A medicment delivey system and a drive sub-assembly

Abstract

The present invention relates to an advantageous a reusable drive sub-assembly for a medicament delivery system configured to be removably attachable to a syringe sub-assembly. The reusable drive sub-assembly system comprises a housing, a piston rod configured to be moved between a proximal position and a distal position, a piston rod biasing member configured to bias the piston rod into the distal position, and a recharge mechanism configured to engage the piston rod and to move the piston rod from the distal position towards the proximal position against the force of the piston rod biasing member when operated. The present invention also relates to a medicament delivery system and a method of recharging a reusable drive sub-assembly.

Description

[0001] A MEDICMENT DELIVEY SYSTEM AND A DRIVE SUB-ASSEMBLY

[0002] FIELD OF INVENTION

[0003] The present invention relates to a medicament delivery device and a method of recharging a medicament delivery device for reuse.

[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] It is an object of the present invention to provide an advantageous a reusable drive subassembly for a medicament delivery system configured to be removably attachable to a syringe sub-assembly. The reusable drive sub-assembly system comprises a housing, a piston rod configured to be moved between a proximal position and a distal position, a piston rod biasing member configured to bias the piston rod into the distal position, and a recharge mechanism configured to engage the piston rod and to move the piston rod from the distal position towards the proximal position against the force of the piston rod biasing member when operated.

[0009] Therefore, an advantageous drive sub-assembly is provided for a medicament delivery system. The reusable drive sub-assembly therefore reduces waste. Furthermore, the invention reduces the amount of force required to move the piston rod into its proximal position so that the drive sub-assembly is ready for reuse. The reduction in force required to recharge the drive subassembly makes the medicament delivery system easily operable for the elderly or those with a weakened grip.

[0010] In some embodiments, the recharge mechanism may comprise a piston rack located on the piston rod, a drive mechanism comprising a drive member having a drive rack; and a gear assembly connected to the piston rack and the drive rack, the gear assembly being configured to transform movement of the drive mechanism into proximal movement of the piston rod.

[0011] Thus, the recharge mechanism may move the piston rod into is proximal position by simply moving the drive mechanism. The gear assembly may take advantage of the gear ratio to overcome the force of the piston rod biasing member with minimal force input from an operator.

[0012] In some embodiments, the gear assembly may comprise a first gear mated with the drive rack, a second gear mated with the piston rack, and a double ratchet mechanism configured to selectively prevent movement of the piston rod in the distal direction.

[0013] Thus, the gear assembly can control the motion of the piston rod to prevent premature discharge of the piston rod.

[0014] In some embodiments, the double ratchet mechanism may comprise a ratchet gear comprising an external gear and a face gear, a piston ratchet gear lock configured to be movable into engagement with the external gear of the ratchet gear, and a third gear comprising a face ratchet configured to engage the face gear of the ratchet gear.

[0015] Thus, the double ratchet mechanism may be configured to selectively allow or prevent motion of the piston rod in the proximal direction and in the distal direction.

[0016] In some embodiments, the double ratchet mechanism may further comprise a common shaft for the each of the gears, the first and third gears being rotationally fixed to the shaft. Thus, the gear assembly may be simplified.

[0017] In some embodiments, the second gear may be rotationally fixed to the ratchet gear. Thus, the second gear may be free to rotate when the ratchet gear is no longer engaged such that the piston rod is released to move distally under the force of the piston rod biasing member.

[0018] In some embodiments, the double ratchet mechanism may comprise a first ratchet mechanism comprising the ratchet gear and the piston ratchet gear lock, the piston ratchet gear lock being configured to selectively prevent rotational motion of the ratchet gear in a direction to move the piston rod from its proximal position to its distal position and allow rotational motion of the ratchet gear in a direction to move the piston rod from its distal position to its proximal position. Thus, the first ratchet mechanism allows the piston rod to be moved towards its distal position without the piston rod being able to move distally when the drive member is returning to its first position. Thus, facilitating recharging without premature discharge of the piston rod.

[0019] In some embodiments, the reusable drive sub-assembly may further comprise a cam configured to move the piston ratchet gear lock into engagement with the ratchet gear when the drive mechanism is activated. In some embodiments, the cam may also be configured to move the piston ratchet gear lock out of engagement with the ratchet gear to activate the injection process.

[0020] In some embodiments, the double ratchet mechanism may comprise a second ratchet mechanism comprising the ratchet gear and the third gear, the third gear being rotationally locked to the ratchet gear in a first direction and configured to move the piston rod proximally, and the third gear being configured to allow the ratchet gear to move relative to the third gear in the second direction.

[0021] Thus, the second ratchet mechanism allows the drive member to return to its first position without affecting the location or condition of the piston rod.

[0022] In some embodiments, the first gear may be is larger than the second gear. Thus, the gear ratio between the gears may result in a larger displacement of the piston rod in the proximal direction than of the drive member.

[0023] In some embodiments, the drive mechanism may comprise a depressable button connected to the drive rack configured to be moved by an operator from a first position to a second position to move the piston rod proximally via the gear assembly, and a drive member biasing member configured to bias the drive member into its first position.

[0024] Thus, the drive sub-assembly can be at least partially recharged by the simple depression of a button by an operator. In some embodiments, the drive sub-assembly may be recharged by depressing the button in the range of about 1 to 6 times.

[0025] In another aspect of the present invention, there is provided an advantageous medicament delivery system. The medicament delivery system comprises a reusable drive sub-assembly according to any one of claim 1 to claim 11 , and a removable syringe sub-assembly comprising a cassette or a syringe carrier configured to receive a syringe. Therefore, an advantageous medicament delivery system is provided. The invention reduces waste by reusing the drive sub-assembly and the amount of force required to move the piston rod into its proximal position so that the drive sub-assembly is ready for reuse for the next injection. The reduction in force required to recharge the drive sub-assembly makes the medicament delivery system easily operable for the elderly or those with a weakened grip.

