Medicament delivery device

Abstract

The present disclosure relates to a medicament delivery device comprising a housing configured to contain a medicament container, a dose dispensing mechanism comprising a biasing sleeve and a resilient member configured to exert a biasing force on the biasing sleeve, and a trigger member. The trigger member is movable relative to the housing in a first direction to load the resilient member and move the biasing sleeve, such that the resilient member and biasing sleeve dispense a first medicament dose from the medicament container. After the first dose has been dispensed, the trigger member is movable relative to the housing in the first direction to load the resilient member and move the biasing sleeve, such that the resilient member and biasing sleeve dispense a second medicament dose. The present disclosure also relates to a medicament delivery system and to a method of using a medicament delivery system.

Description

[0001] Attorney Docket No.: 46567-1790WO1

[0002] MEDICAMENT DELIVERY DEVICE

[0003] CROSS-REFERENCE TO RELATED APPLICATIONS

[0004] This application claims the benefit of priority to European Patent Application No.

[0005] 25159419.8, filed February 21, 2025, the contents of which are herein incorporated by reference.

[0006] TECHNICAL FIELD

[0007] The present disclosure relates to a medicament delivery device. The present disclosure also relates to a medicament delivery system and a method of using a medicament delivery device.

[0008] BACKGROUND

[0009] 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.

[0010] The nasal administration of medicaments represents an alternative route to intravenous, intramuscular or subcutaneous medicament administration. Devices for nasal administration of medicaments may include a nozzle for insertion into the patient’s nose and delivering medicament to the patient’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 patient.

[0011] In some cases, it may be desirable to administer multiple doses of a medicament to a patient, such as delivering a dose to each nostril. Traditional devices that deliver only a single dose may require a healthcare professional to refill the device after each administration, which may be time-consuming, can compromise sterility, and may result in inaccurate dosing. While devices capable of administering multiple doses without refilling with medicament may exist, the operation of such devices may be complex and it may be challenging to execute accurate administration of multiple doses.Attorney Docket No.: 46567-1790WO1

[0012] It may be desirable to provide a medicament delivery device that is easy to operate to administer a plurality of doses of a medicament.

[0013] SUMMARY

[0014] According to the present disclosure, there is provided a medicament delivery device comprising: a housing configured to contain a medicament container; a dose dispensing mechanism comprising a biasing sleeve and a resilient member configured to exert a biasing force on the biasing sleeve; and a trigger member, wherein the trigger member and the dose dispensing mechanism are arranged such that, in use: the trigger member is movable relative to the housing in a first direction from an initial position to a first intermediate position to load the resilient member and to subsequently move the biasing sleeve from a first hold position to a first release position such that the biasing sleeve is moved by the resilient member in the first direction to dispense a first dose of the medicament from the medicament container, and after the first dose of the medicament has been dispensed, the trigger member is movable relative to the housing in the first direction from a second intermediate position to a final position to load the resilient member and to subsequently move the biasing sleeve from a second hold position to a second release position such that the biasing sleeve is moved by the resilient member in the first direction to dispense a second dose of the medicament from the medicament container.

[0015] In some examples, the trigger member may be axially movable relative to the housing in the first direction from the initial position to the first intermediate position and / or the trigger member may be axially movable relative to the housing in the first direction from the second intermediate position to the final position.

[0016] In some embodiments, the resilient member comprises a spring, and the trigger member is configured to load the resilient member by compressing the spring. In some embodiments, the spring is a helical compression spring.

[0017] In some embodiments, the resilient member is arranged between the trigger member and the biasing sleeve.

[0018] In some embodiments, movement of the trigger member from the first intermediate position to the second intermediate position prior to dispensing the second dose requires axial movement of the trigger member relative to the housing in a second direction that is opposite to the first direction. In some embodiments, the trigger member is biased to move from the first intermediate position to the second intermediate position by the resilient member.Attorney Docket No.: 46567-1790WO1

[0019] In some embodiments, the biasing sleeve moves from the first release position to the second hold position during movement in the first direction to dispense the first dose of the medicament.

[0020] In some embodiments, the trigger member is configured to move the biasing sleeve from the first hold position to the first release position by rotating the biasing sleeve in a first rotational direction (R1) relative to the housing.

[0021] In some embodiments, the trigger member comprises a translating engagement element configured to engage a first ramped surface of the biasing sleeve during movement of the trigger member from the initial position to the first intermediate position to rotate the biasing sleeve in the first rotational direction.

[0022] In some embodiments, the trigger member is configured to move the biasing sleeve from the second hold position to the second release position by rotating the biasing sleeve in a second rotational direction (R2) relative to the housing. In some embodiments, the second rotational direction is a rotational direction opposite to the first rotational direction.

[0023] In some embodiments, the trigger member comprises a trigger member sleeve arranged to move axially within the housing and a button portion arranged to be pushed by a user in the first direction to move the trigger member sleeve in the first direction.

[0024] In some embodiments, the trigger member sleeve comprises a trigger member track comprising: an axially-extending first track section; a circumferentially-extending second track section; and an axially-extending third track section, and wherein the housing comprises a first guide protrusion configured to: travel axially along the first track section as the trigger member moves from the initial position to the first intermediate position; travel circumferentially along the second track section as the trigger member moves from the first intermediate position to the second intermediate position; and travel axially along the third track section as the trigger member moves from the second intermediate position to the final position.

[0025] In some embodiments, the housing comprises an engaging element arranged to engage a biasing element of the trigger member sleeve when the trigger member is in the first intermediate position, such that the biasing element rotates the trigger member sleeve relative to the housing to cause the first guide protrusion to travel from the first track section to the third track section via the second track section.Attorney Docket No.: 46567-1790WO1

[0026] In some embodiments, the biasing sleeve comprises a biasing sleeve track having a first holding surface and a second holding surface, wherein the housing comprises a second guide protrusion configured to sequentially engage the first holding surface to hold the biasing sleeve in the first hold position and the second holding surface to hold the biasing sleeve in the second hold position, wherein movement of the biasing sleeve from the first hold position to the first release position disengages the second guide protrusion from the first holding surface, and wherein movement of the biasing sleeve from the second hold position to the second release position disengages the second guide protrusion from the second holding surface.

[0027] In some embodiments, the biasing sleeve is configured to receive and engage a proximal end of a plunger rod such that movement of the biasing sleeve in the first direction moves the plunger rod in the first direction to dispense the medicament.

[0028] In some embodiments, the housing comprises a pair of finger flanges.

[0029] In some embodiments, the finger flanges each extend radially outwards from an outer surface of the housing.

[0030] In some embodiments, the finger flanges are arranged approximately midway between a distal end and a proximal end of the housing.

[0031] In some embodiments, the finger flanges are arranged symmetrically about an axis (X-X) of the medicament delivery device.

[0032] In some embodiments, the housing comprises at least one window arranged such that, when the medicament container is provided in the housing, at least a portion of the medicament container is visible through the at least one window.

[0033] In some embodiments, when the medicament container is provided in the housing, the at least one window is aligned with a portion of a barrel of the medicament container such that a level of the medicament remaining in medicament container is visible.

[0034] In some embodiments, the first direction is a distal direction, the second intermediate position is proximal to the first intermediate position, and the trigger member is biased to move from the first intermediate position to the second intermediate position by the resilient member.Attorney Docket No.: 46567-1790WO1

[0035] In some embodiments, the medicament delivery device is an intranasal medicament delivery device.

[0036] 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.

[0037] 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 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.

[0038] 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.

[0039] 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.

[0040] The intranasal medicament delivery device may be an intranasal atomization delivery device.

[0041] The intranasal medicament delivery device may be configured to deliver about % of a dose to each nostril.

[0042] The intranasal medicament delivery device may be configured to deliver about 0.2mL, wherein about 0.1 mL is delivered to each nostril.

[0043] The intranasal medicament delivery device may deliver an average droplet size Dv50 of about 10-120 pm.

[0044] 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.Attorney Docket No.: 46567-1790WO1

[0045] 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.

[0046] 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).

[0047] 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.

[0048] According to one or more aspects of the present disclosure, there is provided a medicament delivery system comprising: a medicament delivery device as disclosed herein; and a medicament container. In some embodiments, the medicament container contains a medicament. The medicament may preferably be a vaccine.

[0049] In some embodiments, the medicament delivery system further comprises a medicament delivery member. In some embodiments, the medicament delivery member may be an intranasal nozzle, a hollow needle, or an oral nozzle.

[0050] The intranasal nozzle 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 delivered. The atomiser and / or outlet may comprise a luer lock to sealingly connect the atomiser to an outlet of the medicament container. In another embodiment, the outlet itself is configured to atomize the medicament.

[0051] 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.Attorney Docket No.: 46567-1790WO1

[0052] The medicament may be any medicament described herein. The medicament may be a vaccine, for example a vaccine adapted for nasal administration. The vaccine may be an RSV vaccine.

[0053] The medicament delivery system may be an intranasal medicament delivery system. The intranasal medicament delivery system may comprise an intranasal atomization delivery device.

[0054] The intranasal medicament delivery system may be configured to deliver about % of a dose to each nostril.

[0055] The intranasal medicament delivery system may be configured to deliver about 0.2mL, wherein about 0.1 mL is delivered to each nostril.

[0056] The intranasal medicament delivery system may deliver an average droplet size DV5o of about 10-120 pm.

[0057] The intranasal medicament delivery system may deliver an average droplet size DV5o 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

[0058] The intranasal medicament delivery system 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.

[0059] In some embodiments, the intranasal medicament delivery system is configured to deliver in the range of 20 to 2000 microlitres (0.02 to 2 ml) volume of medicament and, optionally, in the range of 100 to 400 microlitres (0.1 to 0.4 ml) and, optionally, in the range of 10 to 300 microlitres (0.1 to 0.3 ml) and, optionally, about 200 microlitres (0.2 ml).

[0060] In some embodiments, the intranasal medicament delivery system 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, optionally, in the range of 50 to 200 microlitres (0.05 to 0.2 ml) and, optionally, in the range of 50 to 150 microlitres (0.05 to 0.1 ml) and, optionally, about 100 microlitres (0.1 ml) of medicament to each nostril of the user.Attorney Docket No.: 46567-1790WO1

[0061] In some embodiments, the intranasal nozzle comprises first and second medicament delivery conduits.

[0062] In other embodiments, the medicament delivery device is an oral medicament delivery device or an injection medicament delivery device.

[0063] According to one or more aspects of the present disclosure, there is provided a method of using a medicament delivery device as disclosed herein, the method comprising: moving the trigger member relative to the housing in a first direction from an initial position to a first intermediate position to load the resilient member and to subsequently dispense a first dose of the medicament from the medicament container, and after the first dose of the medicament has been dispensed, moving the trigger member relative to the housing in the first direction from a second intermediate position to a final position to load the resilient member and to subsequently dispense a second dose of the medicament from the medicament container. The movement of the trigger relative to the housing in the first direction from the initial position to the first intermediate position may be an axial movement relative to the housing. The movement of the trigger relative to the housing in the first direction from the second intermediate position to the final position may be an axial movement relative to the housing.

[0064] According to one or more aspects of the present disclosure, there is provided a method of using a medicament delivery device as disclosed herein, the method comprising: moving the trigger member relative to the housing in a first direction from an initial position to a first intermediate position to load the resilient member and to subsequently move the biasing sleeve from a first hold position to a first release position such that the biasing sleeve is moved by the resilient member in the first direction to dispense a first dose of the medicament from the medicament container, and after the first dose of the medicament has been dispensed, moving the trigger member relative to the housing in the first direction from a second intermediate position to a final position to load the resilient member and to subsequently move the biasing sleeve from a second hold position to a second release position such that the biasing sleeve is moved by the resilient member in the first direction to dispense a second dose of the medicament from the medicament container. The movement of the trigger relative to the housing in the first direction from the initial position to the first intermediate position may be an axial movement relative to the housing. The movement of the trigger relative to the housing in the first direction from the second intermediate position to the final position may be an axial movement relative to the housing.Attorney Docket No.: 46567-1790WO1

[0065] In some embodiments, the resilient member comprises a spring, wherein loading the resilient member comprises compressing the spring.

[0066] In some embodiments, moving the biasing sleeve from the first hold position to the first release position comprises rotating the biasing sleeve in a first rotational direction (R1) relative to the housing.

[0067] In some embodiments, the method further comprises axially moving the biasing sleeve from the first release position to the second hold position.

[0068] In some embodiments, moving the biasing sleeve from the second hold position to the second release position comprises rotating the biasing sleeve in a second rotational direction (R2) relative to the housing.

[0069] In some embodiments, the method further comprises: applying a first actuation force to an actuation surface of a button portion of the medicament delivery device in the first direction, to cause the trigger member to move axially from the initial position to the first intermediate position.

[0070] In some embodiments, the method further comprises: applying a second actuation force to the actuation surface of the button portion in the first direction, to cause the trigger member to move axially from the second intermediate position to the final position.

[0071] In some embodiments, the method further comprises: axially moving the trigger member relative to the housing in a second direction, from the first intermediate position to the second intermediate position, the second direction being opposite to the first direction.

[0072] In some embodiments, the trigger member is axially moved from the first intermediate position to the second intermediate position by the resilient member.

[0073] In some examples, the method may be performed prior to the delivery of medicament to a patient. For example, the first dose and / or second dose may be a priming dose not delivered to a patient.

[0074] The method may comprise expelling / administering an RSV vaccine.Attorney Docket No.: 46567-1790WO1

[0075] The medicament may be expelled / delivered intranasally with about % dose delivered to each nostril.

[0076] The intranasal dose of the medicament may be delivered in about 0.2 mL, wherein about 0.1 mL is delivered to each nostril.

[0077] The method may comprise intranasal atomization delivery of an average droplet size Dv50 of about 10-120 pm.

[0078] 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.

[0079] 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 pLto about 115 pL.

[0080] In some embodiments, the method comprises removing the medicament delivery device from a sealed pack.

[0081] In some embodiments, the method comprises coupling a medicament delivery member to the medicament container. The medicament delivery member may comprise a needle or an intranasal nozzle. In some embodiments, the method comprises removing the medicament delivery member from a sealed pack and coupling the medicament delivery member to the medicament container.

[0082] In some embodiments, the method comprises drawing medicament into the medicament container.

[0083] In some embodiments, the method comprises expelling medicament from the medicament container for delivery to a user.

