Adapter for an intranasal nozzle

Abstract

An adapter for an intranasal nozzle, the adapter having an external surface for resting against a user's nostril and an aperture that extends from a first opening at a first end of the adapter to a second opening at a second end of the adapter. The aperture is configured to receive a conduit of the intranasal nozzle for fixing the adapter to the conduit. Different adapters can be fitted with the same intranasal nozzle to adapt the intranasal nozzle to different users.

Description

[0001] Attorney Docket No. : 46567-1771WO1

[0002] Adapter for an intranasal nozzle

[0003] CROSS-REFERENCE TO RELATED APPLICATIONS

[0004] This application claims the benefit of European Application Serial No. 24214968.0, filed on November 22, 2024. The entire contents of the foregoing are hereby incorporated by reference.

[0005] Field of the invention

[0006] This application relates to an adapter for an intranasal nozzle for delivering medicament into a nostril, a system comprising an adaptor and an intranasal nozzle, and a kit of parts comprising an intranasal nozzle and a plurality of adapters.

[0007] Background

[0008] It is known to provide an intranasal fluid delivery device for delivering a fluid, such as a medicament, into a nostril. However, a problem with these devices is that they are not always comfortable for a user. Furthermore, a particular device will not necessarily be suitable for different users since different users have different anatomies. For example, a baby will have smaller nostrils and a different insertion depth compared to an adult.

[0009] It is an object of the present invention to address one or more of the problems mentioned above.

[0010] 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 1 18,000 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.

[0011] Summary of the invention i Attorney Docket No. : 46567-1771WO1

[0012] The present invention provides an adapter for an intranasal nozzle, wherein the adapter has an external surface for resting against a user’s nostril, wherein the external surface is flexible, and wherein the adapter comprises an aperture that extends from a first opening at a first end of the adapter to a second opening at a second end of the adapter, wherein the aperture is configured to receive a conduit of the intranasal nozzle through the second opening.

[0013] The adapter can be used to adapt the intranasal nozzle for use with a particular user. Medicament can be dispensed through the conduit when the adapter is received on the conduit.

[0014] The adapter may be made from silicone rubber.

[0015] The second opening may have a greater diameter than the first opening.

[0016] The adapter may be configured to be attached to the conduit of the intranasal nozzle. For example, the aperture may comprise an inner recess for fixing the adapter to the conduit, and optionally wherein the inner recess comprises a circumferentially-extending recess.

[0017] The or each conduit of the intranasal nozzle may comprise a protrusion which fits into the inner recess when the or each conduit is located in the aperture for attaching the adapter to the conduit. If the intranasal nozzle comprises a first conduit and a second conduit, then the first conduit may comprise a first protrusion for fitting into the inner recess, and the second conduit may comprise a second protrusion for fitting into the inner recess.

[0018] A plurality of adapters may be provided, wherein the plurality of adapters comprises a first adapter and a second adapter. At least two or more or four or more adapters may be provided, for example.

[0019] The first adaptor may have an external surface for resting against a user’s nostril, and wherein the first adapter comprises an aperture that extends from a first opening at a first end of the adapter to a second opening at a second end of the Attorney Docket No. : 46567-1771WO1 adapter. The external surface is flexible. The aperture of the first adapter is configured to receive a conduit of an intranasal nozzle through the second opening. If the intranasal nozzle comprises a first conduit and a second conduit, then the aperture of the first adapter may be configured to receive the first conduit and / or the second conduit through the second opening.

[0020] The second adaptor may have an external surface for resting against a user’s nostril, and wherein the second adapter comprises an aperture that extends from a first opening at a first end of the adapter to a second opening at a second end of the adapter. The external surface is flexible. The aperture of the second adapter is configured to receive a conduit of the intranasal nozzle through the second opening. If the intranasal nozzle comprises a first conduit and a second conduit, then the aperture of the second adapter may be configured to receive the first conduit and / or the second conduit through the second opening.

[0021] The aperture of the first adapter may comprise a first inner recess for attaching the adapter to the first conduit and / or the second conduit. The aperture of the second adapter may comprise a second inner recess for attaching the second adapter to the first conduit and / or the second conduit.

[0022] The first protrusion fits into the first inner recess when the first conduit is located in the aperture of the first adapter for attaching the first adapter to the first conduit. The second protrusion fits into the second inner recess when the second conduit is located in the aperture of the second adapter for attaching the second adapter to the second conduit. The first inner recess may comprise a circumferentially- extending recess. The second inner recess may comprise a circumferentially- extending recess. The aperture may comprise an internal diameter which is configured to fit the aperture to the conduit by a transition fit for attaching the adapter to the conduit, and optionally wherein the internal diameter is less than the diameter of the second opening.

[0023] The internal diameter may be the same or fractionally smaller than a diameter of the or each conduit for attaching the adapter to the or each conduit by a transition fit. Attorney Docket No. : 46567-1771WO1

[0024] If the intranasal nozzle comprises a first conduit and a second conduit, then the internal diameter may be the same or fractionally smaller than a diameter of the first conduit and / or a diameter of the second conduit.

[0025] The intranasal nozzle may be an intranasal atomization delivery device.

[0026] A plurality of adapters may be provided comprising a first adapter and a second adapter, as discussed herein. The internal diameter of the aperture of the first adapter may be the same or fractionally smaller than a diameter of the first conduit for attaching the first adapter to the first conduit by a transition fit. An internal diameter of the aperture of the second adapter may be the same or fractionally smaller than a diameter of the second conduit for attaching the second adapter to the second conduit by a transition fit.

[0027] A spray nozzle for spraying medicament into a nostril may be located within the aperture. The spray nozzle may be attached to the aperture. The spray nozzle may be rigid. However, even when the spray nozzle is rigid, the device can still be comfortable for a user since the external surface of the adapter is flexible. The adapter may comprise the spray nozzle.

[0028] The spray nozzle may comprise a valve for spraying medicament at a desired pressure. The valve may be located within the aperture.

[0029] The external surface of the or each adapter may comprise a rounded shape or a frustoconical shape.

[0030] The present invention further provides a plurality of adapters for an intranasal medicament delivery device, wherein each adapter of the plurality of adapters is defined according to any of the adapters discussed herein.

[0031] The plurality of adapters may comprise a plurality of smaller adapters and a plurality of larger adapters, wherein a diameter of the external surface of each of the smaller adapters is smaller than a diameter of the external surface of each of the larger adapters. The diameter of the external surface of each of the smaller Attorney Docket No. : 46567-1771WO1 adapters and the diameter of the external surface of each of the larger adapters may be measured at a predetermined axial distance from the first opening of each of the smaller and larger adapters.

[0032] The aperture of each of the plurality of smaller adapters may be configured to receive the first conduit of the or each intranasal nozzle. The aperture of each of the plurality of smaller adapters may be configured to receive the second conduit of the or each intranasal nozzle. The aperture of each of the plurality of larger adapters may be configured to receive the first conduit of the or each intranasal nozzle. The aperture of each of the plurality of larger adapters may be configured to receive the second conduit of the or each intranasal nozzle.

[0033] At least two or more smaller adaptors and at least two or more larger adaptors may be provided.

[0034] In one example, a plurality of smaller adapters each have a first diameter at their external surface 60, and a plurality of larger adapters each have a second diameter at their external surface 60. The first and the second diameters may be measured at a predetermined axial distance from the first opening of each of the smaller and larger adapters. The first diameter is smaller than the second diameter.

[0035] The smaller and larger diameter adapters may be provided so that a user can select the most appropriate size adapter to adapt the intranasal nozzle for use with a particular patient. For example, smaller adapters can be attached to an intranasal nozzle if the device is to be used with a baby, and larger adapters can be attached to the intranasal nozzle if the device is to be used with an adult. In this way, an intranasal nozzle can be adapted for use with different users.

[0036] The adapters may additionally or alternatively be provided in different shapes. If the plurality of adaptors have different features then a user has a choice of adaptors, and can then select the most appropriate adapter to adapt the intranasal medicament delivery device for use with a particular patient. Attorney Docket No. : 46567-1771WO1

[0037] When the intranasal nozzle has a first conduit and a second conduit, usually, two adaptors of the same size and having the same features would be selected to be provided on the first and second conduits.