[0026] In some embodiments, the removable syringe sub-assembly may comprise a needle and a needle cover that is movable between an extended position, in which the needle is covered by the needle cover, and a retracted position, in which the needle is exposed, wherein the needle cover is configured to move the piston ratchet gear lock out of engagement with the piston ratchet gear when the needle cover is in its retracted position to allow distal movement of the piston rod.

[0027] Therefore, the syringe sub-assembly provides a needle safety mechanism. In addition, the syringe sub-assembly is configured to release the piston ratchet gear such that the piston rod can be moved distally. Thus, the needle cover may initiate the injection process when pressed against the injection site.

[0028] In some embodiments, the cassette or syringe carrier may comprise a syringe comprising a medicament.

[0029] In another aspect of the present invention, there is provided an advantageous method of recharging a reusable drive sub-assembly of a medicament delivery system. The method comprises engaging a piston ratchet gear lock with a ratchet gear to prevent distal motion of a piston rod, activating a drive member engaged with a first gear to rotate the first gear of a gear assembly, transmitting rotation of the first gear through the gear assembly to a second gear engaged with the piston rod, and transforming rotational motion of the second gear into proximal linear motion of the piston rod to move the piston rod proximally.

[0030] Thus, the amount of force required to move the piston rod into its proximal position so that the drive sub-assembly is ready for reuse for the next injection is reduced. The reduction in force required to recharge the drive sub-assembly makes the medicament delivery system easily operable for the elderly or those with a weakened grip.

[0031] These and other aspects of the invention will be apparent from and elucidated with reference to the embodiments described hereinafter. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Embodiments of the invention will now be described, by way of example only, with reference to the accompanying drawings, in which:

[0033] FIGS. 1A and 1 B show a schematic side view of an injector device with a cap attached and a cap removed

[0034] FIG. 2A to 2C show a schematic perspective views of medicament delivery system comprising a reusable drive sub-assembly and a removable syringe sub-assembly in attached configuration and detached configurations;

[0035] FIG. 3 shows a schematic side view of a medicament delivery system;

[0036] FIG. 4 shows a schematic perspective view of a medicament delivery system when activated to deliver a medicament;

[0037] FIG. 5 shows a schematic perspective view of a medicament delivery system after medicament has been delivered;

[0038] FIG. 6 shows a schematic exploded perspective view of a recharge assembly;

[0039] FIG. 7 shows a schematic perspective view of a medicament delivery system being recharged; and

[0040] FIG. 8 shows a schematic perspective view of the recharge assembly with movement of the components indicated.

[0041] DETAILED DESCRIPTION

[0042] 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).

[0043] 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.

[0044] 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.

[0045] 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.

[0046] 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.

[0047] 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). According to some embodiments of the present disclosure, an exemplary drug delivery device 10 is shown in Figs. 1A & 1 B. Device 10, as described above, is configured to inject a medicament into a patient’s body. Device 10 includes a housing 11 which typically contains a reservoir containing the medicament to be injected (e.g., a syringe) and the components required to facilitate one or more steps of the delivery process. Device 10 can also include a cap assembly 12 that can be detachably mounted to the housing 11. Typically a user must remove cap 12 from housing 1 1 before device 10 can be operated.

[0048] As shown, housing 1 1 is substantially cylindrical and has a substantially constant diameter along the longitudinal axis X. The housing 11 has a distal region 20 and a proximal region 21 . 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.

[0049] Device 10 can also include a needle sleeve 13 coupled to housing 1 1 to permit movement of sleeve 13 relative to housing 1 1 . For example, sleeve 13 can move in a longitudinal direction parallel to longitudinal axis X. Specifically, movement of sleeve 13 in a proximal direction can permit a needle 17 to extend from distal region 20 of housing 1 1 .

[0050] Insertion of needle 17 can occur via several mechanisms. For example, needle 17 may be fixedly located relative to housing 11 and initially be located within an extended needle sleeve 13. Proximal movement of sleeve 13 by placing a distal end of sleeve 13 against a patient’s body and moving housing 11 in a distal direction will uncover the distal end of needle 17. Such relative movement allows the distal end of needle 17 to extend into the patient’s body. Such insertion is termed “manual” insertion as needle 17 is manually inserted via the patient’s manual movement of housing 11 relative to sleeve 13.

[0051] Another form of insertion is “automated,” whereby needle 17 moves relative to housing 11 . Such insertion can be triggered by movement of sleeve 13 or by another form of activation, such as, for example, a button 22. As shown in Figs. 1A & 1 B, button 22 is located at a proximal end of housing 11 . However, in other embodiments, button 22 could be located on a side of housing 1 1.

[0052] Other manual or automated features can include drug injection or needle retraction, or both. Injection is the process by which a bung or piston 23 is moved from a proximal location within a syringe (not shown in Figures 1A and 1 B) to a more distal location within the syringe in order to force a medicament from the syringe through needle 17. In some embodiments, a drive spring (not shown in Figures 1A and 1 B) is under compression before device 10 is activated. A proximal end of the drive spring can be fixed within proximal region 21 of housing 11 , and a distal end of the drive spring can be configured to apply a compressive force to a proximal surface of piston 23. Following activation, at least part of the energy stored in the drive spring can be applied to the proximal surface of piston 23. This compressive force can act on piston 23 to move it in a distal direction. Such distal movement acts to compress the liquid medicament within the syringe, forcing it out of needle 17.

[0053] Following injection, needle 17 can be retracted within sleeve 13 or housing 1 1 . Retraction can occur when sleeve 13 moves distally as a user removes device 10 from a patient’s body. This can occur as needle 17 remains fixedly located relative to housing 11 . Once a distal end of sleeve 13 has moved past a distal end of needle 17, and needle 17 is covered, sleeve 13 can be locked. Such locking can include locking any proximal movement of sleeve 13 relative to housing 11.

