A medicment delivey system

Abstract

A medicament delivery system (10) comprising a reusable injector device (100) and a cartridge (200) for use with the reusable injector device. The cartridge and device are combinable for medicament delivery and separable thereafter. The cartridge comprises: a pre-filed syringe (230) comprising a needle (233); a cassette (210) partially housing the pre-filled syringe so that the needle extends from a proximal end of the cassette; and a needle cover (240) extending over the proximal end of the cassette to surround the needle. The reusable injector device comprises: a housing (110); a needle cover shuttle (120) displaceable within the housing against a needle cover shuttle spring (120s); a cassette shuttle (150) displaceable within the housing against a cassette shuttle spring (150s); and a plunger rod (170) configured to dispense medicament from the pre-filed syringe in use. When the cartridge and the reusable injector device are combined, the needle cover engages the needle cover shuttle and the cassette engages the cassette shuttle. The needle is displaceable against the needle cover shuttle spring between a primed position, in which the needle cover extends from a proximal end of the housing, and a dose delivery position, distal of the primed position. The cassette shuttle is configured to advance the cassette in a proximal direction so that the needle extends from a proximal end of the needle cover only after the needle cover has been displaced into the dose delivery position.

Description

[0001] A MEDICMENT DELIVEY SYSTEM

[0002] FIELD OF INVENTION

[0003] The present invention relates to a medicament delivery system comprising a cartridge and reusable injector device.

[0004] BACKGROUND

[0005] Medicament delivery devices, such as auto-injectors, are known in the art for dispensing a medicament to an injection site of a patient. Such medicament delivery devices typically comprise needle in fluid communication with a syringe and a piston rod that is moveable to dispense the medicament within the syringe through the needle into the injection site.

[0006] In such medicament delivery devices the piston rod is biased towards the injection site to dispense the medicament. Once the medicament has been dispensed, the needle is covered by a needle shield and / or needle cover and the medicament delivery device is dispensed of.

[0007] SUMMARY

[0008] In a first aspect of the invention, , there is provided a reusable injector device for use with a cartridge containing a pre-filled syringe, the device comprising: a housing; a needle cover shuttle displaceable within the housing against a needle cover shuttle spring; a cassette shuttle displaceable within the housing against a cassette shuttle spring; and a plunger rod configured to dispense medicament from the pre-filed syringe in use; wherein the reusable injector device is configured so that, when a cartridge for use with the device is connected thereto, the needle cover shuttle is displaceable against the needle cover shuttle spring between a primed position and a dose delivery position, distal of the primed position; and wherein the cassette shuttle is configured to advance in a proximal direction only after the needle cover shuttle has been displaced into the dose delivery position.

[0009] The device may further comprise an opening in the proximal end of the housing for insertion of a cartridge for use with the device.

[0010] Insertion of a cartridge into the housing may distally displace the needle cover shuttle into the primed position, charging the needle cover shuttle spring. The needle cover shuttle may comprise a track in its outer surface that engages a pin extending from the inner surface of the housing, so that movement of the needle cover shuttle along the longitudinal axis of the device causes the pin to traverse the track; and wherein the track comprises ramped portions configured to rotate the needle cover shuttle to cause the needle cover shuttle to lock to and unlock from a cartridge inserted into the device as the needle cover shuttle moves between different positions.

[0011] The track may comprise a first distal terminus which, when the pin abuts the first distal terminus, defines the primed position of the needle cover shuttle, and a second distal terminus which, when the pin abuts the second distal terminus, defines a post delivery position of the needle cover shuttle.

[0012] The device may be provided with an activation button pressable into the housing to begin an injection when a cartridge for use with the device is inserted into the device and the needle cover is in the dose delivery position; and wherein, when the needle cover is in the primed position, the needle cover blocks the activation button being pressed into the housing

[0013] The activation button is configured to hold the cassette shuttle against the cassette shuttle spring, and wherein pressing the activation button into the housing releases the cassette shuttle so that the cassette shuttle is advanced in a proximal direction by the cassette shuttle spring.

[0014] In a second aspect of the invention, there is provided a cartridge for use with a reusable injector device, wherein the cartridge comprises: a pre-filed syringe comprising a needle; a cassette partially housing the pre-filled syringe so that the needle extends from a proximal end of the cassette; and a needle cover extending over the proximal end of the cassette to surround the needle.

[0015] The cassette may comprises a clip configured to releasably engage a reusable injector device for use with the cartridge.

[0016] The cartridge may comprise a cap, and wherein the cap comprises a clip having a blocking element that extends through a window of the needle cover and a window of the cassette to prevent relative axial movement of the needle cover, the cassette and the cap.

[0017] The needle cover may comprise a needle cover pin engageable with the window of the cassette to lock the needle cover in a needle shielding position following removal of the cap. In a third aspect of the invention, there is provided a medicament delivery system comprising a reusable injector device and a cartridge for use with the reusable injector device; the cartridge and device being combinable for medicament delivery and separable thereafter; wherein, the cartridge comprises: a pre-filed syringe comprising a needle; a cassette partially housing the pre-filled syringe so that the needle extends from a proximal end of the cassette; and a needle cover extending over the proximal end of the cassette to surround the needle; wherein, the reusable injector device comprises: a housing; a needle cover shuttle displaceable within the housing against a needle cover shuttle spring; a cassette shuttle displaceable within the housing against a cassette shuttle spring; and a plunger rod configured to dispense medicament from the pre-filed syringe in use; wherein, when the cartridge and the reusable injector device are combined, the needle cover engages the needle cover shuttle and the cassette engages the cassette shuttle, the needle cover being displaceable against the needle cover shuttle spring between a primed position in which the needle cover extends from a proximal end of the housing and a dose delivery position, distal of the primed position; and wherein the cassette shuttle is configured to advance the cassette in a proximal direction so that the needle extends from a proximal end of the needle cover only after the needle cover has been displaced into the dose delivery position.

[0018] Therefore, a medicament delivery system is provided in which components of the system are reusable, reducing waste. Furthermore, the invention provides a two step injection process for increased safety in which the needle cover must first be displaced before the needle is advanced.

[0019] The cartridge may be connected to the device by insertion of a distal end of the cartridge into an opening in the proximal end of the housing.

[0020] In this way, the device is intuitively and simply assembled.

[0021] During insertion of the cartridge into the housing, a distal end of the needle cover may engage a proximal end of the needle cover shuttle, displacing the needle cover shuttle in a distal direction and charging the needle cover shuttle spring.

[0022] In this way the act of combing the cartridge and device charges the needle cover shuttle spring, making for a simple and reliable device.