[0038] The present invention further provides a system comprising an adapter and an intranasal nozzle comprising a first conduit for dispensing medicament, wherein the first conduit is configured to be located in the aperture of the adapter.

[0039] In the system, the adapter may be a first adapter and the intranasal nozzle may further comprise a second conduit for dispensing medicament, and wherein the second conduit is configured to be located in the aperture of a second adapter.

[0040] The first conduit may be located in the aperture of the first adapter.

[0041] The second conduit may be located in the aperture of the second adapter.

[0042] The system may further comprise a fluid flow generator for dispensing medicament from the intranasal nozzle. The fluid flow generator may be a bulb or a syringe.

[0043] The fluid flow generator may be integrally formed with the intranasal nozzle, for example by a blow-fill-seal manufacturing method.

[0044] The syringe may be couplable to or coupled to the intranasal nozzle via a Luer lock connection. The system may further comprise a Luer lock connection for connecting the syringe to the intranasal nozzle.

[0045] The intranasal nozzle may comprise a first closure which seals a first opening of the first conduit, wherein the first closure is configured to be removed from the first opening of the first conduit to unseal the first opening for dispensing medicament therethrough.

[0046] The intranasal nozzle may comprise a second closure which seals a second opening of the second conduit, wherein the second closure is configured to be Attorney Docket No. : 46567-1771WO1 removed from the second opening of the second conduit to unseal the second opening for dispensing medicament therethrough.

[0047] The first closure may be configured to be removed from the first opening by a user. The second closure may be configured to be removed from the second opening by a user.

[0048] A plurality of adapters may be provided.

[0049] The intranasal nozzle may comprise a first conduit for dispensing medicament from the device, and a second conduit for dispensing medicament from the device, and wherein the aperture of each of the plurality of adapters is configured to receive the first conduit and / or the second conduit. The plurality of adapters may comprise a first adapter and a second adapter. The first adapter may be positioned on the first conduit and the second adapter may be positioned on the second conduit. The first and second adapters may be attached to the first and second conduits respectively.

[0050] Medicament can be dispensed through the first conduit when the first adapter is received on the first conduit, and medicament can be dispensed through the second conduit when the second adapter is received on the second conduit. The first conduit comprises a first opening through which medicament can be dispensed. The second conduit comprises a second opening through which the medicament can be dispensed.

[0051] The present invention further provides a kit of parts comprising an intranasal nozzle and a plurality of adaptors. The intranasal nozzle comprises a first conduit for dispensing medicament. The intranasal nozzle may comprise a second conduit for dispensing medicament. The plurality of adapters may comprise two or more adapters or four or more adapters.

[0052] The kit of parts may comprise a plurality of intranasal nozzles. The intranasal nozzle may be a first intranasal nozzle, wherein the kit of parts further comprises one or more further intranasal nozzles. The one or more further intranasal nozzles Attorney Docket No. : 46567-1771WO1 may be identical to each other. The one or more further intranasal nozzles may be identical to the first intranasal nozzle.

[0053] The first intranasal nozzle may comprise a first conduit for dispensing medicament. The first intranasal nozzle may comprise a second conduit for dispensing medicament. Each further intranasal nozzle may comprise a first conduit for dispensing medicament. Each further intranasal nozzle may comprise a second conduit for dispensing medicament.

[0054] If the plurality of adapters are different, for example they have different shapes or different sizes, then the kit of parts allows a user to select the most appropriate adapter to adapt an intranasal nozzle for use with a particular patient.

[0055] The plurality of adapters may comprise a plurality of smaller adapters and a plurality of larger adapters, wherein a diameter of the external surface of each of the smaller adapters is smaller than a diameter of the external surface of each of the larger adapters. The plurality of adapters may comprise two or more smaller adapters and two or more larger adapters.

[0056] The kit of parts may further comprise a fluid flow generator for dispensing medicament from the intranasal nozzle. The fluid flow generator may be a bulb or a syringe.

[0057] The fluid flow generator may be integrally formed with the intranasal nozzle.

[0058] If the intranasal medicament nozzle is a blow-fill-seal intranasal medicament delivery device and / or made from a plastic, such as polypropylene, then the intranasal nozzle may be convenient to manufacture but uncomfortable for a user to use. However, the adapters allow the nozzle to be fitted to a particular use and / or be more comfortable for a user to use since the external surface of the adapters is flexible.

[0059] Medicament may be located in the intranasal nozzle. Attorney Docket No. : 46567-1771WO1

[0060] The intranasal nozzle may be formed by a blow-fill-seal manufacturing method. The intranasal nozzle may be a blow-fill-seal intranasal nozzle. If the intranasal nozzle is formed by a blow-fill-seal manufacturing method then it is referred to as a blow-fill-seal intranasal nozzle. This is a particularly convenient way of manufacturing the nozzle. The nozzle can be made in a generic form, and it can be adapted for use with different users using the adapters discussed herein. The intranasal nozzle may additionally or alternatively be made from a plastic, optionally wherein the plastic is polypropylene. In some embodiments, the intranasal nozzle is configured to deliver medicament to the nasal structures of the user. In some embodiments, the intranasal nozzle is configured to deliver medicament to the nasal structures of the user to elicit an immune response.

[0061] In some embodiments, the fluid flow generator is permanently coupled to the body.

[0062] In some embodiments, the fluid flow generator is a gas flow generator.

[0063] In some embodiments, the fluid flow generator comprises a chamber for containing a fluid and is configured such that, in use, the volume of the chamber is decreasable upon the application of a force by a user to expel the fluid from the chamber to expel medicament from the intranasal nozzle.

[0064] In some embodiments, the fluid flow generator comprises a syringe or flexible container. In another embodiment, the fluid flow generator is a balloon. In yet another embodiment, the fluid flow generator comprises a pressurised gas source, for example, pressurised air or oxygen. In one embodiment, the fluid flow generator is a metered dose inhaler. The intranasal nozzle may be configured to couple to a mouthpiece of the metered dose inhaler.

[0065] The intranasal nozzle may be configured to atomize the medicament and, optionally, may further comprise an atomiser. Such atomiser may facilitate insertion of the atomiser and outlet into an orifice of a patient into which the medicament is to be delivered. The atomiser and / or outlet may comprise a luer lock to sealingly connect the atomiser to the outlet. In another embodiment, the outlet itself is configured to atomize the medicament. Attorney Docket No. : 46567-1771WO1

[0066] 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.

[0067] 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.

[0068] The intranasal medicament delivery system may comprise an intranasal atomization delivery device.

[0069] The intranasal nozzle may be configured to deliver about of a dose to each nostril.

[0070] The intranasal nozzle may be configured to deliver about 0.2mL, wherein about 0.1 mL is delivered to each nostril.

[0071] The intranasal nozzle may deliver an average droplet size Dv50 of about 10-120 pm.

[0072] The intranasal nozzle may deliver an average droplet size Dv50 delivered to each nostril may be about 10-120 pm, about 30-110 pm, about 50-110 pm, about 70- 110 pm, or about 80-110 pm.

[0073] The intranasal nozzle 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.

[0074] In some embodiments, the intranasal nozzle 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. : 46567-1771WO1

[0075] In some embodiments, the intranasal nozzle 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.

[0076] In some embodiments, the fluid flow generator is attachable to the intranasal nozzle. In other embodiments, the fluid flow generator is integrally formed with the intranasal nozzle.

[0077] The present invention further provides a method of preparing an intranasal nozzle, comprising inserting a first conduit of the intranasal nozzle into a first aperture of a first adapter, wherein the first adapter has a flexible external surface for resting against a user’s nostril and wherein the first aperture extends through the first adapter for allowing medicament to be dispensed through the first conduit when the first adapter is attached to the first conduit.

[0078] The method of preparing the intranasal nozzle may be performed prior to the delivery of medicament to a patient.

