An intranasal nozzle

Abstract

The present disclosure relates to an intranasal nozzle for medicament delivery. The intranasal nozzle comprises first and second delivery members. The first delivery member is configured to be inserted into a first nostril of a patient and comprises a first end portion that has a first medicament outlet. The second delivery member is configured to be inserted into a second nostril of the patient and comprises a second end portion that has a second medicament outlet. A gap is disposed between the first and second delivery members that is configured to receive at least a portion of the septum of the patient's nose when the first and second delivery members are inserted into the first and second nostrils. The width of the gap between the end portions of the first and second delivery members is at least 6 mm and the external width of the intranasal nozzle at the end portions is at most 20 mm. The present disclosure also relates to an intranasal medicament delivery system and to a method of delivering medicament to a patient.

Description

[0001] Attorney Docket No.: 46567-1784WO1

[0002] An intranasal nozzle

[0003] Cross-reference to related applications

[0004] The present application claims priority to EP patent application No. 24306951.5, 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 and to a method of delivering medicament to a patient.

[0007] This invention was created in the performance of a Cooperative Research and Development Agreement with the National Institutes of Health, an Agency of the Department of Health and Human Services. The Government of the United States has certain rights in this invention.

[0008] Background

[0009] It is known to provide a device for delivering medicament nasally to a patient. It has been found that it is desirable to deliver medicament to both nostrils of the patient simultaneously. This is particularly desirable where the patient is a paediatric patient.

[0010] However, it has been found that the nose size (including septum size and nostril diameter and shape) can vary significantly between patients (including due to factors such as age, race and sex). This variation in nose size between patients makes it difficult to deliver medicament to different patients using a single nozzle size.

[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.

[0012] It is an object of the present invention to address one or more of the problems mentioned above. Attorney Docket No.: 46567-1784WO1

[0013] Summary of the invention

[0014] According to the present disclosure, there is provided an intranasal nozzle for medicament delivery, the intranasal nozzle comprising: a first delivery member configured to be inserted into a first nostril of a patient and comprising a first end portion that has a first medicament outlet; and, a second delivery member configured to be inserted into a second nostril of the patient and comprising a second end portion that has a second medicament outlet, wherein a gap is disposed between the first and second delivery members that is configured to receive at least a portion of the septum of the patient’s nose when the first and second delivery members are inserted into the first and second nostrils, and wherein the width of the gap between the end portions of the first and second delivery members is at least 6 mm and wherein the external width of the intranasal nozzle at the end portions is at most 20 mm.

[0015] Advantageously, because the width of the gap is at least 6 mm and the external width W2 of the intranasal nozzle at the end potions is at most 20 mm, the intranasal nozzle can comfortably fit into a wide variety of sizes and shapes of nose of different paediatric patients. This means that a single size of intranasal nozzle can be manufactured and transported and used with many different paediatric patients.

[0016] In some embodiments, the width of the gap between the end portions is at least 6.5 mm and, preferably, is at least 7, 8, 8.5, 9 or 9.5 mm. In one embodiment, the width of the gap between the end portions is about 9.5 mm.

[0017] In some embodiments, the width of each end portion is at most 5 mm and, preferably, is at most 4, 3 or 2.5 mm.

[0018] In some embodiments, the width of each end portion is at least 2 mm.

[0019] In some embodiments, each delivery member is configured to have a maximum insertion depth into the nostril of at most 6 mm and, optionally, at most 5, 4, 3, 2 or 1 mm.

[0020] In some embodiments, each delivery member has a length of at least 1 mm and, preferably, at least 2 mm. Attorney Docket No.: 46567-1784WO1

[0021] In some embodiments, each end portion is the end 0.5 mm of length of the respective delivery member. In some embodiments, each end portion is the end 1 mm, 1.5 mm or 2 mm of the length of the respective delivery member.

[0022] In some embodiments, each delivery member has a length of at most 8 mm and, preferably, at most 6, 5, 4, 3 or 2 mm.

[0023] In some embodiments, each end portion has a length of at least 1 mm and, preferably, at least 1 .5 mm or at least 2 mm.

[0024] In some embodiments, each delivery member is flared to increase in width in a direction away from the respective end portion.

[0025] In some embodiments, the rate of increase in width of each flared delivery member is nonconstant. For example, there may be a relatively small rate of increase of the width of each delivery member nearer to the end portions and a relatively larger rate of increase of the width of each delivery member further away from the end portions (for instance, nearer to the body of the intranasal nozzle).

[0026] Each delivery member may have a first tapered section that increases in width with a relatively shallow taper and a second tapered section that increases in width with a relatively steep taper. The first section may be proximate to, or may comprise, the end portion of the respective delivery member. The second section may be spaced further away from the nozzle outlets than the first section. Each first section may extend from the respective second section. In some embodiments, the first section has a length in the range of 1 to 2 mm.

[0027] In some embodiments, the first section only increases in width in a direction away from the gap between the first and second delivery members. The gap between the delivery members may remain constant or substantially constant over the length of the first sections of the delivery members.

[0028] In some embodiments, the external width of the intranasal nozzle at the end portions is at most 19 mm and, optionally, at most 18, 17, 16, 15 or 14.5 mm. Attorney Docket No.: 46567-1784WO1

[0029] In some embodiments, the width of the gap between the end portions is at least 8 mm and the external width of the intranasal nozzle at the end portions is at most 17 mm. This has been found to comfortably fit within a particularly wide variety of sizes and shapes of nose of different paediatric patients. This means that a single size of intranasal nozzle can be manufactured and transported and used with many different paediatric patients. In some such embodiments, the width of each end portion is at most 4.5 mm.

[0030] In some embodiments, the intranasal nozzle is configured such that the first and second delivery members can be inserted into the first and second nostrils respectively of at least 70% of paediatric patients in the age range of 4 months to 24 months without deformation of the nose of the paediatric patient and, preferably, at least 75%, 80%, 85%, 90% or 95% of paediatric patients in the age range of 4 months to 24 months without deformation of the nose of the paediatric patient.

[0031] In some embodiments, the size, shape and spacing of the first and second delivery members is such that the first and second delivery members can be inserted into the first and second nostrils respectively of at least 70% of paediatric patients in the age range of 4 months to 24 months without deformation of the nose of the paediatric patient and, preferably, at least 75%, 80%, 85%, 90% or 95% of paediatric patients in the age range of 4 months to 24 months without deformation of the nose of the paediatric patient.

[0032] In some embodiments, each delivery member comprises a second portion that has a width of at least 3 mm and, preferably, at least 4, 5 or 5.5 mm.

[0033] In some embodiments, the second portion has a generally circular cross-section.

[0034] In some embodiments, each delivery member comprises a first section that tapers in width and a second section that tapers in width and is disposed further away from the nozzle outlets than the first section. In some embodiments, each second section tapers to reduce in width at a greater rate than the first section.

[0035] The first and second sections taper to reduce in width towards the nozzle outlets.

[0036] In some embodiments, a distance between the first sections of the respective delivery members remains relatively constant along the length of the first sections. Attorney Docket No.: 46567-1784WO1

[0037] In some embodiments, a distance between the second sections of the respective delivery members remains relatively constant along the length of the second sections.

[0038] In some embodiments, the second sections are longer than the first sections.

[0039] In some embodiments, each delivery member comprises at least one planar or substantially planar portion that is configured to abut the patient’s face when the delivery members are inserted into the patient’s nose.

[0040] In some embodiments, the or each planar or substantially planar portion is configured to abut a nasal sill of the patient when the delivery members are inserted into the patient’s nose.

[0041] In some embodiments, the or each planar or substantially planar portion extends along at least part of the length of the respective delivery member.

[0042] In some embodiments, at least one recess is provide in proximity to each substantially planar portion, wherein each recess configured to receive a portion of the patient’s face when the delivery members are inserted into the patient’s nose.

[0043] In some embodiment, each delivery member comprises first and second substantially planar portions that are on opposite sides of the respective delivery member.

[0044] In some embodiments, each end portion has a section of substantially constant width.

[0045] Each end portion may be substantially cylindrical.

[0046] In some embodiments, the intranasal nozzle is an intranasal nozzle for paediatric patients. The paediatric patients may be in the age range of 4 months to 24 months.

[0047] In some embodiments, each delivery member has a depth of at most 4.5 mm and, optionally, at most 4 mm, 3.5 mm, 3 mm, or 2.5 mm. The depth of each delivery member may be measured in a direction perpendicular to the width of the gap between the end portions of the first and second delivery members. The depth of each delivery member may be measured in a direction perpendicular to the height of the delivery members (e.g. Attorney Docket No.: 46567-1784WO1 measured in a direction perpendicular to the height of the delivery members from the base of the intranasal nozzle to the end portions).

[0048] In some embodiments, the intranasal nozzle comprises a body and wherein the first and second delivery members extend from the body. Optionally, the body is configured to abut the nose of the patient to limit insertion depth of the delivery members.

[0049] In some embodiments, the body comprises one or more base surfaces. The or each base surface may be substantially planar.

[0050] In some embodiments, the first and second delivery members extend from the one or more base surfaces.

[0051] In some embodiments, the one or more base surfaces are substantially perpendicular to a central axis of the end portions.

[0052] In some embodiments, the intranasal nozzle comprises a space that is configured to receive at least a portion of the patient’s lips and / or portion of the patient’s face between the lips and nose (e.g. the philtrum).

[0053] In some embodiments, the body comprises the space.

[0054] The space may be a recess.

[0055] In some embodiments, the intranasal nozzle further comprises a second space that is configured to receive at least a portion of the patient’s lips and / or portion of the patient’s face between the lips and nose (e.g. the philtrum), depending on the orientation of the intranasal nozzle.

