed. The clearance C between ribs 191 and arms 154 before priming is shown in representation (a) and R denotes the piston rod rotation during prime dose delivery (e.g. 120°) with IR denoting the rotation of the indicator after the clearance has been closed.

[0150] In option B, the indicator could be configured and used in the same manner as in the reference device as the rotation of the piston rod is 120° as well during dose delivery.

[0151] In option A, the piston rod 150 rotates 180° during priming. If the piston rod with one flexible arm 154 is used, the indicator could be used in a similar manner as in option B (or the reference device), e.g. with the same rotation angle of the indicator 190, albeit with just one driven rib 191 (which may be driven by the rotating piston rod via the one flexible arm). For the piston rod with two flexible arms with axially offset proximal ends, it may be difficult to implement an indicator 190 which is driven simultaneously by both arms 154 and the same rotation angle as in the reference device. Clearance between the flexible arms and driven ribs could only be increased to have the same rotation angle of the indicator as in the reference device by removing material. This might reduce strength of the arms 154 or ribs 191, for example. This may not be desirable. Hence, in option A, with the piston rod having two flexible arms 154 only the longer arm may drive the indicator via one rib 191.

[0152] Instead of having a prime indicator, the initial distance between the bearing 170 and the bung 201 can be adjusted to have a defined value before the device is operated for the first time, i.e. a separate priming step can be avoided. Then already the first dose delivered from the device may be accurate. A variety of solutions can be used to eliminate a priming step. For example, a piston rod assembly with an adjustable axial bearing position relative to the piston rod can be used. In other words, the length of the piston rod assembly comprising piston rod and bearing can be adjusted. For example, the bearing 170 may be connected (e.g. axially locked and rotatable) to an adjuster. The adjuster may be arranged in the interior of the piston rod and / or be threadedly engaged to the piston rod. By rotating the adjuster, the axial position of the bearing relative to the piston rod can be adjusted such that a desired initial distance or gap between piston rod and bung is achieved. Once the desired length of the piston rod assembly has been set, the adjuster can be axially and rotationally locked to the piston rod. Expediently, during the adjustment procedure, the bearing is moved into contact with the bung while the back-off resilient structure is biased, e.g. with dose member 120 fully depressed in the distal direction. Then, the resilient structure may establish the desired gap once the dose member is released by the user (in the same manner as it would after delivery of the second dose in a primed device).

[0153] In some embodiments, the size or length of the bearing can be varied to avoid priming, e.g. by connecting a dedicated bearing of a desired size or length to the piston rod, e.g. its distal end, to result in a desired initial distance.

[0154] Solutions which are suitable to avoid a priming step before the first dose of drug is delivered are disclosed in WO 2015 / 024874 A1 (e.g. relating to a piston rod assembly with an adjustable piston rod length), WO 2015 / 024873 A1 (e.g. relating to a piston rod assembly with an adjustable piston rod length), WO 2010 / 124961 A1 , WO 2010 / 133676 A1, WO 2011 / 039218 A1, and WO 2011 / 051365 A2. The disclosure of each of these documents is incorporated herein by reference for all purposes.

[0155] We note that positions and / or directions herein may be specified with respect to the longitudinal axis of the piston rod 150 or of the device 100 and / or with respect to the rotation axis of the piston rod (see axis A in figure 3 for the longitudinal axis and also for the rotation axis).

[0156] The terms “drug” or “medicament” may be 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.

[0157] As described below, a drug or medicament can include at least one API, or combinations thereof, in various types of 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.

[0158] The drug or medicament may be contained in a primary package or “drug container” adapted for use with a drug delivery device. The drug container may be, e.g., a cartridge, syringe, reservoir, or other solid or flexible vessel configured to provide a suitable chamber for storage (e.g., shorter 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 container may be or may include a dualchamber 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 dual-chamber 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.

[0159] 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.

[0160] 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.

[0161] 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.

[0162] 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.

[0163] Examples of DPP4 inhibitors are Linagliptin, Vildagliptin, Sitagliptin, Denagliptin, Saxagliptin, Berberine.

[0164] 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.

[0165] 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.

[0166] 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).

[0167] 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.

[0168] 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.

[0169] 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).

[0170] 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, 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.

[0171] 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 11608-1 :2014(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.

[0172] 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).

[0173] 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).