[0023] The cassette may comprise a clip configured to releasably engage the cassette shuttle when the cartridge and device are combined. As the clip is configured to be releasable, the cartridge may still be removed from the device after combination of the cartridge and the device. This may be useful if the wrong cartridge has been selected.

[0024] The proximal end of the needle cover may be flush with a proximal end of the housing when the needle cover is in the dose delivery position.

[0025] In this way, the needle cover may be displaced into the dose delivery position by pressing a proximal end of the needle cover against an injection site until the proximal end of the needle cover and proximal end of the housing are flush. This provides a simple mechanism that is easy to operate.

[0026] The cartridge may comprises a cap, wherein the cap comprises a clip having a blocking element that extends through a window of the needle cover and a window of the cassette to prevent relative axial movement of the needle cover, the cassette and the cap.

[0027] In this way, the cartridge is provided in a safe and stable state prior to removal of the cap.

[0028] The housing may comprise a circumferential ramp depending from its inner surface that is configured to engage the clip of the cap when the cartridge and the device are combined, the clip and the ramp being configured to cooperate so that, on rotation of the cap about a longitudinal axis of the device, the clip is lifted by the ramp to remove the blocking element from the windows in the cassette and needle cover, allowing removal of the cap.

[0029] In this way, combination of the cartridge and the device facilitates removal of the cap in a simple and intuitive way.

[0030] Following removal of the cap, the needle cover may advanced in a proximal direction to the primed position by the needle cover shuttle spring.

[0031] Following an injection, the needle cover shuttle spring may be configured to proximally advance the needle cover into a post delivery position, proximal of the primed position, to conceal the needle.

[0032] In this way, the needle remains concealed from a user at every stage, preventing unintended needle stick injury. The needle cover shuttle may comprises a track in its outer surface that engages a pin extending from the inner surface of the housing, so that movement of the needle cover shuttle along the longitudinal axis of the device causes the pin to traverse the track; and wherein the track comprises ramped portions configured to rotate the needle cover shuttle to cause the needle cover shuttle to lock to and unlock from the needle cover as the needle cover shuttle moves between different positions.

[0033] In this way, movement of the needle cover shuttle following removal of the cap locks the cartridge to the device.

[0034] Proximal movement of the needle cover into the primed position may cause the pin to traverse the ramped portion of the track to cause the needle cover shuttle to lock to the needle cover.

[0035] A locking tab on the needle cover shuttle may rotate into alignment with a locking tab on the needle cover to cause the needle cover shuttle to lock to the needle cover during proximal movement of the needle cover into the primed position.

[0036] Proximal movement of the needle cover from the dose delivery position to the post delivery position may cause the pin to traverse the other ramped portion of the track to cause the needle cover shuttle to unlock from the needle cover.

[0037] In this way, automatic unlocking of the cartridge from the device can be effected by removal of the device from the injection site.

[0038] The device may be provided with an activation button pressable into the housing to begin an injection when the needle cover is in the dose delivery position; and wherein, when the needle cover is in the primed position, the needle cover blocks the activation button being pressed into the housing.

[0039] In this way, the injection process is prevented from being started prematurely.

[0040] The activation button may be configured to hold the cassette shuttle against the cassette shuttle spring, and wherein pressing the activation button into the housing releases the cassette shuttle so that the cassette shuttle is advanced in a proximal direction by the cassette shuttle spring, thereby advancing the cassette and causing the needle to protrude from the proximal end of the housing. In a fourth aspect of the invention, there is provided a method of use of a medicament delivery system, the method comprising: inserting the cartridge in the housing of the device; and removing the cap of the cartridge to cause the device to advance the needle cover into the primed position.

[0041] BRIEF DESCRIPTION OF THE DRAWINGS

[0042] Exemplary embodiments of the present invention are described with reference to the accompanying drawings, in which:

[0043] Fig. 1 shows a schematic view of a cartridge according to an exemplary embodiment of the invention;

[0044] Fig. 2 shows a schematic view of a reusable injector device according to an exemplary embodiment of the invention;

[0045] Fig. 3 is a section of the cartridge shown in perspective view;

[0046] Fig. 4 is a section of the reusable auto injector device shown in perspective view;

[0047] Fig. 5 is a section of the reusable auto injector device and the cartridge aligned for assembly;

[0048] Fig. 6 is a section of the cartridge and the reusable auto injector device in an assembled preuse state;

[0049] Fig. 7 is a detail section showing an interface between the cartridge and the reusable auto injector device;

[0050] Figs. 8a to 8c show three positions of a cassette shuttle of the cartridge as the cartridge and the reusable auto injector device are assembled;

[0051] Fig. 9 is a detail view of a needle cover shuttle of the reusable auto injector device in a recharged state;

[0052] Fig. 10 is a detail view of an interface between the cartridge and the reusable auto injector device;

[0053] Fig. 11 is a section of the cartridge and the reusable auto injector device in a primed pre-use state;

[0054] Fig. 12 is a detail view of the needle cover shuttle in a primed state;

[0055] Fig. 13 is a detail view of an interface between the cartridge and the reusable auto injector device;

[0056] Fig. 14 is a section of the cartridge and the reusable auto injector device in a primed and on body state;

[0057] Fig. 15 is a detail view of the needle cover shuttle in a primed and on body state;

[0058] Fig. 16 is a detail section showing an injection activation button and the needle cover shuttle in the primed state;

[0059] Fig. 17 is a detail section showing the injection activation button and the needle cover shuttle in the primed and on body state; Figs. 18a to 18c show three stages of operation of the injection activation button;

[0060] Fig. 19 is a detail view of the needle cover shuttle in a drug delivery state;

[0061] Fig. 20 is a detail section showing an interface between the cartridge and the reusable auto injector device;

[0062] Fig. 21 is a section of the cartridge and the reusable auto injector device in a drug delivery state;

[0063] Fig. 22 is a detail view of the needle cover shuttle in a post delivery state;

[0064] Fig. 23 is a section of the cartridge and the reusable auto injector device in a post delivery state; Fig. 24 is a detail section showing an interface between the cartridge and the reusable auto injector device;

[0065] Fig. 25 is a section of the cartridge and the reusable auto injector device in a post deliver, plunger recharged state;

[0066] Fig. 26 is a section showing the cartridge and reusable autoinjector device in post delivery separated state;

[0067] Fig. 27 shows the cartridge pre-use;

[0068] Fig. 28 shows the cartridge post-use;

[0069] Fig. 29 is a detail view of the cartridge according to another embodiment of the invention; and Figs. 30a and 30b are schematic illustrations showing a plunger release mechanism and a plunger recharging mechanism.

