An intranasal nozzle and an intranasal medicament delivery system

Abstract

According to the present disclosure, there is provided an intranasal nozzle (200') for an intranasal medicament delivery device (100, 100'). The intranasal nozzle comprises first and second nozzle outlets (203', 204'), a seal (128), and a valve member (130). The seal (128) is configured to seal against the intranasal medicament delivery device (100, 100'). The valve member (130) is configured such that, when the seal (128) is sealed against the intranasal medicament delivery device, the valve member (130) inhibits the ingress of air into an outlet (1213) of the intranasal medicament delivery device via the intranasal nozzle (200') and wherein, in use, the intranasal medicament delivery device (100, 100') is operable to expel medicament from the outlet (1213) and through the first and second nozzle outlets (203', 204') for delivery to a user. The present disclosure also relates to an intranasal medicament delivery system (1, 1'), a kit of parts for an intranasal medicament delivery system, and a method (2000) of preparing an intranasal medicament delivery system.

Description

[0001] Attorney Docket No.: 46567-1783WO1

[0002] An intranasal nozzle and an intranasal medicament delivery system

[0003] Cross-reference to related applications

[0004] The present application claims priority to EP patent application no. 24214981.3, filed on November 22, 2024, the disclosure of which is incorporated herein by reference.

[0005] Field of the invention

[0006] The present disclosure relates to an intranasal nozzle. The present disclosure also relates to an intranasal medicament delivery system, a kit of parts for an intranasal medicament delivery system and a method of preparing an intranasal medicament delivery system.

[0007] Background

[0008] The nasal administration of medicaments represents an alternative route to intravenous, intramuscular or subcutaneous medicament administration. Devices for nasal administration of medicaments typically include a nozzle for insertion into the patient’s nose and delivering medicament to the user’s nose from a medicament source. As nasal administration devices do not typically pierce the skin of the user, the process of administering the medicament may be less painful for the user. Nasal medicament administration devices are also relatively simple to use and can be operated with less training than conventional medicament delivery devices. They can also deliver relatively large volumes of medicament to a user.

[0009] It is desirable to provide a medicament delivery device that is easy to use.

[0010] It is an object of the present invention to address one or more of the problems mentioned above.

[0011] Respiratory syncytial virus (RSV) is an important cause of severe acute lower respiratory illness (LRI) in infants and children and a common cause of severe pneumonia requiring hospital admission in children worldwide. According to global estimates, RSV caused approximately 33 million cases of LRI and approximately 118,000 deaths in children <5 years of age in 2015. Greater than 80% of all RSV-associated LRIs (RSV-LRIs) and more than 50% of the RSV-associated deaths in low- and middle-income countries were estimated to occur in infants >6 months old. Attorney Docket No.: 46567-1783WO1

[0012] Summary of the invention

[0013] According to the present disclosure, there is provided an intranasal nozzle for an intranasal medicament delivery device, the intranasal nozzle comprising: first and second nozzle outlets; a seal configured to seal against the intranasal medicament delivery device; and, a valve member configured such that, when the seal is sealed against the intranasal medicament delivery device, the valve member inhibits the ingress of air into an outlet of the medicament deliver device via the intranasal nozzle and wherein, in use, the intranasal medicament delivery device is operable to expel medicament from the outlet and through the first and second nozzle outlets for delivery to a user.

[0014] In some embodiments, the seal is configured to seal around the outlet of the intranasal medicament delivery device.

[0015] In some embodiments, the intranasal nozzle is configured to couple to a component of the intranasal medicament delivery device and, optionally, wherein the component is a housing of the intranasal medicament delivery device.

[0016] In some embodiments, the seal is integrally formed with the valve member.

[0017] In some embodiments, the valve member comprises a flap of material.

[0018] In some embodiments, the seal is substantially annular.

[0019] In some embodiments, the seal is substantially planar.

[0020] In some embodiments, the seal and valve member are substantially co-planar.

[0021] In some embodiments, the valve member is configured such that, in use, the valve member is moveable from a closed position, wherein the valve member is seated against a portion of the intranasal medicament delivery device to inhibit the ingress of air into the outlet via the intranasal nozzle, to an open position, wherein medicament can flow out of the outlet.

[0022] In some embodiments, the valve member moves away from said portion of the intranasal medicament delivery device to move to the open position. Attorney Docket No.: 46567-1783WO1

[0023] In some embodiments, the valve member is configured to protrude into the outlet and, preferably, comprises a rounded or chamfered portion.

[0024] In some embodiments, the valve member is configured to move distally when the intranasal medicament delivery device is operated to expel medicament from the outlet.

[0025] In some embodiments, the valve member projects in a proximal direction.

[0026] In some embodiments, the seal comprises a substantially flat surface.

[0027] In some embodiments, the seal comprises a substantially annular surface. In some embodiments, the seal comprises a substantially flat and substantially annular surface.

[0028] In some embodiments, the seal is disposed radially outwardly of the valve member.

[0029] In some embodiments, the seal surrounds the valve member.

[0030] In some embodiments, the intranasal medicament delivery device is operable to expel medicament past the valve member. The medicament moves from upstream of the valve member to downstream of the valve member.

[0031] In some embodiments, the valve member is configured to protrude into the opening.

[0032] In some embodiments, the seal and / or one-way valve comprises an elastomeric material.

[0033] In some embodiments, the intranasal nozzle comprises a coupling and, optionally, the coupling comprises a bayonet connection.

[0034] In some embodiments, the intranasal nozzle comprises a base that comprises the coupling.

[0035] In some embodiments, the base comprises a manifold that is configured to fluidly communicate the first and second nozzle outlets with the outlet of the intranasal medicament delivery device.

[0036] In some embodiments, the intranasal nozzle comprises a first medicament delivery conduit that comprises the first nozzle outlet and a second medicament delivery conduit Attorney Docket No.: 46567-1783WO1 that comprises the second nozzle outlet and, optionally, wherein the first and second medicament delivery conduits are substantially parallel and / or are substantially the same length.

[0037] In some embodiments, the first and second nozzle outlets are spaced apart.

[0038] In some embodiments, the device has an intended filling orientation, and wherein the port is arranged such that during filling of the device the medicament container is orientated such that medicament flows towards the cannula under the influence of gravity when the device is in the intended filling orientation. This helps to encourage medicament to flow from the medicament container and into the cannula. In some embodiments, the cannula is located below the medicament container. In some embodiments, the port is configured such that when the device is in the intended filling position, the cartridge is orientated vertically or substantially vertically. In some embodiments, in the intended filling orientation of the device, a central axis of the piston is horizontal.

[0039] In some embodiments, the intranasal nozzle is configured to attach to the intranasal medicament delivery device such that the seal abuts and seals against the intranasal medicament delivery device. In some embodiments, a substantially flat surface of the seal abuts and seals against the intranasal medicament delivery device.

[0040] In some embodiments, the medicament delivery device comprises a chamber configured to fluidly communicate with a medicament container such that medicament can be drawn into the chamber from the medicament container whilst the valve prevents the ingress of air into the chamber.

[0041] In some embodiments, the medicament delivery device comprises a port that is configured to interface with the medicament container. In some embodiments, the medicament delivery device comprises a housing that comprises the port. In some embodiments, the port comprises a cannula.

[0042] According to the present disclosure, there is also provided an intranasal medicament delivery system or a kit of parts for an intranasal medicament delivery system, the system or kit of parts comprising an intranasal medicament delivery device and an intranasal nozzle that comprises first and second nozzle outlets, wherein the intranasal medicament delivery device or intranasal nozzle comprises a seal configured to form a seal between Attorney Docket No.: 46567-1783WO1 the medicament delivery device and intranasal nozzle, and wherein the intranasal medicament delivery device or intranasal nozzle comprises a valve member configured such that, when the seal is formed between the intranasal medicament delivery device and intranasal nozzle, the valve member inhibits the ingress of air into an outlet of the intranasal medicament delivery device and wherein, in use, the intranasal medicament delivery device is operable to expel medicament through the first and second nozzle outlets for delivery to a user.

[0043] In some embodiments, the medicament delivery device comprises the valve member. The medicament delivery device or intranasal nozzle may comprise the seal.

[0044] In some embodiments, the intranasal nozzle comprises the valve member. The medicament delivery device or intranasal nozzle may comprise the seal.

[0045] In some embodiments, the valve member is configured such that, in use, the valve member is moveable from a closed position, wherein the valve member is seated against a portion of the intranasal medicament delivery device to inhibit the ingress of air into the outlet via the intranasal nozzle, to an open position, wherein medicament can flow out of the outlet.

[0046] In some embodiments, the medicament delivery device comprises a chamber configured to fluidly communicate with a medicament container such that medicament can be drawn into the chamber from the medicament container whilst the valve prevents the ingress of air into the chamber.

