A medicament delivery device

Abstract

The present disclosure relates to a medicament delivery device comprising a housing, a plunger, and an actuator moveable relative to the housing to urge the plunger to move in a first direction relative to the housing. The device comprises a drive mechanism configured such that, in use, the drive mechanism is operable to move the plunger in a second direction to expel medicament from the device. The device comprises a trigger configured such that, prior to movement of the actuator relative to the housing the trigger is prevented from being actuated to operate the drive mechanism, and such that once the actuator has been moved relative to the housing the trigger is permitted to be actuated by a user to operate the drive mechanism. The present disclosure also relates to a medicament delivery system and to a method of preparing a medicament delivery system.

Description

[0001] Attorney Docket No.: 46567-1782WO1

[0002] A medicament delivery device

[0003] Cross-reference to related applications

[0004] The present application claims priority to EP patent application No. 24214977.1 , filed on November 22, 2024, the disclosure of which is incorporated herein by reference.

[0005] Field of the invention

[0006] The present disclosure relates to a medicament delivery device. The present disclosure also relates to a medicament delivery system and to a method of preparing a medicament delivery system.

[0007] Background

[0008] Medicaments can be administered using a variety of different methods and devices. For example, a medicament delivery device may comprise a hypodermic needle for piercing the skin of a patient and transferring medicament from a medicament source to the user intravenously, intramuscularly or subcutaneously.

[0009] The nasal administration of medicaments represents an alternative route to intravenous, intramuscular or subcutaneous medicament administration. Devices for nasal administration of medicaments typically include a nozzle for insertion into the patient’s nose and delivering medicament to the user’s nose from a medicament source. As nasal administration devices do not typically pierce the skin of the user, the process of administering the medicament may be less painful for the user. Nasal medicament administration devices are also relatively simple to use and can be operated with less training than conventional medicament delivery devices. They can also deliver relatively large volumes of medicament to a user.

[0010] It is desirable to provide a medicament delivery device that is easy to use and store.

[0011] Summary of the invention

[0012] According to the present disclosure, there is provided a medicament delivery device comprising: a housing; a plunger; an actuator moveable relative to the housing to urge the plunger to move in a first direction relative to the housing; a drive mechanism configured such that, in use, the drive mechanism is operable to move the plunger in a second direction to expel medicament from the device; and, a trigger configured such that, prior to Attorney Docket No.: 46567-1782WO1 movement of the actuator relative to the housing the trigger is prevented from being actuated to operate the drive mechanism, and such that once the actuator has been moved relative to the housing the trigger is permitted to be actuated by a user to operate the drive mechanism.

[0013] Advantageously, the trigger is prevented from being actuated to operate the drive mechanism until a pre-filled medicament container has been inserted into the housing or medicament from a medicament container has been drawn into a chamber (in optional embodiments that comprise such a chamber). In some embodiments, the trigger is prevented from being actuated because the trigger is prevented from moving relative to the housing to operate the drive mechanism until the actuator has been moved relative to the housing (for example, the trigger is prevented from being retracted into the housing to operate the drive mechanism until the actuator has been moved relative to the housing). In other embodiments, the trigger is prevented from being actuated because it is initially in a position in which it is not actuatable to operate the drive mechanism, and wherein movement of the actuator relative to the housing causes the trigger to move to a position wherein it can be actuated by the user to operate the drive mechanism.

[0014] In some embodiments, the medicament delivery device comprises a chamber for receiving medicament from a container of medicament, and wherein movement of the plunger in the first direction draws medicament into the chamber from the container of medicament. In some embodiments, the housing comprises the chamber.

[0015] In some embodiments, the actuator is moveable relative to the housing to urge the plunger to move in the first direction relative to the housing and relative to chamber.

[0016] In some embodiments, the actuator is moveable relative to the housing to urge the plunger to move in the first direction relative to the housing and relative to the medicament container.

[0017] In some embodiments, the actuator is moveable relative to the housing and relative to the medicament container to urge the plunger to move in the first direction relative to the housing.

[0018] In some embodiments, the actuator is moveable relative to the housing and relative to the chamber to urge the plunger to move in the first direction relative to the housing. Attorney Docket No.: 46567-1782WO1

[0019] In some embodiments, the actuator is moveable relative to a portion of the housing that is configured to interface with the medicament container. In some embodiments, the housing comprises an inlet port that is configured to interface with the medicament container, and wherein the actuator is moveable relative to the inlet port.

[0020] In other embodiments, the housing comprises a receiving space for receiving a container of medicament such that the plunger interfaces with the container of medicament to expel medicament from the container of medicament (for example, the container may comprise a piston or bung that is moved in the second direction by the plunger to expel medicament). In some embodiments, the plunger can be moved in the first direction to create space to accommodate the container and then can be moved in the second direction to engage the container (e.g. to engage the piston or bung of the container) and take up a gap or play between the container and the plunger (which may be due to different lengths of containers, e.g. due to different types of containers being used with the device or due to manufacturing tolerances) and then expel medicament from the container (e.g. by moving the piston or bung within the container to expel the medicament).

[0021] In some embodiments, is the medicament delivery device is configured such that movement of the actuator relative to the housing causes the trigger to move to a ready position wherein the trigger is ready to be actuated by a user to operate the drive mechanism and, optionally, wherein the trigger is configured to rotate relative to the housing to move to the ready position.

[0022] In some embodiments, the trigger is configured to rotate about a central axis of the housing to move to the ready position.

[0023] In some embodiments, the housing comprises a circumferentially extending slot and wherein the trigger is configured to move within the slot.

[0024] In some embodiments, the medicament delivery device comprises a stop moveable from a first position to a second position upon movement of the actuator relative to the housing, wherein when the stop is in the first position actuation of the trigger is prevented and wherein when the stop is in the second position actuation of the trigger is permitted. Attorney Docket No.: 46567-1782WO1

[0025] In some embodiments, the stop is configured to align with a portion of a component of the medicament delivery device when the stop is in the first position. In some embodiments, the stop aligns with a locking element of the component of the medicament delivery device. In some embodiments, the stop aligns with a portion of a shuttle of the medicament delivery device.

[0026] In some embodiments, the stop prevents axial movement of the trigger relative to the housing to operate the drive mechanism when the stop is in the first position. In some embodiments, the stop prevents axial proximal movement of the trigger relative to the housing to operate the drive mechanism when the stop is in the first position.

[0027] In some embodiments, when the stop is in the second position, axial movement of the trigger relative to the housing to operate the drive mechanism is permitted. In some embodiments, when the stop is in the second position, axial proximal movement of the trigger relative to the housing to operate the drive mechanism is permitted.

[0028] In some embodiments, locking element aligns with a slot when the stop is in the second position, such that the locking element moves into the slot.

[0029] In some embodiments, the trigger comprises a trigger button and, optionally, comprises a lever.

[0030] In some embodiments, the trigger is configured to be pressed against a body of a user to operate the drive mechanism and, optionally, comprises a sleeve.

[0031] In some embodiments, the trigger comprises a needle sleeve.

[0032] In some embodiments, the trigger is at a distal end of the medicament delivery device.

[0033] In some embodiments, the trigger is moved proximally to operate the drive mechanism.

[0034] In some embodiments, the plunger is moveable axially within the housing in first and second directions. In some embodiments, the plunger is slidable axially within the housing. Attorney Docket No.: 46567-1782WO1

[0035] In some embodiments, the actuator is a knob. In some embodiments, the actuator is located at a proximal end of the housing.

[0036] In some embodiments, the device can be combined with the medicament container and then medicament drawn into the chamber. In some embodiments, multiple doses can be sequentially drawn into the chamber such that the device is reusable. In some embodiments, the medicament container can be removed and replaced with an alternative medicament container such that the device is further reusable.

[0037] In some embodiments, the drive mechanism comprises a drive biasing member configured to urge the plunger to expel medicament from the chamber.

[0038] In some embodiments, the actuator is configured such that movement of the actuator relative to the housing to urge the plunger in the first direction compresses the drive biasing member.

[0039] In some embodiments, the actuator is moveable relative to the housing to urge the plunger to move in a first direction relative to the housing and against the force of the drive biasing member.

[0040] In some embodiments, the medicament delivery device comprises a medicament delivery member. The medicament delivery member may comprise, for example, an intranasal nozzle or a needle.

[0041] In some embodiments, the actuator is moveable relative to the housing and relative to the medicament delivery member to urge the plunger to move in a first direction relative to the housing.

[0042] In some embodiments, the actuator is moveable relative to the housing to urge the plunger to move in a first direction relative to the housing, and wherein the medicament delivery member is located at a distal end of the housing.

[0043] In some embodiments, the actuator is rotatable to urge the plunger to move in the first direction relative to the housing. Attorney Docket No.: 46567-1782WO1

[0044] In some embodiments, the plunger is configured such that, in use, the plunger is moveable relative to the housing in a first direction to draw medicament into the chamber from the container and is moveable relative to the housing in a second direction to expel medicament from the chamber for delivery to a user.

[0045] In some embodiments, the housing is configured to interface with the container of medicament.

[0046] In some embodiments, the trigger is configured to move from a first position to a second position to operate the drive mechanism, and wherein the trigger is prevented from moving to the second position until the actuator has been moved relative to the housing.

[0047] In some embodiments, the plunger is configured such that, in use, the plunger is moveable relative to the housing in a first direction from a first position to a second position to draw medicament into the chamber from the container and is moveable relative to the housing in a second direction from the second position to a primed position to expel a priming volume of the medicament from the chamber and, optionally, wherein the drive mechanism is configured to move the plunger from the primed position in the second direction to expel a dosage volume of the medicament from the chamber for delivery to a user.

[0048] Advantageously, this priming helps to ensure that air is not present in the delivery member (e.g. needle or intranasal nozzle) of the device prior to delivery of the medicament.

[0049] In some embodiments, the plunger is configured such that, in use, the plunger is moveable relative to the housing in a first direction from a first position to a second position to provide space to accommodate a container (e.g. a pre-filled container that already contains medicament) within the housing and is moveable relative to the housing in a second direction from the second position to a primed position to engage the container (e.g. to take up play between the plunger and the container), and optionally, wherein the drive mechanism is configured to move the plunger from the primed position in the second direction to expel a dosage volume of the medicament from the container for delivery to a user. The plunger may move from the second position to the primed position under the force of a biasing member (e.g. the drive biasing member) or due to a force being applied by the user (e.g. to the actuator). Attorney Docket No.: 46567-1782WO1

[0050] In some embodiments, the medicament delivery device comprises an inlet that is configured to fluidly communicate the chamber with the medicament container and, optionally, wherein the inlet is sealed by the plunger when the plunger is in the primed position. Advantageously, this helps to prevent medicament from being urged from the chamber back into the medicament container during delivery of medicament to the user.

[0051] In some embodiments, the housing comprises a port that is configured to interface with the container of medicament. In other embodiments, the housing is configured to receive the container within the housing to interface with the container.

[0052] In some embodiments, the port comprises an aperture in the housing that is configured to receive an end of the container of medicament.

[0053] In some embodiments, the port is configured to interface with the container of medicament such that a central axis of the container of medicament is at an angle to the central axis of the medicament delivery device and, optionally, is substantially perpendicular to the central axis of the medicament delivery device.

[0054] In some embodiments, the port comprises a needle that is configured to penetrate a sealing element of the container of medicament.

[0055] In some embodiments, the device has an intended filling orientation, and wherein the port is arranged such that during filling of the device the medicament container is orientated such that medicament flows towards the cannula under the influence of gravity when the device is in the intended filling orientation. This helps to encourage medicament to flow from the medicament container and into the cannula. In some embodiments, the cannula is located below the medicament container. In some embodiments, the port is configured such that when the device is in the intended filling position, the cartridge is orientated vertically or substantially vertically. In some embodiments, in the intended filling orientation of the device, a central axis of the piston is horizontal.

[0056] In some embodiments, the drive mechanism comprises a drive biasing member and, optionally, comprises a spring.

[0057] In some embodiments, the actuator is moveable to urge the plunger in the first direction from the first position to the second position against the force of the plunger biasing Attorney Docket No.: 46567-1782WO1 member and, optionally, wherein further movement of the actuator releases the plunger such that the plunger is urged in the second direction to the primed position.

[0058] Advantageously, this helps to make the device easier to use, because the user can move the actuator to draw medicament into the chamber and then release the plunger to the primed position ready for medicament delivery.

[0059] In some embodiments, movement of the plunger from the first position to the second position primes the biasing member.

[0060] In some embodiments, the actuator is moveable in a first direction to urge the plunger to the second position, and wherein further movement of the actuator in the first direction releases the plunger.

[0061] In some embodiments, the trigger is located at a distal end of the medicament delivery device and is configured to be urged in a proximal direction to operate the drive mechanism to move the plunger in the second direction or wherein the trigger comprises a trigger button that is configured to be operated by a user.

[0062] The distal end is located nearer to the medicament delivery site during use of the medicament delivery device to deliver medicament (e.g. nearer to the injection site for an injection device or nearer to a user’s nasal structures for an intranasal device).

[0063] In some embodiments, the medicament delivery device comprises a needle sleeve or intranasal nozzle that comprises the trigger.

[0064] In other embodiments, the medicament delivery device comprises a trigger button that comprises the trigger. In some embodiments, the button is configured to be pushed, slid or rotated relative to the housing to release the locking mechanism. The button may be a lever.

[0065] In some embodiments, the medicament delivery device comprises a locking member that is moveable relative to the plunger from a locked position to an unlocked position, in which the plunger is released to expel medicament from the chamber and, optionally, the locking member is rotatable between the locked and unlocked positions and, optionally, wherein the locking member comprises a collar that is rotatable between the locked and unlocked positions. Attorney Docket No.: 46567-1782WO1

[0066] In some embodiments, the medicament delivery device comprises a locking biasing member configured to bias the locking member to rotate relative to the housing when the actuator is moved to draw medicament into the chamber.

[0067] In some embodiments, the locking biasing member is configured to bias the locking member to rotate relative to the housing in a first rotational direction as the plunger moves from the first position to the second position and, optionally, wherein one of the plunger and locking member comprises a ramp section configured such that when the plunger is moved from the second position to the primed position in the second direction, the other one of the plunger and locking member engages the ramp section to move the locking member in a second rotational direction, opposite to the first rotational direction.

[0068] In some embodiments, the ramp section is configured such that when the plunger is moved from the ready (primed) position to the second position in the first direction, the locking member (e.g. collar) is permitted to move in a first rotational direction under the force of the locking member biasing member.

[0069] In some embodiments, the trigger is configured to urge the locking member to move from the locked to the unlocked position and, optionally, wherein the trigger is fixed relative to the locking member and, optionally, wherein the trigger extends from the locking member.

[0070] In some embodiments, the trigger button extends radially outwardly from the locking member (e.g. collar).

[0071] In some embodiments, the trigger button is integrally formed with the locking member.

[0072] In some embodiments, one of the plunger and locking member comprises a protrusion and the other one of the plunger and locking member comprises a track configured to cooperate with the protrusion.

[0073] In some embodiments, the track comprises a stop section and a longitudinal section distal of the stop section, the stop section being configured to cooperate with the protrusion to prevent movement of the plunger in the second direction, and wherein rotation of the locking member causes the protrusion to move out of cooperation with the stop section and into the longitudinal section to allow the plunger to be moved in the second direction. Attorney Docket No.: 46567-1782WO1

[0074] In some embodiments, the track comprises the ramp section configured such that when the plunger is moved from the primed position to the second position in the first direction, the locking member is permitted to move in a first rotational direction under the force of a locking member biasing member, and such that when the plunger is moved from the second position to the primed position in the second direction, the protrusion of the plunger engages the ramp section to move the locking member in a second rotational direction, opposite to the first rotational direction.

[0075] In some embodiments, the medicament delivery device comprises a shuttle that is moveable relative to the housing from a first position to a second position to urge the locking member from the locked position to the unlocked position and, optionally, wherein one of the shuttle and locking member comprises a cam surface configured to engage the other one of the shuttle and locking member to rotate the locking member from the locked position to the unlocked position upon movement of the shuttle from the first position to the second position. In some embodiments, the shuttle is moveable axially relative to the housing.

[0076] In some embodiments, the medicament delivery device comprises an indicator member that is configured to move from an initial position to an indicating position. In other embodiments, the indicator member is omitted.

[0077] In some embodiments, movement of the indicator member from the initial position to the indicating position indicates to a user that the plunger has moved in the first direction against the force of the drive biasing member.

[0078] In some embodiments, the indicator member comprises an indicator ring.

[0079] In some embodiments, the indicator member is configured to remain in the indicating position when the locking member is moved in the second rotational direction.

[0080] In some embodiments, the indicator member comprises the stop. In some embodiments, when the indicator member is in the initial position the shuttle is prevented from being moved from the first position to the second position by the stop, and wherein when the indicator member is in the indicating position the shuttle is moveable from the first position to the second position. Attorney Docket No.: 46567-1782WO1

[0081] In some embodiments, one of the indicating member and shuttle comprises the slot that is configured to align with a locking element of the other one of the indicating member and shuttle when the indicating member is in the indicating position such that the locking element can enter through the slot to permit the shuttle to move from the first position to the second position.

[0082] It should be recognised that in other embodiments the indicating member may be omitted and instead the stop may be part of a rotatable components that, for example, does not indicate a state of the device to the user and may not be visible through a viewing window of the housing.

[0083] In some embodiments, movement of the shuttle from the first position to the second position is in the proximal direction.

[0084] In some embodiments, the medicament delivery device comprises a needle sleeve or intranasal nozzle that is moveable towards and / or into the housing to urge the shuttle from the first position to the second position.