[0079] The method may further comprise inserting a second conduit of the intranasal nozzle into a second aperture of a second adapter, wherein the second adapter has a flexible external surface for resting against a user’s nostril and wherein the second aperture extends through the second adapter for allowing medicament to be dispensed through the second conduit when the second adapter is attached to the second conduit.

[0080] The method may further comprise removing the intranasal nozzle from packaging.

[0081] The method may further comprise removing a first closure to unseal a first opening of the first conduit prior to inserting the first conduit of the intranasal nozzle into the first aperture of the first adapter. Attorney Docket No. : 46567-1771WO1

[0082] The method may further comprise removing a second closure to unseal a second opening of the second conduit prior to inserting the second conduit of the intranasal nozzle into the second aperture of the second adapter.

[0083] The method may further comprise selecting the first adapter. Selecting the first adapter may comprise selecting an appropriate adapter for a user. Selecting an appropriate adapter for a user may comprise selecting an adaptor having an optimum size and / or shape for the user.

[0084] The method may further comprise selecting the second adapter. Selecting the second adapter may comprise selecting an appropriate adapter for a user. Selecting an appropriate adapter for a user may comprise selecting an adaptor having an optimum size and / or shape for the user.

[0085] The first adapter may be the same as the second adapter.

[0086] The method may further comprise resting the first adapter against a user’s nostril.

[0087] The method may further comprise resting the second adapter against a user’s nostril.

[0088] The method may further comprise dispensing medicament into a user’s nostril via the first conduit and optionally via the second conduit.

[0089] Dispensing medicament into the user’s nostril may comprise squeezing a bulb or pushing a plunger into a syringe.

[0090] The method may further comprise removing the medicament delivery device from the user’s nostril or nostrils.

[0091] The method may further comprise disposing of the medicament delivery device.

[0092] The first adapter and the second adapter, and the intranasal medicament delivery device may have any of the features discussed herein. Attorney Docket No. : 46567-1771WO1

[0093] The method may comprise expelling / administering an RSV vaccine.

[0094] The medicament may be expelled / delivered intranasally with about Y dose delivered to each nostril.

[0095] The intranasal dose of the medicament may be delivered in about 0.2 mL, wherein about 0.1 mL is delivered to each nostril.

[0096] The method may comprise intranasal atomization delivery of an average droplet size Dv50 of about 10-120 pm.

[0097] 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 50-1 10 pm, about 70-110 pm, or about 80-1 10 pm.

[0098] 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.

[0099] In some embodiments, the method comprises removing the intranasal nozzle from a sealed pack.

[0100] In some embodiments, the method comprises attaching the intranasal nozzle to a fluid flow generator.

[0101] Brief description of the drawings

[0102] So that the invention may be more fully understood, reference is made to the accompanying drawings, in which:

[0103] Fig. 1 shows an intranasal medicament delivery device in a sealed configuration;

[0104] Fig. 2A shows an example of an adapter according to the present invention, and part of an intranasal medicament delivery device;

[0105] Fig. 2B shows the adapter of Fig. 2A fixed to the part of an intranasal medicament delivery device; Attorney Docket No. : 46567-1771WO1

[0106] Fig. 3 shows an example of a first adapter and a second adapter, according to the present invention;

[0107] Fig. 4A shows an example of an adapter according to the present invention, and part of an intranasal medicament delivery device;

[0108] Fig. 4B shows the adapter of Fig. 4A fixed to the part of the intranasal medicament delivery device;

[0109] Fig. 5 shows an example of an adapter according to the present invention;

[0110] Fig. 6 shows an example of an adapter according to the present invention, and part of an intranasal medicament delivery device;

[0111] Fig. 7 shows an intranasal medicament delivery device with adapters located therein in use;

[0112] Fig. 8 is a flowchart showing an example method of using adaptors with an intranasal medicament delivery device; and

[0113] Fig. 9 is a further example of an intranasal medicament delivery device.

[0114] Fig. 1 shows an intranasal medicament delivery device 100 for delivering medicament into a user’s nostrils, with the device in a sealed configuration. The intranasal medicament delivery device 100 has an intranasal nozzle 1 which has a first conduit 3 comprising a first nozzle outlet 4 for dispensing medicament form the device, and a second conduit 6 comprising a second nozzle outlet 7 for dispensing medicament from the device. The first nozzle outlet 4 comprises a first opening 5 through which the medicament can be dispensed. The second nozzle outlet 7 comprises a second opening 8 through which the medicament can be dispensed. In the sealed configuration shown in Fig. 1 , the first opening 5 is sealed by a first closure 9a. The second opening 8 is sealed by a second closure 9b. In this example, the first closure 9a is formed by a planar tab. The second closure 9b is formed by a planar tab but the closures 9a, 9b could have other shapes in another embodiment. In another embodiment, the intranasal nozzle has a single conduit, such as the first conduit 3.

[0115] The first conduit 3 has a first protrusion 17. The first protrusion 17 may extend partially or fully around the circumference of the first conduit 3. The second conduit 6 has a second protrusion 17. The second protrusion 17 may extend partially or fully around the circumference of the second conduit 6. Attorney Docket No. : 46567-1771WO1

[0116] The intranasal nozzle 1 is connected to a squeezable bulb 2 which can be squeezed to dispense fluid from the intranasal medicament delivery device 100 via the first and second openings 5, 8. The squeezable bulb 2 can be referred to as a fluid flow generator. Alternatively, the intranasal nozzle 1 may be connected or connectable to another type of fluid flow generator such as a pressurised gas source or a syringe 902 as shown, for example, in Fig. 9. The intranasal nozzle 1 is intended for single use.

[0117] In the example shown in Fig. 1 , the intranasal medicament delivery device 100 is formed by a blow-fill-seal manufacturing method. The squeezable bulb 2 and the intranasal nozzle 1 are integrally formed. The squeezable bulb and the intranasal nozzle may additionally or alternatively be made from a plastic such as polypropylene, for example. The first and second closures 9a, 9b are formed with the device 1 during the manufacturing method. The closures may be removing by snapping or twisting it off from the device 1 , for example, to unseal the first and second openings 5, 8.

[0118] When the first and second closures 9a, 9b are removed from the intranasal nozzle, they may leave a rough edge at the first and second openings 5, 8 respectively. The first conduit may be said to comprise a first opening 5 having a rough edge. The second conduit may be said to comprise a second opening 8 having a rough edge. The adaptors allow the device to be more comfortable for a user to use.

[0119] The first closure 9a is configured to be removed from the first opening 5 by a user. The second closure 9b is configured to be removed from the second opening 8 by the user.

[0120] The medicament may be a medicament such as a vaccine. The intranasal medicament delivery device 100 may be an intranasal atomization delivery device.

[0121] Fig. 2A shows an example of an adapter 10, according to the present invention. Fig. 2A also shows part of an intranasal nozzle, such as the first conduit 3 of the intranasal nozzle, as shown and described in relation to Fig. 1 , when the nozzle is Attorney Docket No. : 46567-1771WO1 initially separated from the adapter 10. The adapter 10 can then be fixed to the first conduit 3, as shown in Fig. 2B.

[0122] The adapter 10 has an aperture 11 that extends from a first opening 12 at a first end 13 of the adapter to a second opening 14 at a second end of the adapter 15. The aperture 11 is configured to receive the first conduit 3 of an intranasal nozzle, such as the device shown in Fig. 1 , through the second opening 14. The second opening 14 of the aperture has a greater diameter than the first opening 12. In other embodiments (not shown) the second opening 14 has the same diameter as the first opening 12. The aperture 11 extends along an axis 50 of the adapter 10.

[0123] The aperture 11 has an inner recess 16 for fixing the adapter 10 to the conduit. The inner recess 16 extends around the entire circumference of the aperture although in other embodiments the recess 16 could extend only partly around the circumference of the aperture or be a square-shaped recess, for example.

[0124] The protrusion 17 of the first conduit 3 fits in the recess 16 when the adapter is attached to the device. This attaches the adapter 10 to the intranasal medicament delivery device as shown, for example, in fig. 2B. The protrusion 17 may extend partially or fully around the circumference of the first conduit 3.