[0047] In some embodiments, the medicament delivery device comprises a port that is configured to interface with the medicament container. In some embodiments, the medicament delivery device comprises a housing that comprises the port. In some embodiments, the port comprises a cannula.

[0048] In some embodiments, the medicament delivery device comprises a plunger rod within the housing and configured such that, in use, the plunger rod is moveable relative to the housing in a first direction to draw medicament into the chamber from the container and is moveable in a second direction to expel medicament from the chamber via the outlet. In some embodiments, the valve member is configured to inhibit the ingress of air into the outlet when the plunger rod is moved in the first direction. In some embodiments, the Attorney Docket No.: 46567-1783WO1 valve member is configured to permit medicament to be expelled from the outlet when the plunger rod is moved in the second direction.

[0049] In some embodiments, the medicament delivery device comprises a drive mechanism operable to exert a force on the plunger rod to urge the plunger rod in the second direction to expel the medicament from the chamber via the outlet.

[0050] In some embodiments, the intranasal nozzle has any of the features of the intranasal nozzle described herein.

[0051] In some embodiments, the system or kit of parts comprises a medicament container that contains a medicament and, optionally, wherein the medicament is a vaccine.

[0052] 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.

[0053] 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.

[0054] 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.

[0055] 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.

[0056] In some embodiments, the seal is substantially annular.

[0057] In some embodiments, the seal is substantially planar. Attorney Docket No.: 46567-1783WO1

[0058] In some embodiments, the seal and valve member are substantially co-planar.

[0059] In some embodiments, the valve member is configured such that, in use, the valve member is moveable from a closed position, wherein the valve member is seated against a portion of the intranasal medicament delivery device to inhibit the ingress of air into the outlet via the intranasal nozzle, to an open position, wherein medicament can flow out of the outlet.

[0060] In some embodiments, the valve member moves away from said portion of the intranasal medicament delivery device to move to the open position.

[0061] In some embodiments, the valve member is configured to protrude into the opening and, preferably, comprises a rounded or chamfered portion.

[0062] In some embodiments, the valve member is configured to move distally when the intranasal medicament delivery device is operated to expel medicament from the outlet.

[0063] In some embodiments, the valve member projects in a proximal direction.

[0064] In some embodiments, the seal comprises a substantially flat surface.

[0065] In some embodiments, the seal comprises a substantially annular surface. In some embodiments, the seal comprises a substantially flat and substantially annular surface.

[0066] In some embodiments, the seal is disposed radially outwardly of the valve member.

[0067] In some embodiments, the seal surrounds the valve member.

[0068] In some embodiments, the intranasal medicament delivery device is operable to expel medicament past the valve member. The medicament moves from upstream of the valve member to downstream of the valve member.

[0069] In some embodiments, the intranasal nozzle is configured to attach to the intranasal medicament delivery device such that the seal abuts and seals against the intranasal medicament delivery device. In some embodiments, a substantially flat surface of the seal abuts and seals against the intranasal medicament delivery device. Attorney Docket No.: 46567-1783WO1

[0070] In some embodiments, the medicament delivery device comprises a chamber configured to fluidly communicate with a medicament container such that medicament can be drawn into the chamber from the medicament container whilst the valve prevents the ingress of air into the chamber.

[0071] In some embodiments, the medicament delivery device comprises a port that is configured to interface with the medicament container. In some embodiments, the medicament delivery device comprises a housing that comprises the port. In some embodiments, the port comprises a cannula.

[0072] The intranasal medicament delivery device may be an intranasal atomization delivery device.

[0073] The intranasal medicament delivery device may be configured to deliver about1 / 2of a dose to each nostril.

[0074] The intranasal medicament delivery device may be configured to deliver about 0.2mL, wherein about 0.1 mL is delivered to each nostril.

[0075] The intranasal medicament delivery device may deliver an average droplet size Dv50 of about 10-120 pm.

[0076] 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

[0077] 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.

[0078] In some embodiments, the intranasal medicament delivery device is configured to deliver in the range of 20 to 2000 microlitres (0.02 to 2 ml) volume of medicament and, preferably, in the range of 100 to 400 microlitres (0.1 to 0.4 ml) and, preferably, in the range of 10 to 300 microlitres (0.1 to 0.3 ml) and, preferably, about 200 microlitres (0.2 ml). Attorney Docket No.: 46567-1783WO1

[0079] 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.

[0080] According to the present disclosure, there is also provided an intranasal medicament delivery system or a kit of parts for an intranasal medicament delivery system, the system or kit of parts comprising: a housing; a chamber for receiving medicament from a container of medicament; an outlet through which medicament can be expelled from the chamber for delivery to a user; a plunger rod within the housing and configured such that, in use, the plunger rod is moveable relative to the housing in a first direction to draw medicament into the chamber from the container and in a second direction to expel the medicament from the chamber via the outlet; and, a blocking member configured to seal the outlet to inhibit the ingress of air into outlet when the plunger rod is moved in the first direction, and wherein the blocking member is moveable to unseal the outlet.

[0081] In some embodiments, the intranasal medicament delivery system comprises a drive biasing member configured to exert a force on the plunger rod to urge the plunger rod in the second direction to expel the medicament from the chamber via the outlet. The drive mechanism may comprise a drive biasing member, for example, a drive spring.

[0082] In some embodiments, the blocking member comprises a plug and, optionally, wherein the plug is detachable from the medicament delivery device.

[0083] In some embodiments, the medicament delivery device comprises an aperture configured to receive the plug.

[0084] In some embodiments, the intranasal nozzle has any of the features of the intranasal nozzle described herein.

[0085] In some embodiments, the system or kit of parts comprises a medicament container that contains a medicament and, optionally, wherein the medicament is a vaccine.

[0086] 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 Attorney Docket No.: 46567-1783WO1 medicament delivery device is configured to deliver medicament to the nasal structures of the user to elicit an immune response.

[0087] 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.

[0088] 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.

[0089] 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.

[0090] The intranasal medicament delivery device may be an intranasal atomization delivery device.

[0091] The intranasal medicament delivery device may be configured to deliver about % of a dose to each nostril.

[0092] The intranasal medicament delivery device may be configured to deliver about 0.2ml_, wherein about 0.1 mL is delivered to each nostril.

[0093] The intranasal medicament delivery device may deliver an average droplet size Dv50 of about 10-120 pm.

[0094] 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

[0095] 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. Attorney Docket No.: 46567-1783WO1

[0096] 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).

[0097] 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.

[0098] According to the present disclosure, there is provided a method of preparing an intranasal medicament delivery system, the method comprising: coupling an intranasal nozzle to a component of an intranasal medicament delivery device such that a seal is formed between the intranasal nozzle and the intranasal medicament delivery device and such that the valve member inhibits the ingress of air into an outlet of the medicament delivery device via the intranasal nozzle.

[0099] The method of preparing the intranasal medicament delivery system may be performed prior to the delivery of medicament to a patient.

[0100] According to the present disclosure, there is also provided a method of operating an intranasal medicament delivery system, the method comprising: coupling an intranasal nozzle to a component of an intranasal medicament delivery device such that the intranasal nozzle seals around an outlet of the intranasal medicament delivery device and such that the valve member inhibits the ingress of air into the outlet via the intranasal nozzle; and, expelling medicament from the intranasal medicament delivery device such that the medicament flows past the valve member and out of the intranasal nozzle.

[0101] The method may comprise expelling / administering an RSV vaccine.

[0102] The medicament may be expelled / delivered intranasally with about % dose delivered to each nostril. Attorney Docket No.: 46567-1783WO1

[0103] The intranasal dose of the medicament may be delivered in about 0.2 mL, wherein about 0.1 mL is delivered to each nostril.

[0104] The method may comprise intranasal atomization delivery of an average droplet size Dv50 of about 10-120 pm.

[0105] 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.

[0106] The method may comprise intranasal atomization delivery so that an average shot volume to each nostril is between about 85 pL to about 120 pL, about 90 pL to about 115 pL, or about 95 pL to about 115 pL.

[0107] In some embodiments, the method comprises removing the medicament delivery device from a sealed pack.

[0108] In some embodiments, the method comprises removing the intranasal nozzle from a sealed pack and coupling the intranasal nozzle to the medicament delivery device.

[0109] In some embodiments, the method comprises interfacing a medicament container with a housing of the medicament delivery device. In some embodiments, the method comprises removing the medicament container from a sealed pack and interfacing the medicament container with the housing.

[0110] In some embodiments, the method comprises drawing medicament from a medicament container into a chamber.

[0111] In some embodiments, the method comprises expelling medicament from the chamber for delivery to a user.