[0054] Another form of needle retraction can occur if needle 17 is moved relative to housing 11 . Such movement can occur if the syringe within housing 1 1 is moved in a proximal direction relative to housing 11. This proximal movement can be achieved by using a retraction spring (not shown), located in distal region 20. A compressed retraction spring, when activated, can supply sufficient force to the syringe to move it in a proximal direction. Following sufficient retraction, any relative movement between needle 17 and housing 11 can be locked with a locking mechanism. In addition, button 22 or other components of device 10 can be locked as required.

[0055] Referring now to FIGS. 2A to 2C, a schematic perspective side view of an embodiment of a medicament delivery system 100 is shown. The medicament delivery system 100 is a medicament delivery device with a reusable portion and a consumable or replaceable portion.

[0056] The medicament delivery system 100 comprises a reusable drive sub-assembly 101 and a removable syringe sub-assembly 102. The reusable drive sub-assembly 101 is configured to be removably attached to a removable syringe sub-assembly 102. The reusable drive subassembly 101 and the removable syringe sub-assembly 102 may be configured to be moved between an attached configuration and a detached configuration. The medicament delivery system 100 may further comprise a removably replaceable cap sub-assembly 103. The removably replaceable cap sub-assembly 103 may be configured to be removed and reattached to a distal end of the removable syringe sub-assembly 102. In some embodiments, the cap subassembly 103 may be a part of the removable syringe sub-assembly 102. Referring to FIG. 2A, the medicament delivery system 100 may be provided in the detached configuration. That is, the medicament delivery system 100 may be provided in a state where the removable syringe sub-assembly 102 is detached from the reusable drive sub-assembly 101. In the detached configuration, the cap sub-assembly 103 may be attached to the removable syringe sub-assembly.

[0057] Referring to FIG. 2B, the medicament delivery system 100 may be placed into its attached configuration by attaching the removable syringe sub-assembly 102 to the reusable drive subassembly 101 . The removable syringe sub-assembly 102 may be attached to the reusable drive sub-assembly by sliding the removable syringe sub-assembly 102 relative to the reusable drive sub-assembly 101 until a locking mechanism (not shown) is engaged.

[0058] Referring to FIG. 2C, when the medicament delivery system 100 is to be used, the reusable drive sub-assembly 101 and the removable syringe sub-assembly 102 are kept in the attached configuration and the cap sub-assembly 103 is removed. The cap sub-assembly 103 may be replaced on the removable syringe sub-assembly 102 after use. The removable syringe subassembly 102 may then be removed from the reusable drive sub-assembly 101 to the detached configuration, as shown in FIG. 2A.

[0059] Referring now to FIG. 3, FIG. 4, and FIG. 5, a schematic side view, and two schematic perspective views of the medicament delivery system 100 are shown. The medicament delivery system 100 illustrated comprises the reusable drive sub-assembly 101 and the removable syringe sub-assembly 102 in their attached configuration with the cap sub-assembly 103 attached to the removable syringe sub-assembly 102.

[0060] The reusable drive sub-assembly 101 comprises a housing 111. The housing may be configured to house the other components of the reusable drive sub-assembly 101. In FIGS. 3 and 4, the housing 111 is illustrated translucently so as to show the components housed within the housing 11 1.

[0061] The reusable drive sub-assembly 101 further comprises a piston rod 121 configured to be moved between a proximal position, as shown in FIG. 3, and a distal position, and a piston rod biasing member 122, shown in FIGS. 4, configured to bias the piston rod 121 into the distal position, shown in FIG. 5. The reusable drive sub-assembly further comprises a recharge mechanism 131 . The recharge mechanism 131 is configured to engage the piston rod 121 . The recharge mechanism 131 is also configured to move the piston rod 121 from the distal position , shown in FIG. 5, towards the proximal position, shown in FIG. 3, against the force of the piston rod biasing member 122, when operated.

[0062] The housing 111 may comprise a main housing body 112. The main housing body 112 may be generally tubular. The main housing body 112 may comprise an empty internal volume 113 for receiving the other components of the reusable drive sub-assembly 101. The main housing body 112 may be generally cylindrical or elliptically cylindrical, although it will be appreciated that in other embodiments the main housing body 1 12 may have any hollow shape.

[0063] The housing 111 may further comprise a removable syringe sub-assembly receiving portion 1 15. The removable syringe sub-assembly receiving portion 1 15 may be configured to receive a removable syringe sub-assembly 102 when the removable syringe sub-assembly 102 and reusable drive sub-assembly 101 are in the attached configuration. The removable syringe subassembly receiving portion 115 may extend from the main housing body 112 in the distal direction.

[0064] The housing 111 may further comprise a cut-out section 117. The cut-out section 1 17 may be configured to receive a user operable component of the reusable drive sub-assembly 101 , as will be described in more detail hereinafter.

[0065] Referring now to FIGS. 3 and 6, the piston rod 121 may comprise a main body 124. The main body 124 may be cylindrical and elongate. The piston rod 121 may be configured to contact a bung or a piston of the removable syringe sub-assembly 102. The main body 124 may comprise a piston rack 125. The piston rack 125 may extend in a longitudinal direction along the circumferential surface of the piston rod 121 . The piston rack 125 may extend along the majority of the length of the piston rod 121. In some embodiments, the piston rack 125 may extend along substantially the whole length of the piston rod 121. The piston rack 125 on the piston rod 121 may comprise a plurality of teeth 126. The piston rack 125 may engage with another component of the reusable drive sub-assembly 101 , as will be described in more detail hereinafter, to cause linear motion of the piston rod 121.