[0070] DETAILED DESCRIPTION

[0071] A drug delivery device, as described herein, may be configured to inject a medicament into a patient. For example, delivery could be sub-cutaneous, intra-muscular, or intravenous. Such a device could be operated by a patient or care-giver, such as a nurse or physician, and can include various types of safety syringe, pen-injector, or auto-injector. The device can include a cartridge-based system that requires piercing a sealed ampule before use. Volumes of medicament delivered with these various devices can range from about 0.5 ml to about 2 ml. Yet another device can include a large volume device (“LVD”) or patch pump, configured to adhere to a patient’s skin for a period of time (e.g., about 5, 15, 30, 60, or 120 minutes) to deliver a “large” volume of medicament (typically about 2 ml to about 10 ml).

[0072] In combination with a specific medicament, the presently described devices may also be customized in order to operate within required specifications. For example, the device may be customized to inject a medicament within a certain time period (e.g., about 3 to about 20 seconds for auto-injectors, and about 10 minutes to about 60 minutes for an LVD). Other specifications can include a low or minimal level of discomfort, or to certain conditions related to human factors, shelf-life, expiry, biocompatibility, environmental considerations, etc. Such variations can arise due to various factors, such as, for example, a drug ranging in viscosity from about 3 cP to about 50 cP. Consequently, a drug delivery device will often include a hollow needle ranging from about 25 to about 31 Gauge in size. Common sizes are 27 and 29 Gauge.

[0073] The delivery devices described herein can also include one or more automated functions. For example, one or more of needle insertion, medicament injection, and needle retraction can be automated. Energy for one or more automation steps can be provided by one or more energy sources. Energy sources can include, for example, mechanical, pneumatic, chemical, or electrical energy. For example, mechanical energy sources can include springs, levers, elastomers, or other mechanical mechanisms to store or release energy. One or more energy sources can be combined into a single device. Devices can further include gears, valves, or other mechanisms to convert energy into movement of one or more components of a device.

[0074] The one or more automated functions of an auto-injector may each be activated via an activation mechanism. Such an activation mechanism can include one or more of a button, a lever, a needle sleeve, or other activation component. Activation of an automated function may be a one-step or multi-step process. That is, a user may need to activate one or more activation components in order to cause the automated function. For example, in a one-step process, a user may depress a needle sleeve against their body in order to cause injection of a medicament. Other devices may require a multi-step activation of an automated function. For example, a user may be required to depress a button and retract a needle shield in order to cause injection.

[0075] In addition, activation of one automated function may activate one or more subsequent automated functions, thereby forming an activation sequence. For example, activation of a first automated function may activate at least two of needle insertion, medicament injection, and needle retraction. Some devices may also require a specific sequence of steps to cause the one or more automated functions to occur. Other devices may operate with a sequence of independent steps.

[0076] Some delivery devices can include one or more functions of a safety syringe, pen-injector, or auto-injector. For example, a delivery device could include a mechanical energy source configured to automatically inject a medicament (as typically found in an auto-injector) and a dose setting mechanism (as typically found in a pen-injector). The present invention relates to a reusable injector device 100 and a cartridge 200 for use with the reusable injector device 100. Figs. 1 to 30b represent an exemplary embodiments of the invention.

[0077] In the foregoing description, the terms ‘square’ and ‘ramped’ are used. Respectively, square and ramped refer to planar surfaces that extend perpendicular and obliquely to the longitudinal axis of either the cartridge or injector device. The term “distal” refers to a location that is relatively closer to a site of injection, and the term "proximal" refers to a location that is relatively further away from the injection site.

[0078] The Cartridge

[0079] The cartridge 200 is shown in longitudinal section in Fig. 3. The cartridge 200 is a single use component that is attached to the reusable injector device 100 to administer a dose of medicament to a patient. The cartridge 200 comprises a cassette 210, a pre-filled syringe 230, a needle cover 240 and a cap 260; each of which have a generally cylindrical body that is arranged coaxially along a cartridge axis Xc-Xc.

[0080] The cassette 210 comprises a cylindrical body 211 with a distal region 211 ’ having a first external diameter and a proximal region 211 ” having a second external diameter, less than the first external diameter. A shoulder 212 defines the boundary between the proximal and distal regions 211 ’, 211 ” of the cassette 210. The shoulder 212 is square to the proximal and distal regions 211 , 211’. The pre-filled syringe 230 is received within an internal bore 213 of the cassette 210 and extends along its length. A clip 214 extends from a distal end 215 of the cassette 210 for attachment to cassette shuttle of the reusable injector device as explained further below. The clip 214 comprises two spring prongs 216 that extend parallel to and either side the axis of the cartridge 200. The spring prongs 216 terminate at their distal end in a retaining block 217. Each retaining block comprises a square proximal surface 217’ and a ramped distal surface 217”.

[0081] The needle cover 240 comprises a tubular wall 241 with a flange 242 at its distal end. The flange 242 is a radial wall that extends around a distal opening of the tubular wall 241. The needle cover 240 is received over the proximal region 211 ” of the cassette 210 so that the internal surface of the tubular wall of the needle cover 240 is closely spaced to or abutting the external surface of the proximal region 211” of the cassette 210. Prior to use of the cartridge 200, a distal surface 242’ of the flange 242 abuts the shoulder 212 of the cassette 210. The cap 260 comprises a tubular wall 261 that is open at one end and closed at the other by an end wall 262. The end wall 262 is circular and overhangs the outer surface of the tubular wall 261 to provide an edge for a user to grip if they need to remove the cartridge 200 from the auto injector device 100. Prior to use of the cartridge 200, the proximal end of the needle cover 240 extends within the tubular wall 261 of the cap 260. The cap 260 also comprises a clip 263 formed in the tubular wall 261 . The clip 263 comprises a portion of the tubular wall defined between two parallel cuts 264 that extend to the distal edge of the tubular wall 261. Therefore, the clip 263 is free to flex in a radial direction, hinging between the proximal ends of the cuts 264. The clip 263 comprises a blocking element 265 at its distal end. The blocking element 265 projects in a radial direction both outwardly and inwardly of the tubular wall 261. The inwardly projecting part 265’ of the blocking element 265 extends through a window 243 in the tubular wall 241 of the needle cover 240 and into a window 218 in the proximal region 211 ” of the cassette 210. In this way the blocking element 265 prevents relative axial movement of the needle cover 240, the cassette 210 and the cap 260.