[0056] In some embodiments, the space and second space are on opposite sides of the intranasal nozzle.

[0057] In some embodiments, the space and second space are on opposite sides of the body of the intranasal nozzle. Attorney Docket No.: 46567-1784WO1

[0058] In some embodiments, the space and / or second space is a generally curved recess into the intranasal nozzle.

[0059] In some embodiments, the end portions have a substantially circular cross-section.

[0060] In some embodiments, the first and second delivery members are in a fixed position relative to each other. In some embodiments, the spacing between the first and second delivery members cannot be adjusted.

[0061] In some embodiments, the first and second delivery members are integrally formed.

[0062] In some embodiments, the intranasal nozzle comprises a coupling configured to couple to a fluid flow generator and, optionally, wherein the coupling comprises a Luer lock.

[0063] The fluid flow generator may optionally be a syringe. The syringe may contain a medicament, such as a vaccine.

[0064] In some embodiments, the first and second delivery members are generally frustoconical or conical.

[0065] In some embodiments, the first and second delivery members are configured to atomize medicament.

[0066] In some embodiments, the intranasal nozzle is configured to deliver a liquid medicament.

[0067] In some embodiments, the centres of the first and second medicament outlets are spaced apart by a distance in the range of 9 to 15 mm and, optionally, in the range of 11 to 13 mm.

[0068] In some embodiments, the centre of the first and second medicament outlets are spaced apart by a distance of at least 8 mm and, optionally, at least 9, 10 or 11 mm.

[0069] In some embodiments, the centre of the first and second medicament outlets are spaced apart by a distance of at most 15 mm and, optionally, at most 14, 13, or 12 mm. Attorney Docket No.: 46567-1784WO1

[0070] In some embodiments, the intranasal nozzle comprises one or more indicator regions configured to indicate the position of the medicament outlets. The or each indicator region may comprise, for example, one or more graphic symbols (e.g. a pictogram) and / or text.

[0071] In some embodiments, the delivery members each comprise an indicator region. For example, a first indicator region may indicate the position of the first medicament outlet and a second indicator region may indicate the position of the second medicament outlet.

[0072] In some embodiments, each delivery member comprises a fluid conduit that communicates with the respective medicament outlet. In some embodiments, each fluid conduit has a width in the range of 0.1 to 0.7 mm.

[0073] In some embodiments, the intranasal nozzle comprises one or more gripping portions that are configured to be gripped by a user.

[0074] In some embodiments, each gripping portion may comprise one or more ribs.

[0075] According to the present disclosure, there is also provided a medicament delivery system comprising an intranasal nozzle according to the disclosure herein and a fluid flow generator. In some embodiments, the medicament delivery system contains a medicament and, optionally, wherein the medicament is a vaccine.

[0076] 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.

[0077] In some embodiments, the fluid flow generator is permanently coupled to the body.

[0078] In some embodiments, the fluid flow generator is a gas flow generator.

[0079] 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.

[0080] In some embodiments, the fluid flow generator comprises a syringe or flexible container.

[0081] In another embodiment, the fluid flow generator is a balloon. In yet another embodiment, Attorney Docket No.: 46567-1784WO1 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.

[0082] 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.

[0083] 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.

[0084] 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.

[0085] The medicament delivery system may comprise an intranasal atomization delivery device.

[0086] The intranasal nozzle may be configured to deliver about % of a dose to each nostril.

[0087] The intranasal nozzle may be configured to deliver about 0.2ml_, wherein about 0.1 mL is delivered to each nostril.

[0088] The intranasal nozzle may deliver an average droplet size Dv50 of about 10-120 pm.

[0089] 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

[0090] 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. Attorney Docket No.: 46567-1784WO1

[0091] 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).

[0092] 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.

[0093] 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.

[0094] According to the present disclosure, there is provided an intranasal nozzle for medicament delivery, the intranasal nozzle comprising: a first delivery member configured to be inserted into a first nostril of a paediatric user and comprising a first end portion that has a first medicament outlet; and, a second delivery member configured to be inserted into a second nostril of the paediatric user and comprising a second end portion that has a second medicament outlet, wherein a gap is disposed between the first and second delivery members that is configured to receive at least a portion of the septum of the paediatric user’s nose when the first and second delivery members are inserted into the first and second nostrils, and wherein the width of the gap between the end portions of the first and second delivery members is at least 6 mm and wherein the external width of the intranasal nozzle at the end portions is at most 20 mm. In some embodiments, the paediatric user may be in the age range of 4 months to 24 months. In some embodiments, the width of the gap between the end portions of the first and second delivery members is at least 8 mm and wherein the external width of the intranasal nozzle at the end portions is at most 18 mm or at most 17 mm.

[0095] According to the present disclosure, there is provided an intranasal nozzle for medicament delivery, the intranasal nozzle comprising: a first delivery member configured to be inserted into a first nostril of a patient and comprising a first end portion that has a first medicament outlet; and, a second delivery member configured to be inserted into a second nostril of the patient and comprising a second end portion that has a second medicament outlet, wherein a gap is disposed between the first and second delivery Attorney Docket No.: 46567-1784WO1 members that is configured to receive at least a portion of the septum of the patient’s nose when the first and second delivery members are inserted into the first and second nostrils, and wherein the width of the gap between the end portions of the first and second delivery members is at least 8 mm, the external width of the intranasal nozzle at the end portions is at most 17 mm and wherein each delivery member has a depth of at most 4.5 mm.

[0096] According to the present disclosure, there is also provided a method of delivering medicament to a patient, the method comprising inserting the end portions of first and second delivery members of an intranasal nozzle into first and second nostrils of the patient, wherein the width of a gap between the end portions is at least 6 mm and wherein the external width of the intranasal nozzle at the end portions is at most 20 mm; and, expelling medicament from the first and second delivery members.

[0097] The method may comprise expelling / administering an RSV vaccine.

[0098] The medicament may be expelled / delivered intranasally with about % dose delivered to each nostril.

[0099] The intranasal dose of the medicament may be delivered in about 0.2 mL, wherein about 0.1 mL is delivered to each nostril.

[0100] The method may comprise intranasal atomization delivery of an average droplet size Dv50 of about 10-120 pm.

[0101] 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.

[0102] 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.

[0103] In some embodiments, the method comprises removing the intranasal nozzle from a sealed pack. Attorney Docket No.: 46567-1784WO1

[0104] In some embodiments, the method comprises attaching the intranasal nozzle to a fluid flow generator.

[0105] According to the present disclosure, there is also provided an intranasal nozzle for medicament delivery, the intranasal nozzle comprising: a first delivery member configured to be inserted into a first nostril of a patient and comprising a first end portion that has a first medicament outlet; and, a second delivery member configured to be inserted into a second nostril of the patient and comprising a second end portion that has a second medicament outlet, wherein the intranasal nozzle is configured such that the first and second delivery members can be inserted into the first and second nostrils respectively of at least 70% of paediatric patients in the age range of 4 months to 24 months with generally no deformation of the nose of the paediatric patient.

[0106] In some embodiments, generally no deformation of the nose means no deformation of the nose.

[0107] In some embodiments, the size, shape and spacing of the first and second delivery members is such that the first and second delivery members can be inserted into the first and second nostrils respectively of at least 70% of paediatric patients in the age range of 4 months to 24 months without deformation of the nose of the paediatric patient.

[0108] In some embodiments, the intranasal nozzle is configured such that the first and second delivery members can be inserted into the first and second nostrils respectively of at least 75% of paediatric patients in the age range of 4 months to 24 months without deformation of the nose of the paediatric patient and, optionally, at least 80%, 85%, 90% or 95% of paediatric patients in the age range of 4 months to 24 months without deformation of the nose of the paediatric patient.

[0109] In some embodiments, the intranasal nozzle has any of the features of the intranasal nozzle described herein.

[0110] According to the present disclosure, there is also provided an intranasal nozzle for medicament delivery, the intranasal nozzle comprising: a first delivery member configured to be inserted into a first nostril of a patient and comprising a first medicament outlet; and, a second delivery member configured to be inserted into a second nostril of the patient and comprising a second medicament outlet, wherein a gap is disposed between the first Attorney Docket No.: 46567-1784WO1 and second delivery members that is configured to receive at least a portion of the septum of the patient’s nose when the first and second delivery members are inserted into the first and second nostrils, wherein at least a portion of each delivery member has a width of at most 5 mm, and wherein the width of the gap or at least a part of the gap between said portions of the delivery members is at least 6 mm.

[0111] Advantageously, because the width of the gap is at least 6 mm and the portion (e.g. end portion) of each delivery member is at most 5 mm, the intranasal nozzle can comfortably fit into a wide variety of sizes and shapes of nose of different paediatric patients. This means that a single size of intranasal nozzle can be manufactured and transported and used with many different paediatric patients.

[0112] In some embodiments, the width of the gap is constant or substantially constant over the length of the delivery members or said portions of the delivery members. In other embodiments, the width of the gap varies over the length of the delivery members or said portions of the delivery members (and, optionally, the width of the gap is only at least 6 mm over part of the length of the delivery members / said portions of the delivery members).

[0113] In some embodiments, the portions of the first and second delivery members are end portions.

[0114] In some embodiments, the width of each portion of the first and second delivery members is at most 4 mm and, preferably, is at most 3 or 2.5 mm.

[0115] In some embodiments, the width of the gap is at least 6.5 mm and, preferably, is at least 7, 8, 8.5, 9 or 9.5 mm. In one embodiment, the width of the gap is about 9.5 mm.

[0116] In some embodiments, the width of each portion is measured in the same direction as the width of the gap. In some embodiments, the width of each portion is the diameter of the portion.

[0117] In some embodiments, the intranasal nozzle has any of the features of the intranasal nozzle described herein.