[0066] The piston rod biasing member 122 may be a coil spring 122. The piston rod biasing member 122 may extend coaxially with the piston rod 121. The piston rod 121 may comprise an internal bore 129. The internal bore 129 may have an open end at the proximal end of the piston rod 121 and a closed end of the bore. The piston rod biasing member 122 may be configured to extend into the internal bore 129 of the piston rod 121. Therefore, a proximal end of the piston rod biasing member 122 may be in contact with a proximal end of the housing 1 11 and the distal end of the piston rod biasing member 122 may be in contact with the closed end of the internal bore 129.

[0067] The recharge mechanism 131 is configured to move the piston rod 121 from a distal position after an injection has been performed to its proximal position to prime the reusable drive subassembly 101. Thus, the recharge mechanism 131 moves the piston rod 121 proximally to compress the piston rod biasing member 122 so that the reusable drive sub-assembly 101 is ready to be reused.

[0068] The recharge mechanism 131 may comprise the piston rack 124 located on the piston rod 121. The recharge mechanism 131 may further comprise a drive mechanism 141. The drive mechanism 141 may be configured to move between a first position and a second position. The first position may be a position in which the drive mechanism 141 is located in a proximal position and the second position may be a position in which the drive mechanism 141 is located in a distal position. Movement of the drive mechanism 141 from the first position to the second position may cause movement of the piston rod 121 from its distal position towards its proximal position.

[0069] The drive mechanism 141 may comprise a drive member 142. The drive member 142 may be elongate. The drive member 142 may extend parallel to the longitudinal axis of the housing 111 of the reusable drive sub-assembly 101.

[0070] The drive member 142 may comprise a drive rack 143. The drive rack 143 may extend longitudinally within the housing 1 11. The drive rack 143 may comprise a plurality of teeth 144. The drive rack 143 may engage with another component of the reusable drive sub-assembly 101 , as will be described in more detail hereinafter, to effect linear motion of the piston rod 121.

[0071] The drive mechanism 141 may further comprise a button 146. The button 146 may be configured to be operated by a user. The button 146 may be connected to the drive member 142. The button 146 may be a depressable button 146. That is, the button 146 may be pushed by a user to move the drive mechanism 141 , especially the drive member 142, from the first position to the second position. Thus, the button 146 may be moved from a proximal position to a distal position. The button 146 may be located in the cut-out section 117 of the housing 111. Distal movement of the button 146 may be limited by the housing 11 1 at the distal end of the cut-out section 117. The button 146 may be movable by a distance that is up to equal to the length of the drive rack 143 on the drive member 142. The drive mechanism 141 may further comprise a drive rack biasing member 148. The drive rack biasing member 148 may be configured to bias the drive member 142 towards its first position. The drive member biasing member 148 may be a coil spring 148. The drive rack biasing member 148 may extend coaxially with the drive member 142. A proximal end of the drive rack biasing member 148 may be in contact with a distal end of the drive member 148. A distal end of the drive rack biasing member 148 may be in contact with a part of the housing 1 11. The part of the housing 11 1 that the drive member biasing member 148 may be in contact with may be the, or a protrusion extending from the, removable syringe sub-assembly receiving portion 115 of the housing 11 1.

[0072] The recharge mechanism 131 may further comprise a gear assembly 151. The gear assembly 151 may be mated with the piston rack 125 on the piston rod 121 and the drive rack 143 on the drive member 142. The gear assembly 151 may be configured to transform movement of the drive mechanism 141 into proximal movement of the piston rod 121. More specifically, the gear assembly 151 may be configured to transform longitudinal distal linear movement of the drive mechanism 141 from its first position to its second position into longitudinal proximal linear movement of the piston rod 121 , as will be explained in further detail hereinafter.

[0073] Referring now to FIG. 6, a schematic perspective exploded view of the gear assembly 151 is shown. The gear assembly 151 may comprise a first gear 161 . The first gear 161 may be mated with the drive rack 143 on the drive member 142 of the drive mechanism 141. The first gear 161 may be generally circular with a plurality of teeth 162 extending around its circumferential surface. The plurality of teeth 162 of the first gear 161 may be configured to interlock with the plurality of teeth 144 of the drive rack 143. The first gear 161 may further comprise a central aperture 163. The central aperture 163 may be configured to receive a shaft.

[0074] The gear assembly 151 may further comprise a second gear 165. The second gear 165 may be mated with the piston rack 125 on the piston rod 121 . The second gear 165 may be generally circular with a plurality of teeth 166 extending around its circumferential surface. The plurality of teeth 166 of the second gear 165 may be configured to interlock with the plurality of teeth 126 of the piston rack 125. The second gear 165 may further comprise a central aperture 167. The central aperture 167 may be configured to receive a shaft. The first gear 161 may be larger than the second gear 165. That is, the first gear 161 may have a larger diameter than the second gear 165. Thus, the gear ratio between the first gear 161 and the second gear 165 may mean that for a given movement of the drive member 142 in the distal direction a larger movement of the piston rod 121 in the proximal direction may be achieved. The gear assembly 151 may further comprise a double ratchet mechanism 171. The double ratchet mechanism 171 may be configured to selective prevent movement of the piston rod 121 in the distal direction.

[0075] The double ratchet mechanism 171 may comprise a first ratchet mechanism 172. The first ratchet mechanism 172 may be configured to allow proximal movement of the piston rod 121 when engaged. That is, the first ratchet mechanism 172 may be configured to allow rotation of the second gear 165 in a first direction to move the piston rod 121 proximally. The first ratchet mechanism 172 may be configured to prevent distal movement of the piston rod 121 when engaged. That is, the first ratchet mechanism 172 may be configured to prevent rotation of the second gear 165 in a second direction to hold the piston rod 121 in its position. The first ratchet mechanism 172 may be configured to allow distal movement of the piston rod 121 , when the first ratchet mechanism 172 is not engaged. That is, the first ratchet mechanism 172 may be configured to allow rotation of the second gear 165 in the second direction to allow the piston rod 121 to move distally.