[0112] According to the present disclosure, there is also provided a method of preparing an intranasal medicament delivery system, the method comprising: drawing medicament into a chamber of a medicament delivery device, wherein a blocking member seals an outlet of the chamber to inhibit the ingress of air into the chamber via the outlet; and, replacing the blocking member with an intranasal nozzle. Attorney Docket No.: 46567-1783WO1

[0113] According to the present disclosure, there is also provided a method of operating an intranasal medicament delivery system, the method comprising: drawing medicament into a chamber of a medicament delivery device, wherein a blocking member seals an outlet of the chamber to inhibit the ingress of air into the chamber via the outlet; replacing the blocking member with an intranasal nozzle; and, expelling medicament from the chamber such that the medicament flows past the valve member and out of the intranasal nozzle.

[0114] The method may comprise expelling / administering an RSV vaccine.

[0115] The medicament may be expelled / delivered intranasally with about % dose delivered to each nostril.

[0116] The intranasal dose of the medicament may be delivered in about 0.2 mL, wherein about 0.1 mL is delivered to each nostril.

[0117] The method may comprise intranasal atomization delivery of an average droplet size Dv50 of about 10-120 pm.

[0118] 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.

[0119] The method may comprise intranasal atomization delivery so that an average shot volume to each nostril is between about 85 pL to about 120 pL, about 90 pL to about 115 pL, or about 95 pL to about 115 pL.

[0120] In some embodiments, the method comprises removing the medicament delivery device from a sealed pack.

[0121] In some embodiments, the method comprises coupling the intranasal nozzle to the medicament delivery device.

[0122] In some embodiments, the method comprises removing the intranasal nozzle from a sealed pack and coupling the intranasal nozzle to the medicament delivery device. Attorney Docket No.: 46567-1783WO1

[0123] In some embodiments, the method comprises interfacing a medicament container with a housing of the medicament delivery device. In some embodiments, the method comprises removing the medicament container from a sealed pack and interfacing the medicament container with the housing.

[0124] In some embodiments, the method comprises drawing medicament from a medicament container into a chamber.

[0125] In some embodiments, the method comprises expelling medicament from the chamber for delivery to a user.

[0126] Brief description of the drawings

[0127] So that the invention may be more fully understood, reference is made to the accompanying drawings, in which:

[0128] Fig. 1 is a cross-sectional side view of a medicament delivery device of an embodiment of an intranasal medicament delivery system;

[0129] Fig. 2 is a side view of an intranasal nozzle;

[0130] Fig. 3 is a cross-sectional side view of the intranasal medicament delivery system, wherein a blocking member seals an outlet of the medicament delivery device;

[0131] Fig. 4 is a cross-sectional side view of the intranasal medicament delivery system, wherein medicament has been drawn into a chamber of the device;

[0132] Fig. 5 is a cross-sectional side view of the intranasal medicament delivery system, wherein the blocking member has been removed;

[0133] Fig. 6 is a cross-sectional side view of the intranasal medicament delivery system, wherein an intranasal nozzle has been attached to the medicament delivery device; Fig. 7 is a cross-sectional side view of the intranasal medicament delivery system, wherein a trigger has been pressed to operate a drive mechanism;

[0134] Fig. 8 is a cross-sectional side view of the intranasal medicament delivery system, wherein medicament has been expelled from the chamber;

[0135] Fig. 9 is a perspective view of another embodiment of an intranasal medicament delivery system;

[0136] Fig. 10 is a perspective view of the intranasal medicament delivery system, wherein a blocking member seals an outlet of the medicament delivery device;

[0137] Fig. 11 is a perspective view of the blocking member;

[0138] Fig. 12 is a perspective view of the intranasal medicament delivery system of Fig. 9, wherein the blocking member has been replaced with an intranasal nozzle; Attorney Docket No.: 46567-1783WO1

[0139] Fig. 13 is a perspective view of the intranasal medicament delivery system of Fig. 9, wherein medicament has been drawn into a chamber of the system;

[0140] Fig. 14 is a perspective view of the intranasal medicament delivery system of Fig. 9, wherein the system is positioned for medicament deliver to a patient;

[0141] Fig. 15 is a perspective view of an intranasal nozzle of the system of Fig. 9;

[0142] Fig. 16 is a cross-sectional view of the intranasal nozzle;

[0143] Fig. 17 is an end view of the intranasal nozzle;

[0144] Fig. 18 is a cross-sectional side view of a distal region of the system of Fig. 9;

[0145] Fig. 19 is a disassembled perspective view of a distal region of another embodiment of an intranasal medicament delivery system;

[0146] Fig. 20 is a flowchart showing an example method of preparing an intranasal medicament delivery system; and,

[0147] Fig. 21 is a flowchart showing another example method of preparing an intranasal medicament delivery system.

[0148] A drug delivery device, as described herein, may be configured to inject a medicament into a patient or to deliver medicament intranasally or orally. For example, delivery could be sub-cutaneous, intra-muscular, intravenous or the delivery could be to the mouth or nasal structures. Such a device could be operated by a patient or care-giver, such as a nurse or physician, and can include various types of safety syringe, pen-injector, or autoinjector. The device can include a cartridge-based system that requires piercing a sealed ampule before use. Volumes of medicament delivered with these various devices can range from about 0.5 ml to about 2 ml. Yet another device can include a large volume device (“LVD”) or patch pump, configured to adhere to a patient’s skin for a period of time (e.g., about 5, 15, 30, 60, or 120 minutes) to deliver a “large” volume of medicament (typically about 2 ml to about 10 ml).

[0149] In combination with a specific medicament, the presently described devices may also be customized in order to operate within required specifications. For example, the device may be customized to inject a medicament within a certain time period (e.g., about 3 to about 20 seconds for auto-injectors, and about 10 minutes to about 60 minutes for an LVD). Other specifications can include a low or minimal level of discomfort, or to certain conditions related to human factors, shelf-life, expiry, biocompatibility, environmental considerations, etc. Such variations can arise due to various factors, such as, for example, a drug ranging in viscosity from about 3 cP to about 50 cP. Consequently, a Attorney Docket No.: 46567-1783WO1 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.

[0150] 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.

[0151] The one or more automated functions of an auto-injector may each be activated via an activation mechanism. Such an activation mechanism can include one or more of a button, a lever, a needle sleeve, or other activation component. Activation of an automated function may be a one-step or multi-step process. That is, a user may need to activate one or more activation components in order to cause the automated function. For example, in a one-step process, a user may depress a needle sleeve against their body in order to cause injection of a medicament. Other devices may require a multi-step activation of an automated function. For example, a user may be required to depress a button and retract a needle sleeve in order to cause injection.

[0152] 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.

[0153] Some delivery devices can include one or more functions of a safety syringe, pen-injector, or auto-injector. For example, a delivery device could include a mechanical energy source configured to automatically inject a medicament (as typically found in an autoinjector) and a dose setting mechanism (as typically found in a pen-injector).

[0154] The present disclosure relates to a medicament delivery system comprising a medicament delivery device and an intranasal nozzle for use with the medicament delivery device. The medicament delivery device may be reusable or single-use. Attorney Docket No.: 46567-1783WO1

[0155] The intranasal medicament delivery device, as described herein, is configured to deliver medicament intranasally. For example, delivery is to the nasal structures. Such a device could be operated by a patient or care-giver, such as a nurse or physician. The device can include a cartridge-based system that requires piercing a sealed ampule before use.

[0156] The delivery devices described herein can also include one or more automated functions. For example, medicament delivery 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.

[0157] The one or more automated functions 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.

[0158] Referring now to Figs. 1 to 8, an embodiment of an intranasal medicament delivery system 1 is shown. The intranasal medicament delivery system 1 comprises an intranasal medicament delivery device 100, an intranasal nozzle 200, a medicament container 300 and a blocking member 400. The intranasal medicament delivery device 100 (hereinafter ‘medicament delivery device 100’) may be reusable or single-use.

[0159] The intranasal nozzle 200 is configured to deliver medicament to the nasal structures of a patient. In the present example, the intranasal nozzle 200 comprises a nozzle outlet 203.

[0160] Optionally, the intranasal nozzle 200 comprises first and second medicament delivery conduits (not shown) configured to deliver medicament to both of the external nostrils of the patient simultaneously. The first and second medicament delivery conduits comprise first and second nozzle outlets respectively.

[0161] In the foregoing description, 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 user’s nose when the medicament is delivered intranasally). Attorney Docket No.: 46567-1783WO1

[0162] Figs. 3 and 4 show the medicament device 100 with the blocking member 400 received in a receiving space 117 of the device 100 such that the blocking member 400 is coupled to the medicament delivery device 100. Figs. 6 to 8 show the medicament device 100 with the intranasal nozzle 200 received in the receiving space 117 of the device 100 such that the intranasal nozzle 200 is coupled to the medicament delivery device 100.

[0163] The device 100 comprises: a housing 110 and a dose delivery mechanism provided within the housing 110.