[0118] Brief description of the drawings Attorney Docket No.: 46567-1784WO1

[0119] So that the invention may be more fully understood, reference is made to the accompanying drawings, in which:

[0120] Fig. 1 is a front view of an embodiment of an intranasal medicament delivery system, wherein a fluid flow generator is disconnected from an intranasal nozzle of the system; Fig. 2 is a front view of the system of Fig. 1 , wherein the fluid flow generator is connected to the intranasal nozzle;

[0121] Fig. 3 is a perspective view of the intranasal nozzle of the system of Fig. 1 ;

[0122] Fig. 4 is a front view of the intranasal nozzle of the system of Fig. 1 ;

[0123] Fig. 5 is a cross-sectional front view of the intranasal nozzle of the system of Fig. 1 ;

[0124] Fig. 6 is a top view of the intranasal nozzle of the system of Fig. 1 ;

[0125] Fig. 7 is a side view of the intranasal nozzle of the system of Fig. 1 ;

[0126] Fig. 8 is a perspective view of another embodiment of an intranasal nozzle;

[0127] Fig. 9 is a front view of the intranasal nozzle of Fig. 8;

[0128] Fig. 10 is a top view of the intranasal nozzle of Fig. 8;

[0129] Fig. 11 is a side view of the intranasal nozzle of Fig. 8;

[0130] Fig. 12 is a perspective view of another embodiment of an intranasal nozzle;

[0131] Fig. 13 is a front view of the intranasal nozzle of Fig. 12;

[0132] Fig. 14 is a top view of the intranasal nozzle of Fig. 12;

[0133] Fig. 15 is a side view of the intranasal nozzle of Fig. 12;

[0134] Fig. 16 is a perspective view of another embodiment of an intranasal nozzle;

[0135] Fig. 17 is a front view of the intranasal nozzle of Fig. 16;

[0136] Fig. 18 is a top view of the intranasal nozzle of Fig. 16;

[0137] Fig. 19 is a side view of the intranasal nozzle of Fig. 16;

[0138] Fig. 20 is a flowchart showing an example method of delivering medicament to a patient;

[0139] Fig. 21 is a perspective view of another embodiment of an intranasal nozzle;

[0140] Fig. 22 is a front view of the intranasal nozzle of Fig. 21 ;

[0141] Fig. 23 is a first side view of the intranasal nozzle of Fig. 21 ; and, Fig. 24 is a second side view of the intranasal nozzle of Fig. 21.

[0142] Detailed description

[0143] Referring now to Figs. 1 to 7, an embodiment of an intranasal medicament delivery system 100 is shown.

[0144] In the present example, the intranasal medicament delivery system 100 is an intranasal medicament delivery device 100. The intranasal medicament delivery system 100 Attorney Docket No.: 46567-1784WO1 comprises an intranasal nozzle 1 for delivering medicament to a paediatric patient’s nostrils. In the present example, the paediatric patient is in the range of 4 to 24 months old. However, it should be recognised that in each of the examples described herein, the paediatric may be older or younger than this age range.

[0145] The intranasal medicament delivery system 100 further comprises a fluid flow generator 2, which in the present example is a syringe 2.

[0146] The intranasal nozzle 1 comprises a first medicament delivery member 3 comprising a first nozzle outlet 4 for dispensing medicament from the nozzle 1 , and a second medicament delivery member s comprising a second nozzle outlet 7 for dispensing medicament from the nozzle 1.

[0147] In the present example, the first and second nozzle outlets 4, 7 are spray nozzles. The nozzle outlets 4, 7 may be configured to atomize the medicament when it is expelled from the nozzle outlets 4, 7.

[0148] The medicament may be a vaccine. The intranasal nozzle 1 may be an intranasal atomization delivery nozzle 1 .

[0149] An advantage of the intranasal nozzle 1 comprising two nozzle outlets 4, 7 is that medicament can simultaneously be delivered to both nostrils of the patient, 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). In addition, delivering medicament to both nostrils simultaneously helps to ensure medicament delivery to the patient even in the event that one of the nostrils is blocked.

[0150] The first delivery member 3 comprises a first medicament delivery conduit 5 and the second delivery member 6 comprises a second medicament delivery conduit 8.

[0151] The intranasal nozzle 1 is configured to couple to the fluid flow generator 2 such that the first and second medicament delivery conduits 5, 8 fluidly communicate with the fluid flow generator 2. The intranasal nozzle 1 comprises a coupling 10 that is configured to couple to the fluid flow generator 2. In the present example, the coupling 10 is a Luer lock Attorney Docket No.: 46567-1784WO1 connection that is configured to couple to a corresponding Luer lock connection 15 of the fluid flow generator 2 (which in the present example is a syringe 2).

[0152] In some embodiments, the fluid flow generator 2 is configured to generate a fluid flow. The fluid flow generator 2 may comprise, for example, a syringe, a flexible container or balloon that can be squeezed by a user, or a pressurised gas source (for example, a cannister of pressurised gas). The fluid may be a gas such as air or another gas (e.g. oxygen or carbon dioxide). However, in other embodiments, the fluid flow generator is configured to deliver a flow of liquid (for example, liquid medicament) and may comprise, for example, an injector device such as a pen-injector or autoinjector.

[0153] In the present embodiment, the fluid flow generator 2 contains the medicament such that operation of the fluid flow generator 2 expels medicament from the fluid flow generator 2 and into the intranasal nozzle 1 for delivery to the patient. However, it should be recognised that in other embodiments the intranasal nozzle 1 may store the medicament and wherein the fluid flow generator 2 is operable to expel a fluid (e.g. air or another gas) from the fluid flow generator 2 that enters the intranasal nozzle 1 to expel the medicament from the intranasal nozzle 1 for delivery to the patient. That is, the flow of gas or liquid expels medicament from the intranasal nozzle 1. In embodiments (not shown) in which the medicament is stored in the intranasal nozzle 1 , the intranasal nozzle 1 may comprise one or more sealing members (not shown) configured to seal the inlet of the intranasal nozzle and the outlets 4, 7 prior to connection of the fluid flow generator to the intranasal nozzle. The sealing members may comprise, for example, removable tabs, plugs or labels.

[0154] In the present example, the fluid flow generator 2 comprises a chamber 11 for containing the medicament. The fluid flow generator 2 is configured such that, in use, the volume of the chamber 11 is decreasable upon the application of a force by a user to expel the medicament from the chamber 11 and into the first and second medicament delivery conduits 5, 8 of the respective delivery members 3, 6.

[0155] In the present example, the fluid flow generator 2 is a syringe 2. The syringe 2 forms a medicament delivery device 2. The syringe 2 has a body 12 and a plunger 13. The chamber 11 is disposed within the body 12. The plunger 13 is disposed at one end of the chamber 11 and is slidable within the body 12. Attorney Docket No.: 46567-1784WO1

[0156] The syringe 2 further comprises a coupling 15 at an end of the body 12 for connecting to the coupling 10 of the intranasal nozzle 1 . In the present example, the coupling 15 of the syringe 2 comprises a Luer lock connection to engage the Luer lock connection of the coupling 10 of the nozzle 1. The syringe 2 may comprise a male Luer lock fitting 15 that engages a female Luer lock fitting 10 of the nozzle 1 . Advantageously, this means that the nozzle 1 can be used with a standard syringe 2.

[0157] In other examples, the coupling 10 of the nozzle 1 and the coupling 15 of the syringe 2 may have a different configuration, for example, a bayonet connection, snap-fit or screw threads.

[0158] The coupling 15 of the syringe 2 comprises an outlet 14 that fluidly communicates with an inlet 16 of the intranasal nozzle 1 that is located within the coupling 10 of the nozzle 1. Therefore, in use, the syringe 2 is operable to generate a medicament flow that enters the intranasal nozzle 1. More particularly, the user exerts a force on the plunger 13 of the syringe 2 to slide the plunger 13 within the body 12 towards the outlet 14 such that the volume of the chamber 11 is decreased, thereby expelling medicament out of the chamber 11 via the outlet 14.

[0159] In alternative embodiments (not shown) wherein the medicament is instead stored in the intranasal nozzle 1 , then the plunger 13 may be slid to expel air (or an alternative gas or liquid) from the chamber 11 via the outlet 14 to displace the medicament in the intranasal nozzle 1 .

[0160] It should be recognised that in other embodiments, the fluid flow generator 2 may take a different form. In one such embodiment (not shown), the fluid flow generator 2 may instead comprise a flexible container that is squeezed to expel fluid (which may be the medicament if stored in the fluid flow generator 2) from the flexible container via a coupling that is connected to the coupling 10 of the nozzle 1. The flexible container may comprise a bulb or balloon that is squeezed to generate the fluid flow.

[0161] In some embodiments (not shown), the fluid flow generator 2 is permanently attached to the intranasal nozzle 1 and, optionally, may be integrally formed therewith.

[0162] The intranasal nozzle 1 comprises a body 17 with a passage 18 for fluidly communicating with the gas flow generator 2 via the inlet 16. Attorney Docket No.: 46567-1784WO1

[0163] The first and second medicament delivery conduits 5, 8 are located within the first and second delivery members 3, 6 respectively and are fluidly communicated with the passage 18. The first and second medicament delivery conduits 5, 8 may form a manifold that extends from the passage 18.

[0164] In use, the intranasal nozzle 1 is attached to the fluid flow generator 2 (unless the intranasal nozzle 1 and fluid flow generator 2 are already provided in an attached or integrally formed configuration). This may involve first removing a seal (e.g. a sealing label or stopper, not shown) from the outlet 14 of the fluid flow generator 2. Alternatively, the fluid flow generator 2 may be removed from a pack and then filled with medicament, for example, by pulling the plunger 13 to draw medicament into the chamber 11.