[0076] The double ratchet mechanism 171 may comprise a second ratchet mechanism 173. The second ratchet mechanism 173 may be configured to prevent relative rotation of the first gear 161 relative to the second gear 165 in a first direction in order to move the piston rod 121 from its distal position towards its proximal position. The second ratchet mechanism 173 may be configured to allow relative rotation of the second gear 165 relative to the first gear 161 in the second direction. When the first ratchet mechanism 172 is engaged, the second ratchet mechanism 172 may allow the first gear 161 to rotate relative to the second gear 165 in the second direction. Thus, the drive mechanism 141 can be moved back into the first position so that it can be repressed. When the first ratchet mechanism 172 is not engaged, the second ratchet mechanism 172 may allow the second gear 165 to rotate relative to the first gear 161 in the second direction. Thus, the piston rod 121 can be moved distally under the force of the piston rod biasing member 122.

[0077] The double ratchet mechanism 171 may comprise a ratchet gear 175. The ratchet gear 175 may be generally circular. The ratchet gear 175 may comprise an external gear 176 and a face gear 177. The external gear 176 may comprise a plurality of teeth 178 that extend around the circumferential surface of the ratchet gear 175. The face gear 177 may comprise a plurality of teeth 179 that extend from an end surface of the ratchet gear 175. The plurality of teeth 179 of the face gear 177 may extend circularly around the centre of the ratchet gear 175. The ratchet gear 175 may further comprise a central aperture 180. The central aperture 180 may be configured to receive a shaft. The ratchet gear 175 may be rotationally locked to the second gear 165.

[0078] The double ratchet mechanism 171 may further comprise a piston ratchet gear lock 182. The piston ratchet gear lock 182 may be configured to be movable into engagement with the external gear 176 of the ratchet gear 175. The piston ratchet gear lock 182 may be in the form of pawl 182. The piston ratchet gear lock 182 may be configured to engage with one side of the plurality of teeth 178 of the external gear 176 of the ratchet gear 175 to prevent rotational movement in the first direction, i.e. the direction that allows distal movement of the piston rod 121. That is, the piston ratchet gear lock 182 may be contoured to prevent rotation of the ratchet gear 175 in the first direction. The piston ratchet gear lock 182 may be configured to allow rotation of the ratchet gear 175 in the second direction. That is, the piston ratchet gear lock 182 may be contoured so as to slide against but not engage the other side of the plurality of teeth 178 of the external gear 176 of the ratchet gear 175 to allow the piston rod 121 to be moved proximally.

[0079] As previously mentioned, the piston ratchet gear lock 182 may be a pawl 182. The pawl 182 may comprise an aperture 183. The aperture 183 may be configured to receive a shaft. The pawl 182 may rotate partially about the shaft. Alternatively, the pawl 182 may be rotationally locked to the shaft. Therefore, when the ratchet gear 175 is moved in the second direction, the pawl 182 may be rotated about the shaft or the pawl 182 and shaft may be rotated about the axis of rotation of the shaft to allow the ratchet gear 175 to rotate in the second direction.

[0080] The double ratchet mechanism 171 may further comprise a cam 185. The cam 185 may be configured to move the piston ratchet gear lock 182 into locking engagement with the ratchet gear 175 when the drive mechanism 131 is activate. In some embodiments, the cam 185 may also be configured to move the piston ratchet gear lock 182 out of engagement with the ratchet gear 175 to activate the injection process. The cam 185 may be urged by a needle cover of the syringe sub-assembly 102 to move the cam 185 out of locking engagement with the ratchet gear 175. In some embodiments, the piston ratchet gear lock 182 may be moved laterally, i.e. perpendicular to the longitudinal axis of the housing 1 1 1 , between its locking and non-locking engagement.

[0081] Thus, the first ratchet mechanism 172 may comprise the ratchet gear 175 and the piston ratchet gear lock 182. The double ratchet mechanism 171 may further comprise a third gear 191. The third gear 191 may be generally circular or hexagonal as illustrated in FIGS. 3 to 6. It will be appreciated that the third gear 191 may have other shapes. The third gear 191 may comprise a face ratchet 192. The face ratchet 192 may be configured to engage the face gear 177 of the ratchet gear 175.

[0082] The face ratchet 192 may be formed on face surface of the third gear 191 . The face ratchet 192 may face the ratchet gear 175. The face ratchet 175 may be in the form of at least one face pawl 193. It will be appreciated that there may be a plurality of face pawls 193. The at least one face pawl 193 may be formed by a resiliently deformable arm. The face pawl may be biased outwards from the face of the third gear 191 and configured to engage with the face gear 177 on the ratchet gear 175. Therefore, the face pawl 193 may be configured to engage with one side of the plurality of teeth 179 of the face gear 177 of the ratchet gear 175 to rotate the ratchet gear 175 in the second direction. That is, the face ratchet 192 may be configured to rotate the ratchet gear 175 in the second direction to move the piston rod proximally. The face pawl 193 may be configured to slide against the other side of the plurality of teeth 179 of the face gear 177 of the ratchet gear 175 to allow the ratchet gear 175 to rotate in the first direction, when the piston ratchet gear lock 182 is not engaged, i.e. the direction that allows distal movement of the piston rod 121. The third gear 191 may further comprise a central aperture 194. The central aperture 194 may be configured to receive a shaft.

[0083] Thus, the second ratchet mechanism 173 may comprise the ratchet gear 175 and the third gear 191.