[0174] The scope of protection is not limited to the examples given herein above. Any invention disclosed herein is embodied in each novel characteristic and each combination of characteristics, which particularly includes every combination of any features which are stated in the claims, even if this feature or this combination of features is not explicitly stated in the claims or in the examples. Reference signs

[0175] 100 drug delivery device

[0176] 110 housing

[0177] 120 dose member

[0178] 121 window

[0179] 130 cap

[0180] 140 container holder

[0181] 150 piston rod

[0182] 151 piston rod main body

[0183] 152 piston rod thread structure

[0184] 153 piston rod drive portion

[0185] 154 flexible arm

[0186] 154a thread interaction portion

[0187] 154b connecting portion

[0188] 155 rotation prevention structure

[0189] 156 last dose stop feature

[0190] 157 flat section

[0191] 158 gap

[0192] 160 nut member

[0193] 161 nut structure

[0194] 170 bearing

[0195] 180 drive member

[0196] 181 stop feature

[0197] 182 drive member thread structure

[0198] 182a thread

[0199] 182b thread

[0200] 190 indicator

[0201] 200 container

[0202] 201 bung

[0203] 202 septum

Claims

PAT24241-WO-PCTClaims1. A drug delivery device (100), comprising:- a housing (110) with a proximal end and a distal end,- a piston rod (150) movable in the distal direction relative to the housing, the piston rod (150) being rotatably coupled to the housing via a threaded interface,- a drive member (180) movable relative to the housing in the proximal direction in a setting movement to set a dose and movable in the distal direction relative to the housing in a delivery movement to deliver the set dose, wherein the drug delivery device (100) is configured such that the drive member (180), during the delivery movement, is coupled to the piston rod (150) via a drive interface such that the piston rod (150) rotates relative to the housing driven by the delivery movement of the drive member (180) and such that the piston rod (150) moves in the distal direction on account of the threaded interface.

2. The drug delivery device (100) of the preceding claim, wherein the drive interface is a helical interface formed by a drive member thread structure (182) of the drive member (180) engaging a piston rod drive portion (153) of the piston rod (150), and wherein the threaded interface is formed by a piston rod thread structure (152), which extends circumferentially around the piston rod (150), and an associated nut structure (161), wherein the nut structure (161) is axially fixed relative to the housing (110) and engages the piston rod thread structure (152), wherein the piston rod drive portion (153) is or comprises a flexible portion, wherein the flexible portion comprises one or more flexible sections (154), and wherein each flexible section has a thread structure interaction portion (154a) which is configured to interact with the drive member thread structure (182).

3. The drug delivery device (100) of any one of the preceding claims, wherein the piston rod drive portion (153) comprises just one flexible section (154).

4. The drug delivery device (100) of any one of the preceding claims 1 to 2, wherein the piston rod drive portion (153) has a plurality of flexible sections (154), and wherein the thread structure interaction portions (154a) of the plurality of flexible sections (154) are axially offset from one another.

5. The drug delivery device (100) of the preceding claim 2 to 4, wherein the thread structure interaction portions (154a) of the plurality of flexible sections (154) are designed to engage the same helix of a thread of the drive member thread structure (182).

6. The drug delivery device (100) of any one of the preceding claims 2 to 5, wherein the number of thread starts of the drive member thread structure (182) is different from the number of thread starts of the piston rod thread structure (152).

7. The drug delivery device (100) of any one of the preceding claims 2 to 6, wherein the drive member thread structure (182) is a single-start thread structure with one helix.

8. The drug delivery device (100) of any one of the preceding claims 2 to 7, wherein the piston rod thread structure (152) is a multi-start thread structure with more than one helix.

9. The drug delivery device (100) of any one of the preceding claims 2 to 8, wherein the respective thread structure interaction portion (154a) is connected to the piston rod main body (151) by a connecting portion (154b) of the flexible section (154) wherein the connecting portions (154b) of different flexible sections have different axial extensions.

10. The drug delivery device (100) of any one of the preceding claims 2 to 9, wherein the thread structure interaction portions (154a) of different flexible sections have the same axial extension.

11. The drug delivery device (100) of any one of the preceding claims 2 to 10, wherein the piston rod (150) comprises one or more last dose stop features (156), wherein the respective last dose stop feature (156) protrudes radially from the piston rod (150), and wherein the respective last dose stop feature is arranged to interact with an associated stop feature (181) of the drive member (180) to prevent setting of a dose when the piston rod (150) has reached a distal end position relative to the housing (110) after the last delivery movement of the drive member (180).

12. The drug delivery device (100) of claim 11, wherein two stop features (181) of the drive member (180) are axially offset from each other and angularly offset from each other by less than 180°.

13. The drug delivery device (100) of claim 11 , wherein the drive member (180) comprises just one stop feature (181).

14. The drug delivery device (100) of any one of the preceding claims, wherein the piston rod (150) comprises a plurality of rotation prevention structures (155), which are arranged to interact with one or more features of the drive member (180) to prevent rotation of the piston rod (150) in the setting movement, and wherein the axial extension of the rotation prevention structures (155) is greater than an axial gap between two adjacent rotation prevention structures.

15. The drug delivery device (100) of any one of the preceding claims, wherein the drug delivery device (100) comprises a container (200) with a drug or medicament.

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