[0165] The intranasal nozzle 1 can then be positioned to deliver medicament to the user. In the present example, the end of the intranasal nozzle 1 can be inserted into the patient’s nostrils, as will be described in more detail below.

[0166] The medicament M can then be dispensed from the intranasal fluid delivery nozzle 1 by a user operating the fluid flow generator 2. In the present example, the user presses the plunger 13 into the body 12 of the syringe 2 such that the volume of the chamber 11 is decreased and thus the medicament in the chamber 11 is forced through the inlet 16 of the intranasal nozzle 1 , wherein the medicament is expelled from the nozzle outlets 4, 7 for delivery to the patient.

[0167] The first delivery member 3 is configured to be inserted into a first nostril of the patient and comprises a first end portion 3A that comprises the first nozzle outlet 4. The second delivery member 6 is configured to be inserted into a second nostril of the patient and comprises a second end portion 6A that comprises the second nozzle outlet 7.

[0168] A gap 19 is located between the first and second delivery members 3, 6 that is configured to receive at least a portion of the septum of the patient’s nose when the first and second delivery members 3, 6 are inserted into the first and second nostrils. The width W1 of the gap 19 between the end portions 3A, 6A of the first and second delivery members 3, 6 is at least 6 mm. It has been found that if the gap 19 is too small, then it cannot accommodate larger noses with a larger septum without causing discomfort (the septum being uncomfortably compressed between the delivery members 3, 6). Attorney Docket No.: 46567-1784WO1

[0169] The width W1 of the gap 19 is measured in a direction between the first and second delivery members 3, 6, and the width W1 may be generally perpendicular to the central axis of the first and second delivery members 3, 6.

[0170] In addition, the external width W2 of the intranasal nozzle 1 at the end portions 3A, 6A is at most 20 mm. It has been found that if the external width W2 of the intranasal nozzle 1 is too large, then it cannot be readily accommodated within smaller noses without causing discomfort. For example, the alae / wings of the nose may be uncomfortably deformed.

[0171] The external width W2 is measured in the same direction as the width W1 of the gap 19.

[0172] Advantageously, because the width W1 of the gap 19 is at least 6 mm and the external width W2 of the intranasal nozzle 1 at the end potions 3A, 6A is at most 20 mm, the intranasal nozzle 1 can comfortably fit into a wide variety of sizes and shapes of nose of different paediatric patients. This means that a single size of intranasal nozzle 1 can be manufactured and transported and used with many different paediatric patients.

[0173] In some embodiments, the width W1 of the gap 19 between the end portions 3A, 6A is at least 6.5 mm and, preferably, is at least 7, 7.5, 8, 8.5, 9 or 9.5 mm. Increasing the width W1 of the gap 19 allows for the gap 19 to accommodate larger septum sizes. In the present example, the width W1 of the gap 19 between the end portions 3A, 6A is about 8.5 mm. A width W1 of gap 19 of at least 8, 8.5, 9 or 9.5 mm has been found to particularly advantageously be able to accommodate a very large range of septum sizes.

[0174] In some embodiments, the external width W2 of the intranasal nozzle 1 at the end portions 3A, 6A is at most 19 mm and, preferably, at most 18, 17, 16, 15 or 14.5 mm. Decreasing the width W2 of the intranasal nozzle 1 at the end portions 3A, 6A allows for the nozzle 1 to fit within smaller noses (in particular, wherein the outsides of the nostrils or alae / wings of the nose are spaced closer together). In the present example, the external width W2 of the intranasal nozzle 1 at the end portions 3A, 6A is about 15.1 mm. This has been found to be able to fit within a very large range of nose sizes.

[0175] It has been found that the first and second delivery members 3, 6 can be inserted into the first and second nostrils respectively of 93% of paediatric patients in the age range of 4 months to 24 months with generally no deformation of the nose of the paediatric patient Attorney Docket No.: 46567-1784WO1

[0176] (e.g. generally no stretching of the nasal wings and generally no compression of the septum). This means that the intranasal nozzle 1 can be used with a wide variety of nose shapes of different paediatric patients within this age range. In practice, the intranasal nozzle 1 can be used with even greater than 93% of paediatric patients in this age range, because some stretching of the nasal wings is acceptable and also (to a lesser extent) some compression of the septum is acceptable without causing unacceptable discomfort to the patient.

[0177] The W1 of the gap 19 and the external width W2 of the intranasal nozzle 1 at the end portions 3A, 6A are both measured on the same imaginary plane P-P. The plane P-P extends perpendicular to the first and second delivery members 3, 6. The plane P-P intersects the first and second delivery members 3, 6 at the same distance along the length of the first and second delivery members 3, 6 from the outlets 4, 7.

[0178] It should be recognised that in some embodiments only a portion of the gap 19 has a width W1 that is at least 6 mm, and other portions of the gap 19 may have a width W1 that is smaller than 6 mm. For instance, the width W1 of the gap 19 may reduce towards the body 17 of the intranasal nozzle 1.

[0179] In some embodiments, the width W3 of each end portion 3A, 6A is at most 5 mm and, preferably, is at most 4, 3.5, 3 or 2.5 mm. This helps to ensure that the end portions 3A, 6A comfortably fit within smaller nostrils.

[0180] In some embodiments, the width W3 of each end portion 3A, 6A is at least 2 mm. This helps to promote durability of the end portions 3A, 6A and more accurate positioning of the nozzle outlets 4, 7 within the respective nostrils.

[0181] In the present example, the width W3 of each end portion 3A, 6A is about 3.3 mm.

[0182] In some embodiments, the end portions 3A, 6A each have a substantially circular crosssection. Thus, the width W3 is the diameter of the end portion 3A, 6A.

[0183] In some embodiments, the centre of the first nozzle outlet 4 and the centre of the second nozzle outlet 7 are a distance in the range of 8 to 16 mm from each other and, preferably, a distance in the range of 10 to 14 mm or in the range of 11 to 13 mm from each other. It Attorney Docket No.: 46567-1784WO1 has been found that this advantageously helps to ensure that the centre of the nozzle outlets 4, 7 remain towards the centre of the nostrils of the patient.

[0184] In some embodiments, the centre of the first nozzle outlet 4 and the centre of the second nozzle outlet 7 are a distance of at least 8 mm from each other and, optionally, at least 9, 10 or 11 mm from each other.

[0185] In some embodiments, the centre of the first nozzle outlet 4 and the centre of the second nozzle outlet 7 are a distance of at most 16 mm from each other and, optionally, at most 15, 14, 13, or 12 mm from each other.

[0186] In the present example, the centre of the first nozzle outlet 4 and the centre of the second nozzle outlet 7 are a distance of 11 .8 mm from each other.

[0187] In some embodiments, the first and / or second medicament delivery conduit 5, 8 has a width in the range of 0.1 to 0.7 mm.

[0188] In some embodiments, the first and second nozzle outlets 4, 7 are located within the centre of the end portions 3A, 6A of the respective delivery members 3, 6. This may make the nozzle 1 easier to manufacture and easier to use.

[0189] The first and second delivery members 3, 6 are in a fixed position relative to each other such that the gap 19 therebetween cannot be adjusted. This may help to ensure that the intranasal nozzle 1 remains the dimensions to fit a variety of nose sizes.

[0190] The first and second delivery members 3, 6 may be integrally formed with each other. In the present example, the intranasal nozzle 1 is integrally formed from a single piece of material.

[0191] The first and second delivery members 3, 6 extend from the body 17 of the intranasal nozzle 1. In the present example, the delivery members 3, 6 extend in parallel. Each delivery member 3, 6 may be in the form of a pin. The first and second end portions 3A, 6A are located remote to the body 17. The first and second end portions 3A, 6A are configured to be inserted into the patient’s nostrils. Attorney Docket No.: 46567-1784WO1

[0192] The body 17 may be configured to abut the nose of the infant, if the nose is sufficiently large enough, thereby limiting the insertion depth of the intranasal nozzle 1 into the patient’s nose. This helps to improve comfort for the patient during use of the intranasal nozzle 1 .

[0193] In some embodiments, each delivery member 3, 6 is configured to have an insertion depth into the nostrils of the patient of at most 6 mm and, optionally, at most 5, 4, 3 or 2 mm.

[0194] In some embodiments, each delivery member 3, 6 has a length of at most 8 mm and, preferably, at most 6, 5, 4, 3 or 2 mm.

[0195] In some embodiments, each delivery member 3, 6 has a length of at least 1 mm and, preferably, at least 2 mm.

[0196] In some embodiments, each end portion 3A, 6A is the end 0.5 mm of length of the respective delivery member 3, 6. In some embodiments, each end portion 3A, 6A is the end 1 mm, 1.5 mm or 2 mm of the length of the respective delivery member s, 6.

[0197] In some embodiments, each end portion 3A, 6A has a length of at least 1 mm and, preferably, at least 2 mm.

[0198] In some embodiments, the body 17 comprises one or more base surfaces 20. In the present example, the body 17 comprises a single base surface 20, and wherein both of the delivery members 3, 6 extend from the base surface 20. However, in an alternative embodiment (not shown), the body 17 may comprise first and second base surfaces, and wherein each delivery member 3, 6 extends from a respective base surface.

[0199] In some embodiments, the or each base surface 20 is planar or substantially planar.

[0200] In the present example, the base surface 20 is substantially perpendicular to a central axis of the end portions 3A, 6A.