[0084] The double ratchet mechanism 171 may further comprise a shaft 196. The shaft 196 may be a common shaft. That is, the shaft 201 may extend through the central apertures 163, 167, 180, 194 of each of the first gear 161 , the second gear 162, the ratchet gear 175, and the third gear 191. The shaft 196 may comprise a non-circular portion 197. The non-circular portion 197 may have a cross-section shape that is non-circular in a plane perpendicular to the longitudinal axis of the shaft 196. The shaft 196 may further comprise a circular portion 198. The circular portion 198 may have a cross-section shape that is circular in a plane perpendicular to the longitudinal axis of the shaft 196.

[0085] As shown in FIG. 6, the shaft 196 may comprise a plurality of non-circular portions 197. For example, the shaft 196 may comprise a non-circular portion 197a, 197b at each end of the shaft 196 and either side of a circular portion 198. The first gear 161 and the third gear 191 may be rotationally fixed to the shaft 196. That is, the first gear 161 and the third gear 191 may be rotationally fixed to the non-circular portions 197. For example, the first gear 161 may be rotationally fixed to a non-circular portion 197a at one end of the shaft 196 and the third gear 191 may be rotationally fixed to the non-circular portion 197b at the other end of the shaft 196, i.e. on the other side of the circular portion 198.

[0086] The first gear 161 may be rotationally fixed to the non-circular portion 197a of the shaft 196 by having a non-circular central aperture 163 that matches the cross-sectional shape of the non- circular portion 197a of the shaft 196. The third gear 191 may be rotationally fixed to the non- circular portion 197b of the shaft 196 by having a non-circular central aperture 194 that matches the cross-sectional shape of the non-circular portion 197b of the shaft 196. The second gear 165 and the ratchet gear 175 may be rotationally free with respect to the circular portion 198 of the shaft 196 by virtue of having circular central apertures 167, 180. Each of the gears 161 , 165, 175, 180 may be fixed in the direction of the longitudinal axis of the shaft 196.

[0087] Referring briefly back to FIGS. 1A to 1C, an embodiment of the removable syringe subassembly 102 is shown. In the illustrated embodiments, the removable syringe sub-assembly 102 comprises a cassette 201. The cassette 201 may comprise a housing 202 that houses a pre-filled syringe 203. The pre-filled syringe 203 may comprise a syringe 204 that holds medicament 205. The pre-filled syringe 203 may further comprise a needle 206 located at a distal end of the syringe 204 and a piston 207 located at a proximal end of the syringe 204.

[0088] The cassette 201 may further comprise a needle cover 211 and a needle cover biasing member 212. The needle cover 211 may be configured to be moved between an extended position, in which the needle cover 21 1 extends from the distal end of the housing 202 of the cassette 201 to cover the needle 206, and a retracted position, in which the needle 206 is exposed. The needle cover biasing member 212 may be configured to bias the needle cover 211 into the extended position. The needle cover biasing member 212 may be a coil spring 212.

[0089] The needle cover 211 may comprise a cover portion 213 and at least one arm 214. The cover portion 213 may be configured to cover the needle 206 when the needle cover 211 is in its extended position. The at least one arm 214 may extend proximally from the cover portion 213 of the needle cover 211. The needle cover 211 may comprise two arms 214. The two arms 214 may be diametrically opposed. The at least one arm 214 may be configured to move the piston ratchet gear lock 182 out of engagement with the external gear 176 of the ratchet gear 175 when the needle cover 211 is in the retracted position. The at least one arm 214 may either directly engage the piston ratchet gear lock 182 or the shaft or the cam 185. In the illustrated embodiment, the cap sub-assembly 103 may form a part of the removable syringe sub- assembly 102. The cap sub-assembly 103 may comprise a cap 215. The cap 215 may be configured to close the distal end of the cassette 201 before and after use. The cap sub-assembly 103 may further comprise a removable needle shield 216. The removable needle shield 216 may be configured to shield the needle 206 of the cassette 201 when the cap subassembly 103 is attached to the cassette 201 . The needle shield 216 may be removable from the cassette 201 with the cap 215 before use. In addition, the needle shield 216 may be replaceable on the cassette 201 with the cap 215 after use. The needle shield 216 may comprise a locking mechanism (not shown) such that once it has been replaced on the cassette 201 it cannot be removed from the needle. Thus, accidental reuse of the needle may be prevented.

[0090] In another embodiment, the removable syringe sub-assembly 102 may comprise a pre-filled syringe carrier body 221 . The pre-filled syringe carrier body 221 may be configured to receive a pre-filled syringe 222. The pre-filled syringe 202 may comprise a syringe 204 storing a medicament 205, a plug or piston 207 located in proximal region of the pre-filled syringe 222, and a needle 206 located at the distal end of the pre-filled syringe 222.

[0091] The pre-filled syringe carrier body 221 may comprise a needle cover 211 as described previously in relation to the cassette 201.

[0092] A method of use of the medicament delivery system 100 will now be described hereinafter for completeness. Referring back to FIG. 1A, an operator may retrieve the reusable drive subassembly 101 from storage. The operator may also retrieve a removable syringe sub-assembly 102 from storage and connected the syringe sub-assembly 102 to the reusable drive subassembly 101 , as shown in FIG. 1 B. The operator may then remove the cap sub-assembly 103 from the syringe sub-assembly 102, as shown in FIG. 1C.

[0093] Referring briefly to FIG. 4, the piston rod 121 may begin in its proximal position. The operator places the medicament delivery system 100 against a patients skin and pushes such that the needle cover 211 is moved from its extended position to its retracted position, as shown in FIG. 4. In the retracted position, the arm 216 of the needle cover 211 may move the piston ratchet gear lock 182 out of engagement with the ratchet gear 175, as shown in FIG. 4. Thus, the piston rod 121 is no longer held in its proximal position, i.e. is released, and under the force of the piston rod biasing member 122 the piston rod 121 is moved distally. The distal end of the piston rod 121 may engage the piston 207. As the piston 207 is moved distally by the piston rod, medicament is forced out of the syringe 204 through the needle 206.