[0084] In some embodiments, the method is performed as part of a priming operation of the medicament delivery device, and the first dose and the second dose are priming doses not delivered to a patient.Attorney Docket No.: 46567-1790WO1

[0085] BRIEF DESCRIPTION OF THE DRAWINGS

[0086] Embodiments will now be described, by way of example only, with reference to the accompanying drawings, in which:

[0087] Fig. 1 is a perspective view of a medicament delivery system according to an exemplary embodiment of the present disclosure;

[0088] Fig. 2 is an exploded side-view showing components of a medicament delivery device and a medicament container of the medicament delivery system of Fig. 1 ;

[0089] Fig. 3A is side-view of a housing of the medicament delivery device of Fig. 2;

[0090] Fig. 3B is a perspective view of a proximal end of the housing of Fig. 3A;

[0091] Fig. 4A is perspective side-view of a trigger member of the medicament delivery device of Fig. 2;

[0092] Fig. 4E3 is a perspective end-view of a distal end of the trigger member of Fig. 4A;

[0093] Fig. 5A is a perspective side-view of a dose dispensing mechanism of the medicament delivery device of Fig. 2, showing a biasing sleeve and a resilient member;

[0094] Fig. 5E3 is perspective end-view of a distal end of the dose dispensing mechanism of Fig. 5A; Fig. 6A is a longitudinal cross-section of the medicament delivery system of Fig. 1 , when the medicament delivery device is in a first configuration;

[0095] Fig. 6E3 is another longitudinal cross-section of the medicament delivery system of Fig. 1 , when the medicament delivery device is in the first configuration;

[0096] Fig. 7 A is a detailed side-view of a portion of the medicament delivery system of Fig. 1 , showing relative positions of the trigger member and the housing when the medicament delivery device is in the first configuration;

[0097] Fig. 7E3 is a detailed side-view of a portion of the medicament delivery system of Fig. 1 , showing relative positions of the housing and the biasing sleeve when the medicament delivery device is in the first configuration;

[0098] Fig. 8 is a longitudinal cross-section of the medicament delivery system of Fig. 6E3, when the medicament delivery device is in a second configuration;

[0099] Fig. 9A is a detailed side-view of a portion of the medicament delivery system of Fig. 1 , showing relative positions of the trigger member and the housing as the medicament delivery device is moved from the first configuration towards the second configuration; Fig. 9E3 is a detailed side-view of a portion of the medicament delivery system of Fig. 1 , showing relative positions of the housing and the biasing sleeve as the medicament delivery device is moved from the first configuration towards the second configuration;

[0100] Fig. 9C is a detailed side-view of a portion of the medicament delivery system of Fig. 1 , showing relative positions of the housing and the biasing sleeve when the medicament delivery device is in the second configuration;Attorney Docket No.: 46567-1790WO1

[0101] Fig. 10A is a detailed side-view of a portion of the medicament delivery system of Fig. 1 , showing relative positions of the trigger member and the housing when the medicament delivery device is in a third configuration;

[0102] Fig. 10B is a detailed side-view of a portion of the medicament delivery system of Fig. 1 , showing relative positions of the housing and the biasing sleeve when the biasing sleeve has moved distally to dispense a first dose of medicament;

[0103] Fig. 11 is a longitudinal cross-section of the medicament delivery system of Fig. 1, when the medicament delivery device is in the third configuration, after a first dose of medicament has been dispensed;

[0104] Fig. 12A is a detailed side-view of a portion of the medicament delivery system of Fig. 1 , showing relative positions of the trigger member and the housing after the medicament delivery device has moved from the third configuration into a fourth configuration;

[0105] Fig. 12B is a detailed side-view of a portion of the medicament delivery system of Fig. 1 , showing relative positions of the housing and the biasing sleeve as the medicament delivery device is moved from the third configuration towards the fourth configuration;

[0106] Fig. 12C is a detailed side-view of a portion of the medicament delivery system of Fig. 1, showing relative positions of the housing and the biasing sleeve when the medicament delivery device is in the fourth configuration;

[0107] Fig. 13A is a side-view of the medicament delivery system of Fig. 1 , when the medicament delivery device is in the first configuration prior to dispensing the medicament;

[0108] Fig. 13B is a side-view of the medicament delivery system of Fig. 1 , when the medicament delivery device is in the second configuration, after a first dose of the medicament has been dispensed;

[0109] Fig. 13C is a side-view of the medicament delivery system of Fig. 1 , when the medicament delivery device is in the third configuration, prior to dispensing a second dose of the medicament;

[0110] Fig. 13D is a side-view of the medicament delivery system of Fig. 1 , when the medicament delivery device is in the fourth configuration, after the second dose of the medicament has been dispensed;

[0111] Fig. 14 is a block diagram illustrating a method of operating a medicament delivery device according to an exemplary embodiment of the present disclosure;

[0112] Fig. 15A is a perspective view of an alternative medicament delivery member taking the form of a dual nozzle atomizer;

[0113] Fig. 15B is a perspective view of a medicament delivery system comprising the dual nozzle atomizer of Fig. 15A;

[0114] Fig. 16A is a perspective view of an alternative medicament delivery member taking the form of a hollow needle; andAttorney Docket No.: 46567-1790WO1

[0115] Fig. 16B is a perspective view of a medicament delivery system comprising the hollow needle of Fig. 16A.

[0116] DETAILED DESCRIPTION

[0117] 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 subcutaneous, intramuscular, intravenous or the delivery could be to the mouth or nasal structures. Such a device could be operated by a patient or caregiver, such as a nurse or physician, and can include various types of safety syringe, pen-injector, or auto-injector. The device can include a cartridge-based system that requires piercing a sealed ampule before use. Volumes of medicament delivered with these various devices can range from about 0.5 ml to about 2 ml.

[0118] 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). 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.

[0119] 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.

[0120] The one or more automated functions of the drug delivery device 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 oneAttorney Docket No.: 46567-1790WO1

[0121] 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.

[0122] In addition, activation of one automated function may activate one or more subsequent automated functions, thereby forming an activation sequence. For example, activation of a first automated function may activate at least two of needle insertion, medicament injection, and needle retraction. Some devices may also require a specific sequence of steps to cause the one or more automated functions to occur. Other devices may operate with a sequence of independent steps.

[0123] Some delivery devices can include one or more functions of a safety syringe, pen-injector, or auto-injector. For example, a delivery device could include a mechanical energy source configured to automatically inject a medicament (as typically found in an auto-injector) and a dose setting mechanism (as typically found in a pen-injector).

[0124] The present disclosure relates to a medicament delivery device 100, and to a medicament delivery system 1000 comprising the medicament delivery device 100 and a medicament container 200 for use with the medicament delivery device 100. The medicament delivery device 100 may be reusable or single-use. The medicament container 200 may take the form of a syringe, for example.

[0125] 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 medicament delivery device 100 or the medicament container 200. 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 patient’s nose when the medicament is delivered intranasally, or the patient’s mouth when the medicament is delivered orally).

[0126] Fig. 1 shows the medicament delivery system 1000 comprising the medicament delivery device 100 and a medicament container 200 provided within the medicament delivery device 100. The medicament delivery device 100 is herein referred to simply as the ‘device 100’ for brevity.Attorney Docket No.: 46567-1790WO1

[0127] Fig. 2 is an exploded view of the medicament delivery system 1000, wherein the medicament container 200 and various components of the device 100 have been separated along the device axis X-X. Fig. 1 shows the components of the medicament delivery system 1000 assembled, ready for use.

[0128] As shown in Figs. 1 and 2, the device 100 comprises a housing 110, a dose dispensing mechanism 120 and a trigger member 130, each extending along the device axis X-X.

[0129] The trigger member 130 is axially movable relative to the housing 110 along the device axis X-X. To operate the device 100, the trigger member 130 is configured to be moved distally by a user relative to the housing 110 in the distal direction A1 with a first axial movement, to dispense a first dose of a medicament 220 contained within the medicament container 200. Subsequent to the first dose being delivered, the trigger member 130 is configured to be moved by the user again in the distal direction A1 relative to the housing 110 with a second axial movement, to dispense a second dose of the medicament 220 contained within the medicament container 200. Operation of the device 100 for dispensing the first and second doses of medicament 220 is described in more detail later, in relation to Figs. 6A to 14.

[0130] As shown in Figs. 1 and 2, the housing 110 is configured to contain the medicament container 200 such that the medicament container 200 extends along the device axis X-X. The medicament container 200 comprises a barrel 210, the interior of which defines a reservoir 211 for containing the medicament 220 to be administered to a patient. The housing 110 is configured to retain the medicament container 200 such that the barrel 210 is axially fixed relative to the housing 110. That is, axial movement of the barrel 210 along the device axis X-X relative to the housing 110 is inhibited when the medicament container 200 is retained in the housing 110.

[0131] The medicament container 200 may further comprise a plunger rod 230 arranged to extend through an opening 2100 at a proximal end 2101 of the barrel 210, and an outlet 240 arranged at a distal end 2102 of the barrel 210. The plunger rod 230 extends along the device axis X-X and is axially movable within the reservoir 211 of the barrel 210 such that a distal movement of the plunger rod 230 relative to the barrel 210 (i.e., a movement of the plunger rod 230 in the distal direction A1 relative to the barrel 210) causes at least a portion of the medicament 220 to be dispensed from the barrel 210, via the outlet 240. However, it should be understood that in some examples the plunger rod 230 may form part of the device 100 rather than the medicament container 200.Attorney Docket No.: 46567-1790WO1

[0132] In some examples, a plunger rod flange 260 may be arranged at a proximal end 231 of the plunger rod 230 to assist with distal movement of the plunger rod 230, the plunger rod flange 260 extending radially outwards from the plunger rod 230, away from the device axis X-X.

[0133] When the system 1000 is assembled as shown in Fig. 1, the medicament container 200 is arranged within the housing 110 such that the medicament 220 is dispensed from the medicament container 200 via an opening 115 in the housing 110 that is arranged at a distal end 118 of the housing 110.

[0134] Figs. 1 and 2 show a medicament delivery member 250 in the form of an intranasal nozzle coupled to the distal end 2102 of the barrel 210.

[0135] In some embodiments, the intranasal nozzle comprises one or more medicament delivery conduits 2501. In some embodiments, each medicament delivery conduit 2501 comprises a respective nozzle outlet 2501 A, which may be configured to promote a spray of medicament as it is expelled from the respective conduit 2501. Each nozzle outlet 2501 A may be configured to atomize the medicament.

[0136] In the present example, the intranasal nozzle comprises a single medicament delivery conduit 2501 for delivering medicament to a nostril of a user.

[0137] When coupled, the medicament delivery member 250 is in fluid communication with the reservoir 211 of the barrel 210, via the outlet 240 (and optionally a valve), such that distal movement of the plunger rod 230 in the distal direction A1 relative to the barrel 210 causes at least a portion of the medicament 220 to be dispensed from the barrel 210 via the outlet 240 and via the medicament delivery member 250.

[0138] Fig. 1 shows the medicament container 200 arranged within the housing 110 such that the medicament delivery member 250 extends through the opening 115 in the housing 110, with a distal end 251 of the medicament delivery member 250 arranged distal to the opening 115 in the housing 110. However, it should be understood that this is not meant to be limiting and that in one or more other examples the medicament delivery member 250 does not extend through the opening 115 in the housing 110, and the distal end 251 of the medicament delivery member 250 is not distal to the opening 115.

[0139] In one or more examples, the medicament delivery member 250 may be permanently coupled to the medicament container 200 (e.g., the medicament delivery member 250 mayAttorney Docket No.: 46567-1790WO1

[0140] be integrally formed with the medicament container 200). Alternatively, in one or more other examples, the medicament delivery member 250 may be releasably couplable to the medicament container 200 such that the medicament delivery member 250 may be coupled and uncoupled from the medicament container 200. For instance, the medicament delivery member 250 may be releasably couplable such that it can be replaced with a new medicament delivery member 250 between the dispensing of each dose of medicament 220 using the device 100.

[0141] A user may couple and / or uncouple the medicament delivery member 250 to the medicament container 200 via the opening 105 of the housing 110. The medicament delivery member 250 may be couplable to the medicament container 200 via any suitable coupling interface arranged between the medicament delivery member 250 and the medicament container 200, such as a Luer lock coupling interface, a Luerslip coupling interface, a bayonet coupling interface, an adhesive coupling interface, or the like. In some examples, the medicament delivery member 250 may be couplable to the medicament container 200 only once (i.e., once the medicament delivery member 250 has been coupled to the medicament container 200, it cannot be uncoupled from the medicament container 200).

[0142] Fig. 15A shows an alternative medicament delivery member 250’ suitable for use with one or more embodiments of the present disclosure. Similar to the medicament delivery member 250, the medicament delivery member 250’ takes the form of an intranasal nozzle, however the intranasal nozzle 250’ comprises first and second medicament delivery conduits 2501 , 250T comprising respective nozzle outlets 2501 A, 2501 A’, for delivering medicament to the respective nostrils of a user. The medicament delivery member 250’ may be known as a dual nozzle atomizer.

[0143] Fig. 15B shows a medicament delivery system 1000’ which may be similar or identical to the medicament delivery system 1000, comprising a medicament delivery device 100 and a medicament container 200 provided within the medicament delivery device 100. However, the medicament delivery system 1000’ comprises the medicament delivery member 250’ coupled to the medicament container 200, rather than the medicament delivery member 250. medicament delivery member 250. The first and second medicament delivery conduits 2501 , 2501 ’ extend through the opening 115. The medicament delivery member 250’ may allow medicament to be delivered to the respective nostrils of a user simultaneously.

[0144] Fig. 16A shows another alternative medicament delivery member 250” suitable for use with one or more embodiments of the present disclosure. In this example, the medicamentAttorney Docket No.: 46567-1790WO1

[0145] delivery member 250” comprises a hollow needle 2502 for delivering medicament to the user, for example subcutaneously, intramuscularly or intravenously.

[0146] Fig. 16B shows a medicament delivery system 1000” which may be similar or identical to the medicament delivery system 1000 and / or the medicament delivery system 1000’, comprising a medicament delivery device 100 and a medicament container 200 provided within the medicament delivery device 100. However, the medicament delivery system 1000” comprises the medicament delivery member 250” coupled to the medicament container 200, rather than the medicament delivery member 250 or the medicament delivery member 250’. The hollow needle 2502 extends through the opening 115.

[0147] In examples in which the medicament delivery member 250, 250’ takes the form of an intranasal nozzle (e.g., an intranasal atomization nozzle, for atomising the medicament as it is dispensed), the device 100 may be, for example, an intranasal medicament delivery device (e.g., an intranasal atomization device) and the system 1000, 1000’ may be an intranasal medicament delivery system (e.g., an intranasal atomization system). In some examples, where the medicament delivery member 250” comprises a hollow needle 2502, the medicament delivery device 100 may be, for example, an injector device and the system 1000” may be an injector system. However, it should be recognised that in other examples the medicament delivery member 250 may take a different form than an intranasal nozzle or a hollow needle. For example, the medicament delivery member 250 may instead comprise an oral nozzle. Where the medicament delivery member 250 takes the form of an oral nozzle, the medicament delivery device 100 may be, for example, an oral medicament delivery device such as an inhalerand the system 1000 may be an oral medicament delivery system.

[0148] The dose dispensing mechanism 120 shown in Fig. 2 is operable to cause a first dose of the medicament 220 and a second dose of the medicament 220 to be dispensed from the medicament container 200. As shown in Fig. 2, the dose dispensing mechanism 120 comprises a biasing sleeve 121 and a resilient member 122. The resilient member 122 is arranged proximal to the biasing sleeve 121 along the device axis X-X, extending proximally from a proximal end 1211 of the biasing sleeve 121.

[0149] The biasing sleeve 121 has a substantially cylindrical form and extends along the device axis X-X such that it surrounds the axis X-X, with at least a distal portion 1213 of the biasing sleeve 121 arranged to extend distally within the housing 110 when the device 100 is assembled for use.Attorney Docket No.: 46567-1790WO1

[0150] The biasing sleeve 121 may be configured to receive at least a proximal end of the medicament container 200 through an opening 1215 at the distal end 1212 of the biasing sleeve 121, such that the proximal end of the medicament container 200 extends proximal to the distal end 1212 of the biasing sleeve 121 and the biasing sleeve 121 surrounds the proximal end of the medicament container 200. More particularly, in use, the biasing sleeve 121 may be configured to receive at least a proximal end 231 of the plunger rod 230 through the opening 1215 at the distal end 1212 of the biasing sleeve 121 , such that the proximal end 231 of the plunger rod 230 extends proximal to the distal end 1212 of the biasing sleeve 121 and such that the biasing sleeve 121 surrounds the at least proximal end 231 of the plunger rod 230. The biasing sleeve 121 is configured to engage the proximal end 231 of the plunger rod 230 such that an axial movement of the biasing sleeve 121 in the distal direction A1 moves the plunger rod 230 in the distal direction A1 due to engagement between the biasing sleeve 121 and the plunger rod 230, for dispensing a dose of the medicament 220.