[0082] The pre-filled syringe 230 comprises a cylindrical vial 231 filled with medicament, a bung 232, a needle 233, a rigid needle shield (RNS) 234 and a piston 235. The bung 232 seals the proximal end of the vial 231 and the piston 235 the distal end. The needle 233 extends through the bung 232 and into the vial 231 . The piston 235 is configured for proximal displacement through the vial 231 during operation of the device to dispense the medicament through the needle 233. The needle 233 protrudes from an opening in the proximal end of the cassette 210 and is enclosed by the RNS 234. The RNS 234 is a cylindrical block of protective material with a cavity in which the needle 233 extends. The RNS 234 is tightly fitted within an internal RNS holder 266 of the cap 260 so that the RNS 234 is removed with the cap 260 when the cap 260 is removed.

[0083] Reusable Injector Device

[0084] Fig. 4 shows the reusable injector device 100 in section. The reusable injector device 100 is herein referred to simply as the ‘device 100’ for brevity. The device 100 comprises: a housing 110; a needle cover shuttle 120 and associated needle cover shuttle spring 120s; a cassette shuttle 150 and associated cassette shuttle spring 150s, a plunger rod 170 and associated plunger rod spring 170s; and an injection activation button 180. The springs 120s, 150s, 170s are not shown in Fig. 4 so as not to obscure the view of the other features. However, the springs 120s, 150s, 170s are shown schematically in Fig. 2, which is a schematic cross section of the device 100. The housing 110 comprises a tubular wall 111 that is open at the proximal end and closed by an end wall 112 at the distal end. The outer surface of the tubular wall 111 forms the outer surface of the device 100 which is, therefore, cylindrical in appearance.

[0085] The needle cover shuttle 120 (herein also ‘NC shuttle 120’) is received within the housing 110 and comprises a tubular wall 121. The outer surface of the tubular wall 121 of the NC shuttle 120 is closely spaced to the inner surface of the tubular wall 111 of the housing 110. A track 122 on the outer surface of the tubular wall 121 of the NC shuttle 120 engages a pin 113 protruding from the inner surface of the tubular wall 111 of the housing 110 (hereinafter ‘housing pin 113’). During use, the NC shuttle 120 moves axially within the housing 110 causing the housing pin 113 to traverse the track 122.

[0086] The NC shuttle 120 comprises a cut out 123 that extends into the tubular wall 121 from its distal end. The cut out 123 provides clearance for an actuator arm of the injection activation button as will be explained further below. The NC shuttle 120 further comprises a locking tab 124 at its proximal end that is configured to engage a corresponding locking tab on the needle cover 240 during use. Prior to use of the device, the NC shuttle 120 is in a first position, which is the most proximal position of its axial range of motion. The NC shuttle spring 120s is a helical coil spring that extends between a distal end of the housing 110 and a distal end of the NC shuttle 120. With the NC shuttle 120 in the first position, the NC shuttle spring 120s is in a discharged state, meaning the NC shuttle spring 120s is unwound and at maximum extension.

[0087] The cassette shuttle 150 is disc shaped with a central opening 151 centred on the longitudinal axis Xd-Xd of the device 100. The central opening 151 allows the plunger rod 170 to pass through the cassette shuttle 150. Prior to use of the device, the cassette shuttle 150 is in a first position, which is the most proximal position of its axial range of motion. The cassette shuttle spring 150s is a helical coil spring that extends between a distal end of the housing 110 and a distal end of the cassette shuttle 150. With the cassette shuttle 150 in the first position, the cassette shuttle spring 150s is in a discharged state, meaning the cassette shuttle spring 150s is unwound and at maximum extension.

[0088] The injection activation button 180 (herein also simply ‘button 180’) comprises a block 181 , a button pin 182, a button spring (not shown) and an actuator arm 183. The block 181 is set into an opening 114 in the tubular wall 111 of the housing 110 and comprises an outer surface 184 that presents to a user for pressing during operation of the device 100. The outer surface 184 is outwardly offset from the outer surface of the tubular wall 111 after assembly of the device 110 so that the button 180 is easier to press during use. As will be explained further below, the button 180 is pressed to allow the cassette shuttle 150 and cassette 210 to advance in a proximal direction. The actuator arm 183 extends from an inner surface of the block 181. The actuator arm 183 is C shaped and extends along a minor arc of substantially the same diameter as the diameter of the tubular wall 121 of the NC shuttle 120. The button pin 182 extends radially from the inner surface of the block 181 for interaction with a window in the tubular wall 121 of the NC shuttle 120. The button spring biases the button 180 radially outward to react the press force of a user.

[0089] The plunger rod 170 is configured to engage and displace the piston 235 under the force of the plunger rod spring 170s. Prior to use of the device, the plunger rod 170 is in a first position, which is the most distal position of its axial range of motion. The plunger rod spring 170s is a helical coil spring that extends between a distal end of the housing 110 and a distal end of the plunger rod 170. With the plunger rod 170 in the first position, the plunger rod spring 170s is in a charged state, meaning the plunger rod spring 170s is compressed ready for extension.

[0090] Referring again to the schematic of Fig. 2, each of the plunger rod spring 170s, cassette shuttle spring 150s and NC shuttle spring 120s have a different diameter, allowing them to be coaxial while overlapping longitudinally. In order of ascending radial position are: the plunger rod spring 170s, the cassette shuttle spring 150s and the NC shuttle spring 120s. In an unillustrated embodiment, the plunger rod spring 170s may overlap the plunger rod 170. In other words, the plunger rod spring 170s may be wound around the plunger rod 170. In this way the plunger rod 170 provides stability to the plunger rod spring 170s.

[0091] Cartridge and device assembly

[0092] Fig. 5 shows the cartridge 200 and device 100 aligned for assembly but separate. Fig. 6 shows the cartridge 200 and the device 100 in an assembled pre-use state in which the cartridge 200 is connected to the device 100.

[0093] The cartridge 200 is connected to the device 100 by insertion of the distal end of the cartridge 200 into an opening 115 in the proximal end of the housing 110. During insertion of the cartridge 200 into the housing 110, the clip 214 of the cassette engages a first region 152 of the central opening 151 of the cassette shuttle 150. As the cartridge 200 is moved into the housing 110, the cassette shuttle 150 is displaced in a distal direction, charging a cassette shuttle spring 150s.

[0094] The first region 152 of the inner edge of the cassette shuttle 150 is configured to allow removal of the cartridge 200 from the device 100 after connection, but prior to removal of the cap 260. This allows the cartridge 200 to be removed and changed if, for example, a cartridge containing the wrong medicament has been installed. As shown in Fig. 7, the first region 152 of the inner edge of the cassette shuttle 150 comprises ramped proximal and distal surfaces 152’, 152” to displace the spring prongs 216 of the clip 214 inward as the cartridge 200 is connected to, and removed from, the device 100, respectively.