[0164] The housing 110 comprises a primary tubular wall 111 that extends along the device axis X-X and houses the dose delivery mechanism; and a secondary tubular wall 112 that extends from the primary tubular wall 111 , perpendicular to the device axis X-X. The secondary tubular wall 112 is integrally formed with the primary tubular wall 111 and surrounds a port 113 which is configured to receive a medicament container 300, which in the present example, is a cylindrical medicament cartridge 300. The port 113 comprises a cannula 114 that communicates with a dosing chamber 121 of the dose delivery mechanism 120 via an inlet 114A. The cannula 114 penetrates a bung of the medicament cartridge 300 to allow medicament to flow from the cartridge 300 and into the dosing chamber 121 via the inlet 114A.

[0165] In some embodiments, the device 100 has an intended filling orientation (for instance, wherein the device axis X-X is horizontal with respect to the ground, as shown in Fig. 3 in respect of the device 100 of the present embodiment and Fig. 15A in respect of the device 100’ of the later embodiment). The port 113 is arranged such that during filling of the device 100 the cartridge 300 is orientated such that medicament flows towards the cannula 114 under the influence of gravity when the device 100 is in the intended filling orientation. This helps to encourage medicament to flow from the cartridge 300 and into the cannula 114. That is, the cannula 114 is located below the cartridge 300 (or other such medicament container). In some embodiments, the port 113 is configured such that when the device 100 is in the filling position, the cartridge 300 is orientated vertically or substantially vertically. In some embodiments, in the intended filling orientation of the device 100, a central axis of the piston 1241 is horizontal.

[0166] Optionally, the device 100 is configured to rest on a flat surface such that the device 100 is orientated in the intended filling orientation. Thus, a user can place the device 100 on the flat surface (e.g. a table) and then fill the dosing chamber 121 (e.g. by rotating the dosing knob 126 to draw medicament into the device 100, as is described in more detail Attorney Docket No.: 46567-1783WO1 below). The device 100 may comprise one or more contact portions that are configured to engage the flat surface such that the device 100 is orientated in the intended filling orientation. The contact portion(s) may comprise, for example, a flat bottom of the housing 110 or one or more feet / legs of the device 100. For instance, the housing 110 may comprise a flat bottom (not shown), on the opposite side of the housing 110 to the port 113, such that the device 100 can be rested on the flat bottom with the port 113 extending vertically such that the cartridge 300 is orientated vertically and thus medicament in the cartridge 300 flows down towards the cannula 114. As another example, the housing 110 may comprise a plurality of feet (not shown), such that the device 100 can be rested on the feet with the port 113 extending vertically such that the cartridge 300 is orientated vertically and thus medicament flows down towards the cannula 114.

[0167] Optionally, in some embodiments, the device 100 comprises one or more indicators configured to indicate to a user the intended filling orientation of the device 100. The indicators may comprise, for example, one or more graphic symbols or text on the device 100. In some embodiments, the user may hold the device 100 in the filling orientation according to the indicator(s) (rather than placing the device 100 on a flat surface) when filling the device 100 with medicament from the container 300.

[0168] The components of the dose delivery mechanism are arranged coaxially along the device axis X-X and comprise a drive mechanism 120, a plunger rod 124 and a dosing actuator 126. In the present example, the drive mechanism 120 comprises a drive biasing member 124s. However, it should be recognised that in other embodiments (not shown) the drive mechanism 120 may have a different configuration, for example, comprising an energy course which can include, for example, mechanical, pneumatic, chemical, or electrical energy. For example, mechanical energy sources can include springs, levers, elastomers, or other mechanical mechanisms to store or release energy to move the plunger rod 124.

[0169] The plunger 124 is optionally in the form of a plunger rod 124. The plunger rod 124 comprises a piston 1241 at its distal end that is configured to traverse the dosing chamber 121 to dispense medicament in use. The piston 1241 may comprise, for example, an elastomer stopper that is located at a distal end of the plunger rod 124.

[0170] The dosing chamber 121 comprises a tubular wall 1211 that is partially closed by an annular wall 1212 at its distal end. The tubular wall 1211 and annular wall 1212 may be Attorney Docket No.: 46567-1783WO1 integrally formed and may be part of the housing 110 of the medicament delivery device 100.

[0171] The proximal end of the tubular wall 1211 is open to receive the piston 1241 of the plunger rod 124. A central opening 1213 in the annular wall 1212 provides an outlet 1213 of the dosing chamber 121.

[0172] A proximal end 1242 of the plunger rod 124 protrudes from a proximal end of the housing 110 of the medicament delivery device 100. The dosing actuator 126 is connected to the proximal end 1242 of the plunger rod 124. In other embodiments, the dosing actuator 126 is integrally formed with the plunger rod 124.

[0173] The dosing actuator 126 is configured to be moved in a first direction A1 , which in the present example is a proximal direction, such that the plunger rod 124 is also moved in the first direction A1 relative to the housing 110. In some embodiments, this compresses the drive biasing member 124s and therefore ‘charges’ or ‘primes’ the drive biasing member 124s ready for use. For example, the drive biasing member 124s may comprise a drive spring 124s and wherein movement of the plunger rod 124 in the first direction A1 may compress the drive spring 124s.

[0174] The housing 110 comprises a chamber 116 that receives the drive biasing member 124s. The housing 110 comprises a radial wall 115 that is located at a proximal end of the chamber 116. A proximal end of the drive biasing member 124s is located against the radial wall 115.

[0175] The plunger rod 124 comprises a flange 1243 that extends radially outwardly from the plunger rod 124. An annular element 1244 is located about the plunger rod 124, on the proximal side of the flange 1243 such that a proximally facing surface of the flange 1243 abuts the annular element 1244. A distal end of the drive biasing member 124s is located against the annular element 1244. It should be recognised that in other embodiments (not shown) the annular element 1244 is integrally formed with the flange 1243 or is omitted entirely such that the flange 1242 (or other protruding part of the plunger rod 124) abuts the distal end of the drive biasing member 124s.

[0176] The drive biasing member 124s is therefore located between the radial wall 115 and the annular element 1244. Therefore, when the user pulls the actuator 126 relative to the housing 110 in the first direction A1 , the flange 1243 of the plunger rod 124 also moves in the first direction A1 such that the annular element 1244 moves in the first direction A1 . Attorney Docket No.: 46567-1783WO1

[0177] This decreases the distance between the annular element 1244 and the radial wall 115 such that the drive biasing member 124s is compressed between the annular element 1244 and the radial wall 115. This causes a biasing force to be exerted on the plunger rod

[0178] 124 by the drive biasing member 124s, that urges the plunger rod 124 in a second direction A2, opposite to the first direction A1 .

[0179] The plunger rod 124 is prevented from moving in the second direction A2 under the force of the drive biasing member 124s by a locking mechanism 125 that is initially in a locked position (as shown in Figs. 1 and 3 to 6). The locking mechanism 125 is configured to move to an unlocked position (shown in Figs. 7 and 8) upon actuation of a trigger 350. In the present example, the trigger 350 comprises a button 350 that is configured to be pressed by a user to move the locking mechanism 125 to the unlocked position. This releases the plunger rod 124 such that the plunger rod 124 is moved in the second direction A2 under to biasing force of the drive biasing member 124s to expel medicament from the chamber 121 and through the intranasal nozzle 200, as will be described in more detail below.

[0180] The locking mechanism 125 comprises an elongate member 351 that extends from the trigger 350 in a direction generally perpendicular to the central axis X-X of the medicament delivery device 100. The trigger 350 is located at a first end 351 A of the elongate member 351 . The elongate member 351 extends through a first slot 111 A or aperture in the tubular wall 111 of the housing 110. A second end 351 B of the elongate member 351 is received in a second slot 111 B in the tubular wall 111 of the housing 110.

[0181] When the user presses the trigger 350 towards the housing 110, the elongate member 351 sides within the first and second slots 111 A, 111 B such that the locking mechanism

[0182] 125 moves to the unlocked position, wherein a locking portion 352 of the elongate member 351 is moved out of engagement with the plunger rod 124, thereby allowing the plunger rod 124 to move in the second direction A2 under the biasing force of the drive biasing member 124s.

[0183] In the present example, the locking portion 352 is configured to frictionally engage the plunger rod 124 to hold the plunger rod 124 in position against the biasing force of the drive biasing member 125. The locking portion 352 comprises a projection 352 that protrudes from the elongate member 351 . When the elongate member 351 is slide relative to the housing 110 due to the user pressing the trigger 350, the locking portion 352 moves Attorney Docket No.: 46567-1783WO1 out of frictional engagement with the plunger rod 124 (or the friction therebetween is reduces).