[0085] In some embodiments, the needle sleeve or intranasal nozzle is a separate and discrete component to the shuttle. In other embodiments, the needle sleeve or intranasal nozzle is integrally formed with the shuttle.

[0086] In some embodiments, the trigger button is fixed relative to the locking member and is configured to be rotated relative to the housing by the user to urge the locking member from the locked position to the unlocked position to release the plunger. The trigger button may be integrally formed with the locking member. The trigger button may extend radially from the locking member. The trigger button may comprise a lever.

[0087] In other embodiments, the medicament delivery device is configured such that the user manually moves the plunger from the second position to the primed position to expel the priming volume of medicament from the chamber. For example, the user may push the plunger from the second position to the primed position.

[0088] In some embodiments, the movement of the plunger from the second position to the primed position in the second direction is a first discrete step of operation of the Attorney Docket No.: 46567-1782WO1 medicament delivery device and the movement of the plunger from the primed position in the second direction to expel the dosage volume is a second discrete step of operation of the medicament delivery device.

[0089] In some embodiments, the plunger is moveable from the first position to the second position via the primed position.

[0090] In some embodiments, the actuator is configured to engage the plunger to urge the plunger in the first direction and, optionally, wherein the actuator is configured to engage the plunger to urge the plunger in the first direction over a first range of movement of the actuator and wherein further movement of the actuator causes the actuator to disengage the plunger such that the plunger moves in the second direction under the force of the drive biasing member. Advantageously, this helps to make the device easier to use, because the user can move the actuator move the plunger against the force of the biasing member and then release the plunger.

[0091] In some embodiments, the actuator is rotatable relative to the housing to urge the piston to move to draw medicament into the chamber. Advantageously, this may reduce the force that is exerted by the user to move the plunger in the first direction against the force of the drive biasing member.

[0092] In some embodiments, at least one of the plunger and actuator comprises an engaging portion that is configured to engage with the other one of the plunger and actuator such that rotation of the actuator urges the plunger to move to draw medicament into the chamber.

[0093] In some embodiments, the engaging portion subtends less than 360 degrees about the longitudinal axis of the plunger.

[0094] In some embodiments, said one of the plunger and actuator comprises a thread that comprises the engaging portion.

[0095] In some embodiments, the actuator is rotatable in a first rotational direction relative to the housing to urge the piston in the first direction, and wherein the medicament delivery device comprises a ratchet mechanism configured to resist the actuator from being rotated relative to the housing in a second rotational direction, opposite to the first Attorney Docket No.: 46567-1782WO1 rotational direction. Advantageously, the ratchet mechanism helps to prevent the force of the drive biasing member from returning the plunger in the second direction if the user pauses movement of the actuator.

[0096] In another embodiment, the actuator is rotatable relative to the housing to move the piston from the first position to the primed position, and is configured to be pulled by the user to move the plunger from the primed position to the second position.

[0097] In one embodiment, the actuator is configured such that once the user has pulled the plunger from the primed position to the second position, release of the dosing member by the user causes the plunger to be moved from the second position to the primed position. In some embodiments, the plunger is pulled from the primed position to the second position against the force of the drive biasing member.

[0098] In some embodiments the actuator is configured to move relative to the housing to urge the plunger from the first position to the second position.

[0099] In some embodiments, further movement of the actuator when the plunger is in the second position allows the plunger to move to the primed position.

[0100] In some embodiments, said further movement of the actuator when the plunger is in the second position causes the dosing actuator to disengage the plunger. For example, the engaging portion (e.g. thread) of said one of the plunger and actuator disengages the other one of the actuator and plunger.

[0101] In some embodiments, the medicament delivery device is an intranasal medicament delivery device.

[0102] In some embodiments, the intranasal medicament delivery device is configured to deliver medicament to the nasal structures of the user. In some embodiments, the intranasal medicament delivery device is configured to deliver medicament to the nasal structures of the user to elicit an immune response.

[0103] The intranasal medicament delivery device may be configured to atomize the medicament and, optionally, may further comprise an atomiser. Such atomiser may facilitate insertion of the atomiser and outlet into an orifice of a patient into which the medicament is to be Attorney Docket No.: 46567-1782WO1 delivered. The atomiser and / or outlet may comprise a luer lock to sealingly connect the atomiser to the nozzle outlet(s). In another embodiment, the nozzle outlet(s) itself is configured to atomize the medicament.

[0104] An atomiser, plug, adaptor or other component may be configured to atomise a liquid medicament as the medicament is expelled through the outlet and through a medicament passage in the atomiser, plug, adaptor or other component.

[0105] The medicament may be any medicament described herein. The medicament may be a vaccine adapted for nasal administration. The vaccine may be an RSV vaccine.

[0106] The intranasal medicament delivery device may be an intranasal atomization delivery device.

[0107] The intranasal medicament delivery device may be configured to deliver about % of a dose to each nostril.

[0108] The intranasal medicament delivery device may be configured to deliver about 0.2mL, wherein about 0.1 mL is delivered to each nostril.

[0109] The intranasal medicament delivery device may deliver an average droplet size Dv50 of about 10-120 pm.

[0110] The intranasal medicament delivery device may deliver an average droplet size Dv50 delivered to each nostril may be about 10-120 pm, about 30-110 pm, about 50-110 pm, about 70-110 pm, or about 80-110 pm.

[0111] The intranasal medicament delivery device may be configured so that an average shot volume to each nostril is between about 85 pL to about 120 pL, about 90 pL to about 115 pL, or about 95 pL to about 115 pL.

[0112] In some embodiments, the intranasal medicament delivery device is configured to deliver in the range of 20 to 2000 microlitres (0.02 to 2 ml) volume of medicament and, preferably, in the range of 100 to 400 microlitres (0.1 to 0.4 ml) and, preferably, in the range of 10 to 300 microlitres (0.1 to 0.3 ml) and, preferably, about 200 microlitres (0.2 ml). Attorney Docket No.: 46567-1782WO1

[0113] In some embodiments, the intranasal medicament delivery device is configured to deliver in the range of 10 to 1000 microlitres (0.01 to 1 ml) volume of medicament to each nostril of the user and, preferably, in the range of 50 to 200 microlitres (0.05 to 0.2 ml) and, preferably, in the range of 50 to 150 microlitres (0.05 to 0.1 ml) and, preferably, about 100 microlitres (0.1 ml) of medicament to each nostril of the user.

[0114] According to the present disclosure, there is also provided a medicament delivery system comprising a medicament delivery device as disclosed herein and a container of medicament and, preferably, wherein the medicament is a vaccine.

[0115] In some embodiments, the medicament delivery system is an intranasal medicament delivery system. The intranasal medicament delivery system may comprise an intranasal nozzle.

[0116] In some embodiments, the intranasal nozzle comprises first and second nozzle outlets for delivering medicament to a user. Advantageously, medicament can be delivered to both external nostrils of a user simultaneously.

[0117] In some embodiments, the intranasal nozzle comprises first and second medicament delivery conduits.

[0118] In other embodiments, the medicament delivery device is an oral medicament delivery device or an injection medicament delivery device.

[0119] According to the present disclosure, there is provided a medicament delivery device comprising: a housing; a chamber for receiving medicament from a container of medicament; a plunger within the housing; an actuator moveable relative to the housing to urge the plunger relative to the housing such that, in use, medicament is drawn into the chamber from the container; a drive mechanism configured such that, in use, the drive mechanism is operable to move the plunger to expel medicament from the chamber; and, a trigger configured such that, prior to movement of the actuator relative to the housing the trigger is prevented from being actuated to operate the drive mechanism, and such that once the actuator has been moved relative to the housing the trigger is permitted to be actuated by a user to operate the drive mechanism. Attorney Docket No.: 46567-1782WO1

[0120] The medicament delivery device may have any of the features described above.

[0121] Advantageously, the trigger is prevented from being actuated to operate the drive mechanism until medicament has been drawn into the chamber. In some embodiments, the trigger is prevented from being actuated because the trigger is prevented from moving relative to the housing to operate the drive mechanism until the actuator has been moved relative to the housing (for example, the trigger is prevented from being retracted into the housing to operate the drive mechanism until the actuator has been moved relative to the housing). In other embodiments, the trigger is prevented from being actuated because it is initially in a position in which it is not actuatable to operate the drive mechanism, and wherein movement of the actuator relative to the housing causes the trigger to move to a position wherein it can be actuated by the user to operate the drive mechanism.

[0122] According to the present disclosure, there is also provided a method of preparing a medicament delivery system, the method comprising: moving an actuator relative to a housing to draw medicament into a chamber from a container and such that the actuator is moved from a position wherein a trigger is prevented from being actuated to operate a drive mechanism to a position wherein the trigger is permitted to be actuated by a user to operate the drive mechanism to expel medicament from the chamber.

[0123] The method of preparing the medicament delivery system may be performed prior to the delivery of medicament to a patient.

[0124] In some embodiments, the medicament delivery system comprises a chamber for receiving medicament from a container of medicament, and wherein movement of the plunger in the first direction draws medicament into the chamber from the container of medicament. In some embodiments, the housing comprises the chamber.

[0125] In some embodiments, the method comprises moving the actuator relative to the housing to urge the plunger to move in the first direction relative to the housing and relative to chamber.

[0126] In some embodiments, the method comprises moving the actuator relative to the housing to urge the plunger to move in the first direction relative to the housing and relative to the medicament container. Attorney Docket No.: 46567-1782WO1

[0127] In some embodiments, the method comprises moving the actuator relative to the housing and relative to the medicament container to urge the plunger to move in the first direction relative to the housing.

[0128] In some embodiments, the method comprises moving the actuator relative to the housing and relative to the chamber to urge the plunger to move in the first direction relative to the housing.

[0129] In some embodiments, the method comprises moving the actuator relative to a portion of the housing that is configured to interface with the medicament container. In some embodiments, the housing comprises an inlet port that is configured to interface with the medicament container, and wherein the actuator is moveable relative to the inlet port.

[0130] In some embodiments, the trigger is configured to rotate about a central axis of the housing to move to a ready position.

[0131] In some embodiments, the drive mechanism comprises a drive biasing member configured to urge the plunger to expel medicament from the chamber.

[0132] In some embodiments, the method comprises moving the actuator relative to the housing to urge the plunger in the first direction to compress the drive biasing member.

[0133] In some embodiments, the method comprises moving the actuator relative to the housing to urge the plunger to move in a first direction relative to the housing and against the force of the drive biasing member.

[0134] In some embodiments, the medicament delivery device comprises a medicament delivery member. The medicament delivery member may comprise, for example, an intranasal nozzle or a needle.

[0135] In some embodiments, the method comprises moving the actuator relative to the housing and relative to the medicament delivery member to urge the plunger to move in a first direction relative to the housing. Attorney Docket No.: 46567-1782WO1

[0136] In some embodiments, the method comprises moving the actuator relative to the housing to urge the plunger to move in a first direction relative to the housing, and wherein the medicament delivery member is located at a distal end of the housing.

[0137] In some embodiments, the actuator is rotatable to urge the plunger to move in the first direction relative to the housing.

[0138] According to the present disclosure there is also provided a method of operating a medicament delivery system, the method comprising: moving an actuator relative to a housing in a first direction such that the actuator is moved from a position wherein a trigger is prevented from being actuated to operate a drive mechanism to a position wherein the trigger is permitted to be actuated by a user to operate the drive mechanism to expel medicament from the system; and, actuating the trigger to operate the drive mechanism to expel medicament from the system.

[0139] The method may comprise expelling / administering an RSV vaccine.

[0140] The medicament may be expelled / delivered intranasally with about % dose delivered to each nostril.

[0141] The intranasal dose of the medicament may be delivered in about 0.2 mL, wherein about 0.1 mL is delivered to each nostril.

[0142] The method may comprise intranasal atomization delivery of an average droplet size Dv50 of about 10-120 pm.

[0143] The method may comprise intranasal atomization delivery of an average droplet size Dv50 delivered to each nostril may be about 10-120 pm, about 30-110 pm, about 50-110 pm, about 70-110 pm, or about 80-110 pm.

[0144] The method may comprise intranasal atomization delivery so that an average shot volume to each nostril is between about 85 pL to about 120 pL, about 90 pL to about 115 pL, or about 95 pL to about 115 pL.

[0145] In some embodiments, the method comprises removing the medicament delivery device from a sealed pack. Attorney Docket No.: 46567-1782WO1

[0146] In some embodiments, the method comprises coupling a delivery member to the housing. The delivery member may comprise a needle or an intranasal nozzle. In some embodiments, the method comprises removing the delivery member from a sealed pack and coupling the delivery member to the housing.

[0147] In some embodiments, the method comprises interfacing a medicament container with a housing of the medicament delivery device. In some embodiments, the method comprises removing the medicament container from a sealed pack and interfacing the medicament container with the housing.

[0148] In some embodiments, the method comprises drawing medicament from a medicament container into a chamber.

[0149] In some embodiments, the method comprises expelling medicament from the chamber for delivery to a user.

[0150] According to the present disclosure there is also provided a method of operating a medicament delivery system, the method comprising: moving an actuator relative to a housing to draw medicament into a chamber from a container and such that the actuator is moved from a position wherein a trigger is prevented from being actuated to operate a drive mechanism to a position wherein the trigger is permitted to be actuated by a user to operate the drive mechanism to expel medicament from the chamber; and, actuating the trigger to operate the drive mechanism to expel medicament from the chamber.

[0151] Brief description of the drawings

[0152] So that the invention may be more fully understood, reference is made to the accompanying drawings, in which:

[0153] Fig. 1 is a perspective view of a medicament delivery system according to an exemplary embodiment of the invention;

[0154] Fig. 2 is a perspective view showing a distal end of a delivery member and a proximal end of a reusable injector device of the medicament delivery system;

[0155] Fig. 3 is a longitudinal cross section of the medicament delivery system;

[0156] Fig. 4 is a detail view of a plunger rod and dose setting knob of the reusable injector device; Attorney Docket No.: 46567-1782WO1

[0157] Figs. 5a-5e show the medicament delivery system in longitudinal section in various stages of operation;

[0158] Fig. 6a-6f show the plunger rod and a release collar of the reusable injector device in various stages of operation;

[0159] Fig. 7 shows a shuttle and the release collar of the reusable injector device;

[0160] Figs. 8a-8b show an indicator ring and the shuttle in various stages of operation;

[0161] Figs. 9a to 9e schematically show relative positions of the indicator ring, release collar and housing;

[0162] Fig. 10 is a perspective view of the delivery member;

[0163] Figs. 11 a and 11 b show the delivery member in various stages of operation; and

[0164] Figs. 12a to 12c show the delivery member in various stages of operation;

[0165] Fig. 13 is a perspective view of a medicament delivery system according to another exemplary embodiment of the invention;

[0166] Figs. 14a to 14e show a perspective view of relative positions of the indicator ring, release collar and housing;

[0167] Figs. 15a to 15e show a cross-sectional view of relative positions of the indicator ring, release collar and housing;

[0168] Figs. 16a to 16e schematically show relative positions of the indicator ring, release collar and housing;

[0169] Fig. 17a-17c show the plunger rod and a release collar of the reusable injector device in various stages of operation;

[0170] Fig. 18 is a cross-sectional view of a medicament delivery system according to another exemplary embodiment of the invention; and,

[0171] Fig. 19 is a block diagram illustrating a method of preparing a medicament delivery system.

[0172] Detailed description

[0173] A drug delivery device, as described herein, may be configured to inject a medicament into a patient or to deliver medicament intranasally or orally. For example, delivery could be sub-cutaneous, intra-muscular, intravenous or the delivery could be to the mouth or nasal structures. 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 autoinjector. 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 Attorney Docket No.: 46567-1782WO1

[0174] (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).

[0175] 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.

[0176] 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.

[0177] 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 sleeve in order to cause injection.

[0178] 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 Attorney Docket No.: 46567-1782WO1 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.

[0179] 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 autoinjector) and a dose setting mechanism (as typically found in a pen-injector).

[0180] The present disclosure relates to a medicament delivery system 1 comprising a medicament delivery device 100 and a medicament delivery member 211 for use with the medicament delivery device 100. The medicament delivery device 100 may be reusable or single-use.

[0181] In the embodiment of Figs. 1 to 12C, the medicament delivery member 211 is a needle 211 and the medicament delivery device 100 is an injector device 100. However, it should be recognised that in other embodiments the medicament delivery member 211 may have a different configuration, for example, the medicament delivery member may instead be an intranasal nozzle or an oral nozzle. In some embodiments, the medicament delivery device 100 may be, for example, an intranasal medicament delivery device or an oral medicament delivery device such as an inhaler.

[0182] 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 delivery member 211 or medicament delivery device 100. The term “distal” refers to a location that is relatively closer to a site of drug delivery, and the term "proximal" refers to a location that is relatively further away from the drug delivery site (e.g. the injection site when the medicament is delivered by injection, the user’s nose when the medicament is delivered intranasally, or the user’s mouth when the medicament is delivered orally).

[0183] Fig. 1 shows the medicament delivery device 100 with the delivery member 211 attached to the medicament delivery device 100. In particular, the delivery member 211 is part of a medicament delivery unit 200 that is attached to the medicament delivery device 100. The medicament delivery device 100 is herein referred to simply as the ‘device 100’ for brevity. Attorney Docket No.: 46567-1782WO1

[0184] Fig. 3 shows the device 100 attached to the medicament delivery unit 200 in a section taken along the device 100 axis X-X. The device 100 comprises: a housing 110 and a dose delivery mechanism provided within the housing 110.