[0151] As shown in Fig. 2, the resilient member 122 may take the form of a spring, in this example a helical compression spring. The resilient member 122 extends along the device axis X-X, and is arranged proximal to the biasing sleeve 121. That is, the resilient member 122 is arranged at the proximal end 1211 of the biasing sleeve 121 and extends in a proximal direction A2 from the proximal end of the biasing sleeve 121. The resilient member 122 is configured to exert a biasing force on the biasing sleeve 121 to dispense a dose of medicament.

[0152] As shown in Fig. 2, the resilient member 122 may be coupled to the biasing sleeve 121. For example, the resilient member 122 may be integrally formed with the biasing sleeve 121. However, it should be understood that this is not meant to be limiting and that in other examples the resilient member 122 may not be coupled to or integrally formed with the biasing sleeve 121. For example, the resilient member 122 may be disengaged from the biasing sleeve 121 in an initial state but may be moved into engagement with the biasing sleeve 121 during distal movement of the resilient member 122 in the distal direction A1 relative to the biasing sleeve 121 (e.g., a distal end 1221 of the resilient member 122 may be configured to move into engagement with the proximal end 1211 of the biasing sleeve 121).

[0153] The resilient member 122 is configured to be loaded (or ‘primed’) by compressing the resilient member 122 to store potential energy in the resilient member 122. The resilient member 122 is compressed by axial movement of the trigger member 130 in the distal direction A1 relative to the housing 110, as described later in relation to Fig. 8. As the resilient member 122 is loaded by compression, an increasing biasing force is exerted on theAttorney Docket No.: 46567-1790WO1

[0154] biasing sleeve 121 by the resilient member 122, which biases the biasing sleeve 121 in the distal direction A1. When the resilient member 122 is released after being loaded, the stored potential energy and the biasing force provided by the resilient member 122 move the biasing sleeve 121 in the distal direction A1. Movement of the biasing sleeve 121 in the distal direction A1 in turn moves the plunger rod 230 of the medicament container 200 in the distal direction A1 due to engagement between the biasing sleeve 121 and the plunger rod 230, to dispense a dose of the medicament 220.

[0155] It should be understood that the resilient member 122 taking the form of a helical compression spring is provided by way of example only, and that in one or more other examples the resilient member 122 may take the form of a spring other than a helical compression spring, such as, but not limited to, a wave spring, a leaf spring or a rubber spring. In other examples, the resilient member 122 may take a form otherthan a spring, for example, but not limited to, a pneumatic system, a hydraulic system or a memory foam arrangement.

[0156] As shown in Figs. 1 and 2, the trigger member 130 is arranged along the device axis X-X. When the device 100 is assembled for use, at least a distal portion 1301 of the trigger member 130 extends within the housing 110 and at least a proximal portion 1302 of the trigger member 130 extend proximally from the proximal end 119 of the housing 110, through the opening 1191 at the proximal end 119 of the housing 110.

[0157] The trigger member 130 is axially movable relative to the housing 110 along the device axis X-X to cause a plurality of discrete doses of the medicament 220 to be dispensed, as described later in relation to Figs. 6A to 13D.

[0158] The trigger member 130 comprises a trigger member sleeve 131, and a button portion 132 coupled to the trigger member sleeve 131. The trigger member sleeve 131 and the button portion 132 are arranged along the device axis X-X such that the button portion 132 is proximal to the trigger member sleeve 131. That is, the button portion 132 is arranged at a proximal end 1311 of the trigger member sleeve 131 and extends proximally from the proximal end 1311 of the trigger member sleeve 131.

[0159] The trigger member sleeve 131 has a substantially cylindrical form and is arranged coaxially along the device axis X-X with the dose dispensing mechanism 120. The trigger member sleeve 131 is configured to receive at least a portion of the biasing sleeve 121 through an opening 1310 at a distal end 1312 of the trigger member sleeve 131 when the system 1000Attorney Docket No.: 46567-1790WO1

[0160] is assembled for use, such that the trigger member sleeve 131 and the biasing sleeve 121 are coaxial along the device axis X-X and the trigger member sleeve 131 surrounds the portion of the biasing sleeve 121 , as described later in relation to Fig. 6A.

[0161] The trigger member 130 is also configured to retain the resilient member 122 such that the resilient member 122 is arranged between the trigger member 130 and the biasing sleeve 121 , within the button portion 132, as described later in relation to Fig. 6A.

[0162] The button portion 132 of the trigger member 130 extends through the opening 1191 arranged at the proximal end 119 of the housing 110 such that at least a proximal portion of the button portion 132 is proximal to the proximal end 119 of the housing 110. The button portion 132 is arranged to extend proximally from the proximal end 119 of the housing 110 such that the button portion 132 is accessible to the user and may be actuated by a finger or thumb of a user. More particularly, a proximally-facing actuation surface 133 may be provided at a proximal end 1321 of the button portion 132, the actuation surface 133 configured to be directly pressed by a finger of thumb of the user to actuate the trigger member 130, for causing the trigger member 130 to move distally along the device axis X-X relative to the housing 110 in the distal direction A1 to dispense doses of medicament 220.

[0163] As shown in Figs. 1 and 2, the housing 110 comprises a pair of finger flanges 114a, 114b that each extend radially outwards from an outer surface 117 of the housing 110. The finger flanges 114a, 114b are configured to assist a user in moving the trigger member 130 relative to the housing 110 to dispense a dose of medicament 220. For example, the finger flanges 114a, 114b may be arranged to be engaged by respective fingers of the user while a thumb or finger of the user simultaneously engages and pushes the actuation surface 133 of the trigger member 130 relative to the housing 110.

[0164] Although Figs. 1 and 2 show the housing 110 comprising two finger flanges 114a, 114b, it should be understood that this is not meant to be limiting and that in other examples the housing 110 may have no finger flanges, a single finger flange, three finger flanges, or greater than three finger flanges. Furthermore, although Figs. 1 and 2 show the pair of finger flanges 114a, 114b arranged approximately midway between the distal end 118 and the proximal end 119 of the housing 110 and arranged symmetrically about the device axis X-X, it should be understood that this is not meant to be limiting and that in other examples the finger flange(s), where present, may be arranged at locations of the housing 110 different than those shown in Figs. 1 and 2 (for example adjacent the proximal end 119 of theAttorney Docket No.: 46567-1790WO1

[0165] housing, adjacent the distal end 118 of the housing 110, and / or non-symmetrically about the device axis X-X, etc.).

[0166] As shown in Figs. 1 and 2, the housing 110 further comprises a pair of windows 116a, 116b arranged such that at least a portion of the medicament container 200 may be visible to the user through the windows 116a, 116b when the medicament container 200 is provided in the housing 110. For example, where the windows 116a, 116b are aligned with a portion of the barrel 210 of the medicament container 200 that is transparent or translucent, the user may be able to view the reservoir 211 of the barrel 210 through each of the windows 116a, 116b, for example to determine a level of medicament 220 remaining in the reservoir 211.

[0167] Although Figs. 1 and 2 show the housing 110 comprising two windows 116a, 116b, it should be understood that this is not meant to be limiting and that in other examples the housing 110 may have no windows, a single window, three windows, or greater than three windows. Furthermore, although Figs. 1 and 2 show the windows 116a, 116b arranged adjacent the distal end 118 of the housing and arranged symmetrically about the device axis X-X, it should be understood that this is not meant to be limiting and that in other examples the window(s), where present, may be arranged at locations of the housing 110 different than those shown in Figs. 1 and 2 (for example at a midpoint of the housing 110, adjacent the proximal end 119 of the housing 110, and / or non-symmetrically about the device axis X-X, etc.).

[0168] Figs. 3A and 3B show the housing 110 in isolation from the remainder of the device 100. Fig.

[0169] 3A shows a perspective side-view of the housing 110, while Fig. 3E3 shows a perspective end-view of the housing 110 when viewing the proximal end 119 of the housing 110 in an approximately distal direction.

[0170] As shown in Figs. 3A and 3E3, the housing 110 comprises a substantially cylindrical outer wall 111 and a substantially cylindrical inner wall 112, both arranged to extend along the device axis X-X. The outer wall 111 and the inner wall 112 are arranged coaxially along the device axis X-X, with the inner wall 112 extending coaxially within the outer wall 111 such that it is surrounded by the outer wall 111. The outer wall 111 and the inner wall 112 may be integrally formed. The inner wall 112 may be coupled to the outer wall 111 adjacent a distal end of the inner wall 112.

[0171] The inner wall 112 and the outer wall 111 are arranged such that an annular chamber 310 is formed therebetween, the annular chamber 310 formed between an inner surface 311 of theAttorney Docket No.: 46567-1790WO1

[0172] outer wall 111 and an outer surface 312 of the inner wall 112. The annular chamber 310 is open at a proximal end. The annular chamber 310 is configured to receive the biasing sleeve 121 and the trigger member sleeve 131 through its open proximal end such that the biasing sleeve 121 and the trigger member sleeve 131 extend into the housing 110 and are arranged between the inner wall 112 and the outer wall 111 , in the annular chamber 310.

[0173] A circumferential inner surface 313 of the inner wall 112 forms a cavity 314 for receiving the medicament container 200 when the system 1000 is assembled for use. As shown in Fig.

[0174] 3B, the housing 110 further comprises a medicament container holding arrangement 320 for holding the medicament container 200 within the cavity 314, and in particular for holding the barrel 210 of the medicament container 200 in a fixed axial position relative to the housing 110. In this example, the medicament container holding arrangement 320 comprises a plurality of medicament container engagement elements 315a-d (e.g., a plurality of ribs) arranged around the device axis X-X and each projecting radially inwards from the inner surface 313 of the inner wall 112, into the cavity 314. Each medicament container engagement element 315a-d is configured to engage the medicament container 200 (e.g., the barrel 210 of the medicament container 200) to hold the barrel 210 in a fixed axial (and, in some instances, radial) position within the housing 110.

[0175] Fig. 3E3 shows four medicament container engagement elements 315a-d, however this number of medicament container engagement elements 315a-d is not meant to be limiting and it should be understood that in other examples the medicament container holding arrangement 320 may instead comprise one, two, three, five or more medicament container engagement elements. Additionally / alternatively, the medicament container engagement element(s) 315a-d may take a different form to the rib-like forms shown in Fig. 3E3.

[0176] As shown in Fig. 3E3, the housing 110 further comprises a first guide protrusion 341 , a second guide protrusion 342 and an engaging element 351, the purpose of which are described later in more detail in relation to Figs. 6A to 12C.

[0177] The first guide protrusion 341 projects radially inwards from the inner surface 311 of the outer wall 111 and is configured to be received within the trigger member sleeve 131 when the device 100 is assembled, as later described in relation to Fig. 7 A.

[0178] The second guide protrusion 342 projects radially outwards from the outer surface 312 of the inner wall 112 and is configured to be received within the biasing sleeve 121 when the device 100 is assembled, as later described in relation to Fig. 7E3.Attorney Docket No.: 46567-1790WO1

[0179] The engaging element 351 projects radially inwards from the inner surface 311 of the outer wall 111 and is configured to engage the trigger member sleeve 131 when the device 100 is assembled, as later described in relation to Fig. 9A. Fig. 3B shows the engaging element 351 taking the form of a rib that extends longitudinally along the inner surface 311 of the outer wall 111 , substantially parallel to the device axis X-X, however it should be understood that this is not meant to be limiting and that in other examples the engaging element 351 may take a different form than a rib. The engaging element 351 is arranged at the inner surface 311 of the outer wall 111 such that it is spaced from the first guide protrusion 341 in a circumferential direction along the inner surface 311 .

[0180] Figs. 4A and 4E3 show the trigger member 130 in isolation from the remainder of the device 100. Fig. 4A shows a perspective side-view of the trigger member 130, while Fig. 4E3 shows a perspective end-view of the trigger member 130, viewing the trigger member 130 in an approximately proximal direction.

[0181] As shown in Figs. 4A and 4E3, the trigger member 130 comprises a trigger member track 410 arranged at the trigger member sleeve 131 . The trigger member track 410 is arranged at an outer surface 421 of the trigger member sleeve 131 and extends substantially axially along the trigger member sleeve 131 , substantially parallel to the device axis X-X. The trigger member track 410 is configured to receive the first guide protrusion 341 of the housing 110, as described later in relation to Fig. 7 A.

[0182] Figs. 4A and 4E3 show the trigger member track 410 taking the form of a cutout in the trigger member sleeve 131 that extends from an outer surface 421 of the trigger member sleeve 131 through to an inner surface 422 of the trigger member sleeve 131. However, it should be understood that this is not meant to be limiting and that in one or more other examples the trigger member track 410 may be arranged at the outer surface 421 of the trigger member sleeve 131 without extending through to the inner surface 422 of the trigger member sleeve 131 (e.g., the trigger member track 410 may be formed as a groove in the outer surface 421 of the trigger member sleeve 131).

[0183] As shown in Figs. 4A and 4E3, the trigger member track 410 comprises an axially-extending first track section 411 , a circumferentially-extending second track section 412, and an axially-extending third track section 413, together forming the ‘z-shaped’ trigger member track 410. The first track section 411 , second track section 412 and third track section 413 are arranged end-to-end such that the first guide protrusion 341 of the housing 110 canAttorney Docket No.: 46567-1790WO1

[0184] travel from the first track section 411 to the third track section 413, via the second track section 412.

[0185] The first track section 411 extends substantially axially along the outer surface 421 of the trigger member sleeve 131 , substantially parallel to the device axis X-X, for guiding the first guide protrusion 341 of the housing 110 to travel axially along the first track section 411 as the trigger member 130 moves in the distal direction A1 relative to the housing 110, as later described in relation Fig. 9A. The first guide protrusion is guided to travel from a distal end 4111 of the first track section 411 to a proximal end 4112 of the first track section 411.

[0186] The second track section 412 is arranged at the proximal end 4112 of the first track section 411 and extends circumferentially around the trigger member sleeve 131 from the proximal end 4112 of the first track section 411 , for guiding the first guide protrusion 341 of the housing 110 to travel circumferentially along the second track section 412, from the proximal end 4112 of the first track section 411 to a distal end 4131 of the third track section 413, as later described in relation to Fig. 10A.

[0187] The third track section 413 is arranged at an opposite end of the second track section 412 to the first track section 411 and extends substantially axially along the trigger member sleeve 131 , substantially parallel to the device axis X-X, for guiding the first guide protrusion 341 to travel axially along the third track section 413 from the distal end 4131 of the third track section 413 to the proximal end 4132 of the third track section 413 as the trigger member 130 moves in the distal direction A1 relative to the housing 110, as later described in relation Fig. 12A. As shown in Figs. 4A and 4B, the third track section 413 is circumferentially offset from the first track section 411 around the outer surface 421 of the trigger member sleeve 131 such that the third track section 413 extends substantially along an axis that is parallel to, but separated from in a circumferential direction, the axis along which the first track section 411 substantially extends.

[0188] As shown in Figs. 4A and 4E3, the trigger member track 410 comprises a non-return mechanism 430. The non-return mechanism 430 is arranged to inhibit distal movement of the first guide protrusion 341 relative to the trigger member 130 once the first guide protrusion 341 has travelled proximally along the first track section 411 from the distal end 4111 of the first track section 411 to the proximal end 4112 of the first track section 411 , as later described in relation to Figs. 9A and 10A.Attorney Docket No.: 46567-1790WO1

[0189] Figs. 4A and 4B show an ‘L-shaped’ non-return-mechanism 430 comprising a first arm 431 having a distally-facing surface 4311 and a second arm 432 having a proximally-facing surface 4321. The first arm 431 extends at least partially into the first track section 411 such that it can be engaged by the first guide protrusion 341 during proximal movement of the first guide protrusion 341 along the first track section 411. A distal end of the first arm 431 is coupled to the trigger member sleeve 131 while a proximal end of the first arm 431 extends at least partially across the first track section 411. A first end of the second arm 432 extends from the proximal end of the first arm 431 in a substantially circumferential direction such that a second, free end of the second arm 432 is extends into the second track section 412. The non-return mechanism 430 is resilient such that it is reversibly movable between a blocking configuration as shown in Fig. 4A and a passing configuration as shown in Fig. 9A. The non-return mechanism 430 may move from the blocking configuration to the passing configuration by pivoting relative to the trigger member sleeve 131. For example, the first arm 431 may be pivotably coupled to the trigger member sleeve 131 such that the first arm 431 and the second arm 432 may pivot relative to the trigger member sleeve 131.