[0125] When the adapter 10 is fixed to the intranasal nozzle, the first opening 5 of the intranasal nozzle may be flush with the first opening 12 of the adapter 10. Alternatively, the first opening 5 of the intranasal nozzle may protrude from the first opening 12 of the adapter 10 or the first opening 5 may be located within the adapter 10. When medicament is dispensed from the intranasal nozzle it must be able to travel through the first conduit 3 and out of the first opening 5 to be received in a user’s nostril.

[0126] The adapter 10 may be made from an elastomeric material. The adapter may be made from a biocompatible material. The adapter map be made from silicone rubber. Attorney Docket No. : 46567-1771WO1

[0127] The adapter 10 has an external surface 60 for resting against a user’s nostril. The external surface 60 is flexible. The configuration and dimensions of the external surface 60 will vary depending on the anatomy of the user. For example if the adapter is to be used for a baby then the external surface 60 will have a relatively smaller diameter compared to if it was being used for an adult.

[0128] The adapter 10 has been described in relation to it being fixed to the first conduit 3 of the intranasal nozzle 1 but the adapter 10 can also be fixed to the second conduit 6 of the intranasal nozzle. The second conduit 6 has a second protrusion 17 which fits in the recess 16 of the adapter for attaching the adapter 10 to the second conduit 6.

[0129] If the intranasal nozzle 1 has two conduits, a first adapter will need to be received on the first conduit and a second adapter will need to be received on the second conduit. In one example, each of the first and second adapters has the same features as described above in relation to the adapter 10.

[0130] The adapters may be provided in different sizes. For example, as shown in Figs. 2A and 2B, the external surface 60 of the adapter 10 has a diameter d1 . The diameter d1 may be measured at a predetermined axial distance from the first opening 12. A smaller adapter may have a smaller diameter d1 relative to a diameter d1 of a larger adapter.

[0131] In one example, a plurality of smaller adapters each have a first diameter at their external surface 60, and a plurality of larger adapters each have a second diameter at their external surface 60. The first and second diameters may be measured at the same axial distance from the first opening 12. The first diameter is smaller than the second diameter.

[0132] The smaller and larger diameter adapters may be provided in a kit, so that a user can select the most appropriate size adapter to adapt the intranasal nozzle for use with a particular patient. If the intranasal nozzle is a blow-fill-seal intranasal nozzle and / or made from a plastic then it may be convenient to manufacture but uncomfortable for a user to use. However, the shape and / or the size of the Attorney Docket No. : 46567-1771WO1 adaptors allows the device to be fitted to a particular user and / or be more comfortable for a user to use since the external surface of the adapters is flexible.

[0133] In use, a user will take an intranasal nozzle, and unseal the first and second openings 5, 8 by snapping or twisting the first and second closure 9a, 9b off the intranasal nozzle.

[0134] A user will then fix a first adapter 10 to the first conduit 3 and will fix a separate second adapter 10 to the second conduit 6.

[0135] If the adapters 10 are available in different sizes then the size of the first and second adapters 10 may be selected based on the user. For example, if the user is a baby then the first adapter and the second adapter are both smaller adapters. If the user is an adult then the first adapter and the second adapter are both larger adapters.

[0136] The first adapter 10 can be rested against a user’s first nostril, and the second adapter 10 can be rested against a user’s second nostril. Medicament can then be dispensed from the intranasal nozzle via the first and second conduits 3, 6 by gravity and / or by a user squeezing the bulb 2.

[0137] Fig. 7 shows the intranasal medicament delivery device with adapters 10 attached thereto, as it approaches the nostrils of a user 700.

[0138] A kit of parts may be provided which has an intranasal nozzle and a plurality of adapters. The fluid flow generator may be provided with the kit of parts or it may be provided separately. The plurality of adapters may have the features as described above in relation to Figs. 2A and 2B, or the features of any of the other adapters which are described or contemplated herein. The plurality of adapters may have different sizes and / or shapes which enable them to be suitable for different users. The intranasal nozzle can then be adapted to be used with different users by attaching the most appropriate adapters to the intranasal nozzle. Attorney Docket No. : 46567-1771WO1

[0139] The kit of parts may include a plurality of intranasal nozzles. Each of the intranasal nozzles may have the features of the intranasal nozzles as described and / or contemplated herein. Each of the plurality of intranasal nozzles may be identical to each other.

[0140] The kit of parts may comprise a first intranasal nozzle 1 , 901 and one or more further intranasal nozzles 1 , 901 . The first intranasal nozzle 1 , 901 may comprise a first conduit 3, 203, 903 for dispensing medicament. The first intranasal nozzle may comprise a second conduit 6, 906 for dispensing medicament. Each further intranasal nozzle 1 , 901 may comprise a first conduit 3, 203, 903 for dispensing medicament. Each further intranasal nozzle may comprise a second conduit 6, 906 for dispensing medicament.

[0141] The further intranasal nozzles may be identical to each other. The first intranasal nozzle may be identical to the or each further intranasal nozzle. The further intranasal nozzles may have the features of the intranasal nozzles as described and / or contemplated herein, for example the intranasal nozzle 1 shown and described in relation to Fig. 1 or the intranasal nozzle shown and described in relation to Fig. 9.

[0142] Fig. 3 shows an alternative adapter, according to the present invention, in which a first adapter 110 is attached to a second adapter 120. Fig. 3 also shows part of an intranasal nozzle, such as the first conduit 3 and the second conduit 6 of the intranasal nozzle 1 shown and described in relation to Fig. 1 , when the nozzle is initially separated from the first and second adapters 110, 120.

[0143] The first and second adapters 110, 120, have the same features as described above in relation to the adapter 10 except that the first and second adapters 110, 120 are attached to each other. The first adapter 110 may be attached to the second adapter 120 by a bridge 122. The bridge 122 may be made from the same material as the first adapter 110 and the second adapter 120. The same material may be silicone rubber. Attorney Docket No. : 46567-1771WO1

[0144] The first adapter 110 has a first aperture 111 that extends from a first opening 112 at a first end 113 of the adapter to a second opening 114 at a second end 115 of the adapter. The aperture 111 is configured to receive the first conduit 3 of an intranasal nozzle, such as the nozzle shown in Fig. 1 , through the second opening 1 14. The second opening 114 of the aperture has a greater diameter than the first opening 112. In other embodiments (not shown) the second opening 114 has the same diameter as the first opening 112. The aperture 111 extends along an axis 150 of the adapter 1 10.

[0145] The aperture 111 has an inner recess 116 for fixing the adapter 110 to the first conduit 3. The inner recess 116 extends around the entire circumference of the aperture although in other embodiments the recess 116 could extend only partly around the circumference of the aperture or be a square-shaped recess, for example.

[0146] The first conduit 3 has a protrusion 17 which fits in the recess 116 when the adapter is fixed to the device. This attaches the adapter 110 to the intranasal medicament delivery device.

[0147] The first adapter 110 has an external surface 160 for resting against a user’s nostril. The external surface 160 is flexible.

[0148] The first adapter 110 and the second adapter 120 are identical in this embodiment.

[0149] The second adapter 120 has a second aperture 131 that extends from a first opening 132 at a first end 133 of the adapter to a second opening 134 at a second end 135 of the adapter. The aperture 131 is configured to receive the second conduit 6 of an intranasal nozzle, such as the device shown in Fig. 1 , through the second opening 134. The second opening 134 of the aperture has a greater diameter than the first opening 132. In other embodiments (not shown) the second opening 134 has the same diameter as the first opening 132. The aperture 131 extends along an axis 151 of the adapter 120. Attorney Docket No. : 46567-1771WO1

[0150] The aperture 131 has an inner recess 136 for fixing the adapter 120 to the conduit. The inner recess 136 extends around the entire circumference of the aperture although in other embodiments the recess 136 could extend only partly around the circumference of the aperture or be a square-shaped recess, for example.

[0151] The protrusion 17 of the second conduit 6 fits in the recess 136 when the second adapter 120 is fixed to the device. This attaches the second adapter 120 to the intranasal nozzle.

[0152] The second adapter 120 has an external surface 161 for resting against a user’s nostril. The external surface 161 is flexible.