[0185] The housing 110 comprises a primary tubular wall 111 that extends along the device axis X-X and houses the dose delivery mechanism; and a secondary tubular wall 112 that extends from the primary tubular wall 111 , perpendicular to the device axis X-X. The secondary tubular wall 112 is integrally formed with the primary tubular wall 111 and surrounds a port 113 which is configured to receive a medicament container 300, which in the present example, is a cylindrical medicament cartridge 300. The port 113 comprises a cannula 114 that communicates with a dosing chamber 121 of the dose delivery mechanism via an inlet 114A. The cannula 114 penetrates a bung of the medicament cartridge 300 to allow medicament to flow from the cartridge 300 and into the dosing chamber 121 via the inlet 114A.

[0186] The port 113 is configured to receive an end 303 of the medicament container 300. In the present example, the port 113 comprises a well 113A that is configured to receive the end 303 of the medicament container 300. The cannula 114 projects into the well 113A. The cannula 114 is configured to penetrate a sealing element 304 (e.g. a septum 303) of the medicament container 300 when the medicament container 300 is inserted into the well 113A.

[0187] The port 113 comprises a gripping portion 112A that is configured to engage the medicament container 300 to retain the medicament container 300 in position. In the present example, the gripping portion 112A is resiliently deformable. In use, the user inserts the end 303 of the medicament container 300 into the port 113 such that the gripping portion 112A grips the cylindrical wall 301 of the medicament container 300.

[0188] In the present example, the tubular wall 112 of the housing 110 comprises the gripping portion 112A. The tubular wall 112 comprises at least one slit 112B that allows for a portion of the tubular wall 112 to flex such that the tubular wall 112 is resiliently deformable to grip the medicament container 300. When the medicament container 300 is inserted into the port 113, the tubular wall 112 flexes outwardly slightly such that the tubular wall 112 is pressed against the cylindrical wall 301 of the medicament container 300 to retain the medicament container 300 in position within the port 113. It should be recognised that in other embodiments (not shown), the gripping portion may have a different configuration and, for example, may comprise a portion of resilient material (e.g. Attorney Docket No.: 46567-1782WO1 rubber) that grips the neck of the medicament container 300 such that the gripping portion snaps past the neck to retain the medicament container 300 in position.

[0189] The port 113 is provided in an exterior of the housing 110 such that the user can insert the medicament container 300 into the port 113 without first having to open the housing 110.

[0190] The port 113 is configured such that the medicament container 300 can be inserted into the port 113 in a direction along the central axis of the medicament container 300.

[0191] In some embodiments, the port 113 is configured such that when the medicament container 300 is interfaced with the port 113, the central axis of the medicament container 300 is at an angle with respect to a central axis of the plunger 124. In the present example, the central axis of the medicament container 300 is substantially perpendicular to the central axis of the plunger 124.

[0192] In some embodiments, the port 113 is configured such that medicament container 300 is inserted into the inlet port in an insertion direction Y. The insertion direction Y is at an angle with respect to a central axis of the plunger 124 and, optionally, is substantially perpendicular thereto.

[0193] In some embodiments, the port 113 is configured to interface with medicament containers 300 of different lengths. That is, the user can interface a first medicament container having a first length with the port 113 or can interface a second medicament container having a second length with the port 113.

[0194] In some embodiments, the port 113 is configured to interface with containers of medicament that are either vials or cartridges. That is, the user can interface either a cartridge 300 or a vial 300’ (as shown in Fig. 18) with the port 113.

[0195] In some embodiments, the device 100 has an intended filling orientation (for instance, wherein the device axis X-X is horizontal with respect to the ground, as shown in Fig. 3 in respect of the device 100 of the present embodiment and Fig. 15A in respect of the device 100’ of the later embodiment). The port 113 is arranged such that during filling of the device 100 the cartridge 300 is orientated such that medicament flows towards the cannula 114 under the influence of gravity when the device 100 is in the intended filling orientation. This helps to encourage medicament to flow from the cartridge 300 and into the cannula 114. That is, the cannula 114 is located below the cartridge 300 (or other Attorney Docket No.: 46567-1782WO1 such medicament container). In some embodiments, the port 113 is configured such that when the device 100 is in the filling position, the cartridge 300 is orientated vertically or substantially vertically. In some embodiments, in the intended filling orientation of the device 100, a central axis of the piston 1241 is horizontal.

[0196] Optionally, the device 100 is configured to rest on a flat surface such that the device 100 is orientated in the intended filling orientation. Thus, a user can place the device 100 on the flat surface (e.g. a table) and then fill the dosing chamber 121 (e.g. by rotating the dosing knob 126 to draw medicament into the device 100, as is described in more detail below). The device 100 may comprise one or more contact portions that are configured to engage the flat surface such that the device 100 is orientated in the intended filling orientation. The contact portion(s) may comprise, for example, a flat bottom of the housing 110 or one or more feet / legs of the device 100. For instance, the housing 110 may comprise a flat bottom (not shown), on the opposite side of the housing 110 to the port 113, such that the device 100 can be rested on the flat bottom with the port 113 extending vertically such that the cartridge 300 is orientated vertically and thus medicament in the cartridge 300 flows down towards the cannula 114. As another example, the housing 110 may comprise a plurality of feet (not shown), such that the device 100 can be rested on the feet with the port 113 extending vertically such that the cartridge 300 is orientated vertically and thus medicament flows down towards the cannula 114.

[0197] Optionally, in some embodiments, the device 100 comprises one or more indicators configured to indicate to a user the intended filling orientation of the device 100. The indicators may comprise, for example, one or more graphic symbols or text on the device 100. In some embodiments, the user may hold the device 100 in the filling orientation according to the indicator(s) (rather than placing the device 100 on a flat surface) when filling the device 100 with medicament from the container 300.

[0198] The components of the dose delivery mechanism are arranged coaxially along the device axis X-X and comprise a shuttle 122, a shuttle biasing member 122s, a release collar 123, a plunger rod 124, a drive mechanism 120, an indicator member 125, and a dosing knob 126. In the present example, the drive mechanism 120 comprises a plunger biasing member 124s. However, it should be recognised that in other embodiments (not shown) the drive mechanism 120 may have a different configuration, for example, comprising an energy course which can include, for example, mechanical, pneumatic, chemical, or electrical energy. For example, mechanical energy sources can include springs, levers, Attorney Docket No.: 46567-1782WO1 elastomers, or other mechanical mechanisms to store or release energy to move the plunger rod 124.

[0199] The plunger 124 is optionally in the form of a plunger rod 124. The plunger rod 124 comprises a piston 1241 at its distal end that is configured to traverse the dosing chamber 121 to dispense medicament in use. The piston 1241 may comprise, for example, an elastomer stopper that is located at a distal end of the plunger rod 124.

[0200] The dosing chamber 121 comprises a tubular wall 1211 that is partially closed by an annular wall 1212 at its distal end. The proximal end of the tubular wall 1211 is open to receive the piston 1241 of the plunger rod 124. A central opening 1213 in the annular wall 1212 provides an outlet of the dosing chamber 121 . A one-way valve 127 is provided externally across the central opening 1213 of the annular wall 1212. The one-way valve 127 is adjacent the distal end of the housing 110 and configured for engagement with the medicament delivery unit 200.

[0201] The one-way valve 127 comprises a gasket 128, as shown in Fig. 2. The one-way valve 127 is moulded from a resilient material with sealing properties, such as rubber. The gasket 128 is an outer annular ring that seals to the medicament delivery unit 200 when the medicament delivery unit 200 and device 100 are combined. The gasket 128 thus prevents the leakage of medicament from the interface between the injector device 100 and the medicament delivery unit 200.

[0202] A valve member 130 is provided concentrically within the gasket 128 and connected thereto by a stem 129. In the present example, the valve member is a plug 130.

[0203] The valve member 130 comprises a chamfered portion 130A that sits against an edge 1213A of the opening 1213 in the annular wall 1212 of the dosing chamber 121. The edge 1213A may be chamfered. The edge 1213A may form a valve seat 1213A. During operation of the one-way valve 127, the stem 129 flexes to allow medicament to flow through the opening 1213 and past the valve member 130 to flow through the delivery member 200.

[0204] The gasket 128 may be integrally formed with the plug 130 from a single portion of material.

[0205] The dosing knob 126 extends from the proximal end of the housing 110. The dosing knob 126 is configured to be rotated to prime the device 100 by drawing medicament into the Attorney Docket No.: 46567-1782WO1 dosing chamber 121 . The dosing knob 126 comprises a tubular wall 1261 that is closed by an end wall 126A at its proximal end to present a continuous external surface to the user. A proximal end of the plunger rod 124 is received within the tubular wall 1261 of the dosing knob 126.

[0206] The dosing knob 126 is configured to engage the plunger rod 124. At least one of the plunger rod 124 and dosing knob 126 comprises an engaging portion 1242 that is configured to engage with the other one of the plunger rod 124 and dosing knob 126 such that rotation of the dosing knob 126 urges the plunger rod 124 to move in the first direction A1. In some embodiments, said one of the plunger rod 124 and dosing knob 126 comprises a thread 1242 that comprises the engaging portion 1242.

[0207] In the present example, the plunger rod 124 comprises a thread 1242 on its external surface, which in the present example is a male thread 1242.

[0208] As shown in Fig. 4, the male thread 1242 of the plunger rod 124 is configured to engage a projection 1262 extending from the internal surface of the tubular wall 1261 of the dosing knob 126.

[0209] It should be recognised that in another embodiment (not shown), the plunger rod 124 may comprise a projection and the dosing knob 126 may comprise a thread that engages with the projection of the plunger rod 124. In yet another embodiment (not shown), the plunger rod 124 and dosing knob 126 may comprise cooperating threads.

[0210] The dosing knob 126 is axially fixed within the housing 110 but is rotatable relative to the housing 110. As the dose setting knob 126 is rotated by a user, the projection 1262 tracks along the male thread 1242 of the plunger rod 124. The thread 1242 is configured to translate rotational movement of the dosing knob 126 into axial movement of the plunger rod 124, such that the plunger rod 124 is drawn in a first direction, which in the present example is a proximal direction. In some embodiments, this compresses the plunger biasing member 124s and therefore ‘charges’ or ‘primes’ the plunger biasing member 124s ready for use. For example, the plunger biasing member 124s may comprise a plunger spring 124s and wherein movement of the plunger rod 124 in the first direction may compress the plunger spring 124s.

[0211] In the present example, the plunger biasing member 124s is compressed between the piston 1241 and a radially-inwardly extending annular wall 1232 or other protrusion of the Attorney Docket No.: 46567-1782WO1 release collar 123. In another embodiment (not shown), the plunger biasing member 124s is compressed between the piston 1241 and a portion of the housing 110, for example, a radially-inwardly extending annular wall or protrusion of the housing 110. In yet another embodiment (not shown), the plunger biasing member 124s is compressed between the housing 110 / release collar 123 and a radially-outwardly extending annular wall or protrusion of the plunger rod 124.

[0212] In some embodiments, the male thread 1242 consists of less than a single turn. That is to say, the helical path defined by the male thread 1242 extends less than a single rotation about the axis of the plunger rod 124, namely less than 360 degrees. The pitch of the male thread 1242 is equal to the longitudinal distance between the furthest distal position of the plunger rod 124 and the furthest proximal position of the plunger rod 124.

[0213] Therefore, rotating the dosing knob 126 by the amount that the thread 1242 subtends about the axis imparts the full range of movement of the plunger rod 124 between its furthest distal position and furthest proximal position (and so less than a full rotation of the dosing knob 126 is required). In other embodiments, the male thread 1242 subtends a full rotation about the axis of the plunger rod 124, or more than a full rotation about the axis of the plunger rod 124.

[0214] A ratchet mechanism 1263 may be provided so that the dosing knob 126 is configured only for unidirectional rotation. The ratchet mechanism 1263 comprises one or more ratchet members. In the present example, the ratchet members are one or more ratchet teeth 1263A. The ratchet teeth 1263A are provided on one of the dosing knob 126 and housing 110 and are configured to engage with one or more formations (not shown) on the other one of the dosing knob 126 and housing 110. For example, the one or more formations may be stepped portions over which the ratchet teeth 1263A can slide in a first direction when the dosing knob 126 is moved in a first rotational direction (shown by arrow ‘R1’ in Figs. 1 and 4) relative to the housing 110, but wherein the ratchet teeth 1263A catch on the one or more formations to prevent movement of the dosing knob 126 relative to the housing 110 in a second rotational direction that is opposite to the first rotational direction R1 .

[0215] Figs. 3 and 5a to 5e show the different positions of the plunger rod 124 at different stages of use. In Fig. 3, the plunger rod 124 is in the furthest distal position, which is a first position of the plunger rod 124. In this position, the piston 1241 abuts the annular wall 1212 of the dosing chamber 121 , preventing distal movement of the plunger rod 124. Rotation of the dose setting knob 126 in the first rotational direction R1 relative to the Attorney Docket No.: 46567-1782WO1 housing 110 causes the projection 1262 to track along the male thread 1242 such that the plunger rod 124 is urged to move in a proximal direction (shown by arrow ‘A1 ’ in Fig. 3), which is a first direction, drawing the piston 1241 away from the annular wall 1212 of the dosing chamber 121. This increases the volume defined between the piston 1241 and walls 1211 , 1212 of the dosing chamber 121 , causing a pressure drop or vacuum which will draw medicament through the cannula 114 and inlet 114A and into the dosing chamber 121 from the medicament container 300. In the present embodiment, the medicament enters the dosing chamber 121 once the piston 1241 has moved proximally within the dosing chamber 121 to a position proximally past the inlet 114A. In another embodiment (not shown), the inlet 114A is positioned such that medicament begins to enter the dosing chamber 121 immediately upon movement of the piston 1241 in the proximal direction A1 (and a one-way valve may be positioned in the inlet 114A or cannula 114 to prevent medicament returning to the medicament container 300).

[0216] When the dosing knob 126 is rotated in the first rotational direction R1 relative to the housing 110, the plunger rod 124 is urged in the proximal direction A1 against the force of the plunger biasing member 124s, which in the present example is a plunger spring 124s. If the user pauses operation and stops rotating the dosing knob 126, the thread 1242 of the plunger rod 124 is urged distally by the plunger biasing member 124s against the projection 1262 and thus the dosing knob 126 is urged to rotate in a second rotational direction R2 opposite to the first rotational direction R1 . However, as discussed above, the ratchet mechanism 1263 prevents such rotation of the dosing knob 126 in the second rotational direction R2. Thus, when the user pauses rotation of the dosing knob 126, the dosing knob 126 is held in position relative to the housing 110 and thus the plunger rod 124 is prevented from moving distally under the force of the plunger biasing member 124s.

[0217] The thread 1242 of the plunger rod 124 (or dosing knob 126 in alternative embodiments) reduces the force that must be exerted by a user to move the plunger rod 124 in the proximal direction A1 against the force of the plunger biasing member 124s (in comparison to manually pulling the plunger rod 124 axially in the proximal direction A1 against the biasing force of the plunger biasing member 124s). The smaller the pitch of the thread 1242, the greater the apparent gearing effect provided by the thread 1242, and thus the less torque that is required to be exerted by the user to rotate the dosing knob 126 in the first rotational direction R1 to move the plunger rod 124 axially in the proximal direction A1 . Attorney Docket No.: 46567-1782WO1

[0218] Fig. 5a shows the plunger rod 124 in the furthest proximal position, which is an intermediate position of the plunger rod 124, which may also be referred to as a “second position” of the plunger rod 124. In this position, the projection 1262 is at a proximal end of the male thread 1242 due to rotation of the dosing knob 126 in the first rotational direction R1. Once in this position, further rotation of the dosing knob 126 in the first rotational direction R1 causes the projection 1262 to depart the proximal end of the male thread 1242, releasing the plunger rod 124 for distal movement under the force of the plunger biasing member 124s. That is, said further rotation of the dosing knob 126 in the first rotational direction R1 moves the projection 1262 out of engagement with the thread 1242 to permit axial movement of the plunger rod 124 in a distal direction (shown by arrow ‘A2’ in Fig. 5b) relative to the housing 110, also referred to as a second direction A2.

[0219] Figs. 6a to 6c show the interaction between the plunger rod 124 and the release collar 123 during movement of the plunger rod 124 between the furthest distal position (Fig. 6a, also referred to as the first position of the plunger rod 124) and the furthest proximal position (Fig. 6c, also referred to as the intermediate position of the plunger rod 124). The release collar 123 surrounds a mid-section of the plunger rod 124 and comprises a tubular wall 1231 having a distal region 123T and a proximal region 1231 ” separated by an annular wall 1232 that extends internally within the tubular wall 1231 (see Fig. 3).

[0220] A track 1233 is provided in relief in the internal surface of the proximal region 1231 ” of the tubular wall 1231 of the release collar 123. The track 1233 cooperates with a protrusion 1244 that extends radially from the external surface of the mid-section of the plunger rod 124. In some embodiments, the release collar 123 comprises two tracks 1233 that each receives a respective protrusion 1244 of the plunger rod 124. In other embodiments (not shown), the plunger rod 124 comprises the track and the release collar 123 comprises the protrusion that interfaces with the track.

[0221] The track 1233 comprises a ramped section 1233’ at its proximal end and a longitudinal section 1233” at its distal end. A stop or square section 1233”’ of the track 1233 is provided in between the ramped and longitudinal sections 1233’, 1233” (see Figs. 6a to 6e). The annular wall 1232 is provided at the distal end of the longitudinal section 1233’ and, optionally, acts as a stop to limit distal movement of the plunger rod 124 relative to the release collar 123.