[0190] The trigger member 130 comprises a channel 440 that extends axially along the outer surface 421 of the trigger member sleeve 131 , substantially parallel to the device axis X-X. The channel 440 is configured to receive and guide the engaging element 351 of the housing 110 during axial movement of the trigger member 130 relative to the housing 110, as described later in relation to Figs. 7 A and 9A.

[0191] The trigger member 130 further comprises a resilient biasing element 442 for rotating the trigger member sleeve 131 relative to the housing 110, as later described in relation to Figs.

[0192] 9A and 10A. The biasing element 442 is configured to be engaged by the engaging element 351 of the housing 110, to bias the trigger member 130 to rotate relative to the housing 110 about the device axis X-X. Figs. 4A and 4B show the biasing element 442 taking the form of a circumferentially-extending flexible arm. A coupling end 4421 of the flexible arm is coupled to the trigger member sleeve 131 while an opposite, free end 4422 of the flexible arm extends into the channel 440 such that it is engageable by the engaging element 351 as the engaging element 351 slides along the channel 440 in the proximal direction A2.

[0193] As shown in Fig. 4B, the trigger member 130 further comprises a translating engagement element 450 arranged at the inner surface 422 of the trigger member sleeve 131 , the translating engagement element 450 projecting radially inwards from the inner surface 422 of the trigger member sleeve 131. Fig. 4B shows the translating engagement element 450 taking the form of a rib extending axially along the inner surface 422 of the trigger memberAttorney Docket No.: 46567-1790WO1

[0194] sleeve 131 , however it should be understood that this is not meant to be limiting and that in other examples the translating engagement element 450 may take a form other than a rib. The translating engagement element 450 is configured to rotate the biasing sleeve 121 during distal axial movement of the trigger member sleeve 131 relative to the biasing sleeve 121 , as described later in relation to Figs. 9B and 9C.

[0195] Fig. 4E3 shows the translating engagement element 450 comprising a first distally-facing ramped surface 451 and a second distally-facing ramped surface 452, both arranged at a distal end 4501 of the translating engagement element 450. The first distally-facing ramped surface 451 and the second distally-facing ramped surface 452 each extend obliquely to the device axis X-X. The first distally-facing ramped surface 451 and the second distally-facing ramped surface 452 each face in a distal direction, however they face away from each other, in opposing directions about an axis parallel to the device axis X-X.

[0196] As shown in Figs. 4A and 4E3, the trigger member 130 further comprises an initial retaining element 480 (e.g., a clip) and a final retaining element 490 (e.g., a clip). The initial retaining element 480 is arranged at the first track section 411 to retain the first guide protrusion 341 of the housing at the distal end 4111 of the first track section 411 , as later described in relation to Fig. 7A. The final retaining element 490 is arranged at the third track section 413 to retain the first guide protrusion 341 of the housing at the proximal end 4132 of the third track section 413, as later described in relation to Fig. 12A.

[0197] Figs. 5A and 5E3 show the dose dispensing mechanism 120 in isolation from the remainder of the device 100. Fig. 5A shows a perspective side-view of the dose dispensing mechanism 120, while Fig. 5E3 shows a perspective end-view of the dose dispensing mechanism 120, viewing a distal end of the dose dispensing mechanism 120 in an approximately proximal direction.

[0198] As shown in Figs. 5A and 5E3, the dose dispensing mechanism 120 comprises a biasing sleeve track 510 formed at the biasing sleeve 121 . The biasing sleeve track 510 is formed at an inner surface 522 of the biasing sleeve 121 and extends substantially axially along the biasing sleeve 121 , substantially parallel to the device axis X-X. The biasing sleeve track 510 is configured to receive the second guide protrusion 342 of the housing 110, as described later in relation to Fig. 7E3.

[0199] Figs. 5A and 5E3 show the biasing sleeve track 510 taking the form of a cutout in the biasing sleeve 121 , extending from an outer surface 521 of the biasing sleeve 121 through to theAttorney Docket No.: 46567-1790WO1

[0200] inner surface 522 of the biasing sleeve 121. However, it should be understood that this is not meant to be limiting and that in one or more other examples the biasing sleeve track 510 may be arranged at the inner surface 522 of the biasing sleeve 121 without extending through to the outer surface 521 of the biasing sleeve 121 (i.e., not as a cutout in the biasing sleeve 121). For example, the biasing sleeve track 510 may take the form of a groove formed in the inner surface 522 of the biasing sleeve 121.

[0201] As shown in Figs. 5A and 5B, the biasing sleeve track 510 comprises a circumferentially-extending first track section 511 , an axially-extending second track section 512, a circumferentially-extending third track section 513 and an axially-extending fourth track section 514. The first track section 511, second track section 512, third track section 513 and fourth track section 514 are arranged end-to-end such that the second guide protrusion 342 of the housing 110 can travel sequentially from the first track section 511 to the second track section 513 to the third track section 513 to the fourth track section 514, in that order, as described later in relation to Figs. 7E3, 9E3, 9C,10E3, 12E3 and 12C.

[0202] The first track section 511 extends substantially circumferentially around the inner surface 511 of the biasing sleeve 121 , in a direction substantially perpendicular to the device axis X-X. The first track section 511 is configured to guide the second guide protrusion 342 of the housing 110 to travel circumferentially along the first track section 511 as the biasing sleeve 121 is rotated relative to the housing 110 in a first rotational direction R1 about the device axis X-X, as later described in relation Figs. 9E3 and 9C. The first track section 511 comprises a first holding surface 541 configured to be engaged by the second guide protrusion 342 of the housing 110 to inhibit axial movement of the biasing sleeve 121 relative to the housing 110 and thereby hold the biasing sleeve 121 in a first hold position, as described later in relation to Fig. 7E3. Figs. 5A and 5E3 show the first holding surface 541 formed as a distally-facing square surface of the first track section 511.

[0203] The second track section 512 extends substantially axially in the proximal direction A2 from an end of the first track section 511. The second track section 512 is configured to guide the second guide protrusion 342 of the housing 110 to travel axially along the second track section 512, from a distal end 5121 of the second track section 512 to a proximal end 5122 of the second track section 512, as later described in relation to Figs. 9C and 10E3. The second track section 512 comprises a second holding surface 542 configured to be engaged by the second guide protrusion 342 of the housing 110 to inhibit axial movement of the biasing sleeve 121 relative to the housing 110 and thereby hold the biasing sleeve 121 in a second hold position, as described later in relation to Fig. 10E3. Figs. 5A and 5E3 show theAttorney Docket No.: 46567-1790WO1

[0204] second holding surface 542 formed as a distally-facing square surface of the second track section 512.

[0205] The third track section 513 extends substantially circumferentially around the inner surface 522 of the biasing sleeve 121, in a direction substantially perpendicular to the device axis X-X. The third track section 513 is configured to guide the second guide protrusion 342 of the housing 110 to travel circumferentially along the third track section 513 as the biasing sleeve 121 is rotated relative to the housing 110 in a second rotational direction R2 about the device axis X-X, as later described in relation Figs. 12B and 12C, wherein the second rotational direction R2 may be an opposite rotational direction to the first rotational direction R1. The third track section 513 extends substantially circumferentially from the proximal end 5122 of the second track section 512 to a distal end 5141 of the fourth track section 514.

[0206] The fourth track section 514 extends substantially axially in the proximal direction A2 from an end of the third track section 513. The fourth track section 514 is configured to guide the second guide protrusion 342 of the housing 110 to travel axially along the fourth track section 514, from the distal end 5141 of the fourth track section 514 to a proximal end 5142 of the fourth track section 514, as later described in relation to Figs. 9C and 10E3. The fourth track section 514 comprises a third holding surface 543 configured to be engaged by the second guide protrusion 342 of the housing 110 to inhibit axial movement of the biasing sleeve 121 relative to the housing 110, as described later in relation to Fig. 10E3. Figs. 5A and 5E3 show the third holding surface 543 formed as a distally-facing square surface of the fourth track section 514.

[0207] As shown in Figs. 5A and 5E3, the biasing sleeve 121 further comprises an rotational engagement feature 540. The rotational engagement feature 540 is arranged at the outer surface 521 of the biasing sleeve 121 and is configured to be engaged by the translating engagement element 450 of the trigger member 130 during distal movement of the trigger member 130 to rotate the biasing sleeve 121, as described later in relation to Figs. 9E3, 9C, 12B and 12C.

[0208] The rotational engagement feature 540 comprises a pair of engagement surfaces in the form of a first ramped surface 531 and a second ramped surface 532, each arranged at the outer surface 521 of the biasing sleeve 121. The first ramped surface 531 and the second ramped surface 532 are both proximally-facing and each extend obliquely to the device axis X-X, however they face in different circumferential directions around the biasing sleeve 121. Figs.

[0209] 5A and 5B show the rotational engagement feature 540 as a projection (e.g., a raisedAttorney Docket No.: 46567-1790WO1

[0210] platform) that projects radially outwards from the outer surface 521 of the biasing sleeve 121 , with the first ramped surface 531 and the second ramped surface 532 formed as proximally-facing surfaces of the projection. The first ramped surface 531 and the second ramped surface 532 face away from one another. Figs. 5A and 5B further show that the first ramped surface 531 is arranged on the biasing sleeve 121 such that it is distal to the second ramped surface 532.

[0211] Use of the system 1000 and device 100 described in relation to Figs. 1 to 5E3 shall now be described in relation to Figs. 6A to 12C.

[0212] Figs. 6A and 6E3 show cross-sections of the device 100 taken along the device axis X-X. Fig.

[0213] 6A shows a cross-section of the device 100 in a plane that is perpendicular to the plane of the cross-section shown in Fig. 6E3.

[0214] Figs. 6A and 6E3 show the device 100 in a first configuration, which may be a configuration of the device 100 prior to any medicament 220 being dispensed.

[0215] The device 100 contains the medicament container 200, which itself contains the medicament 220 to be dispensed to a patient. In some examples, the device 100 may be provided to a user with the medicament container 200 already contained within the device 100 (e.g., the medicament container 200 may have been inserted into the device 100 during assembly of the device 100, or may be integrally formed with the device 100). Alternatively, the medicament container 200 may be provided to the user separate to the device 100 (e.g., as a kit of parts) and may subsequently be inserted into the device 100 by the user prior to dispensing of the medicament 220.

[0216] In some examples, the user may couple a medicament delivery member 250 (such as an intranasal nozzle) to the medicament container 200 if this is not already coupled, for example as previously described in relation to Figs. 1 and 2.

[0217] Figs. 6A and 6E3 show the plunger rod 230, the biasing sleeve 121 , the trigger member sleeve 131 and the housing 110 arranged coaxially along the device axis X-X. The proximal end 231 of the plunger rod 230 is retained within the biasing sleeve 121 . Figs 6A and 6E3 show the proximal end 231 of the plunger rod 230 engaged with a distally-facing surface 551 of a rear wall 550 of the biasing sleeve 121. The biasing sleeve 121 is surrounded by the trigger member sleeve 131 , which is in turn surrounded by the housing 110.Attorney Docket No.: 46567-1790WO1

[0218] The button portion 132 of the trigger member 130 extends proximally from the proximal end 119 of the housing 110 such that the proximally-facing actuation surface 133 is proximal to the housing 110 and is directly accessible to a user for actuation by the user’s finger or thumb.

[0219] Figs. 6A and 6B show the resilient member 122 (in this example a helical compression spring) arranged between the biasing sleeve 121 and the trigger member 130 with respect to the device axis X-X. The resilient member 122 extends proximally from the biasing sleeve 121, into a cavity 1325 within the button portion 132. A proximal end 1222 of the resilient member 122 is configured to engage the trigger member 130, for example to engage a distally-facing surface 139 of the trigger member 130. Figs. 6A and 6E3 show the distally-facing surface 139 of the trigger member 130 arranged within the cavity 1325 of the button portion 132, at a proximal end of the button portion 132.

[0220] In the first configuration of the device 100 shown in Figs. 6A and 6E3, the barrel 210 of the medicament container 200 is axially fixed relative to the housing 110, for example due to the barrel 210 being held by the medicament container holding arrangement 320 described previously in relation to Figs. 3A and 3E3. The plunger rod 230 is at a first axial position relative to the barrel 210. The biasing sleeve 121 is in a first hold position relative to the housing 110, in which axial movement of the biasing sleeve 121 in the distal direction A1 relative to the housing 110 is inhibited due to engagement between the biasing sleeve 121 and the housing 110, and more specifically due to engagement between the first holding surface 541 of the biasing sleeve 131 and the second guide protrusion 342 of the housing 110. The biasing sleeve 121 is, however, rotatable relative to the housing 110 and the trigger member 130 from the first hold position to a first release position in the rotational direction R1 about the device axis X-X.

[0221] In the first configuration of the device 100 shown in Figs. 6A and 6E3, the trigger member 130 is in an initial position relative to the housing 110. When in the initial position, the trigger member 130 may be at its maximally-proximal position relative to the housing (e.g., the button portion 132 and the actuation surface 133 may be at their most-proximal positions along the device axis X-X relative to the housing 110).

[0222] In some examples, the resilient member 122 is partially loaded (e.g. partially compressed) while the trigger member 130 is in its initial position relative to the housing 110. In such examples, the resilient member 122 exerts a biasing force on the biasing sleeve 121 in the distal direction A1 and a biasing force on the trigger member 130 in the proximal directionAttorney Docket No.: 46567-1790WO1

[0223] A2. However, because the axial movement of the biasing sleeve 121 in the distal direction A1 relative to the housing 110 is inhibited due to engagement between the biasing sleeve 121 and the housing 110, the distal biasing force applied by the resilient member 122 does not yet move the biasing sleeve 121 in the distal direction A1 relative to the housing 110. Movement of the trigger member 130 in the proximal direction A2 relative to the housing 110 due to the proximal biasing force exerted by the resilient member is also inhibited by an engagement between the trigger member 130 and the housing 110 (e.g., engagement between the first guide protrusion 341 of the housing 110 and the trigger member sleeve 131 , and / or between the trigger member 130 and some other feature of the housing 110 that inhibits the trigger member 130 from moving proximally relative to the housing 110 beyond a predetermined maximum distance). However, it should be understood that in one or more other examples, the resilient member 122 is not loaded (e.g. not compressed) while the trigger member 130 is in its initial position relative to the housing 110. In such examples, the resilient member 122 does not exert a biasing force on the biasing sleeve 121 and the trigger member 130.

[0224] In the first configuration of the device 100 shown in Figs. 6A and 6B, the trigger member 130 is free to be moved axially by the user in the distal direction A1 relative to the housing 110, to load the resilient member 122 and move the biasing sleeve 121 from its first hold position to its first release position for dispensing the first dose of medicament 220.

[0225] Fig. 7 A is a detailed side-view of a portion of the device 100 when in its first configuration shown in Figs. 6A and 6E3, the detailed side-view showing interactions between the housing 110 and the trigger member 130.

[0226] As shown in Fig. 7A, when the device 100 is in its first configuration and the trigger member 130 is in its initial position relative to the housing 110, the first guide protrusion 341 of the housing 110 is received within the trigger member track 410. More specifically, the first guide protrusion 341 is located at a first position P1 of the trigger member track 410, at the distal end 4111 of the first track section 411.