[0201] The intranasal nozzle 1 comprises first and second spaces 21 , 22 that are configured to receive at least a portion of the infant’s lips and / or portion of the infant’s face between the lips and nose (e.g. the philtrum) when the end portions 3A, 6A are received in the user’s nostrils. This is advantageous because it means that the said potion of the patient’s Attorney Docket No.: 46567-1784WO1 face / lips can be accommodated within one of the spaces 21 , 22 during use of the intranasal nozzle 1 , thereby preventing or reducing pressure being applied to the patient’s face / lips during use of the nozzle 1 and thus increasing comfort and the accuracy with which the intranasal nozzle 1 can be positioned to deliver medicament.

[0202] In the present example, the intranasal nozzle 1 comprises a first space 21 on a first side of the intranasal nozzle 1 and a second space 22 on an opposite second side of the intranasal nozzle 1. This increases ease of use and helps to save time when the intranasal nozzle 1 is to be used to deliver medicament to the patient, because the intranasal nozzle 1 can either be orientated in a first position with the aforementioned portion of the patient’s lips / face received in the first space 21 or orientated in a second position with the aforementioned portion of the patient’s lips / face received in the second space 22. However, it should be recognised that in other embodiments (not shown) the intranasal nozzle 1 may comprise only a single space or the spaces may be omitted entirely.

[0203] In the present example, the body 17 comprises the first and second spaces 21 , 22. The body 17 comprises a concave surface 21 A on a first side of the body 17 and wherein the first space 21 is formed in the concavity of the surface 21 A (i.e. in a curved recess of the body 17). The body 17 comprises a concave surface 22A on an opposite second side of the body 17 and wherein the second space 22 is formed in the concavity of the surface 22A (i.e. in a curved recess of the body 17). The concave surfaces 21A, 22A may be generally curved. Although in the above described embodiment the first and second spaces 21 , 22 are formed by a concave surface, it should be recognised that in other embodiments the spaces 21 , 22 may have a different shape and still accommodate the portion of the patient’s face.

[0204] The intranasal nozzle 1 optionally comprises one or more indicator regions 23, 24 configured to indicate the position of the nozzle outlets 4, 7. This helps the user (for example, a health care practitioner) to accurately position the intranasal nozzle 1 for the delivery of medicament to the patient, with the first end portion 3A received in a first nostril and the second end portion 6A received in a second nostril. In some embodiments, the delivery members 3, 6 each comprise an indicator region 23, 24. For example, a first indicator region 23 may indicate the position of the first nozzle outlet 4 and a second indicator region 24 may indicate the position of the second nozzle outlet 7. However, it Attorney Docket No.: 46567-1784WO1 should be recognised that in other embodiments the intranasal nozzle 1 may comprise a single indicator region or the indicator regions may be omitted entirely.

[0205] The or each indicator region 23, 24 may comprise, for example, graphics (such as arrows 23, 24 as shown in Fig. 4) and / or text.

[0206] Referring now to Figs. 8 to 11 , another embodiment of an intranasal nozzle 1 ’ is shown. The intranasal nozzle 1 ’ is similar to the intranasal nozzle 1 of the embodiment of Figs. 1 to 7, with like features retaining the same reference numerals. A difference is that the intranasal nozzle 1 ’ has a width W1 of gap 19 of 11.2 mm at the end portions 3A, 6A, the external width W2 of the intranasal nozzle 1 at the end portions 3A, 6A is 17.8 mm. The width W3 of the end portions 3A, 6A is 3.3 mm, as described previously.

[0207] It has been found that the first and second delivery members 3, 6 can be inserted into the first and second nostrils respectively of 80% of paediatric patients in the age range of 4 months to 24 months with generally no deformation of the nose of the paediatric patient (e.g. generally no stretching of the nasal wings and generally no compression of the septum). This means that the intranasal nozzle 1 can be used with a wide variety of nose shapes of different paediatric patients within this age range. In practice, the intranasal nozzle 1 can be used with even greater than 80% of paediatric patients in this age range, because some stretching of the nasal wings is acceptable and also (to a lesser extent) some compression of the septum is acceptable without causing unacceptable discomfort to the patient.

[0208] Each delivery member s, 6 of the intranasal nozzle 1’ comprises a generally frustoconical second portion 3B, 6B that extends from the body 17. The end portions 3A, 6A of the delivery members 3, 6 extend from the respective second portions 3B, 6B. The second portion 3B, 6B of each delivery member 3, 6 is tapered to increase in width in a direction away from the end portion 3A, 6A.

[0209] The second portions 3B, 6B are generally flared, increasing in width in a direction away from the end portions 3A, 6A. This has been found to improve comfort when the intranasal nozzle 1 ’ is inserted into the nose of a patient that is of a size and shape that the nose (e.g. the wings) are stretched by the intranasal nozzle 1 ’. This is because the flared width of the second portions 3B, 6B helps to gradually and gently stretch the nose as the intranasal nozzle 1’ is inserted rather than the nose suddenly being deformed by a step- Attorney Docket No.: 46567-1784WO1 change in the dimensions of the intranasal nozzle 1’. The flared width of the second portions 3B, 6B also helps to limit the maximum insertion depth of the delivery members 3, 6, and can provide a tactile feedback to the user (e.g. healthcare practitioner) when inserting the delivery members 3, 6 into the patient’s nose.

[0210] The flared base of each second portion 3B, 6B may have a width of at least 3 mm and, preferably, at least 4, 5 or 5.5 mm. In the present example, the flared base of each second portion 3B, 6B has a width of 5.8 mm. That is, the second portion 3B, 6B tapers from a width of 3.3 mm (at the end portions 3A, 6A) to 5.8 mm (at the body 17). The width of the second portion 3B, 6B may be measured in the same direction as the width W3 of the respective end portion 3A, 6A.

[0211] Referring now to Figs. 12 to 15, another embodiment of an intranasal nozzle 1” is shown. The intranasal nozzle 1 ” is similar to the intranasal nozzle 1 ’ of the embodiment of Figs. 8 to 11 , with like features retaining the same reference numerals. The intranasal nozzle 1 ” has the same dimensions of width W1 of gap 19, external width W2 and width W3 of end portions 3A, 6A as described previously in respect of the intranasal nozzle 1 ’ of Figs. 8 to 11.

[0212] In some embodiments, the second portion 3B, 6B of each delivery member 3, 6 has a depth (in the direction of arrows ‘D2’ and ‘D3’ in Fig. 14) of at most 4 mm and, preferably, at most 3.5 mm, 3 mm, or 2.5 mm in a direction perpendicular to width W1 , W2 and W3. This helps to prevent or reduce pressure being applied to the patient’s face / lips during use of the nozzle 1’ (which may otherwise be caused by the second portion 3B, 6B pressing against the patient if it has too much depth) and thus increasing comfort and the accuracy with which the intranasal nozzle 1 ” can be positioned to deliver medicament.

[0213] In some embodiments, each delivery member 3, 6 has a depth (in the direction of arrows ‘D2’ and ‘D3’ in Fig. 14) of at most 4.5 mm and, preferably, at most 4 mm, 3.5 mm, 3 mm, or 2.5 mm in a direction perpendicular to width W1 , W2 and W3.

[0214] Optionally, each delivery member 3, 6 further comprises a substantially planar portion 25A, 25B, 26A, 26B that is configured to abut the patient’s face when the delivery members 3, 6 are inserted into the patient’s nose. That is, a space 27A, 27B, 28A, 28B in proximity to each flat portion 25A, 25B, 26A, 26B can receive a portion of the patient’s face, which may then abut the substantially flat portion 25A, 25B, 26A, 26B.This helps to Attorney Docket No.: 46567-1784WO1 prevent or reduce pressure being applied to the patient’s face / lips during use of the nozzle T (which may otherwise be caused by the flared second portion 3B, 6B pressing against the patient) and thus increasing comfort and the accuracy with which the intranasal nozzle T can be positioned to deliver medicament.

[0215] In some embodiment, the first delivery member 3 comprises first and second substantially planar portions 25A, 25B that are on opposite sides of the first delivery member 3 and / or the second delivery member 6 comprises first and second substantially planar portions 26A, 26B that are on opposite sides of the second delivery member 6. This helps to improve ease of use and save time when the intranasal nozzle 1 ” is to be used to deliver medicament to the patient, because the intranasal nozzle 1” can either be orientated in a first position with the first planar portions 25A, 26A in contact with (or facing towards) the patient’s face or orientated in a second position with the second planar portions 25B, 26B in contact with (or facing towards) the patient’s face. However, it should be recognised that in other embodiments (not shown) each delivery member 3, 6 of the intranasal nozzle 1 ” may comprise only a single planar portion or the planar portions may be omitted entirely.

[0216] In some embodiments, the first and second delivery members 3, 6 have a substantially constant depth measured in a direction perpendicular to the width W1 of the gap 19. The depth of the delivery members 3, 6 is measured in the same direction as arrows D2 and D3.

[0217] Referring now to Figs. 16 to 19, another embodiment of an intranasal nozzle 1’” is shown. The intranasal nozzle 1 ’” is similar to the intranasal nozzle 1 ” of the embodiment of Figs. 12 to 15, with like features retaining the same reference numerals. A difference is that the intranasal nozzle 1 ’” has a width W1 of gap 19 of 9.5 mm at the end portions 3A, 6A, and the external width W2 of the intranasal nozzle 1 at the end portions 3A, 6A is 14.1 mm. The width W3 of the end portions 3A, 6A is 2.3 mm.

[0218] Another difference is that the intranasal nozzle 1 ’” has a body 17 with a reduced depth (shown by the combination of arrows ‘D2’ and ‘D3’ in Fig. 18). The depth is measured perpendicular to the width W1 of the gap 19 and external width W2 of the intranasal nozzle 1 . Attorney Docket No.: 46567-1784WO1

[0219] In the present example, the depth extends from the first surface 21 A of the body 17 (which may be a concave surface 21 A) to the second surface 22A of the body 17 (which may be a concave surface 22A).