[0222] The engagement between the track 1233 and protrusion 1244 is shown schematically in Figs 6d to 6f. Attorney Docket No.: 46567-1782WO1

[0223] The plunger rod 124 is initially in the furthest distal position wherein the piston 1241 is received at the distal end of the dosing chamber 121. In this position, the protrusion 1244 of the plunger rod 124 abuts the annular wall 1232 of the release collar 123 (as shown in Figs. 6a and 6d). In this position, the protrusion 1244 engages the longitudinal section 1233” of the track 1233 to prevent rotation of the release collar 123 relative to the housing 110 under the biasing force of a locking member biasing member 140, which in the present example is a collar biasing member 140 (depicted in Fig. 3), that is configured to bias the release collar 123 to rotate relative to the housing 110. The collar biasing member 140 may be a torsional spring 140. The torsional spring 140 may be mounted between the release collar 123 and housing 110 to urge the release collar 123 to rotate relative to the housing 110.

[0224] Rotation of the dosing dial 126 in the first rotational direction R1 causes the plunger rod 124 to move in the proximal direction A1 relative to the housing 110 and release collar 123 such that the protrusion 1244 moves proximally along the longitudinal section 1233” of the track 1233. The release collar 123 is rotatable within the housing 110 but is fixed in the axial direction. However, whilst the protrusion 1244 engages the longitudinal section 1233” of the track 1233, rotation of the release collar 123 relative to the housing 110 under the biasing force of the collar biasing member 140 is prevented. Continued rotation of the dosing dial 126 causes the protrusion 1244 to exit the longitudinal section 1233” of the track 1233 such that the longitudinal section 1233” no longer prevents rotational movement of the release collar 123 under the force of the collar biasing member 140. Thus, the release collar 123 rotates in the first rotational direction R1 under the force of the collar biasing member 140 such that the stop section 1233”’ circumferentially aligns with the protrusion 1244 (as shown in Figs. 6b and 6e). With the protrusion 1244 abutting the stop section 1233”’of the track 1233 a dosage volume of medicament has been drawn into the dosing chamber 121 from the cartridge 300.

[0225] Continued rotation of the dosing dial 126 in the first rotational direction R1 causes the plunger rod 124 to move further in the proximal direction A1 relative to the housing 110 and release collar 123 such that the protrusion 1244 moves along the ramp section 1233’ of the track 1233 (as shown in Figs. 6c and 6f). Meanwhile, the release collar 123 continues to rotate in the first rotational direction R1 under the force of the collar biasing member 140 whilst the plunger rod 124 moves in the proximal direction A1. This further movement of the plunger rod 124 in the proximal direction A1 causes an additional volume, referred to as a ‘priming volume’, of medicament to be drawn into the dosing chamber 121 from the cartridge 300. Attorney Docket No.: 46567-1782WO1

[0226] Further rotation of the dosing knob 126 causes the projection 1262 of the dosing knob 126 to move out of engagement with the male thread 1242 of the plunger rod 124 such that the plunger rod 124 is no longer held against the biasing force of the plunger biasing member 124s. Thus, the plunger rod 124 moves axially in the distal direction A2 under the force of the plunger biasing member 124s until the protrusion 1244 of the plunger rod 124 abuts the stop section 1233”’ of the track 1233, wherein the plunger rod 124 is in the primed position (see Figs. 6b and 6e), ready to dispense the dosage volume of medicament. This movement of the plunger rod 124 to the primed position causes the piston 1241 to be urged in the distal direction A2 to urge the additional volume (priming volume) of medicament out of the dosing chamber 121 via the delivery member 211 (e.g. a needle or intranasal nozzle). This movement therefore primes the delivery member 200, replacing air in the delivery member 211 with medicament. When the plunger rod 124 is in the primed position, the piston 1241 of the plunger rod 124 blocks the inlet 114A from the medicament in the dosing chamber 121 (as shown in Fig. 5b). Furthermore, with the plunger rod 124 in the primed position such that the protrusion 1244 abuts the stop section 1233”’ of the track 1233, the stop section 1233’” prevents further movement of the plunger rod 124 in the distal direction A2.

[0227] Movement of the protrusion 1244 along the ramp section 1233’ as the plunger rod 124 moves to the primed position causes the release collar 123 to move in the second rotational direction R2, against the biasing force of the collar biasing member 140 (which in the present example is a torsional spring).

[0228] With the plunger rod 124 in the primed position, the dose of medicament contained in the dosing chamber 121 can then be delivered through the delivery member 211 to administer the dose to the user. In particular, the release collar 123 is rotated further in the second rotational direction R2 due to operation of an actuator 210, which in the present example is a needle sleeve 210, as will be explained in more detail below. This rotation of the release collar 123 causes the stop section 1233’” of the track 1233 to move out of abutment with the protrusion 1244 of the plunger rod 124 such that the plunger rod 124 is permitted to move further in the distal direction A2 under the force of the plunger biasing member 124s. Therefore, the plunger rod 124 moves in the distal direction A2 such that the projection 1244 moves within the longitudinal section 1233” of the track 1233 and there is a corresponding distal movement of the piston 1241 within the dosing chamber 121 to expel the dosage volume of medicament from the chamber 121 and through the delivery member 211. This movement of the piston 1241 will continue until the protrusion 1244 abuts the annular wall 1232 of the release collar 123 and / or the piston 1241 abuts Attorney Docket No.: 46567-1782WO1 the annular wall 1212 of the dosing chamber 121 , at which point the entire dose of medicament has been expelled from the dosing chamber 121 via the delivery member 211. For example, the delivery member 211 may comprise an injection needle 211 or one or more intranasal nozzles.

[0229] The collar biasing member 140, which may be a torsion spring (not shown), rotates the release collar 123 in the first rotational direction R1 relative to the housing 110 from an initial rotational position (see Fig. 9a) to a first intermediate rotational position (see Fig. 9b) and then to a second intermediate rotational position (see Fig. 9c). In some embodiments, the release collar 123 moves continuously from the initial rotational position to the second intermediate rotational position (e.g. without stopping at the first intermediate rotational position).

[0230] When the plunger rod 124 is released by rotation of the dosing knob 126, the protrusion 1244 engages the ramped section 1233’ of the track 1233, rotating the release collar 123 in the second rotational direction R2 into a primed rotational position (see Fig. 9d). As explained previously, following traversal of the ramped section 1233’, the protrusion 1244 abuts the stop section 1233’” of the track 1233 which stops distal progress of the plunger rod 124 such that the piston rod 124 is held in the primed position. The relative positions of the plunger rod 124 and the release collar 123 are shown in Figs. 5b, 6b and 6e with the release collar 123 in the primed rotational position (see also Fig. 9d) and the plunger rod 124 in the primed position. Movement of the plunger rod 124 from the furthest proximal position (also referred to as the intermediate position) to the primed position displaces some medicament through, or into, the delivery member 211. This ensures that the delivery member 211 contains medicament rather than air, priming the delivery member 211 ready for medicament delivery to the user.

[0231] To deliver the full dose of medicament, the release collar 123 is rotated in the second rotational direction R2 into a dose delivery rotational position (see Fig. 9e) by engagement of the shuttle 122 to cause the stop section 1233’” of the track 1233 to move out of abutment with the protrusion 1244 and so that the protrusion 1244 is received in the longitudinal section 1233” of the track 1233. In the present example, the dose delivery rotational position of the release collar 123 is the same as the initial rotational position thereof. The protrusion 1244 travels along the longitudinal section 1233” as the plunger rod 124 moves into the furthest distal position under the action of the plunger biasing member 124s to displace all of the medicament from the dosing chamber 121. The relative positions of the plunger rod 124 and the release collar 123 are shown in Figs.5d Attorney Docket No.: 46567-1782WO1 and 6a with the plunger rod 124 in the furthest distal position and the release collar 123 in a dose delivery rotational position (see also Fig. 9e).

[0232] Fig. 7 shows the shuttle 122 and the release collar 123 in more detail. The shuttle 122 is configured to move in a longitudinal direction of the device 100 between a first position, in which it is adjacent the distal end of the housing 110, and a second position, proximal to the first position. That is, the shuttle 122 moves in the proximal direction A1 from the first position to the second position. This movement into the second position causes the shuttle 122 to urge the release collar 123 to rotate to release the plunger rod 124 from the primed position (shown in Figs. 5b, 6b and 6e) to expel the dose of medicament from the dosing chamber 121. Movement of the shuttle 122 to the second position causes the release collar 123 to rotate into the dose delivery rotational position (shown in Fig. 9e) such that the stop section 1233”’ of the track 1233 moves out of abutment with the protrusion 1244 of the plunger rod 124.

[0233] In alternative embodiments (not shown), the shuttle 122 may be integrally formed with the needle sleeve 210, or the shuttle 122 may be omitted.

[0234] The shuttle 122 comprises a tubular wall 1221 with a proximal region 1221’ that extends over the distal region 1231’ of the tubular wall 1231 of the release collar 123. A proximal end of the tubular wall 1221 of the shuttle 122 comprises a cam surface 1222, which in the present example is an angular cut out 1222. By ‘angular’ it is meant that the cut out 1222 provides the tubular wall 1221 with a ramped edge 1223 that faces in the proximal direction A1 and which optionally is at the proximal end of the shuttle 122. The ramped edge 1223 is configured to engage a protrusion 1234 of the release collar 123. In the present example, the protrusion 1234 is a rib 1234 of the release collar 123. The ramped edge 1223 engages the rib 1234 as the shuttle 122 moves proximally into the second position, thereby causing the release collar 123 to rotate in the second rotational direction R2 into the dose delivery rotational position (see Fig. 9e).

[0235] As explained previously, such rotation of the release collar 123 causes the stop section 1233’” of the track 1233 to move out of abutment with the protrusion 1244 of the plunger rod 124 such that the plunger rod 124 is permitted to move in the distal direction A2 under the force of the plunger biasing member 124s to expel the dose of medicament from the chamber 121 and through the delivery member 211 for delivery to the user. Therefore, the dose delivery mechanism is configured so that movement of the shuttle 122 into the second position releases the plunger rod 124 from the primed position to deliver Attorney Docket No.: 46567-1782WO1 medicament. The biasing member 124s thus acts as a drive mechanism to urge the plunger rod 124 distally to deliver medicament to the user.

[0236] The shuttle 122 further comprises a circumferentially extending shoulder 1224. The shuttle biasing member 122s is compressed between the shoulder 1224 and radially- inwardly projecting element 115 of the housing 110(e.g. a radial wall 115) as the shuttle 122 is displaced into the second position. Thus, the shuttle biasing member 122s provides a biasing force that biases the shuttle 122 back from the second position to the first position. Following medicament delivery, the shuttle biasing member 122s returns the shuttle 122 to the first position under the force of the shuttle biasing member 122s. In some embodiments, the shuttle biasing member 122s is a shuttle spring 122s.

[0237] The proximal end of the shuttle 122 and the indicator member 125 are shown in more detail in Figs. 8a and 8b. In the present example, the indicator member 125 is an indicator ring 125. The indicator ring 125 is curved and subtends at least part of the way around the release collar 123. The indicator ring 125 comprises a tubular wall 1251 that surrounds the proximal end of the release collar 123. However, it should be recognised that in other embodiments (not shown), the indicator member 125 (e.g. indicator ring) may be omitted or may not be visible during use of the device 100.

[0238] The indicator ring 125 is axially located between a flange 1235 of the release collar 123 and the radially-inwardly projecting element 115 of the housing 110, which in the present example is a radial wall 115. The indicator ring 125 can rotate about the same rotational axis as the release collar 123 but is axially restrained by the radial wall 115 and the flange

[0239] 1235 (or in other embodiments (not shown) by a second radially-inwardly projecting element of the housing 110, which may be a second radial wall).

[0240] The indicator ring 125 comprises an engaging element 1252 that projects radially-inwardly from an internal surface of the tubular wall 1251 toward the external surface of the release collar 123. In the present example, the engaging element 1252 is a rib 1252. The rib 1252 is configured to engage first engaging element 1236 of the release collar 123, which project radially-outwardly from the external surface of the release collar 123. In the present example, the first engaging element 1236 of the release collar 123 is a first rib 1236.

[0241] In the present example, the first engaging element 1236 of the release collar 123 is a rib

[0242] 1236 that projects radially-outwardly from the external surface of the release collar 123 and the engaging element 1252 of the indicator ring 125 is a rib 1252 that projects Attorney Docket No.: 46567-1782WO1 radially-inwardly from the internal surface of the indicator ring 125. However, it should be recognised that in alternative embodiments (not shown) the first engaging element 1236 of the release collar 123 and / or the engaging element 1252 of the indicator ring 125 may take a different form. For example, one of the release collar 123 and indicator ring 125 may comprise a circumferential groove into which a projection of the other one of the release collar 123 and indicator ring 125 may be received, wherein when the projection reaches an end of the groove the release collar 123 and indicator member 125 rotate together. Thus, the projection and end of the groove are respective engaging elements of the release collar 123 and indicator ring 125.

[0243] The indicator ring 125 is visible to a user of the device through a window 116 in the housing 110. The external surface of the indicator ring 125 comprises at least one indictor region 1254 that becomes visible through the window 116 once the indicator ring 125 has rotated relative to the housing 110 due to rotation of the release collar 123 to the second intermediate rotational position (see Fig. 9c) and primed rotational position (see Fig. 9d). In some embodiments, the indicator ring 125 remains in the position wherein the indicator region 1254 is visible through the window 116 once the release collar 123 has moved to the dose delivery rotational position (shown in Fig. 9e). The indicator ring 125 may be rotatable from an initial position to an indicating position (shown in Fig. 8b).

[0244] In the present example, the indicator ring 125 comprises first and second indicia 1253, 1254. The first indicium 1253 indicates a pre-delivery state in which the device 100 is not yet disposed to allow the delivery of medicament. The second indicium 1254 indicates a primed state in which the device 100 is disposed ready to allow the delivery of medicament. The first and second indicium 1253, 1254 may be visibly different. In one example, the first indicium 1253 is the colour red and the second indicium 1254 is the colour green. The first and second indicia 1253, 1254 are positioned at least partially around the indicator member 125 so that second indicium 1254 is visible through the window 116 when the release collar 123 is in the second intermediate rotational position (see Fig. 9c) and primed rotational position (see Fig. 9d). When the release collar 123 is in the initial rotational position (see Fig. 9a) and first intermediate rotational position (see Fig. 9b, which may be the same as the initial rotational position), the first indicium 1253 is visible through the window 116.

[0245] The indicator ring 125 may indicate to the user when the priming and dosage volumes of medicament have been draw into the chamber 121 . Attorney Docket No.: 46567-1782WO1

[0246] A stop 1255 of the indicator ring 125 is arranged to cooperate with a second cut out 1225 in the tubular wall 1221 of the shuttle 122. The stop 1255 may be an internal rib 1255 that extends radially inwardly from the tubular wall 1251 of the indicator ring 125. When the release collar 123 is in the initial position, the stop 1255 is circumferentially aligned with a locking element 1228 of the tubular wall 1221 of the shuttle 122, preventing the shuttle 122 being displaced in the proximal direction A1 out of the first position (see Fig. 8a). When the release collar 123 is in the second intermediate rotational direction and primed rotational position, the stop 1255 is circumferentially aligned with the second cut out 1225, enabling displacement of the shuttle 122 out of the first position (see Fig. 8b). A longitudinal slot 1256 in the indicator ring 125 is aligned with the locking element 1228 of the shuttle 122 (or vice versa) such that the locking element 1228 can pass through the slot 1256. In this way the indicator ring 125 acts as a lock to prevent medicament dispensation prior to the device 100 adopting the primed state. Furthermore, the indicator ring 125 is configured to indicate to the user when the release collar 123 has reached the second intermediate rotational direction and primed rotational position (and the release collar 123 moves automatically from the second intermediate rotational position to the primed rotational position under the force of the plunger biasing member 124s moving the plunger rod 124). That is, the indicator region 1254 (which in the present example is the second indicium 1254, and in other embodiments the first indicium 1253 may be omitted) becomes visible in the window 116.

[0247] Interaction of the release collar 123 and indicator ring 125 is illustrated schematically in Figs. 9a to 9e.

[0248] An exemplary operation of the device 100 will now be described. The user may fluidly couple the medicament container 300 to the port 113 by urging the end of the medicament container 300 into the port 113 until the cannula 114 penetrates a sealing element 304 (e.g. septum 304) at an end 303 of the medicament container 300.

[0249] Initially, the plunger rod 124 is in a distal position (see Fig. 3), the release collar 123 is in the initial rotational position (see Figs. 6a, 6d and 9a), and the indicator ring 125 is in an initial position in which the first indicium 1253 is visible through the window 116 (or in alternative configurations, no part of the indicator member 125 is visible through the window 116).

[0250] To operate the device 100, the user / operator firstly charges the dosing chamber 121 with a dosage volume of medicament by rotating the dosing knob 126 in the first rotational Attorney Docket No.: 46567-1782WO1 direction R1 . This causes the plunger rod 124 to be urged in the proximal direction A1 , against the force of the plunger biasing member 124s, such that suction is created in the dosing chamber 121 and thus medicament is drawn into the dosing chamber 121 from the medicament container 300 via the cannula 114 and inlet 114A once the piston 1241 passes the cannula 114. As explained previously, during this movement the protrusion 1244 of the plunger rod 124 engages the longitudinal section 1233” of the track 1233 to prevent rotation of the release collar 123 relative to the housing 110 under the biasing force of the collar biasing member 140, that is configured to bias the release collar 123 to rotate relative to the housing 110 in the first rotational direction R1 . Thus, during this initial rotation of the dosing knob 126, the release collar 123 remains in the initial rotational position of Fig. 9a. Meanwhile, the indicator ring 125 is in the position shown in Figs. 8a and 9a, and thus prevents the shuttle 122 moving in the proximal direction A1 from the first position to the second position.