[0227] The initial retaining element 480 is arranged at the first track section 411 to retain the first guide protrusion 341 of the housing at the distal end 4111 of the first track section 411 , at the first position P1. The initial retaining element 480 is arranged such that it impedes axial movement of the first guide protrusion 341 along the first track section 411 in the proximal direction A2, and therefore impedes axial movement of the trigger member 130 in the distal direction A1 relative to the housing 110. Fig. 7A shows the initial retaining element 480Attorney Docket No.: 46567-1790WO1

[0228] taking the form of a projection (e.g., bump) arranged at a side wall of the first track section 411 , proximal to the first guide protrusion 341 of the housing 110. The initial retaining element 480 is configured to impede axial movement of the first guide protrusion 341 along the first track section 411 in the proximal direction A2 by engaging the first guide protrusion 341. For example, axial movement of the trigger member 130 relative to the housing 110 in the distal direction A1 brings a proximally-facing surface 3411 of the first guide protrusion 341 into engagement with the initial retaining element 480 such that further axial movement of the trigger member 130 relative to the housing 110 in the distal direction A1 is impeded by the engagement between the proximally-facing surface 3411 and the initial retaining element 480.

[0229] The presence of initial retaining element 480 is optional, however it can be beneficial in hindering accidental distal movement of the trigger member 130 relative to the housing 110 and can therefore hinder accidental dispensing of the first dose of the medicament 220. The initial retaining element 480 impedes but does not fully prevent distal movement of the trigger member 130 relative to the housing 110. That is, the initial retaining element 480 is arranged to allow distal movement of the trigger member 130 in the distal direction A1 relative to the housing 110 if a distal force is applied to the trigger member 130 that exceeds a non-zero threshold force for overcoming the initial retaining element 480. Fig. 7 A shows that the proximally-facing surface 3411 of the first guide protrusion 341 may be ramped to overcome the initial retaining element 480.

[0230] As shown in Fig. 7A, when the trigger member 130 is in its initial position relative to the housing 110, the engaging element 351 of the housing 110 is received within the channel 440 of the trigger member sleeve 131. The engaging element 351 is axially-aligned with the biasing element 442 of the trigger member 130, but is distal to the biasing element 442 and does not yet engage the biasing element 442.

[0231] Fig. 7B is cutaway side-view of another portion of the device 100 when the device is in its first configuration shown in Figs. 6A and 6E3, the cutaway side-view showing interactions between the housing 110, the biasing sleeve 121 and the trigger member sleeve 131.

[0232] As shown in Fig. 7E3, when the device 100 is in its first configuration, axial movement of the biasing sleeve 121 relative to the housing 110 in the distal direction A1 is inhibited by engagement between the biasing sleeve 121 and the housing 110, and more particularly by engagement between the second guide protrusion 342 of the housing 110 and the first holding surface 541 of the biasing sleeve track 510. The second guide protrusion 342Attorney Docket No.: 46567-1790WO1

[0233] projects radially outwards from outer surface 312 of the inner wall 112 of the housing 110 such that it is received within the first track section 511 of the biasing sleeve track 510. Distal axial movement of the biasing sleeve 121 relative to the housing 110 is inhibited by engagement between a proximally-facing surface 3421 of the second guide protrusion 342 and the distally-facing first holding surface 541 of the biasing sleeve track 510, wherein first holding surface 541 is a distally-facing square surface that may be formed from a proximal wall of the first track section 511.

[0234] As shown in Fig. 7B, the first track section 511 extends in a circumferential direction around the biasing sleeve 121 such that the biasing sleeve 121 can rotate relative to the housing 110 in the rotational direction R1 about the device axis X-X, from its first hold position relative to the housing 110 (shown in Fig. 7E3) to a first release position relative to the housing 110 (shown in Fig. 9C), as described later in relation to Figs. 9E3 and 9C.

[0235] As shown in Fig. 7E3, the translating engagement element 450 of the trigger member 130 is axially aligned with the first ramped surface 531 of the biasing sleeve 121 but is located proximal to, and separated from, the first ramped surface 531.

[0236] To dispense a first dose of the medicament 220 held in the medicament container 200, the user moves the device 100 from its first configuration shown in Fig. 6A to a second configuration shown in Fig. 8. Movement of the device 100 from the first configuration to the second configuration causes the first dose of the medicament 220 to be dispensed from the medicament container 200.

[0237] Prior to moving the device 100 from the first configuration to the second configuration, the user may position the device 100, and more particularly the dose delivery member 250, at an appropriate position relative to the patient. For example, where the dose delivery member 250 takes the form of an intranasal nozzle as shown in Figs. 6A and 8, the user may position the device 100 such that at least a distal end of the dose delivery member 250 is adjacent to, or inserted through, a first nostril of the patient, to allow the first dose of the medicament 220 to be dispensed intranasally through the first nostril.

[0238] In other examples, where the dose delivery member 250 takes the form of an oral nozzle, the user may position the device 100 such that at least a distal end of the dose delivery member 250 is adjacent to, or inserted into, a mouth of the patient, to allow the first dose of medicament 220 to be dispensed orally into the mouth. In yet other examples, where the dose delivery member 250 comprises a hollow needle, the user may position the device 100Attorney Docket No.: 46567-1790WO1

[0239] such that at least a distal end of the hollow needle is inserted into the patient, to allow the first dose of medicament 220 to be dispensed into the patient, for example subcutaneously, intramuscularly, or intravenously.

[0240] To move the device 100 from the first configuration to the second configuration, the user performs a first distal movement of the trigger member 130 relative to the housing 110 by moving the trigger member 130 axially relative to the housing 110 in the distal direction A1 , such that the trigger member 130 moves from its initial position relative to the housing 110 shown in Figs. 6A and 6B to a first intermediate position relative to the housing 110 as shown in Fig. 8. The user may perform the first distal movement by applying an actuation force to the actuation surface 133 of the button portion 132 in the distal direction A1 , to cause the trigger member 130 to move axially from the initial position to the first intermediate position. As shown in Figs. 6A and 8, the first intermediate position of the trigger member 130 is distal to the initial position of the trigger member 130.

[0241] The axial movement of the trigger member 130 relative to the housing 110 from the initial position to the first intermediate position loads the resilient member 122 by compressing the resilient member 122. As the trigger member 130 is moved distally, the trigger member 130 (e.g., the distally-facing surface 139 of the trigger member 130) engages the proximal end 1222 of the resilient member 122. The distal end 1221 of the resilient member 122 is engaged with the proximal end 1211 of the biasing sleeve 121. Since the biasing sleeve 121 is inhibited from moving distally relative to the housing 110, the distal end 1221 of the resilient member 122 is also inhibited from moving distally. As such, the distal movement of the proximal end 1222 of the resilient member 122 causes the resilient member 122 to be compressed, storing potential energy to later be released for dispensing the first dose of medicament. It can be seen that the resilient member 122 in Fig. 8 is compressed relative to the resilient member 122 shown in Fig. 6A.

[0242] Fig. 9A is a cutaway side-view of a portion of the device 100 as it moves from its first configuration shown in Figs. 6A and 6E3 to its second configuration shown in Fig. 8. Fig. 9A shows the portion of the device 100 just prior to the device 100 reaching the second configuration. The cutaway side-view of Fig. 9A illustrates interactions between the housing 110 and the trigger member 130.

[0243] Fig. 9A shows the trigger member 130 after it has been moved axially in the distal direction A1 relative to the housing 110 by the first distal movement. Fig. 9A shows the triggerAttorney Docket No.: 46567-1790WO1

[0244] member 130 shortly before it has reached its first intermediate position relative to the housing 110.

[0245] The first distal movement of the trigger member 130 relative to the housing 110, in which the trigger member 130 moves from the initial position to the first intermediate position, causes the first guide protrusion 341 to travel axially along the first track section 411 from a first position P1 in the first track section 411 to a second position P2 in the first track section 411 , the second position P2 proximal to the first position P1 but aligned with the first position P1 along an axis substantially parallel to the device axis X-X. Fig. 9A shows the first guide protrusion 341 after it has moved past the initial retaining element 480, but just prior to the first guide protrusion 341 reaching the second position P2 (and therefore just prior to the trigger member 130 reaching its first intermediate position).

[0246] During an initial portion of the first distal movement of the trigger member 130 relative to the housing 110, the first guide protrusion 341 engages the initial retaining element 480 arranged at the first track section 411 , with the engagement impeding further distal movement of the trigger member 130. Once the user applies sufficient force to the trigger member 130 in the distal direction to overcome a threshold retaining force, the first guide protrusion 341 moves past the initial retaining element 480 to allow the trigger member 130 to continue to move in the distal direction relative to the housing 110. For example, sufficient force applied by the user may cause a slight movement or deforming of the first guide protrusion 341 and / or initial retaining element 480 to allow the first guide protrusion 341 to move proximal to the initial retaining element 480.

[0247] Fig. 9A shows the first guide protrusion 341 as it moves past the non-return mechanism 430 while travelling along the first track section 411 , shortly prior to reaching the second position P2. Prior to the first distal movement of the trigger member 130, the first guide protrusion 341 was distal to, and disengaged from, the non-returning element 430, as shown in Fig. 7 A. As the first guide protrusion 341 travels proximally along the first track section 411 , the first guide protrusion 341 engages the non-return mechanism 430. Due to this engagement, continued movement of the first guide protrusion 341 along the first track section moves the non-return mechanism 430 relative to the trigger member sleeve 131 from a blocking configuration shown in Fig. 7A to a passing configuration shown in Fig. 9A, to allow the first guide protrusion 341 to pass the non-return mechanism 430 and continue travelling along the first track section 411 to the second position P2. More particularly, the proximally-facing surface 3411 of the first guide protrusion 341 may engage the distally-facing surface 4311 of the first arm 431 as the first guide protrusion 341 moves in the proximal direction A2 alongAttorney Docket No.: 46567-1790WO1

[0248] the first track section 411. Continued proximal movement of the first guide protrusion 341 causes the first guide protrusion 431 to apply a force to the distally-facing surface 4311 of the first arm 431 , which pivots the first arm 431 about an axis substantially perpendicular to the device axis X-X, as indicated by the arrow T1 in Fig. 9A, to move the non-return mechanism 430 to the passing configuration.

[0249] As the first guide protrusion 341 continues to move proximally, a side surface 3412 of the first guide protrusion 341 engages and then slides across the distally-facing surface 4311 of the first arm 431 , wherein engagement between the side surface 3412 and the distally-facing surface 4311 of the first arm 431 maintains the non-return mechanism 430 in the passing configuration. Once the first guide protrusion reaches the position P2, or shortly before, the first guide protrusion 341 disengages the distally-facing surface 4311 of the non-return mechanism 430, causing the non-return mechanism 430 to return from its passing configuration to its blocking configuration due to its resiliency.

[0250] Fig. 9A also shows that the distal movement of the trigger member 130 relative to the housing 110 has caused the engaging element 351 to travel axially through the channel 440 in the proximal direction A2 until it engages and then flexes the biasing element 442 of the trigger member 130. The biasing element 442 is flexed by the engaging element 351 such that the biasing element 442 exerts a biasing force on the engaging element 351 , for rotating the trigger member sleeve 131 relative to the housing 110 in the first rotational direction R1 , as later described in relation to Fig. 10A.

[0251] Rotation of the trigger member sleeve 131 relative to the housing 110 is initially inhibited during the movement of the trigger member 130 from its initial position to its first intermediate position, due to the first guide protrusion 341 being retained in the first track section 411 (e.g., by side walls of the first track section 411 and / or the non-return mechanism 430). As such, and as shown in Fig. 9A, the biasing force exerted by the biasing element 442 on the engaging element 351 has not yet caused the trigger member sleeve 131 to rotate.

[0252] Fig. 9B is a cutaway side-view of a portion of the device 100 just prior to the device 100 reaching the second configuration, the cutaway side-view showing interactions between the housing 110, the biasing sleeve 121 and the trigger member sleeve 131.

[0253] As shown in Fig. 9B, axial movement of the trigger member 130 in the distal direction A1 relative to the housing 110 has caused the translating engagement element 450 of theAttorney Docket No.: 46567-1790WO1

[0254] trigger member 130 to move axially in the distal direction A1 until it engages the first ramped surface 531 of the rotational engagement feature 540. Fig. 9B shows the translating engagement element 450 having just engaged the first ramped surface 531. More specifically, the first distally-facing ramped surface 451 of the translating engagement element 450 has just engaged the first ramped surface 531. The translating engagement element 450 and the first ramped surface 531 are arranged such that the engagement occurs shortly before the trigger member 130 has reached its first intermediate position relative to the housing 110. As such, the resilient member 122 has been loaded prior to engagement between the translating engagement element 450 and the first ramped surface 531. The position of the trigger member 130 relative to the housing 110 as shown in Fig. 9E3 is the same as the position of the trigger member 130 relative to the housing 110 as shown in Fig. 9A.

[0255] As shown in Fig. 9E3, the biasing sleeve 121 remains in its first hold position, with the second guide protrusion 342 of the housing 110 engaging the first holding surface 541 such that axial movement of the biasing sleeve 121 in the distal direction A1 relative to the housing 110 is inhibited.

[0256] Continued axial movement of the trigger member 130 relative to the housing 110 during the first distal movement moves the biasing sleeve 121 from its first hold position shown in Fig.

[0257] 9E3 to a first release position shown in Fig. 9C. Specifically, once the translating engagement element 450 has engaged the first ramped surface 531 , further axial movement of the trigger member 130 relative to the housing 110 moves the biasing sleeve 121 from the first hold position to the first release position by rotating the biasing sleeve 121 in the first rotational direction R1 relative to the housing 110. That is, axial movement of the translating engagement element 450 causes the first distally-facing ramped surface 451 of the translating engagement element 450 to slide along the first ramped surface 531 , in doing so exerting a force on the first ramped surface 531 that causes the biasing sleeve 121 to rotate about the axis X-X in the first rotational direction R1 relative to the housing 110.

[0258] Fig. 9C is a cutaway side-view of the same portion of the device 100 shown in Fig. 9E3, after distal movement of the trigger member 130 has rotated the biasing sleeve 121 from its first hold position to its first release position. Fig. 9C shows the translating engagement element 450 after it has slid across the first ramped surface 531 and thereby caused the biasing sleeve 121 to rotate in the first rotational direction R1. The trigger member 130 is now in its first intermediate position relative to the housing 110, with the first guide protrusion 341 at the second position P2 in the first track section 411.Attorney Docket No.: 46567-1790WO1

[0259] As the biasing sleeve 121 is rotated from its first hold position to its first release position, the second guide protrusion 342 of the housing 110 travels circumferentially along the first track section 511 of the biasing sleeve track 510 until enters the second track section 512 of the biasing sleeve track 510, at which point the second guide protrusion 342 of the housing 110 disengages the first holding surface 541. Fig. 9C shows the second guide protrusion 342 of the housing 110 disengaged from the first holding surface 541 when the biasing sleeve 121 is in its first release position.

[0260] When the biasing sleeve 121 is in its first release position, the biasing sleeve 121 is no longer inhibited from moving axially in the distal direction A1 relative to the housing 110, due to the second guide protrusion 342 of the housing 110 no longer engaging the first holding surface 541. As such, the biasing sleeve 121 is now free to be moved axially in the distal direction A1 relative to the housing 110 by the resilient member 122, to deliver the first dose of the medicament from the medicament container 200.

[0261] Fig. 10B is a cutaway side-view of the same portion of the device 100 shown in Fig. 9C, after the biasing sleeve 121 has been moved axially in the distal direction A1 by the resilient member 122, to deliver the first dose of the medicament. Since the biasing sleeve 121 is no longer inhibited from moving axially relative to the housing 110 in the distal direction A1, the loaded (e.g., compressed) resilient member 122 has been allowed to unload (e.g., extend, or relax) and, in doing so, exert a distal biasing force on the biasing sleeve 121 that has caused the biasing sleeve 121 to move axially within the housing 110 in the distal direction A1.