[0220] The depth may optionally be in the range of 4 to 10 mm and, preferably, 4 to 8 mm.

[0221] In the present example, the distance (shown by arrow ‘D2’ in Fig. 18) between the first surface 21A of the body 17 (which may be a concave surface 21A) and an imaginary plane P1-P1 intersecting the centre of the nozzle outlets 4, 7) is in the range of 2 to 4 mm. This allows for easier positioning of the nozzle outlets 4, 7 within the nostrils of the patient without the body 17 fouling on the patient’s face when the intranasal nozzle 1 ”’ is orientated in a first orientation (with the first surface 21 A facing towards the patient’s face).

[0222] In the present example, the distance (shown by arrow ‘D3’ in Fig. 18) between the second surface 22A of the body 17 (which may be a concave surface 22A) and an imaginary plane P1-P1 intersecting the centre of the nozzle outlets 4, 7) is in the range of 2 to 4 mm. This allows for easier positioning of the nozzle outlets 4, 7 within the nostrils of the patient without the body 17 fouling on the patient’s face when the intranasal nozzle 1 ’” is orientated in a second orientation (with the second surface 22A facing towards the patient’s face). However, it should be recognised that in alternative embodiments distances D2 and / or D3 may be greater than the ranges set out above and, optionally, the intranasal nozzle 1 , 1 ’, 1 ”, T” may have an asymmetrical shape or sizing.

[0223] In some embodiments, the width W1 of the gap 19 is at least 6 mm and, preferably, at least 7, 8, 8.5, 9 or 9.5 mm over at least 50% and, preferably, at least 60%, 70%, 80%, 90%, or 95% of the length or substantially the entire length of each delivery member 3, 6. This has found to help prevent compression of the septum of larger noses, thereby improving comfort. In the present example, the width W1 of the gap 19 is at least 9.5 mm over substantially the entire length of the delivery members 3, 6.

[0224] In some embodiments, the width W1 of the gap 19 is at least 6 mm and, preferably, at least 7, 8, 8.5, 9 or 9.5 mm over at least 2 mm and, preferably, at least 3 mm, 3.5 mm or 4 mm of the length of each delivery member 3, 6. This has found to help prevent compression of the septum of larger noses, thereby improving comfort. Attorney Docket No.: 46567-1784WO1

[0225] In some embodiments, the width W1 of the gap 19 is substantially constant over at least 2 mm and, preferably, at least 3 mm, 3.5 mm or 4 mm of the length of each delivery member 3, 6.

[0226] The intranasal nozzle 1 comprises gripping portions 30 on opposite sides of the body 17 in order to facilitate gripping of the intranasal nozzle 1 by the user. In the present example, each gripping portion 30 comprises one or more ribs 30A. However, it should be recognised that in other embodiments the gripping portions 30 may take a different form (not shown), for example a textured surface, raised dots or a roughened surface.

[0227] Referring now to Fig. 16, a block diagram illustrating an embodiment of a method 200 of delivering medicament to a patient, and in the present example a paediatric patient. The method 200 comprises (S1) inserting the end portions of first and second delivery members of an intranasal nozzle into first and second nostrils of the patient, wherein the width of a gap between the end portions of the first and second delivery members is at least 6 mm and wherein the external width of the intranasal nozzle at the end portions is at most 20 mm. The method 200 further comprises (S2) expelling medicament from the first and second delivery members.

[0228] In the present example, the method 200 comprises: removing the intranasal nozzle from a pack; orientating the intranasal nozzle in proximity to a patient’s nose; and, operating a fluid flow generator (e.g. depressing a plunger of a syringe or squeezing a flexible container such as a bulb or balloon) to expel medicament through the intranasal nozzle.

[0229] The step of removing the intranasal nozzle from the pack may comprise removing the intranasal nozzle from a sealed pack.

[0230] In some embodiments, the method 200 comprises attaching the intranasal nozzle to the fluid flow generator.

[0231] In some embodiments, the method 200 comprises delivering the medicament to two external nostrils of the user simultaneously.

[0232] Referring now to Figs. 21 to 24, another embodiment of an intranasal nozzle 1 ”” is shown. The intranasal nozzle 1 ”” is similar to the intranasal nozzle T” of the embodiment of Fig. 16, with like features retaining the same reference numerals. A difference is that each Attorney Docket No.: 46567-1784WO1 delivery member 3, 6 comprises a first section that tapers in width W3 and a second section that tapers in width W3 and is disposed further away from the nozzle outlets 4, 7 than the first section 103A, 106A, wherein each second section 103B, 106B tapers to reduce in width W3 at a greater rate than the first section 103A, 106A.

[0233] The intranasal nozzle 1 ”” comprises a coupling for coupling to a fluid flow generator. The coupling may have any of the features of the previously described embodiments and is not shown in Figs. 21 to 24.

[0234] In the present example, the first sections 103A, 106A comprise the end portions 3A, 6A of the respective delivery members 3, 6. In another embodiment (not shown), the end portions may be another part of the delivery member 3, 6 that is downstream of the first sections 103A, 106A.

[0235] The first portion 103A, 106A of each delivery member 3, 6 is tapered to reduce in width W3 in a direction towards the respective nozzle outlet 4, 7.

[0236] In the present example, each second portion 103B, 106B extends from the body 17. In the present example, each first portion 103A, 106A extends from a respective second portion 103B, 106B. The second portion 103B, 106B of each delivery member 3, 6 is tapered to reduce in width W3 in a direction towards the first portion 103A, 103B.

[0237] In the present example, the first portions 103A, 106A of the delivery members 3, 6 extend from the respective second portions 103B, 106B. The second portion 103B, 106B of each delivery member 3, 6 is tapered to reduce in width W3 in a direction towards from the first portion 103A, 106A and towards the nozzle outlets 4, 7.

[0238] The tapered first and second portions 103A, 106A, 103B, 106B have been found to improve comfort when the intranasal nozzle 1 ”” is inserted into the nose of a patient that is of a size and shape that the nose (e.g. the wings) are stretched by the intranasal nozzle 1 This is because the tapering helps to gradually and gently stretch the nose as the intranasal nozzle 1”” is inserted rather than the nose suddenly being deformed by a stepchange in the dimensions of the intranasal nozzle 1””. The tapering also helps to limit the maximum insertion depth of the delivery members 3, 6, and can provide tactile feedback to the user (e.g. healthcare practitioner) when inserting the delivery members 3, 6 into the patient’s nose. Attorney Docket No.: 46567-1784WO1

[0239] The external width of the first portions 103A, 106A are generally flared, increasing in width in a direction away from the nozzle outlets 4, 7. Each first section 103A, 106A tapers to reduce in width W3 at a smaller rate than the second section 103B, 106B, which has been found to be particularly comfortable with smaller nostril sizes and spacings.

[0240] The width W1 of the gap 19 between the first portions 103A, 106A may be constant or substantially constant. This has been found to improve comfort by minimising compression of the septum of the patient. The width W1 of the gap 19 between the first portions 103A, 106A may be constant or substantially constant along the length of the first portions 103A, 106A.

[0241] The external width of the second portions 103B, 106B are generally flared, increasing in width in a direction away from the first portions 103A, 106A. Each second section 103B, 106B tapers to reduce in width W3 at a greater rate than the first section 103A, 106A, which has been found to be particularly comfortable with larger nostril sizes and spacings.

[0242] The width W1 of the gap 19 between the second portions 103B, 106B may be constant or substantially constant. This has been found to improve comfort by minimising compression of the septum of the patient. The width W1 of the gap 19 between the second portions 103B, 106B may be constant or substantially constant along the length of the second portions 103B, 106B.

[0243] Optionally, each delivery member 3, 6 further comprises a substantially planar portion 25A, 25B, 26A, 26B that is configured to abut the patient’s face when the delivery members 3, 6 are inserted into the patient’s nose. That is, a space 27A, 27B, 28A, 28B in proximity to each flat portion 25A, 25B, 26A, 26B can receive a portion of the patient’s face, which may then abut the substantially flat portion 25A, 25B, 26A, 26B. This helps to prevent or reduce pressure being applied to the patient’s face / lips during use of the nozzle 1 ”” (which may otherwise be caused by the delivery members 3, 6 pressing against the patient) and thus increasing comfort and the accuracy with which the intranasal nozzle 1 ”” can be positioned to deliver medicament. In some embodiments, a pair of the substantially planar portions 25A, 25B, 26A, 26B are configured to abut the nasal sill of the patient when the delivery members 3, 6 are inserted into the patent’s nose. Attorney Docket No.: 46567-1784WO1

[0244] In some embodiment, the first delivery member 3 comprises first and second substantially planar portions 25A, 25B that are on opposite sides of the first delivery member 3 and / or the second delivery member 6 comprises first and second substantially planar portions 26A, 26B that are on opposite sides of the second delivery member 6. This helps to improve ease of use and save time when the intranasal nozzle 1 ”” is to be used to deliver medicament to the patient, because the intranasal nozzle 1”” can either be orientated in a first position with the first planar portions 25A, 26A in contact with (or facing towards) the patient’s face (for example the nasal sill of the patient) or orientated in a second position with the second planar portions 25B, 26B in contact with (or facing towards) the patient’s face (for example the nasal sill of the patient). However, it should be recognised that in other embodiments (not shown) each delivery member s, 6 of the intranasal nozzle 1 ”” may comprise only a single planar portion or the planar portions may be omitted entirely.

[0245] In some embodiments, the first and second delivery members 3, 6 have a substantially constant depth measured in a direction perpendicular to the width W1 of the gap 19. This has been found to improve comfort by minimising compression of the septum of the patient. In some embodiments, the first and second delivery members 3, 6 have a substantially constant depth along the length of the delivery members 3, 6.