[0095] Figs. 8a - 8c show the interaction between the cassette shuttle 150 and the actuator arm 183 of the button 180 during insertion of the cartridge 200 into the housing 110. A ramped outer surface 153 of the cassette shuttle 150 contacts a ramped inner surface 185 of the actuator arm 183, deflecting the button 180 into the device 100 against the button spring, as shown by Fig. 8b. Once the ramped surfaces 153, 185 have passed over each other, the button 180 is displaced by the button spring to protrude again from the housing 110 and the cassette shuttle 150 is locked in a distal position by the button actuator arm 183, as shown by Fig. 8c.

[0096] Also during insertion of the cartridge 200 into the housing 110, the flange 242 of the needle cover 240 engages a proximal end of the needle cover shuttle 120, displacing the needle cover shuttle 120 in a distal direction and charging the needle cover shuttle spring 120s.

[0097] As the needle cover shuttle 120 is displaced, the housing pin 113 traverses a first portion 1221 of the track 122, as illustrated by the dotted line in Fig. 9. The first portion 1221 of the track 122 comprises an axially extending portion 1221 ’ and a first ramped portion 1221 ”. The housing pin 113 first traverses the axially extending portion 1221 ’ before traversing the first ramped portion 1221 ”. As the housing pin 113 traverses the ramped portion 1221 ”, the axial movement of the needle cover shuttle 120 is converted into a rotational movement of the needle cover shuttle 120. At the end of the first track portion 1221 , the housing pin 113 abuts a proximal terminus 1222 of the track 122, preventing further distal movement of the needle cover shuttle 120 and the cartridge 200. So arranged, the housing pin 113 is aligned with a second portion of the track which the housing pin 113 will traverse when the needle cover shuttle 120 travels in proximal direction, as explained further below.

[0098] Once the cartridge 200 is connected to the device 100, the clip 263 is engaged with a circumferential ramp 116 depending from the inner surface of the housing 110, as shown in Fig. 10. The cap 260 may be removed by twisting the cap 260 to rotate it about the axis xd - xd of the device, as shown by arrow A1 in Fig. 11 . This rotation causes the outwardly projecting part 265” of the blocking element 265 of the clip 263 to ride along the circumferential ramp 116, lifting the clip 263 so that the inwardly projecting part 265’ of the blocking element 265 moves clear of the windows 218, 243 in the cassette 210 and needle cover 240. With the blocking element 265 clear of the windows 218, 243, the cap 260 is free to be removed by pulling the cap in a proximal direction (indicated by arrow A2).

[0099] With the cap 260 removed and the needle cover 240 no longer locked to the cassette 210 by the blocking element 265, the needle cover 240 and the needle cover shuttle 120 are advanced in a proximal direction by the needle cover shuttle spring 120s.

[0100] The proximal movement of the needle cover shuttle 120 causes the housing pin 113 to traverse the second portion of the track 1223 comprising a second ramped portion 1223’, as illustrated by Fig. 12. As the pin 113 traverses the second ramped portion 1223’, the axial movement of the needle cover shuttle 120 is converted into a rotational movement of the needle cover shuttle 120. At the end of the second track portion 1223 the pin 113 abuts a first distal terminus 1224, preventing further proximal movement of the needle cover shuttle 120 and the needle cover 240. The rotation of the needle cover shuttle 120 causes the locking tab 124 on the needle cover shuttle 120 to rotate into alignment with the locking tab 244 on the needle cover 240, as shown in Fig. 13. The aligned tabs 124, 244 overlap each other to lock the needle cover 240 to the needle cover shuttle 120 and thereby prevent the cartridge 200 from being removed from the device 100.

[0101] With the housing pin 113 abutting the first distal terminus 1224 of the needle cover shuttle 120, the needle cover 240 is in a primed position in which it protrudes from the proximal end of the housing 110. This allows the needle cover 240 to be pressed up against an injection site to trigger an injection as will be explained further below.

[0102] Referring again to Fig. 3, a pin 245 extends from an internal surface of the needle cover 240 (hereinafter needle cover pin 245) and into an axially extending slot 219 of the cassette 210 which the needle cover pin 245 traverses when the needle cover 240 moves relative to the cassette 210. The needle cover pin 245 prevents the rotation of the needle cover shuttle 120 causing rotation of the needle cover 240 when the needle cover 240 is displaced.

[0103] To begin an injection, the needle cover 240 is pushed up against the injection site causing the needle cover 240 and the needle cover shuttle 120 to be displaced in a distal direction relative to the housing 110. This distal movement of the needle cover 240 is shown illustrated by arrow A3 in Fig. 14. With the device 100 pressed against the injection site, the proximal end of the needle cover 240 is flush with the proximal end of the housing 110. As illustrated by Fig. 15, the distal movement of the needle cover shuttle 120 causes the housing pin 113 to traverse a third portion of the track 1225. At the end of the third portion of the track 1225, the housing pin 113 abuts an intermediate terminus 1226 of the track 122 preventing further distal movement of the needle cover shuttle 120 and the needle cover 240. The housing pin 113 abutting the intermediate terminus 1226 corresponds with the proximal end of the needle cover 240 being flush with the proximal end of the housing 110. This position of the needle cover 240 and the needle cover shuttle 120 is herein referred to as the dose delivery position.

[0104] With the needle cover 240 in the primed position, the button pin 182 extends into contact with the outer surface of the tubular wall 121 of the needle cover shuttle 120, thereby preventing the button 180 being pressed into the housing 110 - as shown in Fig. 16. With the needle cover 240 in the dose delivery position (i.e. with the device 100 pressed up against the injection site so that the needle cover 240 is disposed so that its proximal end is flush with the proximal end of the housing 110), a window 125 in the tubular wall 121 of the needle cover shuttle 120 aligns with the button pin 182, enabling the button 180 to be pressed into the housing 110 - as shown in Fig. 17.

[0105] To begin an injection, the button 180 is pressed into the housing 110, causing the actuator arm 183 to move out of the way of the cassette shuttle 150 so that the cassette shuttle 150 is advanced in a proximal direction by the cassette shuttle spring 150s - as shown in Figs. 18a- 18c. As the button 180 is pressed, the actuator arm 183 engages an edge 126 of the cut out 123 in the needle cover shuttle 120 and causes the needle cover shuttle 120 to rotate. This rotation moves the housing pin 113 along a fourth portion of the track 1227 that leads into the axially extending portion 1221 ’ of the first track portion 1221 , as shown in Fig. 19.

[0106] The cassette shuttle 150 then advances the cassette 210 in a proximal direction under the cassette shuttle spring 150s force. A track 117 on the inner surface of the housing 110 (hereinafter housing track 117) engages a pin 154 protruding from the cassette shuttle 150 (hereinafter cassette shuttle pin 154). During proximal movement of the cassette shuttle 150, the cassette shuttle pin 154 traverses a ramped portion 117’ of the housing track 117 converting the axial movement of the cassette shuttle 150 into a rotational movement of the cassette shuttle 150 until the cassette shuttle pin 154 reaches a proximal terminus 1171 of the housing track 117.