[0262] The axial movement of the biasing sleeve 121 in the first direction by the resilient member 122 moves the plunger rod 230 in the distal direction A1 due to engagement between the biasing sleeve 121 and the plunger rod 230. Since the barrel 210 of the medicament container 200 is axially fixed relative to the housing 110, the distal movement of the plunger rod 230 by the biasing sleeve 121 causes the plunger rod 230 to move distally relative to the barrel 210 from its fist axial position shown in Fig. 6B to a second axial position show in in Fig. 11 , thereby dispensing the first dose of medicament via the medicament delivery member 250.

[0263] As the biasing sleeve 121 moves axially in the distal direction A1 , the second guide protrusion 342 of the housing 110 travels substantially axially along the second track section 512 of the biasing sleeve track 510, in the proximal direction A2 relative to the biasing sleeve 121 , until it engages the second holding surface 542 as shown in Fig. 10B. Fig. 10B shows the biasing sleeve 121 in a second hold position relative to the housing 110, whereinAttorney Docket No.: 46567-1790WO1

[0264] engagement between the second guide protrusion 342 and the second holding surface 542 inhibits further axial movement of the biasing sleeve 121 in the distal direction A1 relative to the housing 110. The second holding surface 542 is located at the biasing sleeve 121 such that it is engaged by the second guide protrusion 342 once the first dose of medicament has been dispensed. That is, the position of the second holding surface 542 is chosen such that it inhibits further distal movement of the biasing sleeve 121 relative to the housing 110 once a predetermined volume of the medicament 220 corresponding to the first dose has been dispensed. As such, the device 100 is configured to dispense a discrete first dose of the medicament 220 that has a predetermined volume.

[0265] As shown in Fig. 10B, the second track section 512 may be configured to engage the second guide protrusion 342 as the second guide protrusion 342 travels along the second track section 512 to cause the biasing sleeve 121 to rotate in the second rotation direction as it moved from its first release position (shown in Fig. 9C) to its second hold position (shown in Fig. 10E3). For example, Figs. 9C and 10E3 show the second track section 512 comprising a distal portion 5123 and a proximal portion 5124, wherein the proximal portion 5124 is shifted in a circumferential direction relative to the distal portion 5123. The second guide protrusion 342 initially travels axially along the distal portion 5123 in the proximal direction A2 until it engages a ramped side surface 5125 of the second track section 512.

[0266] Engagement between the second guide protrusion 342 and the ramped side surface 5125 causes the biasing sleeve 121 to rotate relative to the housing 110 in the second rotational direction R2 as the second guide protrusion 342 slides across the ramped side surface 5125. After the biasing sleeve 121 has been rotated, the second guide protrusion 342 enters the proximal portion 5124 of the second track section 512 and continues to move axially until it engages the second holding surface 542. As shown in Fig. 10E3, the rotation of the biasing sleeve 121 relative to the housing 110 as it moves distally within the housing 110 has also rotated the biasing sleeve 121 relative to the trigger member sleeve 131 , such that the translating engagement element 450 of the trigger member sleeve 131 has been moved into axial alignment with the second ramped surface 532 of the rotational engagement feature 540. The translating engagement element 450 is positioned proximal to the second ramped surface 532 and does not yet engage the second ramped surface 532.

[0267] Once the trigger member 130 has reached its first intermediate position, axial movement of the first guide protrusion 341 along the first track section is inhibited by the non-return mechanism 430, which has moved from its passing configuration back to its blocking configuration shortly before the first guide protrusion 341 reached the second position P2. When the non-return mechanism 430 is in its blocking configuration, the proximally-facingAttorney Docket No.: 46567-1790WO1

[0268] ramped surface 4321 of the second arm 432 of the non-return mechanism 430 extends at least partially across the first track section 411 such that engagement between the proximal-facing ramped surface 4321 of the non-return mechanism 430 and a distally-facing surface 3415 of the first guide protrusion 341 inhibits distal movement of the first guide protrusion 341 along the first track section 411, thereby inhibiting the trigger member 130 from moving from its first intermediate position back to its initial position relative to the housing 110.

[0269] To deliver a second dose of the medicament 220, the device 100 must be moved from its second configuration shown in Fig. 8 to a third configuration shown in Fig. 11. To move the device 100 from its second configuration to its third configuration, the trigger member 130 must be moved from its first intermediate position relative to the housing 110, as shown in Fig. 8, to its second intermediate position relative to the housing 110, as shown in Fig. 11.

[0270] Movement of the trigger member 130 from the first intermediate position to the second intermediate position prior to dispensing the second dose may require axial movement of the trigger member 130 relative to the housing 110 in the proximal direction A2. The trigger member 130 may be biased to move from the first intermediate position to the second intermediate position by the resilient member 122, which may remain partially loaded (e.g., compressed) while the device 100 is in its second configuration and therefore exert a biasing force on the trigger member 130 in the proximal direction A2. As such, the user may move the trigger member 130 from the first intermediate position to the second intermediate position by removing the actuation force applied to the actuation surface 133 of the trigger member 130 by the user’s thumb or finger, thereby allowing the trigger member 130 to move in the proximal direction A2 relative to the housing 110 under the proximal biasing force of the resilient member 122.

[0271] Fig. 11 shows the device 100 in its third configuration, wherein the trigger member 130 has moved from its first intermediate position to its second intermediate position relative to the housing 110.

[0272] As shown in Fig. 11 , the resilient member 122 has expanded to move the biasing sleeve 121 in the distal direction A1 relative to the housing 110, in turn moving the plunger rod 230 in the distal direction A1 relative to the housing 110 to dispense the first dose of the medicament 220 through the medicament delivery member 250.

[0273] As the device 100 moves from its second configuration to its third configuration and the trigger member 130 moves from its first intermediate position to its second intermediateAttorney Docket No.: 46567-1790WO1

[0274] position, the trigger member 130 is also rotated in the first rotational direction R1 relative to the housing 110, about the device axis X-X. The trigger member 130 is rotated by the biasing element 442 of the trigger member sleeve 131 , which was previously flexed by the engaging element 351 of the housing 110 as the trigger member 130 moved from its initial position to its first intermediate position. More particularly, when the trigger member 130 is in the first intermediate position, a biasing force exerted in the engaging element 351 by the biasing element 442 rotates the trigger member sleeve 131 relative to the housing 110. This rotation causes the first guide protrusion 341 to travel from the first track section 411 to the third track section 413 via the second track section 412.

[0275] Rotation of the trigger member sleeve 131 in the first rotational direction R1 as the trigger member 130 moves from its first intermediate position to its second intermediate position may be aided by engagement between the first guide protrusion 341 and the non-return mechanism 430. More particularly, a distally-facing surface 3415 of the first guide protrusion 341 may be brought into engagement with the proximally-facing surface 4321 of the nonreturn mechanism 430 as the trigger member 130 moves from its first intermediate position to its second intermediate position. The distally-facing surface 3415 and / or proximally-facing surface 4321 may be ramped such that movement of the trigger member 130 from its first intermediate position to its second intermediate position causes the distally-facing surface 3415 to slide along the proximally-facing surface 4321 and rotate the trigger member sleeve 131 in the first rotation direction R1 relative to the housing 110.

[0276] Fig. 10 A shows a detailed portion of the device 100 when the device is in its third configuration, with the trigger member 130 in its second intermediate position relative to the housing 110, and the trigger member sleeve 131 having been rotated in the first rotational direction R1. As can be seen in Fig. 10A, the first guide protrusion 341 has travelled circumferentially along the second track section 412 of the trigger member track 410 as the trigger member 130 has moved from the first intermediate position to the second intermediate position and rotated in the first rotational direction R1. The first guide protrusion 341 has moved from its second position P2 in the first track section 411 to a third position P3 in the third track section 413, via the second track section 412. The third position P3 is distal to the second position P2 and circumferentially spaced from the second position P2 in the second rotational direction R2. When the first guide protrusion 341 is in the third position P3, axial movement of the trigger member 130 in the proximal direction A2 relative to the housing 110 is inhibited by engagement between the distally-facing surface 3415 of the first guide protrusion 341 and the proximally-facing surface 4321 of the non-return mechanism 430.Attorney Docket No.: 46567-1790WO1

[0277] After using the device 100 to dispense a discrete first dose of the medicament 220, the user may now use the device 100 to dispense a discrete second dose of the medicament 220. If the second dose is to be administered at a different administration site to the first dose, then the user moves the device 100 to the new administration prior to administering the second dose.

[0278] In one or more examples, the user may use the device 100 to dispense the second dose of the medicament 220 to the same patient to whom the first dose of the medicament 220 was administered. For example, where the device 100 is an intranasal medicament delivery device, the user may deliver the first dose through a first nostril of the patient and the second dose through a second nostril of the patient different to the first nostril of the patient. In one or more other examples, the user may use the device 100 to dispense the second dose of the medicament 220 to a different patient to whom the first dose of the medicament 220 was administered. For example, where the device 100 is an intranasal medicament delivery device, the user may deliver the first dose through a nostril of a first patient and the second dose through a nostril of a second patient different to the first patient.

[0279] After dispensing the first dose of the medicament 220 and prior to administering the second dose of the medicament 220, the user may replace the medicament delivery member 250 (if present, and releasably couplable) with a new medicament delivery member (e.g., as previously described in relation to Figs. 1 and 2).

[0280] To dispense the second dose of the medicament, the user (ora different user to the user that dispensed the first dose) axially moves the trigger member 130 in the distal direction A1 relative to the housing 110 with a second axial movement, for example by applying an actuation force to the actuation surface 133 of the trigger member 130 in the distal direction by holding the housing 110 and pushing the actuation surface 133 distally with respect to the housing 110. The second axial movement moves the trigger member 130 relative to the housing 110 in the distal direction A2 from its second intermediate position to a final position, to again load the resilient member 122 in a similar manner as previously described.

[0281] Fig. 12A shows a detailed side-view of a portion of the device 100 after the trigger member 130 has been moved axially in the distal direction A1 from its second intermediate position to its final position, thereby moving the device from its third configuration to a fourth configuration. Distal movement of the trigger member 130 from the second intermediate position to the final position has caused the first guide protrusion 341 of the housing 110 to travel axially along the third track section 413 in the proximal direction A2, from its thirdAttorney Docket No.: 46567-1790WO1

[0282] position P3 at a distal end 4131 of the third track section 413 to a fourth position P4 at a proximal end 4132 of the third track section 413. Fig. 12A shows the first guide protrusion 341 in the fourth position P4. Further distal movement of the trigger member 130 relative to the housing 110 may be inhibited by engagement between the first guide protrusion 341 and a distally-facing surface 4135 of the third track section 413.

[0283] As shown in Fig. 12, the first guide protrusion 341 passes the final retaining element 490 arranged at the third track section 413 as it travels along the third track section 413 such that it is proximal to the final retaining element 490 when in the position P4. The final retaining element 490 may be flexed by the first guide protrusion 341 as the first guide protrusion 341 engages and then moves past the final retaining element 490. The final retaining element 490 may then return to its original position due to resiliency of the final retaining element 490 once the first guide protrusion 341 has passed and disengaged the final retaining element 490, such that the final retaining element 490 retains the first guide protrusion 341 of the housing at the proximal end 4132 of the third track section 413 and inhibits distal movement of the trigger member 130 relative to the housing 110.

[0284] Fig. 12B shows a detailed side-view of a portion of the device 100 as the trigger member 130 has moved from its second intermediate position towards its final position relative to the housing 110. Fig. 12E3 shows the portion of the device 100 just prior to the trigger member 130 reaching its final position relative to the housing 110. The biasing sleeve 121 is in its second hold position, in which axial movement of the biasing sleeve 121 relative to the housing 110 is inhibited by engagement between the second guide protrusion 342 of the housing 110 and the second holding surface 541. As such, distal movement of the trigger member 130 relative to the housing 110 as the trigger member 130 is moved from its second intermediate position to its final position causes the resilient member 122 to be loaded, for example through compression of the resilient member 122 between the trigger member 130 and the biasing sleeve 121 , in a similar manner as previously described in relation to Figs.

[0285] 6B and 8.

[0286] As shown in Fig. 12B, distal movement of the trigger member 130 has brought the translating engagement element 450 of the trigger member sleeve 131 into engagement with the rotational engagement feature 540 of the biasing sleeve 131, for rotating the biasing sleeve 131 in the second rotational direction R2 relative to the housing 110. More specifically, the second distally-facing ramped surface 452 of the translating engagement element 450 has just engaged the second ramped surface 532 of the rotational engagement feature 540. The translating engagement element 450 and the second ramped surface 532Attorney Docket No.: 46567-1790WO1

[0287] are arranged such that the engagement occurs shortly before the trigger member 130 has reached its final position relative to the housing 110. As such, the resilient member 122 has been loaded prior to engagement between the translating engagement element 450 and the second ramped surface 532.

[0288] As shown in Fig. 12B, the biasing sleeve 121 remains in its second hold position, with the second guide protrusion 342 of the housing 110 engaging the second holding surface 542 such that axial movement of the biasing sleeve 121 in the distal direction A1 relative to the housing 110 is inhibited.

[0289] Continued axial movement of the trigger member 130 relative to the housing 110 during the second distal movement moves the biasing sleeve 121 from its second hold position shown in Fig. 12E3 to a second release position shown in Fig. 12C. Specifically, once the translating engagement element 450 has engaged the second ramped surface 532, further axial movement of the trigger member 130 relative to the housing 110 moves the biasing sleeve 121 from the second hold position to the second release position by rotating the biasing sleeve 121 in the second rotational direction R2 relative to the housing 110. That is, axial movement of the translating engagement element 450 causes the second distally-facing ramped surface 452 of the translating engagement element 450 to slide along the second ramped surface 532, in doing so exerting a force on the second ramped surface 532 that causes the biasing sleeve 121 to rotate about the axis X-X in the second rotational direction R2 relative to the housing 110.

[0290] Fig. 12C is a cutaway side-view of the same portion of the device 100 shown in Fig. 12E3, after distal movement of the trigger member 130 has rotated the biasing sleeve 121 from its second hold position to its second release position. Fig. 12C shows the translating engagement element 450 after it has slid across the second ramped surface 532 and thereby caused the biasing sleeve 121 to rotate in the second rotational direction R2. The trigger member 130 is now in its final position relative to the housing 110, with the first guide protrusion 341 at the fourth position P4 in the third track section 413.

[0291] As the biasing sleeve 121 is rotated from its second hold position to its second release position, the second guide protrusion 342 of the housing 110 travels circumferentially along the third track section 513 of the biasing sleeve track 510 until enters the fourth track section 514 of the biasing sleeve track 510, at which point the second guide protrusion 342 of the housing 110 disengages the second holding surface 542. Fig. 12C shows the second guideAttorney Docket No.: 46567-1790WO1

[0292] protrusion 342 of the housing 110 disengaged from the second holding surface 542 when the biasing sleeve 121 is in its second release position.

[0293] When the biasing sleeve 121 is in its second release position, the biasing sleeve 121 is no longer inhibited from moving axially in the distal direction A1 relative to the housing 110, due to the second guide protrusion 342 of the housing 110 no longer engaging the second holding surface 542. As such, the biasing sleeve 121 is now free to be moved axially in the distal direction A1 relative to the housing 110 by the resilient member 122, to deliver the second dose of the medicament from the medicament container 200. Engagement between the biasing sleeve 121 and the plunger rod 230 means that distal movement of the biasing sleeve 121 causes the plunger rod 230 to be moved distally. Such distal movement of the plunger rod 230 by the biasing sleeve 121 causes the plunger rod 230 to move distally relative to the barrel 210 from its second axial position to a third axial position that is distal to the second axial position, thereby dispensing the second dose of medicament 220 via the medicament delivery member 250.