[0153] In use, a user will fix the first adapter 110 to the first conduit 3 and the second adapter 210 to the second conduit 6.

[0154] The first adapter 110 can be rested against a user’s first nostril, and the second adapter 120 can be rested against a user’s second nostril. Medicament can then be dispensed from the intranasal nozzle via the first and second conduits 3, 6 by gravity and / or by a user squeezing the bulb 2.

[0155] A bridge may be provided with any of the other adapters described herein, to attach a first adapter to a second adapter.

[0156] As noted above in relation to Figs. 2A and 2B, the adapters may be provided in different sizes. The external surfaces 160, 161 of the first and second adapters 1 10, 120 each have a diameter d1 . The diameter d1 may be measured at a predetermined axial distance from the first opening 112. A smaller adapter may have a smaller diameter d1 relative to a diameter d1 of a larger adapter.

[0157] In one example, a plurality of smaller adapters each have a first diameter at the external surface 160 of the first adapter 1 10, and the same-sized diameter at the external surface 161 of the second diameter. A plurality of larger adapters each have a second diameter at the external surface 160 of the first adapter 110 and the same-sized diameter at the external surface 161 of the second diameter. The Attorney Docket No. : 46567-1771WO1 first and second diameters may be measured at the same axial distance from the first opening 112 or the second opening 132. The first diameter is smaller than the second diameter.

[0158] The smaller and larger diameter adapters may be provided in a kit, so that a user can select the most appropriate size adapter to adapt the intranasal nozzle for use with a particular patient. Two or more smaller adapters and two or more larger adapters may be provided in the kit.

[0159] Fig. 4A shows an alternative example of an adapter 210, according to the present invention. Fig. 4A also shows part of a first conduit 203 of an alternative intranasal nozzle which may be formed by a blow-fill-seal manufacturing method and / or be made from a plastic such as polypropylene. The alternative intranasal nozzle has the same features as described above in relation to Fig. 1 except that the first and second conduits do not have a protrusion which fits into a recess on the adapters. In Fig. 4A, the conduit 203 is shown to be separated from the adapter 210. The adapter 210 can then be fixed to the first conduit 203, as shown in Fig. 4B.

[0160] The adapter 210 has an aperture 211 that extends from a first opening 212 at a first end 213 of the adapter to a second opening 214 at a second end 215 of the adapter. The aperture 211 is configured to receive the first conduit 203 of an intranasal nozzle through the second opening 214. The second opening 214 of the aperture has a greater diameter than the first opening 212. In other embodiments (not shown) the second opening 214 has the same diameter as the first opening 212. The aperture 211 extends along an axis 250 of the adapter 210.

[0161] The aperture 211 has an internal diameter d2 which is less than the diameter of the second opening 214. The internal diameter d2 is the same as or fractionally smaller than a diameter d3 of the first conduit 203 for attaching the adapter 210 to the first conduit 203 via a transition fit. Mild force is required to assemble and / or disassemble the adapter 210 and the first conduit 203.

[0162] The first conduit 203 comprises a first nozzle 204. The first nozzle 204 comprises a first opening 205 through which the medicament can be dispensed. When the Attorney Docket No. : 46567-1771WO1 adapter 210 is fixed to the first conduit 203 via the transition fit, as shown in Fig.

[0163] 4B, medicament can be dispensed through the first conduit 203 and out of the first opening 205 to be received in a user’s nostril.

[0164] The adapter 210 may be made from an elastomeric material. The adapter 210 may be made from a biocompatible material. The adapter 210 map be made from silicone rubber.

[0165] The adapter 210 has an external surface 260 for resting against a user’s nostril. The external surface 260 is flexible. The external surface 260 has a rounded shape. The rounded shape is provided at the distal end of the adapter for resting against a user’s nostril. The rounded shape provides a comfortable surface and / or assists with positioning the device against a user’s nostril.

[0166] The adapter 210 has been described in relation to it being fixed to the first conduit 203 of the intranasal nozzle but the adapter 210 can also be fixed to the second conduit. The internal diameter d2 is the same as or fractionally smaller than a diameter of the second conduit. Mild force is required to assemble and / or disassemble the adapter 210 and the second conduit.

[0167] When the intranasal nozzle has two conduits, a first adapter will need to be received on the first conduit and a second adapter will need to be received on the second conduit. In one example, each of the first and second adapters has the same features as described above in relation to the adapter 210.

[0168] The adapters may be provided in different sizes. For example, as shown in Figs. 4A and 4B, the external surface 260 of the adapter 210 has a diameter d1. The diameter d1 may be measured at a predetermined axial distance from the first opening 212. A smaller adapter may have a smaller diameter d1 relative to a diameter d1 of a larger adapter.

[0169] The smaller and larger diameter adapters 210 may be provided in a kit, so that a user can select the most appropriate size adapter to adapt the intranasal nozzle for use with a particular patient. Attorney Docket No. : 46567-1771WO1

[0170] In use, a user will then fix a first adapter 210 to the first conduit 203 and will fix a separate second adapter 210 to the second conduit.

[0171] The first and second adapters can be rested against a user’s first and second nostrils. Medicament can then be dispensed from the intranasal nozzle 1 via the first and second conduits by gravity and / or by a user squeezing the bulb 2.

[0172] Fig. 5 shows an alternative example of an adapter 210, according to the present invention. The adapter 210 has the same features as described above in relation to Figs. 4A and 4B except that the external surface 261 of the adapter has a frustoconical shape. The external surface 261 is flexible. The frustoconical shape is provided at the distal end of the adapter for resting against a user’s nostril. The frustoconical shape provides a comfortable surface and / or assists with positioning the adapter against the user’s nostril.

[0173] The external surface has have a diameter d1. The diameter d1 may be measured at a predetermined axial distance from the first opening 12. A smaller adapter may have a smaller diameter d1 relative to a diameter d1 of a larger adapter.

[0174] The other embodiments of the adapter which are described herein may also have an external surface comprising a frustoconical shape, as described above in relation to Fig. 5.

[0175] Fig. 6 shows an alternative example of an adapter 310, according to the present invention, and part of a first conduit 303 of an alternative intranasal nozzle which may be formed by a blow-fill-seal manufacturing method and / or be made from a plastic such as polypropylene. The alternative intranasal medicament delivery device is similar to that described above in relation to Fig. 1 but the first conduit and the second conduit (not shown) do not have a protrusion which fits into a recess on the adapters.

[0176] The adapter 310 has an aperture 311 that extends from a first opening 312 at a first end 313 of the adapter to a second opening 314 at a second end 315 of the Attorney Docket No. : 46567-1771WO1 adapter. The aperture 311 is configured to receive the first conduit 303 of an intranasal nozzle through the second opening 314. The second opening 314 of the aperture has a greater diameter than the first opening 312. In other embodiments (not shown) the second opening 314 has the same diameter as the first opening 312. The aperture 311 extends along an axis of the adapter 310.

[0177] The aperture 311 has an internal diameter which is the same as or fractionally smaller than a diameter of the first conduit 203 for fixing the adapter 310 to the first conduit 303 via a transition fit. Alternatively, the adapter can be fixed to the conduit in other ways, such as via a protrusion on the first conduit which fits in a recess in the aperture of the adapter, as described above in relation to Figs. 2A and 2B.

[0178] The first conduit 303 comprises a first opening 305 through which the medicament can be dispensed.

[0179] The adapter 310 comprises a spray nozzle 370 for spraying medicament into a nostril. The spray nozzle 370 may be attached to the aperture 311 . Alternatively, the spray nozzle 370 may be integrally formed with the adapter 310. The spray nozzle 370 may be rigid. However, even when the spray nozzle 370 is rigid, the device can still be comfortable for a user since the external surface of the adapter is flexible.

[0180] The spray nozzle 370 may be made of a different material to the adapter 310. The spray nozzle 370 may consist of a plastic material for example polypropylene or polyethylene and may be made from a different material to other parts of the adapter, which may be made from silicone rubber, for example.