[0246] In some embodiments, the first portions 103A, 106A have a substantially constant depth measured in a direction perpendicular to the width W1 of the gap 19. This has been found to improve comfort by minimising compression of the septum of the patient. In some embodiments, the first portions 103A, 106A have a substantially constant depth along the length of the first portions 103A, 106A.

[0247] In some embodiments, the second portions 103B, 106B have a substantially constant depth measured in a direction perpendicular to the width W1 of the gap 19. This has been found to improve comfort by minimising compression of the septum of the patient. In some embodiments, the second portions 103B, 106B have a substantially constant depth along the length of the second portions 103B, 106B.

[0248] The width W1 of the gap 19 between the end portions 3A, 6A of the first and second delivery members 3, 6 is at least 6 mm. In some embodiments, the width W1 of the gap 19 between the end portions 3A, 6A is at least 6.5 mm and, preferably, is at least 7, 7.5, 8, 8.5, 9 or 9.5 mm. Increasing the width W1 of the gap 19 allows for the gap 19 to accommodate larger septum sizes. In the present example, the width W1 of the gap 19 Attorney Docket No.: 46567-1784WO1 between the end portions 3A, 6A is about 9.5 mm. A width W1 of gap 19 of at least 8, 8.5, 9 or 9.5 mm has been found to particularly advantageously be able to accommodate a very large range of septum sizes.

[0249] In addition, the external width W2a of the intranasal nozzle 1 at the end portions 3A, 6A is at most 20 mm. In some embodiments, the external width W2 of the intranasal nozzle 1 at the end portions 3A, 6A is at most 19 mm and, preferably, at most 18, 17, 16, 15 or 14.5 mm. Decreasing the width W2 of the intranasal nozzle 1 at the end portions 3A, 6A allows for the nozzle 1 to fit within smaller noses (in particular, wherein the outsides of the nostrils or alae / wings of the nose are spaced closer together). In the present example, the external width W2 of the intranasal nozzle 1 at the end portions 3A, 6A is about 15 mm. This has been found to be able to fit within a very large range of nose sizes.

[0250] In some embodiments, the external width W2b of the intranasal nozzle 1”” at the transition between the first sections 103a, 106a and the second sections 103B, 106B is at most 1 mm greater than the external width W2a of the intranasal nozzle T” at the end portions 3A, 6A and, optionally, at most 0.5 mm greater. In the present example, the external width W2b of the intranasal nozzle 1 ”” at the transition between the first sections 103A, 106A and the second sections 103B, 106B is about 0.3 mm greater than the external width W2a of the intranasal nozzle T” at the end portions 3A, 6A. In the present example, the external width W2b of the intranasal nozzle 1 ”” at the transition between the first sections 103A, 106A and the second sections 103B, 106B is about 15.3 mm.

[0251] In some embodiments, the external width W2c of the intranasal nozzle 1 ”” at the base of the second sections 103B, 106B is at least 13 mm and, optionally, is at least 14, 15, 16 or 17 mm.

[0252] In some embodiments, the external width W2c of the intranasal nozzle 1 ”” at the base of the second sections 103Bb, 106B is at most 23 mm and, optionally, is at least 22, 21 , 20, 19, 18 or 17 mm. In some embodiments, the external width W2c of the intranasal nozzle 1 ”” at the base of the second tapered sections 103b, 106b is about 17 mm.

[0253] In some embodiments, the second sections 103B, 106B are longer than the first sections 103A, 106A. Attorney Docket No.: 46567-1784WO1

[0254] In some embodiments, the length hi of each of the first portions 103A, 106A is at least 0.5 mm and, optionally, at least 1 , 1.1 , 1.2 or 1.3 mm.

[0255] In some embodiments, the length hi of each of the first portions 103A, 106A is at most 3 mm and, optionally, at most 2.5 mm. the length hi of each of the first portions 103A, 106A is at most 2 mm and, optionally, at most 1.7, 1.6, 1.5, 1.4 or 1.3 mm.

[0256] In some embodiments, the length hi of each of the first portions 103A, 106A is about 1.3 mm.

[0257] In some embodiments, the length h2 of each of the second portions 103B, 106B is at least 0.5 mm and, optionally, at least 1 , 1.5, 2, 2.3, 2.4, 2.5, 2.6 or 2.7 mm.

[0258] In some embodiments, the length h2 of each of the second portions 103B, 106B is at most 6 mm and, optionally, at most 5, 4, 3.5, 3, 2.9, 2.8 or 2.7 mm.

[0259] In some embodiments, the length h2 of each of the second portions 103B, 106B is about 2.7 mm.

[0260] In some embodiments, the centre of the first nozzle outlet 4 and the centre of the second nozzle outlet 7 are a distance in the range of 8 to 16 mm from each other and, preferably, a distance in the range of 10 to 14 mm or in the range of 11 to 13 mm from each other. It has been found that this advantageously helps to ensure that the centre of the nozzle outlets 4, 7 remain towards the centre of the nostrils of the patient.

[0261] In some embodiments, the centre of the first nozzle outlet 4 and the centre of the second nozzle outlet 7 are a distance of about 12.2 mm from each other.

[0262] In some embodiments, the width W3 of each end portion 3A, 6A is at most 5 mm and, preferably, is at most 4, 3.5, 32.9, 2.8, 2.7, 2.6 or 2.5 mm. This helps to ensure that the end portions 3A, 6A comfortably fit within smaller nostrils. Attorney Docket No.: 46567-1784WO1

[0263] In some embodiments, the width W3 of each end portion 3A, 6A is at least 2 mm. This helps to promote durability of the end portions 3A, 6A and more accurate positioning of the nozzle outlets 4, 7 within the respective nostrils.

[0264] In some embodiments, the first section 103A, 106A of each delivery member 3, 6 has a depth of at most 4.5 mm and, preferably, at most 4 mm, 3.5 mm, 3 mm, or 2.5 mm in a direction perpendicular to width W1 , W2a, W2b, W2c, W3. This helps to prevent or reduce pressure being applied to the patient’s face / lips during use of the nozzle 1 ”” (which may otherwise be caused by the first section 103A, 106A pressing against the patient if it has too much depth) and thus increasing comfort and the accuracy with which the intranasal nozzle 1 ”” can be positioned to deliver medicament.

[0265] In some embodiments, the second section 103B, 106B of each delivery member 3, 6 has a depth of at most 4.5 mm and, preferably, at most 4 mm, 3.5 mm, 3 mm, or 2.5 mm in a direction perpendicular to width W1 , W2a, W2b, W2c, W3. This helps to prevent or reduce pressure being applied to the patient’s face / lips during use of the nozzle 1 ”” (which may otherwise be caused by the second section 103B, 106B pressing against the patient if it has too much depth) and thus increasing comfort and the accuracy with which the intranasal nozzle 1”” can be positioned to deliver medicament.

[0266] In some embodiments, each delivery member 3, 6 has a depth D4 of at most 4.5 mm and, preferably, at most 4 mm, 3.5 mm, 3 mm, or 2.5 mm in a direction perpendicular to width W1 and W2a, W2b, W2c, W3.

[0267] The depth D4 of each delivery member 3, 6 may be measured in a direction perpendicular to the width W1 of the gap between the end portions 3A, 6A of the first and second delivery members 3, 6. The depth D4 of each delivery member 3, 6 may be measured in a direction perpendicular to the height (h1+h2) of the delivery members 3, 6.

[0268] In each of the embodiments described above, the intranasal nozzle 1 , T, 1”, 1’”, 1”” is fluidly communicated with a fluid flow generator 2. The fluid flow generator 2 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 fluid flow generator 2 may take a different form. In some embodiments, the fluid flow generator comprises a syringe or flexible container such as a Attorney Docket No.: 46567-1784WO1 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, 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.

[0269] 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.

[0270] As used herein, “RSV ANS2 / A1313 / I1314L” refers to an RSV ANS2 / A1313 / I1314L (NIH) or an RSV ANS2 / A1313 / I1314L (Sanofi). Each of the ANS2 / A1313 / I1314L (NIH) and the RSV ANS2 / A1313 / I1314L (Sanofi) comprise a live-attenuated RSV with (i) a 523 nucleotide (nt) deletion of the NS2 gene (ANS2), (ii) an amino acid deletion in the L protein, and (iii) a genetically stabilizing mutation in the L gene. The live-attenuated RSV of the RSV ANS2 / A1313 / I1314L (Sanofi) also includes a nucleotide modification at position 14456 that represents a change from a thymine (T) to an adenine (A) in a noncoding region.

[0271] 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).

[0272] Exemplary Methods and Uses

[0273] In some embodiments, provided are methods of delivering a dose of an RSV vaccine using an intranasal atomization delivery device.

[0274] 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 Attorney Docket No.: 46567-1784WO1 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).

[0275] 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.

[0276] In some embodiments, the RSV vaccine is delivered intranasally using the intranasal atomization delivery device to deliver about1 / 2dose to each nostril. In some embodiments, the RSV vaccine is delivered intranasally so that the whole dose is delivered to one nostril. In some embodiments, the RSV vaccine is delivered intranasally with % dose delivered to one nostril and the other % dose is delivered to the same nostril after the first % dose is absorbed. In some embodiments, the RSV vaccine is delivered intranasally using the intranasal atomization delivery device to deliver a dose in unequal amounts to one or both nostrils.

[0277] 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.

[0278] 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. Attorney Docket No.: 46567-1784WO1

[0279] 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 deliver1 / 2dose to each nostril of the subject.

[0280] 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.

[0281] 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).

[0282] Immunogenicity Attorney Docket No.: 46567-1784WO1

[0283] 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.