[0294] As the biasing sleeve 121 moves axially in the distal direction A1 , the second guide protrusion 342 of the housing 110 travels substantially axially along the fourth track section 514 of the biasing sleeve track 510, in the proximal direction A2 relative to the biasing sleeve 121 , until it engages the third holding surface 543. Engagement between the second guide protrusion 342 and the third holding surface 542 inhibits further axial movement of the biasing sleeve 121 in the distal direction A1 relative to the housing 110. The third holding surface 543 is located at the biasing sleeve 121 such that it is engaged by the second guide protrusion 342 once the second dose of medicament has been dispensed. That is, the position of the third holding surface 543 is chosen such that it inhibits further distal movement of the biasing sleeve 121 relative to the housing 110 once a predetermined volume of the medicament 220 corresponding to the second dose has been dispensed. As such, the device 100 is configured to dispense a discrete second dose of the medicament 220 that has a predetermined volume.

[0295] In some examples, the volume of the second dose of medicament 220 dispensed by the device 100 is equal to the volume of the first dose of medicament 220 dispensed by the device 100. In other examples, the volume of the second dose of medicament 220 dispensed by the device 100 is different (e.g., greater or less) than the volume of the first dose of medicament 220 dispensed by the device 100.Attorney Docket No.: 46567-1790WO1

[0296] Figs. 13A to 13D show the medicament delivery device 100 during various stages of operation for dispensing a first and second dose of medicament.

[0297] Fig. 13A shows the device 100 in its first configuration, as previously described in relation to Figs. 6A and 6B, prior to dispensing a first dose of medicament. The trigger member 130 is in its initial position relative to the housing 110 of the device 100, with the button portion 132 extending its greatest proximal distance relative to the housing 110. While the device 100 is in its first configuration, the user may move the medicament delivery member 250 to an appropriate delivery site of a patient, ready for delivery of the first dose of medicament. For example, where the device 100 is an intranasal medicament delivery device and the medicament delivery member 250 is an intranasal nozzle, the user may move the intranasal nozzle to a first nostril of the patient such that the first dose may be administered through the first nostril.

[0298] Fig. 13E3 shows the device 100 in its second configuration, wherein the first dose of medicament has been delivered to the patient. The user has moved the trigger member 130 from its initial position to its first intermediate position by applying an actuation force to the actuation surface 133 of the trigger member 130, pushing the trigger member 130 distally with respect to the housing 110. The distal movement of the trigger member 130 has loaded the resilient member and subsequently moved the biasing sleeve from its first hold position to its first release position to dispense the first dose of the medicament from the medicament container 200, for example as previously described in relation to Figs. 9C and 10B.

[0299] Fig. 13C shows the device 100 in its third configuration, after the first dose of medicament has been dispensed but prior to the second dose of medicament being dispensed. The user has removed the distal actuation force from the trigger member 130, causing the trigger member 130 to move proximally from the housing 110, from its first intermediate position to its second intermediate position, for example as previously described in relation to Fig. 10A. The device 100 is now ready to administer the second dose of medicament.

[0300] Prior to administering the second dose of medicament, the user may move the medicament delivery member 250 to a different delivery site of the patient (or a different patient). For example, where the device 100 is an intranasal medicament delivery device and the medicament delivery member 250 is an intranasal nozzle, the user may move the intranasal nozzle to a second nostril of the patient (or of a different patient) such that the second dose may be administered through the second nostril. However, this is not meant to be limiting and it should be understood that, in one or more other examples, the user does not moveAttorney Docket No.: 46567-1790WO1

[0301] the medicament delivery member 250 to a different delivery site (e.g., if the second dose is to be administered to the same delivery site as the first dose). In one or more examples, the user may replace the medicament delivery member 250 with a new medicament delivery member prior to administering the second dose.

[0302] Fig. 13D shows the device 100 in its fourth configuration, wherein the second dose of medicament has been delivered to the patient. The user has moved the trigger member 130 from its second intermediate position to its final position by applying another actuation force to the actuation surface 133 of the trigger member 130, pushing the trigger member 130 distally with respect to the housing 110. The distal movement of the trigger member 130 has once again loaded the resilient member, and subsequently moved the biasing sleeve from its second hold position to its second release position to dispense the second dose of the medicament from the medicament container 200, for example as previously described in relation to Figs. 12A to 12C. The trigger member 130 may now be held in its final position by the final retaining element 490, for example as previously described in relation to Fig. 12A. The user may now dispose of the device 100 if the device 100 is single-use.

[0303] In the present example, the medicament delivery system 1000 is an intranasal medicament delivery system 1000. The intranasal medicament delivery system 1000 may be an intranasal atomization delivery system 1000.

[0304] The intranasal medicament delivery system 1000 may be configured to deliver about % of a dose to each nostril.

[0305] The intranasal medicament delivery system 1000 may be configured to deliver about 0.2mL, wherein about 0.1 mL is delivered to each nostril.

[0306] The medicament delivery member 250 in the form of an intranasal nozzle may deliver an average droplet size Dv50 of about 10-120 pm.

[0307] The intranasal nozzle 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.

[0308] The intranasal medicament delivery system 1000 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.Attorney Docket No.: 46567-1790WO1

[0309] In some embodiments, the intranasal medicament delivery system 1000 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).

[0310] In some embodiments, the intranasal medicament delivery system 1000 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.

[0311] Fig. 14 is a block diagram illustrating a method 1400 of using a medicament delivery system 1000 disclosed herein, the medicament delivery system 1000 comprising a medicament delivery device 100 and a medicament container 200 disclosed herein. The method 1400 is for dispensing a first dose and a second dose of medicament from the device 100.

[0312] A first operation 1410 of the method 1400 comprises axially moving the trigger member 130 of the medicament delivery device 100 relative to the housing 110 of the device 100 in a first direction (e.g., distal direction A1) from an initial position to a first intermediate position to load the resilient member 122 and to subsequently move the biasing sleeve 121 from a first hold position to a first release position such that the biasing sleeve 121 is moved by the resilient member 122 in the first direction to dispense a first dose of the medicament 220 from the medicament container 200.

[0313] A second operation 1420 of the method 1400 comprises, after the first dose of the medicament 220 has been dispensed, axially moving the trigger member 130 relative to the housing 110 in the first direction from a second intermediate position to a final position to load the resilient member 122 and to subsequently move the biasing sleeve 121 from a second hold position to a second release position such that the biasing sleeve is moved by the resilient member 122 in the first direction to dispense a second dose of the medicament 220 from the medicament container 200.

[0314] While it has generally been described herein that that the first and second doses of medicament are to be administered to one or more patients, it should be understood that this is not meant to be limiting and that in one or more examples at least one of the first dose or the second dose may be dispensed without being administered to a patient. For instance, in such examples, at least one of the first dose or the second dose may be a priming dose ofAttorney Docket No.: 46567-1790WO1

[0315] medicament that is not to be administered to a patient. As such, one or more devices, systems and / or methods disclosed herein may be used to dispense a first priming dose of medicament and / or a second priming dose of medicament during a priming operation of the device, without actually administering medicament to a patient. For example, operation 1410 and / or operation 1420 of method 1400 may be performed during a priming operation of a medicament delivery system, prior to administering medicament to a patient.

[0316] While it has been generally described herein that the resilient member 122 is loaded by being compressed, it should be understood that this is not meant to be limiting and that in other examples the resilient member 122 (e.g., a helical spring) may instead be loaded by being stretched. In such examples, after the resilient member 122 has been stretched, it may be released such that it contracts, with the contraction providing the biasing force to move the biasing sleeve 121 in the distal direction A1.

[0317] While it has generally been contemplated that the user of any of the systems, devices, components, and methods disclosed herein is a different person to the patient to whom one or more doses of medicament is administered, it should be understood that this is not meant to be limiting and that in one or more examples the user may also be the patient (e.g., during self-administration).

[0318] 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.

[0319] 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.

[0320] As used herein, “RSV ANS2 / A1313 / I1314L” refers to an RSV ANS2 / A1313 / I1314L (NIH) or an RSV ANS2 / A1313 / I1314L (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 non-coding region.Attorney Docket No.: 46567-1790WO1

[0321] As used herein, “RSV ANS2 / A1313 / 11314L 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).

[0322] Exemplary Methods and Uses

[0323] In some embodiments, provided are methods of delivering a dose of an RSV vaccine using an intranasal atomization delivery device.

[0324] 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).

[0325] 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.

[0326] In some embodiments, the RSV vaccine is delivered intranasally using the intranasal atomization delivery device to deliver about % 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 % dose delivered to one nostril and the other % dose is delivered to the same nostril after the first % 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.Attorney Docket No.: 46567-1790WO1

[0327] 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, 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.

[0328] 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.

[0329] 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.

[0330] In some embodiments, the intranasal atomization delivery device delivers an average droplet size DV5O of 10-120 pm. In some embodiments, the intranasal atomization delivery device delivers an average droplet size DV5o 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 orAttorney Docket No.: 46567-1790WO1

[0331] 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.

[0332] 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 / 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).

[0333]

[0334] 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.

[0335] 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.

[0336] Vaccine virus shedding and Infectivity

[0337] 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 andAttorney Docket No.: 46567-1790WO1

[0338] second vaccine administration respectively) is supportive of a promising vaccine candidate associated with good vaccine take. When infectivity was considered after either 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.

[0339] Interim analysis results showed a promising safety, immunogenicity and infectivity profile of the RSV ANS2 / A1313 / I1314L (Sanofi) candidate.

[0340] 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.

[0341] 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-naTve recipients attained a 4-fold response in serum neutralizing antibody responses post the second vaccine administration for both dose levels in RSV-naTve participants.

[0342] 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 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 mayAttorney Docket No.: 46567-1790WO1

[0343] 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.

[0344] Additional Exemplary Methods and Uses

[0345] The terms “drug” or “medicament” are used synonymously herein and may describe a pharmaceutical formulation containing one or more active pharmaceutical ingredients or pharmaceutically acceptable salts or solvates thereof, and optionally a pharmaceutically acceptable carrier. An active pharmaceutical ingredient (“API”), in the broadest terms, is a chemical structure that has a biological effect on humans or animals. In pharmacology, a drug or medicament is used in the treatment, cure, prevention, or diagnosis of disease or used to otherwise enhance physical or mental well-being. A drug or medicament may be used for a limited duration, or on a regular basis for chronic disorders.

[0346] As described below, a drug or medicament suitable for use in one or more embodiments disclosed herein can include at least one API, or combinations thereof, in various types of formulations, for the treatment of one or more diseases. Examples of API may include small molecules having a molecular weight of 500 Da or less; polypeptides, peptides and proteins (e.g., hormones, growth factors, antibodies, antibody fragments, and enzymes); carbohydrates and polysaccharides; and nucleic acids, double or single stranded DNA (including naked and cDNA), RNA, antisense nucleic acids such as antisense DNA and RNA, small interfering RNA (siRNA), ribozymes, genes, and oligonucleotides. Nucleic acids may be incorporated into molecular delivery systems such as vectors, plasmids, or liposomes. Mixtures of one or more drugs are also contemplated.

[0347] The drugs or medicaments contained in the drug delivery devices as described herein can be used for the treatment and / or prophylaxis of many different types of medical disorders. Examples of disorders include, e.g., diabetes mellitus or complications associated with diabetes mellitus such as diabetic retinopathy, thromboembolism disorders such as deep vein or pulmonary thromboembolism. Further examples of disorders are acute coronary syndrome (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and / or rheumatoid arthritis. Examples of APIs and drugs are those as described in handbooks such as Rote Liste 2014, for example, without limitation, main groups 12 (anti-diabetic drugs) or 86 (oncology drugs), and Merck Index, 15th edition.Attorney Docket No.: 46567-1790WO1

[0348] Examples of APIs for the treatment and / or prophylaxis of type 1 or type 2 diabetes mellitus or complications associated with type 1 or type 2 diabetes mellitus include an insulin, e.g., human insulin, ora human insulin analogue or derivative, a glucagon-like peptide (GLP-1), GLP-1 analogues or GLP-1 receptor agonists, or an analogue or derivative thereof, a dipeptidyl peptidase-4 (DPP4) inhibitor, ora pharmaceutically acceptable salt or solvate thereof, or any mixture thereof. As used herein, the terms “analogue” and “derivative” refers to a polypeptide which has a molecular structure which formally can be derived from the structure of a naturally occurring peptide, for example that of human insulin, by deleting and / or exchanging at least one amino acid residue occurring in the naturally occurring peptide and / or by adding at least one amino acid residue. The added and / or exchanged amino acid residue can either be codable amino acid residues or other naturally occurring residues or purely synthetic amino acid residues. Insulin analogues are also referred to as "insulin receptor ligands". In particular, the term ..derivative” refers to a polypeptide which has a molecular structure which formally can be derived from the structure of a naturally occurring peptide, for example that of human insulin, in which one or more organic substituent (e.g., a fatty acid) is bound to one or more of the amino acids. Optionally, one or more amino acids occurring in the naturally occurring peptide may have been deleted and / or replaced by other amino acids, including non-codeable amino acids, or amino acids, including non-codeable, have been added to the naturally occurring peptide.

[0349] Examples of insulin analogues are Gly(A21), Arg(B31), Arg(E332) human insulin (insulin glargine); Lys(E33), Glu(E329) human insulin (insulin glulisine); Lys(E328), Pro(E329) human insulin (insulin lispro); Asp(E328) human insulin (insulin aspart); human insulin, wherein proline in position E328 is replaced by Asp, Lys, Leu, Vai or Ala and wherein in position E329 Lys may be replaced by Pro; Ala(E326) human insulin; Des(B28-E330) human insulin;

[0350] Des(B27) human insulin and Des(B30) human insulin.

[0351] Examples of insulin derivatives are, for example, B29-N-myristoyl-des(B30) human insulin, Lys(B29) (N- tetradecanoyl)-des(B30) human insulin (insulin detemir, Levemir®); B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin; B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30 human insulin; B29-N-(N-palmitoyl-gamma-glutamyl)-des(B30) human insulin, B29-N-omega-carboxypentadecanoyl-gamma-L-glutamyl-des(B30) human insulin (insulin degludec, Tresiba®); B29-N-(N-lithocholyl-gamma-glutamyl)-des(B30) human insulin; B29-N-(oj-carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(OJ-carboxyheptadecanoyl) human insulin.Attorney Docket No.: 46567-1790WO1

[0352] Examples of GLP-1, GLP-1 analogues and GLP-1 receptor agonists are, for example, Lixisenatide (Lyxumia®), Exenatide (Exendin-4, Byetta®, Bydureon®, a 39 amino acid peptide which is produced by the salivary glands of the Gila monster), Liraglutide (Victoza®), Semaglutide, Taspoglutide, Albiglutide (Syncria®), Dulaglutide (Trulicity®), rExendin-4, CJC-1134-PC, PB-1023, TTP-054, Langlenatide I HM-11260C (Efpeglenatide), HM-15211, CM-3, GLP-1 Eligen, GRMD-0901 , NN-9423, NN-9709, NN-9924, NN-9926, NN-9927, Nodexen, Viador-GLP-1, CVX-096, ZYOG-1 , ZYD-1 , GSK-2374697, DA-3091 , MAR-701 , MAR709, ZP-2929, ZP-3022, ZP-DI-70, TT-401 (Pegapamodtide), BHM-034. MOD-6030, CAM-2036, DA-15864, ARI-2651 , ARI-2255, Tirzepatide (LY3298176), Bamadutide (SAR425899), Exenatide-XTEN and Glucagon-Xten.

[0353] An example of an oligonucleotide is, for example: mipomersen sodium (Kynamro®), a cholesterol-reducing antisense therapeutic for the treatment of familial hypercholesterolemia or RG012 for the treatment of Alport syndrom.

[0354] Examples of DPP4 inhibitors are Linagliptin, Vildagliptin, Sitagliptin, Denagliptin, Saxagliptin, Berberine.