[0181] The spray nozzle 370 may have an inlet 373 having a diameter which is the same or substantially similar to the diameter of the first opening 305 of the first conduit 303. The spray nozzle 370 also has an aperture 371 and an outlet 372. The inlet 373 is connected to the aperture 371 which is connected to the outlet 372. Attorney Docket No. : 46567-1771WO1

[0182] The diameter of the aperture 371 is smaller than the diameter of the inlet 373. This increases the velocity of the medicament as it passes through the aperture.

[0183] The outlet 372 is flared for creating a cone of sprayed medicament. The outlet 372 has a greater diameter than the diameter of the aperture 371 . When medicament is released from the outlet 372 it may be atomised.

[0184] The spray nozzle 370 may comprise a valve 374 for spraying medicament at a desired pressure. The valve 374 may be spring-loaded. The valve 374 is located within the aperture 311. As noted, the aperture 311 extends from the first opening 312 at the first end 313 of the adapter to the second opening 314 at the second end 315 of the adapter.

[0185] The spray nozzle 370 described above may be used in conjunction with the features of any of the other adapters described herein.

[0186] When the adapter 310 is fixed to the first conduit 303, medicament can be dispensed through the first conduit 303 and out of the first opening 305, and through the aperture of the spray nozzle 370 to be received in a user’s nostril.

[0187] The adapter 310 has an external surface 360 for resting against a user’s nostril. The external surface 360 is flexible. The external surface 360 has a rounded shape although it could alternatively have another shape such as a frustoconical shape.

[0188] When the intranasal nozzle 1 has two conduits, a first adapter will need to be received on the first conduit and a second adapter will need to be received on the second conduit. Each of the first and second adapters has the same features as described above in relation to the adapter 310.

[0189] The adapters may be provided in different sizes. For example, as shown in Fig. 6, the external surface 360 of the adapter 310 has a diameter d1. The diameter d1 may be measured at a predetermined axial distance from the first opening 12. A Attorney Docket No. : 46567-1771WO1 smaller adapter may have a smaller diameter d1 relative to a diameter d1 of a larger adapter.

[0190] The smaller and larger diameter adapters 310 may be provided in a kit, so that a user can select the most appropriate size adapter to adapt the intranasal nozzle for use with a particular patient.

[0191] In use, a user will fix a first adapter 310 to the first conduit 303 and will fix a separate second adapter 310 to the second conduit.

[0192] The first and second adapters can be rested against a user’s first and second nostrils. Medicament can then be dispensed from the intranasal medicament delivery device via the first and second conduits by gravity and / or by a user squeezing the bulb and / or via an alternative fluid flow generator.

[0193] The present application has described adaptors having different features, and the adaptors being provided in different sizes. In one example, a kit can be provided having adaptors with different features, such as comprising some adaptors having the features of Figs. 2A and 2B, and some adaptors having the features of Fig. 3. The adapters may also be provided in different sizes. A user has a choice of adaptors, and can then select the most appropriate adapter to adapt the intranasal nozzle 1 for use with a particular patient. The intranasal nozzle 1 is intended for single use.

[0194] Fig. 8 is a flow chart illustrating example method steps of using an adapter, in accordance with the present invention.

[0195] A first step S1 comprises inserting a first conduit of an intranasal nozzle into a first aperture of a first adapter.

[0196] A second step S2 comprises inserting a second conduit of an intranasal nozzle into a second aperture of a second adapter. Attorney Docket No. : 46567-1771WO1

[0197] A third step S3 comprises dispensing medicament through the first conduit when the first adapter is attached to the first conduit. If a second conduit is provided then step S3 additionally comprises dispensing medicament through the second conduit when the second adapter is attached to the second conduit. The medicament may be dispensed through the first conduit into a user’s first nostril, and through the second conduit into a user’s second nostril. The method comprises resting the first adapter against a user’s nostril. The method comprises resting the second adapter against a user’s nostril. Dispensing medicament into the user’s nostril may comprise squeezing a bulb or pushing a plunger into a syringe.

[0198] The method may additionally comprise unsealing a first opening of the first conduit to allow medicament to be dispensed through the first conduit and / or unsealing a second opening of the second conduit to allow medicament to be dispensed through the second conduit, before the first step S1 is performed.

[0199] The method may further comprise removing the intranasal nozzle from packaging, prior to the first step S1 .

[0200] The method may further comprise selecting the first adapter prior to the first step S1 . Selecting the first adapter may comprise selecting an appropriate adapter for a user. Selecting an appropriate adapter for a user may comprise selecting an adaptor having an optimum size and / or shape for the user.

[0201] The method may further comprise selecting the second adapter prior to the second step S2. Selecting the second adapter may comprise selecting an appropriate adapter for a user. Selecting an appropriate adapter for a user may comprise selecting an adaptor having an optimum size and / or shape for the user.

[0202] The first adapter may be the same as the second adapter.

[0203] The method may further comprise removing the medicament delivery device from the user’s nostril or nostrils after the third step S3. The method may then further comprise disposing of the medicament delivery device. Attorney Docket No. : 46567-1771WO1

[0204] The method may be used with any of the adapters and intranasal nozzles described herein.

[0205] Fig. 9 shows an intranasal medicament delivery device 900 for delivering medicament into a user’s nostrils, with the device in a sealed configuration. The intranasal medicament delivery device may be used with any of the adapters described or contemplated herein.

[0206] The intranasal medicament delivery device 900 has an intranasal nozzle 901 which has a first conduit 903 comprising a first nozzle outlet 904 for dispensing medicament from the device, and a second conduit 906 comprising a second nozzle outlet 907 for dispensing medicament from the device. The first nozzle outlet 904 comprises a first opening 905 through which the medicament can be dispensed. The second nozzle outlet 907 comprises a second opening 908 through which the medicament can be dispensed. In the sealed configuration shown in Fig. 9, the first and second openings 905, 908 are sealed by a first closure 9a and a second closure 9b respectively. In another embodiment, the intranasal nozzle has a single conduit, such as the first conduit 903.

[0207] The intranasal nozzle 901 may have any of the features described herein in relation to the other intranasal nozzles, for example the first and second conduits 903, 906 may have protrusions.

[0208] The intranasal nozzle 1 is configured to couple to the fluid flow generator, which in the example of Fig. 9 is a gas flow generator in the form of a syringe 902, such that the first and second conduits 903, 906 fluidly communicate with the gas flow generator. The intranasal nozzle 901 comprises a coupling 910 that is configured to couple to the syringe 902. In the present example, the coupling 910 is a Luer lock connection that is configured to couple to a corresponding Luer lock connection of the syringe 902.

[0209] The syringe 902 comprises a chamber 911 for containing a gas. The syringe 902 is configured such that, in use, the volume of the chamber 911 is decreasable Attorney Docket No. : 46567-1771WO1 upon the application of a force by a user to expel the gas from the chamber 911 and into the first and second medicament delivery conduits 903, 906, to thereby cause medicament in the intranasal nozzle 901 to be dispensed through the first and second openings 905, 908.

[0210] The syringe 902 has a body 912 and a plunger 913. The chamber 911 is disposed within the body 912. The plunger 913 is disposed at one end of the chamber 911 and is slidable within the body 912. The syringe 902 further comprises a coupling 915 at an end of the body 912 for connecting to the coupling 910 of the intranasal nozzle 901. In the present example, the coupling 915 of the syringe 902 comprises a Luer lock connection to engage the Luer lock connection of the coupling 910 of the nozzle 901. The syringe 902 may comprise a male Luer lock fitting 915 that engages a female Luer lock fitting 910 of the nozzle 901. Advantageously, this means that the nozzle 901 can be used with a standard syringe 902.

[0211] In other examples, the coupling 910 of the nozzle 901 and the coupling 915 of the syringe 902 may have a different configuration, for example, a bayonet connection, snap-fit or screw threads.

[0212] The coupling 915 of the syringe 902 comprises an outlet 914 that fluidly communicates with an inlet 916 of the intranasal nozzle 901 that is located within the coupling 910 of the intranasal nozzle 901 . Therefore, in use, the syringe 902 is operable to generate a gas flow that enters the intranasal nozzle 901 . More particularly, the user exerts a force on the plunger 913 of the syringe 902 to slide the plunger 913 within the body 912 towards the outlet 914 such that the volume of the chamber 911 is decreased, thereby expelling air (or an alternative gas or a liquid) in the chamber 911 out of the chamber 911 via the outlet 914.