[0251] Rotation of the dosing dial 126 in the first rotational direction R1 causes the plunger rod 124 to move in the proximal direction A1 relative to the housing 110 and release collar 123 such that the protrusion 1244 of the plunger rod 124 moves proximally along the longitudinal section 1233” of the track 1233 of the release collar 123. Continued rotation of the dosing dial 126 by the user in the first rotational direction R1 causes the protrusion 1244 of the plunger rod 124 to exit the longitudinal section 1233” of the track 1233 such that the longitudinal section 1233” no longer prevents rotational movement of the release collar 123 under the force of the collar biasing member 140. Thus, the release collar 123 rotates in the first rotational direction R1 under the force of the collar biasing member 140 such that the stop section 1233”’ circumferentially aligns with, and subsequently passes, the protrusion 1244 (as shown in Figs. 6b and 6e). With the protrusion 1244 aligned with and abutting the stop section 1233”’of the track 1233 a dosage volume of medicament has been drawn into the dosing chamber 121 from the cartridge 300. Furthermore, the movement of the plunger rod 124 in the proximal direction A1 compresses the plunger biasing member 124s to prime the plunger biasing member 124s.

[0252] The release collar 123 is now in the first intermediate rotational position (as shown in Fig. 9b). During rotation of the release collar 123 from the initial rotational position of Fig. 9a to the first intermediate rotational position of Fig. 9b, the release collar 123 rotates relative to the indicator ring 125. That is, the release collar 123 rotates in the first rotational direction R1 relative to the housing 110 whilst the indicator ring 125 remains stationary relative to the housing 110. Once the release collar 123 reaches the first intermediate rotational Attorney Docket No.: 46567-1782WO1 position (as shown in Fig. 9b), the first engaging element 1236 of the release collar 123 abuts the engaging element 1252 of the indicator ring 125.

[0253] Continued rotation of the dosing dial 126 in the first rotational direction R1 causes the plunger rod 124 to move further in the proximal direction A1 relative to the housing 110 and release collar 123 such that the protrusion 1244 moves along the ramp section 1233’ of the track 1233 (as shown in Figs. 6c and 6f). This movement of the protrusion 1244 along the ramp section 1233’ is because the release collar 123 is further rotated in the first rotational direction R1 under the action of the collar biasing member 140. The further movement of the plunger rod 124 in the proximal direction A1 causes an additional volume (or ‘priming volume’) of medicament to be drawn into the dosing chamber 121 from the cartridge 300. Meanwhile, the release collar 123 continues to rotate in the first rotational direction R1 under the force of the collar biasing member 140 from the first intermediate rotational position (as shown in Fig. 9b) towards the second intermediate rotational position (as shown in Fig. 9c). Movement of the release collar 123 in the first rotational direction R1 from the first intermediate rotational position to the second intermediate rotational position causes corresponding movement of the indicator ring 125, due to the first engaging element 1236 of the release collar 123 abutting, and being pressed against, the engaging element 1252 of the indicator ring 125. The release collar 123 and indicator ring 125 thus rotate together from the first intermediate rotational position of Fig. 9b towards the second intermediate rotational position of Fig. 9c. When the release collar 123 reaches the second intermediate rotational position, the corresponding rotation of the indicator ring 125 causes the second indicium 1254 of the indicator ring 125 to become visible through the window 116.

[0254] Further rotation of the dosing knob 126 in the first rotational direction R1 causes the projection 1262 of the dosing knob 126 to move out of engagement with the male thread 1242 of the plunger rod 124 such that the plunger rod 124 is no longer held axially against the biasing force of the plunger biasing member 124s. Thus, the plunger rod 124 moves axially in the distal direction A2 under the force of the plunger biasing member 124s (which has been primed / charged by the previous movement of the plunger rod in the proximal direction A1 compressing the plunger biasing member 124s) until the protrusion 1244 of the plunger rod 124 abuts the stop section 1233’” of the track 1233, wherein the plunger rod 124 is in a primed position (see Figs. 6b and 6e). This causes the piston 1241 to be urged in the distal direction A2 to urge the additional volume (or ‘priming volume’) of medicament out of the dosing chamber 121 via the delivery member 211. This movement therefore primes the delivery member 211 , replacing (or partially replacing) air in the Attorney Docket No.: 46567-1782WO1 delivery member 211 with medicament. In the primed position, the piston 1241 blocks the inlet 114A from the medicament in the dosing chamber 121. This is advantageous because then, when the device 100 is actuated to delivery the dose of medicament to the user, the medicament is expelled out of the dosing chamber 121 via the delivery member 211 for delivery to the user rather than being urged back into cartridge 300 via the inlet 114A. With the plunger rod 124 in the primed position such that the protrusion 1244 abuts the stop section 1233”’ of the track 1233, the stop section 1233”’ prevents further movement of the plunger rod 124 in the distal direction A2 until the device 100 is actuated by the user.

[0255] Movement of the protrusion 1244 along the ramp section 1233’ as the plunger rod 124 moves in the distal direction A2 to the primed position causes the release collar 123 to move in the second rotational direction R2, against the biasing force of the collar biasing member 140. Thus, the release collar 123 moves from the second intermediate rotational position (as shown in Fig. 9c) to the primed rotational position (as shown in Fig. 9d). During this rotation of the release collar 123, the first engaging element 1236 of the release collar 123 moves away from the engaging element 1252 of the indicator ring 125 and there is no corresponding movement of the indicator ring 125 in the second rotational direction R2 (thus the second indicium 1254 remains visible through the window 116). Optionally, the indicator ring 125 may remain in position due to slight friction between the indicator ring 125 and the housing 110. The relative positions of the release collar 123 and indicator ring 125 are shown in Fig. 8b. Alternatively, or additionally, the shuttle 122 may be configured to move a small distance in the proximal direction A1 once the indicator ring 125 has rotated to the indicating position wherein the locking element 1228 moves slightly into the slot 1256 to rotationally lock the indicator ring 125 in position. For example, the device 100 may comprise a biasing member or cam mechanism (not shown) that is configured to urge the shuttle 122 said small distance in the proximal direction A1 once the indicator ring 125 has rotated to the indicating position.

[0256] The device 100 is now ready to be actuated to deliver the medicament to the patient. That is, the dose of medicament contained in the dosing chamber 121 can be delivered through the delivery member 211 to administer the dose to the user. In particular, the release collar 123 is rotated further in the second rotational direction R2 due to operation of an actuator, which in the present example is the needle sleeve 210 but could alternatively take the form of, for example, an intranasal nozzle or a button of the device 100 (which could be a push button, slide button or lever button). Attorney Docket No.: 46567-1782WO1

[0257] To deliver the medicament, the operator pushes needle sleeve 210 against an injection site while holding the device 100 by the housing 110. This displaces the needle sleeve 210 in the proximal direction A1 through an opening 1191 in an annular wall 119 at the distal end of the device 100 and moves the needle sleeve 210 relative to a needle holder 240 from a first position to a second position, as shown in Fig. 5c. With the needle sleeve 210 in the second position, the needle 211 protrudes from the needle sleeve 210 to penetrate the injection site. The shuttle 122 is displaced with the needle sleeve 210 in the proximal direction A1 to engage the release collar 123 and release the plunger rod 124 from the primed position. That is, the indicator ring 125 is in the position of Fig. 8b and thus the locking element 1228 of the shuttle 122 is out of circumferential alignment with the stop 1255 of the indicator ring 125 and therefore the locking element 1228 of the shuttle 122 can move into the slot 1256 of the indicator ring 125 such that the shuttle 122 can be moved in the proximal direction A1 from the first position to the second position under the force of the operator pushing the needle sleeve 210 (or another component of the medicament delivery unit 200 in alternative embodiments) against the injection site.

[0258] This movement of the shuttle 122 in the proximal direction A1 from the first position to the second position causes the ramped edge 1223 of the shuttle 122 to engage the rib 1234 of the release collar 123, thereby causing the release collar 123 to rotate in the second rotational direction R2 into the dose delivery rotational position (see Fig. 9e). This rotation of the release collar 123 causes the stop section 1233”’ of the track 1233 to move out of abutment with the protrusion 1244 of the plunger rod 124 such that the plunger rod 124 is permitted to move further in the distal direction A2 under the force of the plunger biasing member 124s. Therefore, the plunger rod 124 moves in the distal direction A2 such that the projection 1244 moves within the longitudinal section 1233” of the track 1233 and there is a corresponding distal movement of the piston 1241 within the dosing chamber 121 to expel the dose of medicament from the chamber 121 and through the delivery member 211. This movement of the piston 1241 will continue until the protrusion 1244 abuts the annular wall 1232 of the release collar 123 and / or the piston 1241 abuts the annular wall 1212 of the dosing chamber 121 , at which point the entire dose of medicament has been expelled from the dosing chamber 121 via the delivery member 211.

[0259] In the present example, as the plunger rod 124 moves from the primed position into the furthest distal position shown by Fig. 5d, medicament flows past the plug 130, into an antechamber 244 and along the needle 211 into the patient. Following medicament delivery, the device 100 is moved away from the patient, causing the needle sleeve 21 O to Attorney Docket No.: 46567-1782WO1 move in the distal direction A2 relative to the housing 110 under the force of the shuttle biasing member 122s, restoring the needle sleeve 210 to the first position, as shown in Fig. 5e.

[0260] When the indicator ring 125 is in the position wherein the second indicium 1254 is visible through the window 116 and the release collar 123 has moved in the second rotational direction R2 to the primed rotational position (as shown in Figs. 8b and 9d), the longitudinal slot 1256 in the indicator ring 125 is aligned with the locking element 1228 of the shuttle 122. The subsequent movement of the shuttle 122 in the proximal direction A1 during actuation of the device 100 causes the locking element 1228 to enter the slot 1256 (or further move into the slot 1256). This prevents rotational movement of the indicator ring 125. Optionally, the subsequent rotation of the release collar 123 in the second rotational direction R2 under the force of the plunger biasing member 124s causes an indicator biasing member (not shown) to be deformed to bias the indicator ring 125 in the second rotational direction R2. When the shuttle 122 is in the second position such that the locking element 1228 thereof is received in the slot 1256 of the indicator ring 125, the indicator ring 125 is prevented from moving in the second rotational direction R2 under the action of the indicator biasing member. However, once the shuttle 122 has returned to the first position under the action of the shuttle biasing member 122s after the medicament has been delivered to the user (so that the needle sleeve 210 covers the end of the needle 211), the locking element 1228 moves out of the slot 1256 and thus the indicator biasing member moves the indicator ring 125 in the second rotational direction R2 back to its original position (shown in Fig. 9a) wherein the first indicium 1253 is again visible through the window 116. In some embodiments, the device 100 may then be re-used to deliver further doses of medicament.

[0261] In some embodiments, the indicator biasing member may comprise a torsion spring (not shown) coupled to the release collar 123 and indicator ring 125, such that when the release collar 123 rotates to the position of Fig. 9e relative to the indicator ring 125 the torsion spring is deformed. In one such embodiment, an inwardly-radially projecting element (not shown) of the indicator ring 125 is coupled to a first end of the torsion spring and an outwardly-radially projecting element (not shown) of the release collar 123 engages a second end of the torsion spring when the collar 123 moves from the position of Fig. 9d to the position of Fig. 9e to deform the torsion spring. In another embodiment (not shown), the indicator biasing member is omitted. Attorney Docket No.: 46567-1782WO1

[0262] With reference to Fig. 10, the medicament delivery unit 200 comprises a needle sleeve

[0263] 210, a needle holder 240, and a delivery member 211 comprising a needle 211. The needle sleeve 210 comprises a tubular wall 212 that is partially closed at the distal end by an annular wall 213. The proximal end of the tubular wall 212 is open to receive the needle holder 240. The needle holder 240 sits within the tubular wall 212 of the needle sleeve 210 and holds the needle 211 so that it extends along a central axis of the needle

[0264] 211. The needle 211 is aligned with an opening 214 in the annular wall 213 of the needle sleeve 210. The needle holder 240 is configured to slide within the needle sleeve 210 as the needle sleeve 210 moves from a first position, in which the needle 211 is enclosed by the needle sleeve 210, to a second position in which the needle 211 extends from the opening 214 of the annular wall 213 for penetration of an injection site (as shown in Fig. 12a).

[0265] The needle holder 240 comprises a tubular wall 241 that fits within the tubular wall 212 of the needle sleeve 210. The tubular wall 241 of the needle holder 240 and the tubular wall 212 of the needle sleeve 210 are closely spaced to keep the needle sleeve 210 and the needle holder 240 in coaxial alignment and, thereby, ensure the alignment of the needle 211 with the opening 214 in the needle sleeve 210.

[0266] A base wall 242 of the needle holder 240 closes the proximal end of the tubular wall 241 . The base wall 242 comprises a frustoconical portion 243 (shown in Figs. 11 a and 11 b) that partially defines an antechamber 244. The antechamber 244 is formed between the frustoconical portion 243 of the base wall 242 and the device 100 when the medicament delivery unit 200 and the device 100 are combined. During medicament delivery, medicament flows past the one-way valve 127 and into the antechamber 244 before flowing through the needle 211 .

[0267] The needle 211 is supported in a tubular projection 245 that extends from the distal end of the frustoconical portion 243. Four radial walls 2461 , 2462, 2463, 2464 extend between the tubular projection 245 and the tubular wall 241 . The radial walls 2461 , 2462, 2463, 2464 are integrally formed with the tubular projection 245 and the tubular wall 241 to strengthen the needle holder 240. The radial walls 2461 , 2462, 2463, 2464 are evenly spaced at 90-degree intervals about the axis of the needle holder 240.

[0268] The tubular wall 241 is provided with cut outs 2471 , 2472 around distal regions 2461 ’, 2463’ of two of the radial walls 2461 , 2463 The distal regions 2461 ', 2463’ of said radial walls 2461 , 2463 are herein referred to as ‘flexible portions 2461 ’, 2463’ as they are Attorney Docket No.: 46567-1782WO1 unsupported by the tubular wall 241 and therefore free to flex in a cantilever fashion from the tubular projection 245 (as shown in Fig. 11 b and Fig. 12b). The flexible portions 2461 ’, 2463’ are spaced 180 degrees apart around the axis of the needle holder 240.

[0269] The medicament delivery unit 200 is shown in a locked configuration in Fig. 11a. The needle holder 240 comprises locking tabs 248 that project radially outward from a proximal end of the tubular wall 241. The locking tabs 248 project into respective L- shaped cut outs 218 in the tubular wall 212 of the needle sleeve 210. With the medicament delivery unit 200 in the locked configuration, the locking tabs 248 are received in circumferentially extending portions 218’ of the L-shaped cut outs 218 to prevent the needle sleeve 210 moving into the second position. In the illustrated example, two tabs 248 and corresponding L-shaped cut outs 218 are shown, though it will be appreciated that the needle holder 240 may have only one tab and corresponding L shaped cut out or, indeed, more than two.

[0270] The needle holder 240 further comprises lugs 250 that project radially outward from a distal end of the tubular wall 241. The lugs 250 project into respective rectangular windows 219 in the tubular wall 212 of the needle sleeve 210. When the needle sleeve 210 is in the first position, the lugs 250 abut a proximal edge of their respective window 219, preventing the needle holder 240 from falling out of the bottom of the needle sleeve 210. The lugs 250 travel along the length of their respective window 219 during movement of the needle sleeve 210 into the second position. In the illustrated example, two lugs 250 and corresponding windows 219 are shown, though it will be appreciated that the delivery member 200 may have only one lug and corresponding window or, indeed, more than two.

[0271] The distal end of the device 100 and the proximal end of the medicament delivery unit 200 are shown in a detached state in the perspective view in Fig. 2. An annular wall 119 of the device 100 extends internally within the primary tubular wall 111 of the housing 110. The annular wall 119 is recessed from the open distal end of the primary tubular wall 111 and defines a receiving space 117 for the medicament delivery unit 200. When the medicament delivery unit 200 and the device 100 are combined, a proximal end of the medicament delivery unit 200 is received in the receiving space 117 and abuts the annular wall 119.

[0272] The receiving space 117 comprises retaining members 118 configured to cooperate with the locking tabs 248 of the needle holder 240 for bayonet style attachment. The retaining Attorney Docket No.: 46567-1782WO1 members 118 each comprise a slot 1181 formed between the annular wall 119 and a lip 1182 that projects radially inward from the primary tubular wall 111 of the housing 110. One end of each slot 1181 is provided with a stop 1183, the other is open ended. To attach the medicament delivery unit 200 to the device 100, the proximal end of the medicament delivery unit 200 is placed within the receiving space 117 so that the tabs 248 are aligned with an open end of each slot 1181. The medicament delivery unit 200 is then rotated in a first direction so that the tabs 248 are received within the slot 1181.

[0273] In the present example, the device 100 comprises a pair of locking elements 1184 that are configured to retain the tabs 248 within the respective slots 1181 to prevent detachment of the medicament delivery unit 200 from the device 100. The locking elements 1184 protrude from the end of the slots 1181 in the proximal direction such that the locking elements 1184 snap past the tabs 248 when the tabs 248 are inserted into the slots 1181. The locking elements 1184 may be provided at the opposite end of the respective slots 1181 to the stops 1183. However, it should be recognised that in other embodiments the locking elements 1184 may be omitted such that the medicament delivery unit 200 is detachable from the medicament delivery device 100. In some embodiments, the medicament delivery unit 200 is configured to be releasably coupled to the device 100 by a coupling, for example, a threaded connection or bayonet connection.