[0284] 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.

[0285] Vaccine virus shedding and Infectivity

[0286] 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 Attorney Docket No.: 46567-1784WO1 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.

[0287] Interim analysis results showed a promising safety, immunogenicity and infectivity profile of the RSV ANS2 / A1313 / I1314L (Sanofi) candidate.

[0288] 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.

[0289] 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.

[0290] 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.

[0291] List of Reference Numbers Attorney Docket No.: 46567-1784WO1

[0292] 1 - intranasal nozzle

[0293] 1 ’ - intranasal nozzle

[0294] 1 ” - intranasal nozzle

[0295] 1 ”’ - intranasal nozzle

[0296] 1 ”” - intranasal nozzle

[0297] 2 - fluid flow generator

[0298] 3 - first medicament delivery member

[0299] 3A - first end portion

[0300] 4 - first nozzle outlet

[0301] 5 - first medicament delivery conduit

[0302] 6 - second medicament delivery member 6A - second end portion

[0303] 7 - second nozzle outlet

[0304] 8 - second medicament delivery conduit

[0305] 10 - coupling (of intranasal nozzle)

[0306] 11 - chamber

[0307] 12 - body (of fluid flow generator)

[0308] 13 - plunger

[0309] 14 - outlet (of fluid flow generator)

[0310] 15 - coupling (of fluid flow generator)

[0311] 16 - inlet (of intranasal nozzle)

[0312] 17 - body (of intranasal nozzle)

[0313] 18 - passage (of intranasal nozzle)

[0314] 19 - gap

[0315] 20 - base surface

[0316] 21 - first space

[0317] 21 A - concave surface

[0318] 22 - second space

[0319] 22A - concave surface

[0320] 23 - first indicator region

[0321] 24 - second indicator region

[0322] 25A - first planar portion

[0323] 25B - second planar portion

[0324] 26A - first planar portion

[0325] 26B - second planar portion

[0326] 27A - first space Attorney Docket No.: 46567-1784WO1

[0327] 27B - second space

[0328] 28A - first space

[0329] 28B - second space

[0330] 30 - gripping portion

[0331] 30A - rib

[0332] 100 - intranasal medicament delivery system

[0333] 103A - first section of first medicament delivery member

[0334] 103B - second section of first medicament delivery member 106A - first section of second medicament delivery member

[0335] 106B - second section of second medicament delivery member 200 - method of delivering medicament

[0336] W1 - width of gap

[0337] W2 - external width of nozzle

[0338] W3 - width of end portions

[0339] D2 - depth of half of body

[0340] D3 - depth of half of body

[0341] D4 - depth of end portion of delivery member hi - length of first section of delivery member h2 - length of second section of delivery member

[0342] P-P - plane extending through delivery members perpendicular thereto P1-P1 - plane interesting nozzle outlets

Claims

Attorney Docket No.: 46567-1784WO1Claims1 . An intranasal nozzle (1 , 1 1 ”, 1 1 ””) for medicament delivery, the intranasal nozzle (1 , 1 ’, 1 ”, 1 ”’, 1 ””) comprising: a first delivery member (3) configured to be inserted into a first nostril of a patient and comprising a first end portion (3A) that has a first medicament outlet (4); and, a second delivery member (6) configured to be inserted into a second nostril of the patient and comprising a second end portion (6A) that has a second medicament outlet (7), wherein a gap (19) is disposed between the first and second delivery members (3, 6) that is configured to receive at least a portion of the septum of the patient’s nose when the first and second delivery members (3, 6) are inserted into the first and second nostrils, and wherein the width (W1) of the gap (19) between the end portions (3A, 6A) of the first and second delivery members (3, 6) is at least 6 mm and wherein the external width (W2) of the intranasal nozzle (1 , 1’, 1 ”, 1 ”’, 1 ””) at the end portions (3A, 6A) is at most 20 mm.

2. An intranasal nozzle (1 , 1 ’, 1 ”, 1 1 ””) according to claim 1 , wherein the width of the gap (19) between the end portions (3A, 6A) is at least 6.5 mm and, preferably, is at least 7, 8, 8.5, 9 or 9.5 mm.

3. An intranasal nozzle (1 , 1 ’, 1 ”, 1 1 ””) according to any one of the preceding claims, wherein the width (W3) of each end portion (3A, 6A) is at least 2 mm and / or wherein the width (W3) of each end portion (3A, 6A) is at most 5 mm and, preferably, is at most 4, 3 or 2.5 mm.

4. An intranasal nozzle (1 , 1 ’, 1 ”, 1 1 ””) according to any one of the preceding claims, wherein each delivery member (3, 6) is flared to increase in width in a direction away from the respective end portion (3A, 6A).

5. An intranasal nozzle (1 , 1 ’, 1 ”, 1 1 ””) according to any one of the preceding claims, wherein the external width (W2) of the intranasal nozzle (1 , 1 ’, 1 ”, 1 ”) at the end portions (3A, 6A) is at most 19 mm and, optionally, at most 18, 17, 16, 15 or 14.5 mm.

6. An intranasal nozzle (1 , 1 ’, 1 ”, 1 1 ””) according to any one of the preceding claims, wherein each delivery member (3, 6) comprises at least one substantially planarAttorney Docket No.: 46567-1784WO1 portion (25A, 25B, 26A, 26B) that is configured to abut the patient’s face when the delivery members (3, 6) are inserted into the patient’s nose and, optionally is configured to abut a nasal sill of the patient when the delivery members (3, 6) are inserted into the patient’s nose and / or wherein the intranasal nozzle comprises a space (21 , 22) that is configured to receive at least a portion of the patient’s lips and / or portion of the patient’s face between the lips and nose (e.g. the philtrum)..

7. An intranasal nozzle (1 , 1 ’, 1 ”, 1 ’”, 1 ””) according to any one of the preceding claims, comprising a coupling (10) configured to couple to a fluid flow generator (2) and, optionally, wherein the coupling (10) comprises a Luer lock, and / or comprising a body (17) and wherein the first and second delivery members (3, 6) extend from the body (17) and, optionally, wherein the body (17) is configured to abut the nose of the patient.

8. An intranasal nozzle (1 , 1 ’, 1 ”, 1 ’”, 1 ””) according to any one of the preceding claims, wherein each delivery member (3, 6) comprises a first section (103A, 106A) that tapers in width and a second section (103B, 106B) that tapers in width and is disposed further away from the nozzle outlets (4, 7) than the first section (103A, 106A) and, optionally, wherein each second section (103B, 106B) tapers to reduce in width at a greater rate than the first section (103A, 106A).

9. An intranasal nozzle (1 , 1 ’, 1 ”, 1 ’”, 1 ””) according to any one of the preceding claims, wherein the centres of the first and second medicament outlets (4, 7) are spaced apart by a distance in the range of 9 to 15 mm and, optionally, in the range of 11 to 13 mm.

10. An intranasal nozzle (1 , 1 ’, 1 ”, 1 ’”, 1 ””) according to any one of the preceding claims, wherein each delivery member (3, 6) has a depth of at most 4.5 mm and, optionally, at most 4 mm, 3.5 mm, 3 mm, or 2.5 mm and / or wherein each delivery member (3, 6) is configured to have a maximum insertion depth into the nostril of at most 6 mm and, optionally, at most 5, 4, 3, 2 or 1 mm.

11. An intranasal nozzle (1 , 1 ’, 1 ”, 1 ’”, 1 ””) for medicament delivery, the intranasal nozzle (1 , 1 ’, 1 ”, 1 ’”, 1 ””) comprising: a first delivery member (3) configured to be inserted into a first nostril of a patient and comprising a first end portion (3A) that has a first medicament outlet (4); and,Attorney Docket No.: 46567-1784WO1 a second delivery member (6) configured to be inserted into a second nostril of the patient and comprising a second end portion (6A) that has a second medicament outlet (7), wherein the intranasal nozzle is configured such that the first and second delivery members (3, 6) can be inserted into the first and second nostrils respectively of at least 70% of paediatric patients in the age range of 4 months to 24 months with generally no deformation of the nose of the paediatric patient.

12. An intranasal nozzle (1 , 1 ’, 1”, 1”’, 1 ””) according to claim 11 , wherein the intranasal nozzle is configured such that the first and second delivery members (3, 6) can be inserted into the first and second nostrils respectively of at least 75% of paediatric patients in the age range of 4 months to 24 months without deformation of the nose of the paediatric patient and, optionally, at least 80%, 85%, 90% or 95% of paediatric patients in the age range of 4 months to 24 months without deformation of the nose of the paediatric patient.

13. An intranasal nozzle (1 , 1 ’, 1”, 1 ”’, 1””) according to claim 11 or claim 12, wherein the intranasal nozzle has any of the features of the intranasal nozzle of any one of the claims 1 to 10.

14. A medicament delivery system (100) comprising an intranasal nozzle (1 , 1 ’, 1 ”, 1”’, 1 ””) according to any one of the preceding claims and a fluid flow generator (2) and, optionally, wherein the medicament delivery system (100) contains a medicament and, optionally, wherein the medicament is a vaccine.

15. A method (200) of delivering medicament to a patient, the method (200) comprising inserting the end portions (3A, 6A) of first and second delivery members (3, 6) of an intranasal nozzle (1 , 1 ’, 1 ”, 1 1 ””) into first and second nostrils of the patient, wherein the width (W1) of a gap (19) between the end portions (3A, 6A) is at least 6 mm and wherein the external width (W2) of the intranasal nozzle (1 , 1 ’, 1 ”, 1 ”’, 1 ””) at the end portions (3A, 6A) is at most 20 mm; and, expelling medicament from the first and second delivery members (3, 6).

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