[0213] It should be recognised that in other embodiments, the fluid flow generator may take a different form. In one such embodiment (not shown), the gas flow generator may instead comprise a flexible container that is squeezed to expel air (or an alternative gas or a liquid) from the flexible container via a coupling that is connected to the coupling 910 of the intranasal nozzle 901. The flexible container may comprise a bulb or balloon that is squeezed to generate the gas flow. Attorney Docket No. : 46567-1771WO1

[0214] In some embodiments (not shown), the fluid flow generator is permanently attached to the intranasal nozzle 901 and, optionally, may be integrally formed therewith. In other embodiments, the fluid flow generator is attachable to the intranasal nozzle 901 and may be removably attachable to the intranasal nozzle.

[0215] The intranasal medicament delivery device 901 may be formed by a blow-fill-seal manufacturing method and / or be made from a plastic such as polypropylene.

[0216] In embodiments described above, the intranasal nozzle 1 is fluidly communicated with a fluid flow generator. The fluid flow generator is configured to generate a fluid flow to expel medicament from the intranasal nozzle. The fluid flow generated by the fluid flow generator may be a liquid (for example, medicament, water or saline solution) or a gas (for example, air or oxygen). It should be recognised that in each of the embodiments, the gas flow generator may take a different form. In some embodiments, the fluid flow generator comprises a syringe or flexible container such as a flexible bulb. In another embodiment, the fluid flow generator is a balloon. In yet another embodiment, the fluid flow generator comprises a pressurised gas source, for example, a cannister of pressurised air or oxygen. In one embodiment, the fluid flow generator is a metered dose inhaler. The intranasal nozzle may be configured to attach to an outlet of the metered dose inhaler, for example, to the mouthpiece of the metered dose inhaler.

[0217] In each of the embodiments described above, the intranasal medicament delivery system comprises an intranasal nozzle that comprises first and second nozzle outlets and, preferably, comprises first and second medicament delivery conduits. The advantage of two nozzle outlets is that medicament can simultaneously be delivered to both external nostrils, which increases speed and ease of use, and is particularly advantageous when delivering medicament to infants who are more likely to become unsettled / upset after the dose has been delivered (and therefore delivering a further dose to a second nostril may be more difficult). However, it should be recognised that in each of these embodiments, the intranasal medicament delivery system may comprise a single nozzle outlet, such that medicament is sequentially delivered to each external nostril of the user. In some Attorney Docket No. : 46567-1771WO1 embodiments, the medicament delivery system comprises a single medicament delivery conduit.

[0218] 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.

[0219] As used herein, “RSV ANS2 / A1313 / 11314L” refers to an RSV ANS2 / A1313 / 11314L (NIH) or an RSV ANS2 / A1313 / I1314L (Sanofi). Each of the ANS2 / A1313 / I1314L (NIH) and the RSV ANS2 / A1313 / I1314L (Sanofi) comprise a live-attenuated RSV with (i) a 523 nucleotide (nt) deletion of the NS2 gene (ANS2), (ii) an amino acid deletion in the L protein, and (iii) a genetically stabilizing mutation in the L gene. The live-attenuated RSV of the RSV ANS2 / A1313 / I1314L (Sanofi) also includes a nucleotide modification at position 14456 that represents a change from a thymine (T) to an adenine (A) in a non-coding region.

[0220] As used herein, “RSV ANS2 / A1313 / 11314L vaccine” refers to an “RSV ANS2 / A1313 / I1314L (NIH) vaccine” or an “RSV ANS2 / A1313 / I1314L (Sanofi) vaccine.” An RSV ANS2 / A1313 / I1314L (NIH) vaccine comprises an effective amount of RSV ANS2 / A1313 / I 1314L (NIH). An RSV ANS2 / A1313 / I1314L (Sanofi) vaccine comprises an effective amount of RSV ANS2 / A1313 / I1314L (Sanofi).

[0221] Exemplary Methods and Uses

[0222] In some embodiments, provided are methods of delivering a dose of an RSV vaccine using an intranasal atomization delivery device.

[0223] 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 / 11314L Attorney Docket No. : 46567-1771WO1

[0224] (NIH) vaccine) or RSVA NS2 / A1313 / 11314L (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).

[0225] 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.

[0226] In some embodiments, the RSV vaccine is delivered intranasally using the intranasal atomization delivery device to deliver about 14 dose to each nostril. In some embodiments, the RSV vaccine is delivered intranasally so that the whole dose is delivered to one nostril. In some embodiments, the RSV vaccine is delivered intranasally with 14 dose delivered to one nostril and the other 14 dose is delivered to the same nostril after the first 14 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.

[0227] 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. Attorney Docket No. : 46567-1771WO1

[0228] 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.

[0229] In some embodiments, provided are methods of administering a first dose of an RSV vaccine using an intranasal atomization delivery device wherein the intranasal atomization delivery device comprises a spray nozzle to atomize the RSV vaccine and direct a spray plume toward a top of a nasal passageway into a nasal cavity. In some embodiments, provided are methods of administering a dose of an RSV vaccine using an intranasal atomization delivery device wherein the intranasal atomization delivery device comprises a spray nozzle to atomize the RSV vaccine and direct a spray plume toward a top of a nasal passageway into a nasal cavity. In some embodiments, the intranasal atomization delivery device comprises a barrel operably connected to the spray nozzle and a plunger movable within the barrel to advance the RSV vaccine through the spray nozzle. In some embodiments, the intranasal atomization delivery device further includes a dose divider for splitting the dose of the RSV vaccine into two or more deliveries. In some embodiments, the dose divider may divide the dose of the RSV vaccine in about half of a volume to be delivered to a subject. In some embodiments the dose divider is used to deliver1Z> dose to each nostril of the subject.

[0230] In some embodiments, the intranasal atomization delivery device delivers an average droplet size Dv50 of 10-120 pm. In some embodiments, the intranasal atomization delivery device delivers an average droplet size Dv50 of 10-120 pm, about 30-1 10 pm, about 50-110 pm, about 70-1 10 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.

[0231] 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 Attorney Docket No. : 46567-1771WO1 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 / 11314L (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).

[0232] Immunogenicity

[0233] Approximately seventy percent (70%) of vaccine recipients attained a 4-fold response in neutralizing antibody titer following the second vaccine dose in both low and high dose groups, compared to 61 and 47% following one vaccine dose in low and high dose RSV naive participants. This increase in the percentage of participants attaining a 4-fold response following a second administration supports the use of a second vaccine administration in this population. The 70% attaining this fold rise post second vaccine administration aligns with the expected clinical efficacy goal of 70% for the candidate. After one or two vaccinations, 75% attained a 4-fold rise in serum neutralizing antibody titers. The percentage of RSV experienced participants (36% and 22% in the low and high dose groups respectively) also attaining a 4 -fold response in neutralizing antibody titers post vaccination 1 suggests potential benefit for this sub-group as well. It must be noted that this comes from a modest sample of participants (n = 20 of 97 vaccine recipients) at this point of interim analysis.

[0234] 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.

[0235] Vaccine virus shedding and Infectivity

[0236] 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 Attorney Docket No. : 46567-1771WO1

[0237] 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.

[0238] Interim analysis results showed a promising safety, immunogenicity and infectivity profile of the RSV ANS2 / A1313 / I1314L (Sanofi) candidate.

[0239] 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.

[0240] 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-naive participants.

[0241] 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 Attorney Docket No. : 46567-1771WO1 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.