[0184] In another embodiment (not shown), the plunger rod 124 comprises a plurality of ratchet teeth (not shown). The ratchet teeth are configured to ride over the locking portion 352 as the plunger rod 124 is urged in the first direction A1. The locking portion 352 engages the ratchet teeth when the locking mechanism 125 is in the locked position to prevent the plunger rod 124 from moving in the second direction A2 under the biasing force of the drive biasing member 124s. When the elongate member 351 is slide relative to the housing 110 due to the user pressing the trigger 350, the locking portion 352 moves out of engagement with the plunger rod 124 such that the plunger rod 124 is moved in the second direction A2 under the force of the drive biasing member 124s.

[0185] The locking mechanism 125 further comprises a biasing member 353 (shown in Fig. 1 , but not shown in the remaining drawings) configured to urge the locking mechanism into the locked position. In the present example, the biasing member 353 is a spring. In the present example, the biasing ember 353 is located in the second slot 111 B of the housing 110 and is configured to urge the elongate member 351 to the position shown in Figs. 1 and 3 to 6 wherein the trigger 350 is spaced from the housing 110. To operate the drive mechanism 120, the user presses the trigger 350 towards the housing 110 against the force of the biasing member 353 such that the locking mechanism moves to the unlocked position. When the user releases the trigger 350, the biasing member 353 returns the trigger 350 to its initial position such that the locking mechanism returns to the locked position.

[0186] The blocking member 400 comprises a plug 400. The plug 400 may be a blind plug 400.

[0187] The blocking member 400 comprises a sealing portion 401 and a gripping portion 402. The sealing portion 401 is configured to be received within the receiving space 117 of the medicament delivery device 100 in order to seal the outlet 1213 of the chamber 121. In the present example, the sealing portion 401 is retained within the receiving space 117 by friction. However, it should be recognised that in other embodiments (not shown) the blocking member 400 and / or medicament delivery device 100 may comprise a coupling to retain the blocking member 400 in position relative to the medicament delivery device 100. The coupling may comprise, for example, a threaded connection or bayonet connection. Attorney Docket No.: 46567-1783WO1

[0188] The gripping portion 402 extends from the sealing portion 401 and is configured to be gripped by a user to attach and remove the blocking member 400 from the receiving space 117.

[0189] An exemplary operation of the intranasal medicament delivery system 1 will now be described. The user may fluidly couple the medicament container 300 to the port 113 by urging the end of the medicament container 300 into the port 113 until the cannula 114 penetrates a sealing element 304 (e.g. septum 304) at an end 303 of the medicament container 300. Furthermore, the user couples the blocking member 400 to the receiving space 117 such that the blocking member 400 seals the outlet 1213 of the chamber 121.

[0190] Initially, the plunger rod 124 is in a distal position (see Fig. 3). To operate the device 100, the user / operator firstly charges the dosing chamber 121 with a dosage volume of medicament by pulling the dosing actuator 126 in the first direction A1 relative to the housing 110. This causes the plunger rod 124 to be urged in the first direction A1 , against the force of the plunger biasing member 124s, such that suction is created in the dosing chamber 121 and thus medicament is drawn into the dosing chamber 121 from the medicament container 300 via the cannula 114 and inlet 114A once the piston 1241 passes the cannula 114 (as shown in Fig. 4). During the movement of the plunger rod 124 in the first direction A1 , the blocking member 400 advantageously prevents air from being drawn into chamber 121 via the outlet 1213. During this movement of the plunger rod 124 in the first direction A1 , the drive biasing member 124 is primed, wherein the locking mechanism 125 holds the plunger rod 124 in position against the biasing force of the drive biasing member 124.

[0191] Once a dose of medicament has been drawn into the chamber 121 , the user then removes the blocking member 400 from the receiving space 117 (as shown in Fig. 5) and inserts the intranasal nozzle 200 into the receiving space 117 (as shown in Fig. 6) such that the intranasal nozzle 200 is fluidly communicated with the outlet 1213 of the chamber 121.

[0192] In the present example, the intranasal nozzle 200 comprises a base 205 that is configured to be received in the receiving space 117. The intranasal nozzle 200 optionally further comprises a gripping portion 206 configured to be gripped by the user to aid in manipulation of the intranasal nozzle 200. The nozzle outlet 203 is located at the distal end of the intranasal nozzle 200. A conduit or passage (not shown) extends through the intranasal nozzle from the base 205 to the nozzle outlet 203 such that, in use, Attorney Docket No.: 46567-1783WO1 medicament expelled from the outlet 1213 of the chamber 121 can enter the base 205 and flow through the intranasal nozzle 200 to the nozzle outlet 203 for delivery to the user.

[0193] In the present example, the base 205 is retained within the receiving space 117 by friction. However, it should be recognised that in other embodiments (not shown) the intranasal nozzle 200 and / or medicament delivery device 100 may comprise a coupling to retain the base 205 in position relative to the medicament delivery device 100. The coupling may comprise, for example, a threaded connection or bayonet connection.

[0194] Once the intranasal nozzle 200 has been communicated with the chamber 121 (which in the present example involves inserting the base 205 into the receiving space 117, but in other embodiments the receiving space 117 is omitted and instead the intranasal nozzle 200 is attached in a different manner), the medicament delivery device 100 is positioned such that the intranasal nozzle 200 is located in proximity to the nose of a patient. The user (who may be the patient or may be another person, such as a healthcare practitioner) then presses the trigger 350 towards the body 110 such that the locking mechanism is moved from the locked position to the unlocked position (as shown in Fig. 7). This causes the plunger rod 124 to be released such that it moves in the second direction A2 under the force of the drive biasing member 124s. The piston 1241 thus moves in the second direction A2 within the chamber 121 such that the medicament contained in the chamber 121 is expelled from the outlet 1213 and into the intranasal nozzle 200, wherein the medicament flows out of the nozzle outlet 203 for delivery to the nasal structures of the patient.

[0195] Optionally, the medicament delivery device 100 may then be reused, by repeating the steps of Figs. 3 to 8 to deliver further doses of medicament from the intranasal nozzle 200 (or from a different intranasal nozzle 200, which is particularly advantageous if the medicament is to be delivered to a different patient).

[0196] Referring now to Figs. 9 to 18, another embodiment of an intranasal medicament delivery system 1 ’ is shown. The intranasal medicament delivery system 1 ’ is similar to the intranasal medicament delivery system 1 of the embodiment of Figs. 1 to 8, with like features retaining the same reference numerals.

[0197] The intranasal medicament delivery system T comprises a medicament delivery device 100’, an intranasal nozzle 200’, a medicament container 300’ and a blocking member 400. Attorney Docket No.: 46567-1783WO1

[0198] The medicament delivery device 100’ has a similar dose delivery mechanism to the medicament delivery device 100 of Figs. 1 to 8, comprising a plunger rod (not shown) that is moveable within the housing 110 to urge a piston (not shown) to move within a chamber 121. The user pulls the actuator 126 in a first direction A1 to draw medicament into the chamber 121 from the medicament container 300’ against the force of a drive biasing member (not shown). A locking mechanism then retains the plunger rod in position against the biasing force of the drive biasing member until the user presses the trigger button 350 towards the housing 110 to move the locking mechanism to the unlocked position, thereby operating the drive mechanism such that the drive biasing member urges the plunger rod in the second direction A2 to expel the medicament from the chamber 121 and out of the intranasal nozzle 200’ for delivery to a user. A difference is that the actuator 126 comprises a sleeve 126A that surrounds the plunger rod so that the plunger rod is not visible when the actuator 126 is pulled in the first direction A1. The sleeve 126A extends into the housing 110.

[0199] Another difference is that in the embodiment of Figs. 9 to 18, the intranasal medicament delivery system 1 ’ comprises a medicament container 300’ that is in the form of a vial 300’. However, it should be recognised that in all of the embodiments described herein, the system 1 , 1’, 1 ” can be used with a medicament container in the form of a cartridge or vial, or another configuration of medicament container.

[0200] The intranasal medicament delivery system 1 ’ of Figs. 9 to 18 comprises an intranasal nozzle 200’ that has first and second medicament delivery conduits 20T, 202’. The first medicament delivery conduit 201 ’ comprises a first nozzle outlet 203’ and the second medicament delivery conduit 202’ comprises a second nozzle outlet 204’. This allows for the medicament to be delivered to both nostrils of a user simultaneously, thereby reducing the medicament delivery duration and improving comfort for the user.

[0201] The intranasal nozzle 200’ comprises a one-way valve 127. The one way-valve 127 is provided on a proximal side of a base 205’ of the intranasal nozzle 200’. The one-way valve 127 is configured for engagement with the medicament delivery device 100’, for example, with the housing 110 such as an end wall 1212 of the medicament delivery device 100’.