[0355] Examples of hormones include hypophysis hormones or hypothalamus hormones or regulatory active peptides and their antagonists, such as Gonadotropine (Follitropin, Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin, Buserelin, Nafarelin, and Goserelin.

[0356] Examples of polysaccharides include a glucosaminoglycane, a hyaluronic acid, a heparin, a low molecular weight heparin or an ultra-low molecular weight heparin ora derivative thereof, or a sulphated polysaccharide, e.g. a poly-sulphated form of the above-mentioned polysaccharides, and / or a pharmaceutically acceptable salt thereof. An example of a pharmaceutically acceptable salt of a poly-sulphated low molecular weight heparin is enoxaparin sodium. An example of a hyaluronic acid derivative is Hylan G-F 20 (Synvisc®), a sodium hyaluronate.

[0357] The term “antibody”, as used herein, refers to an immunoglobulin molecule or an antigenbinding portion thereof. Examples of antigen-binding portions of immunoglobulin molecules include F(ab) and F(ab')2 fragments, which retain the ability to bind antigen. The antibody can be polyclonal, monoclonal, recombinant, chimeric, de-immunized or humanized, fully human, non-human, (e.g., murine), or single chain antibody. In some embodiments, the antibody has effector function and can fix complement. In some embodiments, the antibody has reduced or no ability to bind an Fc receptor. For example, the antibody can be anAttorney Docket No.: 46567-1790WO1

[0358] isotype or subtype, an antibody fragment or mutant, which does not support binding to an Fc receptor, e.g., it has a mutagenized or deleted Fc receptor binding region. The term antibody also includes an antigen-binding molecule based on tetravalent bispecific tandem immunoglobulins (TBTI) and / or a dual variable region antibody-like binding protein having cross-over binding region orientation (CODV).

[0359] The terms “fragment” or “antibody fragment” refer to a polypeptide derived from an antibody polypeptide molecule (e.g., an antibody heavy and / or light chain polypeptide) that does not comprise a full-length antibody polypeptide, butthat still comprises at least a portion of a full-length antibody polypeptide that is capable of binding to an antigen. Antibody fragments can comprise a cleaved portion of a full length antibody polypeptide, although the term is not limited to such cleaved fragments. Antibody fragments that are useful in the present invention include, for example, Fab fragments, F(ab')2 fragments, scFv (single-chain Fv) fragments, linear antibodies, monospecific or multispecific antibody fragments such as bispecific, trispecific, tetraspecific and multispecific antibodies (e.g., diabodies, triabodies, tetrabodies), monovalent or multivalent antibody fragments such as bivalent, trivalent, tetravalent and multivalent antibodies, minibodies, chelating recombinant antibodies, tribodies or bibodies, intrabodies, nanobodies, small modular immunopharmaceuticals (SMIP), binding-domain immunoglobulin fusion proteins, camelized antibodies, and VHH containing antibodies. Additional examples of antigen-binding antibody fragments are known in the art.

[0360] The terms “Complementarity-determining region” or “CDR” refer to short polypeptide sequences within the variable region of both heavy and light chain polypeptides that are primarily responsible for mediating specific antigen recognition. The term “framework region” refers to amino acid sequences within the variable region of both heavy and light chain polypeptides that are not CDR sequences, and are primarily responsible for maintaining correct positioning of the CDR sequences to permit antigen binding. Although the framework regions themselves typically do not directly participate in antigen binding, as is known in the art, certain residues within the framework regions of certain antibodies can directly participate in antigen binding or can affect the ability of one or more amino acids in CDRs to interact with antigen.

[0361] Examples of antibodies are anti PCSK-9 mAb (e.g., Alirocumab), anti IL-6 mAb (e.g., Sarilumab), and anti IL-4 mAb (e.g., Dupilumab).Attorney Docket No.: 46567-1790WO1

[0362] Pharmaceutically acceptable salts of any API described herein are also contemplated for use in a drug or medicament in a drug delivery device. Pharmaceutically acceptable salts are for example acid addition salts and basic salts.

[0363] Those of skill in the art will understand that modifications (additions and / or removals) of various components of the embodiments described herein may be made without departing from the full scope and spirit of the present invention, which encompass such modifications and any and all equivalents thereof.

[0364] List of Reference Numbers

[0365] 100 - medicament delivery device / device

[0366] 1000 - medicament delivery system

[0367] 110 - housing

[0368] 115 - opening (distal end of housing)

[0369] 118 - distal end (of housing)

[0370] 119 - proximal end (of housing)

[0371] 1191 - opening (proximal end of housing)

[0372] 120 - dose dispensing mechanism

[0373] 121 - biasing sleeve

[0374] 1211 - proximal end (of biasing sleeve)

[0375] 1212 - distal end (of biasing sleeve)

[0376] 1213 - distal portion (of biasing sleeve)

[0377] 1215 - opening (distal end of biasing sleeve)

[0378] 122 - resilient member

[0379] 1221 - distal end (of resilient member)

[0380] 1222 - proximal end (of resilient member)

[0381] 114a / 114b - finger flanges

[0382] 116a / 116b - windows

[0383] 117 - outer surface (of housing)

[0384] 111 - outer wall (of housing)

[0385] 112 - inner wall (of housing)

[0386] 200 - medicament container

[0387] 210 - barrel

[0388] 2100 - opening (proximal end of barrel)Attorney Docket No.: 46567-1790WO1

[0389] 2101 - proximal end (of barrel)

[0390] 2102 - distal end (of barrel)

[0391] 211 - reservoir

[0392] 220 - medicament

[0393] 230 - plunger rod

[0394] 231 - proximal end (of plunger rod)

[0395] 240 - outlet

[0396] 250, 250’, 250” - medicament delivery member

[0397] 2501 , 2501 ’ - medicament delivery conduit

[0398] 2501A, 2501A’ - nozzle outlet

[0399] 2502 - needle

[0400] 251 - distal end (of medicament delivery member)

[0401] 260 - plunger rod flange

[0402] 311 - inner surface (of outer wall)

[0403] 312 - outer surface (of inner wall)

[0404] 310 - annular chamber

[0405] 130 - trigger member

[0406] 1301 - distal portion (of trigger member)

[0407] 1302 - proximal portion (of trigger member)

[0408] 131 - trigger member sleeve

[0409] 1310 - opening (of trigger member)

[0410] 1311 - proximal end (of trigger member sleeve)

[0411] 1312 - distal end (of trigger member sleeve)

[0412] 132 - button portion

[0413] 1321 - proximal end (of button portion)

[0414] 1325 - cavity (of button portion)

[0415] 133 - actuation surface

[0416] 313 - circumferential inner surface (of inner wall)

[0417] 314 - cavity (formed by inner wall)

[0418] 315a-d - medicament container engagement elements

[0419] 320 - medicament container holding arrangement

[0420] 341 - first guide protrusion

[0421] 3411 - proximally-facing surface (of first guide protrusion) 3412 - side surface (of first guide protrusion)

[0422] 3415 - distally-facing surface (of first guide protrusion)

[0423] 342 - second guide protrusion

[0424] 3421 - proximally-facing surface ( of second guide protrusion)Attorney Docket No.: 46567-1790WO1

[0425] 351 - engaging element

[0426] 410 - trigger member track

[0427] 411 - first track section (of trigger member track)

[0428] 4111 - distal end (of first track section)

[0429] 4112 - proximal end (of first track section)

[0430] 412 - second track section (of trigger member track)

[0431] 413 - third track section (of trigger member track)

[0432] 4131 - distal end (of third track section)

[0433] 4132 - proximal end (of third track section)

[0434] 4135 - distally-facing surface (of third track section)

[0435] 421 - outer surface (of trigger member sleeve)

[0436] 422 - inner surface (of trigger member sleeve)

[0437] 430 - non-return mechanism

[0438] 431 - first arm

[0439] 4311 - distally-facing surface (of first arm)

[0440] 432 - second arm

[0441] 4321 - proximally-facing surface (of second arm)

[0442] 440 - channel

[0443] 442 - biasing element

[0444] 4421 - coupling end (of flexible arm)

[0445] 4422 - free end (of flexible arm)

[0446] 450 - translating engagement element

[0447] 451 - first distally-facing ramped surface (of translating engagement element) 452 - second distally-facing ramped surface (of translating engagement element) 480 - initial retaining element

[0448] 490 - final retaining element

[0449] 510 - biasing sleeve track

[0450] 511 - first track section (of biasing sleeve track)

[0451] 512 - second track section (of biasing sleeve)

[0452] 513 - third track section (of biasing sleeve)

[0453] 514 - fourth track section (of biasing sleeve)

[0454] 521 - outer surface (of biasing sleeve)

[0455] 522 - inner surface (of biasing sleeve)

[0456] 531 - first ramped surface (of rotational engagement feature)

[0457] 532 - second ramped surface (of rotational engagement feature)

[0458] 540 - rotational engagement feature

[0459] 541 - first holding surfaceAttorney Docket No.: 46567-1790WO1

[0460] 542 - second holding surface

[0461] 543 - third holding surface

[0462] 550 - rear wall (of biasing sleeve)

[0463] 551 - distally-facing surface (of rear wall)

[0464] P1 - first position (of trigger member track)

[0465] P2 - second position (of trigger member track)

[0466] P3 - third position (of trigger member track)

[0467] P4 - fourth position (of trigger member track)

[0468] R1 - first rotational direction

[0469] R2 - second rotational direction

[0470] T1 - arrow indicating pivot direction (of non-return mechanism) A1 - distal direction

[0471] A2 - proximal direction

[0472] X-X - device axis

Claims

Attorney Docket No.: 46567-1790WO1Claims1. A medicament delivery device (100) comprising:a housing (110) configured to contain a medicament container (200);a dose dispensing mechanism (120) comprising a biasing sleeve (121) and a resilient member (122) configured to exert a biasing force on the biasing sleeve; anda trigger member (130),wherein the trigger member and the dose dispensing mechanism are arranged such that, in use:the trigger member is movable relative to the housing in a first direction (A1) from an initial position to a first intermediate position to load the resilient member and to subsequently move the biasing sleeve from a first hold position to a first release position such that the biasing sleeve is moved by the resilient member in the first direction to dispense a first dose of the medicament from the medicament container, andafter the first dose of the medicament has been dispensed, the trigger member is movable relative to the housing in the first direction from a second intermediate position to a final position to load the resilient member and to subsequently move the biasing sleeve from a second hold position to a second release position such that the biasing sleeve is moved by the resilient member in the first direction to dispense a second dose of the medicament from the medicament container.

2. The medicament delivery device according to claim 1 , wherein the resilient member comprises a spring, and wherein the trigger member is configured to load the resilient member by compressing the spring, optionally wherein the spring is a helical compression spring.

3. The medicament delivery device according to claim 1 or claim 2, wherein the resilient member is arranged between the trigger member and the biasing sleeve.

4. The medicament delivery device according to claim 1 , 2 or 3, wherein movement of the trigger member from the first intermediate position to the second intermediate position prior to dispensing the second dose requires movement of the trigger member relative to the housing in a second direction that is opposite to the first direction, optionally wherein the trigger member is biased to move from the first intermediate position to the second intermediate position by the resilient member.Attorney Docket No.: 46567-1790WO15. The medicament delivery device according to any preceding claim, wherein the biasing sleeve moves from the first release position to the second hold position during movement in the first direction to dispense the first dose of the medicament.

6. The medicament delivery device according to any preceding claim, wherein the trigger member is configured to move the biasing sleeve from the first hold position to the first release position by rotating the biasing sleeve in a first rotational direction (R1) relative to the housing,optionally wherein the trigger member comprises a translating engagement element (450) configured to engage a first ramped surface (531) of the biasing sleeve during movement of the trigger member from the initial position to the first intermediate position to rotate the biasing sleeve in the first rotational direction.

7. The medicament delivery device according to claim 6, wherein the trigger member is configured to move the biasing sleeve from the second hold position to the second release position by rotating the biasing sleeve in a second rotational direction (R2) relative to the housing, optionally wherein the second rotational direction is a rotational direction opposite to the first rotational direction.

8. The medicament delivery device according to any preceding claim, wherein the trigger member comprises a trigger member sleeve (131) arranged to move axially within the housing and a button portion (132) arranged to be pushed by a user in the first direction to move the trigger member sleeve in the first direction.

9. The medicament delivery device according to claim 8, wherein the trigger member sleeve comprises a trigger member track (410) comprising:an axially-extending first track section (411);a circumferentially-extending second track section (412); andan axially-extending third track section (413), andwherein the housing comprises a first guide protrusion (341) configured to:travel axially along the first track section as the trigger member moves from the initial position to the first intermediate position;travel circumferentially along the second track section as the trigger member moves from the first intermediate position to the second intermediate position; and travel axially along the third track section as the trigger member moves from the second intermediate position to the final position.Attorney Docket No.: 46567-1790WO110. The medicament delivery device according to claim 9, wherein the housing comprises an engaging element (351) arranged to engage a biasing element (442) of the trigger member sleeve when the trigger member is in the first intermediate position, such that the biasing element rotates the trigger member sleeve relative to the housing to cause the first guide protrusion to travel from the first track section to the third track section via the second track section.

11. The medicament delivery device according to any preceding claim,wherein the biasing sleeve comprises a biasing sleeve track (510) having a first holding surface (541) and a second holding surface (542),wherein the housing comprises a second guide protrusion (342) configured to sequentially engage the first holding surface to hold the biasing sleeve in the first hold position and the second holding surface to hold the biasing sleeve in the second hold position,wherein movement of the biasing sleeve from the first hold position to the first release position disengages the second guide protrusion from the first holding surface, and wherein movement of the biasing sleeve from the second hold position to the second release position disengages the second guide protrusion from the second holding surface.

12. The medicament delivery device according to any preceding claim, wherein the biasing sleeve is configured to receive and engage a proximal end (231) of a plunger rod (230) of the medicament container such that movement of the biasing sleeve in the first direction moves the plunger rod in the first direction to dispense the medicament.

13. The medicament delivery device according to any preceding claim, wherein the medicament delivery device is an intranasal medicament delivery device.

14. The medicament delivery device according to any preceding claim, wherein the first direction is a distal direction, wherein the second intermediate position is proximal to the first intermediate position, and wherein the trigger member is biased to move from the first intermediate position to the second intermediate position by the resilient member.

15. A medicament delivery system (1000) comprising:a medicament delivery device (100) according to any preceding claim; and a medicament container (200), optionally wherein the medicament container contains a medicament (220), the medicament preferably being a vaccine.

16. A method (1400) of using a medicament delivery device, the method comprising:Attorney Docket No.: 46567-1790WO1moving (1410) a trigger member relative to a housing in a first direction from an initial position to a first intermediate position to load a resilient member and to subsequently dispense a first dose of a medicament from a medicament container, andafter the first dose of the medicament has been dispensed, moving (1420) the trigger member relative to the housing in the first direction from a second intermediate position to a final position to load the resilient member and to subsequently dispense a second dose of the medicament from the medicament container.

17. The method according to claim 16, wherein the method is performed as part of a priming operation of the medicament delivery device, and wherein the first dose and the second dose are priming doses not delivered to a patient.

18. A method (1400) of using a medicament delivery device according to any one of claims 1 to 14, the method comprising:moving (1410) the trigger member relative to a housing in the first direction from the initial position to the first intermediate position to load the resilient member and to subsequently dispense the first dose of the medicament from the medicament container, optionally wherein the first dose is a first priming dose not delivered to a patient.

19. The method of claim 18, further comprising:after the first dose of the medicament has been dispensed, moving (1420) the trigger member relative to the housing in the first direction from the second intermediate position to the final position to load the resilient member and to subsequently dispense the second dose of the medicament from the medicament container, optionally wherein the second dose is a second priming dose not delivered to a patient.

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