[0242] Reference numeral key:

[0243] I - intranasal nozzle

[0244] 3 - first conduit

[0245] 4 - first nozzle

[0246] 5 - first opening

[0247] 6 - second conduit

[0248] 7 - second nozzle

[0249] 8 - second opening

[0250] 9 - closure

[0251] 10 - adapter

[0252] I I - aperture

[0253] 12 - first opening

[0254] 13 - first end

[0255] 14 - second opening

[0256] 15 - second end

[0257] 16 - inner recess

[0258] 17 - protrusion 50 - axis Attorney Docket No. : 46567-1771WO1 0 - external surface

[0259] 100 - intranasal medicament delivery device

[0260] 110 - first adapter

[0261] 120 - second adapter

[0262] 122 - bridge

[0263] 111 - aperture

[0264] 112 - first opening

[0265] 113 - first end

[0266] 114 - second opening

[0267] 115 - second end

[0268] 116 - inner recess

[0269] 117 - protrusion

[0270] 131 - aperture

[0271] 132 - first opening

[0272] 133 - first end

[0273] 134 - second opening

[0274] 135 - second end

[0275] 136 - inner recess

[0276] 150 - axis

[0277] 151 - axis

[0278] 160 - external surface

[0279] 151 - axis

[0280] 203 - first conduit

[0281] 204 - first nozzle

[0282] 205- first opening

[0283] 210 - adapter

[0284] 211 - aperture

[0285] 212 - first opening

[0286] 213 - first end

[0287] 214 - second opening

[0288] 215 - second end

[0289] 250 - axis

[0290] 260 - external surface

[0291] 261 - external surface Attorney Docket No. : 46567-1771WO1

[0292] 310 - adapter

[0293] 311 - aperture

[0294] 312 - first opening

[0295] 313 - first end

[0296] 314 - second opening

[0297] 315 - second end

[0298] 350 - axis

[0299] 360 - external surface

[0300] 371 - aperture

[0301] 372 - outlet

[0302] 373 - inlet

[0303] 374 - valve700 - user

[0304] 900 - intranasal medicament delivery device

[0305] 901 - intranasal nozzle

[0306] 903 - first conduit

[0307] 904 - first nozzle outlet

[0308] 905 - first opening

[0309] 906 - second conduit

[0310] 907 - second nozzle outlet

[0311] 908 - second opening

[0312] 910 - coupling

[0313] 911 - chamber

[0314] 912 - body

[0315] 913 - plunger

[0316] 914 - outlet

[0317] 915 - coupling

[0318] 916 - inlet

Claims

Attorney Docket No. : 46567-1771WO1Claims1. An adapter (10, 110, 120, 210, 310) for an intranasal nozzle (1 , 901), wherein the adapter has an external surface (60, 160, 161 , 260, 261 , 360) for resting against a user’s nostril, wherein the external surface is flexible, and wherein the adapter comprises an aperture (11 , 111 , 131 , 211 , 311 , 371 ) that extends from a first opening (12, 112, 132, 212, 312) at a first end (13, 113, 133, 213, 313) of the adapter to a second opening (14, 114, 134, 214, 314) at a second end (15, 115, 135, 215, 315) of the adapter, wherein the aperture (11 , 111 , 131 , 211 , 311 , 371) is configured to receive a conduit of the intranasal nozzle through the second opening.

2. The adapter according to claim 1 , wherein the adapter (10, 110, 120, 210, 310) is made from silicone rubber.

3. The adapter according to claim 1 or 2, wherein the second opening (14, 114, 134, 214, 314) has a greater diameter than the first opening and / or wherein the external surface (60, 160, 161 , 260, 261 , 360) comprises a rounded shape or a frustoconical shape.

4. The adapter according to any preceding claim, wherein the aperture (11 , 111 , 131 , 211 , 311 , 371) comprises an inner recess (16, 116, 136) for fixing the adapter to the conduit, and optionally wherein the inner recess (16, 116, 136) comprises a circumferentially-extending recess.

5. The adapter according to any one of claims 1 to 4, wherein the aperture (11 ,111 , 131 , 211 , 311 , 371 ) comprises an internal diameter (d2) which is configured to fit the aperture (11 , 111 , 131 , 211 , 311 , 371) to the conduit by a transition fit for attaching the adapter to the conduit, and optionally wherein the internal diameter (d2) is less than the diameter of the second opening (14, 114, 134, 214, 314).

6. The adapter according to any preceding claim, wherein a spray nozzle (370) is located within the aperture (11 , 111 , 131 , 211 , 311 , 371), and optionally wherein the spray nozzle is rigid.Attorney Docket No. : 46567-1771WO17. The adapter according to claim 6, wherein the spray nozzle (370) comprises a valve (374) for spraying medicament at a desired pressure and optionally wherein the valve (374) is located within the aperture.

8. A system comprising an adapter, as defined in any one of the preceding claims, and an intranasal nozzle (1 , 901 ) comprising a first conduit (3, 903) for dispensing medicament, wherein the first conduit is configured to be located in the aperture of the adapter, and optionally wherein the adapter is a first adapter and the intranasal nozzle further comprises a second conduit (6, 906) for dispensing medicament, and wherein the second conduit is configured to be located in the aperture of a second adapter, wherein the second adapter is defined according to any one of the preceding claims.

9. A kit of parts comprising an intranasal nozzle (1 , 901) and a plurality of adaptors, wherein each adapter of the plurality of adapters is defined according to any one of claims 1 to 7, and wherein the intranasal nozzle comprises a first conduit (3, 203, 903) for dispensing medicament, and optionally wherein the intranasal nozzle comprises a second conduit (6, 906) for dispensing medicament, and optionally wherein the plurality of adapters comprise two or more adapters or four or more adapters.

10. The kit of parts as defined in claim 9, wherein the plurality of adapters comprise a plurality of smaller adapters and a plurality of larger adapters, wherein a diameter of the external surface (60, 160, 161 , 260, 261 , 360) of each of the smaller adapters is smaller than a diameter of the external surface (60, 160, 161 , 260, 261 , 360) of each of the larger adapters and optionally comprising two or more smaller adapters and two or more larger adapters.11 . The kit of parts according to claim 9 or 10, wherein the intranasal nozzle (1 , 901) is a first intranasal nozzle (1 , 901 ) and wherein the kit of parts further comprises one or more further intranasal nozzles (1 , 901 ) and optionally wherein the or each further intranasal nozzle (1 , 901 ) comprises a first conduit (3, 203, 903) for dispensing medicament, and optionally wherein the or each further intranasal nozzle comprises a second conduit (6, 906) for dispensing medicament.Attorney Docket No. : 46567-1771WO112. The system according to claim 8 or the kit of parts according to any one of claims 9 to 11 , further comprising a fluid flow generator, such as a bulb (2) or a syringe (902), for dispensing medicament from the intranasal nozzle (1 , 901) and / or wherein the intranasal nozzle (1 , 901) comprises a first closure (9a) which seals a first opening (5, 905) of the first conduit, wherein the first closure (9a) is configured to be removed from the first opening (5) of the first conduit to unseal the first opening for dispensing medicament therethrough and optionally wherein the intranasal nozzle (1 , 901 ) comprises a second closure (9b) which seals a second opening (8, 908) of the second conduit, wherein the second closure (9b) is configured to be removed from the second opening (8) of the second conduit to unseal the second opening for dispensing medicament therethrough and / or optionally wherein the first closure (9a) is configured to be removed from the first opening (5) by a user and / or wherein the second closure (9b) is configured to be removed from the second opening (8) by a user.

13. The system according to claim 8 or 12 or the kit of parts according to any one of claims 9 to 11 , wherein medicament is located in the intranasal nozzle (1 , 901 ).

14. A system according to claim 8, 12 or 13, or the kit of parts according to any one of claims 9 to 11 , wherein the intranasal nozzle (1 , 901 ) is a blow-fill-seal intranasal nozzle and / or is made from a plastic, such as polypropylene.

15. A method of preparing an intranasal nozzle (1 , 901 ), comprising inserting a first conduit (3, 203) of the intranasal nozzle into a first aperture (11 , 111 , 131 , 211 , 311 , 371) of a first adapter, wherein the first adapter has a flexible external surface (60, 160, 161 , 260, 261 , 360) for resting against a user’s nostril and wherein the first aperture (11 , 111 , 131 , 211 , 311 , 371) extends through the first adapter for allowing medicament to be dispensed through the first conduit (3, 203) when the first adapter is attached to the first conduit.

Images