[0202] When the intranasal nozzle 200’ is coupled to the medicament delivery device 100, the one-way valve is provided externally across the central opening 1213 of the annular wall 1212. Attorney Docket No.: 46567-1783WO1

[0203] The one-way valve 127 comprises a gasket 128. The one-way valve 127 is moulded from a resilient material with sealing properties, such as rubber. The gasket 128 is an outer annular ring that seals to the medicament delivery device 100’ when the intranasal nozzle 200’ and medicament delivery device 100’ are combined. The gasket 128 thus prevents the leakage of medicament from the interface between the medicament delivery device 100’ and the intranasal nozzle 200’. In the present example, the gasket 128 is configured to seal about the outlet 1213 of the medicament delivery device 100’.

[0204] A valve member 130 is provided concentrically within the gasket 128 and connected thereto by a stem 129. In the present example, the valve member is a plug 130.

[0205] The valve member 130 comprises a chamfered portion 130A that is configured to sit against an edge 1213A of the opening 1213 in the annular wall 1212 of the dosing chamber 121 when the intranasal nozzle 200’ is coupled to the medicament delivery device 100’ (as shown in Fig. 18). The edge 1213A may be chamfered. The edge 1213A may form a valve seat 1213A. During operation of the one-way valve 127, the stem 129 flexes to allow medicament to flow through the opening 1213 and past the valve member 130 to flow through the intranasal nozzle 200’.

[0206] The gasket 128 may be integrally formed with the plug 130 from a single portion of material.

[0207] Advantageously, the one-way valve 127 prevents the ingress of air into the outlet 1213 via the intranasal nozzle 200’ but permits medicament to be expelled from the outlet 1213 for delivery to the user via the intranasal nozzle 200’.

[0208] An exemplary operation of the intranasal medicament delivery system T will now be described. The user may fluidly couple the medicament container 300 to the port 113 by urging the end of the medicament container 300’ into the port 113 until the cannula penetrates a sealing element 304 (e.g. septum 304) at an end 303 of the medicament container 300’, which in the present example, is a vial 300’.

[0209] The system 1 ’ may be supplied in a configuration wherein the blocking member 400 is coupled to the medicament delivery device 100’ (e.g. a portion of the blocking member 400 may be received within a receiving space and / or the blocking member 400 may be coupled to the device 100’ by a threaded connection or bayonet connection) such that the blocking member 400 seals the outlet 1213 of the chamber 121 (as shown in Fig. 10). Attorney Docket No.: 46567-1783WO1

[0210] This prevents contaminants from entering the outlet 1213 prior to use of the medicament delivery device 100’. However, it should be recognised that in other embodiments (not shown), the blocking member 400 may be omitted.

[0211] Before or after connecting the medicament container 300’ to the port 113, the user removes the blocking member 400 from the medicament delivery device 100’ and replaces it with the intranasal nozzle 200’ (as shown in Fig. 12).

[0212] Initially, the plunger rod is in a distal position such that the piston of the plunger rod is in a distal position within the chamber 121 . To operate the device 100’, the user / operator firstly charges the dosing chamber 121 with a dosage volume of medicament by pulling the dosing actuator 126 in the first direction A1 relative to the housing 110 (as shown in Fig. 13). This causes the plunger rod to be urged in the first direction A1 , against the force of the plunger biasing member, such that suction is created in the dosing chamber 121 and thus medicament is drawn into the dosing chamber 121 from the medicament container 300’ via the cannula (not shown) and inlet (not shown) once the piston (not shown) axially passes the cannula. During the movement of the plunger rod in the first direction A1 , the one-way valve 127 of the intranasal nozzle 200’ advantageously prevents air from being drawn into chamber 121 via the outlet 1213. During this movement of the plunger rod in the first direction A1 , the drive biasing member is primed, wherein the locking mechanism holds the plunger rod in position against the biasing force of the drive biasing member.

[0213] Once the dose of medicament has been drawn into the chamber 121 , the medicament delivery device 100’ is positioned such that the intranasal nozzle 200’ is located in proximity to the nose of a patient. In the present example, the ends of the first and second medicament delivery conduits 201’, 202’ are slid into the patient’s nostrils. Fig. 14 shows the device 100’ being positioned relative to a patient P for medicament delivery to the nasal structures of the patient P.

[0214] The user (who may be the patient or may be another person, such as a healthcare practitioner) then presses the trigger 350 towards the body 110 such that the locking mechanism is moved from the locked position to the unlocked position. This causes the plunger rod to be released such that it moves in the second direction A2 under the force of the drive biasing member. The piston thus moves in the second direction A2 within the chamber 121 such that the medicament contained in the chamber 121 is expelled from the outlet 1213 and into the intranasal nozzle 200’, wherein the medicament flows out of the nozzle outlets 203’, 204’ for delivery to the nasal structures of the patient. Attorney Docket No.: 46567-1783WO1

[0215] Optionally, the medicament delivery device 100’ may then be reused, by repeating the steps of Figs. 9 to 14 to deliver further doses of medicament from the intranasal nozzle 200’ (or from a different intranasal nozzle 200’, which is particularly advantageous if the medicament is to be delivered to a different patient).

[0216] In an alternative embodiment (not shown), the one-way valve 127 of the intranasal nozzle 200’ is omitted. Instead, the blocking member 400 is coupled to the medicament delivery device 100’ during movement of the plunger rod in the first direction A1 to draw medicament into the chamber 121 , and thus the blocking member 400 prevents the ingress of air into the chamber 121 during this movement of the plunge rod. The blocking member 400 is then replaced with the intranasal nozzle 200’ prior to the delivery of medicament to the patient.

[0217] Referring now to Fig. 19, another embodiment of an intranasal medicament delivery system 1 ” is shown. The intranasal medicament delivery system 1 ” is similar to the intranasal medicament delivery system 1 ’ described above in relation to Figs. 9 to 18, with like features retaining the same reference numerals.

[0218] The intranasal medicament delivery system 1 ” comprises a medicament delivery device 100”, an intranasal nozzle 200” and a medicament container 300.

[0219] A difference is that the medicament delivery device 100” comprises the one-way valve 127 instead of the intranasal nozzle 200” comprising the one-way valve 127.

[0220] The distal end of the medicament delivery device 100” and the proximal end of the intranasal nozzle 200” are shown in a detached state in the perspective view in Fig. 19. An annular wall 119 of the device 100” extends internally within the primary tubular wall 111 of the housing 110. The annular wall 119 is recessed from the open distal end of the primary tubular wall 111 and defines a receiving space 117 for the intranasal nozzle 200”. When the intranasal nozzle 200” and the medicament delivery device 100” are combined, a proximal end of the intranasal nozzle 200” is received in the receiving space 117 and abuts the annular wall 119.

[0221] In the present example, the receiving space 117 comprises retaining members 118 configured to cooperate with locking tabs 248 of the intranasal nozzle 200” for bayonet style attachment. The retaining members 118 each comprise a slot 1181 formed between the annular wall 119 and a lip 1182 that projects radially inward from the primary tubular Attorney Docket No.: 46567-1783WO1 wall 111 of the housing 110. One end of each slot 1181 is provided with a stop 1183, the other is open ended. To attach the intranasal nozzle 200” to the medicament delivery device 100”, the proximal end of the intranasal nozzle 200” is placed within the receiving space 117 so that the tabs 248 are aligned with an open end of each slot 1181. The intranasal nozzle 200” is then rotated in a first direction so that the tabs 248 are received within the slot 1181.

[0222] In the present example, the medicament delivery device 100” comprises a pair of locking elements 1184 that are configured to retain the tabs 248 within the respective slots 1181 to prevent detachment of the intranasal nozzle 200” from the device 100”. The locking elements 1184 protrude from the end of the slots 1181 in the proximal direction such that the locking elements 1184 snap past the tabs 248 when the tabs 248 are inserted into the slots 1181. The locking elements 1184 may be provided at the opposite end of the respective slots 1181 to the stops 1183. However, it should be recognised that in other embodiments the locking elements 1184 may be omitted such that the intranasal nozzle 200” is detachable from the medicament delivery device 100”. In some embodiments, the intranasal nozzle 200” is configured to be releasably coupled to the device 100” by a coupling, for example, a threaded connection or bayonet connection.

[0223] During rotation of the intranasal nozzle 200” in the first direction relative to the housing 110, the locking tabs 248 of the intranasal nozzle 200”abut the stops 1183 of the retaining members 118.

[0224] The medicament delivery device 100” comprises the one-way valve 127. The one-way valve 127 is provided externally across the central opening 1213 of the annular wall 1212. The one-way valve 127 is adjacent the distal end of the housing 110 and configured for engagement with the intranasal nozzle 200”.