[0107] The rotational movement of the cassette shuttle 150 causes the ramped surfaces 152’, 152” of the first region 152 of the central opening 151 of the cassette shuttle 150 to move out of alignment with the clip 214 of the cassette 210. Following traverse of the ramped portion 117’ by the cassette shuttle pin 154, the clip 214 of the cassette 210 is aligned with a second region 155 of the central opening 151 comprising a square surface 155’ (as shown in Fig. 20), thereby locking the cassette 210 to the cassette shuttle 150.

[0108] The plunger rod 170 is released by a plunger rod release mechanism 190 (as illustrated in Figs. 30a and 30b). The plunger rod release mechanism 190 is provided adjacent a distal region of the plunger rod 170 so as not to interfere with the operation of the needle cover shuttle 120. The plunger rod release mechanism 190 is powered by a battery (not shown) and comprises a magnetic spring arm 191 (hereinafter spring arm 191 for brevity) and an electromagnet 192. The electromagnet 192 forms part of an electrical circuit comprising the battery. To release the plunger rod 170, the electrical circuit is completed by a switch, causing the electromagnet 192 to deflect the spring arm 191. The spring arm 191 is connected in cantilever fashion to the housing 110 and comprises a retaining block 193 at its end. The spring arm 191 biases the retaining block 193 toward the plunger rod 170. When the plunger rod 170 is in the first position, the retaining block 193 engages a notch 171 in the plunger rod 170 to hold the plunger rod 170 against the force of the plunger rod spring 170s (as shown in Fig. 30a). When the injection activation button 180 is pressed, the actuator arm 183 makes contact with the switch to complete the electrical circuit. This activates the electromagnet 192 and deflects the spring arm 191 outward, away from the plunger rod 170, releasing the retaining block 193 from the notch 171 (as shown in Fig. 30b). The plunger rod 170 is then free to advance proximally under the force of the plunger rod spring 170s.

[0109] The switch may be a conductive contact (not shown) provided on the actuator arm 183 of the injection activation button 180. The conductive contact may bridge a gap in the electrical circuit. For ease of manufacture, the electrical circuit may comprise conductive tracks printed onto the internal surface of the housing 110. The electrical circuit may comprise a timer delay to provide time for the cassette 210 to be advance before the plunger rod 170 is released.

[0110] Once the plunger rod 170 has fully traversed the pre-filled syringe 230 (as shown in Fig. 21), the user is indicated to remove the device from the injection site. It will be appreciated that the exact manner of plunger rod release may vary and that other solutions may be implemented without departing from the scope of the present invention.

[0111] As the device 100 is removed from the injection site, the needle cover 240 extends proximally under the drive of the needle cover shuttle 120 and the needle cover shuttle spring 120s. During this proximal extension, the housing pin 113 traverses a ramped portion 1227’ of the fourth portion of the track 1227 causing rotation of the needle cover shuttle 120, as shown in Fig. 22. The housing pin 113 then re-traverses the axially extending portion 1221 ’ of the first portion of the track 1221 until the housing pin 113 abuts a second distal terminus 1228 of the track 122, preventing further proximal movement of the needle cover 240. The needle cover 240 is then in its most proximal position, fully covering the needle 233, as shown in Fig. 23.

[0112] With the needle cover 240 in the most proximal position, the needle cover pin 245 is received in the window 218 of the cassette 210 to prevent distal displacement of the needle cover 240 and accidental uncovering of the needle 233. In this way needle stick injuries are prevented.

[0113] The needle cover pin 245 extends from a resiliently displaceable arm 246 defined by a cut 247 through the needle cover 240 that surrounds the arm 246. Therefore, the arm 246 is free to flex in a radial direction, hinging between proximal ends of the cut 247. The needle cover pin 245 comprises a ramped surface 245’on its proximal side and a square surface 245” on its distal side. When the needle cover 240 is displaced in a distal direction during removal of the device 100 from the injection site, the ramped surface 245’ rides up and over a ramped surface 219’ at the proximal end of the slot 219, displacing the arm 246 outward and allowing the needle cover pin 245 to leave the slot 219. Having passed the ramped surface 219’ of the slot 219, the needle cover pin 245 drops into the window 218, which is immediately proximal to the slot 219. The window 218 comprises proximal and distal square surfaces that prevent axial movement of the needle cover pin 245 and, therefore, the needle cover 240.

[0114] As the device 100 is removed from the injection site, the rotation of the needle cover shuttle 120 caused by the traversal of the housing pin 113 along the ramped portion 1227’ of the fourth tracked portion 1227 causes the needle cover shuttle 120 to contact a rib of the cassette shuttle 150, rotating the cassette shuttle 150. This rotation of the cassette shuttle 150 moves the ramped surfaces 152’, 152”of the first region 152 of the central opening 151 back into alignment with the clip 214 of the cassette 210. However, with the plunger rod 170 disposed inside the pre-filled syringe 230, the plunger rod 170 is positioned up against the spring prongs 216 of the clip 214, preventing their displacement and the cartridge’s 200 removal, as shown in Fig. 24. The rotation of the needle cover shuttle 120 also causes the respective locking tabs 124, 244 of the needle cover shuttle 120 and needle cover 240 to move out of alignment such that the cartridge 200.

[0115] The plunger rod spring 170s is then recharged by moving the plunger rod 170 distally to compress the plunger rod spring 170s until the plunger rod 170 reaches its pre-injection position, as shown in Fig. 25. A plunger rod recharging mechanism 194 (herein recharging mechanism 194 for brevity) is provided for this purpose (as illustrated by Figs. 30a and 30b). The recharging mechanism 194 comprises a geared pinion 195 that cooperates with a rack 196 provided in the distal region of the plunger rod 170. During operation, the geared pinion 195 rotates to drive the plunger rod 170 in the distal direction. The geared pinion 195 is powered by an electric motor 197 that is connected to a battery by an electrical circuit (not shown). The recharging mechanism 194 may share the battery of the plunger rod release mechanism 190.

[0116] The electric motor 197 is activated by a switch (not shown). The switch may be a conductive contact provided on needle cover shuttle 120 that bridges a gap in the electrical circuit when the needle cover shuttle 120 is advanced to its most proximal position. In this example, the circuit is broken again by a second switch when the plunger rod 170 is returned to its pre-injection position. The second switch may be a conductive contact (not shown) on the spring arm 191 that breaks the circuit when the retaining block 193 is returned to the notch 171 in the plunger rod 170. For ease of manufacture, the electrical circuit may comprise conductive tracks printed onto the internal surface of the housing 110.