[0274] A coupling notch 215 is provided in the proximal edge of the tubular wall 212 of the needle sleeve 210 and is configured for connection to a correspondingly shaped projection 1226 extending from the distal end of the shuttle 122. With the shuttle 122 in the first position, the projection 1226 extends beyond the annular wall 119 into the receiving space 117.

[0275] As the medicament delivery unit 200 and the device 100 are combined, a proximal edge 220 of the needle sleeve 210 tubular wall 212 presses the shuttle 122 into the housing 110 by the projection 1226. During rotation of the delivery member 200 in the first direction, the locking tabs 248 of the needle holder 240 abut the stops 1183 of the retaining members 118. To complete the combination of the medicament delivery unit 200 and the device 100, needle sleeve 210 is then rotated in the first direction independently of the needle holder 240 until the projection 1226 is aligned with the coupling notch 215 and the shuttle biasing member 122s advances the projection 1226 into the coupling notch 215. So arranged, the proximal edge 220 of the needle sleeve 210 tubular wall 212 abuts a distal edge 1227 of the shuttle 122 tubular wall 1221 through an opening 1191 in the annular wall 119. The gasket 128 abuts the base wall 242 of the needle holder 240 to seal the antechamber 244. Attorney Docket No.: 46567-1782WO1

[0276] As the needle sleeve 210 is rotated independently of the needle holder 240, the medicament delivery unit 200 is moved from the locked configuration shown in Fig. 11a to an unlocked configuration shown in Fig. 11 b by relative movement of the needle holder 240 and the needle sleeve 210. In the unlocked configuration, the locking tabs 248 are each aligned with a longitudinally extending portion 218” of the L-shaped cut out 218 to allow movement of the needle sleeve 210 relative to the needle holder 240 from the first position to the second position.

[0277] The flexible portions 2461 ’, 2463’ of the two radial walls 2461 , 2463 each comprise a protrusion 252, 253 that extends into a respective track 216, 217 provided in relief in the internal surface of the tubular wall 212 of the needle sleeve 210. During the transformation of the medicament delivery unit 200 from the locked configuration to the unlocked configuration, the relative movement of the needle holder 240 and the needle sleeve 210 causes the flexible portions 2461 ’, 2463’ to deflect circumferentially in a first direction, as shown in Fig. 11 b. The force imparted by the deflected flexible portions 2461 ’, 2463’ is resolved by the cooperation of the projection 1226 and coupling notch 215.

[0278] Once the device 100 and medicament delivery unit 200 have been coupled together, an operator can charge the dosing chamber 121 with a dose of medicament by rotating the dosing knob 126 in the first rotational direction R1. As the dosing knob 126 is rotated, the plunger rod 124 moves from the furthest distal position to the furthest proximal position, drawing medicament from the medicament container 300 and through the cannula 114 and inlet 114A and into the dosing chamber 121 .

[0279] T o deliver the medicament to the patient, the operator pushes needle sleeve 210 against an injection site while holding the device 100 by the housing 110. This displaces the needle sleeve 210 through the opening 1191 in the annular wall 119 and moves the needle sleeve 210 relative to the needle holder 240 from the first position to the second position, as shown in Fig. 5c. With the needle sleeve 210 in the second position, the needle 211 extends from the needle sleeve 210 to penetrate the injection site. The shuttle

[0280] 122 is displaced coextensively with the needle sleeve 210 to engage the release collar

[0281] 123 and release the plunger rod 124 from the primed position. As the plunger rod 124 moves from the primed position into the furthest distal position shown by Fig. 5d, medicament flows past the plug 130, into the antechamber 244 and along the needle 211 into the patient. Following medicament delivery, the device 100 is lifted away from the patient, causing the needle sleeve 210 to move in the distal direction under the force of Attorney Docket No.: 46567-1782WO1 the shuttle biasing member 122s, restoring the needle sleeve 210 to the first position, as shown in Fig. 5e.

[0282] As the needle sleeve 210 moves between the first position and the second position, the protrusions 252, 253 of the flexible portions 2461 ’, 2463’ travel along their respective track 216, 217. Each track 216, 217 is substantially P shaped with a longitudinally extending leg 2161 , 2171 that leads into a return leg 2162, 2172 at its distal end. In use, when the needle sleeve 210 is displaced into the housing 110, each protrusion 252, 253 moves along the longitudinal leg 2161 , 2171 of their respective track 216, 217, returning along the return leg 2162, 2172 when the needle sleeve 210 extends from the housing 110 following medicament delivery. As the needle sleeve 210 moves into the second position, each protrusion 252, 253 transitions from the longitudinal leg 2161 , 2171 to the return leg 2162, 2172. The restoring force of the deflected flexible portions 2461 ’, 2463’ is released as the protrusions 252, 253 align with the return leg 2162, 2172, causing the flexible portions 2461 ’, 2463’ to straighten and the protrusions to enter the return leg 2162, 2172, as shown in Fig. 12a.

[0283] Each return leg 2162, 2172 of the illustrated embodiment comprises three sections. A first section 2162’, 2172’ extends from the longitudinal leg’s 2161 , 2171 distal end in a circumferential direction of the tubular wall 212. A second section 2162”, 2172” extends in a longitudinal direction from the first section 2162’, 2172’, parallel to the longitudinal leg 2161 , 2171 of the track 216, 217. A third section 2162’”, 2172’” extends from the proximal end of the second section 2162”, 2172” in a circumferential direction toward the longitudinal leg 2161 , 2171.

[0284] The second section 2162”, 2172” of each return leg 2162, 2172 comprises a ramped distal edge 221 , 222 that serves to deflect the flexible portions 2461 ’, 2463’ in a second circumferential direction as the needle sleeve 210 extends from the housing 110 following medicament delivery (deflection of the flexible portions 2461 ’, 2463’ is shown in Fig. 12b). Once the needle sleeve 210 has returned to the first position, the restoring force of the deflected flexible portions 2461 ’, 2463’ causes the protrusions 252, 253 to enter the third section 2162’”, 2172’” (as shown in Fig. 12c), thereby locking the needle sleeve 210 relative to the needle holder 240. Advantageously, this helps prevent the needle sleeve 210 from being accidently being retracted to expose the needle 211 , which could otherwise result in a needle sharp injury. Attorney Docket No.: 46567-1782WO1

[0285] In some embodiments, the medicament delivery unit 200 may be removed from the device 100 by rotating the medicament delivery unit 200 in a second direction so that the tabs 248 are removed from the retaining members 118. In the present example, the one or more locking elements 1184 prevent such rotation of the medicament delivery unit 200 and thus prevent such removal of the medicament delivery unit 200 from the device 100. This helps prevent the device 100 from being re-used with a different medicament delivery unit 200, which is particularly advantageous if the device and medicament delivery unit 200 have been left for a period if time after use such that the device 100 is no longer sterile (e.g. the dosing chamber 121 may become contaminated due to contaminants travelling along the needle 211).

[0286] A summary of an exemplary method for connecting the medicament delivery unit 200 to the device 100 comprises the following steps:

[0287] 51 - The proximal end of the medicament delivery unit 200 is placed within the receiving space 117 so that the locking tabs 248 are aligned with an open end of each slot 1181 of a retaining member 118.

[0288] 52 - The medicament delivery unit 200 is rotated in a first direction until the locking tabs 248 of the needle holder 240 abut the stops 1183 at the end of each slot 1181.

[0289] 53 - The needle sleeve 210 is then rotated independently of the needle holder 240 in the first direction until the projection 1226 of the shuttle 122 is received within the coupling notch 215.

[0290] Following connection of the medicament delivery unit 200 to the device 100, medicament may be delivered to a patient in accordance with a method comprising the following steps:

[0291] 54 - The dose setting knob 126 is rotated in a first rotational direction R1 until the second indicium 1254 is visible in the window 116.

[0292] 55 - Holding the housing 110 of the device 100, the distal end of the needle sleeve 210 is pressed against a chosen injection site to displace the needle sleeve 210 into the housing 110. This causes the needle sleeve 210 to slide into the second position, the needle 211 to penetrate the injection site and the plunger rod 124 to be released to dispense medicament.

[0293] S6 - The device 100 is lifted from the injection site, allowing the needle sleeve 210 to advance out of the housing 110 and adopt the post-delivery locked state. Attorney Docket No.: 46567-1782WO1

[0294] In the present example, the device 100 and medicament delivery unit 200 are locked together such that the device 100 and medicament delivery unit 200 must be disposed of or taken for recycling. However, in other embodiments, the medicament delivery unit 200 may be removable from the device 100. For instance, the locking elements 1184 may be omitted or the medicament delivery unit 200 may be coupled to the device 100 by a releasable threaded connection or bayonet connection. In embodiments wherein the medicament delivery unit 200 is removable, the method may comprise the following additional steps:

[0295] 57 - The medicament delivery unit 200 is rotated in a second direction until the locking tabs 248 are clear of the retaining stops 118 (or other such relesable coupling is detached).

[0296] 58 - The medicament delivery unit 200 is removed from the device 100 to allow the device 100 to be re-used with a new medicament delivery unit 200 by repeating steps S1 to S8.

[0297] Referring now to Fig. 13 to 17c, another embodiment of a medicament delivery system 1 ’ is shown. The medicament delivery system 1’ comprises a device 100’ and a medicament delivery unit 200’.

[0298] In the present example, the medicament delivery unit 200’ is a medicament delivery member 200’. In the present example, the medicament delivery member 200’ is an intranasal nozzle 200’. The intranasal nozzle 200’ is configured to deliver medicament to the nasal structures of a patient. Optionally, the intranasal nozzle 200’ comprises first and second medicament delivery conduits 201’, 202’ configured to deliver medicament to both of the external nostrils of the patient simultaneously.

[0299] The device 100’ is similar to the device 100 described above in relation to Figs. 1 to 12c, with like features retaining the same reference numerals. A difference is that the device 100’ is not actuated by a component of the medicament delivery unit 200’ and instead comprises a trigger button 350’ that is actuated by a user to deliver the dose of medicament to the patient. In the present example, the trigger button 350’ is a lever 350’. However, it should be recognised that in other embodiments, the button 350’ may be, for example, a slide button or push button. Attorney Docket No.: 46567-1782WO1

[0300] The lever 350’ extends radially outwardly from the release collar 123. The lever 350’ extends through a slot 360’ in the housing 110 of the device 100’ such that an end of the lever 350’ can be accessed by the user. The slot 360’ extends circumferentially.

[0301] The device 100’ comprises a medicament window 370’ in the housing 110 through which the medicament container 300 can be observed by the user.

[0302] The shuttle 122 and shuttle biasing member 122s of the device 100 of Figs. 1 to 12c are omitted. Instead, the lever 350’ of the device 100’ of Figs. 13 to 17c is manipulated by the operator to move the release collar 123 from the primed rotational position (Figs. 14d and 14e) to the dose delivery rotational position (Figs. 14e and 15e), which in the present example is the same as the initial rotational position. That is, the lever 350’ is manipulated by the operator to rotate the release collar 123 such that the stop section 123’” of the release collar 123 moves from a position wherein it abuts the protrusion 1244 of the plunger rod 124 (see Fig. 17b), to prevent movement of the plunger rod 124 in the distal direction A2, to a position wherein the stop section 1233’” no longer abuts the protrusion 1244 and thus the plunger rod 124 can move in the distal direction A2 under the force of the plunger biasing member 124s (see Figs. 14e and 17a).

[0303] Interaction of the release collar 123 and indicator ring 125 is illustrated schematically in Figs. 14a to 14e and Figs. 16a to 16e.

[0304] An exemplary operation of the device 100’ will now be described. Initially, the plunger rod 124 is in a distal position (see Fig. 15a), the release collar 123 is in the initial rotational position (see Figs. 14a, 15a and 16a), and the indicator ring 125 is in an initial position in which the first indicium 1253 is visible through the window 116 (or in alternative configurations, not shown, no part of the indicator member 125 is visible through the window 116).

[0305] To operate the device 100’, the user / operator firstly charges the dosing chamber 121 with a dose of medicament by rotating the dosing knob 126 in the first rotational direction (shown by arrow ‘R1 ’ in Fig. 13). This causes the plunger rod 124 to be urged in the proximal direction A1 , against the force of the plunger biasing member 124s, such that suction is created in the dosing chamber 121 and thus medicament is drawn into the dosing chamber 121 via the cannula 114 once the piston 1241 passes the inlet 114A. As explained previously, during this movement the protrusion 1244 of the plunger rod 124 engages the longitudinal section 1233” of the track 1233 (as shown in Fig. 17a) to prevent rotation of the release collar 123 relative to the housing 110 under the biasing force of the Attorney Docket No.: 46567-1782WO1 collar biasing member 140 (shown in Figs. 15Ato 15E), that is configured to bias the release collar 123 to rotate relative to the housing 110. Thus, the release collar 123 and indicator ring 125 remains in their initial rotational positions of Fig. 14a.

[0306] Rotation of the dosing dial 126 in the first rotational direction R1 causes the plunger rod 124 to move in the proximal direction A1 relative to the housing 110 and release collar

[0307] 123 such that the protrusion 1244 moves proximally along the longitudinal section 1233” of the track 1233. This is because the plunger rod 124 comprises a track or thread 1242 that engages with a projection 1262 of the dosing knob 126. In other embodiments (not shown), the dosing knob 126 may comprise a thread or track that engages with a projection or thread / track of the plunger rod 124.

[0308] Continued rotation of the dosing knob 126 causes the protrusion 1244 of the plunger rod

[0309] 124 to exit the longitudinal section 1233” of the track 1233 such that the longitudinal section 1233” no longer prevents rotational movement of the release collar 123 under the force of the collar biasing member 140. Thus, the release collar 123 rotates in the first rotational direction R1 under the force of the collar biasing member 140 such that the stop section 1233” circumferentially aligns with the protrusion 1244 (as shown in Fig. 17b). With the protrusion 1244 abutting the stop section 1233”of the track 1233 a dose of medicament has been drawn into the dosing chamber 121 from the cartridge 300.

[0310] The release collar 123 continues to rotate until it is in a first intermediate rotational position (as shown in Figs. 14b, 15b and 16b). During rotation of the release collar 123 from the initial rotational position of Fig. 16a to the first intermediate rotational position of Fig. 16b, the release collar 123 rotates relative to the indicator ring 125. That is, the release collar 123 rotates in the first rotational direction R1 relative to the housing 110 whilst the indicator ring 125 remains stationary relative to the housing 110. Once the release collar 123 reaches the first intermediate rotational position, the first engaging element 1236 of the release collar 123 abuts the engaging element 1252 of the indicator ring 125 (as shown in Fig. 16b).

[0311] Continued rotation of the dosing dial 126 in the first rotational direction R1 causes the plunger rod 124 to move further in the proximal direction A1 relative to the housing 110 and release collar 123 such that the protrusion 1244 moves along the ramp section 1233’ of the track 1233 (as shown in Figs. 17c). This further movement of the plunger rod 124 in the proximal direction A1 causes an additional volume (or ‘priming volume’) of medicament to be drawn into the dosing chamber 121 from the cartridge 300. Meanwhile, Attorney Docket No.: 46567-1782WO1 the release collar 123 continues to rotate in the first rotational direction R1 under the force of the collar biasing member 140 from the first intermediate rotational position (as shown in Figs. 14b, 15b and 16b) towards the second intermediate rotational position (as shown in Figs. 14c, 15c and 16c). Movement of the release collar 123 in the first rotational direction R1 from the first intermediate rotational position to the second intermediate rotational position causes corresponding movement of the indicator ring 125, due to the first engaging element 1236 of the release collar 123 abutting, and being pressed against, the engaging element 1252 of the indicator ring 125. The release collar 123 and indicator ring 125 thus rotate together from the first intermediate rotational position (see Fig. 16c) towards the second intermediate rotational position (see Fig. 16c). When the release collar 123 reaches the second intermediate rotational position, the corresponding rotation of the indicator ring 125 causes the second indicium 1254 to become visible through the window 116.

[0312] Further rotation of the dosing knob 126 in the first rotational direction R1 causes the projection 1262 of the dosing knob 126 to move out of engagement with the male thread 1242 of the plunger rod 124 such that the plunger rod 124 is no longer held against the biasing force of the plunger biasing member 124s. Thus, the plunger rod 124 moves axially in the distal direction A2 under the force of the plunger biasing member 124s until the protrusion 1244 of the plunger rod 124 abuts the stop section 1233”’ of the track 1233 (see Fig. 17b), wherein the plunger rod 124 is in a primed position (see Figs. 14d, 15d and 16d). This causes the piston 1241 to be urged in the distal direction A2 to urge the additional volume (priming volume) of medicament out of the dosing chamber 121 via the delivery member 200’, which in the present example is an intranasal nozzle 200’. This movement therefore primes the delivery member 200’, replacing air in the delivery member 200’ with medicament. In the primed position, the piston 1241 blocks the inlet 114A from the medicament in the dosing chamber 121 . Furthermore, with the plunger rod 124 in the primed position such that the protrusion 1244 abuts the stop section 1233’” of the track 1233, the stop section 1233’” prevents further movement of the plunger rod 124 in the distal direction A2.