[0225] The one-way valve 127 comprises a gasket 128, as shown in Fig. 19. The one-way valve

[0226] 127 is moulded from a resilient material with sealing properties, such as rubber. The gasket 128 is an outer annular ring that seals to the intranasal nozzle 200” when the intranasal nozzle 200” and medicament delivery device 100” are combined. The gasket

[0227] 128 thus prevents the leakage of medicament from the interface between the device 100” and the intranasal nozzle 200”. The gasket 128 abuts the base 205’ of the intranasal nozzle 200” to form a seal between the medicament delivery device 100” and the intranasal nozzle 200”. Attorney Docket No.: 46567-1783WO1

[0228] A valve member 130 is provided concentrically within the gasket 128 and connected thereto by a stem 129. In the present example, the valve member is a plug 130.

[0229] The valve member 130 comprises a chamfered portion 130A that sits against an edge 1213A of the opening 1213 in the annular wall 1212 of the dosing chamber 121. The edge 1213A may be chamfered. The edge 1213A may form a valve seat 1213A. During operation of the one-way valve 127, the stem 129 flexes to allow medicament to flow through the opening 1213 and past the valve member 130 to flow through the intranasal nozzle 200”.

[0230] The intranasal medicament delivery system 1 ” of Fig. 19 used in a similar manner to as described above in reference to the intranasal medicament delivery system 1 ’ described above in relation to Figs. 9 to 18. However, since the one-way valve 127 is part of the medicament delivery device 100” (rather than the intranasal nozzle 200”), then medicament can be drawn into the chamber (not shown) prior to attaching the intranasal nozzle 200” to the device 100” (and without a blocking member 400 being present). The one-way valve 127, which in integrated into the device 100”, prevents air being drawn into the chamber via the outlet 1213 whilst the medicament is being drawn into the chamber from the medicament container 300 due to operation of the actuator (not shown).

[0231] In the above-described embodiments, the plunger rod 124 of the device 100, 100’ is configured to move from the first position to the second position against the biasing force of the biasing member 124s and, optionally, movement of the plunger rod 124 from the first position to the second position primes the biasing member 124s. This allows for the biasing member 124s to be primed / compressed when a user prepares the device 100, 100’ for medicament delivery. However, in other embodiments (not shown) the device 100, 100’ may be supplied with the biasing member 124s in a pre-primed / pre-compressed state and wherein when the plunger rod 124 is moved from the first position to the second position this is not against the force of the biasing member 124s (and optionally does not prime the biasing member 124s, which is already primed). In one such embodiment, the device 100, 100’ is supplied with the biasing member 124s in a pre-primed state and held in this state by a locking mechanism. The user pulls the plunger rod 124 from the first position to the second position and then pushes the plunger rod 124 to the primed position (optionally without any force being exerted on the biasing member 124s), and then releases the biasing member 124s such that the plunger rod 124 is urged to the first position to dispense medicament from the device 100, 100’. Attorney Docket No.: 46567-1783WO1

[0232] In some embodiments, the plunger 124 is moveable in the second direction A1 to draw medicament into the device 100. However, it should be recognised that in other embodiments (not shown), the device is pre-filled with medicament such that medicament is not drawn into the device. For example, the device may be provided to the end user with a container (for example, a cartridge or syringe) that contains the medicament. In some embodiments, the plunger is moveable in the first direction to provide space to accommodate the medicament container (which may be pre-filled with medicament) and then the plunger is moveable in the second direction to, firstly, take up a gap or ‘play’ between the plunger and the medicament container (e.g. a piston or bung of the medicament container), and then the plunger is further moveable in the second direction to expel medicament from the medicament container (e.g. by moving the piston or bung of the medicament container to expel medicament).

[0233] Referring now to Fig. 20, a method 1000 of operating an intranasal medicament delivery system is shown. The method 1000 comprises (step S1) coupling an intranasal nozzle to a component of an intranasal medicament delivery device such that the intranasal nozzle seals around an outlet of the intranasal medicament delivery device and such that the valve member inhibits the ingress of air into the outlet via the intranasal nozzle; and, (step S2) expelling medicament from the intranasal medicament delivery device such that the medicament flows past the valve member and out of the intranasal nozzle.

[0234] Referring now to Fig. 21 , a method 2000 of operating an intranasal medicament delivery system is shown. The method 2000 comprises (step S1) drawing medicament into a chamber of a medicament delivery device, wherein a blocking member seals an outlet of the chamber to inhibit the ingress of air into the chamber via the outlet; (step S2) replacing the blocking member with an intranasal nozzle; and, (step S3) expelling medicament from the chamber such that the medicament flows past the valve member and out of the intranasal nozzle.

[0235] 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.

[0236] 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. Attorney Docket No.: 46567-1783WO1

[0237] As used herein, “RSV ANS2 / A1313 / I1314L” refers to an RSV ANS2 / A1313 / I1314L (NIH) or an RSV ANS2 / A1313 / 11314L (Sanofi). Each of the ANS2 / A1313 / I1314L (NIH) and the RSV ANS2 / A1313 / I1314L (Sanofi) comprise a live-attenuated RSV with (i) a 523 nucleotide (nt) deletion of the NS2 gene (ANS2), (ii) an amino acid deletion in the L protein, and (iii) a genetically stabilizing mutation in the L gene. The live-attenuated RSV of the RSV ANS2 / A1313 / I1314L (Sanofi) also includes a nucleotide modification at position 14456 that represents a change from a thymine (T) to an adenine (A) in a noncoding region.

[0238] As used herein, “RSV ANS2 / A1313 / I1314L vaccine” refers to an “RSV ANS2 / A1313 / I1314L (NIH) vaccine” or an “RSV ANS2 / A1313 / I1314L (Sanofi) vaccine.” An RSV ANS2 / A1313 / I1314L (NIH) vaccine comprises an effective amount of RSV ANS2 / A1313 / I1314L (NIH). An RSV ANS2 / A1313 / I1314L (Sanofi) vaccine comprises an effective amount of RSV ANS2 / A1313 / I1314L (Sanofi).

[0239] Exemplary Methods and Uses

[0240] In some embodiments, provided are methods of delivering a dose of an RSV vaccine using an intranasal atomization delivery device.

[0241] 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). Attorney Docket No.: 46567-1783WO1

[0242] 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.

[0243] 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 7> dose delivered to one nostril and the other 7? 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.

[0244] 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.

[0245] 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.

[0246] 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 Attorney Docket No.: 46567-1783WO1 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 14 dose to each nostril of the subject.

[0247] 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 Dvso of 10-120 pm, about 30-110 pm, about 50- 110 pm, about 70-110 pm, or about 80-110 pm. In some embodiments, the intranasal atomization delivery device delivers an average shot weight between about 95 mg to about 135 mg, between about 100 mg to about 130 mg, or between about 100 mg to about 130 mg or between about 105 mg to about 130. In some embodiments, the intranasal atomization delivery device delivers an average shot volume of about 85 pL to about 120 pL, about 90 pL to about 115 pL, or about 95 pL to about 115 pL.

[0248] In some embodiments, use of an intranasal atomization delivery device described herein for administering a dose of an RSV vaccine to a subject is provided wherein the RSV vaccine comprises an effective amount of a live-attenuated RSV. In some embodiments, the use includes a live-attenuated RSV with (i) a 523 nucleotide (nt) deletion of the NS2 gene (ANS2), (ii) an amino acid deletion in the L protein, and (iii) a genetically stabilizing mutation in the L gene (RSVA NS2 / A1313 / 11314L) (NIH) vaccine or RSVA NS2 / A1313 / I1314L (Sanofi) vaccine that further comprises a nucleotide modification in a non-coding region that represents a change from a thymine (T) to an adenine (A).

[0249] Immunogenicity

[0250] 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. Attorney Docket No.: 46567-1783WO1

[0251] 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.

[0252] 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.

[0253] Vaccine virus shedding and Infectivity

[0254] Following each vaccine administration, the shedding of vaccine virus was considered in addition to the fold rise in neutralizing antibody titers or serum IgG as vaccine infectivity. The high level of vaccine infectivity (over 80% and 70% in RSV naive following the first and second vaccine administration respectively) is supportive of a promising vaccine candidate associated with good vaccine take. When infectivity was considered after either 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.

[0255] Interim analysis results showed a promising safety, immunogenicity and infectivity profile of the RSV ANS2 / A1313 / I1314L (Sanofi) candidate. Attorney Docket No.: 46567-1783WO1

[0256] 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.

[0257] 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.

[0258] 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 may be an immune response that protects a subject from infection (prevents infection or prevents the development of disease associated with infection) or reduces the symptoms of infection (for instance an infection by a virus or bacterium as provided above). Vaccines may elicit both prophylactic (preventative) and therapeutic responses.