[0117] It will be appreciated that the exact manner by which the plunger rod spring 170s is recharged may vary and that other solutions may be implemented without departing from the scope of the present invention.

[0118] With the plunger rod 170 returned to its pre-injection position, the cartridge 200 may be removed from the device by pulling on the needle cover 240 in the direction of arrow A4 in Fig. 26. The spring prongs 216 of the clip 214 are displaced inward as they ride over the distal ramped surface 152” of the cassette shuttle 150 and the cartridge 200 is removed. The device 100 is then back in its initial state and able to be reused with another cartridge.

[0119] The removed cartridge 200 is visibly different to the cartridge before use, indicating that the cartridge is spent and is not for use, but disposal only. Fig. 27 shows the cartridge 200 before use and Fig. 28 shows the cartridge 200 post use. The removed cartridge 200 is without a cap

[0120] 260 and is visibly longer due to the needle cover 240 having been displaced over the cassette 210 into its locked and most proximal position. There is therefore little risk of the removed cartridge 200 being mistaken for a pre-used one.

[0121] In another embodiment in which like features retain the same reference numbers, the needle cover 240 may further comprise a track 248 in its outer surface having a ramp 248’ configured to engage a pin 267 (hereinafter cap pin 267) extending from an inner surface of the tubular wall

[0122] 261 of the cap 260. This is illustrated by Fig. 29. When the cap 260 is twisted for removal as described above, the rotation of the cap 260 causes the cap pin 267 to traverse the ramp 248’, pushing the cap 260 in a proximal direction and aiding its removal. This may be particularly beneficial for impaired users who may otherwise struggle to pull the cap 260 away from the needle cover 240. It will be appreciated that all other features of this embodiment remain the same and will not be described again for brevity, Fig. 29 showing only those features necessary for descriptive purposes.

[0123] While the above-described embodiments relate to a mechanical device 100 insofar as the energy sources for the plunger 170, needle cover shuttle 120 and cassette shuttle 150 comprise helical springs 170s, 120s, 150s, it will be appreciated that other energy sources may be used. For example, a battery and linear actuators may be used. Such an arrangement would be understood by the skilled person and does not need to be elaborated on here.

[0124] Operation of the medicament delivery system may be summarised in the following steps:

[0125] 51 - An operator of the system begins by removing the cartridge 200 from a storage area. The storage area may be a refrigerator or other storage area suitable for storing the medicament being used.

[0126] 52 - The operator inserts the distal end of the cassette 210 into the opening 115 in the proximal end of the housing 110 until the cap 260 abuts the housing 110.

[0127] 53 - The operator twists the cap 260 about the device axis and then pulls the cap 260 and device 100 apart, causing the needle cover 240 to advance into the primed position.

[0128] 54 - The operator presses the needle cover 240 against an injection site of a patient so that the needle cover 240 is displaced into the housing 110.

[0129] 55 - The operator presses the injection activation button 180. This advances the needle 233 into the injection site and then releases the plunger rod 170 to dispense the medicament through the needle 233.

[0130] S6 - The operator lifts the device 100 away from the injection site. This causes the needle cover 240 to advance back out of the housing 110 to surround the needle 233.

[0131] S7 - The device 100 is recharged, returning the plunger rod 170 to the pre-delivery position. S8 - The operator removes the cartridge 200 from the device 100, thereby allowing the device 100 to be reused by repeating steps S1-S7.

[0132] 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.

[0133] 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.

[0134] The drug or medicament may be contain 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.

[0135] 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.

[0136] 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.

[0137] 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 ligand”". 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.

[0138] 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.

[0139] 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.

[0140] 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.

[0141] 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 yndromem.

[0142] Examples of DPP4 inhibitors are Linagliptin, Vildagliptin, Sitagliptin, Denagliptin, Saxagliptin, Berberine.

[0143] 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.

[0144] 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(a")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).

[0145] 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(a")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.

[0146] 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.

[0147] 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).

[0148] 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.

[0149] 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.

[0150] 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 :201€). 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.

[0151] 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).

[0152] 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).

[0153] Those of skill in the art will understand that modifications (additions and / or removals) of various components of the substances, 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.

[0154] LIST OF REFERENCE NUMERALS

[0155] 100 - reusable injector device (also 1224 - first distal terminus ‘device’) 123 - cut out

[0156] 110 - housing 40 124 - locking tab

[0157] 111 - tubular wall 1225 - third portion of the track

[0158] 112 - end wall 1226 - intermediate terminus

[0159] 113 - housing pin 125 - window

[0160] 114 - opening (in tubular wall 111) 126 - edge (of the cut out 123)

[0161] 115 - opening (in proximal end) 45 1227 - fourth portion of the track (of

[0162] 116 - circumferential ramp which: ramped portion 1227’)

[0163] 117 - housing track (of which: ramped 1228 - second distal terminus portion 117’) 150 - cassette shuttle

[0164] 1171 - proximal terminus 150s - cassette shuttle spring

[0165] 120 - needle cover shuttle (also ‘nc 50 151 - central opening shuttle’) 152 - first region (of which: ramped

[0166] 120s - needle cover shuttle spring proximal and distal surfaces 152’, 152”)

[0167] 121 - tubular wall 153 - ramped outer surface

[0168] 122 - track 154 - cassette shuttle pin

[0169] 1221 - first portion of the track (of which: 55 155 - second region (of which: square axially extending portion 1221 ’, first surface 155’) ramped portion 1221 ”) 170 - plunger rod

[0170] 1222 - proximal terminus 170s - plunger rod spring

[0171] 1223 - second portion of the track (of 171 - notch which: second ramped portion 1223’) 180 - injection activation button (also 218 - Window (in the proximal region ‘button’) 211 ”)

[0172] 181 - block 219 - slot (of which: ramped surface 219’)

[0173] 182 - button pin 35 230 - PFS

[0174] 183 - actuator arm 231 - cylindrical vial

[0175] 184 - outer surface 232 - bung

[0176] 185 - ramped inner surface 233 - needle

[0177] 234 - RNS

[0178] 190 - plunger rod release mechanism 40 235 - piston

[0179] 191 - magnetic spring arm (also ‘spring 240 - Needle cover arm’) 241 - Tubular wall

[0180] 192 - electromagnet 242 - Flange (of which: distal surface

[0181] 193 - retaining block 242’)

[0182] 194 - plunger rod recharging mechanism 45 243 - Window (in tubular wall 241) (also ‘recharging mechanism’) 244 - locking tab