[0094] Referring briefly to FIG. 5, once the injection has been completed, the medicament delivery system 100 is moved away from the patient’s skin. At this stage, the needle cover 211 moves from its retracted position to its proximal position to cover the needle 206. A needle cover lock 218 may be engaged. Referring to FIG. 7, the operator may then engage the drive mechanism 141. The operator may engage the drive mechanism 141 by depressing the button 146.

[0095] Referring to FIG. 8, the workings of the recharge mechanism 131 are shown, with arrows A to G showing the movements of the components. Distal movement of the button 146, shown in FIG. 7, causes the drive member 142 to move distally, as shown by arrow A. As the plurality of teeth 144 on the drive rack move distally, they engage with the plurality of teeth 162 on the first gear 161. This causes rotation of the first gear 161 in the first direction, as shown by arrow B. Thus, in the illustrated view of the recharge mechanism 131 , the first direction may be anti-clockwise.

[0096] The first gear 161 is rotationally locked to the non-circular portion 197a of the shaft 196, and so rotation of the first gear 161 causes rotation of the shaft 196 in the first direction, as shown by arrow C. The shaft 196 may be a rigid body and so the whole length of the shaft rotates. Thus, the non-circular portion 197b of the shaft 196 also rotates. The non-circular portion 197b of the shaft 196 is rotationally fixed to the third gear 191 . Thus, the third gear 191 also rotates in the first direction, as shown by arrow D.

[0097] As previously described, the face pawl 193 on the third gear 191 is configured to engage the plurality of teeth 179 of the face gear 177 of the ratchet gear 175. The face pawl 193 may be configured to fixed lock the third gear 191 to the ratchet gear 175 for rotation in the first direction. Thus, the ratchet gear 175 is rotated in the first direction, as shown by arrow E, moving the piston ratchet gear lock 182 as it rotates. Due to the ratchet gear 175 being rotationally fixed to the second gear 165, the second gear 165 is also rotated in the first direction, as shown by arrow F. As the second gear 165 rotates, the plurality of teeth 166 of the second gear 165 mesh with the plurality of teeth 126 on the piston rack 125. Thus, the piston rod 121 is driven proximally, as shown by arrow G.

[0098] After the operator has depressed the button 146, the operator releases the button 146 and the button 146 is biased proximally back to it starting position by the drive member biasing member 148. The recharging process may move the piston rod 121 in the range of between a sixth to a quarter of the way from its distal position to its proximal position. The operator may then repeat the recharging process again until the piston rod is in its proximal position. Thus, the recharger mechanism 131 may be operated between 4 and 6 times. Thus, the force required to recharge the reusable drive sub-assembly 101 may be greatly reduced. As a result, the reusable drive sub-assembly 101 can be used by elderly and / or weaker people to inject themselves.

[0099] Once the piston rod 121 reaches its proximal position, a syringe sub-assembly lock (not shown) may unlock and release the syringe sub-assembly 102 from the drive sub-assembly 101 .

[0100] Therefore, the syringe sub-assembly 102 can be removed from the drive sub-assembly 101 and disposed of. The drive sub-assembly 101 can then be stored for reuse.

[0101] Based on the previous description of recharging the drive sub-assembly 101 , it is clear that the method may comprise the steps of engaging a piston ratchet gear lock with a ratchet gear to prevent distal motion of a piston rod; activating a drive member engaged with a first gear to rotate the first gear of a gear assembly, transmitting rotation of the first gear through the gear assembly to a second gear engaged with the piston rod; and transforming rotational motion of the second gear into proximal linear motion of the piston rod to move the piston rod proximally.

[0102] 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.

[0103] 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. 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.

[0104] 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.

[0105] 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.

[0106] 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.

[0107] 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-(cu- carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(w-carboxyheptadecanoyl) human insulin.

[0108] 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- 1 134-PC, PB-1023, TTP-054, Langlenatide / HM-11260C (Efpeglenatide), HM-1521 1 , 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.

[0109] 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.

[0110] Examples of DPP4 inhibitors are Linagliptin, Vildagliptin, Sitagliptin, Denagliptin, Saxagliptin, Berberine.

[0111] 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.

[0112] 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.

[0113] 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).

[0114] 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.

[0115] 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.

[0116] 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).

[0117] 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.

[0118] 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.

[0119] An example drug delivery device may involve a needle-based injection system as described in Table 1 of section 5.2 of ISO 1 1608-1 :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. 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).

[0120] 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).

[0121] 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.

[0122] LIST OF REFERENCE NUMERALS

[0123] 10 Drug Delivery Device 102 Syringe Sub-Assembly

[0124] 1 1 Housing 103 Cap Sub-Assembly

[0125] 12 Cap 40 111 Housing

[0126] 13 Needle Sleeve 112 Main Housing Body 17 Needle 113 Empty Internal Volume

[0127] 20 Distal Region 115 Removable Syringe Sub-Assembly

[0128] 21 Proximal Region Receiving Portion

[0129] 22 Button 45 117 Cut-Out Section

[0130] 23 Bung / Piston 121 Piston Rod

[0131] 122 Piston Rod Biasing Member

[0132] 100 Medicament Delivery Device 124 Main Body

[0133] 101 Drive Sub-Assembly 125 Piston Rack 126 Plurality of Teeth 182 Piston Ratchet Gear Lock