[0313] Movement of the protrusion 1244 along the ramp section 1233’ as the plunger rod 124 moves distally to the primed position causes the release collar 123 to move in the second rotational direction R2, against the biasing force of the collar biasing member 140. Thus, the release collar 123 moves from the second intermediate rotational position (as shown in Figs. 14c, 15c and 16c) to the primed rotational position (as shown in Figs. 14d, 15d and 16d). During this rotation of the release collar 123, the first engaging element 1236 of Attorney Docket No.: 46567-1782WO1 the release collar 123 moves away from the engaging element 1252 of the indicator ring 125 and there is no corresponding movement of the indicator ring 125 in the second rotational direction R2. Once the release collar 123 has fully rotated to the primed rotational position (as shown in Figs. 14d, 15d and 16d), the second engaging element 1237 of the release collar 123 abuts the engaging element 1252 of the indicator ring 125.

[0314] With the plunger rod 124 in the primed position, the dose of medicament contained in the dosing chamber 121 can then be delivered through the delivery member 200’ to administer the dose to the patient. In particular, the release collar 123 is rotated further in the second rotational direction R2 due to operation of the actuator 350’, which in the present example is the trigger button 350’ in the form of the lever 350’. For instance, the user may grip the housing 111 with one hand and press on the lever 350’ with the same / other hand to urge the lever 350’ to move within the slot 360’. The release collar 123 may be fixed relative to the lever 350’.

[0315] This rotation of the release collar 123 causes the stop section 1233’” of the track 1233 to move out of abutment with the protrusion 1244 of the plunger rod 124 such that the plunger rod 124 is permitted to move further in the distal direction A2 under the force of the plunger biasing member 124s. Therefore, the plunger rod 124 moves in the distal direction A2 such that the projection 1244 moves within the longitudinal section 1233” of the track 1233 and there is a corresponding distal movement of the piston 1241 within the dosing chamber 121 to expel the medicament from the chamber 121 and through the delivery member 200’. This movement of the piston 1241 will continue until the protrusion 1244 abuts the annular wall 1232 of the release collar 123 and / or the piston 1241 abuts the annular wall 1212 of the dosing chamber 121 , at which point the entire dose of medicament has been expelled from the dosing chamber 121 via the delivery member 200’. For example, the delivery member 200’ may comprise an intranasal nozzle 200’ or alternatively an injection needle (for example, an injection needle of the configuration described above in relation to the embodiment of Figs. 1 to 12c).

[0316] The movement of the release collar 123 in the second rotational direction R2 from the primed rotational position (see Figs. 14d, 15d and 16d) to the dose delivery rotational position (Figs. 14e, 15e and 16e), in which the stop section 1233’” of the release collar 123 is moved out of engagement with the protrusion 1244 of the plunger rod 124, causes corresponding rotation of the indicator ring 125 due to the second engaging element 1237 of the release collar 123 being urged against the engaging element 1252 of the indicator ring 125. Therefore, the movement of the release collar 123 under the action of the trigger Attorney Docket No.: 46567-1782WO1

[0317] 350’ causes corresponding movement of the indicator ring 125 in the second rotational direction R2 back to its original position wherein the first indicium 1253 is visible through the window 116 (see Figs. 14e, 15e and 16e). In some embodiments, the device 100’ may then be re-used to deliver further doses of medicament.

[0318] In the present example, the dosage volume held in the dosing chamber 121 when the plunger rod 124 is in the primed position corresponds to the dose required for delivery to both nostrils simultaneously via both medicament delivery conduits 201 ’, 202’ of the intranasal nozzle 200’. In other embodiments (not shown), the intranasal nozzle 200’ may comprise a single medicament delivery conduit such that medicament is delivered to each nostril sequentially, by re-using the system 1 ’. In such embodiments, the dosage volume held in the dosing chamber 121 when the plunger rod 124 is in the primed position corresponds to enough medicament for a single nostril.

[0319] In the present example, the medicament delivery system 100’ is an intranasal medicament delivery system 100’. The intranasal medicament delivery system 100’ may be an intranasal atomization delivery system 100’.

[0320] The intranasal medicament delivery system 100’ may be configured to deliver about1 / 2of a dose to each nostril.

[0321] The intranasal medicament delivery system 100’ may be configured to deliver about 0.2mL, wherein about 0.1 mL is delivered to each nostril.

[0322] The intranasal nozzle 200’ may deliver an average droplet size Dv50 of about 10-120 pm.

[0323] The intranasal nozzle 200’ may deliver an average droplet size Dv50 delivered to each nostril may be about 10-120 pm, about 30-110 pm, about 50-110 pm, about 70-110 pm, or about 80-110 pm

[0324] The intranasal medicament delivery system 100’ may be configured so that an average shot volume to each nostril is between about 85 pL to about 120 pL, about 90 pL to about 115 pL, or about 95 pL to about 115 pL.

[0325] In some embodiments, the intranasal medicament delivery system 100’ is configured to deliver in the range of 20 to 2000 microlitres (0.02 to 2 ml) volume of medicament and, preferably, in the range of 100 to 400 microlitres (0.1 to 0.4 ml) and, preferably, in the range of 10 to 300 microlitres (0.1 to 0.3 ml) and, preferably, about 200 microlitres (0.2 ml). Attorney Docket No.: 46567-1782WO1

[0326] In some embodiments, the intranasal medicament delivery system 100’ is configured to deliver in the range of 10 to 1000 microlitres (0.01 to 1 ml) volume of medicament to each nostril of the user and, preferably, in the range of 50 to 200 microlitres (0.05 to 0.2 ml) and, preferably, in the range of 50 to 150 microlitres (0.05 to 0.1 ml) and, preferably, about 100 microlitres (0.1 ml) of medicament to each nostril of the user.

[0327] In the above described embodiments, the dosing knob 126 is rotated relative to the housing 110 to draw an additional volume of medicament (the ‘priming volume’) into the chamber 121. However, it should be recognised that in alternative embodiments (not shown), the dosing knob 126 may instead be pulled in the proximal direction A1 by a user to draw the additional volume of medicament into the chamber 121 and, optionally, may be translated relative to the housing 110 in the proximal direction A1 . This causes the projection 1262 of the dosing knob 1262 to be urged axially against the thread 1242 of the plunger rod 124 to cause corresponding axial movement of the plunger rod 124 in the proximal direction A1 to draw the additional volume (priming volume) of medicament into the chamber 121. The device 100, 100’ may be configured such that once the dosing knob 126 has been pulled to its most proximal position (e.g. the position of Fig. 5c or Fig. 15c), the dosing knob 126 is urged to rotate in the first rotational direction R1 to release the projection 1262 from the thread 1242 such that the plunger rod 124 moves in the distal direction A2 under the force of the plunger biasing member 124s to release the additional volume of medicament in the manner previously described (and such that the protrusion 1244 of the plunger rod 124 rests against the stop section 1233’” of the release collar 123 such that the plunger rod 124 is in the primed position ready for dose delivery). For example, the dosing knob 126 and / or housing 110 may comprise a cam surface (not shown) that is configured to urge the dosing knob 126 to rotate relative to the housing 110 when the dosing knob 126 reaches its furthest proximal position. In one such embodiment (not shown), the housing 110 comprises an angled cam surface (not shown) and the dosing knob 126 comprises a follower (not shown) that engages the angled cam surface when the dosing knob 126 moves to its furthest proximal position such that the follower moves along the cam surface and thereby causes rotation of the dosing knob 126.

[0328] In the above described embodiments, the container 300 is a cartridge 300 that comprises a cylindrical wall 301 and a piston 302 that is slidable within the cartridge 300 as medicament is drawn through the cannula 114 and into the dosing chamber 121 via the inlet 114A. However, it should be recognised that in other embodiment the container 300 may have an alternative configuration. For example, Fig. 18 shows another embodiment wherein the medicament delivery system 1 ” is the same as the system of Figs. 13 to 17c, Attorney Docket No.: 46567-1782WO1 with like features retaining the same reference numerals, except that the cartridge 300 is replaced with a vial 300’ of medicament. Again, the cannula 114 of the device 100” may penetrate a sealing element 304 (e.g. septum 304) at an end of the vial 300’.

[0329] In the above described embodiments, the drive mechanism is configured to move the plunger rod 124 from the intermediate position to the primed position to expel the priming volume of medicament from the chamber 121. That is, the drive mechanism is operable such that the plunger biasing member 124s exerts a force on the plunger rod 124 to move the plunger rod 124 from the intermediate position to the primed position. However, in other embodiments (not shown), the medicament delivery device 100, 100’ is configured such that the user manually moves the plunger rod 124 from the intermediate position to the primed position to expel the priming volume of medicament from the chamber 121. For example, the user may push the plunger rod 124 from the intermediate position to the primed position.

[0330] In the above-described embodiments, the plunger rod 124 of the device 100, 100’ is configured to move from the first position to the second position against the biasing force of the biasing member 124s and, optionally, movement of the plunger rod 124 from the first position to the second position primes the biasing member 124s. This allows for the biasing member 124s to be primed / compressed when a user prepares the device 100, 100’ for medicament delivery. However, in other embodiments (not shown) the device 100, 100’ may be supplied with the biasing member 124s in a pre-primed / pre-compressed state and wherein when the plunger rod 124 is moved from the first position to the second position this is not against the force of the biasing member 124s (and optionally does not prime the biasing member 124s, which is already primed). In one such embodiment, the device 100, 100’ is supplied with the biasing member 124s in a pre-primed state and held in this state by a locking mechanism. The user pulls the plunger rod 124 from the first position to the second position and then pushes the plunger rod 124 to the primed position (optionally without any force being exerted on the biasing member 124s), and then releases the biasing member 124s such that the plunger rod 124 is urged to the first position to dispense medicament from the device 100, 100’.

[0331] In some embodiments, the locking mechanism comprises a release collar 123 that is rotatable relative to the plunger rod 124 from a locked position, in which the plunger rod 124 is prevented from moving from the primed position in the second direction A2, to an unlocked position, in which the plunger 124 is moveable from the primed position in the Attorney Docket No.: 46567-1782WO1 second direction A2. However, it should be recognised that in other embodiments (not shown), the release collar 123 may be omitted. For instance, the device 100, 100’ may comprise an electronic / magnetic lock that holds the plunger rod 124 in the primed position until the user presses a button to release the lock.

[0332] In some embodiments, the plunger 124 is moveable in the first direction A1 from the first position to second position and is then moved in the second direction A2 from the second position to the priming position to expel a priming volume of medicament from the device 100. However, it should be recognised that in other embodiments (not shown), the device does not draw / expel a priming volume of the medicament from the device. Instead, the device only draws a dosage volume of medicament into the device and then expels the dosage volume for delivery to the patient (e.g. without any priming volume being released first).

[0333] In some embodiments, the plunger 124 is moveable in the second direction A1 to draw medicament into the device 100. However, it should be recognised that in other embodiments (not shown), the device is pre-filled with medicament such that medicament is not drawn into the device. For example, the device may be provided to the end user with a container (for example, a cartridge or syringe) that contains the medicament. The device may be supplied with the container pre-loaded in the housing or may be loaded by the user. In some embodiments, the plunger is moveable in the first direction to provide space to accommodate the medicament container (which may be pre-filled with medicament) and then the plunger is moveable in the second direction to, firstly, take up a gap or ‘play’ between the plunger and the medicament container (e.g. a piston or bung of the medicament container), and then the plunger is further moveable in the second direction to expel medicament from the medicament container (e.g. by moving the piston or bung of the medicament container to expel medicament). For instance, the plunger may be moved from a first position to a second position to permit loading of the cartridge, and then may be moved from the second position to a primed position to abut the cartridge (and, for example, take up play between the plunger and cartridge, and / or to expel a small priming volume of medicament from the device). The plunger may then move distally from the primed position to expel medicament from the device. In some embodiments, movement of the plunger between the first, second, primed, and delivery positions (where the plunger has moved distally in the container and the dose volume of medicament has been dispensed) is a number of discrete steps or, the plunger may move continuously between one or more of these positions. Attorney Docket No.: 46567-1782WO1

[0334] Referring now to Fig. 19, a block diagram illustrating an exemplary embodiment of a method 1000 of operating a medicament delivery system is shown. The method 1000 comprises: (step S1) moving an actuator relative to a housing to draw medicament into a chamber from a container and such that the actuator is moved from a position wherein a trigger is prevented from being actuated to operate a drive mechanism to a position wherein the trigger is permitted to be actuated by a user to operate the drive mechanism to expel medicament from the chamber; and, (step S2) actuating the trigger to operate the drive mechanism to expel medicament from the chamber.

[0335] The medicament delivered by any of the embodiments described above may be any medicament described herein. The medicament may be a vaccine adapted for nasal administration. The vaccine may be an RSV vaccine.

[0336] Described herein are systems, devices, components, and methods that may be associated with delivering a respiratory syncytial virus (RSV) vaccine using an intranasal atomization delivery device.

[0337] As used herein, “RSV ANS2 / A1313 / I1314L” refers to an RSV ANS2 / A1313 / I1314L (NIH) or an RSV ANS2 / A1313 / 11314L (Sanofi). Each of the ANS2 / A1313 / I1314L (NIH) and the RSV ANS2 / A1313 / I1314L (Sanofi) comprise a live-attenuated RSV with (i) a 523 nucleotide (nt) deletion of the NS2 gene (ANS2), (ii) an amino acid deletion in the L protein, and (iii) a genetically stabilizing mutation in the L gene. The live-attenuated RSV of the RSV ANS2 / A1313 / I1314L (Sanofi) also includes a nucleotide modification at position 14456 that represents a change from a thymine (T) to an adenine (A) in a noncoding region.

[0338] As used herein, “RSV ANS2 / A1313 / I1314L vaccine” refers to an “RSV ANS2 / A1313 / I1314L (NIH) vaccine” or an “RSV ANS2 / A1313 / I1314L (Sanofi) vaccine.” An RSV ANS2 / A1313 / I1314L (NIH) vaccine comprises an effective amount of RSV ANS2 / A1313 / I1314L (NIH). An RSV ANS2 / A1313 / I1314L (Sanofi) vaccine comprises an effective amount of RSV ANS2 / A1313 / I1314L (Sanofi).

[0339] Exemplary Methods and Uses Attorney Docket No.: 46567-1782WO1

[0340] In some embodiments, provided are methods of delivering a dose of an RSV vaccine using an intranasal atomization delivery device.

[0341] In some embodiments, the methods of administering a dose of an RSV vaccine that comprises a live attenuated RSV use an intranasal atomization delivery device. In some embodiments, provided are methods of administering a dose of an RSV vaccine using an intranasal atomization delivery device, the RSV vaccine comprising an effective amount of a live-attenuated RSV with (i) a 523 nucleotide (nt) deletion of the NS2 gene (ANS2), (ii) an amino acid deletion in the L protein, and (iii) a genetically stabilizing mutation in the L gene (RSVA NS2 / A1313 / I1314L (NIH) vaccine) or RSVA NS2 / A1313 / I1314L (Sanofi) vaccine that further comprises a nucleotide modification in a non-coding region that represents a change from a thymine (T) to an adenine (A). In some embodiments, a codon that encodes a serine at position 1313 of the L protein is deleted resulting in the deletion of the amino acid in the L protein (A1313). In some embodiments, an amino acid residue substitution of leucine for isoleucine at position 1314 results in a genetically stabilizing mutation in the L gene (I1314L).

[0342] In some embodiments, provided are methods of administering a dose of an RSV vaccine using an intranasal atomization delivery device. In some embodiments, the paediatric subject may be 6 to 18 months of age.

[0343] In some embodiments, the RSV vaccine is delivered intranasally using the intranasal atomization delivery device to deliver about 1 dose to each nostril. In some embodiments, the RSV vaccine is delivered intranasally so that the whole dose is delivered to one nostril. In some embodiments, the RSV vaccine is delivered intranasally with 14 dose delivered to one nostril and the other 14 dose is delivered to the same nostril after the first V dose is absorbed. In some embodiments, the RSV vaccine is delivered intranasally using the intranasal atomization delivery device to deliver a dose in unequal amounts to one or both nostrils.

[0344] In some embodiments, the RSV vaccine is delivered intranasally using the intranasal atomization delivery device in a liquid formulation. In some embodiments, the RSV vaccine dose is delivered intranasally using the intranasal atomization delivery device in about 0.2 mL. In some embodiments, the 0.2 mL dose is delivered intranasally wherein about 0.1 mL is delivered to each nostril. In some embodiments, the RSV vaccine dose is delivered intranasally using the intranasal atomization delivery device in about 0.01 mL, Attorney Docket No.: 46567-1782WO1

[0345] 0.02 mL, 0.05 mL, 0.1 mL, 0.2 mL, 0.3 mL, 0.4 mL, 0.5 mL, 0.6 mL, 0.7 mL, 0.8 mL, 0.9 ml_, 1.0 mL, 1.1 mL, 1.2 mL, 1.3 mL, 1.4 mL or 1.5 mL. As described above, the dose may be divided evenly between two nostrils, divided unevenly between two nostrils, or delivered all to one nostril in one or more deliveries.

[0346] In some embodiments, provided are methods of administering a first dose of an RSV vaccine using an intranasal atomization delivery device and administering a second dose of the RSV vaccine using an intranasal atomization delivery device.