[0183] 195 - geared pinion 245 - needle cover pin (of which: ramped

[0184] 196 - rack surface 245’, square surface 245”)

[0185] 197 - electric motor 246 - resiliently displaceable arm

[0186] 50 247 - cut

[0187] 200 - Cartridge 260 - Cap

[0188] 210 - Cassette 261 - Tubular wall

[0189] 211 - Cylindrical body (of which: distal 262 - End wall region 211 ’; proximal region 211 ”) 263 - Clip

[0190] 212 - Shoulder 55 264 - Parallel cuts

[0191] 213 - Internal bore 265 - Blocking element (of which:

[0192] 214 - Clip inwardly projecting part 265’, outwardly

[0193] 215 - Distal end projecting part 265”)

[0194] 216 - Spring prongs 266 - RNS holder

[0195] 217 - Retaining block (of which: square 60 267 - cap pin proximal surface 217’; ramped distal surface 217”)

Claims

CLAIMS1 . A reusable injector device (100) for use with a cartridge (200) containing a pre-filled syringe (230), the device comprising: a housing (110); a needle cover shuttle (120) displaceable within the housing against a needle cover shuttle spring (120s); a cassette shuttle (150) displaceable within the housing against a cassette shuttle spring (120s); and a plunger rod (170) configured to advance proximally under the force of a plunger rod spring (170s) to dispense medicament from the pre-filed syringe in use; wherein the reusable injector device is configured so that, when a cartridge for use with the device is connected thereto, the needle cover shuttle is displaceable against the needle cover shuttle spring between a primed position and a dose delivery position, distal of the primed position; and wherein the cassette shuttle is configured to advance in a proximal direction only after the needle cover shuttle has been displaced into the dose delivery position.

2. The reusable injector device (100) according to claim 1 , further comprising an opening (115) in the proximal end of the housing (110) for insertion of a cartridge (200) for use with the device.

3. The reusable injector device (100) according to claim 2, wherein insertion of a cartridge (200) into the housing (110) distally displaces the needle cover shuttle (120) into the primed position, charging the needle cover shuttle spring (120s).

4. The reusable injector device (100) according to any one of the preceding claims, wherein the needle cover shuttle (120) comprises a track (122) in its outer surface that engages a pin (113) extending from the inner surface of the housing (110), so that movement of the needle cover shuttle along the longitudinal axis of the device causes the pin to traverse the track; and wherein the track comprises ramped portions (1223’, 1227’) configured to rotate the needle cover shuttle to cause the needle cover shuttle to lock to and unlock from a cartridge (200) inserted into the device as the needle cover shuttle moves between different positions.

5. The reusable injector device (100) according to claim 4, wherein the track (122) comprises a first distal terminus (1224) which, when the pin (113) abuts the first distal terminus, defines the primed position of the needle cover shuttle (120), and a second distal terminus (1228) which, when the pin abuts the second distal terminus, defines a post delivery position of the needle cover shuttle.

6. The reusable injector device (100) according to any one of the preceding claims, wherein the device is provided with an activation button (180) pressable into the housing (110) to begin an injection when a cartridge (200) for use with the device is inserted into the device and the needle cover (240) is in the dose delivery position; and wherein, when the needle cover is in the primed position, the needle cover blocks the activation button being pressed into the housing.

7. The reusable injector device (100) according to claim 6, wherein the activation button (180) is configured to hole the cassette shuttle (150) against the cassette shuttle spring (150s), and wherein pressing the activation button into the housing (110) releases the cassette shuttle so that the cassette shuttle is advances in a proximal direction by the cassette shuttle spring.

8. A cartridge (200) for use with a reusable injector device, wherein the cartridge comprises: a pre-filed syringe (230) comprising medicament and a needle (233); a cassette (210) partially housing the pre-filed syringe so that the needle extends from a proximal end of the cassette; and a needle cover (240) extending over the proximal end of the cassette to surround the needle, wherein the cap comprises a clip (263) having a blocking element (265) that extends through a window (243) of the needle cover (240) and a window (218) of the cassette (210) to prevent relative axial movement of the needle cover, the cassette, and the cap.

9. The cartridge (200) according to claim 8, wherein the cassette (210) comprises a clip (214) configured to releasably engage a reusable injector device (100) for use with the cartridge.

10. The cartridge (200) according to claim 9, wherein the needle cover (240) comprises a needle cover pin (245) engageable with the window (243) of the cassette (210) to lock the needle cover (240) in a needle shielding position following removal of the cap (260).

11. A medicament delivery system (10) comprising: a reusable injector device (100) according to any one of claim 1 to claim 7; and a cartridge (200) according to any one of claim 8 to claim 10, the cartridge being for use with the reusable injector device, wherein, when the cartridge and the reusable injector device are combined, the needle cover (240) engages the needle cover shuttle (120) and the cassette (210) engages the cassette shuttle (150), the needle cover being displaceable against the needle cover shuttle spring (150s) between a primed position in which the needle cover extends from a proximal end of the housing (110) and a dose delivery position, distal or the primed position, and wherein the cassette shuttle is configured to advance the cassette in a proximal direction so that the needle (233) extends from a proximal end of the needle cover only after the needle cover has been displaced into the dose delivery position.

12. The medicament delivery system (10) according to claim 11 , wherein the cartridge (200) comprises a cap (260) comprising a clip (263) having a blocking element (265) that extends through a window (243) of the needle cover (240) and a window (218) of the cassette (210), and wherein the housing (110) comprises a circumferential ramp (116) depending from the inner surface of the housing that is configured to engage the clip of the cap when the cartridge and the device are combined, the clip and the ramp being configured to cooperate so that, on rotation of the cap about a longitudinal axis of the device (100), the clip is lifted by the ramp to remove the blocking element from the windows in the cassette and needle cover, allowing removal of the cap.

13. The medicament delivery system (10) according to claim 12, wherein the needle cover shuttle (120) comprises a track (122) in its outer surface that engages a pin (113) extending from the inner surface of the housing, so that movement of the needle cover shuttle along the longitudinal axis of the device (100) causes the pin to traverse the track; and wherein the track comprises ramped portions (1223’, 1227’) configured to rotate the needle cover shuttle to cause the needle cover shuttle to lock and unlock from the needle cover as the needle cover shuttle moves between different positions,wherein proximal movement of the needle cover into the primed position by the needle cover shuttle spring causes the pin to traverse the ramped portion (1223’) of the track to cause the needle cover shuttle to lock to the needle cover.

14. The medicament delivery system (10) according to any one of claim 11 to claim 13, wherein the needle cover shuttle spring is configured to proximally advance the needle cover into a post delivery position, proximal of the primed position, to conceal the needle.

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