[0259] List of Reference Numbers

[0260] 1 - medicament delivery system 1 ’ - medicament delivery system 1 ” - medicament delivery system 100 -medicament delivery device 100’ - medicament delivery device 100” - medicament delivery device

[0261] 110 - housing

[0262] 111 - primary tubular wall Attorney Docket No.: 46567-1783WO1

[0263] 111A- first slot 111B - second slot

[0264] 112- secondary tubular wall

[0265] 113 -port

[0266] 114- cannula

[0267] 114A- inlet

[0268] 115- radial wall

[0269] 116- chamber

[0270] 117- receiving space

[0271] 118- retaining members

[0272] 1181- slot

[0273] 1182 -lip

[0274] 1183- stop

[0275] 1184- locking element

[0276] 119 -annular wall

[0277] 120 - drive mechanism

[0278] 121 - dosing chamber

[0279] 1211 - tubular wall

[0280] 1212 - annular wall

[0281] 1213 -outlet

[0282] 1213A - edge (valve seat)

[0283] 124 - plunger rod

[0284] 124s - drive biasing member

[0285] 1241 - piston

[0286] 1242 - proximal end of plunger rod

[0287] 1243 - flange

[0288] 1244 - annular element

[0289] 125 - locking mechanism

[0290] 126 - actuator

[0291] 126 - sleeve

[0292] 127 - one-way valve

[0293] 128 - gasket

[0294] 129 - stem

[0295] 130 - valve member (plug) 130A - chamfered portion 200 - intranasal nozzle Attorney Docket No.: 46567-1783WO1

[0296] 200’ - intranasal nozzle

[0297] 200” - intranasal nozzle

[0298] 201’ - first medicament delivery conduit

[0299] 202' - second medicament delivery conduit

[0300] 203 -nozzle outlet

[0301] 203’ - first nozzle outlet

[0302] 204’ - second nozzle outlet

[0303] 205 - base

[0304] 205’ - base

[0305] 206 - gripping portion

[0306] 248 - locking tabs

[0307] 300 - medicament cartridge

[0308] 300’ - medicament vial

[0309] 301 - cylindrical wall

[0310] 302 - piston

[0311] 303 - end of cartridge

[0312] 304 - sealing element

[0313] 350 - trigger button

[0314] 351 - elongate member

[0315] 351 A - first end of elongate member

[0316] 351 B - second end of elongate member

[0317] 352 - locking portion

[0318] 353 - biasing member

[0319] 400 - blocking member

[0320] 401 - sealing portion

[0321] 402 - gripping portion

[0322] 1000 - method of preparing a medicament delivery system

[0323] X-X - axis

[0324] A1 - proximal direction

[0325] A2 - distal direction

Claims

Attorney Docket No.: 46567-1783WO1Claims1 . An intranasal nozzle (200’) for an intranasal medicament delivery device (100, 100'), the intranasal nozzle (200’) comprising: first and second nozzle outlets (203’, 204’); a seal (128) configured to seal against the intranasal medicament delivery device (100, 100’); and, a valve member (130) configured such that, when the seal (128) is sealed against the intranasal medicament delivery device (100, 100’), the valve member (130) inhibits the ingress of air into an outlet (1213) of the intranasal medicament delivery device (100, 100’) via the intranasal nozzle (200’) and wherein, in use, the intranasal medicament delivery device (100, 100’) is operable to expel medicament from the outlet (1213) and through the first and second nozzle outlets (203’, 204’) for delivery to a user.

2. An intranasal nozzle (200’) according to claim 1 , wherein the intranasal nozzle (200’) is configured to couple to a component of the intranasal medicament delivery device (100, 100’) and, optionally, wherein the component is a housing (110) of the intranasal medicament delivery device (100, 100’).

3. An intranasal nozzle (200’) according to claim 2, wherein the intranasal nozzle comprises a coupling configured to be rotated relative to the component of the intranasal medicament delivery device (100, 100’) to couple the intranasal nozzle (200’) to the intranasal medicament delivery device (100, 100’) and, optionally, wherein the coupling comprises a thread and / or bayonet connection.

4. An intranasal nozzle (200’) according to any one of the preceding claims, wherein the seal (128) is integrally formed with the valve member (130) and / or wherein the seal (128) is substantially annular and / or wherein the valve member (130) comprises a flap of material (130).

5. An intranasal nozzle (200’) according to any one of the preceding claims, wherein the valve member (130) is configured such that, in use, the valve member (130) is moveable from a closed position, wherein the valve member (130) is seated against a portion of the intranasal medicament delivery device (100’, 100’) to inhibit the ingress of air into the outlet (1213) via the intranasal nozzle (200’), to an open position, wherein medicament can flow out of the outlet (1213).Attorney Docket No.: 46567-1783WO16. An intranasal nozzle (200’) according to any one of the preceding claims, wherein the valve member (130) is configured to protrude into the outlet (1213) and, preferably, comprises a rounded or chamfered portion (130A).

7. An intranasal nozzle (200’) according to any one of the preceding claims, comprising a first medicament delivery conduit (201’) that comprises the first nozzle outlet (203’) and a second medicament delivery conduit (202’) that comprises the second nozzle outlet (204’) and, optionally, wherein the first and second medicament delivery conduits (201 ’, 202’) are substantially parallel and / or are substantially the same length.

8. An intranasal nozzle (200’) according to any one of the preceding claims, wherein the seal (128) comprises a substantially annular surface and / or wherein the seal (128) comprises a substantially flat surface.

9. An intranasal nozzle (200’) according to any one of the preceding claims, wherein the seal (128) is disposed radially outwardly of the valve member (130) and / or wherein the intranasal medicament delivery device (100, 100’) is operable to expel medicament past the valve member (130).

10. An intranasal medicament delivery system (1 ’, 1 ”) or a kit of parts for an intranasal medicament delivery system, the system or kit of parts comprising an intranasal medicament delivery device (100’, 100”) and an intranasal nozzle (200’, 200”) that comprises first and second nozzle outlets (203’, 204’), wherein the intranasal medicament delivery device (100’, 100”) or intranasal nozzle (200’, 200”) comprises a seal (128) configured to form a seal between the medicament delivery device (100’, 100”) and intranasal nozzle (200’, 200”), and wherein the intranasal medicament delivery device (100’, 100”) or intranasal nozzle (200’, 200”) comprises a valve member (130) configured such that, when the seal is formed between the intranasal medicament delivery device (100’, 100”) and intranasal nozzle (200’, 200”), the valve member (130) inhibits the ingress of air into an outlet (1213) of the intranasal medicament delivery device (100’, 100”) and wherein, in use, the intranasal medicament delivery device (100’ 100”) is operable to expel medicament through the first and second nozzle outlets (203’, 204’) for delivery to a user.Attorney Docket No.: 46567-1783WO111. An intranasal medicament delivery system (1 , 1 ’) or kit of parts for an intranasal medicament delivery system, the system or kit of parts comprising: a housing (110); a chamber (121) for receiving medicament from a container of medicament (300, 300’); an outlet (1213) through which medicament can be expelled from the chamber (121) for delivery to a user; a plunger rod (124) within the housing (110) and configured such that, in use, the plunger rod (124) is moveable relative to the housing (110) in a first direction (A1) to draw medicament into the chamber (121) from the container (300, 300’) and in a second direction (A2) to expel the medicament from the chamber (121) via the outlet (1213); and, a blocking member (400) configured to seal the outlet (1213) to inhibit the ingress of air into outlet (1213) when the plunger rod (124) is moved in the first direction (A1), and wherein the blocking member (400) is moveable to unseal the outlet (1213).

12. A system (1 , 1 ’) or kit of parts according to claim 11 , wherein the blocking member (400) comprises a plug (400) and, optionally, wherein the plug (400) is detachable from the medicament delivery device (100, 100’) and / or wherein the system (1 , 1 ’) or kit of parts comprises an intranasal nozzle (200’) that has any of the features of any one of claims 1 to 9.

13. A system (1 , 1 ’, 1”) or kit of parts according to any one of claims 10 to 12, comprising a medicament container (300, 300’) that contains a medicament and, optionally, wherein the medicament is a vaccine.

14. A method (1000) of preparing an intranasal medicament delivery system (1’, 1 ”), the method (1000) comprising: coupling an intranasal nozzle (200’, 200”) to a component of an intranasal medicament delivery device (100’, 100”) such that a seal is formed between the intranasal nozzle (200’, 200”) and the intranasal medicament delivery device (100’, 100”) and such that a valve member (130) inhibits the ingress of air into an outlet (1213) of the medicament delivery device (100’, 100”) via the intranasal nozzle (200’, 200”).

15. A method (2000) of preparing an intranasal medicament delivery system (1 , 1 ’), the method (2000) comprising:Attorney Docket No.: 46567-1783WO1 drawing medicament into a chamber (121) of a medicament delivery device (100, 100’), wherein a blocking member (400) seals an outlet (1213) of the chamber (121) to inhibit the ingress of air into the chamber (121) via the outlet (1213); and, replacing the blocking member (400) with an intranasal nozzle (200, 200’).

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