[0347] In some embodiments, provided are methods of administering a first dose of an RSV vaccine using an intranasal atomization delivery device wherein the intranasal atomization delivery device comprises a spray nozzle to atomize the RSV vaccine and direct a spray plume toward a top of a nasal passageway into a nasal cavity. In some embodiments, provided are methods of administering a dose of an RSV vaccine using an intranasal atomization delivery device wherein the intranasal atomization delivery device comprises a spray nozzle to atomize the RSV vaccine and direct a spray plume toward a top of a nasal passageway into a nasal cavity. In some embodiments, the intranasal atomization delivery device comprises a barrel operably connected to the spray nozzle and a plunger movable within the barrel to advance the RSV vaccine through the spray nozzle. In some embodiments, the intranasal atomization delivery device further includes a dose divider for splitting the dose of the RSV vaccine into two or more deliveries. In some embodiments, the dose divider may divide the dose of the RSV vaccine in about half of a volume to be delivered to a subject. In some embodiments the dose divider is used to deliver % dose to each nostril of the subject.

[0348] In some embodiments, the intranasal atomization delivery device delivers an average droplet size Dv50of 10-120 pm. In some embodiments, the intranasal atomization delivery device delivers an average droplet size Dvso of 10-120 pm, about 30-110 pm, about 50- 110 pm, about 70-110 pm, or about 80-110 pm. In some embodiments, the intranasal atomization delivery device delivers an average shot weight between about 95 mg to about 135 mg, between about 100 mg to about 130 mg, or between about 100 mg to about 130 mg or between about 105 mg to about 130. In some embodiments, the intranasal atomization delivery device delivers an average shot volume of about 85 pL to about 120 pL, about 90 pL to about 115 pL, or about 95 pL to about 115 pL. Attorney Docket No.: 46567-1782WO1

[0349] In some embodiments, use of an intranasal atomization delivery device described herein for administering a dose of an RSV vaccine to a subject is provided wherein the RSV vaccine comprises an effective amount of a live-attenuated RSV. In some embodiments, the use includes a live-attenuated RSV with (i) a 523 nucleotide (nt) deletion of the NS2 gene (ANS2), (ii) an amino acid deletion in the L protein, and (iii) a genetically stabilizing mutation in the L gene (RSVA NS2 / A1313 / 11314L) (NIH) vaccine or RSVA NS2 / A1313 / I1314L (Sanofi) vaccine that further comprises a nucleotide modification in a non-coding region that represents a change from a thymine (T) to an adenine (A).

[0350] Immunogenicity

[0351] Approximately seventy percent (70%) of vaccine recipients attained a 4-fold response in neutralizing antibody titer following the second vaccine dose in both low and high dose groups, compared to 61 and 47% following one vaccine dose in low and high dose RSV naive participants. This increase in the percentage of participants attaining a 4-fold response following a second administration supports the use of a second vaccine administration in this population. The 70% attaining this fold rise post second vaccine administration aligns with the expected clinical efficacy goal of 70% for the candidate. After one or two vaccinations, 75% attained a 4-fold rise in serum neutralizing antibody titers. The percentage of RSV experienced participants (36% and 22% in the low and high dose groups respectively) also attaining a 4 -fold response in neutralizing antibody titers post vaccination 1 suggests potential benefit for this sub-group as well. It must be noted that this comes from a modest sample of participants (n = 20 of 97 vaccine recipients) at this point of interim analysis.

[0352] Taken together, these data strongly support the use of RSV ANS2 / A1313 / I1314L (Sanofi) vaccine at an operative range study for the candidate including doses at 5.6 and 6.2 log PFU / dose.

[0353] Vaccine virus shedding and Infectivity

[0354] Following each vaccine administration, the shedding of vaccine virus was considered in addition to the fold rise in neutralizing antibody titers or serum IgG as vaccine infectivity. The high level of vaccine infectivity (over 80% and 70% in RSV naive following the first and second vaccine administration respectively) is supportive of a promising vaccine candidate associated with good vaccine take. When infectivity was considered after either Attorney Docket No.: 46567-1782WO1 vaccine administration, over 90% of participants had evidence of infection. In the small cohort of RSV experienced participants, relatively high infectivity (80% and 33.3% in low and high dose recipients following one vaccine administration and 60 and 50% following a second vaccine administration) was found, implicating promise for this group. In addition, the marked drop in the percentage of vaccine virus shedders in RSV naive participants after the second vaccine administration (roughly 20%) compared to the first vaccine administration (over 70%) is as previously documented with other efficacious live- attenuated mucosal viral vaccines where subsequent ‘challenge’ in the form of a second vaccine dose is characterized by a marked reduction in vaccine virus shedding. Of note, the shedding data available for this cohort was from data at a single timepoint following each vaccination (seven days post vaccination). While this coincides with the point of peak viral shedding documented in other RSV live-attenuated vaccine (LAV) trials, it is likely that some shedders may have been missed. This limitation in the available shedding data makes the results obtained particularly encouraging.

[0355] Interim analysis results showed a promising safety, immunogenicity and infectivity profile of the RSV ANS2 / A1313 / I1314L (Sanofi) candidate.

[0356] No safety concerns were identified after 1- and 2-dose administrations of either dose level of the investigational RSV ANS2 / A1313 / I1314L (Sanofi) vaccine or by baseline serostatus.

[0357] The vaccine virus shedding, and immunogenicity conclusions based on the IgA serostatus at baseline show marked vaccine take demonstrated at both dose levels, and 70% of vaccine RSV-naive recipients attained a 4-fold response in serum neutralizing antibody responses post the second vaccine administration for both dose levels in RSV-naive participants.

[0358] In other embodiments, one or more vaccines directed to one or more of the following viruses or bacteria may be delivered using components, devices, or systems described herein. The viruses may include severe acute respiratory syndrome coronavirus 1 (SARS- CoV-1), severe acute respiratory syndrome coronavirus 2 (SARS CoV 2), influenza virus, respiratory syncytial virus (RSV), human metapneumovirus (hMPV), human parainfluenza viruses (i.e., HPIV-1 , HPIV-2, HPIV-3, and HPIV 4), rhinovirus, human papillomavirus (HPV), or human immunodeficiency virus (HIV). The bacteria may include Porphyromonas gingivalis, Streptococcus pneumoniae, Bordetella pertussis, Neisseria Attorney Docket No.: 46567-1782WO1 meningitidis, Chlamydia trachomatis, or Neisseria gonorrhoeae. The vaccines may be compositions that generate a protective immune response in a subject. For example, the protective immune response may be an immune response that protects a subject from infection (prevents infection or prevents the development of disease associated with infection) or reduces the symptoms of infection (for instance an infection by a virus or bacterium as provided above). Vaccines may elicit both prophylactic (preventative) and therapeutic responses.

[0359] Attorney Docket No.: 46567-1782WO1

[0360] List of Reference Numbers

[0361] 1 - medicament delivery system

[0362] 1’ - medicament delivery system

[0363] 1 ” - medicament delivery system

[0364] 100 -medicament delivery device

[0365] 100’ - medicament delivery device

[0366] 110- housing

[0367] 111- primary tubular wall

[0368] 112- secondary tubular wall

[0369] 112A- gripping portion

[0370] 112B - slit

[0371] 113 -port

[0372] 113A- well

[0373] 114- cannula

[0374] 114A- inlet

[0375] 115- radial wall

[0376] 116- window

[0377] 117- receiving space

[0378] 118- retaining members

[0379] 1181 - slot

[0380] 1182 -lip

[0381] 1183- stop

[0382] 1184- locking element

[0383] 119- annular wall

[0384] 1191 - opening in annular wall

[0385] 120 - drive mechanism

[0386] 121 - dosing chamber

[0387] 1211 - tubular wall

[0388] 1212 - annular wall

[0389] 1213 - central opening

[0390] 1213A- edge (valve seat)

[0391] 122 - shuttle

[0392] 122s - shuttle biasing member

[0393] 1221 - tubular wall (of which proximal region 1221’)

[0394] 1222 - cut out Attorney Docket No.: 46567-1782WO1

[0395] 1223 - ramped edge

[0396] 1224 - shoulder

[0397] 1225 - second cut out

[0398] 1226 - projection

[0399] 1227 - distal edge of the tubular wall

[0400] 1228 - locking element

[0401] 123 - release collar

[0402] 1231 - tubular wall (of which distal region 1231 ’; proximal region 1231 ”)

[0403] 1232 - annular wall

[0404] 1233 - track (of which ramped section 1233’; longitudinal section 1233”; and square section 1233’”)

[0405] 1234 - rib

[0406] 1235 - flange

[0407] 1236 - first engaging element

[0408] 1237 - second engaging element

[0409] 124 - plunger rod

[0410] 124s - drive biasing member)

[0411] 1241 - piston

[0412] 1242 - male thread

[0413] 1244 - protrusion

[0414] 125 - indicator member

[0415] 1251 - tubular wall

[0416] 1252 - engaging element

[0417] 1253 - first indicia

[0418] 1254 - second indicia

[0419] 1255 - stop

[0420] 1256 - longitudinal slot

[0421] 126 - dosing knob

[0422] 126A - end wall

[0423] 1261 - tubular wall

[0424] 1262 - projection

[0425] 1263 - ratchet mechanism

[0426] 1263A - ratchet teeth

[0427] 127 - one-way valve

[0428] 128 - gasket Attorney Docket No.: 46567-1782WO1

[0429] 129 - stem

[0430] 130 - valve member (plug)

[0431] 130A - chamfered portion

[0432] 140 -collar biasing member (locking member biasing member)

[0433] 200 - medicament delivery unit

[0434] 200’ - intranasal nozzle (medicament delivery member)

[0435] 201’ - first medicament delivery conduit

[0436] 202’ - second medicament delivery conduit

[0437] 210 - needle sleeve

[0438] 211 - needle (medicament delivery member)

[0439] 212 - tubular wall

[0440] 213 - annular wall

[0441] 214 - opening

[0442] 215 - coupling notch

[0443] 216, 217 -tracks

[0444] 2161 , 2171 - longitudinally extending legs

[0445] 2162, 2172 - return legs

[0446] 2162’, 2172’ - first sections of return leg

[0447] 2162”, 2172” - second sections of return leg

[0448] 2162’”, 2172’” - third sections of return leg

[0449] 218 - L-shaped cut outs

[0450] 218’ - circumferentially extending portion of L-shaped cut out

[0451] 218” - longitudinally extending portion

[0452] 219 - windows

[0453] 220 - proximal edge

[0454] 221 , 222 - ramped distal edges of respective first sections 2162’, 2172’ of the return legs

[0455] 240 - needle holder

[0456] 241 - tubular wall

[0457] 242 - base wall

[0458] 243 - frustoconical portion

[0459] 244 - antechamber

[0460] 245 - tubular projection

[0461] 2461 , 2462, 2463, 2464 - radial walls

[0462] 2461 ’, 2463’ - distal regions / flexible portions

[0463] 2471 , 2472 - cut outs

[0464] 248 - locking tabs Attorney Docket No.: 46567-1782WO1

[0465] 250 - lugs

[0466] 252, 253 - protrusions

[0467] 300 - medicament cartridge

[0468] 300’ - medicament vial

[0469] 301 - cylindrical wall

[0470] 302 - piston

[0471] 303 - end of cartridge

[0472] 304 - sealing element

[0473] 350’ - trigger button (lever)

[0474] 360’ - slot

[0475] 370’ - medicament window

[0476] 1000 - method of preparing a medicament delivery system

[0477] X-X - axis

[0478] A1 - proximal direction

[0479] A2 - distal direction

[0480] R1 - first rotational direction

[0481] R2 - second rotational direction

Claims

Attorney Docket No.: 46567-1782WO1Claims1. A medicament delivery device (100, 100’) comprising: a housing (110); a plunger (124); an actuator (126) moveable relative to the housing (110) to urge the plunger (124) to move in a first direction relative to the housing (110); a drive mechanism (120) configured such that, in use, the drive mechanism (120) is operable to move the plunger (124) in a second direction to expel medicament from the device (100, 100’); and, a trigger (210, 350’) configured such that, prior to movement of the actuator (126) relative to the housing (110) the trigger (210, 350’) is prevented from being actuated to operate the drive mechanism (120), and such that once the actuator (126) has been moved relative to the housing (110) the trigger (210, 350’) is permitted to be actuated by a user to operate the drive mechanism (120).

2. A medicament delivery device (100’) according to claim 1 , configured such that movement of the actuator (126) relative to the housing (110) causes the trigger (350’) to move to a ready position wherein the trigger (350’) is ready to be actuated by a user to operate the drive mechanism (120) and, optionally, wherein the trigger (350’) is configured to rotate relative to the housing (110) to move to the ready position.

3. A medicament delivery device (100) according to claim 1 , comprising a stop (1255) moveable from a first position to a second position upon movement of the actuator (126) relative to the housing (110), wherein when the stop (1255) is in the first position actuation of the trigger (210’) is prevented and wherein when the stop (1255) is in the second position actuation of the trigger (210’) is permitted.

4. A medicament delivery device (100’) according to any one of the preceding claims, wherein the trigger (350’) comprises a trigger button (350’) and, optionally, comprises a lever (350’).

5. A medicament delivery device (100) according to any one of claims 1 to 3, wherein the trigger (210) is configured to be pressed against a body of a user to operate the drive mechanism (120) and, optionally, wherein the trigger (210) comprises a sleeve (210).Attorney Docket No.: 46567-1782WO16. A medicament delivery device (100, 100’) according to any one of the preceding claims, comprising a chamber (121) for receiving medicament and, optionally, wherein the actuator (126) is moveable relative to the housing (110) to urge the plunger (124) to move in the first direction relative to the chamber (121) and / or wherein the actuator (126) is moveable relative to the chamber (121) to urge the plunger (124) to move in the first direction relative to the housing (110).

7. A medicament delivery device (100, 100’) according to claim 6, wherein the plunger (124) is configured such that, in use, the plunger (124) is moveable relative to the housing (110) in a first direction (A1) from a first position to a second position to draw medicament into the chamber (121) from a container (300, 300’) and, optionally, is moveable relative to the housing (110) in a second direction (A2) from the second position to a primed position to expel a priming volume of the medicament from the chamber (121) and, optionally, wherein the drive mechanism (120) is configured to move the plunger (124) from the primed position in the second direction (A2) to expel a dosage volume of the medicament from the chamber (121) for delivery to a user.

8. A medicament delivery device (100, 100’) according to any one of the preceding claims, comprising a locking member (123) that is moveable relative to the plunger (124) from a locked position to an unlocked position, in which the plunger (124) is released to expel medicament from the chamber (121) and, optionally, wherein the locking member (123) is rotatable between the locked and unlocked positions and, optionally, wherein the locking member (123) comprises a collar (123) that is rotatable between the locked and unlocked positions.

9. A medicament delivery device (100, 100’) according to claim 8, comprising a locking biasing member (140) configured to bias the locking member (123) to rotate relative to the housing (110) when the actuator (126) is moved to draw medicament into the chamber (121).

10. A medicament delivery device (100, 100’) according to claim 9, when dependent on claim 7, wherein the locking biasing member (140) is configured to bias the locking member (123) to rotate relative to the housing (110) in a first rotational direction (R1) as the plunger (124) moves from the first position to the second position and, optionally, wherein one of the plunger (124) and locking member (123) comprises a ramp section (1233’) configured such that when the plunger (124) is moved from the second position toAttorney Docket No.: 46567-1782WO1 the primed position in the second direction (A2), the other one of the plunger (124) and locking member (123) engages the ramp section (1233’) to move the locking member (123) in a second rotational direction (R2), opposite to the first rotational direction (R1).

11. A medicament delivery device (100, 100’) according to any one of claims 8 to 10, wherein the trigger (210, 350’) is configured to urge the locking member (123) to move from the locked to the unlocked position and, optionally, wherein the trigger (350’) is fixed relative to the locking member (123) and, optionally, wherein the trigger (350’) extends from the locking member (123) and / or wherein the medicament delivery device (100, 100’) further comprises a shuttle (122) that is moveable relative to the housing (110) from a first position to a second position to urge the locking member (123) from the locked position to the unlocked position and, optionally, wherein one of the shuttle (122) and locking member (123) comprises a cam surface (1223) configured to engage the other one of the shuttle (122) and locking member (123) to rotate the locking member (123) from the locked position to the unlocked position upon movement of the shuttle (122) from the first position to the second position.

12. A medicament delivery device (100, 100’) according to any one of the preceding claims, wherein the actuator (126) is rotatable relative to the housing (110) to urge the piston (124) to move in the first direction and, optionally, wherein at least one of the plunger (124) and actuator (126) comprises an engaging portion (1242) that is configured to engage with the other one of the plunger (124) and actuator (126) such that rotation of the actuator (126) urges the plunger (124) to move in the first direction and / or wherein the housing (110) is configured to interface with a medicament container (300) and, optionally, wherein the actuator (126) is moveable relative to the housing (110) to urge the plunger (124) to move in the first direction relative to the medicament container (300) and / or wherein the actuator (126) is moveable relative to the medicament container (300) to urge the plunger (124) to move in the first direction relative to the housing (110).

13. A medicament delivery device (100’) according to any one of the preceding claims, wherein the medicament delivery device (100’) is an intranasal medicament delivery device (100’).

14. A medicament delivery system (1 , 1 ’, 1 ”) comprising a medicament delivery device (100, 100’) according to any one of the preceding claims and a container of medicament (300, 300’) and, preferably, wherein the medicament is a vaccine.Attorney Docket No.: 46567-1782WO115. A method of preparing a medicament delivery system (100, 100’), the method comprising: moving (S1) an actuator (126) relative to a housing (110) in a first direction such that the actuator (126) is moved from a position wherein a trigger (210, 350’) is prevented from being actuated to operate a drive mechanism (120) to a position wherein the trigger (210, 350’) is permitted to be actuated by a user to operate the drive mechanism (120) to expel medicament from the system (100, 100’).

Images