[0134] 129 Internal Bore 183 Aperture

[0135] 131 Recharge Mechanism 185 Cam

[0136] 141 Drive Mechanism 191 Third Gear

[0137] 142 Drive Member 30 192 Face Ratchet

[0138] 143 Drive Rack 193 Face Pawl

[0139] 144 Plurality of Teeth 194 Central Aperture

[0140] 146 Button 196 Shaft

[0141] 148 Drive Member Biasing Member 197 Non-Circular Portion

[0142] 151 Gear Assembly 35 198 Circular Portion

[0143] 161 First Gear

[0144] 162 Plurality of Teeth 201 Cassette

[0145] 163 Central Aperture 202 Housing

[0146] 165 Second Gear 203 Pre-Filled Syringe

[0147] 166 Plurality of Teeth 40 204 Syringe

[0148] 167 Central Aperture 205 Medicament

[0149] 171 Double Ratchet Mechanism 206 Needle

[0150] 172 First Ratchet Mechanism 207 Piston

[0151] 173 Second Ratchet Mechanism 211 Needle Cover

[0152] 175 Ratchet gear 45 212 Needle Cover Biasing Member

[0153] 176 External gear 213 Cover Portion

[0154] 177 Face Gear 214 Arm

[0155] 178 Plurality of Teeth 215 Cap

[0156] 179 Plurality of Teeth 216 Needle Shield

[0157] 180 Central Aperture 50 218 Needle Cover

Claims

CLAIMS1 . A reusable drive sub-assembly (101) for a medicament delivery system (100) configured to be removably attachable to a syringe sub-assembly (102), the reusable drive sub-assembly system comprising: a housing (111); a piston rod (121) configured to be moved between a proximal position and a distal position; a piston rod biasing member (122) configured to bias the piston rod into the distal position; and a recharge mechanism (131) configured to engage the piston rod and to move the piston rod from the distal position towards the proximal position against the force of the piston rod biasing member when operated.

2. The reusable drive sub-assembly (101) according to claim 1 , wherein the recharge mechanism (131) comprises: a piston rack (125) located on the piston rod (121); a drive mechanism (141) comprising a drive member (142) having a drive rack (143); and a gear assembly (151) connected to the piston rack and the drive rack, the gear assembly being configured to transform movement of the drive mechanism into proximal movement of the piston rod.

3. The reusable drive sub-assembly (101) according to claim 2, wherein the gear assembly (151) comprises: a first gear (161) mated with the drive rack (143); a second gear (165) mated with the piston rack (125); and a double ratchet mechanism (171) configured to selectively prevent movement of the piston rod (121) in the distal direction.

4. The reusable drive sub-assembly (101) according to claim 3, wherein the double ratchet mechanism (171) comprises: a ratchet gear (175) comprising an external gear (176) and a face gear (177); a piston ratchet gear lock (182) configured to be movable into engagement with the external gear of the ratchet gear; anda third gear (191) comprising a face ratchet (192) configured to engage the face gear of the ratchet gear.

5. The reusable drive sub-assembly (101) according to claim 4, wherein the double ratchet mechanism (171) further comprises a common shaft (196) for the each of the gears (161 , 165, 175, 191), the first and third gears (161 , 191) being rotationally fixed to the shaft.

6. The reusable drive sub-assembly according to claim 5, wherein the second gear (165) is rotationally fixed to the ratchet gear (175).

7. The reusable drive sub-assembly (101) according claim 6, wherein the double ratchet mechanism (171) comprises a first ratchet mechanism (172) comprising the ratchet gear (175) and the piston ratchet gear lock (182), the piston ratchet gear lock being configured to selectively prevent rotational motion of the ratchet gear in a direction to move the piston rod (121) from its proximal position to its distal position and allow rotational motion of the ratchet gear in a direction to move the piston rod from its distal position to its proximal position.

8. The reusable drive sub-assembly (101) according to claim 7, further comprising a cam (185) configured to move the piston ratchet gear lock (182) into engagement with the ratchet gear (175) when the drive mechanism (141) is activated.

9. The reusable drive sub-assembly (101) according to any one of claim 6 to claim 9, wherein the double ratchet mechanism (171) comprises a second ratchet mechanism (173) comprising the ratchet gear (175) and the third gear (191), the third gear being rotationally locked to the ratchet gear in a first direction and configured to move the piston rod (121) proximally, and the third gear being configured to allow the ratchet gear to move relative to the third gear in the second direction.

10. The reusable drive sub-assembly (101) according to any one of claim 3 to claim 9, wherein the first gear (161) is larger than the second gear (165).1 1 . The reusable drive sub-assembly (101) according to any one of claim 2 to claim 10, wherein the drive mechanism (141) comprises a depressable button (146) connected to the drive rack (143) configured to be moved by an operator from a first position to a second position to move the piston rod (121) proximally via the gear assembly (151), and a drive member biasing member (148) configured to bias the drive member (142) into its first position.

12. A medicament delivery system (100) comprising: a reusable drive sub-assembly (101) according to any one of the preceding claims, and a removable syringe sub-assembly (102) comprising a cassette (201) or a syringe carrier (221) configured to receive a syringe (203, 222).

13. The medicament delivery system (100) according to claim 12, wherein the removable syringe sub-assembly (102) comprises a needle (206) and a needle cover (211) that is movable between an extended position, in which the needle is covered by the needle cover, and a retracted position, in which the needle is exposed, wherein the needle cover is configured to move the piston ratchet gear lock (182) out of engagement with the piston ratchet gear (175) when the needle cover is in its retracted position to allow distal movement of the piston rod (121).

14. The medicament delivery system (100) according to claim 12 or claim 13, wherein the cassette (201) or syringe carrier comprises a syringe (203, 222) comprising a medicament (205).

15. A method of recharging a reusable drive sub-assembly (101) of a medicament delivery system (100), the method comprising: engaging a piston ratchet gear lock (182) with a ratchet gear (175) to prevent distal motion of a piston rod (121); activating a drive member (142) engaged with a first gear (161) to rotate the first gear of a gear assembly (151), transmitting rotation of the first gear through the gear assembly to a second gear (165) engaged with the piston rod; and transforming rotational motion of the second gear into proximal linear motion of the piston rod to move the piston rod proximally.

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